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A chemotherapy regimen is a regimen for chemotherapy, defining the drugs to be used, their dosage, the frequency and duration of treatments, and other considerations. In modern oncology, many regimens combine several chemotherapy drugs in combination chemotherapy. The majority of drugs used in cancer chemotherapy are cytostatic, many via cytotoxicity.
A fundamental philosophy of medical oncology, including combination chemotherapy, is that different drugs work through different mechanisms, and that the results of using multiple drugs will be synergistic to some extent. Because they have different dose-limiting adverse effects, they can be given together at full doses in chemotherapy regimens.
The first successful combination chemotherapy was MOPP, introduced in 1963 for lymphomas.
The term "induction regimen" refers to a chemotherapy regimen used for the initial treatment of a disease. A "maintenance regimen" refers to the ongoing use of chemotherapy to reduce the chances of a cancer recurring or to prevent an existing cancer from continuing to grow.
== Nomenclature ==
Chemotherapy regimens are often identified by acronyms, identifying the agents used in the drug combination. However, the letters used are not consistent across regimens, and in some cases - for example, "BEACOPP" - the same letter combination is used to represent two different treatments.
There is no widely accepted naming convention or standard for the nomenclature of chemotherapy regimens. For example, either generic or brand names may be used for acronyms. This page merely lists commonly used conventions.
== List of chemotherapy regimen acronyms ==
== See also ==
National Comprehensive Cancer Network Treatment Guidelines
Breast cancer chemotherapy
High-dose chemotherapy
Sequential high-dose chemotherapy
== References ==
== External links ==
Chemotherapy regimens and references
Chemotherapy side effects Archived 2012-08-15 at the Wayback Machine
Christie Hospital Chemotherapy Patient Information Sheets | Wikipedia/Chemotherapy_regimens |
Hyperthermia therapy (or hyperthermia, or thermotherapy) is a type of medical treatment in which body tissue is exposed to temperatures above body temperature, in the region of 40–45 °C (104–113 °F). Hyperthermia is usually applied as an adjuvant to radiotherapy or chemotherapy, to which it works as a sensitizer, in an effort to treat cancer.
Hyperthermia uses higher temperatures than diathermy and lower temperatures than ablation. When combined with radiation therapy, it can be called thermoradiotherapy.
== Definition ==
Hyperthermia is defined as supra-normal body temperatures. There is no consensus as to what is the safest or most effective target temperature for the whole body. During treatment the body temperature reaches a level between 39.5 and 40.5 °C (103.1 and 104.9 °F). However, other researchers define hyperthermia between 41.8–42 °C (107.2–107.6 °F) (Europe, USA) to near 43–44 °C (109–111 °F) (Japan, Russia).
=== Types ===
Local hyperthermia heats a very small area and is typically used for cancers near or on the skin or near natural openings in the body (e.g., the mouth). In some instances, the goal is to kill the tumor by heating it, without damaging anything else. The heat may be created with microwave, radiofrequency, ultrasound energy or using magnetic hyperthermia (also known as magnetic fluid hyperthermia)). Depending on the location of the tumor, the heat may be applied to the surface of the body (superficial hyperthermia), inside normal body cavities (intraluminal hyperthermia), or deep in tissue through the use of needles or probes (interstitial hyperthermia). It should not be confused with ablation of small tumors, where higher temperatures (>55 °C) are applied with an aim to kill the tumor cells.
Regional hyperthermia heats a larger part of the body, such as an entire organ or limb. Usually, the goal is to weaken cancer cells so that they are more likely to be killed by radiation and chemotherapeutic medications. This may use the same techniques as local hyperthermia treatment, or it may rely on blood perfusion. In blood perfusion, the patient's blood is removed from the body, heated up, and returned to blood vessels that lead directly through the desired body part. Normally, chemotherapy drugs are infused at the same time. One specialized type of this approach is continuous hyperthermic peritoneal perfusion (CHPP), which is used to treat difficult cancers within the peritoneal cavity (the abdomen), including primary peritoneal mesothelioma and stomach cancer. Hot chemotherapy drugs are pumped directly into the peritoneal cavity to kill the cancer cells.
Whole-body hyperthermia heats the entire body to temperatures of about 39 to 43 °C (102 to 109 °F), with some advocating even higher temperatures. It is typically used to treat metastatic cancer (cancer that spread to many parts of the body). Techniques include infrared hyperthermia domes which include the whole body or the body apart from the head, putting the patient in a very hot room/chamber, or wrapping the patient in hot, wet blankets or a water tubing suit.
== Treatment ==
Research has shown that hyperthermia, when administered with other treatments, can shrink tumours and may assist other treatments kill cancer cells.
Localized hyperthermia treatment is a well-established cancer treatment method with a simple basic principle: If a temperature elevation to 40 °C (104 °F) can be maintained for one hour within a cancer tumor, the cancer cells will be destroyed.
The schedule for treatments has varied between study centers. After being heated, cells develop resistance to heat, which persists for about three days and reduces the likelihood that they will die from direct effects of the heat. Some even suggest maximum treatment schedule of twice a week. Japanese researchers treated people with "cycles" up to four times a week apart. Radiosensitivity may be achieved with hyperthermia, and using heat with every radiation treatment may drive the treatment schedule. Moderate hyperthermia treatments usually maintain the temperature for approximately an hour.
Before the advent of modern antiretroviral therapy extracorporeal whole body hyperthermia was tried as a treatment for HIV/AIDS, with some positive outcomes.
== Adverse effects ==
External application of heat may cause surface burns. Tissue damage to a target organ with a regional treatment will vary with what tissue is heated (e.g. brain treated directly may injure the brain, lung tissue treated directly may cause pulmonary problems). Whole body hyperthermia can cause swelling, blood clots, and bleeding. Systemic shock, may result, but is highly dependent upon method difference in achieving it. It may also cause cardiovascular toxicity. All techniques are often combined with radiation or chemotherapy, muddying how much toxicity is the result of those treatments versus the temperature elevation achieved.
== Technique ==
=== Heat sources ===
There are many techniques by which heat may be delivered. Some of the most common involve the use of focused ultrasound (FUS or HIFU), RF sources, infrared sauna, microwave heating, induction heating, magnetic hyperthermia, infusion of warmed liquids, or direct application of heat such as through sitting in a hot room or wrapping a patient in hot blankets.
=== Controlling temperature ===
One of the challenges in thermal therapy is delivering the appropriate amount of heat to the correct part of the patient's body. For this technique to be effective, the temperatures must be high enough, and the temperatures must be sustained long enough, to damage or kill the cancer cells. However, if the temperatures are too high, or if they are kept elevated for too long, then serious side effects, including death, can result. The smaller the place that is heated, and the shorter the treatment time, the lower the side effects. Conversely, tumor treated too slowly or at too low a temperature will not achieve therapeutic goals. The human body is a collection of tissues with differing heat capacities, all connected by a dynamic circulatory system with variable relationship to skin or lung surfaces designed to shed heat energy. All methods of inducing higher temperature in the body are countered by the thermo-regulatory mechanisms of the body. The body as a whole relies mostly on simple radiation of energy to the surrounding air from the skin (50% of heat lost this way) which is augmented by convection (blood shunting) and vaporization through sweat and respiration. Regional methods of heating may be more or less difficult based on the anatomic relationships, and tissue components of the particular body part being treated. Measuring temperatures in various parts of the body may be very difficult, and temperatures may locally vary even within a region of the body.
To minimize damage to healthy tissue and other adverse effects, attempts are made to monitor temperatures. The goal is to keep local temperatures in tumor bearing tissue under 44 °C (111 °F) to avoid damage to surrounding tissues. These temperatures have been derived from cell culture and animal studies. The body keeps itself normal human body temperature, near 37.6 °C (99.7 °F). Unless a needle probe can be placed with accuracy in every tumor site amenable to measurement, there is an inherent technical difficulty in how to actually reach whatever a treating center defines as an "adequate" thermal dose. Since there is also no consensus as to what parts of the body need to be monitored (common clinically measured sites are ear drums, oral, skin, rectal, bladder, esophagus, blood probes, or even tissue needles). Clinicians have advocated various combinations for these measurements. These issues complicate the ability of comparing different studies and coming up with a definition of exactly what a thermal dose actually should be for tumor, and what dose is toxic to what tissues in human beings. Clinicians may be able to apply advanced imaging techniques, instead of probes, to monitor heat treatments in real time; heat-induced changes in tissue are sometimes perceptible using these imaging instruments.
There is the further difficulty inherent in the devices delivering energy. Regional devices may not uniformly heat a target area, even without taking into account compensatory mechanisms of the body. A great deal of current research focuses on how one might precisely position heat-delivery devices (catheters, microwave and ultrasound applicators, etc.) using ultrasound or magnetic resonance imaging, as well as developing new types of nanoparticles that can more evenly distribute heat within a target tissue.
Among hyperthermia therapy methods, magnetic hyperthermia is well known as the one that produce a controllable heat inside the body. Because of using magnetic fluid in this method, temperature distribution can be controlled by the velocity, size of nanoparticles and distribution of them inside the body. These materials upon application of external, alternating magnetic field convert electromagnetic energy into thermal energy and induce temperature rises.
== Mechanism ==
Hyperthermia can kill cells directly, but its more important use is in combination with other treatments for cancer. Hyperthermia increases blood flow to the warmed area, perhaps doubling perfusion in tumors, while increasing perfusion in normal tissue by ten times or even more. This enhances the delivery of medications. Hyperthermia also increases oxygen delivery to the area, which may make radiation more likely to damage and kill cells, as well as preventing cells from repairing the damage induced during the radiation session.
Cancerous cells are not inherently more susceptible to the effects of heat. When compared in in vitro studies, normal cells and cancer cells show the same responses to heat. However, the vascular disorganization of a solid tumor results in an unfavorable microenvironment inside tumors. Consequently, the tumor cells are already stressed by low oxygen, higher than normal acid concentrations, and insufficient nutrients, and are thus significantly less able to tolerate the added stress of heat than a healthy cell in normal tissue.
Mild hyperthermia, which provides temperatures equal to that of a naturally high fever, may stimulate natural immunological attacks against the tumor. However, it is also induces a natural physiological response called thermotolerance, which tends to protect the treated tumor.
Moderate hyperthermia, which heats cells in the range of 40 to 42 °C (104 to 108 °F), damages cells directly, in addition to making the cells radiosensitive and increasing the pore size to improve delivery of large-molecule chemotherapeutic and immunotherapeutic agents (molecular weight greater than 1,000 daltons), such as monoclonal antibodies and liposome-encapsulated drugs. Cellular uptake of certain small molecule drugs is also increased.
Very high temperatures, above 50 °C (122 °F), are used for ablation (direct destruction) of some tumors. This generally involves inserting a metal tube directly into the tumor, and heating the tip until the tissue next to the tube has been killed.
== History ==
The application of heat to treat certain conditions, including possible tumors, has a long history. Ancient Greeks, Romans, and Egyptians used heat to treat breast masses; this is still a recommended self-care treatment for breast engorgement. Medical practitioners in ancient India used regional and whole-body hyperthermia as treatments.
During the 19th century, tumor shrinkage after a high fever due to infection had been reported in a small number of cases. Typically, the reports documented the rare regression of a soft tissue sarcoma after erysipelas (an acute streptococcus bacterial infection of the skin; a different presentation of an infection by "flesh-eating bacteria") was noted. Efforts to deliberately recreate this effect led to the development of Coley's toxin. A sustained high fever after induction of illness was considered critical to treatment success. This treatment is generally considered both less effective than modern treatments and, when it includes live bacteria, inappropriately dangerous.
Around the same period Westermark used localized hyperthermia to produce tumor regression in patients. Encouraging results were also reported by Warren when he treated patients with advanced cancer of various types with a combination of heat, induced with pyrogenic substance, and x-ray therapy. Out of 32 patients, 29 improved for 1 to 6 months.
Properly controlled clinical trials on deliberately induced hyperthermia began in the 1970s.
== Future directions ==
Hyperthermia may be combined with gene therapy, particularly using the heat shock protein 70 promoter.
Two major technological challenges make hyperthermia therapy complicated: the ability to achieve a uniform temperature in a tumor, and the ability to precisely monitor the temperatures of both the tumor and the surrounding tissue. Advances in devices to deliver uniform levels of the precise amount of heat desired, and devices to measure the total dose of heat received, are hoped for.
In locally advanced adenocarcinoma of middle and lower rectum, regional hyperthermia added to chemoradiotherapy achieved good results in terms of rate of sphincter sparing surgery.
=== Magnetic hyperthermia ===
Magnetic hyperthermia is an experimental treatment for cancer, based on the fact that magnetic nanoparticles can transform electromagnetic energy from an external high-frequency field to heat. This is due to the magnetic hysteresis of the material when it is subjected to an alternating magnetic field. The area enclosed by the hysteresis loop represents losses, which are commonly dissipated as thermal energy. In many industrial applications this heat is undesirable, however it is the basis for magnetic hyperthermia treatment.
As a result, if magnetic nanoparticles are put inside a tumor and the whole patient is placed in an alternating magnetic field, the temperature of the tumor will rise. This elevation of temperature may enhance tumor oxygenation and radio- and chemosensitivity, hopefully shrinking tumors. This experimental cancer treatment has also been investigated for the aid of other ailments, such as bacterial infections.
Magnetic hyperthermia is defined by specific absorption rate (SAR) and it is usually expressed in watts per gram of nanoparticles.
== See also ==
Microwave thermotherapy, use of microwave heating to treat cancer
Photothermal Therapy, use of infrared radiation to treat cancer
Thermotherapy, use of heat for treating other conditions
Coley's toxins, a bacteria mixture used to generate fevers as an alternative cancer treatment
Tronado machine, a device that uses microwave radiation to generate hyperthermia for cancer (no evidence of benefit)
Pyrotherapy, a method of treating infections by raising the body temperature
== References ==
== External links ==
Hyperthermia to Treat Cancer Information from the American Cancer Society
Transurethral Microwave Thermotherapy of the Prostate (TUMT) at eMedicine
Society of Thermal Medicine
European Society of Hyperthermic Oncology | Wikipedia/Hyperthermia_therapy |
Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrients for those who cannot, or will not—due to reduced mental states or otherwise—consume food or water by mouth. It may also be used to administer medications or other medical therapy such as blood products or electrolytes to correct electrolyte imbalances. Attempts at providing intravenous therapy have been recorded as early as the 1400s, but the practice did not become widespread until the 1900s after the development of techniques for safe, effective use.
The intravenous route is the fastest way to deliver medications and fluid replacement throughout the body as they are introduced directly into the circulatory system and thus quickly distributed. For this reason, the intravenous route of administration is also used for the consumption of some recreational drugs. Many therapies are administered as a "bolus" or one-time dose, but they may also be administered as an extended infusion or drip. The act of administering a therapy intravenously, or placing an intravenous line ("IV line") for later use, is a procedure which should only be performed by a skilled professional. The most basic intravenous access consists of a needle piercing the skin and entering a vein which is connected to a syringe or to external tubing. This is used to administer the desired therapy. In cases where a patient is likely to receive many such interventions in a short period (with consequent risk of trauma to the vein), normal practice is to insert a cannula which leaves one end in the vein, and subsequent therapies can be administered easily through tubing at the other end. In some cases, multiple medications or therapies are administered through the same IV line.
IV lines are classified as "central lines" if they end in a large vein close to the heart, or as "peripheral lines" if their output is to a small vein in the periphery, such as the arm. An IV line can be threaded through a peripheral vein to end near the heart, which is termed a "peripherally inserted central catheter" or PICC line. If a person is likely to need long-term intravenous therapy, a medical port may be implanted to enable easier repeated access to the vein without having to pierce the vein repeatedly. A catheter can also be inserted into a central vein through the chest, which is known as a tunneled line. The specific type of catheter used and site of insertion are affected by the desired substance to be administered and the health of the veins in the desired site of insertion.
Placement of an IV line may cause pain, as it necessarily involves piercing the skin. Infections and inflammation (termed phlebitis) are also both common side effects of an IV line. Phlebitis may be more likely if the same vein is used repeatedly for intravenous access, and can eventually develop into a hard cord which is unsuitable for IV access. The unintentional administration of a therapy outside a vein, termed extravasation or infiltration, may cause other side effects.
== Uses ==
=== Medical uses ===
Intravenous (IV) access is used to administer medications and fluid replacement which must be distributed throughout the body, especially when rapid distribution is desired. Another use of IV administration is the avoidance of first-pass metabolism in the liver. Substances that may be infused intravenously include volume expanders, blood-based products, blood substitutes, medications and nutrition.
==== Fluid solutions ====
Fluids may be administered as part of "volume expansion", or fluid replacement, through the intravenous route. Volume expansion consists of the administration of fluid-based solutions or suspensions designed to target specific areas of the body which need more water. There are two main types of volume expander: crystalloids and colloids. Crystalloids are aqueous solutions of mineral salts or other water-soluble molecules. Colloids contain larger insoluble molecules, such as gelatin. Blood itself is considered a colloid.
The most commonly used crystalloid fluid is normal saline, a solution of sodium chloride at 0.9% concentration, which is isotonic with blood. Lactated Ringer's (also known as Ringer's lactate) and the closely related Ringer's acetate, are mildly hypotonic solutions often used in those who have significant burns. Colloids preserve a high colloid osmotic pressure in the blood, while, on the other hand, this parameter is decreased by crystalloids due to hemodilution. Crystalloids generally are much cheaper than colloids.
Buffer solutions which are used to correct acidosis or alkalosis are also administered through intravenous access. Lactated Ringer's solution used as a fluid expander or base solution to which medications are added also has some buffering effect. Another solution administered intravenously as a buffering solution is sodium bicarbonate.
==== Medication and treatment ====
Medications may be mixed into the fluids mentioned above, commonly normal saline, or dextrose solutions. Compared with other routes of administration, such as oral medications, the IV route is the fastest way to deliver fluids and medications throughout the body. For this reason, the IV route is commonly preferred in emergency situations or when a fast onset of action is desirable. In extremely high blood pressure (termed a hypertensive emergency), IV antihypertensives may be given to quickly decrease the blood pressure in a controlled manner to prevent organ damage. In atrial fibrillation, IV amiodarone may be administered to attempt to restore normal heart rhythm. IV medications can also be used for chronic health conditions such as cancer, for which chemotherapy drugs are commonly administered intravenously. In some cases, such as with vancomycin, a loading or bolus dose of medicine is given before beginning a dosing regimen to more quickly increase the concentration of medication in the blood.
The bioavailability of an IV medication is by definition 100%, unlike oral administration where medication may not be fully absorbed, or may be metabolized prior to entering the bloodstream. For some medications, there is virtually zero oral bioavailability. For this reason certain types of medications can only be given intravenously, as there is insufficient uptake by other routes of administration, such is the case of severe dehydration where the patient is required to be treated via IV therapy for a quick recovery. The unpredictability of oral bioavailability in different people is also a reason for a medication to be administered IV, as with furosemide. Oral medications also may be less desirable if a person is nauseous or vomiting, or has severe diarrhea, as these may prevent the medicine from being fully absorbed from the gastrointestinal tract. In these cases, a medication may be given IV only until the patient can tolerate an oral form of the medication. The switch from IV to oral administration is usually performed as soon as viable, as there is generally cost and time savings over IV administration. Whether a medication can be potentially switched to an oral form is sometimes considered when choosing appropriate antibiotic therapy for use in a hospital setting, as a person is unlikely to be discharged if they still require IV therapy.
Some medications, such as aprepitant, are chemically modified to be better suited for IV administration, forming a prodrug such as fosaprepitant. This can be for pharmacokinetic reasons or to delay the effect of the drug until it can be metabolized into the active form.
==== Blood products ====
A blood product (or blood-based product) is any component of blood which is collected from a donor for use in a blood transfusion. Blood transfusions can be used in massive blood loss due to trauma, or can be used to replace blood lost during surgery. Blood transfusions may also be used to treat a severe anaemia or thrombocytopenia caused by a blood disease. Early blood transfusions consisted of whole blood, but modern medical practice commonly uses only components of the blood, such as packed red blood cells, fresh frozen plasma or cryoprecipitate.
==== Nutrition ====
Parenteral nutrition is the act of providing required nutrients to a person through an intravenous line. This is used in people who are unable to get nutrients normally, by eating and digesting food. A person receiving parenteral nutrition will be given an intravenous solution which may contain salts, dextrose, amino acids, lipids and vitamins. The exact formulation of a parenteral nutrition used will depend on the specific nutritional needs of the person it is being given to. If a person is only receiving nutrition intravenously, it is called total parenteral nutrition (TPN), whereas if a person is only receiving some of their nutrition intravenously it is called partial parenteral nutrition (or supplemental parenteral nutrition).
==== Imaging ====
Medical imaging relies on being able to clearly distinguish internal parts of the body from each other. One way this is accomplished is through the administration of a contrast agent into a vein. The specific imaging technique being employed will determine the characteristics of an appropriate contrast agent to increase visibility of blood vessels or other features. Common contrast agents are administered into a peripheral vein from which they are distributed throughout the circulation to the imaging site.
=== Other uses ===
==== Use in sports ====
IV rehydration was formerly a common technique for athletes. The World Anti-Doping Agency prohibits intravenous injection of more than 100 mL per 12 hours, except under a medical exemption. The United States Anti-Doping Agency notes that, as well as the dangers inherent in IV therapy, "IVs can be used to change blood test results (such as hematocrit where EPO or blood doping is being used), mask urine test results (by dilution) or by administering prohibited substances in a way that will more quickly be cleared from the body in order to beat an anti-doping test". Players suspended after attending "boutique IV clinics" which offer this sort of treatment include footballer Samir Nasri in 2017 and swimmer Ryan Lochte in 2018.
==== Use for hangover treatment ====
In the 1960s, John Myers developed the "Myers' cocktail", a non-prescription IV solution of vitamins and minerals marketed as a hangover cure and general wellness remedy. The first "boutique IV" clinic, offering similar treatments, opened in Tokyo in 2008. These clinics, whose target market was described by Elle as "health nuts who moonlight as heavy drinkers", have been publicized in the 2010s by glamorous celebrity customers. Intravenous therapy is also used in people with acute ethanol toxicity to correct electrolyte and vitamin deficiencies which arise from alcohol consumption.
==== Others ====
In some countries, non-prescription intravenous glucose is used to improve a person's energy, but is not a part of routine medical care in countries such as the United States where glucose solutions are prescription drugs. Improperly administered intravenous glucose (called "ringer" ), such as that which is administered clandestinely in store-front clinics, poses increased risks due to improper technique and oversight. Intravenous access is also sometimes used outside of a medical setting for the self-administration of recreational drugs, such as heroin and fentanyl, cocaine, methamphetamine, DMT, and others.
Intravenous therapy is also used for veterinary patient management.
== Types ==
=== Bolus ===
Some medications can be administered as a bolus dose, which is called an "IV push". A syringe containing the medication is connected to an access port in the primary tubing and the medication is administered through the port. A bolus may be administered rapidly (with a fast depression of the syringe plunger) or may be administered slowly, over the course of a few minutes. The exact administration technique depends on the medication and other factors. In some cases, a bolus of plain IV solution (i.e. without medication added) is administered immediately after the bolus to further force the medicine into the bloodstream. This procedure is termed an "IV flush". Certain medications, such as potassium, are not able to be administered by IV push due to the extremely rapid onset of action and high level of effects.
=== Infusion ===
An infusion of medication may be used when it is desirable to have a constant blood concentration of a medication over time, such as with some antibiotics including beta-lactams. Continuous infusions, where the next infusion is begun immediately following the completion of the prior, may also be used to limit variation in drug concentration in the blood (i.e. between the peak drug levels and the trough drug levels). They may also be used instead of intermittent bolus injections for the same reason, such as with furosemide. Infusions can also be intermittent, in which case the medication is administered over a period of time, then stopped, and this is later repeated. Intermittent infusion may be used when there are concerns about the stability of medicine in solution for long periods of time (as is common with continuous infusions), or to enable the administration of medicines which would be incompatible if administered at the same time in the same IV line, for example vancomycin.
Failure to properly calculate and administer an infusion can result in adverse effects, termed infusion reactions. For this reason, many medications have a maximum recommended infusion rate, such as vancomycin and many monoclonal antibodies. These infusion reactions can be severe, such as in the case of vancomycin, where the reaction is termed "red man syndrome".
=== Secondary ===
Any additional medication to be administered intravenously at the same time as an infusion may be connected to the primary tubing; this is termed a secondary IV, or IV piggyback. This prevents the need for multiple IV access lines on the same person. When administering a secondary IV medication, the primary bag is held lower than the secondary bag so that the secondary medication can flow into the primary tubing, rather than fluid from the primary bag flowing into the secondary tubing. The fluid from the primary bag is needed to help flush any remaining medication from the secondary IV from the tubing. If a bolus or secondary infusion is intended for administration in the same line as a primary infusion, the molecular compatibility of the solutions must be considered. Secondary compatibility is generally referred to as "y-site compatibility", named after the shape of the tubing which has a port for bolus administration. Incompatibility of two fluids or medications can arise due to issues of molecular stability, changes in solubility, or degradation of one of the medications.
== Methods and equipment ==
=== Access ===
The simplest form of intravenous access is by passing a hollow needle through the skin directly into a vein. A syringe can be connected directly to this needle, which allows for a "bolus" dose to be administered. Alternatively, the needle may be placed and then connected to a length of tubing, allowing for an infusion to be administered.: 344–348 The type and location of venous access (i.e. a central line versus peripheral line, and in which vein the line is placed) can be affected by the potential for some medications to cause peripheral vasoconstriction, which limits circulation to peripheral veins.
A peripheral cannula is the most common intravenous access method utilized in hospitals, pre-hospital care, and outpatient medicine. This may be placed in the arm, commonly either the wrist or the median cubital vein at the elbow. A tourniquet may be used to restrict the venous drainage of the limb and make the vein bulge, making it easier to locate and place a line in a vein. When used, a tourniquet should be removed before injecting medication to prevent extravasation. The part of the catheter that remains outside the skin is called the connecting hub; it can be connected to a syringe or an intravenous infusion line, or capped with a heplock or saline lock, a needleless connection filled with a small amount of heparin or saline solution to prevent clotting, between uses of the catheter. Ported cannulae have an injection port on the top that is often used to administer medicine.: 349–354
The thickness and size of needles and catheters can be given in Birmingham gauge or French gauge. A Birmingham gauge of 14 is a very large cannula (used in resuscitation settings) and 24-26 is the smallest. The most common sizes are 16-gauge (midsize line used for blood donation and transfusion), 18- and 20-gauge (all-purpose line for infusions and blood draws), and 22-gauge (all-purpose pediatric line). 12- and 14-gauge peripheral lines are capable of delivering large volumes of fluid very fast, accounting for their popularity in emergency medicine. These lines are frequently called "large bores" or "trauma lines".: 188–191, 349
==== Peripheral lines ====
A peripheral intravenous line is inserted in peripheral veins, such as the veins in the arms, hands, legs and feet. Medication administered in this way travels through the veins to the heart, from where it is distributed to the rest of the body through the circulatory system. The size of the peripheral vein limits the amount and rate of medication which can be administered safely. A peripheral line consists of a short catheter inserted through the skin into a peripheral vein. This is usually in the form of a cannula-over-needle device, in which a flexible plastic cannula comes mounted over a metal trocar. Once the tip of the needle and cannula are placed, the cannula is advanced inside the vein over the trocar to the appropriate position and secured. The trocar is then withdrawn and discarded. Blood samples may also be drawn from the line directly after the initial IV cannula insertion.: 344–348
==== Central lines ====
A central line is an access method in which a catheter empties into a larger, more central vein (a vein within the torso), usually the superior vena cava, inferior vena cava or the right atrium of the heart. There are several types of central IV access, categorized based on the route the catheter takes from the outside of the body to the central vein output.: 17–22
==== Peripherally inserted central catheter ====
A peripherally inserted central catheter (also called a PICC line) is a type of central IV access which consists of a cannula inserted through a sheath into a peripheral vein and then carefully fed towards the heart, terminating at the superior vena cava or the right atrium. These lines are usually placed in peripheral veins in the arm, and may be placed using the Seldinger technique under ultrasound guidance. An X-ray is used to verify that the end of the cannula is in the right place if fluoroscopy was not used during the insertion. An EKG can also be used in some cases to determine if the end of the cannula is in the correct location.: Ch.1, 5, 6
==== Tunneled lines ====
A tunneled line is a type of central access which is inserted under the skin, and then travels a significant distance through surrounding tissue before reaching and penetrating the central vein. Using a tunneled line reduces the risk of infection as compared to other forms of access, as bacteria from the skin surface are not able to travel directly into the vein. These catheters are often made of materials that resist infection and clotting. Types of tunneled central lines include the Hickman line or Broviac catheter. A tunnelled line is an option for long term venous access necessary for hemodialysis in people with poor kidney function.
==== Implantable ports ====
An implanted port is a central line that does not have an external connector protruding from the skin for administration of medication. Instead, a port consists of a small reservoir covered with silicone rubber which is implanted under the skin, which then covers the reservoir. Medication is administered by injecting medication through the skin and the silicone port cover into the reservoir. When the needle is withdrawn, the reservoir cover reseals itself. A port cover is designed to function for hundreds of needle sticks during its lifetime. Ports may be placed in an arm or in the chest area.
=== Infusions ===
Equipment used to place and administer an IV line for infusion consists of a bag, usually hanging above the height of the person, and sterile tubing through which the medicine is administered. In a basic "gravity" IV, a bag is simply hung above the height of the person and the solution is pulled via gravity through a tube attached to a needle inserted into a vein. Without extra equipment, it is not possible to precisely control the rate of administration. For this reason, a setup may also incorporate a clamp to regulate flow. Some IV lines may be placed with "Y-sites", devices which enable a secondary solution to be administered through the same line (known as piggybacking). Some systems employ a drip chamber, which prevents air from entering the bloodstream (causing an air embolism), and allows visual estimation of flow rate of the solution.: 316–321, 344–348
Alternatively, an infusion pump allows precise control over the flow rate and total amount delivered. A pump is programmed based on the number and size of infusions being administered to ensure all medicine is fully administered without allowing the access line to run dry. Pumps are primarily utilized when a constant flow rate is important, or where changes in rate of administration would have consequences.: 316–321, 344–348
=== Techniques ===
To reduce pain associated with the procedure, medical staff may apply a topical local anaesthetic (such as EMLA or Ametop) to the skin of the chosen venipuncture area about 45 minutes beforehand.: 344–348
If the cannula is not inserted correctly, or the vein is particularly fragile and ruptures, blood may extravasate into the surrounding tissues; this situation is known as a blown vein or "tissuing". Using this cannula to administer medications causes extravasation of the drug, which can lead to edema, causing pain and tissue damage, and even necrosis depending on the medication. The person attempting to obtain the access must find a new access site proximal to the "blown" area to prevent extravasation of medications through the damaged vein. For this reason it is advisable to site the first cannula at the most distal appropriate vein.: 355–359
== Adverse effects ==
=== Pain ===
Placement of an intravenous line inherently causes pain when the skin is broken and is considered medically invasive. For this reason, when other forms of administration may suffice, intravenous therapy is usually not preferred. This includes the treatment of mild or moderate dehydration with oral rehydration therapy which is an option, as opposed to parenteral rehydration through an IV line. Children in emergency departments being treated for dehydration have better outcomes with oral treatment than intravenous therapy due to the pain and complications of an intravenous line. Cold spray may decrease the pain of putting in an IV.
Certain medications also have specific sensations of pain associated with their administration IV. This includes potassium, which when administered IV can cause a burning or painful sensation. The incidence of side effects specific to a medication can be affected by the type of access (peripheral versus central), the rate of administration, or the quantity of drug administered. When medications are administered too rapidly through an IV line, a set of vague symptoms such as redness or rash, fever, and others may occur; this is termed an "infusion reaction" and is prevented by decreasing the rate of administration of the medication. When vancomycin is involved, this is commonly termed "Red Man syndrome" after the rapid flushing which occurs after rapid administration.
=== Infection and inflammation ===
As placement of an intravenous line requires breaking the skin, there is a risk of infection. Skin-dwelling organisms such as coagulase-negative staphylococcus or Candida albicans may enter through the insertion site around the catheter, or bacteria may be accidentally introduced inside the catheter from contaminated equipment. Infection of an IV access site is usually local, causing easily visible swelling, redness, and fever. However, pathogens may also enter the bloodstream, causing sepsis, which can be sudden and life-threatening. A central IV line poses a higher risk of sepsis, as it can deliver bacteria directly into the central circulation. A line which has been in place for a longer period of time also increases the risk of infection.: 358, 373
Inflammation of the vein may also occur, called thrombophlebitis or simply phlebitis. This may be caused by infection, the catheter itself, or the specific fluids or medication being given. Repeated instances of phlebitis can cause scar tissue to build up along a vein. A peripheral IV line cannot be left in the vein indefinitely out of concern for the risk of infection and phlebitis, among other potential complications. However, recent studies have found that there is no increased risk of complications in those whose IVs were replaced only when clinically indicated versus those whose IVs were replaced routinely. If placed with proper aseptic technique, it is not recommended to change a peripheral IV line more frequently than every 72–96 hours.
Phlebitis is particularly common in intravenous drug users, and those undergoing chemotherapy, whose veins can become sclerotic and difficult to access over time, sometimes forming a hard, painful "venous cord". The presence of a cord is a cause of discomfort and pain associated with IV therapy, and makes it more difficult for an IV line to be placed as a line cannot be placed in an area with a cord.
=== Infiltration and extravasation ===
Infiltration occurs when a non-vesicant IV fluid or medication enters the surrounding tissue as opposed to the desired vein. It may occur when the vein itself ruptures, when the vein is damaged during insertion of the intravascular access device, or from increased vein porosity. Infiltration may also occur if the puncture of the vein by the needle becomes the path of least resistance—such as a cannula which has been left inserted, causing the vein to scar. It can also occur upon insertion of an IV line if a tourniquet is not promptly removed. Infiltration is characterized by coolness and pallor to the skin as well as localized swelling or edema. It is treated by removing the intravenous line and elevating the affected limb so the collected fluids drain away. Injections of hyaluronidase around the area can be used to speed the dispersal of the fluid/drug. Infiltration is one of the most common adverse effects of IV therapy and is usually not serious unless the infiltrated fluid is a medication damaging to the surrounding tissue, most commonly a vesicant or chemotherapeutic agent. In such cases, the infiltration is termed extravasation, and may cause necrosis.
=== Others ===
If the solutions administered are colder than the temperature of the body, induced hypothermia can occur. If the temperature change to the heart is rapid, ventricular fibrillation may result. Furthermore, if a solution which is not balanced in concentration is administered, a person's electrolytes may become imbalanced. In hospitals, regular blood tests may be used to proactively monitor electrolyte levels.
== History ==
=== Discovery and development ===
The first recorded attempt at administering a therapeutic substance via IV injection was in 1492, when Pope Innocent VIII fell ill and was administered blood from healthy individuals. If this occurred, the treatment did not work and resulted in the death of the donors while not healing the pope. This story is disputed by some, who claim that the idea of blood transfusions could not have been considered by the medical professionals at the time, or that a complete description of blood circulation was not published until over 100 years later. The story is attributed to potential errors in translation of documents from the time, as well as potentially an intentional fabrication, whereas others still consider it to be accurate. One of the leading medical history textbooks for medical and nursing students has claimed that the entire story was an anti-semitic fabrication.
In 1656 Sir Christopher Wren and Robert Boyle worked on the subject. As stated by Wren, "I Have Injected Wine and Ale in a liveing Dog into the Mass of Blood by a Veine, in good Quantities, till I have made him extremely drunk, but soon after he Pisseth it out." The dog survived, grew fat, and was later stolen from his owner. Boyle attributed authorship to Wren.
Richard Lower showed it was possible for blood to be transfused from animal to animal and from animal to man intravenously, a xenotransfusion. He worked with Edmund King to transfuse sheep's blood into a man who was mentally ill. Lower was interested in advancing science but also believed the man could be helped, either by the infusion of fresh blood or by the removal of old blood. It was difficult to find people who would agree to be transfused, but an eccentric scholar, Arthur Coga, consented and the procedure was carried out by Lower and King before the Royal Society on 23 November 1667. Transfusion gathered some popularity in France and Italy, but medical and theological debates arose, resulting in transfusion being prohibited in France.
There was virtually no recorded success with any attempts at injection therapy until the 1800s, when in 1831 Thomas Latta studied the use of IV fluid replacements for cholera treatment. The first solutions which saw widespread use for IV injections were simple "saline-like solutions", which were followed by experiments with various other liquids, including milk, sugar, honey, and egg yolk. In the 1830s, James Blundell, an English obstetrician, used intravenous administration of blood to treat women bleeding profusely during or after delivery. This predated the understanding of blood type, leading to unpredictable results.
=== Modern usage ===
Intravenous therapy was expanded by Italian physician Guido Baccelli in the late 1890s and further developed in the 1930s by Samuel Hirschfeld, Harold T. Hyman and Justine Johnstone Wanger but was not widely available until the 1950s. There was a time, roughly the 1910s–1920s, when fluid replacement that today would be done intravenously was likelier to be done with a Murphy drip, a rectal infusion; and IV therapy took years to increasingly displace that route. In the 1960s, the concept of providing a person's complete nutritional needs through an IV solution began to be seriously considered. The first parenteral nutrition supplementation consisted of hydrolyzed proteins and dextrose. This was followed in 1975 with the introduction of intravenous fat emulsions and vitamins which were added to form "total parenteral nutrition", or that which includes protein, fat, and carbohydrates.
== See also ==
== References ==
== Further reading ==
Royal College of Nursing, Standards for Infusion Therapy (Archive of the 4th edition (December 2016) via the Internet Wayback Machine)
== External links ==
Media related to Intravenous therapy at Wikimedia Commons | Wikipedia/Intravenous_therapy |
In pharmacology, the fibrates are a class of amphipathic carboxylic acids and esters. They are derivatives of fibric acid (phenoxyisobutyric acid). They are used for a range of metabolic disorders, mainly hypercholesterolemia (high cholesterol), and are therefore hypolipidemic agents.
== Medical uses ==
Fibrates improve atherogenic dyslipidemia characterized by high triglyceride and/or low HDL-C levels and elevated concentrations of small dense LDL particles, with or without high LDL-C levels. Fibrates may be compared to statin drugs, which reduce LDL-cholesterol (LDL-C) and have only limited effects on other lipid parameters. Clinical trials have shown that the combination of statins and fibrates results in a significantly greater reduction in LDL-C and triglyceride levels and greater increases in high-density lipoprotein cholesterol (HDL-C) compared with monotherapy with either drug. Fibrates are used in accessory therapy in many forms of hypercholesterolemia, but the combination of some fibrates (e.g., gemfibrozil) with statins is contraindicated due to an increased risk of rhabdomyolysis.
Fibrates stimulate peroxisome proliferator activated receptor (PPAR) alpha, which controls the expression of gene products that mediate the metabolism of triglycerides (TG) and high-density lipoprotein (HDL). As a result, synthesis of fatty acids, TG and VLDL is reduced, whilst that of lipoprotein lipase, which catabolises TG, is enhanced. In addition, production of Apo A1 and ATP binding cassette A1 is up-regulated, leading to increased reverse cholesterol transport via HDL. Consequently, fibrates reduce TG by up to 50% and increase HDL-C by up to 20%, but LDL-C changes are variable.
Fewer large-scale trials have been conducted with fibrates than with statins and the results are less conclusive, but reduced rates of cardiovascular disease have been reported with fibrate therapy in the subgroup of patients with low HDL-C levels and elevated TG (e.g. TG > 2.3 mmol/L (200 mg/dL)). Fibrates are usually well tolerated but share a similar side-effect profile to statins. In addition, they may increase the risk of cholelithiasis and prolong the action of anticoagulants. Accumulating evidence suggests that they may also have a protective effect against diabetic microvascular complications.
Clinical trials do support their use as monotherapy agents. Fibrates reduce the number of non-fatal heart attacks, but do not improve all-cause mortality and are therefore indicated only in those not tolerant to statins.
Although less effective in lowering LDL levels, the ability of fibrates to increase HDL and lower triglyceride levels seems to reduce insulin resistance when the dyslipidemia is associated with other features of the metabolic syndrome (hypertension and diabetes mellitus type 2). They are therefore used in many hyperlipidemias. Due to a rare paradoxical decrease in HDL-C seen in some patients on fenofibrate, as per US FDA label change, it is recommended that the HDL-C levels be checked within the first few months after initiation of fibrate therapy. If a severely depressed HDL-C level is detected, fibrate therapy should be withdrawn, and the HDL-C level monitored until it has returned to baseline.
== Side effects ==
Most fibrates can cause mild stomach upset and myopathy (muscle pain with CPK elevations). Fibrates decrease the synthesis of bile acid by down-regulation of cholesterol 7 alpha-hydroxylase and sterol 27-hydroxylase expression, therefore making it easier for cholesterol to precipitate and increasing the risk for gallstones.
In combination with statin drugs, fibrates cause an increased risk of rhabdomyolysis, idiosyncratic destruction of muscle tissue, leading to kidney failure. The less lipophilic statins are less prone to cause this reaction, and are probably safer to be combined with fibrates than the more lipophilic statins are.
Drug toxicity includes acute kidney injury.
== Pharmacology ==
Although used clinically since at least 1962, the mechanism of action of fibrates remained unelucidated until the 1990s, when it was discovered that fibrates activate peroxisome proliferator-activated receptors (PPARs), especially PPARα. The PPARs are a class of intracellular receptors that modulate carbohydrate and fat metabolism and adipose tissue differentiation.
Activating PPARs induces the transcription of a number of genes that facilitate lipid metabolism.
Fibrates are pharmacologically related to the thiazolidinediones, a novel class of anti-diabetic drugs that also act on PPARs (more specifically PPARγ)
Fibrates are a substrate of (metabolized by) CYP3A4.
Fibrates have been shown to extend lifespan in the roundworm C. elegans.
== Members ==
== See also ==
Statin
Hypertriglyceridemia
== References == | Wikipedia/Fibrate |
A scanning electron microscope (SEM) is a type of electron microscope that produces images of a sample by scanning the surface with a focused beam of electrons. The electrons interact with atoms in the sample, producing various signals that contain information about the surface topography and composition. The electron beam is scanned in a raster scan pattern, and the position of the beam is combined with the intensity of the detected signal to produce an image. In the most common SEM mode, secondary electrons emitted by atoms excited by the electron beam are detected using a secondary electron detector (Everhart–Thornley detector). The number of secondary electrons that can be detected, and thus the signal intensity, depends, among other things, on specimen topography. Some SEMs can achieve resolutions better than 1 nanometer.
Specimens are observed in high vacuum in a conventional SEM, or in low vacuum or wet conditions in a variable pressure or environmental SEM, and at a wide range of cryogenic or elevated temperatures with specialized instruments.
== History ==
An account of the early history of scanning electron microscopy has been presented by McMullan. Although Max Knoll produced a photo with a 50 mm object-field-width showing channeling contrast by the use of an electron beam scanner, it was Manfred von Ardenne who in 1937 invented a microscope with high resolution by scanning a very small raster with a demagnified and finely focused electron beam. In the same year, Cecil E. Hall also completed the construction of the first emission microscope in North America, just two years after being tasked by his supervisor, E. F. Burton at the University of Toronto. Ardenne applied scanning of the electron beam in an attempt to surpass the resolution of the transmission electron microscope (TEM), as well as to mitigate substantial problems with chromatic aberration inherent to real imaging in the TEM. He further discussed the various detection modes, possibilities and theory of SEM, together with the construction of the first high resolution SEM. Further work was reported by Zworykin's group, followed by the Cambridge groups in the 1950s and early 1960s headed by Charles Oatley, all of which finally led to the marketing of the first commercial instrument by Cambridge Scientific Instrument Company as the "Stereoscan" in 1965, which was delivered to DuPont.
== Principles and capacities ==
The signals used by an SEM to make an image result from interactions between the electron beam and atoms at various depths within the sample. Various types of signals are produced including secondary electrons (SE), reflected or back-scattered electrons (BSE), characteristic X-rays and light (cathodoluminescence) (CL), absorbed current (specimen current) and transmitted electrons. Secondary electron detectors are standard equipment in all SEMs, but it is rare for a single machine to have detectors for all other possible signals.
Secondary electrons have very low energies on the order of 50 eV, which limits their mean free path in solid matter. Consequently, SEs can only escape from the top few nanometers of the surface of a sample. The signal from secondary electrons tends to be highly localized at the point of impact of the primary electron beam, making it possible to collect images of the sample surface with a resolution of below 1 nm. Back-scattered electrons (BSE) are beam electrons that are reflected from the sample by elastic scattering. Since they have much higher energy than SEs, they emerge from deeper locations within the specimen and, consequently, the resolution of BSE images is less than SE images. However, BSE are often used in analytical SEM, along with the spectra made from the characteristic X-rays, because the intensity of the BSE signal is strongly related to the atomic number (Z) of the specimen. BSE images can provide information about the distribution, but not the identity, of different elements in the sample. In samples predominantly composed of light elements, such as biological specimens, BSE imaging can image colloidal gold immuno-labels of 5 or 10 nm diameter, which would otherwise be difficult or impossible to detect in secondary electron images. Characteristic X-rays are emitted when the electron beam removes an inner shell electron from the sample, causing a higher-energy electron to fill the shell and release energy. The energy or wavelength of these characteristic X-rays can be measured by Energy-dispersive X-ray spectroscopy or Wavelength-dispersive X-ray spectroscopy and used to identify and measure the abundance of elements in the sample and map their distribution.
Due to the very narrow electron beam, SEM micrographs have a large depth of field yielding a characteristic three-dimensional appearance useful for understanding the surface structure of a sample. This is exemplified by the micrograph of pollen shown above. A wide range of magnifications is possible, from about 10 times (about equivalent to that of a powerful hand-lens) to more than 500,000 times, about 250 times the magnification limit of the best light microscopes.
== Sample preparation ==
SEM samples have to be small enough to fit on the specimen stage, and may need special preparation to increase their electrical conductivity and to stabilize them, so that they can withstand the high vacuum conditions and the high energy beam of electrons. Samples are generally mounted rigidly on a specimen holder or stub using a conductive adhesive. SEM is used extensively for defect analysis of semiconductor wafers, and manufacturers make instruments that can examine any part of a 300 mm semiconductor wafer. Many instruments have chambers that can tilt an object of that size to 45° and provide continuous 360° rotation.
Nonconductive specimens collect charge when scanned by the electron beam, and especially in secondary electron imaging mode, this causes scanning faults and other image artifacts. For conventional imaging in the SEM, specimens must be electrically conductive, at least at the surface, and electrically grounded to prevent the accumulation of electrostatic charge. Metal objects require little special preparation for SEM except for cleaning and conductively mounting to a specimen stub. Non-conducting materials are usually coated with an ultrathin coating of electrically conducting material, deposited on the sample either by low-vacuum sputter coating, electroless deposition or by high-vacuum evaporation. Conductive materials in current use for specimen coating include gold, gold/palladium alloy, platinum, iridium, tungsten, chromium, osmium, and graphite. Coating with heavy metals may increase signal/noise ratio for samples of low atomic number (Z). The improvement arises because secondary electron emission for high-Z materials is enhanced.
An alternative to coating for some biological samples is to increase the bulk conductivity of the material by impregnation with osmium using variants of the OTO staining method (O-osmium tetroxide, T-thiocarbohydrazide, O-osmium).
Nonconducting specimens may be imaged without coating using an environmental SEM (ESEM) or low-voltage mode of SEM operation. In ESEM instruments the specimen is placed in a relatively high-pressure chamber and the electron optical column is differentially pumped to keep vacuum adequately low at the electron gun. The high-pressure region around the sample in the ESEM neutralizes charge and provides an amplification of the secondary electron signal. Low-voltage SEM is typically conducted in an instrument with a field emission guns (FEG) which is capable of producing high primary electron brightness and small spot size even at low accelerating potentials. To prevent charging of non-conductive specimens, operating conditions must be adjusted such that the incoming beam current is equal to sum of outgoing secondary and backscattered electron currents, a condition that is most often met at accelerating voltages of 0.3–4 kV.
Embedding in a resin with further polishing to a mirror-like finish can be used for both biological and materials specimens when imaging in backscattered electrons or when doing quantitative X-ray microanalysis.
The main preparation techniques are not required in the environmental SEM outlined below, but some biological specimens can benefit from fixation.
=== Biological samples ===
Since the SEM specimen chamber is under high vacuum, a SEM specimen must be completely dry or cryogenically cooled. Hard, dry materials such as wood, bone, feathers, dried insects, or shells (including egg shells) can be examined with little further treatment, but living cells and tissues and whole, soft-bodied organisms require chemical fixation to preserve and stabilize their structure.
Fixation is usually performed by incubation in a solution of a buffered chemical fixative, such as glutaraldehyde, sometimes in combination with formaldehyde and other fixatives, and optionally followed by postfixation with osmium tetroxide. The fixed tissue is then dehydrated. Because air-drying causes collapse and shrinkage, this is commonly achieved by replacement of water in the cells with organic solvents such as ethanol or acetone, and replacement of these solvents in turn with a transitional fluid such as liquid carbon dioxide by critical point drying. The carbon dioxide is finally removed while in a supercritical state, so that no gas–liquid interface is present within the sample during drying.
The dry specimen is usually mounted on a specimen stub using an adhesive such as epoxy resin or electrically conductive double-sided adhesive tape, and sputter-coated with gold or gold/palladium alloy before examination in the microscope. Samples may be sectioned (with a microtome) if information about the organism's internal ultrastructure is to be exposed for imaging.
If the SEM is equipped with a cold stage for cryo microscopy, cryofixation may be used and low-temperature scanning electron microscopy performed on the cryogenically fixed specimens. Cryo-fixed specimens may be cryo-fractured under vacuum in a special apparatus to reveal internal structure, sputter-coated and transferred onto the SEM cryo-stage while still frozen. Low-temperature scanning electron microscopy (LT-SEM) is also applicable to the imaging of temperature-sensitive materials such as ice and fats.
Freeze-fracturing, freeze-etch or freeze-and-break is a preparation method particularly useful for examining lipid membranes and their incorporated proteins in "face on" view. The preparation method reveals the proteins embedded in the lipid bilayer.
=== Materials ===
Back-scattered electron imaging, quantitative X-ray analysis, and X-ray mapping of specimens often requires grinding and polishing the surfaces to an ultra-smooth surface. Specimens that undergo WDS or EDS analysis are often carbon-coated. In general, metals are not coated prior to imaging in the SEM because they are conductive and provide their own pathway to ground. Fractography is the study of fractured surfaces that can be done on a light microscope or, commonly, on an SEM. The fractured surface is cut to a suitable size, cleaned of any organic residues, and mounted on a specimen holder for viewing in the SEM. Integrated circuits may be cut with a focused ion beam (FIB) or other ion beam milling instrument for viewing in the SEM. The SEM in the first case may be incorporated into the FIB, enabling high-resolution imaging of the result of the process. Metals, geological specimens, and integrated circuits all may also be chemically polished for viewing in the SEM. Special high-resolution coating techniques are required for high-magnification imaging of inorganic thin films.
== Scanning process and image formation ==
In a typical SEM, an electron beam is thermionically emitted from an electron gun fitted with a tungsten filament cathode. Tungsten is normally used in thermionic electron guns because it has the highest melting point and lowest vapor pressure of all metals, thereby allowing it to be electrically heated for electron emission, and because of its low cost. Other types of electron emitters include lanthanum hexaboride (LaB6) cathodes, which can be used in a standard tungsten filament SEM if the vacuum system is upgraded, or field emission guns (FEG), which may be of the cold-cathode type using tungsten single crystal emitters or the thermally assisted Schottky type, that use emitters of tungsten single crystals coated in zirconium oxide.
The electron beam, which typically has an energy ranging from 0.2 keV to 40 keV, is focused by one or two condenser lenses to a spot about 0.4 nm to 5 nm in diameter. The beam passes through pairs of scanning coils or pairs of deflector plates in the electron column, typically in the final lens, which deflect the beam in the x and y axes so that it scans in a raster fashion over a rectangular area of the sample surface.
When the primary electron beam interacts with the sample, the electrons lose energy by repeated random scattering and absorption within a teardrop-shaped volume of the specimen known as the interaction volume, which extends from less than 100 nm to approximately 5 μm into the surface. The size of the interaction volume depends on the electron's landing energy, the atomic number of the specimen, and the specimen's density. The energy exchange between the electron beam and the sample results in the reflection of high-energy electrons by elastic scattering, the emission of secondary electrons by inelastic scattering, and the emission of electromagnetic radiation, each of which can be detected by specialized detectors. The beam current absorbed by the specimen can also be detected and used to create images of the distribution of specimen current. Electronic amplifiers of various types are used to amplify the signals, which are displayed as variations in brightness on a computer monitor (or, for vintage models, on a cathode-ray tube). Each pixel of computer video memory is synchronized with the position of the beam on the specimen in the microscope, and the resulting image is, therefore, a distribution map of the intensity of the signal being emitted from the scanned area of the specimen. Older microscopes captured images on film, but most modern instruments collect digital images.
=== Magnification ===
Magnification in an SEM can be controlled over a range of about 6 orders of magnitude from about 10 to 3,000,000 times. Unlike optical and transmission electron microscopes, image magnification in an SEM is not a function of the power of the objective lens. SEMs may have condenser and objective lenses, but their function is to focus the beam to a spot, and not to image the specimen. Provided the electron gun can generate a beam with a sufficiently small diameter, an SEM could in principle work entirely without condenser or objective lenses. However, it might not be very versatile or achieve very high resolution. In an SEM, as in scanning probe microscopy, magnification results from the ratio of the raster on the display device and dimensions of the raster on the specimen. Assuming that the display screen has a fixed size, higher magnification results from reducing the size of the raster on the specimen, and vice versa. Magnification is therefore controlled by the current supplied to the x, y scanning coils, or the voltage supplied to the x, y deflector plates, and not by objective lens power.
== Detection of secondary electrons ==
The most common imaging mode collects low-energy (<50 eV) secondary electrons that are ejected from conduction or valence bands of the specimen atoms by inelastic scattering interactions with beam electrons. Due to their low energy, these electrons originate from within a few nanometers below the sample surface. The electrons are detected by an Everhart–Thornley detector, which is a type of collector-scintillator-photomultiplier system. The secondary electrons are first collected by attracting them towards an electrically biased grid at about +400 V, and then further accelerated towards a phosphor or scintillator positively biased to about +2,000 V. The accelerated secondary electrons are now sufficiently energetic to cause the scintillator to emit flashes of light (cathodoluminescence), which are conducted to a photomultiplier outside the SEM column via a light pipe and a window in the wall of the specimen chamber. The amplified electrical signal output by the photomultiplier is displayed as a two-dimensional intensity distribution that can be viewed and photographed on an analogue video display, or subjected to analog-to-digital conversion and displayed and saved as a digital image. This process relies on a raster-scanned primary beam. The brightness of the signal depends on the number of secondary electrons reaching the detector. If the beam enters the sample perpendicular to the surface, then the activated region is uniform about the axis of the beam and a certain number of electrons "escape" from within the sample. As the angle of incidence increases, the interaction volume increases and the "escape" distance of one side of the beam decreases, resulting in more secondary electrons being emitted from the sample. Thus steep surfaces and edges tend to be brighter than flat surfaces, which results in images with a well-defined, three-dimensional appearance. Using the signal of secondary electrons image resolution less than 0.5 nm is possible.
== Detection of backscattered electrons ==
Backscattered electrons (BSE) consist of high-energy electrons originating in the electron beam, that are reflected or back-scattered out of the specimen interaction volume by elastic scattering interactions with specimen atoms. Since heavy elements (high atomic number) backscatter electrons more strongly than light elements (low atomic number), and thus appear brighter in the image, BSEs are used to detect contrast between areas with different chemical compositions. The Everhart–Thornley detector, which is normally positioned to one side of the specimen, is inefficient for the detection of backscattered electrons because few such electrons are emitted in the solid angle subtended by the detector, and because the positively biased detection grid has little ability to attract the higher energy BSE. Dedicated backscattered electron detectors are positioned above the sample in a "doughnut" type arrangement, concentric with the electron beam, maximizing the solid angle of collection. BSE detectors are usually either of scintillator or of semiconductor types. When all parts of the detector are used to collect electrons symmetrically about the beam, atomic number contrast is produced. However, strong topographic contrast is produced by collecting back-scattered electrons from one side above the specimen using an asymmetrical, directional BSE detector; the resulting contrast appears as illumination of the topography from that side. Semiconductor detectors can be made in radial segments that can be switched in or out to control the type of contrast produced and its directionality.
Backscattered electrons can also be used to form an electron backscatter diffraction (EBSD) image that can be used to determine the crystallographic structure of the specimen.
== Beam-injection analysis of semiconductors ==
The nature of the SEM's probe, energetic electrons, makes it uniquely suited to examining the optical and electronic properties of semiconductor materials. The high-energy electrons from the SEM beam will inject charge carriers into the semiconductor. Thus, beam electrons lose energy by promoting electrons from the valence band into the conduction band, leaving behind holes.
In a direct bandgap material, recombination of these electron-hole pairs will result in cathodoluminescence; if the sample contains an internal electric field, such as is present at a p-n junction, the SEM beam injection of carriers will cause electron beam induced current (EBIC) to flow. Cathodoluminescence and EBIC are referred to as "beam-injection" techniques, and are very powerful probes of the optoelectronic behavior of semiconductors, in particular for studying nanoscale features and defects.
== Cathodoluminescence ==
Cathodoluminescence, the emission of light when atoms excited by high-energy electrons return to their ground state, is analogous to UV-induced fluorescence, and some materials such as zinc sulfide and some fluorescent dyes, exhibit both phenomena. Over the last decades, cathodoluminescence was most commonly experienced as the light emission from the inner surface of the cathode-ray tube in television sets and computer CRT monitors. In the SEM, CL detectors either collect all light emitted by the specimen or can analyse the wavelengths emitted by the specimen and display an emission spectrum or an image of the distribution of cathodoluminescence emitted by the specimen in real color.
== X-ray microanalysis ==
Characteristic X-rays that are produced by the interaction of electrons with the sample may also be detected in an SEM equipped for energy-dispersive X-ray spectroscopy or wavelength dispersive X-ray spectroscopy. Analysis of the x-ray signals may be used to map the distribution and estimate the abundance of elements in the sample.
== Complementary Techniques ==
Many SEM-based research studies are supported by complementary nanoscale techniques such as atomic force microscopy (AFM) and its electrical imaging modes. These methods provide insights that go beyond surface morphology. For example, AFM can probe the sample’s surface topography at the nanometer scale using a sharp tip in contact or tapping mode. Conductive AFM (C-AFM) enables mapping of local electrical conductivity, useful in studying resistive switching materials and semiconductors. Kelvin probe force microscopy (KPFM) measures surface potential variations, which is valuable for analyzing charge distributions in electronic or photovoltaic materials. When used alongside SEM, these techniques offer a comprehensive understanding of both structural and functional properties of materials.
== Resolution of the SEM ==
A SEM is not a camera and the detector is not continuously image-forming like a CCD array or film. Unlike in an optical system, the resolution is not limited by the diffraction limit, fineness of lenses or mirrors or detector array resolution. The focusing optics can be large and coarse, and the SE detector is fist-sized and simply detects current. Instead, the spatial resolution of the SEM depends on the size of the electron spot, which in turn depends on both the wavelength of the electrons and the electron-optical system that produces the scanning beam. The resolution is also limited by the size of the interaction volume, the volume of specimen material that interacts with the electron beam. The spot size and the interaction volume are both large compared to the distances between atoms, so the resolution of the SEM is not high enough to image individual atoms, as is possible with a transmission electron microscope (TEM). The SEM has compensating advantages, though, including the ability to image a comparatively large area of the specimen; the ability to image bulk materials (not just thin films or foils); and the variety of analytical modes available for measuring the composition and properties of the specimen. Depending on the instrument, the resolution can fall somewhere between less than 1 nm and 20 nm. As of 2009, The world's highest resolution conventional (≤30 kV) SEM can reach a point resolution of 0.4 nm using a secondary electron detector.
== Environmental SEM ==
Conventional SEM requires samples to be imaged under vacuum, because a gas atmosphere rapidly spreads and attenuates electron beams. As a consequence, samples that produce a significant amount of vapour, e.g. wet biological samples or oil-bearing rock, must be either dried or cryogenically frozen. Processes involving phase transitions, such as the drying of adhesives or melting of alloys, liquid transport, chemical reactions, and solid-air-gas systems, in general cannot be observed with conventional high-vacuum SEM. In environmental SEM (ESEM), the chamber is evacuated of air, but water vapor is retained near its saturation pressure, and the residual pressure remains relatively high. This allows the analysis of samples containing water or other volatile substances. With ESEM, observations of living insects have been possible.
The first commercial development of the ESEM in the late 1980s allowed samples to be observed in low-pressure gaseous environments (e.g. 1–50 Torr or 0.1–6.7 kPa) and high relative humidity (up to 100%). This was made possible by the development of a secondary-electron detector capable of operating in the presence of water vapour and by the use of pressure-limiting apertures with differential pumping in the path of the electron beam to separate the vacuum region (around the gun and lenses) from the sample chamber. The first commercial ESEMs were produced by the ElectroScan Corporation in USA in 1988. ElectroScan was taken over by Philips (who later sold their electron-optics division to FEI Company) in 1996.
ESEM is especially useful for non-metallic and biological materials because coating with carbon or gold is unnecessary. Uncoated plastics and elastomers can be routinely examined, as can uncoated biological samples. This is useful because coating can be difficult to reverse, may conceal small features on the surface of the sample and may reduce the value of the results obtained. X-ray analysis is difficult with a coating of a heavy metal, so carbon coatings are routinely used in conventional SEMs, but ESEM makes it possible to perform X-ray microanalysis on uncoated non-conductive specimens; however some specific for ESEM artifacts are introduced in X-ray analysis. ESEM may be the preferred for electron microscopy of unique samples from criminal or civil actions, where forensic analysis may need to be repeated by several different experts. It is possible to study specimens in liquid with ESEM or with other liquid-phase electron microscopy methods.
== Transmission SEM ==
The SEM can also be used in transmission mode by simply incorporating an appropriate detector below a thin specimen section. Detectors are available for bright field, dark field, as well as segmented detectors for mid-field to high angle annular dark-field. Despite the difference in instrumentation, this technique is still commonly referred to as scanning transmission electron microscopy (STEM).
== SEM in Forensic Science ==
The SEM is used often in Forensic Science for magnified analysis of microscopic things such as diatoms and gunshot residue. Because SEM is a nondestructive force on the sample, it can be used to analyze evidence without damaging it. The SEM shoots a beam of high energy electrons to the sample which bounce off of the sample without changing or destroying it. This is great when it comes to analyzing diatoms. When a person dies by drowning, they inhale the water which causes what is in the water (diatoms) to get in the blood stream, brain, kidneys, and more. These diatoms in the body can be magnified with the SEM to determine the type of diatoms which aid in understanding how and where the person died. By using the images produced by the SEM, forensic scientists can compare diatoms types to confirm the body of water a person died in.
Gunshot residue (GSR) analysis can be done with many different analytical instruments, but SEM is a common way to analyze inorganic compounds because of the way it can closely analyze the types of elements (mostly metals) through its three detectors: backscatter electron detector, secondary electron detector, and X-ray detector. GSR can be collected from the crime scene, victim, or shooter and analyzed with the SEM. This can help scientists determine proximity and or contact with the discharged firearm.
== Color in SEM ==
Electron microscopes do not naturally produce color images. A secondary electron detector produces a single value per pixel that corresponds to the number of electrons received by the detector during the short period of time when the beam is targeted to the (x, y) pixel position. For each pixel, this single value is represented by a grey level, forming a monochrome image. However, several methods can used to get color electron microscopy images.
=== False color using a single detector ===
On compositional images of flat surfaces (typically BSE):
The easiest way to get color is to replace each grey level with an arbitrary color, using a color look-up table. This method is known as false color imaging and can help to distinguish phases of the sample with similar properties or composition.
On textured-surface images:
As an alternative to simply replacing each grey level by a color, a sample observed by an oblique beam allows researchers to create an approximative topography image (see further section "Photometric 3D rendering from a single SEM image"). Such topography can then be processed by 3D-rendering algorithms for a more natural rendering of the surface texture.
=== SEM image coloring ===
Very often, published SEM images are artificially colored. This may be done for aesthetic effect, to clarify structure or to add a realistic appearance to the sample and generally does not add information about the specimen.
Coloring may be performed manually with photo-editing software, or semi-automatically with dedicated software using feature-detection or object-oriented segmentation.
=== Color built using multiple electron detectors ===
In some configurations more information is gathered per pixel, often by the use of multiple detectors.
As a common example, secondary electron and backscattered electron detectors are superimposed and a color is assigned to each of the images captured by each detector, with a result of a combined color image where colors are related to the density of the components. This method is known as density-dependent color SEM (DDC-SEM). Micrographs produced by DDC-SEM retain topographical information, which is better captured by the secondary electrons detector and combine it to the information about density, obtained by the backscattered electron detector.
=== Analytical signals based on generated photons ===
Measurement of the energy of photons emitted from the specimen is a common method to get analytical capabilities. Examples are the energy-dispersive X-ray spectroscopy (EDS) detectors used in elemental analysis and cathodoluminescence microscope (CL) systems that analyse the intensity and spectrum of electron-induced luminescence in (for example) geological specimens. In SEM systems using these detectors it is common to color code these extra signals and superimpose them in a single color image, so that differences in the distribution of the various components of the specimen can be seen clearly and compared. Optionally, the standard secondary electron image can be merged with the one or more compositional channels, so that the specimen's structure and composition can be compared. Such images can be made while maintaining the full integrity of the original signal data, which is not modified in any way.
== 3D in SEM ==
SEMs do not naturally provide 3D images contrary to SPMs. However 3D data can be obtained using an SEM with different methods as follows.
=== 3D SEM reconstruction from a stereo pair ===
photogrammetry is the most metrologically accurate method to bring the third dimension to SEM images. Contrary to photometric methods (next paragraph), photogrammetry calculates absolute heights using triangulation methods. The drawbacks are that it works only if there is a minimum texture, and it requires two images to be acquired from two different angles, which implies the use of a tilt stage. (Photogrammetry is a software operation that calculates the shift (or "disparity") for each pixel, between the left image and the right image of the same pair. Such disparity reflects the local height).
=== Photometric 3D SEM reconstruction from a four-quadrant detector by "shape from shading" ===
This method typically uses a four-quadrant BSE detector (alternatively for one manufacturer, a 3-segment detector). The microscope produces four images of the same specimen at the same time, so no tilt of the sample is required. The method gives metrological 3D dimensions as far as the slope of the specimen remains reasonable. Most SEM manufacturers now (2018) offer such a built-in or optional four-quadrant BSE detector, together with proprietary software to calculate a 3D image in real time.
Other approaches use more sophisticated (and sometimes GPU-intensive) methods like the optimal estimation algorithm and offer much better results at the cost of high demands on computing power.
In all instances, this approach works by integration of the slope, so vertical slopes and overhangs are ignored; for instance, if an entire sphere lies on a flat, little more than the upper hemisphere is seen emerging above the flat, resulting in wrong altitude of the sphere apex. The prominence of this effect depends on the angle of the BSE detectors with respect to the sample, but these detectors are usually situated around (and close to) the electron beam, so this effect is very common.
=== Photometric 3D rendering from a single SEM image ===
This method requires an SEM image obtained in oblique low angle lighting. The grey-level is then interpreted as the slope, and the slope integrated to restore the specimen topography. This method is interesting for visual enhancement and the detection of the shape and position of objects; however the vertical heights cannot usually be calibrated, contrary to other methods such as photogrammetry.
=== Other types of 3D SEM reconstruction ===
Inverse reconstruction using electron-material interactive models
Multi-Resolution reconstruction using single 2D File: High-quality 3D imaging may be an ultimate solution for revealing the complexities of any porous media, but acquiring them is costly and time-consuming. High-quality 2D SEM images, on the other hand, are widely available. Recently, a novel three-step, multiscale, multiresolution reconstruction method is presented that directly uses 2D images in order to develop 3D models. This method, based on a Shannon Entropy and conditional simulation, can be used for most of the available stationary materials and can build various stochastic 3D models just using a few thin sections.
Ion-abrasion SEM (IA-SEM) is a method of nanoscale 3D imaging that uses a focused beam of gallium to repeatedly abrade the specimen surface 20 nanometres at a time. Each exposed surface is then scanned to compile a 3D image.
=== Applications of 3D SEM ===
One possible application is measuring the roughness of ice crystals. This method can combine variable-pressure environmental SEM and the 3D capabilities of the SEM to measure roughness on individual ice crystal facets, convert it into a computer model and run further statistical analysis on the model. Other measurements include fractal dimension, examining fracture surface of metals, characterization of materials, corrosion measurement, and dimensional measurements at the nano scale (step height, volume, angle, flatness, bearing ratio, coplanarity, etc.).
SEM is also used by art conservationists to discern threats to paintings' surface stability due to aging, such as the formations of complexes of zinc ions with fatty acids. Forensic scientists use SEM to detect art forgeries.
== Gallery of SEM images ==
The following are examples of images taken using an SEM.
== See also ==
== References ==
== External links ==
General
HowStuffWorks – How Scanning Electron Microscopes Work
Learn to use an SEM – An online learning environment for people wanting to use an SEM. Provided by Microscopy Australia
Virtual SEM – sparkler – an interactive simulation of a scanning electron microscope (SEM)
Multichannel color SEM imaging – and with BSE
Video on the scanning electron microscope, Karlsruhe University of Applied Sciences
Animations and explanations on various types of microscopes including electron microscopes (Université Paris Sud)
History
Environmental Scanning Electron Microscope (ESEM) history
Images
Rippel Electron Microscope Facility Archived 19 March 2007 at the Wayback Machine Many dozens of (mostly biological) SEM images from Dartmouth College.
Lanthanoid staining SEM images from Research Institute of Eye Diseases, Moscow. | Wikipedia/Scanning_electron_micrograph |
Experimental cancer treatments are mainstream medical therapies intended to treat cancer by improving on, supplementing or replacing conventional methods (surgery, chemotherapy, radiation, and immunotherapy). However, researchers are still trying to determine whether these treatments are safe and effective treatments. Experimental cancer treatments are normally available only to people who participate in formal research programs, which are called clinical trials. Occasionally, a seriously ill person may be able to access an experimental drug through an expanded access program. Some of the treatments have regulatory approval for treating other conditions. Health insurance and publicly funded health care programs normally refuse to pay for experimental cancer treatments.
The entries listed below vary between theoretical therapies to unproven controversial therapies. Many of these treatments are alleged to help against only specific forms of cancer. It is not a list of treatments widely available at hospitals.
== Studying cancer treatments ==
The twin goals of research are to determine whether the treatment actually works (called efficacy) and whether it is sufficiently safe. Regulatory processes attempt to balance the potential benefits with the potential harms, so that people given the treatment are more likely to benefit from it than to be harmed by it.
Medical research for cancer begins much like research for any disease. In organized studies of new treatments for cancer, the pre-clinical development of drugs, devices, and techniques begins in laboratories, either with isolated cells or in small animals, most commonly rats or mice. In other cases, the proposed treatment for cancer is already in use for some other medical condition, in which case more is known about its safety and potential efficacy.
Clinical trials are the study of treatments in humans. The first-in-human tests of a potential treatment are called Phase I studies. Early clinical trials typically enroll a very small number of patients, and the purpose is to identify major safety issues and the maximum tolerated dose, which is the highest dose that does not produce serious or fatal adverse effects. The dose given in these trials may be far too small to produce any useful effect. In most research, these early trials may involve healthy people, but cancer studies normally enroll only people with relatively severe forms of the disease in this stage of testing. On average, 95% of the participants in these early trials receive no benefit, but all are exposed to the risk of adverse effects. Most participants show signs of optimism bias (the irrational belief that they will beat the odds).
Later studies, called Phase II and Phase III studies, enroll more people, and the goal is to determine whether the treatment actually works. Phase III studies are frequently randomized controlled trials, with the experimental treatment being compared to the current best available treatment rather than to a placebo. In some cases, the Phase III trial provides the best available treatment to all participants, in addition to some of the patients receiving the experimental treatment.
== Bacterial treatments ==
Chemotherapeutic drugs have a hard time penetrating tumors to kill them at their core because these cells may lack a good blood supply. Researchers have been using anaerobic bacteria, such as Clostridium novyi, to consume the interior of oxygen-poor tumours. These should then die when they come in contact with the tumor's oxygenated sides, meaning they would be harmless to the rest of the body. A major problem has been that bacteria do not consume all parts of the malignant tissue. However, combining the therapy with chemotherapeutic treatments can help to solve this problem.
Another strategy is to use anaerobic bacteria that have been transformed with an enzyme that can convert a non-toxic prodrug into a toxic drug. With the proliferation of the bacteria in the necrotic and hypoxic areas of the tumor, the enzyme is expressed solely in the tumor. Thus, a systemically applied prodrug is metabolised to the toxic drug only in the tumor. This has been demonstrated to be effective with the nonpathogenic anaerobe Clostridium sporogenes.
== Drug therapies ==
=== HAMLET (human alpha-lactalbumin made lethal to tumor cells) ===
HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a molecular complex derived from human breast milk that kills tumor cells by a process resembling programmed cell death (apoptosis). As of 2008, it had been tested in humans with skin papillomas and bladder cancer.
=== p53 activation therapy ===
Several drug therapies are being developed based on p53, the tumour suppressor gene that protects the cell in response to damage and stress. It is analogous to deciding what to do with a damaged car: p53 brings everything to a halt, and then decides whether to fix the cell or, if the cell is beyond repair, to destroy the cell. This protective function of p53 is disabled in most cancer cells, allowing them to multiply without check. Restoration of p53 activity in tumours (where possible) has been shown to inhibit tumour growth and can even shrink the tumour.
As p53 protein levels are usually kept low, one could block its degradation and allow large amounts of p53 to accumulate, thus stimulating p53 activity and its antitumour effects. Drugs that utilize this mechanism include nutlin and MI-219, which are both in phase I clinical trials. As of 2009, there are also other drugs that are still in the preclinical stage of testing, such as RITA and MITA.
=== BI811283 ===
BI811283 is a small molecule inhibitor of the aurora B kinase protein being developed by Boehringer Ingelheim for use as an anti-cancer agent. As of 2010, BI 811283 is currently in the early stages of clinical development and is undergoing first-in-human trials in patients with solid tumors and Acute Myeloid Leukaemia.
=== Itraconazole ===
Itraconazole, sometimes abbreviated ITZ, is an antifungal medication used to treat a number of fungal infections. Recent research works suggest itraconazole (ITZ) could also be used in the treatment of cancer by inhibiting the hedgehog pathway in a similar way to Sonidegib.
=== Selective androgen receptor modulators ===
The majority of breast cancers are androgen receptor (AR) positive and SARMs may help treat these cancers, although promising results have only been obtained with cancers that are both estrogen receptor (ER) positive and AR positive. Anabolic androgenic steroids (AAS) were historically used successfully to treat AR positive breast cancer, but were phased out after the development of anti-estrogen therapies, due to androgenic side effects and concerns about aromatization to estrogen. SARMs have some of the same therapeutic effects as AAS, but fewer side effects, and they cannot be aromatized. Although a trial on AR positive triple negative breast cancer was ended early due to lack of efficacy, ostarine showed benefits in some patients with ER+, AR+ metastatic breast cancer in a phase II study. In patients with more than 40 percent AR positivity as determined by immunohistochemistry, the clinical benefit rate (CBR) was 80 percent and the objective response rate (ORR) was 48 percent—which was considered promising given that the patients had advanced disease and had been heavily pretreated. In 2022, the FDA granted fast track designation to ostarine for AR+, ER+, HER2- metastatic breast cancer. SARMs have also shown antitumor effects in prostate cancer.
== Gene therapy ==
Introduction of tumor suppressor genes into rapidly dividing cells has been thought to slow down or arrest tumor growth. Adenoviruses are a commonly utilized vector for this purpose. Much research has focused on the use of adenoviruses that cannot reproduce, or reproduce only to a limited extent, within the patient to ensure safety via the avoidance of cytolytic destruction of noncancerous cells infected with the vector. However, new studies focus on adenoviruses that can be permitted to reproduce, and destroy cancerous cells in the process, since the adenoviruses' ability to infect normal cells is substantially impaired, potentially resulting in a far more effective treatment.
Another use of gene therapy is the introduction of enzymes into these cells that make them susceptible to particular chemotherapy agents; studies with introducing thymidine kinase in gliomas, making them susceptible to aciclovir, are in their experimental stage.
== Epigenetic options ==
Epigenetics is the study of heritable changes in gene activity that are not caused by changes in the DNA sequence, often a result of environmental or dietary damage to the histone receptors within the cell. Current research has shown that epigenetic pharmaceuticals could be a putative replacement or adjuvant therapy for currently accepted treatment methods such as radiation and chemotherapy, or could enhance the effects of these current treatments. It has been shown that the epigenetic control of the proto-onco regions and the tumor suppressor sequences by conformational changes in histones directly affects the formation and progression of cancer. Epigenetics also has the factor of reversibility, a characteristic that other cancer treatments do not offer.
Some investigators, like Randy Jirtle, PhD, of Duke University Medical Center, think epigenetics may ultimately turn out to have a greater role in disease than genetics.
== Telomerase deactivation therapy ==
Because most malignant cells rely on the activity of the protein telomerase for their immortality, it has been proposed that a drug that inactivates telomerase might be effective against a broad spectrum of malignancies. At the same time, most healthy tissues in the body express little if any telomerase, and would function normally in its absence. Currently, inositol hexaphosphate, which is available over-the-counter, is undergoing testing in cancer research due to its telomerase-inhibiting abilities.
A number of research groups have experimented with the use of telomerase inhibitors in animal models, and as of 2005 and 2006 phase I and II human clinical trials are underway. Geron Corporation is currently conducting two clinical trials involving telomerase inhibitors. One uses a vaccine (GRNVAC1) and the other uses a lipidated oligonucleotide (GRN163L).
== Radiation therapies ==
=== Photodynamic therapy ===
Photodynamic therapy (PDT) is generally a non-invasive treatment using a combination of light and a photosensitive drug, such as 5-ALA, Foscan, Metvix, padeliporfin (Tookad, WST09, WST11), Photofrin, or Visudyne. The drug is triggered by light of a specific wavelength.
=== Hyperthermiatic therapy ===
Localized and whole-body application of heat has been proposed as a technique for the treatment of malignant tumours. Intense heating will cause denaturation and coagulation of cellular proteins, rapidly killing cells within a tumour.
More prolonged moderate heating to temperatures just a few degrees above normal (39.5 °C) can cause more subtle changes. A mild heat treatment combined with other stresses can cause cell death by apoptosis. There are many biochemical consequences to the heat shock response within the cell, including slowed cell division and increased sensitivity to ionizing radiation therapy. The purpose of overheating the tumor cells is to create a lack of oxygen so that the heated cells become overacidified, which leads to a lack of nutrients in the tumor. This in turn disrupts the metabolism of the cells so that cell death (apoptosis) can set in. In certain cases chemotherapy or radiation that has previously not had any effect can be made effective. Hyperthermia alters the cell walls by means of so-called heat shock proteins. The cancer cells then react very much more effectively to the cytostatics and radiation. If hyperthermia is used conscientiously it has no serious side effects.
There are many techniques by which heat may be delivered. Some of the most common involve the use of focused ultrasound (FUS or HIFU), microwave heating, induction heating, magnetic hyperthermia, and direct application of heat through the use of heated saline pumped through catheters. Experiments with carbon nanotubes that selectively bind to cancer cells have been performed. Lasers are then used that pass harmlessly through the body, but heat the nanotubes, causing the death of the cancer cells. Similar results have also been achieved with other types of nanoparticles, including gold-coated nanoshells and nanorods that exhibit certain degrees of 'tunability' of the absorption properties of the nanoparticles to the wavelength of light for irradiation. The success of this approach to cancer treatment rests on the existence of an 'optical window' in which biological tissue (i.e., healthy cells) are completely transparent at the wavelength of the laser light, while nanoparticles are highly absorbing at the same wavelength. Such a 'window' exists in the so-called near-infrared region of the electromagnetic spectrum. In this way, the laser light can pass through the system without harming healthy tissue, and only diseased cells, where the nanoparticles reside, get hot and are killed.
Magnetic Hyperthermia makes use of magnetic nanoparticles, which can be injected into tumours and then generate heat when subjected to an alternating magnetic field.
One of the challenges in thermal therapy is delivering the appropriate amount of heat to the correct part of the patient's body. A great deal of current research focuses on precisely positioning heat delivery devices (catheters, microwave, and ultrasound applicators, etc.) using ultrasound or magnetic resonance imaging, as well as of developing new types of nanoparticles that make them particularly efficient absorbers while offering little or no concerns about toxicity to the circulation system. Clinicians also hope to use advanced imaging techniques to monitor heat treatments in real time—heat-induced changes in tissue are sometimes perceptible using these imaging instruments. In magnetic hyperthermia or magnetic fluid hyperthermia method, it will be easier to control temperature distribution by controlling the velocity of ferrofluid injection and size of magnetic nanoparticles.
=== Noninvasive cancer heat treatment ===
Heat treatment involves using radio waves to heat up tiny metals that are implanted in cancerous tissue. Gold nanoparticles or carbon nanotubes are the most likely candidate. Promising preclinical trials have been conducted, although clinical trials may not be held for another few years.
Another method that is entirely non-invasive referred to as Tumor Treating Fields has already reached clinical trial stage in many countries. The concept applies an electric field through a tumour region using electrodes external to the body. Successful trials have shown the process effectiveness to be greater than chemotherapy and there are no side-effects and only negligible time spent away from normal daily activities. This treatment is still in very early development stages for many types of cancer.
High-intensity focused ultrasound (HIFU) is still in investigatory phases in many places around the world. In China it has CFDA approval and over 180 treatment centres have been established in China, Hong Kong, and Korea. HIFU has been successfully used to treat cancer to destroy tumours of the bone, brain, breast, liver, pancreas, rectum, kidney, testes, and prostate. Several thousand patients have been treated with various types of tumours. HIFU has CE approval for palliative care for bone metastasis. Experimentally, palliative care has been provided for cases of advanced pancreatic cancer. High-energy therapeutic ultrasound could increase higher-density anti-cancer drug load and nanomedicines to target tumor sites by 20x fold higher than traditional target cancer therapy.
== Cold atmospheric plasma treatment ==
Cold atmospheric plasma or CAP for has been proposed for the treatment of solid tumors.
== Electromagnetic treatments ==
Tumor Treating Fields is a novel FDA-approved cancer treatment therapy that uses alternating electric field to disturb the rapid cell division exhibited by cancer cells.
== Complementary and alternative treatments ==
Complementary and alternative medicine (CAM) treatments are the diverse group of medical and healthcare systems, practices, and products that are not part of conventional medicine and have not been proven to be effective. Complementary medicine usually refers to methods and substances used along with conventional medicine, while alternative medicine refers to compounds used instead of conventional medicine. CAM use is common among people with cancer.
Most complementary and alternative medicines for cancer have not been rigorously studied or tested. Some alternative treatments that have been proven ineffective continue to be marketed and promoted.
== References ==
== External links ==
"Questionable Cancer Therapies"
clinicaltrials.gov | Wikipedia/Experimental_cancer_treatment |
An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that cause disease. Each individual antibody recognizes one or more specific antigens, and antigens of virtually any size and chemical composition can be recognized. Antigen literally means "antibody generator", as it is the presence of an antigen that drives the formation of an antigen-specific antibody. Each of the branching chains comprising the "Y" of an antibody contains a paratope that specifically binds to one particular epitope on an antigen, allowing the two molecules to bind together with precision. Using this mechanism, antibodies can effectively "tag" the antigen (or a microbe or an infected cell bearing such an antigen) for attack by cells of the immune system, or can neutralize it directly (for example, by blocking a part of a virus that is essential for its ability to invade a host cell).
Antibodies may be borne on the surface of an immune cell, as in a B cell receptor, or they may exist freely by being secreted into the extracellular space. The term antibody often refers to the free (secreted) form, while the term immunoglobulin can refer to both forms. Since they are, broadly speaking, the same protein, the terms are often treated as synonymous.
To allow the immune system to recognize millions of different antigens, the antigen-binding paratopes at each tip of the antibody come in an equally wide variety. The rest of an antibody's structure is much less variable; in humans, antibodies occur in five classes or isotypes: IgA, IgD, IgE, IgG, and IgM. Human IgG and IgA antibodies are also divided into discrete subclasses (IgG1, IgG2, IgG3, and IgG4; IgA1 and IgA2). The class refers to the functions triggered by the antibody (also known as effector functions), in addition to some other structural features. Antibodies from different classes also differ in where they are released in the body and at what stage of an immune response. Between species, while classes and subclasses of antibodies may be shared (at least in name), their function and distribution throughout the body may be different. For example, mouse IgG1 is closer to human IgG2 than to human IgG1 in terms of its function.
The term humoral immunity is often treated as synonymous with the antibody response, describing the function of the immune system that exists in the body's humors (fluids) in the form of soluble proteins, as distinct from cell-mediated immunity, which generally describes the responses of T cells (especially cytotoxic T cells). In general, antibodies are considered part of the adaptive immune system, though this classification can become complicated. For example, natural IgM, which are made by B-1 lineage cells that have properties more similar to innate immune cells than adaptive, refers to IgM antibodies made independently of an immune response that demonstrate polyreactivity – i.e. they recognize multiple distinct (unrelated) antigens. These can work with the complement system in the earliest phases of an immune response to help facilitate clearance of the offending antigen and delivery of the resulting immune complexes to the lymph nodes or spleen for initiation of an immune response. Hence in this capacity, the functions of antibodies are more akin to that of innate immunity than adaptive. Nonetheless, in general, antibodies are regarded as part of the adaptive immune system because they demonstrate exceptional specificity (with some exceptions), are produced through genetic rearrangements (rather than being encoded directly in the germline), and are a manifestation of immunological memory.
In the course of an immune response, B cells can progressively differentiate into antibody-secreting cells or into memory B cells. Antibody-secreting cells comprise plasmablasts and plasma cells, which differ mainly in the degree to which they secrete antibodies, their lifespan, metabolic adaptations, and surface markers. Plasmablasts are rapidly proliferating, short-lived cells produced in the early phases of the immune response (classically described as arising extrafollicularly rather than from a germinal center) which have the potential to differentiate further into plasma cells. Occasionally plasmablasts are mis-described as short-lived plasma cells; formally this is incorrect. Plasma cells, in contrast, do not divide (they are terminally differentiated), and rely on survival niches comprising specific cell types and cytokines to persist. Plasma cells will secrete huge quantities of antibody regardless of whether or not their cognate antigen is present, ensuring that antibody levels to the antigen in question do not fall to zero, provided the plasma cell stays alive. The rate of antibody secretion, however, can be regulated, for example, by the presence of adjuvant molecules that stimulate the immune response such as toll-like receptor ligands. Long-lived plasma cells can live for potentially the entire lifetime of the organism. Classically, the survival niches that house long-lived plasma cells reside in the bone marrow, though it cannot be assumed that any given plasma cell in the bone marrow will be long-lived. However, other work indicates that survival niches can readily be established within the mucosal tissues- though the classes of antibodies involved show a different hierarchy from those in the bone marrow. B cells can also differentiate into memory B cells which can persist for decades, similarly to long-lived plasma cells. These cells can be rapidly recalled in a secondary immune response, undergoing class switching, affinity maturation, and differentiating into antibody-secreting cells.
Antibodies are central to the immune protection elicited by most vaccines and infections (although other components of the immune system certainly participate and for some diseases are considerably more important than antibodies in generating an immune response, e.g. in the case of herpes zoster). Durable protection from infections caused by a given microbe – that is, the ability of the microbe to enter the body and begin to replicate (not necessarily to cause disease) – depends on sustained production of large quantities of antibodies, meaning that effective vaccines ideally elicit persistent high levels of antibody, which relies on long-lived plasma cells. At the same time, many microbes of medical importance have the ability to mutate to escape antibodies elicited by prior infections, and long-lived plasma cells cannot undergo affinity maturation or class switching. This is compensated for through memory B cells: novel variants of a microbe that still retain structural features of previously encountered antigens can elicit memory B cell responses that adapt to those changes. It has been suggested that long-lived plasma cells secrete B cell receptors with higher affinity than those on the surfaces of memory B cells, but findings are not entirely consistent on this point.
== Structure ==
Antibodies are heavy (~150 kDa) proteins of about 10 nm in size,
arranged in three globular regions that roughly form a Y shape.
In humans and most other mammals, an antibody unit consists of four polypeptide chains; two identical heavy chains and two identical light chains connected by disulfide bonds.
Each chain is a series of domains: somewhat similar sequences of about 110 amino acids each.
These domains are usually represented in simplified schematics as rectangles.
Light chains consist of one variable domain VL and one constant domain CL, while heavy chains contain one variable domain VH and three to four constant domains CH1, CH2, ...
Structurally an antibody is also partitioned into two antigen-binding fragments (Fab), containing one VL, VH, CL, and CH1 domain each, as well as the crystallisable fragment (Fc), forming the trunk of the Y shape.
In between them is a hinge region of the heavy chains, whose flexibility allows antibodies to bind to pairs of epitopes at various distances, to form complexes (dimers, trimers, etc.), and to bind effector molecules more easily.
In an electrophoresis test of blood proteins, antibodies mostly migrate to the last, gamma globulin fraction.
Conversely, most gamma-globulins are antibodies, which is why the two terms were historically used as synonyms, as were the symbols Ig and γ.
This variant terminology fell out of use due to the correspondence being inexact and due to confusion with γ (gamma) heavy chains which characterize the IgG class of antibodies.
=== Antigen-binding site ===
The variable domains can also be referred to as the FV region. It is the subregion of Fab that binds to an antigen.
More specifically, each variable domain contains three hypervariable regions – the amino acids seen there vary the most from antibody to antibody.
When the protein folds, these regions give rise to three loops of β-strands, localized near one another on the surface of the antibody.
These loops are referred to as the complementarity-determining regions (CDRs), since their shape complements that of an antigen.
Three CDRs from each of the heavy and light chains together form an antibody-binding site whose shape can be anything from a pocket to which a smaller antigen binds, to a larger surface, to a protrusion that sticks out into a groove in an antigen.
Typically though, only a few residues contribute to most of the binding energy.
The existence of two identical antibody-binding sites allows antibody molecules to bind strongly to multivalent antigen (repeating sites such as polysaccharides in bacterial cell walls, or other sites at some distance apart), as well as to form antibody complexes and larger antigen-antibody complexes.
The structures of CDRs have been clustered and classified by Chothia et al.
and more recently by North et al.
and Nikoloudis et al. However, describing an antibody's binding site using only one single static structure limits the understanding and characterization of the antibody's function and properties. To improve antibody structure prediction and to take the strongly correlated CDR loop and interface movements into account, antibody paratopes should be described as interconverting states in solution with varying probabilities.
In the framework of the immune network theory, CDRs are also called idiotypes. According to immune network theory, the adaptive immune system is regulated by interactions between idiotypes.
=== Fc region ===
The Fc region (the trunk of the Y shape) is composed of constant domains from the heavy chains. Its role is in modulating immune cell activity: it is where effector molecules bind to, triggering various effects after the antibody Fab region binds to an antigen.
Effector cells (such as macrophages or natural killer cells) bind via their Fc receptors (FcR) to the Fc region of an antibody, while the complement system is activated by binding the C1q protein complex. IgG or IgM can bind to C1q, but IgA cannot, therefore IgA does not activate the classical complement pathway.
Another role of the Fc region is to selectively distribute different antibody classes across the body. In particular, the neonatal Fc receptor (FcRn) binds to the Fc region of IgG antibodies to transport it across the placenta, from the mother to the fetus. In addition to this, binding to FcRn endows IgG with an exceptionally long half-life relative to other plasma proteins of 3-4 weeks. IgG3 in most cases (depending on allotype) has mutations at the FcRn binding site which lower affinity for FcRn, which are thought to have evolved to limit the highly inflammatory effects of this subclass.
Antibodies are glycoproteins, that is, they have carbohydrates (glycans) added to conserved amino acid residues.
These conserved glycosylation sites occur in the Fc region and influence interactions with effector molecules.
=== Protein structure ===
The N-terminus of each chain is situated at the tip.
Each immunoglobulin domain has a similar structure, characteristic of all the members of the immunoglobulin superfamily:
it is composed of between 7 (for constant domains) and 9 (for variable domains) β-strands, forming two beta sheets in a Greek key motif.
The sheets create a "sandwich" shape, the immunoglobulin fold, held together by a disulfide bond.
=== Antibody complexes ===
Secreted antibodies can occur as a single Y-shaped unit, a monomer.
However, some antibody classes also form dimers with two Ig units (as with IgA), tetramers with four Ig units (like teleost fish IgM), or pentamers with five Ig units (like shark IgW or mammalian IgM, which occasionally forms hexamers as well, with six units). IgG can also form hexamers, though no J chain is required. IgA tetramers and pentamers have also been reported.
Antibodies also form complexes by binding to antigen: this is called an antigen-antibody complex or immune complex.
Small antigens can cross-link two antibodies, also leading to the formation of antibody dimers, trimers, tetramers, etc.
Multivalent antigens (e.g., cells with multiple epitopes) can form larger complexes with antibodies.
An extreme example is the clumping, or agglutination, of red blood cells with antibodies in blood typing to determine blood groups: the large clumps become insoluble, leading to visually apparent precipitation.
=== B cell receptors ===
The membrane-bound form of an antibody may be called a surface immunoglobulin (sIg) or a membrane immunoglobulin (mIg). It is part of the B cell receptor (BCR), which allows a B cell to detect when a specific antigen is present in the body and triggers B cell activation. The BCR is composed of surface-bound IgD or IgM antibodies and associated Ig-α and Ig-β heterodimers, which are capable of signal transduction. A typical human B cell will have 50,000 to 100,000 antibodies bound to its surface. Upon antigen binding, they cluster in large patches, which can exceed 1 micrometer in diameter, on lipid rafts that isolate the BCRs from most other cell signaling receptors.
These patches may improve the efficiency of the cellular immune response. In humans, the cell surface is bare around the B cell receptors for several hundred nanometers, which further isolates the BCRs from competing influences.
== Classes ==
Antibodies can come in different varieties known as isotypes or classes. In humans there are five antibody classes known as IgA, IgD, IgE, IgG, and IgM, which are further subdivided into subclasses such as IgA1, IgA2.
The prefix "Ig" stands for immunoglobulin, while the suffix denotes the type of heavy chain the antibody contains: the heavy chain types α (alpha), γ (gamma), δ (delta), ε (epsilon), μ (mu) give rise to IgA, IgG, IgD, IgE, IgM, respectively.
The distinctive features of each class are determined by the part of the heavy chain within the hinge and Fc region.
The classes differ in their biological properties, functional locations and ability to deal with different antigens, as depicted in the table.
For example, IgE antibodies are responsible for an allergic response consisting of histamine release from mast cells, often a sole contributor to asthma (though other pathways exist as do symptoms very similar to yet not technically asthma). The variable region of these antibodies bind to allergic antigen, for example house dust mite particles, while its Fc region (in the ε heavy chains) binds to Fc receptor ε on a mast cell, triggering its degranulation: the release of molecules stored in its granules.
The antibody isotype of a B cell changes during cell development and activation. Immature B cells, which have never been exposed to an antigen, express only the IgM isotype in a cell surface bound form. The B lymphocyte, in this ready-to-respond form, is known as a "naive B lymphocyte." The naive B lymphocyte expresses both surface IgM and IgD. The co-expression of both of these immunoglobulin isotypes renders the B cell ready to respond to antigen. B cell activation follows engagement of the cell-bound antibody molecule with an antigen, causing the cell to divide and differentiate into an antibody-producing cell called a plasma cell. This requires cytokines from T helper cells, unless antigen cross-links B cell receptors. In this activated form, the B cell starts to produce antibody in a secreted form rather than a membrane-bound form. Activated B cells that encounter certain signaling molecules undergo immunoglobulin class switching, also known as isotope switching, which causes the production of antibodies to change from IgM or IgD to the other antibody isotypes, IgE, IgA, or IgG.
=== Light chain types ===
In mammals there are two types of immunoglobulin light chain, which are called lambda (λ) and kappa (κ). However, there is no known functional difference between them, and both can occur with any of the five major types of heavy chains. Each antibody contains two identical light chains: both κ or both λ. Proportions of κ and λ types vary by species and can be used to detect abnormal proliferation of B cell clones. Other types of light chains, such as the iota (ι) chain, are found in other vertebrates like sharks (Chondrichthyes) and bony fishes (Teleostei).
=== In non-mammalian animals ===
In most placental mammals, the structure of antibodies is generally the same.
Jawed fish appear to be the most primitive animals that are able to make antibodies similar to those of mammals, although many features of their adaptive immunity appeared somewhat earlier.
Cartilaginous fish (such as sharks) produce heavy-chain-only antibodies (i.e., lacking light chains) which moreover feature longer chain pentamers (with five constant units per molecule). Camelids (such as camels, llamas, alpacas) are also notable for producing heavy-chain-only antibodies.
== Antibody–antigen interactions ==
The antibody's paratope interacts with the antigen's epitope. An antigen usually contains different epitopes along its surface arranged discontinuously, and dominant epitopes on a given antigen are called determinants.
Antibody and antigen interact by spatial complementarity (lock and key). The molecular forces involved in the Fab-epitope interaction are weak and non-specific – for example electrostatic forces, hydrogen bonds, hydrophobic interactions, and van der Waals forces. This means binding between antibody and antigen is reversible, and the antibody's affinity towards an antigen is relative rather than absolute. Relatively weak binding also means it is possible for an antibody to cross-react with different antigens of different relative affinities.
== Function ==
The main categories of antibody action include the following:
Neutralisation, in which neutralizing antibodies block parts of the surface of a bacterial cell or virion to render its attack ineffective
Agglutination, in which antibodies "glue together" foreign cells into clumps that are attractive targets for phagocytosis
Precipitation, in which antibodies "glue together" serum-soluble antigens, forcing them to precipitate out of solution in clumps that are attractive targets for phagocytosis
Complement activation (fixation), in which antibodies that are latched onto a foreign cell encourage complement to attack it with a membrane attack complex, which leads to the following:
Lysis of the foreign cell
Encouragement of inflammation by chemotactically attracting inflammatory cells
More indirectly, an antibody can signal immune cells to present antibody fragments to T cells, or downregulate other immune cells to avoid autoimmunity.
Activated B cells differentiate into either
antibody-producing cells called plasma cells that secrete soluble antibody or
memory cells that survive in the body for years afterward in order to allow the immune system to remember an antigen and respond faster upon future exposures.
At the prenatal and neonatal stages of life, the presence of antibodies is provided by passive immunization from the mother. Early endogenous antibody production varies for different kinds of antibodies, and usually appear within the first years of life. Since antibodies exist freely in the bloodstream, they are said to be part of the humoral immune system. Circulating antibodies are produced by clonal B cells that specifically respond to only one antigen (an example is a virus capsid protein fragment). Antibodies contribute to immunity in three ways: They prevent pathogens from entering or damaging cells by binding to them; they stimulate removal of pathogens by macrophages and other cells by coating the pathogen; and they trigger destruction of pathogens by stimulating other immune responses such as the complement pathway. Antibodies will also trigger vasoactive amine degranulation to contribute to immunity against certain types of antigens (helminths, allergens).
=== Activation of complement ===
Antibodies that bind to surface antigens (for example, on bacteria) will attract the first component of the complement cascade with their Fc region and initiate activation of the "classical" complement system. This results in the killing of bacteria in two ways. First, the binding of the antibody and complement molecules marks the microbe for ingestion by phagocytes in a process called opsonization; these phagocytes are attracted by certain complement molecules generated in the complement cascade. Second, some complement system components form a membrane attack complex to assist antibodies to kill the bacterium directly (bacteriolysis).
=== Activation of effector cells ===
To combat pathogens that replicate outside cells, antibodies bind to pathogens to link them together, causing them to agglutinate. Since an antibody has at least two paratopes, it can bind more than one antigen by binding identical epitopes carried on the surfaces of these antigens. By coating the pathogen, antibodies stimulate effector functions against the pathogen in cells that recognize their Fc region.
Those cells that recognize coated pathogens have Fc receptors, which, as the name suggests, interact with the Fc region of IgA, IgG, and IgE antibodies. The engagement of a particular antibody with the Fc receptor on a particular cell triggers an effector function of that cell; phagocytes will phagocytose, mast cells and neutrophils will degranulate, natural killer cells will release cytokines and cytotoxic molecules; that will ultimately result in destruction of the invading microbe. The activation of natural killer cells by antibodies initiates a cytotoxic mechanism known as antibody-dependent cell-mediated cytotoxicity (ADCC) – this process may explain the efficacy of monoclonal antibodies used in biological therapies against cancer. The Fc receptors are isotype-specific, which gives greater flexibility to the immune system, invoking only the appropriate immune mechanisms for distinct pathogens.
=== Natural antibodies ===
Humans and higher primates also produce "natural antibodies" that are present in serum before viral infection. Natural antibodies have been defined as antibodies that are produced without any previous infection, vaccination, other foreign antigen exposure or passive immunization. These antibodies can activate the classical complement pathway leading to lysis of enveloped virus particles long before the adaptive immune response is activated. Antibodies are produced exclusively by B cells in response to antigens where initially, antibodies are formed as membrane-bound receptors, but upon activation by antigens and helper T cells, B cells differentiate to produce soluble antibodies. Many natural antibodies are directed against the disaccharide galactose α(1,3)-galactose (α-Gal), which is found as a terminal sugar on glycosylated cell surface proteins, and generated in response to production of this sugar by bacteria contained in the human gut. These antibodies undergo quality checks in the endoplasmic reticulum (ER), which contains proteins that assist in proper folding and assembly. Rejection of xenotransplantated organs is thought to be, in part, the result of natural antibodies circulating in the serum of the recipient binding to α-Gal antigens expressed on the donor tissue.
== Immunoglobulin diversity ==
Virtually all microbes can trigger an antibody response. Successful recognition and eradication of many different types of microbes requires diversity among antibodies; their amino acid composition varies allowing them to interact with many different antigens. It has been estimated that humans generate about 10 billion different antibodies, each capable of binding a distinct epitope of an antigen. Although a huge repertoire of different antibodies is generated in a single individual, the number of genes available to make these proteins is limited by the size of the human genome. Several complex genetic mechanisms have evolved that allow vertebrate B cells to generate a diverse pool of antibodies from a relatively small number of antibody genes.
=== Domain variability ===
The chromosomal region that encodes an antibody is large and contains several distinct gene loci for each domain of the antibody—the chromosome region containing heavy chain genes (IGH@) is found on chromosome 14, and the loci containing lambda and kappa light chain genes (IGL@ and IGK@) are found on chromosomes 22 and 2 in humans. One of these domains is called the variable domain, which is present in each heavy and light chain of every antibody, but can differ in different antibodies generated from distinct B cells. Differences between the variable domains are located on three loops known as hypervariable regions (HV-1, HV-2 and HV-3) or complementarity-determining regions (CDR1, CDR2 and CDR3). CDRs are supported within the variable domains by conserved framework regions. The heavy chain locus contains about 65 different variable domain genes that all differ in their CDRs. Combining these genes with an array of genes for other domains of the antibody generates a large cavalry of antibodies with a high degree of variability. This combination is called V(D)J recombination and discussed below.
=== V(D)J recombination ===
Somatic recombination of immunoglobulins, also known as V(D)J recombination, involves the generation of a unique immunoglobulin variable region. The variable region of each immunoglobulin heavy or light chain is encoded in several pieces—known as gene segments (subgenes). These segments are called variable (V), diversity (D) and joining (J) segments. V, D and J segments are found in Ig heavy chains, but only V and J segments are found in Ig light chains. Multiple copies of the V, D and J gene segments exist, and are tandemly arranged in the genomes of mammals. In the bone marrow, each developing B cell will assemble an immunoglobulin variable region by randomly selecting and combining one V, one D and one J gene segment (or one V and one J segment in the light chain). As there are multiple copies of each type of gene segment, and different combinations of gene segments can be used to generate each immunoglobulin variable region, this process generates a huge number of antibodies, each with different paratopes, and thus different antigen specificities. The rearrangement of several subgenes (i.e. V2 family) for lambda light chain immunoglobulin is coupled with the activation of microRNA miR-650, which further influences biology of B-cells.
RAG proteins play an important role with V(D)J recombination in cutting DNA at a particular region. Without the presence of these proteins, V(D)J recombination would not occur.
After a B cell produces a functional immunoglobulin gene during V(D)J recombination, it cannot express any other variable region (a process known as allelic exclusion) thus each B cell can produce antibodies containing only one kind of variable chain.
=== Somatic hypermutation and affinity maturation ===
Following activation with antigen, B cells begin to proliferate rapidly. In these rapidly dividing cells, the genes encoding the variable domains of the heavy and light chains undergo a high rate of point mutation, by a process called somatic hypermutation (SHM). SHM results in approximately one nucleotide change per variable gene, per cell division. As a consequence, any daughter B cells will acquire slight amino acid differences in the variable domains of their antibody chains.
This serves to increase the diversity of the antibody pool and impacts the antibody's antigen-binding affinity. Some point mutations will result in the production of antibodies that have a weaker interaction (low affinity) with their antigen than the original antibody, and some mutations will generate antibodies with a stronger interaction (high affinity). B cells that express high affinity antibodies on their surface will receive a strong survival signal during interactions with other cells, whereas those with low affinity antibodies will not, and will die by apoptosis. Thus, B cells expressing antibodies with a higher affinity for the antigen will outcompete those with weaker affinities for function and survival allowing the average affinity of antibodies to increase over time. The process of generating antibodies with increased binding affinities is called affinity maturation. Affinity maturation occurs in mature B cells after V(D)J recombination, and is dependent on help from helper T cells.
=== Class switching ===
Isotype or class switching is a biological process occurring after activation of the B cell, which allows the cell to produce different classes of antibody (IgA, IgE, or IgG). The different classes of antibody, and thus effector functions, are defined by the constant (C) regions of the immunoglobulin heavy chain. Initially, naive B cells express only cell-surface IgM and IgD with identical antigen binding regions. Each isotype is adapted for a distinct function; therefore, after activation, an antibody with an IgG, IgA, or IgE effector function might be required to effectively eliminate an antigen. Class switching allows different daughter cells from the same activated B cell to produce antibodies of different isotypes. Only the constant region of the antibody heavy chain changes during class switching; the variable regions, and therefore antigen specificity, remain unchanged. Thus the progeny of a single B cell can produce antibodies, all specific for the same antigen, but with the ability to produce the effector function appropriate for each antigenic challenge. Class switching is triggered by cytokines; the isotype generated depends on which cytokines are present in the B cell environment.
Class switching occurs in the heavy chain gene locus by a mechanism called class switch recombination (CSR). This mechanism relies on conserved nucleotide motifs, called switch (S) regions, found in DNA upstream of each constant region gene (except in the δ-chain). The DNA strand is broken by the activity of a series of enzymes at two selected S-regions. The variable domain exon is rejoined through a process called non-homologous end joining (NHEJ) to the desired constant region (γ, α or ε). This process results in an immunoglobulin gene that encodes an antibody of a different isotype.
=== Specificity designations ===
An antibody can be called monospecific if it has specificity for a single antigen or epitope, or bispecific if it has affinity for two different antigens or two different epitopes on the same antigen. A group of antibodies can be called polyvalent (or unspecific) if they have affinity for various antigens or microorganisms. Intravenous immunoglobulin, if not otherwise noted, consists of a variety of different IgG (polyclonal IgG). In contrast, monoclonal antibodies are identical antibodies produced by a single B cell.
=== Asymmetrical antibodies ===
Heterodimeric antibodies, which are also asymmetrical antibodies, allow for greater flexibility and new formats for attaching a variety of drugs to the antibody arms. One of the general formats for a heterodimeric antibody is the "knobs-into-holes" format. This format is specific to the heavy chain part of the constant region in antibodies. The "knobs" part is engineered by replacing a small amino acid with a larger one. It fits into the "hole", which is engineered by replacing a large amino acid with a smaller one. What connects the "knobs" to the "holes" are the disulfide bonds between each chain. The "knobs-into-holes" shape facilitates antibody dependent cell mediated cytotoxicity. Single-chain variable fragments (scFv) are connected to the variable domain of the heavy and light chain via a short linker peptide. The linker is rich in glycine, which gives it more flexibility, and serine/threonine, which gives it specificity. Two different scFv fragments can be connected together, via a hinge region, to the constant domain of the heavy chain or the constant domain of the light chain. This gives the antibody bispecificity, allowing for the binding specificities of two different antigens. The "knobs-into-holes" format enhances heterodimer formation but does not suppress homodimer formation.
To further improve the function of heterodimeric antibodies, many scientists are looking towards artificial constructs. Artificial antibodies are largely diverse protein motifs that use the functional strategy of the antibody molecule, but are not limited by the loop and framework structural constraints of the natural antibody. Being able to control the combinational design of the sequence and three-dimensional space could transcend the natural design and allow for the attachment of different combinations of drugs to the arms.
Heterodimeric antibodies have a greater range in shapes they can take and the drugs that are attached to the arms do not have to be the same on each arm, allowing for different combinations of drugs to be used in cancer treatment. Pharmaceuticals are able to produce highly functional bispecific, and even multispecific, antibodies. The degree to which they can function is impressive given that such a change of shape from the natural form should lead to decreased functionality.
=== Interchromosomal DNA Transposition ===
Antibody diversification typically occurs through somatic hypermutation, class switching, and affinity maturation targeting the BCR gene loci, but on occasion more unconventional forms of diversification have been documented. For example, in the case of malaria caused by Plasmodium falciparum, some antibodies from those who had been infected demonstrated an insertion from chromosome 19 containing a 98-amino acid stretch from leukocyte-associated immunoglobulin-like receptor 1, LAIR1, in the elbow joint. This represents a form of interchromosomal transposition. LAIR1 normally binds collagen, but can recognize repetitive interspersed families of polypeptides (RIFIN) family members that are highly expressed on the surface of P. falciparum-infected red blood cells. In fact, these antibodies underwent affinity maturation that enhanced affinity for RIFIN but abolished affinity for collagen. These "LAIR1-containing" antibodies have been found in 5-10% of donors from Tanzania and Mali, though not in European donors. European donors did show 100-1000 nucleotide stretches inside the elbow joints as well, however. This particular phenomenon may be specific to malaria, as infection is known to induce genomic instability.
== History ==
The first use of the term "antibody" occurred in a text by Paul Ehrlich. The term Antikörper (the German word for antibody) appears in the conclusion of his article "Experimental Studies on Immunity", published in October 1891, which states that, "if two substances give rise to two different Antikörper, then they themselves must be different". However, the term was not accepted immediately and several other terms for antibody were proposed; these included Immunkörper, Amboceptor, Zwischenkörper, substance sensibilisatrice, copula, Desmon, philocytase, fixateur, and Immunisin. The word antibody has formal analogy to the word antitoxin and a similar concept to Immunkörper (immune body in English). As such, the original construction of the word contains a logical flaw; the antitoxin is something directed against a toxin, while the antibody is a body directed against something.
The study of antibodies began in 1890 when Emil von Behring and Kitasato Shibasaburō described antibody activity against diphtheria and tetanus toxins. Von Behring and Kitasato put forward the theory of humoral immunity, proposing that a mediator in serum could react with a foreign antigen. His idea prompted Paul Ehrlich to propose the side-chain theory for antibody and antigen interaction in 1897, when he hypothesized that receptors (described as "side-chains") on the surface of cells could bind specifically to toxins – in a "lock-and-key" interaction – and that this binding reaction is the trigger for the production of antibodies. Other researchers believed that antibodies existed freely in the blood and, in 1904, Almroth Wright suggested that soluble antibodies coated bacteria to label them for phagocytosis and killing; a process that he named opsoninization.
In the 1920s, Michael Heidelberger and Oswald Avery observed that antigens could be precipitated by antibodies and went on to show that antibodies are made of protein. The biochemical properties of antigen-antibody-binding interactions were examined in more detail in the late 1930s by John Marrack. The next major advance was in the 1940s, when Linus Pauling confirmed the lock-and-key theory proposed by Ehrlich by showing that the interactions between antibodies and antigens depend more on their shape than their chemical composition. In 1948, Astrid Fagraeus discovered that B cells, in the form of plasma cells, were responsible for generating antibodies.
Further work concentrated on characterizing the structures of the antibody proteins. A major advance in these structural studies was the discovery in the early 1960s by Gerald Edelman and Joseph Gally of the antibody light chain, and their realization that this protein is the same as the Bence-Jones protein described in 1845 by Henry Bence Jones. Edelman went on to discover that antibodies are composed of disulfide bond-linked heavy and light chains. Around the same time, antibody-binding (Fab) and antibody tail (Fc) regions of IgG were characterized by Rodney Porter. Together, these scientists deduced the structure and complete amino acid sequence of IgG, a feat for which they were jointly awarded the 1972 Nobel Prize in Physiology or Medicine. The Fv fragment was prepared and characterized by David Givol. While most of these early studies focused on IgM and IgG, other immunoglobulin isotypes were identified in the 1960s: Thomas Tomasi discovered secretory antibody (IgA); David S. Rowe and John L. Fahey discovered IgD; and Kimishige Ishizaka and Teruko Ishizaka discovered IgE and showed it was a class of antibodies involved in allergic reactions. In a landmark series of experiments beginning in 1976, Susumu Tonegawa showed that genetic material can rearrange itself to form the vast array of available antibodies.
== Medical applications ==
=== Disease diagnosis ===
Detection of particular antibodies is a very common form of medical diagnostics, and applications such as serology depend on these methods. For example, in biochemical assays for disease diagnosis, a titer of antibodies directed against Epstein–Barr virus or Lyme disease is estimated from the blood. If those antibodies are not present, either the person is not infected or the infection occurred a very long time ago, and the B cells generating these specific antibodies have naturally decayed.
In clinical immunology, levels of individual classes of immunoglobulins are measured by nephelometry (or turbidimetry) to characterize the antibody profile of patient. Elevations in different classes of immunoglobulins are sometimes useful in determining the cause of liver damage in patients for whom the diagnosis is unclear. For example, IgM levels are often elevated in patients with primary biliary cirrhosis, whereas IgA deposition along hepatic sinusoids can suggest alcoholic liver disease.
Autoimmune disorders can often be traced to antibodies that bind the body's own epitopes; many can be detected through blood tests. Antibodies directed against red blood cell surface antigens in immune mediated hemolytic anemia are detected with the Coombs test. The Coombs test is also used for antibody screening in blood transfusion preparation and also for antibody screening in antenatal women.
Practically, several immunodiagnostic methods based on detection of complex antigen-antibody are used to diagnose infectious diseases, for example ELISA, immunofluorescence, Western blot, immunodiffusion, immunoelectrophoresis, and magnetic immunoassay.
Over-the-counter home pregnancy tests rely on human chorionic gonadotropin (hCG)-directed antibodies.
New dioxaborolane chemistry enables radioactive fluoride (18F) labeling of antibodies, which allows for positron emission tomography (PET) imaging of cancer.
=== Disease therapy ===
Targeted monoclonal antibody therapy is employed to treat diseases such as rheumatoid arthritis, multiple sclerosis, psoriasis, and many forms of cancer including non-Hodgkin's lymphoma, colorectal cancer, head and neck cancer and breast cancer.
Some immune deficiencies, such as X-linked agammaglobulinemia and hypogammaglobulinemia, result in partial or complete lack of antibodies. These diseases are often treated by inducing a short-term form of immunity called passive immunity. Passive immunity is achieved through the transfer of ready-made antibodies in the form of human or animal serum, pooled immunoglobulin or monoclonal antibodies, into the affected individual.
=== Prenatal therapy ===
Rh factor, also known as Rh D antigen, is an antigen found on red blood cells; individuals that are Rh-positive (Rh+) have this antigen on their red blood cells and individuals that are Rh-negative (Rh–) do not. During normal childbirth, delivery trauma or complications during pregnancy, blood from a fetus can enter the mother's system. In the case of an Rh-incompatible mother and child, consequential blood mixing may sensitize an Rh- mother to the Rh antigen on the blood cells of the Rh+ child, putting the remainder of the pregnancy, and any subsequent pregnancies, at risk for hemolytic disease of the newborn.
Rho(D) immune globulin antibodies are specific for human RhD antigen. Anti-RhD antibodies are administered as part of a prenatal treatment regimen to prevent sensitization that may occur when a Rh-negative mother has a Rh-positive fetus. Treatment of a mother with Anti-RhD antibodies prior to and immediately after trauma and delivery destroys Rh antigen in the mother's system from the fetus. This occurs before the antigen can stimulate maternal B cells to "remember" Rh antigen by generating memory B cells. Therefore, her humoral immune system will not make anti-Rh antibodies, and will not attack the Rh antigens of the current or subsequent babies. Rho(D) Immune Globulin treatment prevents sensitization that can lead to Rh disease, but does not prevent or treat the underlying disease itself.
== Research applications ==
Specific antibodies are produced by injecting an antigen into a mammal, such as a mouse, rat, rabbit, goat, sheep, or horse for large quantities of antibody. Blood isolated from these animals contains polyclonal antibodies—multiple antibodies that bind to the same antigen—in the serum, which can now be called antiserum. Antigens are also injected into chickens for generation of polyclonal antibodies in egg yolk. To obtain antibody that is specific for a single epitope of an antigen, antibody-secreting lymphocytes are isolated from the animal and immortalized by fusing them with a cancer cell line. The fused cells are called hybridomas, and will continually grow and secrete antibody in culture. Single hybridoma cells are isolated by dilution cloning to generate cell clones that all produce the same antibody; these antibodies are called monoclonal antibodies. Polyclonal and monoclonal antibodies are often purified using Protein A/G or antigen-affinity chromatography.
In research, purified antibodies are used in many applications. Antibodies for research applications can be found directly from antibody suppliers, or through use of a specialist search engine. Research antibodies are most commonly used to identify and locate intracellular and extracellular proteins. Antibodies are used in flow cytometry to differentiate cell types by the proteins they express; different types of cells express different combinations of cluster of differentiation molecules on their surface, and produce different intracellular and secretable proteins. They are also used in immunoprecipitation to separate proteins and anything bound to them (co-immunoprecipitation) from other molecules in a cell lysate, in Western blot analyses to identify proteins separated by electrophoresis, and in immunohistochemistry or immunofluorescence to examine protein expression in tissue sections or to locate proteins within cells with the assistance of a microscope. Proteins can also be detected and quantified with antibodies, using ELISA and ELISpot techniques.
Antibodies used in research are some of the most powerful, yet most problematic reagents with a tremendous number of factors that must be controlled in any experiment including cross reactivity, or the antibody recognizing multiple epitopes and affinity, which can vary widely depending on experimental conditions such as pH, solvent, state of tissue etc. Multiple attempts have been made to improve both the way that researchers validate antibodies and ways in which they report on antibodies. Researchers using antibodies in their work need to record them correctly in order to allow their research to be reproducible (and therefore tested, and qualified by other researchers). Less than half of research antibodies referenced in academic papers can be easily identified. Papers published in F1000 in 2014 and 2015 provide researchers with a guide for reporting research antibody use. The RRID paper, is co-published in 4 journals that implemented the RRIDs Standard for research resource citation, which draws data from the antibodyregistry.org as the source of antibody identifiers (see also group at Force11).
Antibody regions can be used to further biomedical research by acting as a guide for drugs to reach their target. Several application involve using bacterial plasmids to tag plasmids with the Fc region of the antibody such as pFUSE-Fc plasmid.
== Regulations ==
=== Production and testing ===
There are several ways to obtain antibodies, including in vivo techniques like animal immunization and various in vitro approaches, such as the phage display method. Traditionally, most antibodies are produced by hybridoma cell lines through immortalization of antibody-producing cells by chemically induced fusion with myeloma cells. In some cases, additional fusions with other lines have created "triomas" and "quadromas". The manufacturing process should be appropriately described and validated. Validation studies should at least include:
The demonstration that the process is able to produce in good quality (the process should be validated)
The efficiency of the antibody purification (all impurities and virus must be eliminated)
The characterization of purified antibody (physicochemical characterization, immunological properties, biological activities, contaminants, ...)
Determination of the virus clearance studies
=== Before clinical trials ===
Product safety testing: Sterility (bacteria and fungi), in vitro and in vivo testing for adventitious viruses, murine retrovirus testing..., product safety data needed before the initiation of feasibility trials in serious or immediately life-threatening conditions, it serves to evaluate dangerous potential of the product.
Feasibility testing: These are pilot studies whose objectives include, among others, early characterization of safety and initial proof of concept in a small specific patient population (in vitro or in vivo testing).
=== Preclinical studies ===
Testing cross-reactivity of antibody: to highlight unwanted interactions (toxicity) of antibodies with previously characterized tissues. This study can be performed in vitro (reactivity of the antibody or immunoconjugate should be determined with a quick-frozen adult tissues) or in vivo (with appropriates animal models).
Preclinical pharmacology and toxicity testing: preclinical safety testing of antibody is designed to identify possible toxicity in humans, to estimate the likelihood and severity of potential adverse events in humans, and to identify a safe starting dose and dose escalation, when possible.
Animal toxicity studies: Acute toxicity testing, repeat-dose toxicity testing, long-term toxicity testing
Pharmacokinetics and pharmacodynamics testing: Use for determinate clinical dosages, antibody activities, evaluation of the potential clinical effects
== Structure prediction and computational antibody design ==
The importance of antibodies in health care and the biotechnology industry demands knowledge of their structures at high resolution. This information is used for protein engineering, modifying the antigen binding affinity, and identifying an epitope, of a given antibody. X-ray crystallography is one commonly used method for determining antibody structures. However, crystallizing an antibody is often laborious and time-consuming. Computational approaches provide a cheaper and faster alternative to crystallography, but their results are more equivocal, since they do not produce empirical structures. Online web servers such as Web Antibody Modeling (WAM) and Prediction of Immunoglobulin Structure (PIGS) enable computational modeling of antibody variable regions. Rosetta Antibody is a novel antibody FV region structure prediction server, which incorporates sophisticated techniques to minimize CDR loops and optimize the relative orientation of the light and heavy chains, as well as homology models that predict successful docking of antibodies with their unique antigen. However, describing an antibody's binding site using only one single static structure limits the understanding and characterization of the antibody's function and properties. To improve antibody structure prediction and to take the strongly correlated CDR loop and interface movements into account, antibody paratopes should be described as interconverting states in solution with varying probabilities.
The ability to describe the antibody through binding affinity to the antigen is supplemented by information on antibody structure and amino acid sequences for the purpose of patent claims. Several methods have been presented for computational design of antibodies based on the structural bioinformatics studies of antibody CDRs.
There are a variety of methods used to sequence an antibody including Edman degradation, cDNA, etc.; albeit one of the most common modern uses for peptide/protein identification is liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). High volume antibody sequencing methods require computational approaches for the data analysis, including de novo sequencing directly from tandem mass spectra and database search methods that use existing protein sequence databases. Many versions of shotgun protein sequencing are able to increase the coverage by utilizing CID/HCD/ETD fragmentation methods and other techniques, and they have achieved substantial progress in attempt to fully sequence proteins, especially antibodies. Other methods have assumed the existence of similar proteins, a known genome sequence, or combined top-down and bottom up approaches. Current technologies have the ability to assemble protein sequences with high accuracy by integrating de novo sequencing peptides, intensity, and positional confidence scores from database and homology searches.
== Antibody mimetic ==
Antibody mimetics are organic compounds, like antibodies, that can specifically bind antigens. They consist of artificial peptides or proteins, or aptamer-based nucleic acid molecules with a molar mass of about 3 to 20 kDa. Antibody fragments, such as Fab and nanobodies are not considered as antibody mimetics. Common advantages over antibodies are better solubility, tissue penetration, stability towards heat and enzymes, and comparatively low production costs. Antibody mimetics have been developed and commercialized as research, diagnostic and therapeutic agents.
== Binding antibody unit ==
BAU (binding antibody unit, often as BAU/mL) is a measurement unit defined by the WHO for the comparison of assays detecting the same class of immunoglobulins with the same specificity.
== See also ==
== References ==
== External links ==
Mike's Immunoglobulin Structure/Function Page at University of Cambridge
Antibodies as the PDB molecule of the month Discussion of the structure of antibodies at RCSB Protein Data Bank
A hundred years of antibody therapy History and applications of antibodies in the treatment of disease at University of Oxford
How Lymphocytes Produce Antibody from Cells Alive! | Wikipedia/Antibody |
Antimicrobial chemotherapy is the clinical application of antimicrobial agents to treat infectious diseases.
There are five types of antimicrobial chemotherapy:
Antibacterial chemotherapy, the use of antibacterial drugs to treat bacterial infections
Antifungal chemotherapy, the use of antifungal drugs to treat fungal infections
Anthelminthic chemotherapy, the use of antihelminthic drugs to treat worm infections
Antiprotozoal chemotherapy, the use of antiprotozoal drugs to treat protozoan infections
Antiviral chemotherapy, the use of antiviral drugs to treat viral infections
== See also ==
Antimicrobial Agents and Chemotherapy
British Society for Antimicrobial Chemotherapy
Chemotherapy (journal)
Journal of Antimicrobial Chemotherapy
Chemotherapy § The term chemotherapy
== References == | Wikipedia/Antimicrobial_chemotherapy |
Drug liberalization is a drug policy process of decriminalizing, legalizing, or repealing laws that prohibit the production, possession, sale, or use of prohibited drugs. Variations of drug liberalization include drug legalization, drug relegalization, and drug decriminalization. Proponents of drug liberalization may favor a regulatory regime for the production, marketing, and distribution of some or all currently illegal drugs in a manner analogous to that for alcohol, caffeine and tobacco.
Proponents of drug liberalization argue that the legalization of drugs would eradicate the illegal drug market and reduce the law enforcement costs and incarceration rates. They frequently argue that prohibition of recreational drugs—such as cannabis, opioids, cocaine, amphetamines and hallucinogens—has been ineffective and counterproductive and that substance use is better responded to by implementing practices for harm reduction and increasing the availability of addiction treatment. Additionally, they argue that relative harm should be taken into account in the regulation of drugs. For instance, they may argue that addictive or dependence-forming substances such as alcohol, tobacco and caffeine have been a traditional part of many cultures for centuries and remain legal in most countries, although other drugs which cause less harm than alcohol, caffeine or tobacco are entirely prohibited, with possession punishable with severe criminal penalties.
Opponents of drug liberalization argue that it would increase the amount of drug users, increase crime, destroy families, and increase the amount of adverse physical effects among drug users.
== Policies ==
The 1988 United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances made it mandatory for the signatory countries to "adopt such measures as may be necessary to establish as criminal offences under its domestic law" (art. 3, § 1) all the activities related to the production, sale, transport, distribution, etc. of the substances included in the most restricted lists of the 1961 Single Convention on Narcotic Drugs and 1971 Convention on Psychotropic Substances. Criminalization also applies to the "cultivation of opium poppy, coca bush or cannabis plants for the purpose of the production of narcotic drugs". The Convention distinguishes between the intent to traffic and personal consumption, stating that the latter should also be considered a criminal offence, but "subject to the constitutional principles and the basic concepts of [the state's] legal system" (art. 3, § 2).
Drug liberalization proponents hold differing reasons to support liberalization, and have differing policy proposals. The two most common positions are drug legalization (or re-legalization), and drug decriminalization. The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) defines decriminalization as the removal of a conduct or activity from the sphere of criminal law; depenalisation signifying merely a relaxation of the penal sanction exacted by law. Decriminalization usually applies to offences related to drug consumption and may include either the imposition of sanctions of a different kind (administrative) or the abolition of all sanctions; other (noncriminal) laws then regulate the conduct or activity that has been decriminalized. Depenalisation usually consists of personal consumption as well as small-scale trading and generally signifies the elimination or reduction of custodial penalties, while the conduct or activity still remains a criminal offence. The term legalization refers to the removal of all drug-related offences from criminal law, such as use, possession, cultivation, production, and trading.
Harm reduction refers to a range of public health policies designed to reduce the harmful consequences associated with recreational drug use and other high risk activities. Harm reduction is put forward as a useful perspective alongside the more conventional approaches of demand and supply reduction. Many advocates argue that prohibitionist laws criminalize people for suffering from a disease and cause harm, for example by obliging drug addicts to obtain drugs of unknown purity from unreliable criminal sources at high prices, increasing the risk of overdose and death. Its critics are concerned that tolerating risky or illegal behaviour sends a message to the community that these behaviours are acceptable.
=== The Controlled Substance Act (United States) ===
The Controlled Substance Act (CSA) categorizes all substances in need of regulation into one of the five schedules under the federal law. The categorization of these substances is determined by the potential for abuse and how safe it is to consume. In addition, a big determinant of this is the way in which the substance can be consumed or used medically. In its earliest stages, the CSA was created to combine the needs of two international treaties. These treaties were known as the Single Convention on Narcotic Drugs of 1961 and the Convention of Psychotropic Substances of 1971. Both treaties allowed public health authorities to work with the medical and scientific communities to create a classification system. The Schedule I substances were described as those that have no medical use whatsoever; meaning there is no prescription written for such substance. Schedule II substances are those that can be easily abused and lead to dependence. These substances can only be accessed through a written or electronic prescription from a physician. The schedule III substances are classified as those which have less potential for abuse than Schedule I and II but can still cause the individual to develop a mild dependence. Schedule IV substances are those with the least likeliness for abuse, therefore its medical use is common in the United States. Lastly, the Schedule V substances are those with little to no likelihood of abuse, along with very minimal dependence development.
=== Drug legalization (United States) ===
Drug legalization calls for a return to pre–1906 Pure Food and Drug Act attitudes when almost all drugs were legal. This would require ending government-enforced prohibition on the distribution or sale and personal use of specified (or all) currently banned drugs. Proposed ideas range from full legalization which would completely remove all forms of government control, to various forms of regulated legalization, where drugs would be legally available, but under a system of government control which might mean for instance:
Mandated labels with dosage and medical warnings.
Restrictions on advertising.
Age limitations.
Restrictions on amount purchased at one time.
Requirements on the form in which certain drugs would be supplied.
Ban on sale to intoxicated persons.
Special user licenses to purchase particular drugs.
A possible clinical setting for the consumption of some intravenous drugs or supervised consumption.
The regulated legalization system would probably have a range of restrictions for different drugs, depending on their perceived risk, so while some drugs would be sold over the counter in pharmacies or other licensed establishments, drugs with greater risks of harm might only be available for sale on licensed premises where use could be monitored and emergency medical care made available. Examples of drugs with different levels of regulated distribution in most countries include: caffeine (coffee, tea), nicotine (tobacco), and ethyl alcohol (beer, wine, spirits). Since each country has its own regulations and most distinguish between different classes of drugs, there can be difficulties when it comes to regulating which should be more readily accessible, since a particular drug criminalized in one area might be completely acceptable elsewhere. Full legalization is often proposed by groups, such as libertarians, who object to drug laws on moral grounds, while regulated legalization is suggested by groups like Law Enforcement Against Prohibition who object to the drug laws on the grounds that they fail to achieve their stated aims and instead they say greatly worsen the problems associated with the use of prohibited drugs but acknowledge that there are harms associated with currently prohibited drugs which need to be minimized. Not all proponents of drug re-legalization necessarily share a common ethical framework, and people may adopt this viewpoint for a variety of reasons. In particular, favoring drug legalization does not imply approval of drug use.
=== Drug decriminalization ===
Drug decriminalization calls for reduced or eliminated control or penalties compared to existing laws. There are proponents of drug decriminalization that support a system whereby those who use and possess drugs for personal use are not penalized. While others support the use of fines or other punishments to replace prison terms, and often propose systems whereby illegal drug users who are caught would be fined, but would not receive a permanent criminal record as a result. A central feature of drug decriminalization is the concept of harm reduction. Drug decriminalization is in some ways an intermediate between prohibition and legalization, and has been criticized by Peter Lilley as being "the worst of both worlds", in that drug sales would still be illegal, thus perpetuating the problems associated with leaving production and distribution of drugs to the criminal underworld, while also failing to discourage illegal drug use by removing the criminal penalties that might otherwise cause some people to choose not to use drugs.
In 2001, Portugal began treating use and possession of small quantities of drugs as a public health issue. Rather than incarcerating those in possession, they are referred to a treatment program by a regional panel composed of social workers, medical professionals, and drug experts. This also decreases the amount of money the government spends fighting a war on drugs and money spent keeping drug users incarcerated. HIV infection rates also have dropped from 104.2 new cases per million in 2000 to 4.2 cases per million in 2015. Anyone caught with any type of drug in Portugal, if it is for personal consumption, will not be imprisoned. Portugal is the first country that has decriminalized the possession of small amounts of drugs, to positive results.
As noted by the EMCDDA, across Europe in the last decades, there has been a movement toward "an approach that distinguishes between the drug trafficker, who is viewed as a criminal, and the drug user, who is seen more as a sick person who is in need of treatment" (EMCDDA 2008, 22). A number of Latin American countries have similarly moved to reduce the penalties associated with drug use and personal possession" (Laqueur, 2015, p. 748). Mexico City has decriminalized certain drugs and Greece has just announced that it is going to do so. Spain has also followed the Portugal model. Italy after waiting 10 years to see the result of the Portugal model, which Portugal deemed a success, has since recently followed suit. In May 2014, the Criminal Chamber of the Italian Supreme Court upheld a previous decision in 2013 by Italy's Constitutional Court, to reduce the penalties for the convictions for sale of soft drugs. Some other countries have virtual decriminalization for marijuana only, including in three U.S. states, such as Colorado, Washington, and Oregon, the Australian State of South Australia, and across the Netherlands, where there are legal marijuana cafes. In the Netherlands these cafes are called "coffeeshops".
== History ==
The cultivation, use and trade of psychoactive and other drugs has occurred since the dawn of civilization. Motivations claimed by supporters of drug prohibition laws across various societies and eras have included religious observance, allegations of violence by racial minorities, and public health concerns. Those who are proponents of drug legislation characterize these motivations as religious intolerance, racism, and public healthism. The British had gone to war with China in the 19th century in what became known as the First and Second Opium Wars to protect their valuable trade in narcotics. It was only in the 20th century that Britain and the United States outlawed cannabis. The campaign against alcohol prohibition culminated in the Twenty-first Amendment to the United States Constitution repealing prohibition on 5 December 1933, as well as liberalization in Canada, and some but not all of the other countries that enforced prohibition. Despite this, many laws controlling the use of alcohol continue to exist even in these countries. In the mid-20th century, the United States government led a major renewed surge in drug prohibition called the war on drugs.
Initial attempts to change the punitive drug laws which were introduced all over the world from the late 1800s onwards were primarily based around recreational use. Timothy Leary was one of the most prominent campaigners for the legal and recreational use of LSD. In 1967, a "Legalise pot" rally was held in Britain. As death toll from the drug war rose, other organisations began to form to campaign on a more political and humanitarian basis. Drug Policy Foundation formed in America and Release, a charity which gives free legal advice to drugs users and currently campaigns for drug decriminalization, also incorporated in the 1970s. Into the 21st century, the focus of the world's drug policy reform organisations is on the promotion of harm reduction in the Western World, and attempting to prevent the catastrophic loss of human life in developing countries where much of the world's supply of heroin, cocaine, and marijuana are produced. Drug policy reform advocates point to failed efforts, such as the Mexican Drug War, as signs that a new approach to drug policy is needed. According to some observers, the Mexican Drug War has claimed as many as 80,000 lives.
In 2014, a European Citizens' Initiative called "Weed Like to Talk" was launched within the European Union, with the aim of starting a debate in Europe about the legalization of the production, sale and use of marijuana in the European Union and finding a common policy for all EU member states. As of June 30, 2014, the initiative has collected 100,000 signatures from citizens in European member states. Should they reach 1 million signatures, from nationals of at least one quarter of the member states, the European Commission will be required to initiate a legislative proposal and a debate on the issue.
== Impacts ==
A Independent Scientific Committee on Drugs study found drug harms, such as economic cost, injury, family adversities, environmental damage, and community harm vary between different drugs.
=== Harms to others and society ===
Proponents of drug prohibition argue that many negative externalities, or third party costs, are associated with the consumption of illegal drugs.: 2043 : 183 Externalities like violence, environmental effects on neighborhoods, increased health risks, and increased healthcare costs are often associated with the illegal drug market.: 3
Opponents of prohibition argue that some of those externalities are created by criminalizing drug policies. They believe that much of the violence associated with drug trade is due to the illegal nature of drug trade, where there is no mediating authority to solve disputes peacefully and legally.: 3 : 177 The illegal nature of the market also affects the health of consumers by making it difficult to acquire syringes, which often leads to needle sharing.: 180–181
Economist Milton Friedman argues that prohibition of drugs creates many negative externalities like increased incarceration rates, the undertreatment of chronic pain, corruption, disproportional imprisonment of African Americans, compounding harm to users, the destruction of inner cities and harm to foreign countries. Proponents of legalization also argue that prohibition decrease the quality of the drugs made, which often leads to more physical harm, like accidental overdoses and poisoning, to the drug users.: 179 Steven D. Levitt and Ilyana Kuziemko point to the over crowding of prisons as another negative side effect of the war on drugs. They believe that by sending such a large number of drug offenders to prison, the war on drugs has reduced the prison space available for other offenders. This increased incarceration rate not only costs tax payers more to maintain, it could possibly increase crime by crowding violent offenders out of prison cells and replacing them with drug offenders.: 2043 According to economist Mark Thornton prohibition increases political corruption and crime.
Prohibition can produce more dangerous and addictive drugs. Milton Friedman estimated that over 10,000 deaths a year in the US are caused by the criminalization of drugs, and if drugs were to be made legal, number of innocent victims such as those shot down in drive by shootings would decrease.
=== Cost of law enforcement ===
A Harvard economist, Jeffrey Miron, estimated that ending the war on drugs would inject 76.8 billion dollars into the US economy in 2010 alone. He estimates that the government would save $41.3 billion for law enforcement and the government would gain up to $46.7 billion in tax revenue. Since the war on drugs began under the administration of President Richard Nixon, the federal drug-fighting budget has increased from $100 million in 1970 to $15.1 billion in 2010, with a total cost estimated near 1 trillion dollars over 40 years. In the same time period an estimated 37 million nonviolent drug offenders have been incarcerated. $121 billion was spent to arrest these offenders and $450 billion to incarcerate them. The legalization would reduce the cost of having to mass incarcerate marginalized communities, which are those who are disproportionately affected. Of those arrested for drug possession or drug related crimes, the majority of those individuals arrested are Black or Hispanic.
The economic inefficiency and ineffectiveness of such government intervention in preventing drug trade has been criticised by drug-liberty advocates. The war on drugs of the United States, that provoked legislation within several other Western governments, has also garnered criticism for these reasons.
=== Demand curve ===
Much of the debate surrounding the economics of drug legalization centers on the shape of the demand curve for illegal drugs and the sensitivity of consumers to changes in the prices of illegal drugs. Proponents of drug legalization often assume that the quantity of addictive drugs consumed is unresponsive to changes in price; however, studies into addictive but legal substances like alcohol and cigarettes have shown that consumption can be quite responsive to changes in prices. In the same study, economists Michael Grossman and Frank J. Chaloupka estimated that a 10% reduction in the price of cocaine would lead to a 14% increase in the frequency of cocaine use.: 459 This increase indicates that consumers are responsive to price changes in the cocaine market. There is also evidence that in the long run, consumers are much more responsive to price changes than in the short run,: 454 but other studies have led to a wide range of conclusions.: 2043
Considering that legalization would likely lead to an increase in the supply of drugs, the standard economic model predicts that the quantity of drugs consumed would rise and the prices would fall.: 428 Andrew E. Clark, an economist who has studied the effects of drug legalization, suggests that a specific tax, or sin tax, would counteract the increase in consumption.: 3
== Size of the illegal drug market ==
According to 2013 data from the United Nations Office on Drugs and Crime (UNODC) and European crime-fighting agency Europol, the annual global drugs trade is worth around $435 billion a year, with the annual cocaine trade worth $84 billion of that amount.
== Policies by country ==
=== Asia ===
==== Philippines ====
Senator Bato dela Rosa, despite having the reputation of leading the deadly war on drugs during the presidency of Rodrigo Duterte as chief of the Philippine National Police, filed a bill in the senate in November 2022 proposing the decriminalization of illegal drug use. This bid was an attempt to deal with prison overcrowding and underutilization of drug rehabilitation centers. While the proposal do not include drug trafficking and manufacturing, the bill was met with opposition from law enforcement agencies who believes it would send a "wrong signal" and encourage drug abuse. The Department of Health has supported the proposal.
==== Thailand ====
"A committee tasked with controlling illegal drugs has won a majority vote to have cannabis and hemp reclassified as narcotics, and the listing will take effect on" 1 January 2024, according to media.
Although Thailand has a strict drug policy, in May 2018, the Cabinet approved draft legislation that allows for more research into the effects of marijuana on people. Thus, the Government Pharmaceutical Organization (GPO) will soon begin clinical trials of marijuana as a preliminary step in the production of drugs from this plant. These medical studies are considered exciting, new landmarks in the history of Thailand, because the manufacture, storage, and use of marijuana has been completely outlawed in Thailand since 1979.
On 9 November 2018, the National Assembly of Thailand officially proposed to allow licensed medical use of marijuana, thereby legalizing what was previously considered a dangerous drug. The National Assembly on Friday submitted its amendments to the Ministry of Health, which would place marijuana and vegetable kratom in the category allowing their licensed possession and distribution in regulated conditions. The ministry reviewed the amendments before sending them to the cabinet, which returned it to the National Assembly for a final vote. This process was completed on 25 December 2018. Thus, Thailand became the first Asian country to legalize medical cannabis. These changes did not allow recreational use of drugs. These actions were taken because of the growing interest in the use of marijuana and its components for the treatment of certain diseases. Cannabis became decriminalized in Thailand on 9 June 2022, making recreational use also legal, although smoking in public can still incur penalties due to being considered a public nuisance. Supporters of legalization argue that the legal market for marijuana in Thailand could increase to $5 billion by 2024.
=== Europe ===
==== Czech Republic ====
In the Czech Republic, until 31 December 1998 only drug possession "for other person" (i.e. intent to sell) was criminal (apart from production, importation, exportation, offering or mediation, which was and remains criminal) while possession for personal use remained legal. On 1 January 1999, an amendment of the Criminal Code, which was necessitated in order to align the Czech drug rules with the Single Convention on Narcotic Drugs, became effective, criminalizing possession of "amount larger than small" also for personal use (Art. 187a of the Criminal Code) while possession of small amounts for personal use became a misdemeanor. The judicial practice came to the conclusion that the "amount larger than small" must be five to ten times larger (depending on drug) than a usual single dose of an average consumer.
On 14 December 2009, the Government of the Czech Republic adopted Regulation No. 467/2009 Coll., that took effect on 1 January 2010, and specified what "amount larger than small" under the Criminal Code meant, effectively taking over the amounts that were already established by the previous judicial practice. According to the regulation, a person could possess up to 15 grams of marijuana or 1.5 grams of heroin without facing criminal charges. These amounts were higher (often many times) than in any other European country, possibly making the Czech Republic the most liberal country in the European Union when it comes to drug liberalization, apart from Portugal. Under the Regulation No. 467/2009 Coll, possession of the following amounts or less of illicit drugs was to be considered smaller than large for the purposes of the Criminal Code and was to be treated as a misdemeanor subject to a fine equal to a parking ticket:
Marijuana 15 grams (or five plants)
Hashish 5 grams
Magic mushrooms 40 pieces
Peyote 5 plants
LSD 5 tablets
Ecstasy 4 tablets
Amphetamine 2 grams
Methamphetamine 2 grams
Heroin 1.5 grams
Coca 5 plants
Cocaine 1 gram
In 2013, a District Court in Liberec was deciding a case of a person that was accused of criminal possession for having 3.25 grams of methamphetamine (1.9 grams of straight methamphetamine base), well over the Regulation's limit of 2 grams. The court considered that basing a decision on mere Regulation would be unconstitutional and in breach of Article 39 of the Czech Charter of Fundamental Rights and Freedoms which states that "only a law may designate which acts constitute a crime and what penalties, or other detriments to rights or property, may be imposed for committing them" and proposed to the Constitutional Court to abolish the Regulation. In line with the District Courts' argument, the Constitutional Court abolished the Regulation effective from 23 August 2013, noting that the "amount larger than small" within the meaning of the Criminal Code may be designated only by the means of an Act of Parliament, and not a Governmental Regulation. Moreover, the Constitutional Court further noted that the Regulation merely took over already existing judicial practice of interpretation of what constitutes "amount larger than small" and thus its abolishment will not really change the criminality of drug possession in the country. Thus, the above-mentioned amounts from the now-not-effective Regulation remain as the base for consideration of police and prosecutors, while courts are not bound by the precise grammage.
Sale of any amount (not purchase) remains a criminal act. Possession of "amount larger than a small" of marijuana can result in a jail sentence of up to one year. For other illicit drugs, the sentence is up to two years. Trafficking as well as production (apart from growing up to five plants of marijuana) offenses carry stiffer sentences. Medical use of cannabis on prescription has been legal and regulated since 1 April 2013.
==== France ====
Following a contentious debate France opened its first supervised injection centre on 11 October 2016. Marisol Touraine, the Minister of Health, declared that the centre, located near the Gare du Nord in Paris, was "a strong political response, for a pragmatic and responsible policy that brings high-risk people back towards the health system rather than stigmatizing them."
==== Germany ====
In 1994, the Federal Constitutional Court ruled that drug addiction was not a crime, nor was the possession of small amounts of drugs for personal use. In 2000, the German narcotic law (BtmG) was changed to allow for supervised drug injection rooms. In 2002, a pilot study was started in seven German cities to evaluate the effects of heroin-assisted treatment on addicts, compared to methadone-assisted treatment. The positive results of the study led to the inclusion of heroin-assisted treatment into the services of the mandatory health insurance in 2009. On 4 May 2016, the Cabinet of Germany decided to approve the measure for legal cannabis for seriously ill patients who have consulted with a doctor and "have no therapeutic alternative". German Health Minister, Hermann Gröhe, presented the legal draft on the legalization of medical cannabis to the cabinet which was expected to take effect early 2017.
==== Ireland ====
On 2 November 2015, Aodhán Ó Ríordáin, the minister in charge of the National Drugs Strategy, announced that Ireland planned to introduce supervised injection rooms. The minister also referenced that possession of controlled substances will be decriminalized although supply and production will remain criminalized. On 12 July 2017, the Health Committee of the Irish government rejected a bill that would have legalized medical cannabis.
==== Netherlands ====
The drug policy of the Netherlands is based on two principles: (1) drug use is a public health issue, not a criminal matter, and (2) a distinction between hard and soft drugs exists. Additionally, a policy of non-enforcement has led to a situation where reliance upon non-enforcement has become common; because of this, the courts have ruled against the government when individual cases were prosecuted. Cannabis remains a controlled substance in the Netherlands and both possession and production for personal use are still misdemeanors, punishable by fine. Cannabis coffee shops are also illegal according to the statutes.
==== Norway ====
On 14 June 2010, the Stoltenberg commission recommended implementing heroin assisted treatment and expanding harm reduction measures. On 18 June 2010, Knut Storberget, Minister of Justice and the Police, announced that the ministry was working on new drug policy involving decriminalization by the Portugal model, which was to be introduced to parliament before the next general election. Storberget later changed his statements, saying the decriminalization debate is "for academics", instead calling for coerced treatment. In early March 2013, minister of health and care services Jonas Gahr Støre proposed to decriminalize the inhalation of heroin by 2014 as a measure to decrease drug overdoses. In 2011, there were 294 fatal overdoses, in comparison to only 170 traffic related deaths.
The country was preparing a massive policy change in terms of how to deal with drug use and drug possession for personal use. The reform titled "From punishment to help" was approved by the Norwegian government in 2017 and was in the final phase of approval by the parliament. Changes were expected to be implemented by early 2021. The new reform policy emphasizes that criminalizing drug use has no significant effect on rates of drug consumption and that drug addiction is better dealt with by health care services, hence the slogan "from punishment to help". Instead of fines or prison time, a person caught with a drug quantity for personal use will now be met with an independent panel consisting of social and health care workers that will discuss administrative sanctions or addiction treatment methods. This will hopefully encourage problematic users to seek help rather than fear of prosecution. There is also hope that this will improve the relationship between drug users and law enforcement officers. Opponents of the reform, including the police force and the Progress Party, fear that drug use will increase once a person is no longer at risk of facing criminal charges.
As of 21 July 2022, drug decriminalisation has not materialised in Norway. As of this date, only those who have substance use disorders may go unpunished if the amount of illegal drugs they have meets the criteria of what is deemed an amount for personal use.
==== Portugal ====
In 2001, Portugal became the first European country to abolish all criminal penalties for personal drug possession, under Law 30/2000. In addition, drug users were to be provided with therapy rather than prison sentences. Research commissioned by the Cato Institute and led by Glenn Greenwald found that in the five years after the start of decriminalization, illegal drug use by teenagers had declined, the rate of HIV infections among drug users had dropped, deaths related to heroin and similar drugs had been cut by more than half, and the number of people seeking treatment for drug addiction had doubled. Peter Reuter, a professor of criminology and public policy at the University of Maryland, College Park, suggested that the heroin usage rates and related deaths may have been due to the cyclical nature of drug epidemics. In 2009, he stated that "decriminalization in Portugal has met its central goal. Drug use did not rise." In 2022, drug use had increased to 12.8 percent, compared to 7.8 percent in 2001 when the policies had been implemented.
==== Ukraine ====
The use of marijuana in Ukraine is not prohibited, but the manufacture, storage, transportation and sale of cannabis and its derivatives are under administrative and criminal liability. Speaking on the legalization of soft drugs in Ukraine has been going on for a long time. In June 2016, the Parliament received a bill on the legalization of marijuana for medical purposes. It dealt with changes to the current act "On narcotic drugs, psychotropic substances and precursors" and was registered number 4533. The document must examine the relevant committee, and then submit it to the government. It was expected that this would happen in the fall of 2016, but the bill was not considered. In October 2018, a petition appeared on the website of electronic appeals to the President of Ukraine asking for the legalization of marijuana. In October 2018, the State Service of Ukraine on Drugs and Drug Control issued the first license for the import and re-export of raw materials and products derived from cannabis. The corresponding licenses were obtained by the USA company C21. The company is also in the process of applying for additional licenses, including the cultivation of cannabis.
=== Latin America ===
In the late 2000s and early 2010s, advocacy for drug legalization has increased in Latin America. Spearheading the movement Uruguayan government announced in 2012 plans to legalize state-controlled sales of marijuana in order to fight drug-related crimes. Some countries in this region have already advanced towards depenalization of personal consumption.
==== Argentina ====
In August 2009, the Supreme Court of Argentina declared in a landmark ruling that it was unconstitutional to prosecute citizens for having drugs for their personal use – "adults should be free to make lifestyle decisions without the intervention of the state". The decision affected the second paragraph of Article 14 of the country's drug control legislation (Law Number 23,737) that punishes the possession of drugs for personal consumption with prison sentences ranging from one month to two years (although education or treatment measures can be substitute penalties). The unconstitutionality of the article concerns cases of drug possession for personal consumption that does not affect others.
==== Brazil ====
In 2002 and 2006, Brazil went through legislative changes, resulting in a partial decriminalization of possession for personal use. Prison sentences no longer applied and were replaced by educational measures and community services; however, the 2006 law does not provide objective means to distinguish between users or traffickers. A disparity exists between the decriminalization of drug use and the increased penalization of selling drugs, punishable with a maximum prison sentences of 5 years for the sale of very minor quantities of drugs. Most of those incarcerated for drug trafficking are offenders caught selling small quantities of drugs, among them drug users who sell drugs to finance their drug habits. Since 2006, there has been a long debate whether the anti-drug law goes against the Constitution and principle of personal freedom. In 2009, the Supreme Federal Court re-opened to vote if the law is Constitutional, or if it goes against the Constitution specifically against personal Freedom of choice. Since each Minister inside the tribunal can take a personal time to evaluate the law, the voting can take years. In fact, the voting was re-opened in 2015, 3 ministers voted in favor, and then the law was again paused by another minister.
==== Colombia ====
Guatemalan President Otto Pérez Molina and Colombian President Juan Manuel Santos proposed the legalization of drugs in an effort to counter the failure of the war on drugs, which was said to have yielded poor results at a huge cost. On 25 May 2016, the Colombian congress approved the legalization of marijuana for medical usage.
==== Costa Rica ====
Costa Rica has decriminalized drugs for personal consumption. Manufacturing or selling drugs is still a jailable offense.
==== Ecuador ====
According to the 2008 Constitution of Ecuador, in its Article 364, the Ecuadorian state does not see drug consumption as a crime but only as a health concern. Since June 2013, the state drugs regulatory office CONSEP has published a table which establishes maximum quantities carried by persons so as to be considered in legal possession and that person as not a seller of drugs. The "CONSEP established, at their latest general meeting, that the following quantities be considered the maximum consumer amounts: 10 grams of marijuana or hash, 4 grams of opiates, 100 milligrams of heroin, 5 grams of cocaine, 0.020 milligrams of LSD, and 80 milligrams of methamphetamine or MDMA".
==== Honduras ====
On 22 February 2008, Honduras President Manuel Zelaya called on the United States to legalize drugs in order to prevent the majority of violent murders occurring in Honduras. Honduras is used by cocaine smugglers as a transiting point between Colombia and the US. Honduras, with a population of 7 million affected people an average of 8–10 murders a day, with an estimated 70% being as a result of this international drug trade. According to Zelaya, the same problem is occurring in Guatemala, El Salvador, Costa Rica, and Mexico.
==== Mexico ====
In April 2009, the Mexican Congress approved changes in the General Health Law that decriminalized the possession of illegal drugs for immediate consumption and personal use allowing a person to possess up to 5 g of marijuana or 500 mg of cocaine. The only restriction is that people in possession of drugs should not be within a 300-meter radius of schools, police departments, or correctional facilities. Opium, heroin, LSD, and other synthetic drugs were also decriminalized, it will not be considered as a crime as long as the dose does not exceed the limit established in the General Health Law. Many question this, as cocaine is as much synthesised as heroin, both are produced as extracts from plants. The law establishes very low amount thresholds and strictly defines personal dosage. For those arrested with more than the threshold allowed by the law this can result in heavy prison sentences, as they will be assumed to be small traffickers even if there are no other indications that the amount was meant for selling.
==== Uruguay ====
Uruguay is one of few countries that never criminalized the possession of drugs for personal use. Since 1974, the law establishes no quantity limits, leaving it to the judge's discretion to determine whether the intent was personal use. Once it is determined by the judge that the amount in possession was meant for personal use, there are no sanctions. In June 2012, the Uruguayan government announced plans to legalize state-controlled sales of marijuana in order to fight drug-related crimes. The government also stated that they will ask global leaders to do the same.
On 31 July 2013, the Uruguayan House of Representatives approved a bill to legalize the production, distribution, sale, and consumption of marijuana by a vote of 50 to 46. The bill then passed the Senate, where the left-leaning majority coalition, the Broad Front, held a comfortable majority. The bill was approved by the Senate by 16 to 13 on 10-December-2013. The bill was presented to the President José Mujica, also of the Broad Front coalition, who has supported legalization since June 2012. Relating this vote to the 2012 legalization of marijuana by the U.S. states Colorado and Washington, John Walsh, drug policy expert of the Washington Office on Latin America, stated that "Uruguay's timing is right. Because of last year's Colorado and Washington State votes to legalize, the U.S. government is in no position to browbeat Uruguay or others who may follow."
In July 2014, government officials announced that part of the implementation of the law (the sale of cannabis through pharmacies) is postponed to 2015, as "there are practical difficulties". Authorities will grow all the cannabis that can be sold legal. Concentration of THC shall be 15% or lower. In August 2014, an opposition presidential candidate, who was not elected in the November 2014 presidential elections, claimed that the new law was never going to be applied, as it was not workable. By the end of 2016 the government announced that the sale through pharmacies will be fully implemented during 2017.
=== North America ===
==== Canada ====
The cultivation of cannabis is currently legal in Canada, except in Manitoba and Quebec. Citizens outside those provinces may grow up to four plants per residence for personal use, and recreational use of cannabis by the general public is legal with restrictions on smoking in public locations that vary by jurisdiction. The sale of marijuana seeds is also legal.
In 2001, The Globe and Mail reported that a poll found 47% of Canadians agreed with the statement, "The use of marijuana should be legalized" in 2000, compared to 26% in 1975. A more recent poll found that more than half of Canadians supported legalization. In 2007, Prime Minister Stephen Harper's government tabled Bill C-26 to amend the Controlled Drugs and Substances Act, 1996 to bring forth a more restrictive law with higher minimum penalties for drug crimes. Bill-26 died in committee after the dissolution of the 39th Canadian Parliament in September 2008, but the Bill was subsequently resurrected by the government twice.
In 2015, Prime Minister Justin Trudeau and the Liberal Party of Canada campaigned on a promise to legalize marijuana. The Cannabis Act was passed on 19 June 2018, which made marijuana legal across Canada on 17 October 2018. Since legalization, the country has set up an online framework to allow consumers to purchase a wide variety of merchandise ranging from herbs, extract, oil capsules, and paraphernalia. Most provinces also provide a venue for purchase through physical brick and mortar stores.
In 2021, the city councils of Vancouver and Toronto voted to decriminalize the simple possession of all drugs; and submitted proposals requesting special exemption from the federal Health Minister to do so, citing numerous scientific, psychological, medical, and socio-economic benefits. In early 2022, the Province of British Columbia submitted its own request for exemption, closely following the Vancouver model. By April of that year, the Edmonton City Council had also passed a motion to request exemption from federal drug enforcement laws in order decriminalize "simple personal possession" of illegal drugs, voting in favour 11–2. On 31 May 2022, the federal government of Canada approved British Columbia's proposal to decriminalize all "hard drugs", such as heroin, fentanyl, cocaine, and methamphetamine. As of 1 January 2023, British Columbians aged 18 years or older are allowed to carry up to a cumulative total of 2.5 grams of these substances without the risk of arrest or criminal charges. Police are not to confiscate the drugs, and there is no requirement that people found to be in possession seek treatment; however, the production, trafficking, and exportation of these drugs remain illegal.
==== United States ====
As of 2024, prior to November elections, 38 states, Washington, D.C., and certain U.S. territories allow medical use of cannabis. Of those 38 states, 24 also allow recreational use, as does Washington, D.C. Voters in North and South Dakota and Florida will decide on recreational use in November, and Nebraskans will vote on cannabis use for medical reasons. Legalization in states created significant legal and policy tensions between federal and state governments and sometimes between states. State laws in conflict with federal law about cannabis remain valid, and prevent state level prosecution, despite cannabis being illegal under federal law, as determined in Gonzales v. Raich (2005).
Throughout the United States, various people and groups have been pushing for the legalization of marijuana for medical reasons. Organizations such as NORML and the Marijuana Policy Project work to decriminalize and legalize possession, use, cultivation, and sale of marijuana by adults. In 1996, 56% of California voters voted for California Proposition 215, legalizing the growing and use of marijuana for medical purposes and making California both the first state to outlaw marijuana, in 1913, and the first state to legalize medical marijuana.
On 6 November 2012, the states of Washington and Colorado legalized possession of small amounts of marijuana for private recreational use and created a process for writing rules for legal growing and commercial distribution of marijuana within each state, after having legalized medical cannabis in 1998 and 2000, respectively. In 2014, voters in Oregon, Alaska, and Washington, D.C. voted to legalize marijuana for recreational use, as did California in 2016, with the passage of California Proposition 64, and Michigan in 2018. In 2019, Illinois passed the Illinois Cannabis Regulation and Tax Act, making Illinois the first state to legalize recreational use by an act of the state legislature, which took effect 1 January 2020. In 2020, Oregon decriminalized the possession of all drugs in Measure 110, but in 2024, the Oregon State Senate passed a bill to reverse the decriminalization of hard drugs such as heroin after there was public backlash to the impacts of the measure. In 2021, New York legalized adult-use cannabis when it passed the Marijuana Regulation and Taxation Act (MRTA).
=== Oceania ===
==== Australia ====
In 2016, Australia legalised medicinal cannabis on a federal level. Since 1985, the Federal Government has run a declared war on drugs and while initially Australia led the world in 'harm-minimization' approach, they have since lagged. Australia has a number of political parties that focus on cannabis reform, The (HEMP) Help End Marijuana Prohibition Party was founded in 1993 and registered by the Australian Electoral Commission in 2000. The Legalise Cannabis Queensland Party was established in 2020. A number of Australian and international groups have promoted reform in regard to 21st-century Australian drug policy. Organisations such as Australian Parliamentary Group on Drug Law Reform, Responsible Choice, the Australian Drug Law Reform Foundation, Norml Australia, Law Enforcement Against Prohibition (LEAP) Australia and Drug Law Reform Australia advocate for drug law reform without the benefit of government funding. The membership of some of these organisations is diverse and consists of the general public, social workers, lawyers and doctors, and the Global Commission on Drug Policy has been a formative influence on a number of these organisations. In 1994, the Australian National Task Force on Cannabis formed under the Ministerial Council on Drug Strategy noted that the social harm of cannabis prohibition is greater than the harm from cannabis itself, total prohibition policies have been unsuccessful in reducing drug use and have caused significant social harm, as well as higher law enforcement costs, the use of cannabis is widespread in Australia and that its adverse health effects are modest and only affect a minority of users.
In 2012, the think tank Australia 21, released a report on the decriminalization of drugs in Australia. It noted that "by defining the personal use and possession of certain psychoactive drugs as criminal acts, governments have also avoided any responsibility to regulate and control the quality of substances that are in widespread use." Prohibition has fostered the development of a criminal industry that is corrupting civil society and government and killing our children." The report also highlighted the fact that, just as alcohol and tobacco are regulated for quality assurance, distribution, marketing and taxation, so should currently, unregulated, illicit drugs. There has been a number of enquires in Australia relating to cannabis and other illicit drugs, in 2019 the Queensland government instructed the Queensland Productivity Commission to conduct an enquiry into imprisonment and recidivism in QLD; the final report was sent to the Queensland Government on 1 August 2019 and publicly released on 31 January 2020. The commission found that "all available evidence shows the war on drugs fails to restrict usage or supply" and that "decriminalisation would improve the lives of drug users without increasing the rate of drug use" with the commission ultimately recommending that the Queensland government legalise cannabis. The QPC said the system had also fuelled an illegal market, particularly for methamphetamine. Although the Palaszczuk Queensland Labor Party led state government rejected the recommendations of its own commission and said it had no plans to alter any laws around cannabis, a decision that received heavy scrutiny from supporters of decriminalization, legalisation, progressive and non progressive drug policy advocates alike.
In 2019, The Royal Australasian College of Physicians (RACP) and St. Vincent's Health Australia called on the NSW Government to publicly release the findings of the Special Commission of Inquiry into the Drug 'Ice, saying there was "no excuse" for the delay. The report was the culmination of months of evidence from health and judicial experts, as well as families and communities affected by amphetamine-type substances across NSW. The report made 109 recommendations aimed to strengthen the NSW Governments response regarding amphetamine-based drugs such as crystal meth or ice. Major recommendations included more supervised drug use rooms, a prison needle and syringe exchange program, state-wide clinically supervised substance testing, including mobile pill testing at festivals, decriminalisation of drugs for personal use, a cease to the use of drug detection dogs at music festivals and to limit the use of strip searches. The report, also called for the NSW Government to adopt a comprehensive Drug and Alcohol policy, with the last drug and Alcohol policy expiring over a decade ago. The reports commissioner said the state's approach to drug use was profoundly flawed and said reform would require "political leadership and courage" and "Criminalising use and possession encourages us to stigmatise people who use drugs as the authors of their own misfortunate". Mr Howard said current laws "allow us tacit permission to turn a blind eye to the factors driving most problematic drug use" including childhood abuse, domestic violence and mental illness. The NSW government rejected the reports key recommendations, saying it would consider the other remaining recommendations. Director of the Drug Policy Modelling Program (DPMP) at UNSW Sydney's Social Policy Research Centre said the NSW Government has missed an opportunity to reform the state's response to drugs based on evidence. The NSW Government is yet to officially respond to the inquiry as of November 2020, a statement was released from the government citing intention to respond by the end of 2020.
In the Australian Capital Territory, after a bill was passed on 25 September 2019, new laws came into effect on 31 January 2020. While personal possession and growth of small amounts of cannabis remains prohibited non-medicinal purposes in every other jurisdiction in Australia, it allowed for possession of up to 50 grams of dry material, 150 grams of wet material, and cultivation of 2 plants per individual up to 4 plants per household, effectively legalising the possession and growing of cannabis in the ACT; however the sale and supply of cannabis and cannabis seeds is still illegal, so the effects of the laws are limited and the laws also contradict federal laws. It is also still illegal to smoke or use cannabis in a public place, expose a child or young person to cannabis smoke, store cannabis where children can reach it, grow cannabis using hydroponics or artificial cultivation, grow plants where they can be accessed by the public, share or give cannabis as a gift to another person, to drive with any cannabis in your system, or for people aged under 18 to grow, possess, or use cannabis.
==== New Zealand ====
On 18 December 2018, the Labour-led government announced a nationwide, binding referendum on the legality of cannabis for personal use, set to be held as part of the 2020 general election. This was a condition of the Green Party giving confidence and supply to the Government. On 7 May 2019, the government announced that the 2020 New Zealand cannabis referendum would be a yes/no question to enact a yet-to-be created piece of legislation. Despite the earlier commitment, the referendum was non-binding, the proposed Cannabis Legalisation and Control Bill would have need to be introduced into Parliament and passed like any other piece of legislation; therefore, the government was not in fact bound to the results of the referendum. Official results for the general election and referendums were released on 6 November 2020. The number opposed to legalisation was 50.7% with 48.4% in favour and 0.9% of votes were declared Informal.
== Groups advocating change ==
The Senlis Council, a European development and policy think tank, has, since its conception in 2002, advocated that drug addiction should be viewed as a public health issue rather than a purely criminal matter. The group does not support the decriminalisation of illegal drugs. Since 2003, the council has called for the licensing of poppy cultivation in Afghanistan in order to manufacture poppy-based medicines, such as morphine and codeine, and to combat poverty in rural communities, breaking ties with the illicit drugs trade. The Senlis Council outlined proposals for the implementation of a village based poppy for medicine project and calls for a pilot project for Afghan morphine at the next planting season.
== Organizations involved in lobbying, research and advocacy ==
=== Canada ===
Le Dain Commission of Inquiry into the Non-Medical Use of Drugs
=== Europe ===
Beckley Foundation
Cannabis Law Reform
Drug Equality Alliance (DEA)
European Coalition for Just and Effective Drug Policies (ENCOD) (Branches in Austria, Germany and Norway)
Legalize.net (Netherlands)
Schildower Kreis (Goethe University Frankfurt, Germany)
NORML UK
Re:Vision Drug Policy Network (United Kingdom)
Regulación Responsible (Spain)
Release (agency) (United Kingdom)
Students for Sensible Drug Policy UK (United Kingdom)
Transform Drug Policy Foundation
=== Australia ===
Australian National Council on Drugs
Drug Policy Australia
Network Against Prohibition
=== New Zealand ===
The Helen Clark Foundation
NORML New Zealand
The STAR Trust
=== United States ===
American Civil Liberties Union
Americans for Safe Access
Drug Policy Alliance
High Times
High Times Freedom Fighters
Law Enforcement Against Prohibition
Lindesmith Center
Marijuana Policy Project
MASS CANN/NORML
Multidisciplinary Association for Psychedelic Studies (MAPS)
National Organization for the Reform of Marijuana Laws
Students for Sensible Drug Policy
Veterans for Medical Marijuana Access
November Coalition (United States)
Women Grow
== Political parties with drug liberalization policies ==
Many political parties support, to various degrees, and for various reasons, liberalizing drug control laws, from liberal parties to far-left movements, as well as some right-wing intellectuals. Drug liberalization is fundamental in the platforms of most Libertarian parties. There are also numerous single issue marijuana parties devoted to campaign for the legalization of cannabis exclusively.
=== Australia ===
Australian Greens
Drug Law Reform Australia
Fusion Party
Legalise Cannabis Australia
Legalise Cannabis Queensland
Legalise Cannabis Western Australia Party
Reason Party
=== Canada ===
Liberal Party of Canada
New Democratic Party of Canada
Libertarian Party of Canada
Marijuana Party
=== Hungary ===
MKKP
=== Netherlands ===
GroenLinks
D66
=== Germany ===
Die Linke
=== New Zealand ===
Green Party of Aotearoa New Zealand
=== Portugal ===
Left Bloc
Liberal Initiative
LIVRE
=== United Kingdom ===
Green Party of England and Wales
Liberal Democrats – in March 2016, the Liberal Democrats became the first major political party in the United Kingdom to support the legalisation of cannabis.
=== International ===
Pirate Party
== See also ==
== References ==
== Further reading ==
Anderson, D. Mark, and Daniel I. Rees. 2023. "The Public Health Effects of Legalizing Marijuana." Journal of Economic Literature 61(1): 86–143.
International Coalition on Drug Policy Reform and Environmental Justice. 2023. "Revealing the missing link to Climate Justice: Drug Policy."
== External links ==
Transform Drug Policy Foundation – A UK-based think-tank that works to develop systems for control and regulation that can be applied globally.
Law Enforcement Against Prohibition – Run by retired law enforcement professionals who oppose prohibition.
Voluntary Committee of Lawyers – a New York-based network of judges and lawyers opposed to current federal drug laws.
NORML (US National Organization for the Reform of Marijuana Laws) – a US wide network of activists seeking to liberalize cannabis legislation.
Re:Vision Drug Policy Network – an organisation for young people aged 16–25 campaigning against prohibition.
The Report of the Canadian Government Commission of Inquiry into the Non-Medical Use of Drugs – 1972 – The LeDain Commission Report
Drug Law Reform – a project of the Transnational Institute (TNI)
Draft Plan for Legalization from LIFE – an example of a policy formulation proposed for substance legalization
Count The Costs
Schaffer Library of Drug Policy
Worldwide Psychedelic Laws Tracker | Wikipedia/Drug_policy_reform |
The illegal drug trade, drug trafficking, or narcotrafficking is a global black market dedicated to the cultivation, manufacture, distribution and sale of prohibited drugs. Most jurisdictions prohibit trade, except under license, of many types of drugs through the use of drug prohibition laws. The think tank Global Financial Integrity's Transnational Crime and the Developing World report estimates the size of the global illicit drug market between US$426 and US$652 billion in 2014, which is equal to the UK's national debt alone. With a world GDP of US$78 trillion in the same year, the illegal drug trade may be estimated as nearly 1% of total global trade. Consumption of illegal drugs is widespread globally, and it remains very difficult for local authorities to reduce the rates of drug consumption.
== History ==
Prior to the 20th century, governments rarely made a major effort to proscribe recreational drug use, though several smoking bans were passed by authorities in Europe and Asia during the early modern era. Tobacco and opium were the two first drugs to be subject to prohibitory government legislation, with officials in New Spain, the Ottoman Empire, Germany, Austria and the Russian Empire passing laws against smoking tobacco; the government of the Qing dynasty issued edicts banning opium smoking in 1730, 1796 and 1800. Beginning in the 18th century, the East India Company (EIC) began to smuggle Indian opium to Chinese merchants, resulting in the creation of an illegal drug trade in China. By 1838, there were between four and 12 million opium addicts in China, and Qing officials responded by strengthening their suppression of the illegal opium trade. Incidents such as the destruction of opium at Humen led to the outbreak of the First Opium War between China and Britain in 1839; the 1842 Treaty of Nanking ending the war did not legalize the importation of opium into China, but Western merchants continued to smuggle the drug to Chinese merchants in ever-increasing amounts. The 1858 Treaty of Tianjin, which ended the Second Opium War, stipulated that the Qing government would open several ports to foreign trade, including opium.
Western governments began prohibiting addictive drugs during the late 19th and early 20th centuries. In 1868, as a result of the increased use of opium in Britain, the British government restricted the sale of opium by implementing the 1868 Pharmacy Act. In the United States, control of opium remained under the control of individual US states until the introduction of the Harrison Act in 1914, after 12 international powers signed the International Opium Convention in 1912. Between 1920 and c. 1933, the Eighteenth Amendment to the United States Constitution banned alcohol in the United States. Prohibition proved almost impossible to enforce and resulted in the rise of organized crime, including the modern American Mafia, which identified enormous business opportunities in the manufacturing, smuggling and sale of illicit liquor.
The beginning of the 21st century saw drug use increase in North America and Europe, with a particularly increased demand for marijuana and cocaine. As a result, international organized crime syndicates such as the Sinaloa Cartel and 'Ndrangheta have increased cooperation among each other in order to facilitate trans-Atlantic drug-trafficking. Use of another illicit drug, hashish, has also increased in Europe. Drug trafficking is widely regarded by lawmakers as a serious offense around the world. Penalties often depend on the type of drug (and its classification in the country into which it is being trafficked), the quantity trafficked, where the drugs are sold and how they are distributed. If the drugs are sold to underage people, then the penalties for trafficking may be harsher than in other circumstances.
Drug smuggling carries severe penalties in many countries. Sentencing may include lengthy periods of incarceration, flogging and even the death penalty (in Singapore, Malaysia, Indonesia and elsewhere). In December 2005, Van Tuong Nguyen, a 25-year-old Australian drug smuggler, was hanged in Singapore after being convicted in March 2004. In 2010, two people were sentenced to death in Malaysia for trafficking 1 kilogram (2.2 lb) of cannabis into the country. Execution is mostly used as a deterrent, and many have called upon much more effective measures to be taken by countries to tackle drug trafficking; for example, targeting specific criminal organisations that are often also active in the smuggling of other goods (i.e. wildlife) and even people. In many cases, links between politicians and the criminal organisations have been proven to exist. In June 2021, Interpol revealed an operation in 92 countries that shut down 113,000 websites and online marketplaces selling counterfeit or illicit medicines and medical products a month earlier, led to the arrests of 227 people worldwide, recovered pharmaceutical products worth $23 million, and led to the seizure of approximately nine million devices and drugs, including large quantities of fake COVID-19 tests and face masks.
== Societal effects ==
The countries of drug production and transit are some of the most affected by the trade, though countries receiving the illegally imported substances are also adversely affected. For example, Ecuador has absorbed up to 300,000 refugees from Colombia who are running from guerrillas, paramilitaries and drug lords. While some applied for asylum, others are still illegal immigrants. The drugs that pass from Colombia through Ecuador to other parts of South America create economic and social problems.
Honduras, through which an estimated 79% of cocaine passes on its way to the United States, had, as of 2011, the highest murder rate in the world. According to the International Crisis Group, the most violent regions in Central America, particularly along the Guatemala–Honduras border, are highly correlated with an abundance of drug trafficking activity.
=== Violent crime ===
In several countries, the illegal drug trade is thought to be directly linked to violent crimes such as murder and gun violence. This is especially true in all developing
countries, such as Honduras, but is also an issue for many developed countries worldwide. In the late 1990s in the United States, the Federal Bureau of Investigation estimated that 5% of murders were drug-related. In Colombia, drug violence can be caused by factors such as the economy, poor governments, and no authority within law enforcement.
After a crackdown by US and Mexican authorities in the first decade of the 21st century as part of tightened border security in the wake of the September 11 attacks, border violence inside Mexico surged. The Mexican government estimated that 90% of the killings were drug-related.
A report by the UK government's Drug Strategy Unit that was leaked to the press, stated that due to the expensive price of highly addictive drugs heroin and cocaine, drug use was responsible for the great majority of crime, including 85% of shoplifting, 70–80% of burglaries and 54% of robberies. It concluded "[t]he cost of crime committed to support illegal cocaine and heroin habits amounts to £16 billion a year in the UK"
== Drug trafficking routes ==
=== Africa ===
==== East and South ====
Heroin is increasingly trafficked from Afghanistan to Europe and America through eastern and southern African countries. This path is known as the "southern route" or "smack track". Repercussions of this trade include burgeoning heroin use and political corruption among intermediary African nations.
==== West ====
Cocaine produced in Colombia and Bolivia has increasingly been shipped via West Africa (especially in Nigeria, Cape Verde, Guinea-Bissau, Cameroon, Mali, Benin, Togo, and Ghana). The money is often laundered in countries such as Nigeria, Ghana, and Senegal.
According to the Africa Economic Institute, the value of illicit drug smuggling in Guinea-Bissau is almost twice the value of the country's GDP. Police officers are often bribed. A police officer's normal monthly wage of $93 is less than 2% of the value of 1 kilogram (2.2 lb) of cocaine (€7000 or $8750). The money can also be laundered using real estate. A house is built using illegal funds, and when the house is sold, legal money is earned. When drugs are sent over land, through the Sahara, the drug traders have been forced to cooperate with terrorist organizations, such as Al-Qaeda in Islamic Maghreb.
=== Asia ===
Drugs in Asia traditionally traveled the southern routes – the main caravan axes of Southeast Asia and Southern China – and include the former opium-producing countries of Thailand, Iran, and Pakistan. After the 1990s, particularly after the end of the Cold War (1991), borders were opened and trading and customs agreements were signed so that the routes expanded to include China, Central Asia, and Russia. There are, therefore, diversified drug trafficking routes available today, particularly in the heroin trade and these thrive due to the continuous development of new markets. A large amount of drugs are smuggled into Europe from Asia. The main sources of these drugs are Afghanistan, along with countries that constituted the so-called Golden Crescent. From these producers, drugs are smuggled into the West and Central Asia to its destinations in Europe and the United States. Iran is now a common route for smugglers, having been previously a primary trading route, due to its large-scale and costly war against drug trafficking. The Border Police Chief of Iran said that his country "is a strong barrier against the trafficking of illegal drugs to Caucasus, especially the Republic of Azerbaijan." The drugs produced by the Golden Triangle of Myanmar, Laos, and Thailand, on the other hand, pass through the southern routes to feed the Australian, US, and Asian markets.
=== South America ===
Venezuela has been a path to the United States and Europe for illegal drugs originating in Colombia, through Central America, Mexico and Caribbean countries such as Haiti, the Dominican Republic, and Puerto Rico.
According to the United Nations, cocaine trafficking through Venezuela increased from 2002 to 2008. In 2005, the government of Hugo Chávez severed ties with the United States Drug Enforcement Administration (DEA), accusing its representatives of spying. Following the departure of the DEA from Venezuela and the expansion of DEA's partnership with Colombia in 2005, Venezuela became more attractive to drug traffickers. Between 2008 and 2012, Venezuela's cocaine seizure ranking among other countries declined, going from being ranked fourth in the world for cocaine seizures in 2008 to sixth in the world in 2012.
On 18 November 2016, following what was known as the Narcosobrinos incident, Venezuelan President Nicolás Maduro's two nephews were found guilty of trying to ship drugs into the United States so they could "obtain a large amount of cash to help their family stay in power".
According to a research conducted by the Israel-based Abba Eban Institute as part of an initiative called Janus Initiative, the main routes that Hezbollah uses for smuggling drugs are from Colombia, Venezuela and Brazil into West Africa and then transported through northern Africa into Europe. This route serves Hezbollah in making a profit in the cocaine smuggling market in order to leverage it for their activities.
== Online trafficking ==
Drugs are increasingly traded online on the dark web on darknet markets. Internet-based drug trafficking is the global distribution of narcotics, making extensive use of technology. Similarly, the use of the Internet for the illegal trafficking of two controlled categories of drugs can also be identified as Internet-related drug trafficking. The platform Silk Road provided goods and services to 100,000 buyers before being shut down in October 2013. This prompted the creation of new platforms such as Silk Road 2.0, which were also shut down.
== Profits ==
Statistics about profits from the drug trade are largely unknown due to its illicit nature. An online report published by the UK Home Office in 2007 estimated the illicit drug market in the UK at £4–6.6 billion a year.
In December 2009, United Nations Office on Drugs and Crime Executive Director Antonio Maria Costa claimed illegal drug money saved the banking industry from collapse. He claimed he had seen evidence that the proceeds of organized crime were "the only liquid investment capital" available to some banks on the brink of collapse during 2008. He said that a majority of the $352 billion (£216bn) of drug profits was absorbed into the economic system as a result: "In many instances, the money from drugs was the only liquid investment capital. In the second half of 2008, liquidity was the banking system's main problem and hence liquid capital became an important factor ... Inter-bank loans were funded by money that originated from the drugs trade and other illegal activities...there were signs that some banks were rescued that way".
Costa declined to identify countries or banks that may have received any drug money, saying that would be inappropriate because his office is supposed to address the problem, not apportion blame.
Though street-level drug sales are widely viewed as lucrative, a study by Sudhir Venkatesh suggested that many low-level employees receive low wages. In a study he made in the 1990s working closely with members of the Black Gangster Disciple Nation in Chicago, he found that one gang (essentially a franchise) consisted of a leader (a college graduate named J.T.), three senior officers, and 25 to 75 street level salesmen ('foot soldiers') depending on season. Selling crack cocaine, they took in approximately $32,000 per month over a six-year period. This was spent as follows: $5,000 to the board of twenty directors of the Black Gangster Disciple Nation, who oversaw 100 such gangs for approximately $500,000 in monthly income. Another $5,000 monthly was paid for cocaine, and $4,000 for other non-wage expenses. J.T. took $8,500 monthly for his own salary. The remaining $9,500 monthly went to pay the employees a $7 per hour wage for officers and a $3.30 per hour wage for foot soldiers. Contrary to a popular image of drug sales as a lucrative profession, many of the employees were living with their mothers by necessity. Despite this, the gang had four times as many unpaid members who dreamed of becoming foot soldiers.
== Impact of free trade ==
There are several arguments on whether or not free trade has a correlation to an increased activity in the illicit drug trade. Currently, the structure and operation of the illicit drug industry is described mainly in terms of an international division of labor. Free trade can open new markets to domestic producers who would otherwise resort to exporting illicit drugs. Additionally, extensive free trade among states increases cross-border drug enforcement and coordination between law enforcement agencies in different countries. However, free trade also increases the sheer volume of legal cross-border trade and provides cover for drug smuggling—by providing ample opportunity to conceal illicit cargo in legal trade. While international free trade continues to expand the volume of legal trade, the ability to detect and interdict drug trafficking is severely diminished. Towards the late 1990s, the top ten seaports in the world processed 33.6 million containers. Free trade has fostered integration of financial markets and has provided drug traffickers with more opportunities to launder money and invest in other activities. This strengthens the drug industry while weakening the efforts of law enforcement to monitor the flow of drug money into the legitimate economy. Cooperation among cartels expands their scope to distant markets and strengthens their abilities to evade detection by local law enforcement. Additionally, criminal organizations work together to coordinate money-laundering activities by having separate organizations handle specific stages of laundering process. One organization structures the process of how financial transactions will be laundered, while another criminal group provides the "dirty" money to be cleaned. By fostering expansion of trade and global transportation networks, free trade encourages cooperation and formation of alliances among criminal organizations across different countries.
The drug trade in Latin America emerged in the early 1930s. It saw significant growth in the Andean countries, including Peru, Bolivia, Chile, Ecuador, Colombia and Venezuela. The underground market in the early half of the 20th century mainly had ties to Europe. After World War II, the Andean countries saw an expansion of trade, specifically with cocaine.
== Drug trafficking by country ==
=== Syria ===
The Ba'athist government of Syria ruled by the Al-Assad family is known for its extensive involvement in drug trade since the 1970s. As of 2022, the Syrian government financed the biggest multi-billion dollar drug trade in the world, mostly focused on an illegal drug known as Captagon, making it the world's largest narco-state. Its revenues from Captagon smuggling alone is estimated to worth 57 billion dollars annually in 2022, which is approximately thrice the total trade of all Mexican cartels. General Maher al-Assad, younger brother of Syrian dictator Bashar al-Assad and commander of the Fourth Armoured Division, directly supervised the production, smuggling and profiteering of the drug business. Already suffering from severe financial problems as a result of corruption and civil war, profits from Captagon are said to be the "lifeline" of the Assad regime, through which it earned more than 90% of its total revenue. The smugglers receive direct training from Syrian military to successfully conduct trafficking operations.
Republican Guard, commanded by Maher al-Assad was one of the main Ba'athist military divisions that was engaged in perpetrating brutal crackdowns and mass violence against protestors across the country. In 2018, Bashar al-Assad assigned Maher as the commander of the 4th Armoured Division, a military unit that supervised the Assad regime's criminal enterprises like smuggling, drug trafficking, narcotics production and plunder of goods and resources. Under Maher's supervision, the 4th Armoured Division expanded captagon production and trafficking from Syria into a "business model controlled by the regime".
In 2022, 90% of all captagon pills manufactured in Syria exported by drug cartels affiliated with Assad regime arrived at its customer destinations across the world. Although hundreds of millions of pills were intercepted and seized by police forces, these accounted only for 10% of the total captagon exports of the drug cartels linked to the Assad regime. In 2020, Italian police seized 84 million captagon pills originating from Syrian ports while intercepting a single shipment. In June 2023, US State Department's Bureau of Near Eastern Affairs published a detailed report to the US Congress, elucidating a strategy to eliminate the narcotics production, drug trafficking and drug cartel networks affiliated with the Assad regime and Hezbollah.
A joint investigation conducted by Organized Crime and Corruption Reporting Project (OCCRP) and BBC News Arabic published a documentary in June 2023, revealing further details about the activities of regime officials, Ba'athist military commanders and Assad family members in their involvement in Syria's drug cartel. The investigation found that Lebanese criminal and drug kingpin Hassan Daqou collaborated with Syria's Fourth Armoured Division on trafficiking billions of dollars of drugs, under the command of General Ghassan Bilal, the right-hand man of Maher al-Assad. The report also unearthed Hezbollah's close participation in the drug production and smuggling networks. The Fourth Armoured Division, being an elite military unit permitted to move freely across Assad regime's checkpoints, oversees the smuggling operations from Syria, including the trafficking of cash, weapons, illegal drugs, etc. Days after the publication of the joint BBC-OCCRP documentary; Assad government banned all activities of BBC media outlets and entry of affiliated media personnel in Syria.
The extensive involvement of Syrian Armed Forces in sponsorship of drug production and trade has led to pervasive drug addiction problems amongst pro-Assad soldiers. In many instances, military officials encourage the soldiers to consume Captagon and other illegal drugs, leading to overdose or drug abuse. Pro-Assad fighters in the National Defence Forces and Hezbollah also consume illegal drugs in large quantities. In July 2023, German police busted a major captagon network run by two Syrian-born men in southern German state of Bavaria. Assad regime sponsors the largest Captagon production network in Syria; which is the source of about 80% of total captagon supply in the world.
In an investigative report published by The Insider news-outlet in 2024, journalist Yuriy Matsarsky stated:"...Captagon produced in underground labs—and in actual Syrian pharmaceutical facilities—is distributed to the fighters of Bashar Assad's army. Interestingly, however, the quantities the country produces far exceed its own military’s demand. ... By some estimates, this business gives Syria more money than its entire legal export, and the regime constantly works to increase its profits, primarily by expanding its market reach. To this end, criminal gangs associated with Damascus or Hezbollah have built distribution networks for Captagon in countries where the drug was not previously popular."
=== United States ===
==== Background ====
The effects of the illegal drug trade in the United States can be seen in a range of political, economic and social aspects. Increasing drug related violence can be tied to the racial tension that arose during the late 20th century along with the political upheaval prevalent throughout the 1960s and 70s. The second half of the 20th century was a period when increased wealth, and increased discretionary spending, increased the demand for illicit drugs in certain areas of the United States. Large-scale drug trafficking is one of the capital crimes, and may result in a death sentence prescribed at the federal level when it involves murder.
==== Political impact ====
A large generation, the baby boomers, came of age in the 1960s. Their social tendency to confront the law on specific issues, including illegal drugs, overwhelmed the understaffed judicial system. The federal government attempted to enforce the law, but with meager effect.
Marijuana was a popular drug seen through the Latin American trade route in the 1960s. Cocaine became a major drug product in the later decades. Much of the cocaine is smuggled from Colombia and Mexico via Jamaica. This led to several administrations combating the popularity of these drugs. Due to the influence of this development on the US economy, the Reagan administration began "certifying" countries for their attempts at controlling drug trafficking. This allowed the United States to intervene in activities related to illegal drug transport in Latin America. Continuing into the 1980s, the United States instated stricter policy pertaining to drug transit through sea. As a result, there was an influx in drug-trafficking across the Mexico–US border, which increased the drug cartel activity in Mexico.
By the early 1990s, so much as 50% of the cocaine available in the United States market originated from Mexico, and by the 2000s, over 90% of the cocaine in the United States was imported from Mexico. In Colombia, however, there was a fall of the major drug cartels in the mid-1990s. Visible shifts occurred in the drug market in the United States. Between 1996 and 2000, US cocaine consumption dropped by 11%.
In 2008, the US government initiated another program, known as the Merida Initiative, to help combat drug trafficking in Mexico. This program increased US security assistance to $1.4 billion over several years, which helped supply Mexican forces with "high-end equipment from helicopters to surveillance technology". Despite US aid, Mexican "narcogangs" continue to outnumber and outgun the Mexican Army, allowing for continued activities of drug cartels across the US–Mexico border.
==== Social impacts ====
Although narcotics are illegal in the US, they have become integrated into the nation's culture and are seen as a recreational activity by sections of the population. Illicit drugs are considered to be a commodity with strong demand, as they are typically sold at a high value. This high price is caused by a combination of factors that include the potential legal ramifications that exist for suppliers of illicit drugs and their high demand. Despite the constant effort by politicians to win the war on drugs, the US is still the world's largest importer of illegal drugs.
Throughout the 20th century, narcotics other than cocaine also crossed the Mexican border, meeting the US demand for alcohol during the 1920s Prohibition, opiates in the 1940s, marijuana in the 1960s, and heroin in the 1970s. Most of the US imports of drugs come from Mexican drug cartels. In the United States, around 195 cities have been infiltrated by drug trafficking that originated in Mexico. An estimated $10bn of the Mexican drug cartel's profits come from the United States, not only supplying the Mexican drug cartels with the profit necessary for survival, but also furthering America's economic dependence on drugs.
===== Demographics =====
With a large wave of immigrants in the 1960s and onwards, the United States saw an increased heterogeneity in its public. In the 1980s and 1990s, drug-related homicide was at a record high. This increase in drug violence became increasingly tied to these ethnic minorities. Though the rate of violence varied tremendously among cities in America, it was a common anxiety in communities across urban America. An example of this could be seen in Miami, a city with a host of ethnic enclaves. Between 1985 and 1995, the homicide rate in Miami was one of the highest in the nation—four times the national homicide average. This crime rate was correlated with regions with low employment and was not entirely dependent on ethnicity.
The baby boomer generation also felt the effects of the drug trade in their increased drug use from the 1960s to 1980s. Along with substance use, criminal involvement, suicide and murder were also on the rise. Due to the large amount of baby boomers, commercial marijuana use was on the rise. This increased the supply and demand for marijuana during this time period.
=== Mexico ===
==== Political influences ====
Corruption in Mexico has contributed to the domination of Mexican cartels in the illicit drug trade. Since the beginning of the 20th century, Mexico's political environment allowed the growth of drug-related activity. The loose regulation over the transportation of illegal drugs and the failure to prosecute known drug traffickers and gangs increased the growth of the drug industry. Toleration of drug trafficking has undermined the authority of the Mexican government and has decreased the power of law enforcement officers in regulation over such activities. These policies of tolerance fostered the growing power of drug cartels in the Mexican economy and have made drug traders wealthier. Many states in Mexico lack policies that establish stability in governance. There also is a lack of local stability, as mayors cannot be re-elected. This requires electing a new mayor each term. Drug gangs have manipulated this, using vacuums in local leadership to their own advantage.
In 1929, the Institutional Revolutionary Party (PRI) was formed to resolve the chaos resulting from the Mexican Revolution. Over time, this party gained political influence and had a major impact on Mexico's social and economic policies. The party created ties with various groups as a power play in order to gain influence, and as a result created more corruption in the government. One such power play was an alliance with drug traffickers. This political corruption obscured justice, making it difficult to identify violence when it related to drugs. By the 1940s, the tie between the drug cartels and the PRI had solidified. This arrangement created immunity for the leaders of the drug cartels and allowed drug trafficking to grow under the protection of the government officials.
During the 1990s, the PRI lost some elections to the new National Action Party (PAN). Chaos again emerged as elected government in Mexico changed drastically. As the PAN party took control, drug cartel leaders took advantage of the ensuing confusion and used their existing influence to further gain power. Instead of negotiating with the central government as was done with the PRI party, drug cartels utilized new ways to distribute their supply and continued operating through force and intimidation. As Mexico became more democratized, the corruption fell from a centralized power to the local authorities. Cartels began to bribe local authorities, thus eliminating the structure and rules placed by the government—giving cartels more freedom. As a response, Mexico saw an increase in violence caused by drug trafficking.
The corruption cartels created resulted in distrust of government by the Mexican public. This distrust became more prominent after the collapse of the PRI party. In response, the presidents of Mexico, in the late twentieth century and early twenty-first century, implemented several different programs relating to law enforcement and regulation. In 1993, President Salinas created the National Institute for the Combat of Drugs in Mexico. From 1995 to 1998, President Zedillo established policies regarding increased punishment of organized crime, allowing "[wire taps], protected witnesses, covert agents and seizures of goods", and increasing the quality of law enforcement at the federal level. From 2001 to 2005, President Vicente Fox created the Federal Agency of Investigation.
These policies resulted in the arrests of major drug-trafficking bosses:
==== Mexico's economy ====
Over the past few decades, drug cartels have become integrated into Mexico's economy. Approximately 500 cities are directly engaged in drug trafficking and nearly 450,000 people are employed by drug cartels. Additionally, the livelihood of 3.2 million people is dependent on the drug cartels. Between local and international sales, such as to Europe and the United States, drug cartels in Mexico see a $25–30 bn yearly profit, a great deal of which circulates through international banks such as HSBC. Drug cartels are fundamental in local economics. A percentage of the profits seen from the trade are invested in the local community. Such profits contribute to the education and healthcare of the community. While these cartels bring violence and hazards into communities, they create jobs and provide income for its many members.
==== Culture of drug cartels ====
Major cartels saw growth due to a prominent set culture of Mexican society that created the means for drug capital. One of the sites of origin for drug trafficking within Mexico, was the state of Michoacán. In the past, Michoacán was mainly an agricultural society. This provided an initial growth of trade. Industrialization of rural areas of Mexico facilitated a greater distribution of drugs, expanding the drug market into different provinces. Once towns became industrialized, cartels such as the Sinaloa Cartel started to form and expand. The proliferation of drug cartel culture largely stemmed from the ranchero culture seen in Michoacán. Ranchero culture values the individual as opposed to the society as a whole. This culture fostered the drug culture of valuing the family that is formed within the cartel. This ideal allowed for greater organization within the cartels.
Gangs play a major role in the activity of drug cartels. MS-13 and the 18th Street gang are notorious for their contributions and influence over drug trafficking throughout Latin America. MS-13 has controlled much of the activity in the drug trade spanning from Mexico to Panama. Female involvement is present in the Mexican drug culture. Although females are not treated as equals to males, they typically hold more power than their culture allows and acquire some independence. The increase in power has attracted females from higher social classes. Financial gain has also prompted women to become involved in the illegal drug market. Many women in the lower levels of major drug cartels belong to a low economic class. Drug trafficking offers women an accessible way to earn income. Females from all social classes have become involved in the trade due to outside pressure from their social and economic environments.
=== Colombia ===
==== Political ties ====
It was common for smugglers in Colombia to import liquor, alcohol, cigarettes and textiles, while exporting cocaine. Personnel with knowledge of the terrain were able to supply the local market while also exporting a large amount of product. The established trade initially involved Peru, Bolivia, Colombia, Venezuela and Cuba. Peasant farmers produced coca paste in Peru and Bolivia, while Colombian smugglers would process the coca paste into cocaine in Colombia, and trafficked product through Batista's Cuba. This trade route established ties between Cuban and Colombian organized crime.
From Cuba, cocaine would be transported to Miami, Florida; and Union City, New Jersey. Quantities of the drug were then smuggled throughout the US. The international drug trade created political ties between the involved countries, encouraging the governments of the countries involved to collaborate and instate common policies to eradicate drug cartels. Cuba stopped being a center for transport of cocaine following the Cuban Revolution and the establishment of Fidel Castro's communist government in 1959.
As a result, Miami and Union City became the sole locations for trafficking. The relations between Cuban and Colombian organized crime remained strong until the 1970s, when Colombian cartels began to vie for power. In the 1980s and 90s, Colombia emerged as a key contributor of the drug trade industry in the Western Hemisphere. While the smuggling of drugs such as marijuana, poppy, opium and heroin became more ubiquitous during this time period, the activity of cocaine cartels drove the development of the Latin American drug trade. The trade emerged as a multinational effort as supplies (i.e. coca plant substances) were imported from countries such as Bolivia and Peru, were refined in Colombian cocaine labs and smuggled through Colombia, and exported to countries such as the US.
==== Colombia's economy ====
Colombia has had a significant role in the illegal drug trade in Latin America. While active in the drug trade since the 1930s, Colombia's role in the drug trade did not truly become dominant until the 1970s. When Mexico eradicated marijuana plantations, demand stayed the same. Colombia met much of the demand by growing more marijuana. Grown in the strategic northeast region of Colombia, marijuana soon became the leading cash crop in Colombia. This success was short-lived due to anti-marijuana campaigns that were enforced by the US military throughout the Caribbean. Instead, drug traffickers in Colombia continued their focus on exporting cocaine.
Having been an export of Colombia since the early 1950s, cocaine remained popular for a host of reasons. Colombia's location facilitated its transportation from South America into Central America, and then to its destination of North America. This continued into the 1990s, when Colombia remained the chief exporter of cocaine. The business of drug trafficking can be seen in several stages in Colombia towards the latter half of the 20th century. Colombia served as the dominant force in the distribution and sale of cocaine by the 1980s. As drug producers gained more power, they became more centralized and organized into what became drug cartels.
Cartels controlled the major aspects of each stage in the traffic of their product. Their organization allowed cocaine to be distributed in great amounts throughout the United States. By the late 1980s, intra-industry strife arose within the cartels. This stage was marked by increased violence as different cartels fought for control of export markets. Despite this strife, this power struggle led to then having multiple producers of coca leaf farms. This in turn caused an improvement in quality control and reduction of police interdiction in the distribution of cocaine. This also led to cartels attempting to repatriate their earnings which would eventually make up 5.5% of Colombia's GDP. This drive to repatriate earnings led to the pressure of legitimizing their wealth, causing an increase in violence throughout Colombia.
Throughout the 1980s, estimates of illegal drug value in Colombia ranged from $2bn to $4bn. This made up about 7–10% of the $36bn estimated Gross National Product (GNP) of Colombia during this decade. In the 1990s, the estimates of the illegal drug value remained roughly within the same range (~$2.5bn). As the Colombian GNP rose throughout the 1990s ($68.5bn in 1994 and $96.3bn in 1997), illegal drug values began to comprise a decreasing fraction of the national economy.
By the early 1990s, although Colombia led in the exportation of cocaine, it found increasing confrontations within its state. These confrontations were primarily between cartels and government institutions. This led to a decrease in the drug trade's contribution to the GDP of Colombia; dropping from 5.5% to 2.6%. Though a contributor of wealth, the distribution of cocaine has had negative effects on the socio-political situation of Colombia and has weakened its economy as well.
==== Social impacts ====
By the 1980s, Colombian cartels became the dominant cocaine distributors in the US. This led to the spread of increased violence throughout both Latin America and Miami. In the 1980s, two major drug cartels emerged in Colombia: the Medellín and Cali groups.
Throughout the 1990s however, several factors led to the decline of these major cartels and to the rise of smaller Colombian cartels. The US demand for cocaine dropped while Colombian production rose, pressuring traffickers to find new drugs and markets. In this time period, there was an increase in activity of Caribbean cartels that led to the rise of an alternate route of smuggling through Mexico. This led to the increased collaboration between major Colombian and Mexican drug traffickers. Such drastic changes in the execution of drug trade in Colombia paired with the political instabilities and rise of drug wars in Medellin and Cali, gave way for the rise of the smaller Colombian drug trafficking organizations (and the rise of heroin trade). As the drug trade's influence over the economy increased, drug lords and their networks grew in their power and influence in society. The occurrences in drug-related violence increased during this time period as drug lords fought to maintain their control in the economy.
Typically, a drug cartel had support networks that consisted of a number of individuals. These people individuals ranged from those directly involved in the trade (such as suppliers, chemists, transporters, smugglers, etc.) as well as those involved indirectly in the trade (such as politicians, bankers, police, etc.). As these smaller Colombian drug cartels grew in prevalence, several notable aspects of the Colombian society gave way for further development of the Colombian drug industry. For example, until the late 1980s, the long-term effects of the drug industry were not realized by much of society. Additionally, there was a lack of regulation in prisons where captured traffickers were sent. These prisons were under-regulated, under-funded, and under-staffed, which allowed for the formation of prison gangs, for the smuggling of arms/weapons/etc., for feasible escapes, and even for captured drug lords to continue running their businesses from prison.
=== Western Balkans ===
Since the beginning of the 21st century, the global drug trade network witnessed the emergence of criminal groups from the Western Balkans as crucial players. These groups have moved up from being small-time crooks to major drug distributors. Most of these organized crime groups belonged to Albania, Bosnia and Herzegovina, Kosovo, Montenegro, North Macedonia and Serbia. The illicit trade activities of the Balkans primarily involved Latin America, Western Europe, South Africa, Australia and Turkey. These groups keep their operations outside the Western Balkans, while staying connected to their homeland. Within the network of these groups, the dealmakers operate in a proximity of supply sources and the distribution networks are managed by foot soldiers. However, the bosses of the organized criminal groups stay and keep their wealth in the United Arab Emirates (UAE). The UAE is amongst the enablers of global corruption and illicit financial flows. Analysts have claimed that criminal actors across the world either operate from or through the Emirates. It was a haven for criminals, where the risk for illicit activities remains low.
For the Balkan criminals, a growing trend was to relocate to the UAE, which became an attraction to dirty money and kingpins from several European nations and the United Kingdom. Besides, Dubai was also dubbed as the "new Costa del Crime", replacing the crime hideaway of Spain, the Costa del Sol. The UAE had poor regulations for money laundering and for screening of suspicious transactions. The lack of regulations against illicit financial activities prompted the Financial Action Task Force (FATF) to place the Gulf country on its grey list in March 2022. Consequently, the Emirates' remained a safe option for the criminals. Nearly two-thirds of the Albanian criminal groups, who were active in trade of drugs like cocaine, were believed to be hiding in the UAE. One of such individuals, Eldi Dizdari was accused of international drug trafficking and was living in Dubai. Research revealed that these criminals invested huge amounts in the Emirates' real estate and other economical sectors to live there. Another trafficker of cocaine from Bosnia, Edin Gačanin was living in the UAE using his extensive profits to buy property and protection in the country. Dubbed as the "European Escobar", he connected the supply network between production markets of Latin America and consumer markets of Western European. He was able to evade the arrest and investigations, including by the US Drug Enforcement Administration, by seeking shelter in the Emirates.
== Trade in specific drugs ==
=== Cannabis ===
While the recreational use of (and consequently the distribution of) cannabis is illegal in most countries throughout the world, recreational distribution is legal in some countries, such as Canada, and medical distribution is permitted in some places, such as 38 of the 50 US states (although importation and distribution is still federally prohibited). Beginning in 2014, Uruguay became the first country to legalize cultivation, sale, and consumption of cannabis for recreational use for adult residents. In 2018, Canada became the second country to legalize use, sale and cultivation of cannabis. The first few weeks were met with extremely high demand, most shops being out of stock after operating for only four days.
Cannabis use is tolerated in some areas, most notably the Netherlands, which has legalized the possession and licensed sale (but not cultivation) of the drug. Many nations have decriminalized the possession of small amounts of marijuana. Due to the hardy nature of the cannabis plant, marijuana is grown all across the world; today, it is the world's most popular illegal drug with the highest level of availability. Cannabis is grown legally in many countries for industrial, non-drug use (known as hemp) as well. Cannabis-hemp may also be planted for other non-drug domestic purposes, such as seasoning that occurs in Aceh.
The demand for cannabis around the world, coupled with the drug's relative ease of cultivation, makes the illicit cannabis trade one of the primary ways in which organized criminal groups finance many of their activities. In Mexico, for example, the illicit trafficking of cannabis is thought to constitute the majority of many of the cartels' earnings, and the main way in which the cartels finance many other illegal activities; including the purchase of other illegal drugs for trafficking, and for acquiring weapons that are ultimately used to commit murders (causing a burgeoning in the homicide rates of many areas of the world, but particularly Latin America).
Some studies show that the increased legalization of cannabis in the United States (beginning in 2012 with Washington Initiative 502 and Colorado Amendment 64) has led Mexican cartels to smuggle less cannabis in exchange for more heroin.
=== Alcohol ===
Alcohol, in the context of alcoholic beverages rather than denatured alcohol, is illegal in a number of Muslim countries, such as Saudi Arabia; this has resulted in a thriving illegal trade in alcohol. The manufacture, sale, transportation, import, and export of alcoholic beverages were illegal in the United States during the time known as the Prohibition in the 1920s and early 1930s.
=== Heroin ===
In the 1950s and 1960s, most heroin was produced in Turkey and transshipped in France via the French Connection crime ring, with much of it arriving in the United States. This resulted in the record setting April 26, 1968 seizure of 246 lb (111.6 kg) of heroin smuggled in a vehicle on the SS France (1960) ocean liner. By the time of The French Connection (1971 film), this route was being supplanted.
Then, until c. 2004, the majority of the world's heroin was produced in an area known as the Golden Triangle. However, by 2007, 93% of the opiates on the world market originated in Afghanistan. This amounted to an export value of about US$4 billion, with a quarter being earned by opium farmers and the rest going to district officials, insurgents, warlords and drug traffickers. Another significant area where poppy fields are grown for the manufacture of heroin is Mexico. In November 2023, a U.N report showed that in the entirety of Afghanistan, poppy cultivation dropped by over 95%, removing it from its place as being the world's largest opium producer.
According to the United States Drug Enforcement Administration, the price of heroin is typically valued 8 to 10 times that of cocaine on American streets, making it a high-profit substance for smugglers and dealers. In Europe (except the transit countries Portugal and the Netherlands), for example, a purported gram of street heroin, usually consisting of 700–800 mg of a light to dark brown powder containing 5–10% heroin base, costs €30–70, making the effective value per gram of pure heroin €300–700. Heroin is generally a preferred product for smuggling and distribution—over unrefined opium due to the cost-effectiveness and increased efficacy of heroin.
Because of the high cost per volume, heroin is easily smuggled. A US quarter-sized (2.5 cm) cylindrical vial can contain hundreds of doses. From the 1930s to the early 1970s, the so-called French Connection supplied the majority of US demand. Allegedly, during the Vietnam War, drug lords such as Ike Atkinson used to smuggle hundreds of kilograms of heroin to the US in coffins of dead American soldiers (see Cadaver Connection). Since that time it has become more difficult for drugs to be imported into the US than it had been in previous decades, but that does not stop the heroin smugglers from getting their product across US borders. Purity levels vary greatly by region with Northeastern cities having the most pure heroin in the United States. On 17 October 2018 police in Genoa, Italy discovered 270 kg (600 lb) of heroin hidden in a ship coming from the Iranian southern port of Bandar Abbas. The ship had already passed and stopped at Hamburg in Germany and Valencia in Spain.
Penalties for smuggling heroin or morphine are often harsh in most countries. Some countries will readily hand down a death sentence (e.g. Singapore) or life in prison for the illegal smuggling of heroin or morphine, which are both internationally Schedule I drugs under the Single Convention on Narcotic Drugs.
In May 2021, Romania seized 1.4 tonnes of heroin at Constanța port of a shipment from Iran that was headed for Western Europe.
=== Methamphetamine ===
Methamphetamine is another popular drug among distributors. Three common street names are "meth", "crank", and "ice".
According to the Community Epidemiology Work Group, the number of clandestine methamphetamine laboratory incidents reported to the National Clandestine Laboratory Database decreased from 1999 to 2009. During this period, methamphetamine lab incidents increased in mid-western States (Illinois, Michigan, Missouri, and Ohio), and in Pennsylvania. In 2004, more lab incidents were reported in Missouri (2,788) and Illinois (1,058) than in California (764). In 2003, methamphetamine lab incidents reached new highs in Georgia (250), Minnesota (309), and Texas (677). There were only seven methamphetamine lab incidents reported in Hawaii in 2004, though nearly 59 percent of substance use treatment admissions (excluding alcohol) were for primary methamphetamine use during the first six months of 2004. As of 2007, Missouri leads the United States in drug-lab seizures, with 1,268 incidents reported. Often canine units are used for detecting rolling meth labs which can be concealed on large vehicles, or transported on something as small as a motorcycle. These labs are more difficult to detect than stationary ones, and can often be obscured among legal cargo in big trucks.
Methamphetamine is sometimes used intravenously, placing users and their partners at risk for transmission of HIV and hepatitis C. "Meth" can also be inhaled, most commonly vaporized on aluminum foil or in a glass pipe. This method is reported to give "an unnatural high" and a "brief intense rush".
In South Africa, methamphetamine is called "tik" or "tik-tik". Known locally as "tik", the substance was virtually unknown as late as 2003. Now, it is the country's main addictive substance, even when alcohol is included. Children as young as eight are abusing the substance, smoking it in crude glass vials made from light bulbs. Since methamphetamine is easy to produce, the substance is manufactured locally in staggering quantities.
The government of North Korea currently operates methamphetamine production facilities. There, the drug is used as medicine because no alternatives are available; it also is smuggled across the Chinese border.
The Australian Crime Commission's illicit drug data report for 2011–2012 stated that the average strength of crystal methamphetamine doubled in most Australian jurisdictions within a 12-month period, and the majority of domestic laboratory closures involved small "addict-based" operations.
=== Temazepam ===
Temazepam, a strong hypnotic benzodiazepine, is illicitly manufactured in clandestine laboratories (called jellie labs) to supply the increasingly high demand for the drug internationally. Many clandestine temazepam labs are in Eastern Europe. The labs manufacture temazepam by chemically altering diazepam, oxazepam or lorazepam. "Jellie labs" have been identified and shut down in Russia, Ukraine, Latvia and Belarus.
=== Cocaine ===
Cocaine is a highly trafficked drug. In 2017 the value of the global market for illicit cocaine was estimated at between $94 and $143 billion. In 2022, illicit sales in Europe were estimated at $11.1 billion. In 2020, almost 2,000 tons of cocaine were produced for distribution through illicit markets.
=== Fentanyl ===
Fentanyl, a synthetic opioid, is 20 to 40 times more potent than heroin and 100 times more potent than morphine; its primary clinical utility is in pain management for cancer patients and those recovering from painful surgeries. Illicit use of fentanyl continues to fuel an epidemic of synthetic opioid drug overdose deaths in the US. From 2011 to 2021, synthetic opioid deaths per year increased from 2,600 overdoses to 70,601. Since 2018, fentanyl and its analogues have been responsible for most drug overdose deaths in the US, causing over 71,238 deaths in 2021. Fentanyl is often mixed, cut, or ingested alongside other drugs, including cocaine and heroin. The fentanyl epidemic has erupted in a highly acrimonious dispute between the US and Mexican governments. While US officials blame the flood of fentanyl crossing the border primarily on Mexican crime groups, President Andrés Manuel López Obrador insists that the main source of this synthetic drug is Asia. He believes that the crisis of a lack of family values in the US drives people to use the drug.
== See also ==
Allegations of CIA drug trafficking
Arguments for and against drug prohibition
Corruption
Counterfeit medications
Counterfeit money
Environmental impact of illicit drug production
Rum running
Illicit cigarette trade
Human trafficking
Arms trafficking
Wildlife trafficking
Illegal organ trade
Drug liberalization
Drug trafficking organizations
Golden Crescent
Golden Triangle (Southeast Asia)
Illegal drug trade in the Indian Ocean region
Maritime drug smuggling into Australia
Narco-capitalism
Narco-state
Narcoterrorism
Organized crime
Operation Show Me How
=== International coordination ===
International Day Against Drug Abuse and Illicit Trafficking
Interpol
United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances
== References ==
== External links ==
Official website of the United Nations Office on Drugs and Crime (UNODC)
Illicit drug issues by country, by the CIA. Archived 2010-12-29 at the Wayback Machine. | Wikipedia/Drug_trafficking |
Sex and drugs refers to the influence of substances on sexual function and experience. Sex and drugs date back to ancient humans and have been interlocked throughout human history. Sexual performance is known as the execution of the act of sex and the quality of sexual activity. This includes elements such as libido (a person's sexual drive), sexual function (including erection in males and vaginal lubrication in females), sensation (the ability to achieve orgasm). Drugs are termed as any chemical substance that produces a physiological and or psychological change in an organism. Drugs categorized as psychoactive drugs, antihypertensive drugs, antihistamines, cancer treatment, and hormone medication have a significant impact on sexual performance. Various drugs result in different effects, both positive and negative. Negative effects may include low libido, erection issues (in males), vaginal dryness (in females) and anorgasmia. Positive effects usually address these issues, overall enhancing sexual performance and contributing to a more enjoyable sexual experience. It is crucial to know that the impact of drugs on sexual performance varies among individuals, especially among different genders.
== Understanding sexual performance ==
Understanding sexual performance involves recognizing various factors that are responsible for a person's combined sexual experience and function. This includes libido, a person's overall sexual desire, and drive; sexual function, which encompasses the male's erectile function and a female's vaginal lubrication; and sensations, which in this context refers to a person's ability to have orgasms and/or ejaculations.
=== Libido ===
Libido is primarily regulated by the hypothalamus, where sex hormones (testosterone and estrogen), and neurotransmitters (dopamine, oxytocin and serotonin), are the main components that influence sex drive. A decreased libido is predominantly caused by low testosterone in males For females, serotonin acts as a inhibitor for sexual desire as it reduces the ability of stimulatory systems for sexual cues.
=== Sexual function ===
Penile erection for men is a vascular event caused by the innervation of both autonomic (sympathetic and parasympathetic) and somatic nervous systems (sensory and motor). Sensory information is received from the genitals towards these nervous systems, in which neurotransmitters such as serotonin, dopamine, noradrenaline, and adrenaline would be released to control erectile function.
Vaginal dryness refers to the situation when the vagina lacks lubrication which leads to serious pain during sexual intercourse. The production of lubricants in the vagina are highly sensitive to changes in hormones such as estrogen and testosterone, that are also responsible for blood flow. Low estrogen and testosterone circulating in the body contributes to vaginal dryness.
=== Sensations ===
Orgasms are sensory phenomena that take place in the cerebral cortex with an association with the spinal reflex. Men can achieve orgasm through the penis, and can be categorised to two parts: emission and ejaculation. Neurotransmitters such as serotonin, norepinephrine and dopamine affect ejaculation in males the most. For women, orgasms are induced by stimulation of erotic sites, currently there are no definitive explanations on the chemical triggers for female orgasm.
== Disinhibition ==
Drugs are frequently associated with reduced sexual inhibition, both when used voluntarily in social circumstances, and involuntarily, as in the case of some date rape drugs. Because the use of drugs, including alcohol, is commonly presented as an excuse for risky or socially unacceptable behavior, it is necessary to treat the idea of a direct causal relation between drug use and unsafe sex with caution. Drugs may provide a socially acceptable excuse for engaging in sexual behaviors in which people may want to engage but perhaps feel that they should not.
== Sexual function ==
Some forms of sexual dysfunction such as erectile dysfunction can be treated with drugs. Because of their effects, erectile dysfunction drugs are sometimes used for recreational purposes. Many drugs, both legal and illegal, some sold online, have side effects that affect the user's sexual function. Many drugs can cause loss of libido as a side effect.
Since a partial cause of the refractory period is the inhibition of dopamine by an orgasm-induced secretion of prolactin, such potent dopamine receptor agonists as cabergoline may help achieve multiple orgasms as well as the retention of sexual arousal for longer periods of time.
== Sexual activity, drug use, and risks ==
According to some studies, up to 22.1% of teenagers abused substances during their most recent sexual experience.
Likewise, studies have shown adolescents who regularly abuse substances are more likely to initiate sexual activity at an earlier age, have a more significant number of sexual partners, and engage in unprotected sex more often.
Additionally, substance abuse has been linked to an increased risk of sexually transmitted infection (STI).
== Types of drugs that affect sexual performance ==
Drugs on the market provide both benefits and detrimental effects to the person, especially regarding sexual performance, depending on the use and dosage. Drugs are classified into different categories in respect to their functions, including psychoactive drugs, antihypertensive drugs, antihistamines, cancer treatment drugs and hormone medication.
=== Psychoactive drugs ===
Psychoactive drugs refer to chemical substances that affect an individual's mental processes, such as emotions, cognition, perception, and consciousness. These substances directly impact the central nervous system (CNS), which also has an impact on the neurophysiologic phases of sexual response. Antidepressants are a group of drugs that treat individuals with clinical depression, as well as other mental disorders. This group of drugs have shown to affect sexual functions in both male and females. Alcohol is a group of psychoactive substances where signals of pleasure, rewards are sent to the human brain. It also causes a series of adverse effects on the body, including the brain and the liver, leading to health problems and sexual dysfunction. Antipsychotics are drugs that treat mental disorders such as schizophrenia, and other psychoses. These drugs block certain pathways in humans that contribute to sexual dysfunction, including reduced arousal and sexual desire.
==== Alcohol ====
Alcohol inhibits neuronal excitability through acting on gamma-aminobutyric acid (GABA) receptors. Alcohol is often accessible in a number of social situations across many cultures and is frequently connected with uninhibited social activities. Alcohol has been shown in human research to have surprising effects on the human libido.
While some studies indicates that alcohol improves sexual behavior and desire, other research indicates that alcohol impairs sexual function.
The conditions under which the drinking occurs, laboratory research vs self-report studies from users, as well as the amounts of alcohol consumed, may all contribute to these controversial outcomes.
Laboratory studies have demonstrated that while low blood alcohol levels have no effect on or slightly enhance sexual arousal and responsiveness in men, elevated blood alcohol levels result in decreased erectile responsiveness, decreased arousal, and impaired ability to ejaculate. Other laboratory research, on the other hand, found no significant influence of either low or high blood alcohol levels on measures of arousal.
Even with mild alcohol use, women have decreased vaginal flow responses. In apparent contrast, women self-report heightened sexual desire and pleasure when they consume more alcohol and are more likely to engage in sexual activities with someone when intoxicated.
Heavy alcohol intake impairs sexual and reproductive function, erectile, and ejaculatory dysfunction in males, and sexual arousal, interest, and orgasm in women.
Alcohol and sex although alcohol may have varying impacts on sexual performance depending on the amount drank, it generally impairs sexual functioning and contributes to increased sexual risk taking.
==== Antidepressants ====
Psychiatrists and doctors commonly prescribe different types of antidepressants to patients. SSRIs, SNRIs, and NDRIs are the most common types of antidepressants. Each has slightly different effects on sexual functioning, but generally, it has been found that antidepressants can delay/decrease orgasms and cause females to have breast enlargement. Dapoxetine in particular takes advantage of the side effect of delayed orgasm and is approved specifically as a medication for the treatment of premature ejaculation rather than as an antidepressant.
The side effects on sexual functioning can impact mental health and quality of life. However, the decrease in depressive symptoms from antidepressants make it worth the sexual side effects for many people. They can be managed by changing the dose, switching drugs, or taking "antidotes". Maca, a plant that grows in central Peru, aids with sexual dysfunction caused by antidepressant drugs for women. There are specific Maca products that can also increase sexual desire in men.
=== 2C-B ===
2C-B was first sold commercially in 5 mg pills as a purported aphrodisiac under the trade name "Erox", which was manufactured by the German pharmaceutical company Drittewelle. While being primarily a psychedelic it is also a mild entactogen. 5-MeO-MiPT is another psychedelic that some users find to be euphoric and tactile in low to moderate doses of 4-8 milligrams.
=== Antihypertensive drugs ===
Antihypertensive drugs are a group of drugs that prevent, control and treat hypertension. Hypertension imposes negative sexual effects on both men and women, where antihypertensive drugs help alleviate erectile dysfunction in men.
=== Antihistamines ===
Antihistamines are used for relieving symptoms of allergies and hay fever. Antihistamines may cause a drying effect of the mouth, nose and throat but can also cause a drying effect on other parts of the body, such as the vagina, decreasing moisture and lubrication.
=== Cancer treatment ===
There are a variety of treatment types for cancer, depending on the cancer type. The therapies for treating cancer vary, including hormone therapy, medications that treat pain, depression, nerves and blood vessels. These therapies will affect one's sexual desire and pose possible consequences on sexual response.
=== Hormone medications ===
Hormone therapy directs its treatment towards hormones in the body, including reproductive hormones. One type is hormonal replacement therapy (HRT), which is used to supply menopausal women that lack estrogen and progesterone, increasing vaginal lubrication. Another type is testosterone replacement therapy, which treats men with hypogonadism and it helps increase libido. On the contractionary, selective oestrogen receptor modulators (SERMs) lead to a drop in oestrogen levels that would cause vaginal dryness.
=== Amphetamines ===
Amphetamines may lead to an increase in sexual drive and delay in orgasm.
=== Cocaine ===
Cocaine is a potent psycho-stimulant that boosts dopamine levels by inhibiting dopamine transporters. It has been often linked to enhanced libido and risk-taking behavior in humans.
Cocaine has been observed to increase sexual arousal or to trigger spontaneous erections and orgasms.
In contrast, other data has shown that persistent cocaine use impairs sexual desire and the capacity of both men and women to achieve orgasm.
=== Cannabis ===
Cannabis is the most commonly used illicit substance. Studies on cannabis and sex have shown that THC has been linked to improved sexual desire and function. Specifically, in one study, 70 percent of users said marijuana was an aphrodisiac, and 81 percent said it improved their sexual pleasure and satisfaction.
Other research has found that long-term marijuana use lowers testosterone levels and other reproductive hormones, causing erectile dysfunction in males.
=== MDMA ===
MDMA or "ecstasy" originally gained popularity in the 1980s among college students. According to a survey conducted, 10% of college students at a big US institution reported using MDMA, with alcohol and marijuana being the most often used substances. MDMA users report increased enjoyment in physical contact and proximity rather than a sexual experience. MDMA has been shown to impair sexual performance, including erectile dysfunction and delayed orgasm, as well as to suppress sex desire.
=== Opioids ===
Opioids (also known as narcotics) such as morphine and heroin attach to opioid receptors in the brain. These substances have long been known to inhibit sexual behavior.
Similar to the effects of psycho-stimulants, both men and women who use heroin report engaging in high-risk sexual practices.
Subjects typically report having several sexual partners, using condoms seldom or not at all, and having a high frequency of STI diagnosis.
While small doses of heroin may enhance sexual desire and performance, chronic opiate use, including methadone and buprenorphine, synthetic and semi-synthetic opiates prescribed for opiate addiction treatment, results in decreased sexual desire, response, and orgasms for both men and women, as well as erectile, ejaculatory dysfunction, and vaginismus.
== Positive effects of drugs on sexual performance ==
=== Increased libido ===
Libido refers to a person's overall sexual desire and drive. Since low testosterone levels are associated with low sexual desire, testosterone replacement therapy can be prescribed for increasing testosterone in the body, increasing libido and restoring hormonal balance. While Phosphodiesterase-5 (PDE5) inhibitors such as sildenafil, tadalafil, vardenafil, and avanafil are primarily known for treating erectile dysfunction, it also has a positive effect on libido.
Flibanserin is a drug that is both a serotonin antagonist and agonist that treats hypoactive sexual desire disorder (HSDD) for premenopausal women. The drug acts as antagonist and agonist on two different receptors. The binding of flibanserin causes downstream release of dopamine and noradrenaline and reduces the production of serotonin, increasing sex drive. However, currently there is still no evidence that this drug would enhance sexual performance, therefore this drug still needs to be further investigated.
=== Increased sexual function ===
For males, several drugs increases the blood flow to the penis which allows for the achievement and maintenance of an erection. Phosphodiesterase-5 (PDE5) inhibitors are widely known and commonly prescribed for erectile dysfunction. PDE5 enzymes are blocked by PDE5 inhibitors to prevent their function, this allows for the relaxation of penile blood vessels and muscles, facilitating increased blood circulation to the penis. Alprostadil injections as a vasodilator are also used for the treatment of erectile dysfunction, expanding blood vessels that result in increasing blood flow to the penis.
For females, vaginal lubricant production can be increased by hormone replacement therapy (HRT) medicine such as vaginal estrogen. Vaginal dryness results from a declined level in circulating estrogen within the body, most likely during menopause. Treatment for vaginal dryness typically involves the use of localised estrogen, such as HRT medicine. This drug works by increasing estrogen in the body circulation, thereby enhancing lubrication production in the vaginal area.
=== Achieving orgasm ===
Delayed ejaculation, a type of male sexual disorder that is characterised by the delay of ejaculation or inability to achieve ejaculation. There are no approved drugs for the treatment of delayed ejaculation as of now, The majority of medications used for treating delayed ejaculation are primarily intended for treating different medical conditions. Amantadine, a Parkinson's medication, is known to enhance dopamine agonist release and activate dopamine receptors, which helps with ejaculation. However, there is not sufficient evidence to support the effectiveness of these medications on delayed ejaculation.
== Negative effects of drugs on sexual performance ==
=== Decreased libido ===
Several common medications can contribute to low libido. Antidepressants, especially selective serotonin reuptake inhibitors (SSRIs) antidepressants, increase serotonin levels that decrease testosterone, leading to a decrease in libido. Antipsychotic drugs create blockages of dopamine D2 receptors that are responsible for dopamine production can lead to a low libido. Additionally, these drugs can increase production of prolactin in males which contribute to lower levels of testosterone. Chemotherapy drugs also lead to a decrease in testosterone but it is only temporary during the course of therapy.
Drinking large amounts of alcohol regularly can lead to low libido due to a process called aromatisation. This process refers to the conversion of testosterone or its precursors into estrogen, leading to a decrease in testosterone levels in circulation.
=== Decreased sexual function ===
Impotence refers to the inability of a male's penis to become erect for sexual intercourse, in which the male is not able to get or maintain an erection. The medical term for this phenomenon is erectile dysfunction. Drugs such as antihypertensives including thiazide diuretics, loop diuretics, and beta-blockers used for lowering blood pressure limiting blood flow to the penis area, making it difficult to get or maintain an erection. Direct effects caused by antihypertensives on the penile vascular smooth muscle lead to vasoconstriction which leads to impaired perfusion. Antipsychotic drugs are also responsible for several mechanisms that lead to erectile dysfunction. Mechanisms such as acetylcholine receptor antagonism and alpha-adrenergic receptor antagonism reduces periphery vasodilation, inducing erectile dysfunction.
Overindulgence in alcohol may also cause temporary inability to achieve an erection. Alcohol, being a diuretic, can cause a person to urinate more frequently, resulting in dehydration. Dehydration reduces the volume of blood in the body, consequently decreasing blood flow towards the penis Additionally, dehydration also increases angiotensin levels in the body, which is a hormone associated with erectile dysfunction.
Birth control pills affect hormone levels in the body such as a decrease in estrogen, leading to vaginal dryness by thinning and shrinking of the vaginal tissue. Moreover, SERMs such as Evista and Tamoxifen which are used to treat breast cancer, results in vaginal dryness.
Antihistamines narrow blood vessels, leading to lowering of moisture levels as well as mucous production, which includes lubricant production in the vagina. Anti-hypertensive drugs help reduce blood pressure by decreasing blood flow to organs in the body, resulting in decreased vaginal lubrication as well.
=== Reduced sensations ===
Antidepressants, particularly SSRIs, cause delayed ejaculation and orgasm due to its function of retaining serotonin, which inhibits ejaculation. Similarly, antipsychotics also contribute to delayed ejaculation by affecting dopamine transporters, where dopamine plays a role in ejaculation via D2 receptors.
SSRI prevents reuptake of serotonin, thereby increasing serotonin in the body and decreasing their ability to produce lubricant in the vagina. It has been reported that around 42% of women that intake this type of medication have problems with orgasm production. Other medications such as antipsychotic drugs also reported signs of impaired orgasm.
Intake of too much alcohol can potentially cause depressant effects on the central nervous system (CNS). These effects contribute to sensory dullness, which leads to a delay effect on orgasm and ejaculation.
== Date rape drugs ==
A date rape drug is any drug that is an incapacitating agent which—when administered to another person—incapacitates the person and renders them vulnerable to a drug-facilitated sexual assault (DFSA), including rape. One of the most common types of DFSA are those in which a victim consumes a recreational drug such as alcohol that was administered surreptitiously. The other most common form of DFSA involves the non-surreptitiously administered consumption of alcohol. Here, the victims in these cases are drinking voluntarily which then makes them unable to make informed decisions or give consent.
== Society and culture ==
=== Chemsex ===
Party and play, or chemsex, is the consumption of drugs to facilitate sexual activity. Sociologically, both terms refer to a subculture of recreational drug users who engage in high-risk sexual activities under the influence of drugs within groups. The term PnP is commonly used by gay men and other men who have sex with men (MSM) in North America, while chemsex is more associated with the gay scene in Europe. The drug of choice is typically methamphetamine, known as tina or T, but other drugs are also used, such as mephedrone, GHB, GBL and alkyl nitrites (known as poppers).
=== Contraception and abortion ===
Drug-based contraception has been available since the development of the contraceptive pill. As well as their contraceptive effects, contraceptive drugs can also have adverse sexual and reproductive side-effects. Prior to the availability of effective contraceptives, some substances were also used as abortifacients to terminate pregnancy; medical abortion exists as a modern medical practice.
== See also ==
Abortifacient
Aphrodisiac
Date rape drug
Hormonal contraception
Libido § Medications
Methamphetamine and sex
Nitrite inhalants
Party and play
Sex and alcohol
Sex and Drugs and Rock and Roll
Wine, women, and song
== References == | Wikipedia/Sex_and_drugs |
Drug injection is a method of introducing a drug into the bloodstream via a hollow hypodermic needle, which is pierced through the skin into the body (usually intravenously, but also at an intramuscular or subcutaneous, location). Intravenous therapy, a form of drug injection, is universally practiced in modernized medical care. As of 2004, there were 13.2 million people worldwide who self-administered injection drugs outside of medical supervision, of which 22% are from developed countries.
A wide variety of drugs are injected, often opioids: these may include legally prescribed medicines and medication such as morphine, as well as stronger compounds often favored in recreational drug use, which are often illegal. Although there are various methods of taking drugs, injection is favoured by some people as the full effects of the drug are experienced very quickly, typically in five to ten seconds. It also bypasses first-pass metabolism in the liver, resulting in higher bioavailability and efficiency for many drugs (such as morphine or diacetylmorphine/heroin; roughly two-thirds of which is destroyed in the liver when consumed orally) than oral ingestion would. The effect is that the person gets a stronger (yet shorter-acting) effect from the same amount of the drug. Drug injection is therefore often related to substance dependence.
In recreational-use drug culture, preparation may include mixing the powdered drug with water to create an aqueous solution, and then the solution is injected. This act is often colloquially referred to as "slamming", "shooting up", "smashing", "banging", "pinning", or "jacking-up", often depending on the specific drug subculture in which the term is used (e.g. heroin, cocaine, or methamphetamine).
== Risks ==
In addition to general problems associated with any IV drug administration (see risks of IV therapy), there are some specific problems associated with the injection of drugs by non-professionals, such as:
Increased chance of overdose
Arterial damage – Arterial pseudoaneurysms may form at injection sites, which can rupture, potentially resulting in hemorrhage, distal ischemia, and gangrene. Inadvertent intra-arterial injection can also result in endarteritis and thrombosis, with ultimately similar consequences.
== Methods ==
The drug—usually (but not always) in a powder or crystal form—is dissolved in water, normally in a spoon, tin, bottle cap, the bottom of a soda can, or another metal container. Cylindrical metal containers—sometimes called "cookers"—are provided by needle exchange programs. Users draw the required amount of water into a syringe and squirt this over the drugs. The solution is then mixed and heated from below if necessary. Heating is used mainly with heroin (though not always, depending on the type of heroin), but is also often used with other drugs, especially crushed tablets. Cocaine HCl (powdered cocaine) dissolves quite easily without heat. Heroin prepared for the European market is insoluble in water and usually requires the addition of an acid such as citric acid or ascorbic acid (Vitamin C) powder to dissolve the drug. Due to the dangers from using lemon juice or vinegar to acidify the solution, packets of citric acid and Vitamin C powder are available at needle exchanges in Europe. In the U.S., vinegar and lemon juice are used to shoot crack cocaine. The acids convert the water-insoluble cocaine base in crack to a cocaine salt (cocaine acetate or cocaine citrate), which is water-soluble (like cocaine hydrochloride).
Once the drugs are dissolved, a small syringe (usually 0.5, 1 or 3 cc) is used to draw the solution through a syringe filter, alternatively cotton from a cigarette filter or cotton swab (cotton bud) is used. "Tuberculin" syringes and types of syringes used to inject insulin are commonly used. Commonly used syringes usually have a built-in 28 gauge (or thereabouts) needle typically 1/2 or 5/8 inches long.
The preferred injection site is the crook of the elbow (i.e., the Median cubital vein), on the user's non-writing hand. Other users opt to use the Basilic vein; while it may be easier to "hit", caution must be exercised as two nerves run parallel to the vein, increasing the chance of nerve damage, as well as the chance of an arterial "nick".
Regarding route of administration, much injection drug use, but not all, is intravenous injection, whereas some is subcutaneous injection or intramuscular injection (including skin popping, which often involves a depot injection).
== Recreational drugs ==
=== Risks ===
==== Substances ====
===== Contraindicated substances =====
Codeine - Injectable codeine is available for subcutaneous or intramuscular injection only; intravenous injection is contraindicated as this can result in non-immune mast-cell degranulation and resulting anaphylactoid reaction.
Ethchlorvynol is not compatible with intravenous injection and serious injury (including the loss of limbs due to vascular injury) or death can occur when it is used in this manner.
Hydroxyzine (brand name Atarax, and Vistaril) is contraindicated for subcutaneous, intra-articular, or subcutaneous administration.
===== Street drugs =====
Black tar heroin is notably risky to inject.
==== Infections ====
Risks from drug injection are caused by a variety of factors, including unclean or unsafe injection practices such as blood flashing and repeated injections at the same site. Injection drug users that fail to adequately sanitize the skin or use clean injection products are at increased risk for cellulitis, abscesses, and thrombophlebitis; these infections can subsequently result in sepsis and bacteremia, which can be fatal if untreated. Repetitive injections, especially those with unsafe practices, can result in additional medical concerns that include thrombosis formation and infectious endocarditis. In rare cases osteomyelitis of the chest can be caused by IV drug use.
Additional risks from unsafe injection practices result primarily from sharing materials (needles, cookers, syringes) used in injection. Blood-borne pathogens, such as HIV, Hepatitis B, and Hepatitis C are of particular concern among injection drug users who share supplies, and increase the likelihood of infection. An added challenge, is that not only infected individuals know their positive status and continue to share supplies, placing other users at risk for infection as well. 30-50% of adults will not experience acute Hepatitis B symptoms, and those that do experience lethargy, nausea, upper abdominal pain, muscle aches, or a darkening of urine will need to connect these symptoms to a possible infection to seek care and limit spreading of the virus.
Of all the ways to ingest drugs, injection carries the most risks by far as it bypasses the body's natural filtering mechanisms against viruses, bacteria, and foreign objects. There will always be much less risk of overdose, disease, infections, and health problems with alternatives to injecting, such as smoking, insufflation (snorting or nasal ingestion), or swallowing.
Drug injection is also commonly a component in HIV-related syndemics. Fragments from injection of pills are known to clog the small blood vessels of the lungs, brain, and elsewhere, potentially causing pulmonary embolism (PE), stroke, or venous embolism. A small proportion of PE is due to the embolization of air, fat, and talc in the drugs of people who inject substances. More commonly, the inflammatory response to these foreign objects causes granulation tissue to form in the capillary beds, resulting in vasculitis, and, when it occurs in the pulmonary capillary bed, potentially pulmonary talcosis. Hitting arteries and nerves is dangerous, painful, and presents its own similar spectrum of problems.
The injection of talc from crushed pills has been associated with pulmonary talcosis in intravenous drug users.
=== Harm reduction ===
Harm reduction is a public health approach that serves as an alternative to abstinence-only guidance. While it does not condone the use of illicit or illegal drugs, it does seek to reduce the harms, risks and dangers associated with illicit drug use, both for the person using illicit drugs and the wider community. Injection drug users that re-use drug delivery components put themselves and others at risk for diseases such as HIV, hepatitis B, and hepatitis C, as well as increase their chances of getting a serious infection. In 2015, the CDC performed an HIV Surveillance Report and attributed 2,392 (6%) of new HIV diagnoses to IV drug use in the US.
A prominent method for addressing the issue of disease transmission among intravenous drug users are needle exchange programs (also known as syringe exchange programs, syringe service programs or needle-syringe programs), where people who inject drugs (PWID) can access sterile needles, syringes, and other paraphernalia. In addition to providing sterile devices used in drug injection, these programs often offer access to infectious disease testing, referrals for substance use or mental health treatment programs, and more. The idea behind harm reduction approaches is to slow disease transmission, such as HIV/AIDS and hepatitis B and C, and promote public health by reducing the practice of sharing used needles.
In countries where harm reduction programs are limited or non-existent, it is quite common for IV users to use a single needle repeatedly or share with other users. It is also quite uncommon for a sterilizing agent to be used on needles and syringes. This creates a high risk population for the spread of bloodborne pathogens.
A new approach to reduce harm to IV drug users was recently started in Southern Nevada in 2017. Trac-B Exchange - Southern Nevada Harm Reduction Program was approved in early 2017 to help reduce the spread of HIV in "People Who Inject Drugs". In Nevada, the sharing of needles for drug injections has led to an increase in the spread of HIV and hepatitis B and C. In an effort to reduce the spread of blood borne pathogens, Southern Nevada installed vending machines to give access to sterile needles to those using them for drug injections. Individuals who use these vending machines are required to register with Trac-B and are allowed 2 boxes a week. The boxes contain sterile needles as well as other supplies necessary to reduce the risk of spreading blood borne pathogens. This is a pilot program for increasing injection safety and, if successful, may expand to other areas of the United States.
Although this is a new idea in the United States, it was tested in Europe over 20 years ago. In order to combat the AIDS epidemic that was spreading across Europe, France allowed pharmacies to dispense needles without a prescription and implemented needle exchange programs. In 1996, they began a pilot program of syringe vending machines, similar to a coin-operated vending machine. The first vending machines were placed in Marseille due to its high occurrence of AIDS caused by sharing of needles. The results of their study was published in 1999. They found that when the availability of syringes increased, more and more people began to purchase sterile needles. It also provided a discreet way for people to purchase needles without having to feel embarrassed going into a pharmacy. They theorized that with greater access to sterile needles, they would expect to see a reduction in bloodborne pathogen cases.
Beyond just needle exchange programs, the other major harm reduction strategy for drug users are safe injecting facilities (SIFs). These provide a sterile environment for people who inject drugs to do so cleanly, and with sterile syringes which are forced to be thrown away after use so that no re-use occurs. The first of these facilities opened in Switzerland, but there are now over 100 globally including one in Vancouver - Canada, Sydney - Australia, and most recently, Melbourne - Australia.
== Modifications ==
Particularly for intravenous administration, self-injection in the arm can be awkward, and some people modify a syringe for single-handed operation by removing the plunger and affixing a bulb such as from a large dropper or baby pacifier to the end of the barrel to in effect make it a large dropper with a needle affixed. This is therefore a variant of the common method of injection with a dropper with the hypodermic needle affixed, using a "collar" made of paper or other material to create a seal between the needle and dropper. Removing part of the plunger assembly by cutting off most of the shaft and thumb rest and affixing the bulb to the end of the barrel, thereby allowing the bulb to operate the plunger by suction, also does work in many cases.
An alternative to syringes in the 1970s was to use a glass medicine dropper, supposedly easier to manipulate with one hand. A large hairpin was used to make a hole in the skin and the dropper containing the drug (usually heroin) was inserted and the bulb squeezed, releasing it into the tissues. This method was also reported—by William S. Burroughs and other sources—for intravenous administration at least as far back as 1930.
== Alternatives ==
The closest method to IV/overall injection use, in terms of rapid onset, optimal bioavailability, and reduced health risks for most drugs, tends to be rectal administration via concentrated liquid solution (also known as a suppository), usually consisting of only ~1-3ml of liquid (typically not exceeding 5-10ml) assuming the drug in question possesses sufficient water solubility. While oral morphine has a general bioavailability range is only 20-40%, properly administered rectal use of liquid morphine has an effective bioavailability of roughly 70%, or more than double the overall potency of oral morphine and more than two thirds that of IV use. Swallowing tends to be the safest and slowest method of ingesting drugs. It is safer as the body has a much greater chance to filter out impurities. As orally administered drugs take effect later, the effects tend to last longer as well, making oral administration a preferred method among dance and rave groups for drugs such as amphetamine and MDMA. People rarely take heroin orally, as it is converted to morphine in the stomach and its potency is reduced by more than 65% in the process. However, oral bioavailability of opioids is heavily dependent on the substance, dose, and patient in ways that are not yet understood.
== History ==
IV drug use is a relatively recent phenomenon arising from the invention of re-usable syringes and the synthesis of chemically pure morphine and cocaine.
It was noted that administering drugs intravenously strengthened their effect, and—since such drugs as heroin and cocaine were already being used to treat a wide variety of ailments—many patients were given injections of "hard" drugs for such ailments as alcoholism and depression.
=== Origin and early use ===
The hypodermic needle and syringe in its current form was invented by the French scientist Charles Pravaz in 1851, and became especially known during the wars of that and the subsequent decade. However, the first well-known attempt to inject drugs into the body was a 1667 attempt to inject a solution of opium into a dog, and some had suspected that parenteral administration of drugs may work better based on the practise of rubbing opium and other drugs into sores or cuts on the skin for the purpose of causing systemic absorption and the beginnings of scientific understanding of the functioning of the lungs.
During most of the 1850s, the previously held belief that opiate dependence and addiction (often called "the opium appetite", or, when relevant, the "morphine appetite" or "codeine appetite") was due to the drug's action on the digestive system—just like any hunger or thirst—caused doctors to opt to inject morphine rather than administer it orally, in the hope that addiction would not develop. Certainly, by c. 1870 or earlier, it was manifest that this was not the case and the title of earliest morphine addict as the term is currently understood is often given to Pravaz' wife, although habituation through orally ingesting the drug was known before this time, including Friedrich Sertürner and his associates, followers, wife, and dog. To some extent, it was also believed early on that bypassing the lungs would prevent opium addiction, as well as habituation to tobacco. Ethanol in its usual form generally is not injected and can be very damaging by most routes of injection; in modern times, it is used as an alternative or potentiator of phenol (carbolic acid) in procedures to ablate damaged nerves.
In or shortly after 1851, the drugs which had been discovered and extracted from their plants of origin and refined into pure crystalline salts soluble in water included morphine (1804 or late 1803), codeine (1832), narcotine/noscapine (1803–1805?), papaverine (1814), cocaine (1855), caffeine (1819), quinine (1820), atropine (1831), scopolamine (aka hyoscine, aka laevo-duboisine) (1833?), hyoscyamine or laevo-atropine (1831), opium salts mixtures (c. 1840s), chloral derivatives (1831 et seq.), ephedrine (1836?), nicotine (1828), and many others of all types, psychoactive and not. Morphine in particular was used much more widely after the invention of the hypodermic syringe, and the practise of local anaesthesia by infiltration was another step forward in medicine resulting from the hypodermic needle, discovered at around the same time that it was determined that cocaine produced useful numbing of the mucous membranes and eye.
A wide variety of drugs are injected. Among the most popular in many countries are morphine, heroin, cocaine, amphetamine, and methamphetamine. Prescription drugs—including tablets, capsules, and even liquids and suppositories—are also occasionally injected. This applies particularly to prescription opioids, since some opioid addicts already inject heroin. Injecting preparations which were not intended for this purpose is particularly dangerous because of the presence of excipients (fillers), which can cause blood clots. Injecting codeine into the bloodstream directly is dangerous because it causes a rapid histamine release, which can lead to potentially fatal anaphylaxis and pulmonary edema. Dihydrocodeine, hydrocodone, nicocodeine, and other codeine-based products carry similar risks. Codeine may instead be injected by the intramuscular or subcutaneous route. The effect will not be instant, but the dangerous and unpleasant massive histamine release from the intravenous injection of codeine is avoided. To minimize the amount of undissolved material in fluids prepared for injection, a filter of cotton or synthetic fiber is typically used, such as a cotton-swab tip or a small piece of cigarette filter.
Some manufacturers add the narcotic antagonist naloxone or the anticholinergics atropine and homatropine (in lower than therapeutic doses) to their pills to prevent injection. Unlike naloxone, atropine does indeed help morphine and other narcotics combat neuralgia. The atropine may very well not present a problem, and there is the possibility of atropine content reduction of soluble tablets by placing them on an ink blotter with a drop of water on top, then preparing a shot from the remainder of the pill. Canada and many other countries prohibit manufacturers from including secondary active ingredients for the above reason; their Talwin PX does not contain naloxone. However, as a narcotic agonist–antagonist, pentazocine and its relatives can cause withdrawal in those physically dependent upon narcotics.
== See also ==
Air embolism
Extravasation (intravenous)
Lethal injection
Needle and syringe programmes
Needle remover
Needlestick injury
Safety syringe
Supervised injection site
== References ==
== External links ==
Safer injection and vein care Chicago Recovery Alliance's extremely comprehensive and well designed informational series
United Nations Office on Drugs & Crime | Wikipedia/Drug_injection |
The prohibition of drugs through sumptuary legislation or religious law is a common means of attempting to prevent the recreational use of certain intoxicating substances.
An area has a prohibition of drugs when its government uses the force of law to punish the use or possession of drugs which have been classified as controlled. A government may simultaneously have systems in place to regulate both controlled and non controlled drugs. Regulation controls the manufacture, distribution, marketing, sale, and use of certain drugs, for instance through a prescription system. For example, in some states, the possession or sale of amphetamines is a crime unless a patient has a physician's prescription for the drug; having a prescription authorizes a pharmacy to sell and a patient to use a drug that would otherwise be prohibited. Although prohibition mostly concerns psychoactive drugs (which affect mental processes such as perception, cognition, and mood), prohibition can also apply to non-psychoactive drugs, such as anabolic steroids. Many governments do not criminalize the possession of a limited quantity of certain drugs for personal use, while still prohibiting their sale or manufacture, or possession in large quantities. Some laws (or judicial practice) set a specific volume of a particular drug, above which is considered ipso jure to be evidence of trafficking or sale of the drug.
Some Islamic countries prohibit the use of alcohol (see list of countries with alcohol prohibition). Many governments levy a tax on alcohol and tobacco products, and restrict alcohol and tobacco from being sold or gifted to a minor. Other common restrictions include bans on outdoor drinking and indoor smoking. In the early 20th century, many countries had alcohol prohibition. These include the United States (1920–1933), Finland (1919–1932), Norway (1916–1927), Canada (1901–1948), Iceland (1915–1922) and the Russian Empire/USSR (1914–1925). In fact, the first international treaty to control a psychoactive substance adopted in 1890 actually concerned alcoholic beverages (Brussels Conference). The first treaty on opium only arrived two decades later, in 1912.
== Definitions ==
Drugs, in the context of prohibition, are any of a number of psychoactive substances whose use a government or religious body seeks to control. What constitutes a drug varies by century and belief system. What is a psychoactive substance is relatively well known to modern science. Examples include a range from caffeine found in coffee, tea, and chocolate, nicotine in tobacco products; botanical extracts morphine and heroin, and synthetic compounds MDMA and fentanyl. Almost without exception, these substances also have a medical use, in which case they are called pharmaceutical drugs or just pharmaceuticals. The use of medicine to save or extend life or to alleviate suffering is uncontroversial in most cultures. Prohibition applies to certain conditions of possession or use. Recreational use refers to the use of substances primarily for their psychoactive effect outside of a clinical situation or doctor's care.
In the twenty-first century, caffeine has pharmaceutical uses. Caffeine is used to treat bronchopulmonary dysplasia. In most cultures, caffeine in the form of coffee or tea is unregulated. Over 2.25 billion cups of coffee are consumed in the world every day. Some religions, including the Church of Jesus Christ of Latter-day Saints, prohibit coffee. They believe that it is both physically and spiritually unhealthy to consume coffee.
A government's interest to control a drug may be based on its negative effects on its users, or it may simply have a revenue interest. The British parliament prohibited the possession of untaxed tea with the imposition of the Tea Act of 1773. In this case, as in many others, it is not a substance that is prohibited, but the conditions under which it is possessed or consumed. Those conditions include matters of intent, which makes the enforcement of laws difficult. In Colorado possession of "blenders, bowls, containers, spoons, and mixing devices" is illegal if there was intent to use them with drugs.
Many drugs, beyond their pharmaceutical and recreational uses, have industrial uses. Nitrous oxide, or laughing gas is a dental anesthetic, also used to prepare whipped cream, fuel rocket engines, and enhance the performance of race cars. Ethanol, or drinking alcohol, is also used as a fuel, industrial solvent and disinfectant.
== History ==
The cultivation, use, and trade of psychoactive and other drugs has occurred since ancient times. Concurrently, authorities have often restricted drug possession and trade for a variety of political and religious reasons. In the 20th century, the United States led a major renewed surge in drug prohibition called the "War on Drugs".
=== Early drug laws ===
The prohibition on alcohol under Islamic Sharia law, which is usually attributed to passages in the Qur'an, dates back to the early seventh century. Although Islamic law is often interpreted as prohibiting all intoxicants (not only alcohol), the ancient practice of hashish smoking has continued throughout the history of Islam, against varying degrees of resistance. A major campaign against hashish-eating Sufis were conducted in Egypt in the 11th and 12th centuries resulting among other things in the burning of fields of cannabis.
Though the prohibition of illegal drugs was established under Sharia law, particularly against the use of hashish as a recreational drug, classical jurists of medieval Islamic jurisprudence accepted the use of hashish for medicinal and therapeutic purposes, and agreed that its "medical use, even if it leads to mental derangement, should remain exempt [from punishment]". In the 14th century, the Islamic scholar Az-Zarkashi spoke of "the permissibility of its use for medical purposes if it is established that it is beneficial".
In the Ottoman Empire, Murad IV attempted to prohibit coffee drinking to Muslims as haraam, arguing that it was an intoxicant, but this ruling was overturned soon after he died in 1640. The introduction of coffee in Europe from Muslim Turkey prompted calls for it to be banned as the devil's work, although Pope Clement VIII sanctioned its use in 1600, declaring that it was "so delicious that it would be a pity to let the infidels have exclusive use of it". Bach's Coffee Cantata, from the 1730s, presents a vigorous debate between a girl and her father over her desire to consume coffee. The early association between coffeehouses and seditious political activities in England led to the banning of such establishments in the mid-17th century.
A number of Asian rulers had similarly enacted early prohibitions, many of which were later forcefully overturned by Western colonial powers during the 18th and 19th centuries. In 1360, for example, King Ramathibodi I, of Ayutthaya Kingdom (now Thailand), prohibited opium consumption and trade. The prohibition lasted nearly 500 years until 1851 when King Rama IV allowed Chinese migrants to consume opium. The Konbaung Dynasty prohibited all intoxicants and stimulants during the reign of King Bodawpaya (1781–1819). After Burma became a British colony, the restrictions on opium were abolished and the colonial government established monopolies selling Indian-produced opium.
In late Qing China, opium imported by foreign traders, such as those employed by Jardine Matheson and the East India Company, was consumed by all social classes in Southern China. Between 1821 and 1837, imports of the drug increased fivefold. The wealth drain and widespread social problems that resulted from this consumption prompted the Chinese government to attempt to end the trade. This effort was initially successful, with Lin Zexu ordering the destruction of opium at Humen in June 1839. However, the opium traders lobbied the British government to declare war on China, resulting in the First Opium War. The Qing government was defeated and the war ended with the Treaty of Nanking, which legalized opium trading in Chinese law
=== First modern drug regulations ===
The first modern law in Europe for the regulating of drugs was the Pharmacy Act 1868 in the United Kingdom. There had been previous moves to establish the medical and pharmaceutical professions as separate, self-regulating bodies, but the General Medical Council, established in 1863, unsuccessfully attempted to assert control over drug distribution. The act set controls on the distribution of poisons and drugs. Poisons could only be sold if the purchaser was known to the seller or to an intermediary known to both, and drugs, including opium and all preparations of opium or of poppies, had to be sold in containers with the seller's name and address.
Despite the reservation of opium to professional control, general sales did continue to a limited extent, with mixtures with less than 1 percent opium being unregulated.
After the legislation passed, the death rate caused by opium immediately fell from 6.4 per million population in 1868 to 4.5 in 1869. Deaths among children under five dropped from 20.5 per million population between 1863 and 1867 to 12.7 per million in 1871 and further declined to between 6 and 7 per million in the 1880s.
In the United States, the first drug law was passed in San Francisco in 1875, banning the smoking of opium in opium dens. The reason cited was "many women and young girls, as well as young men of a respectable family, were being induced to visit the Chinese opium-smoking dens, where they were ruined morally and otherwise." This was followed by other laws throughout the country, and federal laws that barred Chinese people from trafficking in opium. Though the laws affected the use and distribution of opium by Chinese immigrants, no action was taken against the producers of such products as laudanum, a tincture of opium and alcohol, commonly taken as a panacea by white Americans. The distinction between its use by white Americans and Chinese immigrants was thus a form of racial discrimination as it was based on the form in which it was ingested: Chinese immigrants tended to smoke it, while it was often included in various kinds of generally liquid medicines often (but not exclusively) used by Americans of European descent. The laws targeted opium smoking, but not other methods of ingestion.
Britain passed the All-India Opium Act of 1878, which limited recreational opium sales to registered Indian opium-eaters and Chinese opium-smokers and prohibiting its sale to emigrant workers from British Burma.
Following the passage of a regional law in 1895, Australia's Aboriginals Protection and Restriction of the Sale of Opium Act 1897 addressed opium addiction among Aborigines, though it soon became a general vehicle for depriving them of basic rights by administrative regulation. Opium sale was prohibited to the general population in 1905, and smoking and possession were prohibited in 1908.
Despite these laws, the late 19th century saw an increase in opiate consumption. This was due to the prescribing and dispensing of legal opiates by physicians and pharmacists to relieve menstruation pain. It is estimated that between 150,000 and 200,000 opiate addicts lived in the United States at the time, and a majority of these addicts were women.
=== Changing attitudes and the drug prohibition campaign ===
Foreign traders, including those employed by Jardine Matheson and the East India Company, smuggled opium into China in order to balance high trade deficits. Chinese attempts to outlaw the trade led to the First Opium War and the subsequent legalization of the trade at the Treaty of Nanking. Attitudes towards the opium trade were initially ambivalent, but in 1874 the Society for the Suppression of the Opium Trade was formed in England by Quakers led by the Rev. Frederick Storrs-Turner. By the 1890s, increasingly strident campaigns were waged by Protestant missionaries in China for its abolition. The first such society was established at the 1890 Shanghai Missionary Conference, where British and American representatives, including John Glasgow Kerr, Arthur E. Moule, Arthur Gostick Shorrock and Griffith John, agreed to establish the Permanent Committee for the Promotion of Anti-Opium Societies.
Due to increasing pressure in the British parliament, the Liberal government under William Ewart Gladstone approved the appointment of a Royal Commission on Opium to India in 1893. The commission was tasked with ascertaining the impact of Indian opium exports to the Far East, and to advise whether the trade should be banned and opium consumption itself banned in India. After an extended inquiry, the Royal Commission rejected the claims made by the anti-opium campaigners regarding the supposed societal harm caused by the trade and the issue was finalized for another 15 years.
The missionary organizations were outraged over the Royal Commission on Opium's conclusions and set up the Anti-Opium League in China; the league gathered data from every Western-trained medical doctor in China and published Opinions of Over 100 Physicians on the Use of Opium in China. This was the first anti-drug campaign to be based on scientific principles, and it had a tremendous impact on the state of educated opinion in the West. In England, the home director of the China Inland Mission, Benjamin Broomhall, was an active opponent of the opium trade, writing two books to promote the banning of opium smoking: The Truth about Opium Smoking and The Chinese Opium Smoker. In 1888, Broomhall formed and became secretary of the Christian Union for the Severance of the British Empire with the Opium Traffic and editor of its periodical, National Righteousness. He lobbied the British parliament to ban the opium trade. Broomhall and James Laidlaw Maxwell appealed to the London Missionary Conference of 1888 and the Edinburgh Missionary Conference of 1910 to condemn the continuation of the trade. As Broomhall lay dying, an article from The Times was read to him with the welcome news that an international agreement had been signed ensuring the end of the opium trade within two years.
In 1906, a motion to 'declare the opium trade "morally indefensible" and remove Government support for it', initially unsuccessfully proposed by Arthur Pease in 1891, was put before the House of Commons. This time the motion passed. The Qing government banned opium soon afterward.
These changing attitudes led to the founding of the International Opium Commission in 1909. An International Opium Convention was signed by 13 nations at The Hague on January 23, 1912, during the First International Opium Conference. This was the first international drug control treaty and it was registered in the League of Nations Treaty Series on January 23, 1922. The Convention provided that "The contracting Powers shall use their best endeavors to control or to cause to be controlled, all person manufacturing, importing, selling, distributing, and exporting morphine, cocaine, and their respective salts, as well as the buildings in which these persons carry such an industry or trade."
The treaty became international law in 1919 when it was incorporated into the Treaty of Versailles. The role of the commission was passed to the League of Nations, and all signatory nations agreed to prohibit the import, sale, distribution, export, and use of all narcotic drugs, except for medical and scientific purposes.
=== Prohibition ===
In the UK the Defence of the Realm Act 1914, passed at the onset of the First World War, gave the government wide-ranging powers to requisition the property and to criminalize specific activities. A moral panic was whipped up by the press in 1916 over the alleged sale of drugs to the troops of the British Indian Army. With the temporary powers of DORA, the Army Council quickly banned the sale of all psychoactive drugs to troops, unless required for medical reasons. However, shifts in the public attitude towards drugs—they were beginning to be associated with prostitution, vice and immorality—led the government to pass further unprecedented laws, banning and criminalising the possession and dispensation of all narcotics, including opium and cocaine. After the war, this legislation was maintained and strengthened with the passing of the Dangerous Drugs Act 1920 (10 & 11 Geo. 5. c. 46). Home Office control was extended to include raw opium, morphine, cocaine, ecogonine and heroin.
Hardening of Canadian attitudes toward Chinese-Canadian opium users and fear of a spread of the drug into the white population led to the effective criminalization of opium for nonmedical use in Canada between 1908 and the mid-1920s.
The Mao Zedong government nearly eradicated both consumption and production of opium during the 1950s using social control and isolation. Ten million addicts were forced into compulsory treatment, dealers were executed, and opium-producing regions were planted with new crops. Remaining opium production shifted south of the Chinese border into the Golden Triangle region. The remnant opium trade primarily served Southeast Asia, but spread to American soldiers during the Vietnam War, with 20 percent of soldiers regarding themselves as addicted during the peak of the epidemic in 1971. In 2003, China was estimated to have four million regular drug users and one million registered drug addicts.
In the US, the Harrison Act was passed in 1914, and required sellers of opiates and cocaine to get a license. While originally intended to regulate the trade, it soon became a prohibitive law, eventually becoming legal precedent that any prescription for a narcotic given by a physician or pharmacist – even in the course of medical treatment for addiction – constituted conspiracy to violate the Harrison Act. In 1919, the Supreme Court ruled in Doremus that the Harrison Act was constitutional and in Webb that physicians could not prescribe narcotics solely for maintenance. In Jin Fuey Moy v. United States, the court upheld that it was a violation of the Harrison Act even if a physician provided prescription of a narcotic for an addict, and thus subject to criminal prosecution. This is also true of the later Marijuana Tax Act in 1937. Soon, however, licensing bodies did not issue licenses, effectively banning the drugs.
The American judicial system did not initially accept drug prohibition. Prosecutors argued that possessing drugs was a tax violation, as no legal licenses to sell drugs were in existence; hence, a person possessing drugs must have purchased them from an unlicensed source. After some wrangling, this was accepted as federal jurisdiction under the interstate commerce clause of the U.S. Constitution.
==== Alcohol prohibition ====
The prohibition of alcohol commenced in Finland in 1919 and in the United States in 1920. Because alcohol was the most popular recreational drug in these countries, reactions to its prohibition were far more negative than to the prohibition of other drugs, which were commonly associated with ethnic minorities, prostitution, and vice. Public pressure led to the repeal of alcohol prohibition in Finland in 1932, and in the United States in 1933. Residents of many provinces of Canada also experienced alcohol prohibition for similar periods in the first half of the 20th century.
In Sweden, a referendum in 1922 decided against an alcohol prohibition law (with 51% of the votes against and 49% for prohibition), but starting in 1914 (nationwide from 1917) and until 1955 Sweden employed an alcohol rationing system with personal liquor ration books ("motbok").
=== War on Drugs ===
In response to rising drug use among young people and the counterculture movement, government efforts to enforce prohibition were strengthened in many countries from the 1960s onward. Support at an international level for the prohibition of psychoactive drug use became a consistent feature of United States policy during both Republican and Democratic administrations, to such an extent that US support for foreign governments has often been contingent on their adherence to US drug policy. Major milestones in this campaign include the introduction of the Single Convention on Narcotic Drugs in 1961, the Convention on Psychotropic Substances in 1971 and the United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances in 1988. A few developing countries where consumption of the prohibited substances has enjoyed longstanding cultural support, long resisted such outside pressure to pass legislation adhering to these conventions. Nepal only did so in 1976.
In 1972, United States President Richard Nixon announced the commencement of the so-called "War on Drugs". Later, President Reagan added the position of drug czar to the President's Executive Office. In 1973, New York introduced mandatory minimum sentences of 15 years to life imprisonment for possession of more than 113 grams (4 oz) of a so-called hard drug, called the Rockefeller drug laws after New York Governor and later Vice President Nelson Rockefeller. Similar laws were introduced across the United States.
California's broader 'three strikes and you're out' policy adopted in 1994 was the first mandatory sentencing policy to gain widespread publicity and was subsequently adopted in most United States jurisdictions. This policy mandates life imprisonment for a third criminal conviction of any felony offense. A similar 'three strikes' policy was introduced to the United Kingdom by the Conservative government in 1997. This legislation enacted a mandatory minimum sentence of seven years for those convicted for a third time of a drug trafficking offense involving a class A drug.
=== Calls for legalization, relegalization or decriminalization ===
The terms relegalization, legalization, legal regulations, or decriminalization are used with very different meanings by different authors, something that can be confusing when the claims are not specified. Here are some variants:
Sales of one or more drugs (e.g., marijuana) for personal use become legal, at least if sold in a certain way.
Sales of an extracts with a specific substance become legal sold in a certain way, for example on prescription.
Use or possession of small amounts for personal use do not lead to incarceration if it is the only crime, but it is still illegal; the court or the prosecutor can impose a fine. (In that sense, Sweden both legalized and supported drug prohibition simultaneously.)
Use or possession of small amounts for personal use do not lead to incarceration. The case is not treated in an ordinary court, but by a commission that may recommend treatment or sanctions including fines. (In that sense, Portugal both legalized and supported drug prohibitions).
There are efforts around the world to promote the relegalization and decriminalization of drugs. These policies are often supported by proponents of liberalism and libertarianism on the grounds of individual freedom, as well as by leftists who believe prohibition to be a method of suppression of the working class by the ruling class.
Prohibition of drugs is supported by proponents of conservatism as well various NGOs. A number of NGOs are aligned in support of drug prohibition as members of the World Federation Against Drugs. In the WFAD constitution, the "Declaration of the World Forum Against Drugs" (2008) advocates for "no other goal than a drug-free world", and states that a balanced policy of drug abuse prevention, education, treatment, law enforcement, research, and supply reduction provides the most effective platform to reduce drug abuse and its associated harms and calls on governments to consider demand reduction as one of their first priorities. It supports the UN drug conventions, the inclusion of cannabis as one of the "hard drugs", and the use of criminal sanctions "when appropriate" to deter drug use. It opposes legalization in any form, and harm reduction in general.
According to some critics, drug prohibition is responsible for enriching "organised criminal networks" while the hypothesis that the prohibition of drugs generates violence is consistent with research done over long time-series and cross-country facts.
In the United Kingdom, where the principal piece of drug prohibition legislation is the Misuse of Drugs Act 1971, criticism includes:
Drug classification: making a hash of it?, Fifth Report of Session 2005–06, House of Commons Science and Technology Committee, which said that the present system of drug classification is based on historical assumptions, not scientific assessment
Development of a rational scale to assess the harm of drugs of potential misuse, David Nutt, Leslie A. King, William Saulsbury, Colin Blakemore, The Lancet, 24 March 2007, said the act is "not fit for purpose" and "the exclusion of alcohol and tobacco from the Misuse of Drugs Act is, from a scientific perspective, arbitrary"
The Drug Equality Alliance (DEA) argue that the Government is administering the Act arbitrarily, contrary to its purpose, contrary to the original wishes of Parliament and therefore illegally. They are currently assisting and supporting several legal challenges to this alleged maladministration.
In February 2008 the then-president of Honduras, Manuel Zelaya, called on the world to legalize drugs, in order, he said, to prevent the majority of violent murders occurring in Honduras. Honduras is used by cocaine smugglers as a transiting point between Colombia and the US. Honduras, with a population of 7 million, suffers an average of 8–10 murders a day, with an estimated 70% being a result of this international drug trade. The same problem is occurring in Guatemala, El Salvador, Costa Rica and Mexico, according to Zelaya. In January 2012 Colombian President Juan Manuel Santos made a plea to the United States and Europe to start a global debate about legalizing drugs. This call was echoed by the Guatemalan President Otto Pérez Molina, who announced his desire to legalize drugs, saying "What I have done is put the issue back on the table."
In a report dealing with HIV in June 2014, the World Health Organization (WHO) of the UN called for the decriminalization of drugs particularly including injected ones. This conclusion put WHO at odds with broader long-standing UN policy favoring criminalization. Eight states of the United States (Alaska, California, Colorado, Maine, Massachusetts, Nevada, Oregon, and Washington), as well as the District of Columbia, have legalized the sale of marijuana for personal recreational use as of 2017, although recreational use remains illegal under U.S. federal law. The conflict between state and federal law is, as of 2018, unresolved.
Since Uruguay in 2014 and Canada in 2018 legalized cannabis, the debate has known a new turn internationally.
On March 14th, 2025, the United Nations Commission on Narcotic Drugs decided to create a panel of independent experts to rethink the global drug control regime.
== Drug prohibition laws ==
The following individual drugs, listed under their respective family groups (e.g., barbiturates, benzodiazepines, opiates), are the most frequently sought after by drug users and as such are prohibited or otherwise heavily regulated for use in many countries:
Among the barbiturates, pentobarbital (Nembutal), secobarbital (Seconal), and amobarbital (Amytal)
Among the benzodiazepines, temazepam (Restoril; Normison; Euhypnos), flunitrazepam (Rohypnol; Hypnor; Flunipam), and alprazolam (Xanax)
Cannabis products, e.g., marijuana, hashish, and hashish oil
Among the dissociatives, phencyclidine (PCP), and ketamine are the most sought after.
hallucinogens such as LSD, mescaline, peyote, and psilocybin
Empathogen-entactogen drugs like MDMA ("ecstasy")
Among the narcotics, it is opiates such as morphine and codeine, and opioids such as diacetylmorphine (Heroin), hydrocodone (Vicodin; Hycodan), oxycodone (Percocet; Oxycontin), hydromorphone (Dilaudid), and oxymorphone (Opana).
Sedatives such as GHB and methaqualone (Quaalude)
Stimulants such as cocaine, amphetamine (Adderall), dextroamphetamine (Dexedrine), methamphetamine (Desoxyn), methcathinone, and methylphenidate (Ritalin)
The regulation of the above drugs varies in many countries. Alcohol possession and consumption by adults is today widely banned only in Islamic countries and certain states of India. Although alcohol prohibition was eventually repealed in the countries that enacted it, there are, for example, still parts of the United States that do not allow alcohol sales, though alcohol possession may be legal (see dry counties). New Zealand has banned the importation of chewing tobacco as part of the Smoke-free Environments Act 1990. In some parts of the world, provisions are made for the use of traditional sacraments like ayahuasca, iboga, and peyote. In Gabon, iboga (tabernanthe iboga) has been declared a national treasure and is used in rites of the Bwiti religion. The active ingredient, ibogaine, is proposed as a treatment of opioid withdrawal and various substance use disorders.
In countries where alcohol and tobacco are legal, certain measures are frequently undertaken to discourage use of these drugs. For example, packages of alcohol and tobacco sometimes communicate warnings directed towards the consumer, communicating the potential risks of partaking in the use of the substance. These drugs also frequently have special sin taxes associated with the purchase thereof, in order to recoup the losses associated with public funding for the health problems the use causes in long-term users. Restrictions on advertising also exist in many countries, and often a state holds a monopoly on manufacture, distribution, marketing, and/or the sale of these drugs.
=== List of principal drug prohibition laws by jurisdiction (non-exhaustive) ===
Australia: Standard for the Uniform Scheduling of Medicines and Poisons
Bangladesh: Narcotics Substances Control Act, 2018
Belize: Misuse of Drugs Act (Belize)
Canada: Controlled Drugs and Substances Act
Estonia: Narcotic Drugs and Psychotropic Substances Act (Estonia)
Germany: Narcotic Drugs Act
India: Narcotic Drugs and Psychotropic Substances Act (India)
Netherlands: Opium Law
New Zealand: Misuse of Drugs Act 1975
Pakistan: Control of Narcotic Substances Act 1997
Philippines: Comprehensive Dangerous Drugs Act of 2002
Poland: Drug Abuse Prevention Act 2005
Portugal: Decree-Law 15/93
Ireland: Misuse of Drugs Act (Ireland)
South Africa: Drugs and Drug Trafficking Act 1992
Singapore: Misuse of Drugs Act (Singapore)
Sweden: Lag om kontroll av narkotika (SFS 1992:860)
Thailand: Psychotropic Substances Act (Thailand) and Narcotics Act
United Kingdom: Misuse of Drugs Act 1971 and Drugs Act 2005
United States: Controlled Substances Act
International: Single Convention on Narcotic Drugs
=== Legal dilemmas ===
The sentencing statutes in the United States Code that cover controlled substances are complicated. For example, a first-time offender convicted in a single proceeding for selling marijuana three times, and found to have carried a gun on him all three times (even if it were not used) is subject to a minimum sentence of 55 years in federal prison.
In Hallucinations: Behavior, Experience, and Theory (1975), senior US government researchers Louis Jolyon West and Ronald K. Siegel explain how drug prohibition can be used for selective social control:
The role of drugs in the exercise of political control is also coming under increasing discussion. Control can be through prohibition or supply. The total or even partial prohibition of drugs gives the government considerable leverage for other types of control. An example would be the selective application of drug laws ... against selected components of the population such as members of certain minority groups or political organizations.
Linguist Noam Chomsky argues that drug laws are currently, and have historically been, used by the state to oppress sections of society it opposes:
Very commonly substances are criminalized because they're associated with what's called the dangerous classes, poor people, or working people. So for example in England in the 19th century, there was a period when gin was criminalized and whiskey wasn't, because gin is what poor people drink.
=== Legal highs and prohibition ===
In 2013 the European Monitoring Centre for Drugs and Drug Addiction reported that there are 280 new legal drugs, known as "legal highs", available in Europe. One of the best known, mephedrone, was banned in the United Kingdom in 2010. On November 24, 2010, the U.S. Drug Enforcement Administration announced it would use emergency powers to ban many synthetic cannabinoids within a month. An estimated 73 new psychoactive synthetic drugs appeared on the UK market in 2012. The response of the Home Office has been to create a temporary class drug order which bans the manufacture, import, and supply (but not the possession) of named substances.
=== Corruption ===
In certain countries, there is concern that campaigns against drugs and organized crime are a cover for corrupt officials tied to drug trafficking themselves. In the United States, Federal Bureau of Narcotics chief Harry Anslinger's opponents accused him of taking bribes from the Mafia to enact prohibition and create a black market for alcohol. More recently in the Philippines, one death squad hitman told author Niko Vorobyov that he was being paid by military officers to eliminate those drug dealers who failed to pay a 'tax'. Under President Rodrigo Duterte, the Philippines has waged a bloody war against drugs that may have resulted in up to 29,000 extrajudicial killings.
When it comes to social control with cannabis, there are different aspects to consider. Not only do we assess legislative leaders and the way they vote on cannabis, but we also must consider the federal regulations and taxation that contribute to social controls. For instance, according to a report on the U.S. customs and border protections, the American industry, although banned the main usage of marijuana, was still using products similar such as hemp seeds, oils etc. leading to the previously discussed marijuana tax act.
The Tax act provisions required importers to register and pay an annual tax of $24 and receive an official stamp. Stamps for Products were then affixed to each original order form and recorded by the state revenue collector. Then, a customs collector was to maintain the custody of imported marijuana at entry ports until required documents were received, reviewed and approved.Shipments were subject to searches, seizures and forfeitures if any provisions of the law were not met. Violations would result in fines of no more than $2000 or potential imprisonment for up to 5 years. Oftentimes, this created opportunity for corruption, stolen imports that would later lead to smuggling, oftentimes by state officials and tight knit elitists.
== Penalties ==
=== United States ===
Drug possession is the crime of having one or more illegal drugs in one's possession, either for personal use, distribution, sale or otherwise. Illegal drugs fall into different categories and sentences vary depending on the amount, type of drug, circumstances, and jurisdiction. In the U.S., the penalty for illegal drug possession and sale can vary from a small fine to a prison sentence. In some states, marijuana possession is considered to be a petty offense, with the penalty being comparable to that of a speeding violation. In some municipalities, possessing a small quantity of marijuana in one's own home is not punishable at all. Generally, however, drug possession is an arrestable offense, although first-time offenders rarely serve jail time. Federal law makes even possession of "soft drugs", such as cannabis, illegal, though some local governments have laws contradicting federal laws.
In the U.S., the War on Drugs is thought to be contributing to a prison overcrowding problem. In 1996, 59.6% of prisoners were drug-related criminals. The U.S. population grew by about +25% from 1980 to 2000. In that same 20 year time period, the U.S. prison population tripled, making the U.S. the world leader in both percentage and absolute number of citizens incarcerated. The United States has 5% of the world's population, but 25% of the prisoners.
About 90% of United States prisoners are incarcerated in state jails. In 2016, about 572,000, over 44%, of the 1.3 million people in these state jails, were serving time for drug offenses. 728,000 were incarcerated for violent offenses.
The data from Federal Bureau of Prisons online statistics page states that 45.9% of prisoners were incarcerated for drug offenses, as of December 2021.
=== European Union ===
In 2004, the Council of the European Union adopted a framework decision harmonizing the minimum penal provisions for illicit drug-related activities. In particular, article 2(9) stipulates that activities may be exempt from the minimum provisions "when it is committed by its perpetrators exclusively for their own personal consumption as defined by national law." This was made, in particular, to accommodate more liberal national systems such as the Dutch coffee shops (see below) or the Spanish Cannabis Social Clubs.
==== The Netherlands ====
In the Netherlands, cannabis and other "soft" drugs are decriminalised in small quantities. The Dutch government treats the problem as more of a public health issue than a criminal issue. Contrary to popular belief, cannabis is still technically illegal. Coffee shops that sell cannabis to people 18 or above are tolerated, and pay taxes like any other business for their cannabis and hashish sales, although distribution is a grey area that the authorities would rather not go into as it is not decriminalised. Many "coffee shops" are found in Amsterdam and cater mainly to the large tourist trade; the local consumption rate is far lower than in the US.
The administrative bodies responsible for enforcing the drug policies include the Ministry of Health, Welfare and Sport, the Ministry of Justice, the Ministry of the Interior and Kingdom Relations, and the Ministry of Finance. Local authorities also shape local policy, within the national framework.
When compared to other countries, Dutch drug consumption falls in the European average at six per cent regular use (twenty-one per cent at some point in life) and considerably lower than the Anglo-Saxon countries headed by the United States with an eight per cent recurring use (thirty-four at some point in life).
=== Australia ===
A Nielsen poll in 2012 found that only 27% of voters favoured decriminalisation. Australia has steep penalties for growing and using drugs even for personal use. with Western Australia having the toughest laws. There is an associated anti-drug culture amongst a significant number of Australians. Law enforcement targets drugs, particularly in the party scene. In 2012, crime statistics in Victoria revealed that police were increasingly arresting users rather than dealers, and the Liberal government banned the sale of bongs that year.
=== Indonesia ===
Indonesia carries a maximum penalty of death for drug dealing, and a maximum of 15 years prison for drug use. In 2004, Australian citizen Schapelle Corby was convicted of smuggling 4.4 kilograms of cannabis into Bali, a crime that carried a maximum penalty of death. Her trial reached the verdict of guilty with a punishment of 20 years imprisonment. Corby claimed to be an unwitting drug mule. Australian citizens known as the "Bali Nine" were caught smuggling heroin. Two of the nine, Andrew Chan and Myuran Sukumaran, were executed April 29, 2015 along with six other foreign nationals. In August 2005, Australian model Michelle Leslie was arrested with two ecstasy pills. She pleaded guilty to possession and in November 2005 was sentenced to 3 months imprisonment, which she was deemed to have already served, and was released from prison immediately upon her admission of guilt on the charge of possession.
At the 1961 Single Convention on Narcotic Drugs, Indonesia, along with India, Turkey, Pakistan and some South American countries opposed the criminalisation of drugs.
=== Republic of China (Taiwan) ===
Taiwan carries a maximum penalty of death for drug trafficking, while smoking tobacco and wine are classified as legal entertainment drug. The Department of Health is in charge of drug prohibition.
== Cost ==
In 2020, the direct cost of drug prohibition to United States taxpayers was estimated at over $40 billion annually. Prohibition can increase organized crime, government corruption, and mass incarceration via the trade in illegal drugs, while racial and gender disparities in enforcement are evident.
Although drug prohibition is often portrayed by proponents as a measure to improve public health, evidence is lacking. In 2016, the Johns Hopkins–Lancet Commission concluded that the "harms of prohibition far outweigh the benefits", citing increased risk of overdoses and HIV infection and detrimental effects on the social determinants of health. Some proponents argue that drug prohibition's effect on suppressing usage rates (although the magnitude of this effect is unknown) outweighs the negative effects of prohibition.
Alternative approaches to prohibition include drug legalization, drug decriminalization, and government monopoly.
== See also ==
Alcohol law
Arguments for and against drug prohibition
Chasing the Scream
Drug liberalization
Demand reduction
Drug policy of the Soviet Union
Harm reduction
List of anti-cannabis organizations
Medellín Cartel
Mexican drug war
Puerto Rican drug war
Prohibitionism
Tobacco control
War on Drugs
US specific:
Allegations of CIA drug trafficking
School district drug policies
Drug Free America Foundation
Drug Policy Alliance
DrugWarRant
Gary Webb
Marijuana Policy Project
National Organization for the Reform of Marijuana Laws
Students for Sensible Drug Policy
Woman's Christian Temperance Union
== References ==
== Further reading ==
== External links ==
Making Contact: The Mission to End Prohibition. Radio piece featuring LEAP founder and former narcotics officer Jack Cole, and Drug Policy Alliance founder Ethan Nadelmann
EMCDDA – Decriminalisation in Europe? Recent developments in legal approaches to drug use Archived January 12, 2007, at the Wayback Machine.
10 Downing Street's Strategy Unit Drugs Report
War on drugs Archived April 30, 2011, at the Wayback Machine Part I: Winners, documentary (50 min) explaining 'War on Drugs' by Tegenlicht of VPRO Dutch television. After short introduction in Dutch (1 min), English spoken. Broadband internet needed.
War on drugs Archived April 30, 2011, at the Wayback Machine Part II: Losers, documentary (50 min) showing downside of the 'War on Drugs' by Tegenlicht of VPRO Dutch television. After short introduction in Dutch (1 min), English spoken. Broadband internet needed.
After the War on Drugs: Options for Control (Report)
The Drug War as a Socialist Enterprise by Milton Friedman
Free from the Nightmare of Prohibition Archived February 23, 2006, at the Wayback Machine by Harry Browne
Prohibition news page – Alcohol and Drugs History Society
Drugs and conservatives should go together | Wikipedia/Drug_laws |
A drug is any chemical substance other than a food or device that affects the function of living things.
Drug(s) or D.R.U.G.S. may also refer to:
== Places ==
Drug or Durg, a city in India
Drug Island, Alaska, U.S.
Drug Dome
== Arts, entertainment and media ==
=== Music ===
==== Groups and production teams ====
DRUGS, a funk musical group founded by Michael "Clip" Payne
D.R.U.G.S. (production team), Directing Reality Undermining Governed Systems
Destroy Rebuild Until God Shows, an American post-hardcore band previously known as D.R.U.G.S.
==== Albums and mixtapes ====
D.R.U.G.S. (album), 2011 album by Destroy Rebuild Until God Shows
D.R.U.G.S. (Death and Reincarnation Under God's Supervision), 2012 mixtape by Flatbush Zombies
==== Songs ====
"Drug", a 2011 song by White Denim from D
"Drugs", 1979 song by Talking Heads from Fear of Music
"D.R.U.G.S.", 2000 song by Phife Dawg from Ventilation: Da LP
"D.R.U.G.S.", 2000 song by Fiend from Can I Burn?
"D.R.U.G.S.", 2009 song by Dead and Divine from The Machines We Are
"D.R.U.G.S.", 2009 song by The Raveonettes from In and Out of Control
"D.R.U.G.S.", 2011 song by Iggy Azalea
"D.R.U.G.S.", 2016 song by Ab-Soul from Do What Thou Wilt.
"Drugs", 2017 song by Charli XCX from Number 1 Angel
Drugs (Ammonia song), 1995
Drugs (Falling in Reverse song), 2019
=== Other arts, entertainment, and media ===
Drûg, a term for a member of the Drúedain, a Middle-earth race in the fiction of J. R. R. Tolkien
Drugs (journal), a peer-reviewed medical journal
"Drugs" (Brass Eye), a 1997 television episode
"Drugs" (Not Going Out), a 2011 television episode
== Grapes ==
Graciano, or Drug, a wine grape
== See also ==
Antiretroviral drug
Antiviral drug
Approved drug, drug approval by the Food and Drug Administration in the United States
Drug abuse
Drug liberalization
Hard and soft drugs
Illegal drug trade
Inverse benefit law
List of drugs
Misuse of Drugs Act 1971, the United Kingdom act under which substances defined as drugs are listed and controlled
Performance-enhancing drug
Pharmaceutical drug
Psychoactive drug, chemical substance used to alter behavior and perception for many differing reasons
Recreational drug use | Wikipedia/Drug_(disambiguation) |
The Narcotics Control Bureau (abbr. NCB) is an Indian central law enforcement and intelligence agency under the Ministry of Home Affairs, Government of India. The agency is tasked with combating drug trafficking and the use of illegal substances under the provisions of Narcotic Drugs and Psychotropic Substances Act.
Established in 1986, it is responsible for coordination with the Indian state governments and other central departments, implementation of India's international obligations with regard to drug trafficking, and assisting international and foreign drug law enforcement agencies.
== Formation ==
The Narcotics Control Bureau was created on 17 March 1986 to enable the full implementation of The Narcotic Drugs and Psychotropic Substances Act, 1985 and fight its violation through the Prevention of Illicit Trafficking in Narcotic Drugs and Psychotropic Substances Act, 1988. The law was established to fulfill India's treaty obligations under the Single Convention on Narcotic Drugs, Convention on Psychotropic Substances, and United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances. Officers in this organisation are drawn from Indian Revenue Service, Indian Police Service and Paramilitary forces in addition to directly recruited members.
== Organisation ==
The Narcotics Control Bureau's national headquarters is located in Delhi, the national capital. Its field units and offices are organised by zones and are located in Mumbai, Indore, Kolkata, Delhi, Chennai, Lucknow, Jodhpur, Chandigarh, Jammu, Ahmedabad, Bengaluru, Guwahati and Patna. In wake of recent cadre restructuring in NCB, new offices were opened at Agartala, Raipur, Visakhapatnam, Gorakhpur, Jalpaiguri, Itanagar, Bhopal, Cochin, Jaipur, Srinagar. Further, erstwhile sub-zonal units viz Amritsar, Dehradun, Mandi, Mandsaur, Imphal etc. were upgraded to Zonal units in same locations or shifted to other location for better drug law enforcement, keeping in view of newer trends in drug trafficking.
The Director General of NCB is mostly an officer from the Indian Police Service (IPS) or the Indian Revenue Service (IRS). Apart from the direct feeder grade, officers in this organisation are also drawn from Indian Revenue Service, Indian Police Service and other Paramilitary forces.
The Narcotics Control Bureau is also represented on the Economic Intelligence Council. NCB is affiliated to Home Ministry, which was made responsible for administering The Narcotic Drugs and Psychotropic Substances Act, 1985. The NCB is outside the ambit of the Right to information Act under Section 24(1) of the RTI act 2005.
== Functions ==
The chief purpose of the Narcotics Control Bureau is to fight drug trafficking on an all-India level. It works in close cooperation with the Customs and Central Excise/GST, State Police Department, State Excise and Prohibition Department, Central Bureau of Investigation (CBI), Central Economic Intelligence Bureau (CEIB) and other Indian intelligence and law enforcement agencies both at the national and states level. The NCB also provides resources and training to the personnel of India's Drug Law Enforcement Agencies in fighting drug trafficking. The NCB also monitors India's frontiers to track down points where smuggling activities take place with foreign traffickers.
== See also ==
Central Bureau of Investigation, anti organised crime which are international, multi-state or multi-agency
Directorate of Revenue Intelligence, anti-smuggling
Enforcement Directorate, anti economic crimes
Financial Intelligence Unit, anti money laundering
National Investigation Agency, anti terrorism
NIA Most Wanted
List of Indian intelligence agencies
== References == | Wikipedia/Narcotics_Control_Bureau |
Neuromuscular-blocking drugs, or Neuromuscular blocking agents (NMBAs), block transmission at the neuromuscular junction, causing paralysis of the affected skeletal muscles. This is accomplished via their action on the post-synaptic acetylcholine (Nm) receptors.
In clinical use, neuromuscular block is used adjunctively to anesthesia to produce paralysis, firstly to paralyze the vocal cords, and permit endotracheal intubation, and secondly to optimize the surgical field by inhibiting spontaneous ventilation, and causing relaxation of skeletal muscles. Because the appropriate dose of neuromuscular-blocking drug may paralyze muscles required for breathing (i.e., the diaphragm), mechanical ventilation should be available to maintain adequate respiration.
This class of medications helps to reduce patient movement, breathing, or ventilator dyssynchrony and allows lower insufflation pressures during laparoscopy. It has several indications for use in the intense care unit. It can help reduce hoarseness in voice as well as injury to the vocal cord during intubation. In addition, it plays an important role in facilitating mechanical ventilation in patients with poor lung function.
Patients are still aware of pain even after full conduction block has occurred; hence, general anesthetics and/or analgesics must also be given to prevent anesthesia awareness.
== Nomenclature ==
Neuromuscular blocking drugs are often classified into two broad classes:
Pachycurares, which are bulky molecules with nondepolarizing activity
Leptocurares, which are thin and flexible molecules that tend to have depolarizing activity.
It is also common to classify them based on their chemical structure.
Acetylcholine, suxamethonium, and decamethonium
Suxamethonium was synthesised by connecting two acetylcholine molecules and has the same number of heavy atoms between methonium heads as decamethonium. Just like acetylcholine, succinylcholine, decamethonium and other polymethylene chains, of the appropriate length and with two methonium, heads have small trimethyl onium heads and flexible links. They all exhibit a depolarizing block.
Aminosteroids
Pancuronium, vecuronium, rocuronium, rapacuronium, dacuronium, malouètine, dihydrochandonium, dipyrandium, pipecuronium, chandonium (HS-310), HS-342 and other HS- compounds are aminosteroidal agents. They have in common the steroid structural base, which provides a rigid and bulky body. Most of the agents in this category would also be classified as non-depolarizing.
Tetrahydroisoquinoline derivatives
Compounds based on the tetrahydroisoquinoline moiety such as atracurium, mivacurium, and doxacurium would fall in this category. They have a long and flexible chain between the onium heads, except for the double bond of mivacurium. D-tubocurarine and dimethyltubocurarine are also in this category. Most of the agents in this category would be classified as non-depolarizing.
Gallamine and other chemical classes
Gallamine is a trisquaternary ether with three ethonium heads attached to a phenyl ring through an ether linkage. Many other different structures have been used for their muscle relaxant effect such as alcuronium (alloferin), anatruxonium, diadonium, fazadinium (AH8165) and tropeinium.
Novel NMB agents
In recent years much research has been devoted to new types of quaternary ammonium muscle relaxants. These are asymmetrical diester isoquinolinium compounds and bis-benzyltropinium compounds that are bistropinium salts of various diacids. These classes have been developed to create muscle relaxants that are faster and shorter acting. Both the asymmetric structure of diester isoquinolinium compounds and the acyloxylated benzyl groups on the bisbenzyltropiniums destabilizes them and can lead to spontaneous breakdown and therefore possibly a shorter duration of action.
== Classification ==
These drugs fall into two groups:
Non-depolarizing blocking agents: These agents constitute the majority of the clinically relevant neuromuscular blockers. They act by competitively blocking the binding of ACh to its receptors, and in some cases, they also directly block the ionotropic activity of the ACh receptors.
Depolarizing blocking agents: These agents act by depolarizing the sarcolemma of the skeletal muscle fiber. This persistent depolarization makes the muscle fiber resistant to further stimulation by ACh.
=== Non-depolarizing blocking agents ===
A neuromuscular non-depolarizing agent is a form of neuromuscular blocker that does not depolarize the motor end plate.
The quaternary ammonium muscle relaxants belong to this class. Quaternary ammonium muscle relaxants are quaternary ammonium salts used as drugs for muscle relaxation, most commonly in anesthesia. It is necessary to prevent spontaneous movement of muscle during surgical operations. Muscle relaxants inhibit neuron transmission to muscle by blocking the nicotinic acetylcholine receptor. What they have in common, and is necessary for their effect, is the structural presence of quaternary ammonium groups, usually two. Some of them are found in nature and others are synthesized molecules.
Below are some more common agents that act as competitive antagonists against acetylcholine at the site of postsynaptic acetylcholine receptors.
Tubocurarine, found in curare of the South American plant Pareira, Chondrodendron tomentosum, is the prototypical non-depolarizing neuromuscular blocker. It has a slow onset (<5 min) and a long duration of action (30 mins). Side-effects include hypotension, which is partially explained by its effect of increasing histamine release, a vasodilator, as well as its effect of blocking autonomic ganglia. It is excreted in the urine.
This drug needs to block about 70–80% of the ACh receptors for neuromuscular conduction to fail, and hence for effective blockade to occur. At this stage, end-plate potentials (EPPs) can still be detected, but are too small to reach the threshold potential needed for activation of muscle fiber contraction.
The speed of onset depends on the potency of the drug, greater potency is associated with slower onset of block. Rocuronium, with an ED95 of 0.3 mg/kg IV has a more rapid onset than Vecuronium with an ED95 of 0.05mg/kg. Steroidal compounds, such as rocuronium and vecuronium, are intermediate-acting drugs while Pancuronium and pipecuronium are long-acting drugs.
In larger clinical dose, some of the blocking agent can access the pore of the ion channel and cause blockage. This weakens neuromuscular transmission and diminishes the effect of acetylcholinesterase inhibitors (e.g. neostigmine). Nondepolarizing NBAs may also block prejunctional sodium channels which interfere with the mobilization of acetylcholine at the nerve ending.
=== Depolarizing blocking agents ===
A depolarizing neuromuscular blocking agent is a form of neuromuscular blocker that depolarizes the motor end plate. An example is succinylcholine. Depolarizing blocking agents work by depolarizing the plasma membrane of the muscle fiber, similar to acetylcholine. However, these agents are more resistant to degradation by acetylcholinesterase, the enzyme responsible for degrading acetylcholine, and can thus more persistently depolarize the muscle fibers. This differs from acetylcholine, which is rapidly degraded and only transiently depolarizes the muscle.
These agents have two phases of block with notably different characteristics. During phase I (depolarizing phase), succinylcholine interacts with nicotinic receptor to open the channel and cause depolarization of the end plate, which later spread to and result in depolarization of adjacent membranes. As a result, there is a disorganised contraction of muscle motor unit. This causes muscular fasciculations (muscle twitches) while they are depolarizing the muscle fibers. The muscle fiber is then held in a partially depolarised state leading to relaxation.
Further administration of the agent leads to phase II block which has a similar clinical behaviour to non-depolarising blocking agents. Phase II block is characterised by complete membrane repolarisation however there is still ongoing neuromuscular blockade, the mechanism of phase II block is not fully understood. Phase I block effect is increased by cholinesterase inhibitors as increase in acetylcholine levels leads to deepening of the phase I block due to the membrane potential being pushed further away from repolarisation, however in phase II block cholinesterase inhibitors inhibit the block.
The prototypical depolarizing blocking drug is succinylcholine (suxamethonium). It is the only such drug used clinically. It has a rapid onset (30 seconds) but very short duration of action (5–10 minutes) because of hydrolysis by various cholinesterases (such as butyrylcholinesterase in the blood). The patient will experience fasciculation due to the depolarisation of muscle neurone fibres and seconds later, flaccid paralysis will occur. Succinylcholine was originally known as diacetylcholine because structurally it is composed of two acetylcholine molecules joined with a methyl group. Decamethonium is sometimes, but rarely, used in clinical practice.
It is indicated for rapid sequence intubation.
==== Dosing/onset of action ====
IV dose 1-1.5mg/kg or 3 to 5 x ED95
Paralysis occurs in one to two minutes.
Clinical duration of action (time from drug administration to recovery of single twich to 25% of baseline) is 7-12 minutes.
If IV access is unavailable, intramuscular administration 3-4mg/kg. Paralysis occurs at 4 minutes.
Use of succinylcholine infusion or repeated bolus administration increase the risk of Phase II block and prolonged paralysis. Phase II block occurs after large doses (>4mg/kg). This occurs when the post-synaptic membrane action potential returns to baseline in spite of the presence of succinylcholine and causes continued activation of nicotinic acetylcholine receptors.
=== Comparison of drugs ===
The main difference is in the reversal of these two types of neuromuscular-blocking drugs.
Non-depolarizing blockers are reversed by acetylcholinesterase inhibitor drugs since non-depolarizing blockers are competitive antagonists at the ACh receptor so can be reversed by increases in ACh.
The depolarizing blockers already have ACh-like actions, so these agents have prolonged effect under the influence of acetylcholinesterase inhibitors. Administration of depolarizing blockers initially produces fasciculations (a sudden twitch just before paralysis occurs). This is due to depolarization of the muscle. Also, post-operative pain is associated with depolarizing blockers.
The tetanic fade is the failure of muscles to maintain a fused tetany at sufficiently high frequencies of electrical stimulation.
Non-depolarizing blockers have this effect on patients, probably by an effect on presynaptic receptors.
Depolarizing blockers do not cause the tetanic fade. However, a clinically similar manifestation called Phase II block occurs with repeated doses of suxamethonium.
This discrepancy is diagnostically useful in case of intoxication of an unknown neuromuscular-blocking drug.
== Physiology at the Neuromuscular Junction ==
Neuromuscular blocking agents exert their effect by modulating the signal transmission in skeletal muscles. An action potential is, in other words, a depolarisation in neurone membrane due to a change in membrane potential greater than the threshold potential leads to an electrical impulse generation. The electrical impulse travels along the pre-synaptic neurone axon to synapse with the muscle at the neuromuscular junction (NMJ) to cause muscle contraction.
When the action potential reaches the axon terminal, it triggers the opening of the calcium ion gated channels, which causes the influx of Ca2+. Ca2+ will stimulate the release of neurotransmitter in the neurotransmitter containing vesicles by exocytosis (vesicle fuses with the pre-synpatic membrane).
The neurotransmitter, acetylcholine(ACh) binds to the nicotinic receptors on the motor end plate, which is a specialised area of the muscle fibre's post-synaptic membrane. This binding causes the nicotinic receptor channels to open and allow the influx of Na+ into the muscle fibre.
Fifty percent of the released ACh is hydrolysed by acetylcholinesterase (AChE) and the remaining bind to the nicotinic receptors on the motor end plate. When ACh is degraded by AChE, the receptors are no longer stimulated and the muscle cannot be depolarized.
If enough Na+ enter the muscle fibre, it causes an increase in the membrane potential from its resting potential of -95mV to -50mV (above the threshold potential -55mV) which causes an action potential to spread throughout the fibre. This potential travels along the surface of the sarcolemma. The sarcolemma is an excitable membrane that surrounds the contractile structures known as myofibrils that are located deep in the muscle fibre. For the action potential to reach the myofibrils, the action potential travels along the transverse tubules (T-tubules) that connects the sarcolemma and center of the fibre.
Later, action potential reaches the sarcoplasmic reticulum which stores the Ca2+ needed for muscle contraction and causes Ca2+ to be released from the sarcoplasmic reticulum.
== Mechanism of action ==
Quaternary muscle relaxants bind to the nicotinic acetylcholine receptor and inhibit or interfere with the binding and effect of ACh to the receptor. Each ACh-receptor has two receptive sites and activation of the receptor requires binding to both of them. Each receptor site is located at one of the two α-subunits of the receptor. Each receptive site has two subsites, an anionic site that binds to the cationic ammonium head and a site that binds to the blocking agent by donating a hydrogen bond.
Non-depolarizing agents
A decrease in binding of acetylcholine leads to a decrease in its effect and neuron transmission to the muscle is less likely to occur. It is generally accepted that non-depolarizing agents block by acting as reversible competitive inhibitors. That is, they bind to the receptor as antagonists and that leaves fewer receptors available for acetylcholine to bind.
Depolarizing agents
Depolarizing agents produce their block by binding to and activating the ACh receptor, at first causing muscle contraction, then paralysis. They bind to the receptor and cause depolarization by opening channels just like acetylcholine does. This causes repetitive excitation that lasts longer than a normal acetylcholine excitation and is most likely explained by the resistance of depolarizing agents to the enzyme acetylcholinesterase. The constant depolarization and triggering of the receptors keeps the endplate resistant to activation by acetylcholine. Therefore, a normal neuron transmission to muscle cannot cause contraction of the muscle because the endplate is depolarized and thereby the muscle paralysed.
Binding to the nicotinic receptor
Shorter molecules like acetylcholine need two molecules to activate the receptor, one at each receptive site. Decamethonium congeners, which prefer straight line conformations (their lowest energy state), usually span the two receptive sites with one molecule (binding inter-site). Longer congeners must bend when fitting receptive sites.
The greater energy a molecule needs to bend and fit usually results in lower potency.
== Structural and conformational action relationship ==
Conformational study on neuromuscular blocking drugs is relatively new and developing. Traditional SAR studies do not specify environmental factors on molecules. Computer-based conformational searches assume that the molecules are in vacuo, which is not the case in vivo. Solvation models take into account the effect of a solvent on the conformation of the molecule. However, no system of solvation can mimic the effect of the complex fluid composition of the body.
The division of muscle relaxants to rigid and non-rigid is at most qualitative. The energy required for conformational changes may give a more precise and quantitative picture. Energy required for reducing onium head distance in the longer muscle relaxant chains may quantify their ability to bend and fit its receptive sites. Using computers it is possible to calculate the lowest energy state conformer and thus most populated and best representing the molecule. This state is referred to as the global minimum. The global minimum for some simple molecules can be discovered quite easily with certainty. Such as for decamethonium the straight line conformer is clearly the lowest energy state. Some molecules, on the other hand, have many rotatable bonds and their global minimum can only be approximated.
=== Molecular length and rigidity ===
Neuromuscular blocking agents need to fit in a space close to 2 nanometres, which resembles the molecular length of decamethonium. Some molecules of decamethonium congeners may bind only to one receptive site. Flexible molecules have a greater chance of fitting receptive sites. However, the most populated conformation may not be the best-fitted one. Very flexible molecules are, in fact, weak neuromuscular inhibitors with flat dose-response curves. On the other hand, stiff or rigid molecules tend to fit well or not at all. If the lowest-energy conformation fits, the compound has high potency because there is a great concentration of molecules close to the lowest-energy conformation. Molecules can be thin but yet rigid. Decamethonium for example needs relatively high energy to change the N-N distance.
In general, molecular rigidity contributes to potency, while size affects whether a muscle relaxant shows a polarizing or a depolarizing effect. Cations must be able to flow through the trans-membrane tube of the ion-channel to depolarize the endplate. Small molecules may be rigid and potent but unable to occupy or block the area between the receptive sites. Large molecules, on the other hand, may bind to both receptive sites and hinder depolarizing cations independent of whether the ion-channel is open or closed below. Having a lipophilic surface pointed towards the synapse enhances this effect by repelling cations. The importance of this effect varies between different muscle relaxants and classifying depolarizing from non-depolarizing blocks is a complex issue. The onium heads are usually kept small and the chains connecting the heads usually keep the N-N distance at 10 N or O atoms. Keeping the distance in mind the structure of the chain can vary (double bonded, cyclohexyl, benzyl, etc.)
Succinylcholine has a 10-atom distance between its N atoms, like decamethonium. Yet it has been reported that it takes two molecules, as with acetylcholine, to open one nicotinic ion channel. The conformational explanation for this is that each acetylcholine moiety of succinylcholine prefers the gauche (bent, cis) state. The attraction between the N and O atoms is greater than the onium head repulsion. In this most populated state, the N-N distance is shorter than the optimal distance of ten carbon atoms and too short to occupy both receptive sites. This similarity between succinyl- and acetyl-choline also explains its acetylcholine-like side-effects.
Comparing molecular lengths, the pachycurares dimethyltubocurarine and d-tubocurarine both are very rigid and measure close to 1.8 nm in total length. Pancuronium and vecuronium measure 1.9 nm, whereas pipecuronium is 2.1 nm. The potency of these compounds follows the same rank of order as their length. Likewise, the leptocurares prefer a similar length. Decamethonium, which measures 2 nm, is the most potent in its category, whereas C11 is slightly too long. Gallamine despite having low bulk and rigidity is the most potent in its class, and it measures 1.9 nm. Based on this information one can conclude that the optimum length for neuromuscular blocking agents, depolarizing or not, should be 2 to 2.1 nm.
The CAR for long-chain bisquaternary tetrahydroisoquinolines like atracurium, cisatracurium, mivacurium, and doxacurium is hard to determine because of their bulky onium heads and large number of rotatable bonds and groups. These agents must follow the same receptive topology as others, which means that they do not fit between the receptive sites without bending. Mivacurium for example has a molecular length of 3.6 nm when stretched out, far from the 2 to 2.1 nm optimum. Mivacurium, atracurium, and doxacurium have greater N-N distance and molecular length than d-tubocurarine even when bent. To make them fit, they have flexible connections that give their onium heads a chance to position themselves beneficially. This bent N-N scenario probably does not apply to laudexium and decamethylene bisatropium, which prefer a straight conformation.
=== Beers and Reich's law ===
It has been concluded that acetylcholine and related compounds must be in the gauche (bent) configuration when bound to the nicotinic receptor. Beers and Reich's studies on cholinergic receptors in 1970 showed a relationship affecting whether a compound was muscarinic or nicotinic. They showed that the distance from the centre of the quaternary N atom to the van der Waals extension of the respective O atom (or an equivalent H-bond acceptor) is a determining factor. If the distance is 0.44 nm, the compound shows muscarinic properties—and if the distance is 0.59 nm, nicotinic properties dominate.)
=== Rational design ===
Pancuronium remains one of the few muscle relaxants logically and rationally designed from structure-action / effects relationship data. A steroid skeleton was chosen because of its appropriate size and rigidness. Acetylcholine moieties were inserted to increase receptor affinity. Although having many unwanted side-effects, a slow onset of action and recovery rate it was a big success and at the time the most potent neuromuscular drug available. Pancuronium and some other neuromuscular blocking agents block M2-receptors and therefore affect the vagus nerve, leading to hypotension and tachycardia. This muscarinic blocking effect is related to the acetylcholine moiety on the A ring on pancuronium. Making the N atom on the A ring tertiary, the ring loses its acetylcholine moiety, and the resulting compound, vecuronium, has nearly 100 times less affinity to muscarin receptors while maintaining its nicotinic affinity and a similar duration of action. Vecuronium is, therefore, free from cardiovascular effects. The D ring shows excellent properties validating Beers and Reich's rule with great precision. As a result, vecuronium has the greatest potency and specificity of all mono-quaternary compounds.
=== Potency ===
Two functional groups contribute significantly to aminosteroidal neuromuscular blocking potency, it is presumed to enable them to bind the receptor at two points. A bis-quaternary two point arrangement on A and D-ring (binding inter-site) or a D-ring acetylcholine moiety (binding at two points intra-site) are most likely to succeed. A third group can have variable effects. The quaternary and acetyl groups on the A and D ring of pipecuronium prevent it from binding intra-site (binding to two points at the same site). Instead, it must bind as bis-quaternary (inter-site). These structures are very dissimilar from acetylcholine and free pipecuronium from nicotinic or muscarinic side-effects linked to acetylcholine moiety. Also, they protect the molecule from hydrolysis by cholinesterases, which explain its nature of kidney excretion. The four methyl-groups on the quaternary N atoms make it less lipophilic than most aminosteroids. This also affects pipecuroniums metabolism by resisting hepatic uptake, metabolism, and biliary excretion. The length of the molecule (2.1 nm, close to ideal) and its rigidness make pipecuronium the most potent and clean one-bulk bis-quaternary. Even though the N-N distance (1.6 nm) is far away from what is considered ideal, its onium heads are well-exposed, and the quaternary groups help to bring together the onium heads to the anionic centers of the receptors without chirality issues.
Adding more than two onium heads in general does not add to potency. Though the third onium head in gallamine seems to help position the two outside heads near the optimum molecular length, it can interfere unfavorably and gallamine turns out to be a weak muscle relaxant, like all multi-quaternary compounds.
Considering acetylcholine a quaternizing group larger than methyl and an acyl group larger than acetyl would reduce the molecule's potency. The charged N and the carbonyl O atoms are distanced from structures they bind to on receptive sites and, thus, decrease potency. The carbonyl O in vecuronium for example is thrust outward to appose the H-bond donor of the receptive site. This also helps explain why gallamine, rocuronium, and rapacuronium are of relatively low potency.
In general, methyl quaternization is optimal for potency but, opposing this rule, the trimethyl derivatives of gallamine are of lower potency than gallamine. The reason for this is that gallamine has a suboptimal N-N distance. Substituting the ethyl groups with methyl groups would make the molecular length also shorter than optimal. Methoxylation of tetrahydroisoquinolinium agents seems to improve their potency. How methoxylation improves potency is still unclear.
Histamine release is a common attribute of benzylisoquinolinium muscle relaxants. This problem generally decreases with increased potency and smaller doses. The need for larger doses increases the degree of this side-effect. Conformational or structural explanations for histamine release are not clear.
== Pharmacokinetics ==
Metabolism and Hofmann elimination
Deacetylating vecuronium at position 3 results in a very active metabolite. In the case of rapacuronium the 3-deacylated metabolite is even more potent than rapacuronium. As long as the D-ring acetylcholine moiety is unchanged they retain their muscle relaxing effect. Mono-quaternary aminosteroids produced with deacylation in position 17 on the other hand are generally weak muscle relaxants. In the development of atracurium the main idea was to make use of Hofmann elimination of the muscle relaxant in vivo. When working with bisbenzyl-isoquinolinium types of molecules, inserting proper features into the molecule such as an appropriate electron withdrawing group then Hofmann elimination should occur at conditions in vivo. Atracurium, the resulting molecule, breaks down spontaneously in the body to inactive compounds and being especially useful in patients with kidney or liver failure. Cis-atracurium is very similar to atracurium except it is more potent and has a weaker tendency to cause histamine release.
Structure relations to onset time
The effect of structure on the onset of action is not very well known except that the time of onset appears inversely related to potency. In general mono-quaternary aminosteroids are faster than bis-quaternary compounds, which means they are also of lower potency. A possible explanation for this effect is that drug delivery and receptor binding are of a different timescale. Weaker muscle relaxants are given in larger doses so more molecules in the central compartment must diffuse into the effect compartment, which is the space within the mouth of the receptor, of the body. After delivery to the effect compartment then all molecules act quickly. Therapeutically this relationship is very inconvenient because low potency, often meaning low specificity can decrease the safety margin thus increasing the chances of side-effects. In addition, even though low potency usually accelerates onset of action, it does not guaranty a fast onset. Gallamine, for example, is weak and slow. When fast onset is necessary then succinylcholine or rocuronium are usually preferable.
Elimination
Muscle relaxants can have very different metabolic pathways and it is important that the drug does not accumulate if certain elimination pathways are not active, for example in kidney failure.
== Medical Use ==
=== Endotracheal intubation ===
Administration of neuromuscular blocking agents (NMBA) during anesthesia can facilitate endotracheal intubation. This can decrease the incidence of postintubation hoarseness and airway injury.
Short-acting neuromuscular blocking agents are chosen for endotracheal intubation for short procedures (< 30minutes), and neuromonitoring is required soon after intubation. Options include succinylcholine, rocuronium or vecuronium if sugammadex is available for rapid reversal block.
Any short or intermediate acting neuromuscular blocking agents can be applied for endotracheal intubation for long procedures (≥ 30 minutes). Options include succinylcholine, rocuronium, vecuronium, mivacurium, atracurium and cisatracurium. The choice among these NMBA depends on availability, cost and patient parameters that affect drug metabolism.
Intraoperative relaxation can be maintained as necessary with additional dose of nondepolarizing NMBA.
Among all NMBA, Succinylcholine establish the most stable and fastest intubating conditions, thus is considered as the preferred NMBA for rapid sequence induction and intubation (RSII). Alternatives for succinylcholine for RSII include high dose rocuronium (1.2mg/kg which is a 4 X ED95 dose), or avoidance of NMBAs with a high dose remifentanil intubation.
=== Facilitation of surgery ===
Nondepolarizing NMBAs can be used to induce muscle relaxation that improves surgical conditions, including laparoscopic, robotic, abdominal and thoracic procedures. It can reduce patient movement, muscle tone, breathing or coughing against ventilator and allow lower insufflation pressure during laparoscopy. Administration of NMBAs should be individualized according to patient’s parameters. However, many operations can be performed without the need to apply any NMBAs as adequate anesthesia during surgery can achieve many of the theoretical benefits of neuromuscular blockage.
== Adverse effects ==
Since these drugs may cause paralysis of the diaphragm, mechanical ventilation should be at hand to provide respiration.
In addition, these drugs may exhibit cardiovascular effects, since they are not fully selective for the nicotinic receptor and hence may have effects on muscarinic receptors. If nicotinic receptors of the autonomic ganglia or adrenal medulla are blocked, these drugs may cause autonomic symptoms. Also, neuromuscular blockers may facilitate histamine release, which causes hypotension, flushing, and tachycardia.
Succinylcholine may also trigger malignant hyperthermia in rare cases in patients who may be susceptible.
In depolarizing the musculature, suxamethonium may trigger a transient release of large amounts of potassium from muscle fibers. This puts the patient at risk for life-threatening complications, such as hyperkalemia and cardiac arrhythmias. Other effects include myalgia, increased intragastric pressure, increased intraocular pressure, increased intracranial pressure, cardiac dysrhythmias (bradycardia is the most common type) and allergic reactions. As a result, it is contraindicated for patients with susceptibility to malignant hyperthermia, denervating conditions, major burns after 48 hours, and severe hyperkalemia.
For nondepolarizing NMBAs except vecuronium, pipecuronium, doxacurium, cisatracurium, rocuronium and rapacuronium, they produce certain extent of cardiovascular effect. Moreover, Tubocurarine can produce hypotension effect while Pancuronium can lead to moderate increase in heart rate and small increase in cardiac output with little or no increase in systemic vascular resistance, which is unique in nondeploarizing NMBAs.
Certain drugs such as aminoglycoside antibiotics and polymyxin and some fluoroquinolones also have neuromuscular blocking action as their side-effect.
== Interactions ==
Some drugs enhance or inhibit the response to NMBAs which require the dosage adjustment guided by monitoring.
=== Combination of NMBAs ===
In some clinical circumstances, succinylcholine may be administered before and after a nondepolarising NMBA or two different nondepolarising NMBAs are administered in sequence. Combining different NMBAs can result in different degrees of neuromuscular block and management should be guided with the use of a neuromuscular function monitor.
The administration of nondepolarising neuromuscular blocking agent has an antagonistic effect on the subsequent depolarising block induced by succinylcholine. If a nondepolarising NMBA is administered prior to succinycholine, the dose of succinylcholine must be increased.
The administration of succinylcholine on the subsequent administration of a nondepolarising neuromuscular block depends on the drug used. Studies have shown that administration of succinylcholien before a nondepolarising NMBA does not affect the potency of mivacurium or rocuronium. But for vecuronium and cisatracurium, it speeds up the onset, increases the potency and prolongs the duration of action.
Combining two nondepolarising NMBAs of the same chemical class (e.g. rocuronium and vecuronium) produces an additive effect, while combining two nondepolarising NMBAs of different chemical class (e.g. rocuronium and cisatracurium) produces a synergistic response.
=== Inhaled anesthetics ===
Inhaled anesthetics inhibit nicotinic acetylcholine receptors (nAChRs) and potentiate neuromuscular blockage with nondepolarising NMBAs. It depends on the type of volatile anesthetic (desflurane > sevoflurane > isoflurane > nitrous oxide), the concentration and the duration of exposure.
=== Antibiotics ===
Tetracycline, aminoglycosides, polymyxins and clindamycin potentiate neuromuscular blockage by inhibiting ACh release or desensitisation of post-synpatic nAChRs to ACh. This interaction happens mostly during maintenance of anesthesia. As antibiotics typically are given after a dose of NMBA, this interaction needs to be considered when re-dosing NMBA.
=== Anti-seizure drugs ===
Patients receiving chronic treatment are relatively resistance to nondepolarising NMBAs due to the accelerated clearance.
=== Lithium ===
Lithium is structurally similar to other cations such as sodium, potassium, magnesium and calcium, this causes lithium to activate potassium channels which inhibit neuromuscular transmission. Patients who take lithium can have a prolonged response to both depolarising and nondepolarising NMBAs.
=== Antidepressants ===
Sertraline and amitriptyline inhibit butyrylcholinesterase and cause prolonged paralysis. Mivacurium causes prolonged paralysis for patients chronically taking sertraline.
=== Local anesthetics (LAs) ===
LAs may enhance the effects of depolarisation and nondepolarising NMBAs through pre and post-synaptic interactions at the NMJ. It may result in blood levels high enough to potentiate NMBA-induced neuromuscular block. Epidurally administered levobupivacaine and mepivacaine potentiate amino-steroidal NMBAs and delay recovery from neuromuscular blockade.
== Estimating effect ==
Methods for estimating the degree of neuromuscular block include valuation of muscular response to stimuli from surface electrodes, such as in the train-of-four test, wherein four such stimuli are given in rapid succession. With no neuromuscular blockade, the resultant muscle contractions are of equal strength, but gradually decrease in case of neuromuscular blockade. It is recommended during use of continuous-infusion neuromuscular blocking agents in intensive care.
== Reversal ==
The effect of non-depolarizing neuromuscular-blocking drugs may be reversed with acetylcholinesterase inhibitors, neostigmine, and edrophonium, as commonly used examples. Of these, edrophonium has a faster onset of action than neostigmine, but it is unreliable when used to antagonize deep neuromuscular block. Acetylcholinesterase inhibitors increase the amount of acetylcholine in the neuromuscular junction, so a prerequisite for their effect is that the neuromuscular block is not complete, because in case every acetylcholine receptor is blocked then it does not matter how much acetylcholine is present.
Sugammadex is a newer drug for reversing neuromuscular block by rocuronium and vecuronium in general anaesthesia. It is the first selective relaxant binding agent (SRBA).
== History ==
Curare is a crude extract from certain South American plants in the genera Strychnos and Chondrodendron, originally brought to Europe by explorers such as Walter Raleigh Edward Bancroft, a chemist and physician in the 16th century brought samples of crude curare from South America back to the Old-World. The effect of curare was experimented with by Sir Benjamin Brodie when he injected small animals with curare, and found that the animals stopped breathing but could be kept alive by inflating their lungs with bellows. This observation led to the conclusion that curare can paralyse the respiratory muscles. It was also experimented by Charles Waterton in 1814 when he injected three donkeys with curare. The first donkey was injected in the shoulder and died afterward. The second donkey had a tourniquet applied to the foreleg and was injected distal to the tourniquet. The donkey lived while the tourniquet was in place but died after it was removed. The third donkey after injected with curare appeared to be dead but was resuscitated using bellows. Charles Waterton's experiment confirmed the paralytic effect of curare.
It was known in the 19th century to have a paralysing effect, due in part to the studies of scientists like Claude Bernard. D-tubocurarine a mono-quaternary alkaloid was isolated from Chondrodendron tomentosum in 1942, and it was shown to be the major constituent in curare responsible for producing the paralysing effect. At that time, it was known that curare and, therefore, d-tubocurarine worked at the neuromuscular junction. The isolation of tubocurarine and its marketing as the drug Intocostrin led to more research in the field of neuromuscular-blocking drugs. Scientists figured out that the potency of tubocurarine was related to the separation distance between the two quaternary ammonium heads.
Neurologist Walter Freeman learned about curare and suggested to Richard Gill, a patient suffering from multiple sclerosis, that he try using it. Gill brought 25 pounds of raw curare from Ecuador. The raw curare was then given to Squibb and Sons to derive an effective antidote to curare. In 1942, Wintersteiner and Dutcher (two scientists working for Squibb and Sons) isolated the alkaloid d-tubocurarine. Soon after, they developed a preparation of curare called Intocostrin.
At the same time in Montreal, Harold Randall Griffith and his resident Enid Johnson at the Homeopathic Hospital administered curare to a young patient undergoing appendectomy. This was the first use of NMBA as muscle relaxant in anesthesia.
The 1940s, 1950s and 1960s saw the rapid development of several synthetic NMBA. Gallamine was the first synthetic NMBA used clinically. Further research led to the development of synthesized molecules with different curariform effects, depending on the distance between the quaternary ammonium groups. One of the synthesized bis-quaternaries was decamethonium a 10-carbon bis-quaternary compound. Following research with decamethonium, scientists developed suxamethonium, which is a double acetylcholine molecule that was connected at the acetyl end. The discovery and development of suxamethonium lead to a Nobel Prize in medicine in 1957. Suxamethonium showed different blocking effect in that its effect was achieved more quickly and augmented a response in the muscle before block. Also, tubocurarine effects were known to be reversible by acetylcholinesterase inhibitors, whereas decamethonium and suxamethonium block were not reversible.
Another compound malouétine that was a bis-quaternary steroid was isolated from the plant Malouetia bequaertiana and showed curariform activity. This led to the synthetic drug pancuronium, a bis-quaternary steroid, and subsequently other drugs that had better pharmacological properties. Research on these molecules helped improve understanding of the physiology of neurons and receptors.
=== Outdated treatment ===
Gallamine triethiodide is originally developed for preventing muscle contractions during surgical procedures. However, it is no longer marketed in the United States according to the FDA orange book.
== See also ==
Ganglionic blocker
Cholinergic blocking drugs
== References ==
== External links ==
Neuromuscular+blocking+agents at the U.S. National Library of Medicine Medical Subject Headings (MeSH) | Wikipedia/Neuromuscular-blocking_drug |
The prohibition of drugs through sumptuary legislation or religious law is a common means of attempting to prevent the recreational use of certain intoxicating substances.
An area has a prohibition of drugs when its government uses the force of law to punish the use or possession of drugs which have been classified as controlled. A government may simultaneously have systems in place to regulate both controlled and non controlled drugs. Regulation controls the manufacture, distribution, marketing, sale, and use of certain drugs, for instance through a prescription system. For example, in some states, the possession or sale of amphetamines is a crime unless a patient has a physician's prescription for the drug; having a prescription authorizes a pharmacy to sell and a patient to use a drug that would otherwise be prohibited. Although prohibition mostly concerns psychoactive drugs (which affect mental processes such as perception, cognition, and mood), prohibition can also apply to non-psychoactive drugs, such as anabolic steroids. Many governments do not criminalize the possession of a limited quantity of certain drugs for personal use, while still prohibiting their sale or manufacture, or possession in large quantities. Some laws (or judicial practice) set a specific volume of a particular drug, above which is considered ipso jure to be evidence of trafficking or sale of the drug.
Some Islamic countries prohibit the use of alcohol (see list of countries with alcohol prohibition). Many governments levy a tax on alcohol and tobacco products, and restrict alcohol and tobacco from being sold or gifted to a minor. Other common restrictions include bans on outdoor drinking and indoor smoking. In the early 20th century, many countries had alcohol prohibition. These include the United States (1920–1933), Finland (1919–1932), Norway (1916–1927), Canada (1901–1948), Iceland (1915–1922) and the Russian Empire/USSR (1914–1925). In fact, the first international treaty to control a psychoactive substance adopted in 1890 actually concerned alcoholic beverages (Brussels Conference). The first treaty on opium only arrived two decades later, in 1912.
== Definitions ==
Drugs, in the context of prohibition, are any of a number of psychoactive substances whose use a government or religious body seeks to control. What constitutes a drug varies by century and belief system. What is a psychoactive substance is relatively well known to modern science. Examples include a range from caffeine found in coffee, tea, and chocolate, nicotine in tobacco products; botanical extracts morphine and heroin, and synthetic compounds MDMA and fentanyl. Almost without exception, these substances also have a medical use, in which case they are called pharmaceutical drugs or just pharmaceuticals. The use of medicine to save or extend life or to alleviate suffering is uncontroversial in most cultures. Prohibition applies to certain conditions of possession or use. Recreational use refers to the use of substances primarily for their psychoactive effect outside of a clinical situation or doctor's care.
In the twenty-first century, caffeine has pharmaceutical uses. Caffeine is used to treat bronchopulmonary dysplasia. In most cultures, caffeine in the form of coffee or tea is unregulated. Over 2.25 billion cups of coffee are consumed in the world every day. Some religions, including the Church of Jesus Christ of Latter-day Saints, prohibit coffee. They believe that it is both physically and spiritually unhealthy to consume coffee.
A government's interest to control a drug may be based on its negative effects on its users, or it may simply have a revenue interest. The British parliament prohibited the possession of untaxed tea with the imposition of the Tea Act of 1773. In this case, as in many others, it is not a substance that is prohibited, but the conditions under which it is possessed or consumed. Those conditions include matters of intent, which makes the enforcement of laws difficult. In Colorado possession of "blenders, bowls, containers, spoons, and mixing devices" is illegal if there was intent to use them with drugs.
Many drugs, beyond their pharmaceutical and recreational uses, have industrial uses. Nitrous oxide, or laughing gas is a dental anesthetic, also used to prepare whipped cream, fuel rocket engines, and enhance the performance of race cars. Ethanol, or drinking alcohol, is also used as a fuel, industrial solvent and disinfectant.
== History ==
The cultivation, use, and trade of psychoactive and other drugs has occurred since ancient times. Concurrently, authorities have often restricted drug possession and trade for a variety of political and religious reasons. In the 20th century, the United States led a major renewed surge in drug prohibition called the "War on Drugs".
=== Early drug laws ===
The prohibition on alcohol under Islamic Sharia law, which is usually attributed to passages in the Qur'an, dates back to the early seventh century. Although Islamic law is often interpreted as prohibiting all intoxicants (not only alcohol), the ancient practice of hashish smoking has continued throughout the history of Islam, against varying degrees of resistance. A major campaign against hashish-eating Sufis were conducted in Egypt in the 11th and 12th centuries resulting among other things in the burning of fields of cannabis.
Though the prohibition of illegal drugs was established under Sharia law, particularly against the use of hashish as a recreational drug, classical jurists of medieval Islamic jurisprudence accepted the use of hashish for medicinal and therapeutic purposes, and agreed that its "medical use, even if it leads to mental derangement, should remain exempt [from punishment]". In the 14th century, the Islamic scholar Az-Zarkashi spoke of "the permissibility of its use for medical purposes if it is established that it is beneficial".
In the Ottoman Empire, Murad IV attempted to prohibit coffee drinking to Muslims as haraam, arguing that it was an intoxicant, but this ruling was overturned soon after he died in 1640. The introduction of coffee in Europe from Muslim Turkey prompted calls for it to be banned as the devil's work, although Pope Clement VIII sanctioned its use in 1600, declaring that it was "so delicious that it would be a pity to let the infidels have exclusive use of it". Bach's Coffee Cantata, from the 1730s, presents a vigorous debate between a girl and her father over her desire to consume coffee. The early association between coffeehouses and seditious political activities in England led to the banning of such establishments in the mid-17th century.
A number of Asian rulers had similarly enacted early prohibitions, many of which were later forcefully overturned by Western colonial powers during the 18th and 19th centuries. In 1360, for example, King Ramathibodi I, of Ayutthaya Kingdom (now Thailand), prohibited opium consumption and trade. The prohibition lasted nearly 500 years until 1851 when King Rama IV allowed Chinese migrants to consume opium. The Konbaung Dynasty prohibited all intoxicants and stimulants during the reign of King Bodawpaya (1781–1819). After Burma became a British colony, the restrictions on opium were abolished and the colonial government established monopolies selling Indian-produced opium.
In late Qing China, opium imported by foreign traders, such as those employed by Jardine Matheson and the East India Company, was consumed by all social classes in Southern China. Between 1821 and 1837, imports of the drug increased fivefold. The wealth drain and widespread social problems that resulted from this consumption prompted the Chinese government to attempt to end the trade. This effort was initially successful, with Lin Zexu ordering the destruction of opium at Humen in June 1839. However, the opium traders lobbied the British government to declare war on China, resulting in the First Opium War. The Qing government was defeated and the war ended with the Treaty of Nanking, which legalized opium trading in Chinese law
=== First modern drug regulations ===
The first modern law in Europe for the regulating of drugs was the Pharmacy Act 1868 in the United Kingdom. There had been previous moves to establish the medical and pharmaceutical professions as separate, self-regulating bodies, but the General Medical Council, established in 1863, unsuccessfully attempted to assert control over drug distribution. The act set controls on the distribution of poisons and drugs. Poisons could only be sold if the purchaser was known to the seller or to an intermediary known to both, and drugs, including opium and all preparations of opium or of poppies, had to be sold in containers with the seller's name and address.
Despite the reservation of opium to professional control, general sales did continue to a limited extent, with mixtures with less than 1 percent opium being unregulated.
After the legislation passed, the death rate caused by opium immediately fell from 6.4 per million population in 1868 to 4.5 in 1869. Deaths among children under five dropped from 20.5 per million population between 1863 and 1867 to 12.7 per million in 1871 and further declined to between 6 and 7 per million in the 1880s.
In the United States, the first drug law was passed in San Francisco in 1875, banning the smoking of opium in opium dens. The reason cited was "many women and young girls, as well as young men of a respectable family, were being induced to visit the Chinese opium-smoking dens, where they were ruined morally and otherwise." This was followed by other laws throughout the country, and federal laws that barred Chinese people from trafficking in opium. Though the laws affected the use and distribution of opium by Chinese immigrants, no action was taken against the producers of such products as laudanum, a tincture of opium and alcohol, commonly taken as a panacea by white Americans. The distinction between its use by white Americans and Chinese immigrants was thus a form of racial discrimination as it was based on the form in which it was ingested: Chinese immigrants tended to smoke it, while it was often included in various kinds of generally liquid medicines often (but not exclusively) used by Americans of European descent. The laws targeted opium smoking, but not other methods of ingestion.
Britain passed the All-India Opium Act of 1878, which limited recreational opium sales to registered Indian opium-eaters and Chinese opium-smokers and prohibiting its sale to emigrant workers from British Burma.
Following the passage of a regional law in 1895, Australia's Aboriginals Protection and Restriction of the Sale of Opium Act 1897 addressed opium addiction among Aborigines, though it soon became a general vehicle for depriving them of basic rights by administrative regulation. Opium sale was prohibited to the general population in 1905, and smoking and possession were prohibited in 1908.
Despite these laws, the late 19th century saw an increase in opiate consumption. This was due to the prescribing and dispensing of legal opiates by physicians and pharmacists to relieve menstruation pain. It is estimated that between 150,000 and 200,000 opiate addicts lived in the United States at the time, and a majority of these addicts were women.
=== Changing attitudes and the drug prohibition campaign ===
Foreign traders, including those employed by Jardine Matheson and the East India Company, smuggled opium into China in order to balance high trade deficits. Chinese attempts to outlaw the trade led to the First Opium War and the subsequent legalization of the trade at the Treaty of Nanking. Attitudes towards the opium trade were initially ambivalent, but in 1874 the Society for the Suppression of the Opium Trade was formed in England by Quakers led by the Rev. Frederick Storrs-Turner. By the 1890s, increasingly strident campaigns were waged by Protestant missionaries in China for its abolition. The first such society was established at the 1890 Shanghai Missionary Conference, where British and American representatives, including John Glasgow Kerr, Arthur E. Moule, Arthur Gostick Shorrock and Griffith John, agreed to establish the Permanent Committee for the Promotion of Anti-Opium Societies.
Due to increasing pressure in the British parliament, the Liberal government under William Ewart Gladstone approved the appointment of a Royal Commission on Opium to India in 1893. The commission was tasked with ascertaining the impact of Indian opium exports to the Far East, and to advise whether the trade should be banned and opium consumption itself banned in India. After an extended inquiry, the Royal Commission rejected the claims made by the anti-opium campaigners regarding the supposed societal harm caused by the trade and the issue was finalized for another 15 years.
The missionary organizations were outraged over the Royal Commission on Opium's conclusions and set up the Anti-Opium League in China; the league gathered data from every Western-trained medical doctor in China and published Opinions of Over 100 Physicians on the Use of Opium in China. This was the first anti-drug campaign to be based on scientific principles, and it had a tremendous impact on the state of educated opinion in the West. In England, the home director of the China Inland Mission, Benjamin Broomhall, was an active opponent of the opium trade, writing two books to promote the banning of opium smoking: The Truth about Opium Smoking and The Chinese Opium Smoker. In 1888, Broomhall formed and became secretary of the Christian Union for the Severance of the British Empire with the Opium Traffic and editor of its periodical, National Righteousness. He lobbied the British parliament to ban the opium trade. Broomhall and James Laidlaw Maxwell appealed to the London Missionary Conference of 1888 and the Edinburgh Missionary Conference of 1910 to condemn the continuation of the trade. As Broomhall lay dying, an article from The Times was read to him with the welcome news that an international agreement had been signed ensuring the end of the opium trade within two years.
In 1906, a motion to 'declare the opium trade "morally indefensible" and remove Government support for it', initially unsuccessfully proposed by Arthur Pease in 1891, was put before the House of Commons. This time the motion passed. The Qing government banned opium soon afterward.
These changing attitudes led to the founding of the International Opium Commission in 1909. An International Opium Convention was signed by 13 nations at The Hague on January 23, 1912, during the First International Opium Conference. This was the first international drug control treaty and it was registered in the League of Nations Treaty Series on January 23, 1922. The Convention provided that "The contracting Powers shall use their best endeavors to control or to cause to be controlled, all person manufacturing, importing, selling, distributing, and exporting morphine, cocaine, and their respective salts, as well as the buildings in which these persons carry such an industry or trade."
The treaty became international law in 1919 when it was incorporated into the Treaty of Versailles. The role of the commission was passed to the League of Nations, and all signatory nations agreed to prohibit the import, sale, distribution, export, and use of all narcotic drugs, except for medical and scientific purposes.
=== Prohibition ===
In the UK the Defence of the Realm Act 1914, passed at the onset of the First World War, gave the government wide-ranging powers to requisition the property and to criminalize specific activities. A moral panic was whipped up by the press in 1916 over the alleged sale of drugs to the troops of the British Indian Army. With the temporary powers of DORA, the Army Council quickly banned the sale of all psychoactive drugs to troops, unless required for medical reasons. However, shifts in the public attitude towards drugs—they were beginning to be associated with prostitution, vice and immorality—led the government to pass further unprecedented laws, banning and criminalising the possession and dispensation of all narcotics, including opium and cocaine. After the war, this legislation was maintained and strengthened with the passing of the Dangerous Drugs Act 1920 (10 & 11 Geo. 5. c. 46). Home Office control was extended to include raw opium, morphine, cocaine, ecogonine and heroin.
Hardening of Canadian attitudes toward Chinese-Canadian opium users and fear of a spread of the drug into the white population led to the effective criminalization of opium for nonmedical use in Canada between 1908 and the mid-1920s.
The Mao Zedong government nearly eradicated both consumption and production of opium during the 1950s using social control and isolation. Ten million addicts were forced into compulsory treatment, dealers were executed, and opium-producing regions were planted with new crops. Remaining opium production shifted south of the Chinese border into the Golden Triangle region. The remnant opium trade primarily served Southeast Asia, but spread to American soldiers during the Vietnam War, with 20 percent of soldiers regarding themselves as addicted during the peak of the epidemic in 1971. In 2003, China was estimated to have four million regular drug users and one million registered drug addicts.
In the US, the Harrison Act was passed in 1914, and required sellers of opiates and cocaine to get a license. While originally intended to regulate the trade, it soon became a prohibitive law, eventually becoming legal precedent that any prescription for a narcotic given by a physician or pharmacist – even in the course of medical treatment for addiction – constituted conspiracy to violate the Harrison Act. In 1919, the Supreme Court ruled in Doremus that the Harrison Act was constitutional and in Webb that physicians could not prescribe narcotics solely for maintenance. In Jin Fuey Moy v. United States, the court upheld that it was a violation of the Harrison Act even if a physician provided prescription of a narcotic for an addict, and thus subject to criminal prosecution. This is also true of the later Marijuana Tax Act in 1937. Soon, however, licensing bodies did not issue licenses, effectively banning the drugs.
The American judicial system did not initially accept drug prohibition. Prosecutors argued that possessing drugs was a tax violation, as no legal licenses to sell drugs were in existence; hence, a person possessing drugs must have purchased them from an unlicensed source. After some wrangling, this was accepted as federal jurisdiction under the interstate commerce clause of the U.S. Constitution.
==== Alcohol prohibition ====
The prohibition of alcohol commenced in Finland in 1919 and in the United States in 1920. Because alcohol was the most popular recreational drug in these countries, reactions to its prohibition were far more negative than to the prohibition of other drugs, which were commonly associated with ethnic minorities, prostitution, and vice. Public pressure led to the repeal of alcohol prohibition in Finland in 1932, and in the United States in 1933. Residents of many provinces of Canada also experienced alcohol prohibition for similar periods in the first half of the 20th century.
In Sweden, a referendum in 1922 decided against an alcohol prohibition law (with 51% of the votes against and 49% for prohibition), but starting in 1914 (nationwide from 1917) and until 1955 Sweden employed an alcohol rationing system with personal liquor ration books ("motbok").
=== War on Drugs ===
In response to rising drug use among young people and the counterculture movement, government efforts to enforce prohibition were strengthened in many countries from the 1960s onward. Support at an international level for the prohibition of psychoactive drug use became a consistent feature of United States policy during both Republican and Democratic administrations, to such an extent that US support for foreign governments has often been contingent on their adherence to US drug policy. Major milestones in this campaign include the introduction of the Single Convention on Narcotic Drugs in 1961, the Convention on Psychotropic Substances in 1971 and the United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances in 1988. A few developing countries where consumption of the prohibited substances has enjoyed longstanding cultural support, long resisted such outside pressure to pass legislation adhering to these conventions. Nepal only did so in 1976.
In 1972, United States President Richard Nixon announced the commencement of the so-called "War on Drugs". Later, President Reagan added the position of drug czar to the President's Executive Office. In 1973, New York introduced mandatory minimum sentences of 15 years to life imprisonment for possession of more than 113 grams (4 oz) of a so-called hard drug, called the Rockefeller drug laws after New York Governor and later Vice President Nelson Rockefeller. Similar laws were introduced across the United States.
California's broader 'three strikes and you're out' policy adopted in 1994 was the first mandatory sentencing policy to gain widespread publicity and was subsequently adopted in most United States jurisdictions. This policy mandates life imprisonment for a third criminal conviction of any felony offense. A similar 'three strikes' policy was introduced to the United Kingdom by the Conservative government in 1997. This legislation enacted a mandatory minimum sentence of seven years for those convicted for a third time of a drug trafficking offense involving a class A drug.
=== Calls for legalization, relegalization or decriminalization ===
The terms relegalization, legalization, legal regulations, or decriminalization are used with very different meanings by different authors, something that can be confusing when the claims are not specified. Here are some variants:
Sales of one or more drugs (e.g., marijuana) for personal use become legal, at least if sold in a certain way.
Sales of an extracts with a specific substance become legal sold in a certain way, for example on prescription.
Use or possession of small amounts for personal use do not lead to incarceration if it is the only crime, but it is still illegal; the court or the prosecutor can impose a fine. (In that sense, Sweden both legalized and supported drug prohibition simultaneously.)
Use or possession of small amounts for personal use do not lead to incarceration. The case is not treated in an ordinary court, but by a commission that may recommend treatment or sanctions including fines. (In that sense, Portugal both legalized and supported drug prohibitions).
There are efforts around the world to promote the relegalization and decriminalization of drugs. These policies are often supported by proponents of liberalism and libertarianism on the grounds of individual freedom, as well as by leftists who believe prohibition to be a method of suppression of the working class by the ruling class.
Prohibition of drugs is supported by proponents of conservatism as well various NGOs. A number of NGOs are aligned in support of drug prohibition as members of the World Federation Against Drugs. In the WFAD constitution, the "Declaration of the World Forum Against Drugs" (2008) advocates for "no other goal than a drug-free world", and states that a balanced policy of drug abuse prevention, education, treatment, law enforcement, research, and supply reduction provides the most effective platform to reduce drug abuse and its associated harms and calls on governments to consider demand reduction as one of their first priorities. It supports the UN drug conventions, the inclusion of cannabis as one of the "hard drugs", and the use of criminal sanctions "when appropriate" to deter drug use. It opposes legalization in any form, and harm reduction in general.
According to some critics, drug prohibition is responsible for enriching "organised criminal networks" while the hypothesis that the prohibition of drugs generates violence is consistent with research done over long time-series and cross-country facts.
In the United Kingdom, where the principal piece of drug prohibition legislation is the Misuse of Drugs Act 1971, criticism includes:
Drug classification: making a hash of it?, Fifth Report of Session 2005–06, House of Commons Science and Technology Committee, which said that the present system of drug classification is based on historical assumptions, not scientific assessment
Development of a rational scale to assess the harm of drugs of potential misuse, David Nutt, Leslie A. King, William Saulsbury, Colin Blakemore, The Lancet, 24 March 2007, said the act is "not fit for purpose" and "the exclusion of alcohol and tobacco from the Misuse of Drugs Act is, from a scientific perspective, arbitrary"
The Drug Equality Alliance (DEA) argue that the Government is administering the Act arbitrarily, contrary to its purpose, contrary to the original wishes of Parliament and therefore illegally. They are currently assisting and supporting several legal challenges to this alleged maladministration.
In February 2008 the then-president of Honduras, Manuel Zelaya, called on the world to legalize drugs, in order, he said, to prevent the majority of violent murders occurring in Honduras. Honduras is used by cocaine smugglers as a transiting point between Colombia and the US. Honduras, with a population of 7 million, suffers an average of 8–10 murders a day, with an estimated 70% being a result of this international drug trade. The same problem is occurring in Guatemala, El Salvador, Costa Rica and Mexico, according to Zelaya. In January 2012 Colombian President Juan Manuel Santos made a plea to the United States and Europe to start a global debate about legalizing drugs. This call was echoed by the Guatemalan President Otto Pérez Molina, who announced his desire to legalize drugs, saying "What I have done is put the issue back on the table."
In a report dealing with HIV in June 2014, the World Health Organization (WHO) of the UN called for the decriminalization of drugs particularly including injected ones. This conclusion put WHO at odds with broader long-standing UN policy favoring criminalization. Eight states of the United States (Alaska, California, Colorado, Maine, Massachusetts, Nevada, Oregon, and Washington), as well as the District of Columbia, have legalized the sale of marijuana for personal recreational use as of 2017, although recreational use remains illegal under U.S. federal law. The conflict between state and federal law is, as of 2018, unresolved.
Since Uruguay in 2014 and Canada in 2018 legalized cannabis, the debate has known a new turn internationally.
On March 14th, 2025, the United Nations Commission on Narcotic Drugs decided to create a panel of independent experts to rethink the global drug control regime.
== Drug prohibition laws ==
The following individual drugs, listed under their respective family groups (e.g., barbiturates, benzodiazepines, opiates), are the most frequently sought after by drug users and as such are prohibited or otherwise heavily regulated for use in many countries:
Among the barbiturates, pentobarbital (Nembutal), secobarbital (Seconal), and amobarbital (Amytal)
Among the benzodiazepines, temazepam (Restoril; Normison; Euhypnos), flunitrazepam (Rohypnol; Hypnor; Flunipam), and alprazolam (Xanax)
Cannabis products, e.g., marijuana, hashish, and hashish oil
Among the dissociatives, phencyclidine (PCP), and ketamine are the most sought after.
hallucinogens such as LSD, mescaline, peyote, and psilocybin
Empathogen-entactogen drugs like MDMA ("ecstasy")
Among the narcotics, it is opiates such as morphine and codeine, and opioids such as diacetylmorphine (Heroin), hydrocodone (Vicodin; Hycodan), oxycodone (Percocet; Oxycontin), hydromorphone (Dilaudid), and oxymorphone (Opana).
Sedatives such as GHB and methaqualone (Quaalude)
Stimulants such as cocaine, amphetamine (Adderall), dextroamphetamine (Dexedrine), methamphetamine (Desoxyn), methcathinone, and methylphenidate (Ritalin)
The regulation of the above drugs varies in many countries. Alcohol possession and consumption by adults is today widely banned only in Islamic countries and certain states of India. Although alcohol prohibition was eventually repealed in the countries that enacted it, there are, for example, still parts of the United States that do not allow alcohol sales, though alcohol possession may be legal (see dry counties). New Zealand has banned the importation of chewing tobacco as part of the Smoke-free Environments Act 1990. In some parts of the world, provisions are made for the use of traditional sacraments like ayahuasca, iboga, and peyote. In Gabon, iboga (tabernanthe iboga) has been declared a national treasure and is used in rites of the Bwiti religion. The active ingredient, ibogaine, is proposed as a treatment of opioid withdrawal and various substance use disorders.
In countries where alcohol and tobacco are legal, certain measures are frequently undertaken to discourage use of these drugs. For example, packages of alcohol and tobacco sometimes communicate warnings directed towards the consumer, communicating the potential risks of partaking in the use of the substance. These drugs also frequently have special sin taxes associated with the purchase thereof, in order to recoup the losses associated with public funding for the health problems the use causes in long-term users. Restrictions on advertising also exist in many countries, and often a state holds a monopoly on manufacture, distribution, marketing, and/or the sale of these drugs.
=== List of principal drug prohibition laws by jurisdiction (non-exhaustive) ===
Australia: Standard for the Uniform Scheduling of Medicines and Poisons
Bangladesh: Narcotics Substances Control Act, 2018
Belize: Misuse of Drugs Act (Belize)
Canada: Controlled Drugs and Substances Act
Estonia: Narcotic Drugs and Psychotropic Substances Act (Estonia)
Germany: Narcotic Drugs Act
India: Narcotic Drugs and Psychotropic Substances Act (India)
Netherlands: Opium Law
New Zealand: Misuse of Drugs Act 1975
Pakistan: Control of Narcotic Substances Act 1997
Philippines: Comprehensive Dangerous Drugs Act of 2002
Poland: Drug Abuse Prevention Act 2005
Portugal: Decree-Law 15/93
Ireland: Misuse of Drugs Act (Ireland)
South Africa: Drugs and Drug Trafficking Act 1992
Singapore: Misuse of Drugs Act (Singapore)
Sweden: Lag om kontroll av narkotika (SFS 1992:860)
Thailand: Psychotropic Substances Act (Thailand) and Narcotics Act
United Kingdom: Misuse of Drugs Act 1971 and Drugs Act 2005
United States: Controlled Substances Act
International: Single Convention on Narcotic Drugs
=== Legal dilemmas ===
The sentencing statutes in the United States Code that cover controlled substances are complicated. For example, a first-time offender convicted in a single proceeding for selling marijuana three times, and found to have carried a gun on him all three times (even if it were not used) is subject to a minimum sentence of 55 years in federal prison.
In Hallucinations: Behavior, Experience, and Theory (1975), senior US government researchers Louis Jolyon West and Ronald K. Siegel explain how drug prohibition can be used for selective social control:
The role of drugs in the exercise of political control is also coming under increasing discussion. Control can be through prohibition or supply. The total or even partial prohibition of drugs gives the government considerable leverage for other types of control. An example would be the selective application of drug laws ... against selected components of the population such as members of certain minority groups or political organizations.
Linguist Noam Chomsky argues that drug laws are currently, and have historically been, used by the state to oppress sections of society it opposes:
Very commonly substances are criminalized because they're associated with what's called the dangerous classes, poor people, or working people. So for example in England in the 19th century, there was a period when gin was criminalized and whiskey wasn't, because gin is what poor people drink.
=== Legal highs and prohibition ===
In 2013 the European Monitoring Centre for Drugs and Drug Addiction reported that there are 280 new legal drugs, known as "legal highs", available in Europe. One of the best known, mephedrone, was banned in the United Kingdom in 2010. On November 24, 2010, the U.S. Drug Enforcement Administration announced it would use emergency powers to ban many synthetic cannabinoids within a month. An estimated 73 new psychoactive synthetic drugs appeared on the UK market in 2012. The response of the Home Office has been to create a temporary class drug order which bans the manufacture, import, and supply (but not the possession) of named substances.
=== Corruption ===
In certain countries, there is concern that campaigns against drugs and organized crime are a cover for corrupt officials tied to drug trafficking themselves. In the United States, Federal Bureau of Narcotics chief Harry Anslinger's opponents accused him of taking bribes from the Mafia to enact prohibition and create a black market for alcohol. More recently in the Philippines, one death squad hitman told author Niko Vorobyov that he was being paid by military officers to eliminate those drug dealers who failed to pay a 'tax'. Under President Rodrigo Duterte, the Philippines has waged a bloody war against drugs that may have resulted in up to 29,000 extrajudicial killings.
When it comes to social control with cannabis, there are different aspects to consider. Not only do we assess legislative leaders and the way they vote on cannabis, but we also must consider the federal regulations and taxation that contribute to social controls. For instance, according to a report on the U.S. customs and border protections, the American industry, although banned the main usage of marijuana, was still using products similar such as hemp seeds, oils etc. leading to the previously discussed marijuana tax act.
The Tax act provisions required importers to register and pay an annual tax of $24 and receive an official stamp. Stamps for Products were then affixed to each original order form and recorded by the state revenue collector. Then, a customs collector was to maintain the custody of imported marijuana at entry ports until required documents were received, reviewed and approved.Shipments were subject to searches, seizures and forfeitures if any provisions of the law were not met. Violations would result in fines of no more than $2000 or potential imprisonment for up to 5 years. Oftentimes, this created opportunity for corruption, stolen imports that would later lead to smuggling, oftentimes by state officials and tight knit elitists.
== Penalties ==
=== United States ===
Drug possession is the crime of having one or more illegal drugs in one's possession, either for personal use, distribution, sale or otherwise. Illegal drugs fall into different categories and sentences vary depending on the amount, type of drug, circumstances, and jurisdiction. In the U.S., the penalty for illegal drug possession and sale can vary from a small fine to a prison sentence. In some states, marijuana possession is considered to be a petty offense, with the penalty being comparable to that of a speeding violation. In some municipalities, possessing a small quantity of marijuana in one's own home is not punishable at all. Generally, however, drug possession is an arrestable offense, although first-time offenders rarely serve jail time. Federal law makes even possession of "soft drugs", such as cannabis, illegal, though some local governments have laws contradicting federal laws.
In the U.S., the War on Drugs is thought to be contributing to a prison overcrowding problem. In 1996, 59.6% of prisoners were drug-related criminals. The U.S. population grew by about +25% from 1980 to 2000. In that same 20 year time period, the U.S. prison population tripled, making the U.S. the world leader in both percentage and absolute number of citizens incarcerated. The United States has 5% of the world's population, but 25% of the prisoners.
About 90% of United States prisoners are incarcerated in state jails. In 2016, about 572,000, over 44%, of the 1.3 million people in these state jails, were serving time for drug offenses. 728,000 were incarcerated for violent offenses.
The data from Federal Bureau of Prisons online statistics page states that 45.9% of prisoners were incarcerated for drug offenses, as of December 2021.
=== European Union ===
In 2004, the Council of the European Union adopted a framework decision harmonizing the minimum penal provisions for illicit drug-related activities. In particular, article 2(9) stipulates that activities may be exempt from the minimum provisions "when it is committed by its perpetrators exclusively for their own personal consumption as defined by national law." This was made, in particular, to accommodate more liberal national systems such as the Dutch coffee shops (see below) or the Spanish Cannabis Social Clubs.
==== The Netherlands ====
In the Netherlands, cannabis and other "soft" drugs are decriminalised in small quantities. The Dutch government treats the problem as more of a public health issue than a criminal issue. Contrary to popular belief, cannabis is still technically illegal. Coffee shops that sell cannabis to people 18 or above are tolerated, and pay taxes like any other business for their cannabis and hashish sales, although distribution is a grey area that the authorities would rather not go into as it is not decriminalised. Many "coffee shops" are found in Amsterdam and cater mainly to the large tourist trade; the local consumption rate is far lower than in the US.
The administrative bodies responsible for enforcing the drug policies include the Ministry of Health, Welfare and Sport, the Ministry of Justice, the Ministry of the Interior and Kingdom Relations, and the Ministry of Finance. Local authorities also shape local policy, within the national framework.
When compared to other countries, Dutch drug consumption falls in the European average at six per cent regular use (twenty-one per cent at some point in life) and considerably lower than the Anglo-Saxon countries headed by the United States with an eight per cent recurring use (thirty-four at some point in life).
=== Australia ===
A Nielsen poll in 2012 found that only 27% of voters favoured decriminalisation. Australia has steep penalties for growing and using drugs even for personal use. with Western Australia having the toughest laws. There is an associated anti-drug culture amongst a significant number of Australians. Law enforcement targets drugs, particularly in the party scene. In 2012, crime statistics in Victoria revealed that police were increasingly arresting users rather than dealers, and the Liberal government banned the sale of bongs that year.
=== Indonesia ===
Indonesia carries a maximum penalty of death for drug dealing, and a maximum of 15 years prison for drug use. In 2004, Australian citizen Schapelle Corby was convicted of smuggling 4.4 kilograms of cannabis into Bali, a crime that carried a maximum penalty of death. Her trial reached the verdict of guilty with a punishment of 20 years imprisonment. Corby claimed to be an unwitting drug mule. Australian citizens known as the "Bali Nine" were caught smuggling heroin. Two of the nine, Andrew Chan and Myuran Sukumaran, were executed April 29, 2015 along with six other foreign nationals. In August 2005, Australian model Michelle Leslie was arrested with two ecstasy pills. She pleaded guilty to possession and in November 2005 was sentenced to 3 months imprisonment, which she was deemed to have already served, and was released from prison immediately upon her admission of guilt on the charge of possession.
At the 1961 Single Convention on Narcotic Drugs, Indonesia, along with India, Turkey, Pakistan and some South American countries opposed the criminalisation of drugs.
=== Republic of China (Taiwan) ===
Taiwan carries a maximum penalty of death for drug trafficking, while smoking tobacco and wine are classified as legal entertainment drug. The Department of Health is in charge of drug prohibition.
== Cost ==
In 2020, the direct cost of drug prohibition to United States taxpayers was estimated at over $40 billion annually. Prohibition can increase organized crime, government corruption, and mass incarceration via the trade in illegal drugs, while racial and gender disparities in enforcement are evident.
Although drug prohibition is often portrayed by proponents as a measure to improve public health, evidence is lacking. In 2016, the Johns Hopkins–Lancet Commission concluded that the "harms of prohibition far outweigh the benefits", citing increased risk of overdoses and HIV infection and detrimental effects on the social determinants of health. Some proponents argue that drug prohibition's effect on suppressing usage rates (although the magnitude of this effect is unknown) outweighs the negative effects of prohibition.
Alternative approaches to prohibition include drug legalization, drug decriminalization, and government monopoly.
== See also ==
Alcohol law
Arguments for and against drug prohibition
Chasing the Scream
Drug liberalization
Demand reduction
Drug policy of the Soviet Union
Harm reduction
List of anti-cannabis organizations
Medellín Cartel
Mexican drug war
Puerto Rican drug war
Prohibitionism
Tobacco control
War on Drugs
US specific:
Allegations of CIA drug trafficking
School district drug policies
Drug Free America Foundation
Drug Policy Alliance
DrugWarRant
Gary Webb
Marijuana Policy Project
National Organization for the Reform of Marijuana Laws
Students for Sensible Drug Policy
Woman's Christian Temperance Union
== References ==
== Further reading ==
== External links ==
Making Contact: The Mission to End Prohibition. Radio piece featuring LEAP founder and former narcotics officer Jack Cole, and Drug Policy Alliance founder Ethan Nadelmann
EMCDDA – Decriminalisation in Europe? Recent developments in legal approaches to drug use Archived January 12, 2007, at the Wayback Machine.
10 Downing Street's Strategy Unit Drugs Report
War on drugs Archived April 30, 2011, at the Wayback Machine Part I: Winners, documentary (50 min) explaining 'War on Drugs' by Tegenlicht of VPRO Dutch television. After short introduction in Dutch (1 min), English spoken. Broadband internet needed.
War on drugs Archived April 30, 2011, at the Wayback Machine Part II: Losers, documentary (50 min) showing downside of the 'War on Drugs' by Tegenlicht of VPRO Dutch television. After short introduction in Dutch (1 min), English spoken. Broadband internet needed.
After the War on Drugs: Options for Control (Report)
The Drug War as a Socialist Enterprise by Milton Friedman
Free from the Nightmare of Prohibition Archived February 23, 2006, at the Wayback Machine by Harry Browne
Prohibition news page – Alcohol and Drugs History Society
Drugs and conservatives should go together | Wikipedia/Drug_prohibition |
Many religions have expressed positions on what is acceptable to consume as a means of intoxication for spiritual, pleasure, or medicinal purposes. Psychoactive substances may also play a significant part in the development of religion and religious views as well as in rituals.
The most common drugs in the historical religions are cannabis and alcohol.
== Neolithic ==
In the 2005 book Inside the Neolithic Mind, the authors, archaeologists David Lewis-Williams and David Pearce argue that hallucinogenic drugs formed the basis of Neolithic religion and rock art.
== Ancient Greece ==
Some scholars have suggested that Ancient Greek mystery religions employed entheogens, such as the ergot-spiked Kykeon central to the Eleusinian Mysteries, which contained LSD-like compounds to induce a trance or dream state. Research conducted by John R. Hale, Jelle Zeilinga de Boer, Jeffrey P. Chanton and Henry A. Spiller suggests that the prophecies of the Delphic Oracle were uttered by Priestesses under the influence of ethylene gas exuded from the ground.
== Ancient Mesoamerica ==
Archaeological, ethnohistorical, and ethnographic data show that Mesoamerican cultures used psychedelic substances in therapeutic and religious rituals. The ancient Aztecs used a variety of entheogenic plants and animals within their society, including ololiuqui (Rivea corymbosa), teonanácatl (Psilocybe spp.), and peyotl (Lophophora williamsii). Goals for the usage of entheogenics by the Maya were spiritual healing, wisdom gain, and religious ceremonies. The effects of psychedelic plants during religious rituals is believed to have had an impact on the development and creation of statues, and sacred images.
== Hinduism ==
=== Soma ===
Hinduism has a history of psychedelic usage going back to the Vedic period. The oldest scriptures of Hinduism Rigveda (1500 BCE), mentions ritualistic consumption of a divine psychedelic known as soma. There are many theories about the recipe of Soma. Non-Indian researchers have proposed candidates including Amanita muscaria, Psilocybe cubensis, Peganum harmala and Ephedra sinica. According to recent philological and archaeological studies, and in addition, direct preparation instructions confirm in the Rig Vedic Hymns (Vedic period) Ancient Soma most likely consisted of poppy, Phaedra/Ephedra and Cannabis.
In the Vedas, the same word soma is used for the drink, the plant, and its deity. Drinking soma produces immortality (Amrita, Rigveda 8.48.3). Indra and Agni are portrayed as consuming soma in copious quantities. In the vedic mythology, Indra drank large amounts of soma while fighting the serpent demon Vritra. The consumption of soma by human beings is well attested in Vedic ritual.
The Rigveda (8.48.3) says:
Ralph T.H. Griffith translates this as:
=== Cannabis ===
The plant Cannabis is also mentioned in the Atharvaveda-Samhita (1200 BCE) and Puranas (c. 200 BCE) as one of the ive of the holy plants.
The Atharvaveda 11.6.15:
'भङ्ग' (bhang) refers to the cannabis plant.
=== Datura ===
The hallucinogenic Datura plant has also been used in Ayurvedic contexts and are often used to adorn the Lingam in many Shiva temples and festivals like Navarathri. The plant goes through a detoxification process to remove the psychoactive elements when utilized in standard Ayurveda practice. In the Vamana Purana, it is mentioned that the Datura flower appeared from the chest of Shiva and offering it the will remove evil, suffering and wrongdoings. There are also Sadhus who are worshipers of Shiva and sometimes smoke the leaves and seeds of Datura plant, though is done with caution because it can be poisonous and cause very vivid hallucinations (delirium).
== Buddhism ==
In Buddhism the Right View (samyag-dṛṣṭi / sammā-diṭṭhi) can also be translated as "right perspective", "right outlook" or "right understanding", is the right way of looking at life, nature, and the world as they really are for us. It is to understand how our reality works. It acts as the reasoning with which someone starts practicing the path. It explains the reasons for our human existence, suffering, sickness, aging, death, the existence of greed, hatred, and delusion. Right view gives direction and efficacy to the other seven path factors. It begins with concepts and propositional knowledge, but through the practice of right concentration, it gradually becomes transmuted into wisdom, which can eradicate the fetters of the mind. An understanding of right view will inspire the person to lead a virtuous life in line with right view. In the Pāli and Chinese canons, it is explained thus:
=== Right livelihood ===
Right livelihood (samyag-ājīva / sammā-ājīva). This means that practitioners ought not to engage in trades or occupations which, either directly or indirectly, result in harm for other living beings. In the Chinese and Pali Canon, it is explained thus:
And what is right livelihood? There is the case where a disciple of the noble ones, having abandoned dishonest livelihood, keeps his life going with right livelihood: This is called right livelihood.
More concretely today interpretations include "work and career need to be integrated into life as a Buddhist," it is also an ethical livelihood, "wealth obtained through rightful means" (Bhikku Basnagoda Rahula) – that means being honest and ethical in business dealings, not to cheat, lie or steal. As people are spending most of their time at work, it's important to assess how our work affects our mind and heart. So important questions include "How can work become meaningful? How can it be a support, not a hindrance, to spiritual practice a place to deepen our awareness and kindness?"
The five types of businesses that should not be undertaken:
Business in weapons: trading in all kinds of weapons and instruments for killing.
Business in human beings: slave trading, prostitution, or the buying and selling of children or adults.
Business in meat: "meat" refers to the bodies of beings after they are killed. This includes breeding animals for slaughter.
Business in intoxicants: manufacturing or selling intoxicating drinks or addictive drugs.
Business in poison: producing or trading in any kind of poison or a toxic product designed to kill.
=== The fifth precept ===
According to the fifth precept of the Pancasila, Buddhists are meant to refrain from any quantity of "fermented or distilled beverages" which would prevent mindfulness or cause heedlessness. In the Pali Tipitaka the precept is explicitly concerned with alcoholic beverages:
"I undertake the training rule to abstain from fermented drink that causes heedlessness."
Surāmerayamajjapamādaṭṭhānā veramaṇī sikkhāpadaṃ samādiyāmi.
However, caffeine and tea are permitted, even encouraged for monks of most traditions, as it is believed to promote wakefulness.
Generally speaking, the vast majority of Buddhists and Buddhist sects denounce and have historically frowned upon the use of any intoxicants by an individual who has taken the five precepts. Most Buddhists view the use and abuse of intoxicants to be a hindrance in the development of an enlightened mind. However, there are a few historical and doctrinal exceptions.
=== Vajrayana ===
Many modern Buddhist schools have strongly discouraged the use of psychoactive drugs of any kind; however, they may not be prohibited in all circumstances in all traditions. Some denominations of tantric or esoteric Buddhism especially exemplify the latter, often with the principle skillful means:
==== Alcohol ====
For example, as part of the ganachakra tsok ritual (as well as Homa, abhisheka and sometimes drubchen) some Tibetan Buddhists and Bönpos have been known to ingest small amounts of grain alcohol (called amrit or amrita) as an offering. If a member is an alcoholic, or for some other reason does not wish to partake in the drinking of the alcoholic offering, then he or she may dip a finger in the alcohol and then flick it three times as part of the ceremony.
Amrita is also possibly the same as, or at least in some sense a conceptual derivative of the ancient Hindu soma (the latter historians often equate with Amanita muscaria or other Amanita psychoactive fungi). Crowley (1996) states:
"Undoubtedly, the striking parallels between "The legend about Chakdor" and the Hindu legend of the origin of soma show that the Buddhist amrita and the Hindu soma were at one time understood to be identical. Moreover, the principal property of amrita is, to this day, perceived by Buddhists as being a species of inebriation, however symbolically this inebriation may be interpreted. Why else would beer (Tibetan chhang, "barley beer") be used by yogins as a symbolic substitute for amrita [Ardussi]? Conversely, why else would the term bDud.rTsi be used as a poetic synonym for beer?
Conversely, in Tibetan and Sherpa lore there is a story about a monk who came across a woman who told him that he must either:
a. kill her goat,
b. sleep with her, or
c. drink a mug of beer.
d. All of the above.
The monk thought to himself, "well, surely if I kill the goat then I will be causing great suffering since a living being will die. If I sleep with the woman then I will have broken another great vow of a monk and will surely be lost to the ways of the world. Lastly, if I drink the beer then perhaps no great harm will come and I will only be intoxicated for a while, and most importantly I will only be hurting myself." (In the context of the story this instance is of particular importance to him because monks in the Mahayana and Vajrayana try to bring all sentient beings to enlightenment as part of their goal.)
So the monk drank the mug of beer and then he became very drunk. In his drunkenness he proceeded to kill the goat and sleep with the woman, breaking all three vows and, at least in his eyes, doing much harm in the world. The lesson of this story is meant to be that, at least according to the cultures from which it delineates, alcohol causes one to break all of one's vows, in a sense that one could say it is the cause of all other harmful deeds.
The Vajrayana teacher Drupon Thinley Ningpo Rinpoche has said that as part of the five precepts which a layperson takes upon taking refuge, that although they must refrain from taking intoxicants, they may drink enough so as they do not become drunk. Bhikkus and Bhikkunis (monks and nuns, respectively), on the other hand, who have taken the ten vows as part of taking refuge and becoming ordained, cannot imbibe any amount of alcohol or other drugs, other than pharmaceuticals taken as medicine.
Tenzin Gyatso, the 14th Dalai Lama of Tibet, is known as teetotaler and non-smoker.
==== Hallucinogens ====
There is some evidence regarding the use of deliriant Datura seeds (known as candabija) in Dharmic rituals associated with many tantras – namely the Vajramahabhairava, Samputa, Mahakala, Guhyasamaja, Tara and Krsnayamari tantras – as well as cannabis and other entheogens in minority Vajrayana sanghas. Ronald M Davidson says that in Indian Vajrayana, Datura was:
"employed as a narcotic paste or as wood in a fire ceremony and could be easily absorbed through the skin or the lungs. The seeds of this powerful narcotic, termed "passion seeds" (candabija), are the strongest elements and contain the alkaloids hyoscine, hyoscyamine, and atropine in forms that survive burning or boiling. In even moderate doses, datura can render a person virtually immobile with severe belladonna-like hallucinations."
In the Profound Summarizing Notes on the Path Presented as the Three Continua, a Sakya Lamdre text, by Jamyang Khyentse Wangchuk (1524–1568), the use of Datura in combination with other substances, is prescribed as part of a meditation practice meant to establish that "All the phenomena included in apparent existence, samsara and nirvana, are not established outside of one's mind."
Ian Baker writes that Tibetan terma literature such as the Vima Nyingtik describes "various concoctions of mind altering substances, including datura and oleander, which can be formed into pills or placed directly in the eyes to induce visions and illuminate hidden contents of the psyche."
A book titled Zig Zag Zen: Buddhism and Psychedelics (2002), details the history of Buddhism and the use of psychedelic drugs, and includes essays by modern Buddhist teachers on the topic.
=== Zen ===
Zen Buddhism is known for stressing the precepts. In Japan, however, where Zen flourished historically, there are a number of examples of misconduct on the part of monks and laypeople alike. This often involved the use of alcohol, as sake drinking has and continues to be a well known aspect of Japanese culture.
The Japanese Zen monk and abbot, shakuhachi player and poet Ikkyu was known for his unconventional take on Zen Buddhism: His style of expressing dharma is sometimes deemed "Red Thread Zen" or "Crazy Cloud Zen" for its unorthodox characteristics. Ikkyu is considered both a heretic and saint in the Rinzai Zen tradition, and was known for his derogatory poetry, open alcoholism and for frequenting the services of prostitutes in brothels. He personally found no conflict between his lifestyle and Buddhism.
There are several koans (Zen riddles) referencing the drinking of sake (rice wine); for instance Mumonkan's tenth koan titled Seizei Is Utterly Destitute:
'Seizei said to Sozan, "Seizei is utterly destitute. Will you give him support?" Sozan called out: "Seizei!" Seizei responded, "Yes sir?!" Sozan said, "You have finished three cups of the finest wine in China, and still you say you have not yet moistened your lips!"'
Another monk, Gudo, is mentioned in a koan called Finding a Diamond on a Muddy Road buying a gallon of sake.
== Judaism ==
Judaism maintains that people do not own their bodies – they belong to God. As a result, Jews are not permitted to harm, mutilate, destroy or take risks with their bodies, life or health with activities such as taking life-threatening drugs. For these reasons, rabbis generally prohibit the use of drugs except in controlled medical situations. Even without a risk to life or health, addictive drugs are discouraged due to their negative social effects.
When issues of physical, mental, and social harm are not present, it is debated whether drugs can have any positive spiritual value. According to Rabbi Walter Wurzburger, "Proximity to God cannot be reached by putting oneself into a trance either through physical or chemical means".
Rabbi Aryeh Kaplan suggested that some medieval kabbalists may have used some psychedelic drugs. Indeed, one can find in Kabbalistic medical manuals cryptic references to the hidden powers of mandrake, harmal and other psychoactive plants, though the exact usage of these powers is hard to decipher. Some kabbalists, including Isaac of Acco and Abraham Abulafia, mention a method of "philosophical meditation", which involves drinking a cup of "strong wine of Avicenna", which would induce a trance and would help the adept to ponder over difficult philosophical questions. The exact recipe of this wine remains unknown; Avicenna refers in his works to the effects of opium and datura extracts.
According to Aryeh Kaplan, some have translated kaneh-bosem (קְנֵה-בֹשֶׂם), an ingredient in the holy anointing oil (Exodus 30:23), as cannabis. However, the term kaneh-bosem literally translates to "sweet cane" (an association that is difficult to make with cannabis), and most lexicographers, botanists, and biblical commentators translate it as "calamus" (Acorus calamus), a species known throughout the Middle East for its fragrance since the mid-2nd millennium BCE.
Use of alcohol in moderation is an accepted part of Judaism. The Hebrew Bible states that "wine gladdens man's heart" (Psalms 104:15), and a single cup of wine is drunk for common rituals such as kiddush (though grape juice may be used instead). Nevertheless, excessive use of alcohol is condemned. Prayer and priestly service are forbidden while intoxicated, and numerous Biblical figures met their downfall through drunkenness. The Talmud states that wine received its Hebrew name (whose sound somewhat resembles a howl) because it "brings lament to the world". The holiday of Purim is exceptional in that on this date drunkenness is encouraged in some communities, in commemoration of the drunkenness which plays a significant role in the Book of Esther.
In Hasidic Judaism alcohol consumption is more common, especially at communal religious events like the farbrengen or tisch, where alcohol often accompanies singing and Torah study. If the drinking is moderate, for the purpose of Divine service, and done together with other chassidim, it is considered useful for expanding the mind and providing enthusiasm in the service of God. Nevertheless, excessive consumption is still discouraged; for example, the Lubavitcher Rebbe forbade his Chassidim under the age of 40 to consume more than 4 small shots of hard liqueurs.
The use of nicotine is well known in Hasidic communities. Stories are told about miracles and spiritual journeys performed by the Baal Shem Tov and other Tzaddikim with the help of their smoking pipe. Hasidim valued smoking both as part of their general goal to raise the spiritual "sparks" that are allegedly present in base physical phenomena, and for the practical goal of experiencing better concentration while under its influence. Nevertheless, since the health impacts of smoking have become understood by modern medicine, there has been a strong movement to discourage and prohibit smoking.
Caffeine use is accepted in Judaism, and played a significant role in the spread of nighttime rituals such as Tikkun Chatzot. Nevertheless, there was initially some opposition from rabbis who were concerned that nighttime gatherings or the coffeehouse atmosphere could lead to illicit behavior.
== Christianity ==
Many Christian denominations disapprove of the use of most illicit drugs. Many denominations permit the moderate use of socially and legally acceptable drugs like alcohol, caffeine and tobacco. Some Christian denominations permit smoking tobacco, while others disapprove of it. Many orthodox or protestant denominations do not have any official stance on drug use, while other Christian denominations (e.g. The Church of Jesus Christ of Latter-day Saints, and Jehovah's Witnesses) discourage or prohibit the use of any of these substances.
In the Eucharist, wine represents (or among Christians who believe in some form of Real Presence, like the Catholic, Lutheran and Orthodox churches, actually is) the blood of Christ. Lutherans believe in the real presence of the body and blood of Christ in the Eucharist, that the body and blood of Christ are "truly and substantially present in, with and under the forms." of the consecrated bread and wine (the elements), so that communicants orally eat and drink the holy body and blood of Christ Himself as well as the bread and wine (cf. Augsburg Confession, Article 10) in this Sacrament. The Lutheran doctrine of the Real Presence is more accurately and formally known as "the Sacramental Union". It has been inaccurately called "consubstantiation", a term which is specifically rejected by most Lutheran churches and theologians.
On the other hand, some Protestant Christian denominations, such as Baptists and Methodists associated with the temperance movement, encourage or require teetotalism, as well as abstinence from cultivating and using tobacco. In some Protestant denominations, grape juice or non-alcoholic wine is used in place of wine in the administration of Holy Communion.
Conservative Anabaptist denominations, such as the Dunkard Brethren Church, teach:
Members of the Dunkard Brethren Church shall abstain from the use of intoxicating or addictive substances, such as narcotics, nicotine, marijuana, or alcoholic beverages (except as directed by a physician). Using, raising, manufacturing, buying or selling them by Christians is inconsistent with the Christian lifestyle and testimony. Members of the Dunkard Brethren Church who do so should be counseled in love and forbearance. If they manifest an unwilling or arbitrary spirit, they subject themselves to the discipline of the church, even to expulsion in extreme cases. We implore members to accept the advice and counsel of the church and abstain from all of the above. Since members are to be examples to the world (Romans 14:20-21) indulgence in any of these activities disqualifies then for Church or Sunday School work or as delegates to District or General Conference.
The best-known Western prohibition against alcohol happened in the United States in the 1920s, where concerned prohibitionists were worried about its dangerous side effects. However, the demand for alcohol remained and criminals stepped in and created the supply. The consequences of organized crime and the popular demand for alcohol led to alcohol being legalized again.
The Seventh-day Adventist Church is supportive of scientific medicine. It promotes eradication of illicit drug use and promotes abstinence against tobacco and alcohol., and promotes a measured and balanced approach to use of both medicinal drugs as well as natural remedies (which it neither discourages or prohibits), promotes the control of medicines that may be abused, and promotes vaccination and immunization.
== Islam ==
Alcohol, or just wine (in the views of some), are considered haram but Nabith a drink that can ferment is halal if drank before it becomes fermented (permissable)
The Muslim-majority nations of Turkey and Egypt were instrumental in banning opium, cocaine, and cannabis when the League of Nations committed to the 1925 International Convention relating to opium and other drugs (later the 1934 Dangerous Drugs Act). The primary goal was to ban opium and cocaine, but cannabis was added to the list, and it remained there largely unnoticed due to the much more heated debate over opium and cocaine. The 1925 Act has been the foundation upon which every subsequent policy in the United Nations has been founded.
There are no prohibitions in Islam on alcohol for scientific, industrial or automotive use and cannabis is generally permitted for medicinal purposes.
In spite of these restrictions on substance use, the recreational use of cannabis still occurs widely throughout many Muslim nations.
== Baháʼí Faith ==
Followers of the Baháʼí Faith are forbidden to drink alcohol or to take drugs, unless prescribed by doctors. Accordingly, the sale and trafficking of such substances is also forbidden. Smoking is discouraged but not prohibited.
== Rastafari movement ==
Many Rastafari believe cannabis, which they call "ganja", "the herb", or "Kaya", is a sacred gift of Jah. It may be used for spiritual purposes to commune with God, but should not be used profanely. The use of other drugs, however, including alcohol, is frowned upon. Many believe that the wine Jesus/Iyesus drank was not an alcoholic beverage, but simply the juice of grapes or other fruits.
While some Rastafari suggest that the Hebrew Bible may refer to marijuana, it is generally held by academics specializing in the lexicography of the text that cannabis is not documented or mentioned. Some popular writers have argued that there is evidence for religious use of cannabis in the Hebrew Bible, although this hypothesis and some of the specific case studies (e.g., John Allegro in relation to Qumran, 1970) have been "widely dismissed as erroneous" (Merlin, 2003). The primary advocate of a religious use of cannabis plant in early Judaism was Sula Benet (1967), who claimed that the plant kaneh bosm קְנֵה-בֹשֶׂם mentioned five times in the Hebrew Bible, and used in the holy anointing oil of the Book of Exodus, was in fact cannabis, although lexicons of Hebrew and dictionaries of plants of the Bible such as by Michael Zohary (1985), Hans Arne Jensen (2004) and James A. Duke (2010) and others identify the plant in question as either Acorus calamus or Cymbopogon citratus.
=== Groundation ===
A "groundation" (also spelled "grounation") or "binghi" is a holy day; the name "binghi" is derived from "Nyabinghi" (literally "Nya" meaning "black" and "Binghi" meaning "victory"). Binghis are marked by much dancing, singing, feasting, and the smoking of "ganja", and can last for several days.
=== Bible verses which Rastas believe justify cannabis use ===
...thou shalt eat the herb of the field.
Genesis 3.18
...eat every herb of the land.
Exodus 10:12
Better is a dinner of herb where love is, than a stalled ox and hatred therewith.
Proverbs 15:17
=== Beliefs about other drugs ===
According to many Rastas, the illegality of cannabis in many nations is evidence of persecution of Rastafari. They are not surprised that it is illegal, viewing Cannabis as a powerful substance that opens people's minds to the truth – something the Babylon system, they reason, clearly does not want. Cannabis use is contrasted with the use of alcohol and other drugs, which they feel destroy the mind.
== Native American religion ==
The Native American Church (NAC) is a syncretic Native American religion that teaches a combination of traditional Native American beliefs and elements of Christianity, with sacramental use of the entheogen peyote. It is the most widespread indigenous religion among Native Americans in the United States (except Alaska Natives and Native Hawaiians), Canada (specifically First Nations people in Saskatchewan and Alberta), and Mexico, with an estimated 250,000 adherents as of the late twentieth century.
== Thelema ==
Aleister Crowley wrote The Gnostic Mass in 1913 while travelling in Moscow, Russia. The structure is similar to the Mass of the Eastern Orthodox Church and Roman Catholic Church, communicating the principles of Crowley's Thelema. It is the central rite of Ordo Templi Orientis and its ecclesiastical arm, Ecclesia Gnostica Catholica.
The ceremony calls for five officers: a Priest, a Priestess, a Deacon, and two adult acolytes, called "the Children". The end of the ritual culminates in the consummation of the eucharist, consisting of a goblet of wine and a Cake of Light, after which the congregant proclaims "There is no part of me that is not of the gods!"
== See also ==
Cannabis and religion
Libation
Food and drink prohibitions
Religion and alcohol
Religious views on smoking
Entheogenic drugs and the archaeological record
Psychology of religion § Religion and drugs
Carl A. P. Ruck § Entheogen theory
Eleusinian Mysteries § Entheogenic theories
Psychonautics
Psychedelic therapy
Entheogen
List of entheogens
List of substances used in rituals
Santo Daime
Native American Church
== References ==
== Further reading ==
Shannon, Benny (March 2008). "Biblical Entheogens: a Speculative Hypothesis". Time and Mind. 1 (1): 51–74. doi:10.2752/175169608783489116. S2CID 163104779.
== External links ==
Media related to Religion and drugs at Wikimedia Commons | Wikipedia/Religion_and_drugs |
APICA (2NE1, SDB-001, N-(1-adamantyl)-1-pentyl-1H-indole-3-carboxamide) is an indole based drug that acts as a potent agonist for the cannabinoid receptors.
It had never previously been reported in the scientific or patent literature, and was first identified by laboratories in Japan in March 2012 as an ingredient in synthetic cannabis smoking blends, along with its indazole derivative APINACA (sold as "AKB48").
Structurally it closely resembles cannabinoid compounds from patent WO 2003/035005 but with an indole core instead of indazole, and a simple pentyl chain on the indole 1-position. Given the known metabolic liberation (and presence as an impurity) of amantadine in the related compound APINACA, it is suspected that metabolic hydrolysis of the amide group of APICA may also release amantadine.
Pharmacological testing determined APICA to have an IC50 of 175 nM at CB1, only slightly less potent than JWH-018 which had an IC50 of 169 nM, but over four times more tightly binding than APINACA, which had an IC50 of 824 nM. The first published synthesis and pharmacological evaluation of APICA revealed that it acts as a full agonist at CB1 (EC50 = 34 nM) and CB2 receptors (EC50 = 29 nM). Furthermore, APICA possesses cannabis-like effects in rats, and appears to be less potent than JWH-018 but more potent than THC.
== Legal Status ==
As of October 2015, APICA is a controlled substance in China.
== See also ==
== References == | Wikipedia/APICA_(synthetic_cannabinoid_drug) |
Crime in Saint Kitts and Nevis is considerably higher than many other parts of the world. In 2012 Saint Kitts and Nevis had a homicide rate of 33.6 per 100,000 citizens, the 8th highest in the world, and the 7th highest during the period from 2005 to 2014. As of 2011 Basseterre had the highest murder rate of any capital city in the world at 131.6 per 100,000 inhabitants (a total of 17 murders in the city that year).
Most violence and criminal activity in the country is believed to be gang and drug related.
== Context and History ==
Saint Kitts and Nevis gained its independence in 1983. In 2001 the country's homicide rate was at an all-time low with only 6 murders reported that year. Since then however there has been a rapid rise in homicides and other crimes. 2011 was the worst year for homicides in the country with 34 murders reported, giving the country a homicide rate of 67.6 per 100,000 citizens, at that time one of the top three in the world. Since 2011 measures and precautions have been placed by the government that have reduced the number of murders. The Saint Kitts government has also claimed that these measures more than halved crime during that period although this claim has been viewed skeptically by independent organizations.
Generally speaking the courts and police in Saint Kitts and Nevis are considered effective and corruption free, and the legal system is considered effective. However there is a lack of civilian oversight and interaction with the police department, as well as occasional reports of abuse perpetrated by the police. The biggest barrier to fighting crime is seen as the country's outdated prison system, with many, if not all, prisons old and overcrowded. Building new prisons and improving the relationships between the police and community are seen as the biggest improvements the government can make to combat crime.
=== Terrance Drew administration ===
As of December 21, 2023, Saint Kitts and Nevis has witnessed its second fatal shooting incident within three days, bringing the murder count for 2023 to 31. Marius Webbe of Pond Hill was found dead in his pigsty at Brown Hill with gunshot injuries. This incident follows the discovery of Glenville 'Short Boss' Syder's lifeless body on December 18, marking the 30th murder of the year. These incidents have raised concerns about the escalating violence in the region.
Prime Minister Dr. Terrance Drew, who has been in office for the last 17 months, faces the challenge of addressing and curbing this alarming trend. The murder count reflects a worrying upward trajectory, necessitating comprehensive efforts to ensure the safety and well-being of the citizens.
The discontinuation of the PEACE Programme by Prime Minister Drew’s administration has raised concerns for St. Kitts and Nevis' youth. Previously successful under Team Unity, the program led to a 50% crime reduction. However, since its abandonment, almost 21 young lives have been lost to violence, with a surge in robbery and violent crimes. Urgent calls from citizens demand the Drew administration to reinstate the PEACE Programme, mirroring its effective Team Unity model. The program's past success played a pivotal role in crime reduction and community safety.
== Effect on Tourism ==
Tourism plays a significant role in the Saint Kitts and Nevis economy, and despite the levels of crime tourists are not usually victims. A rare instance of tourists being targeted happened in 2010 when an elderly British couple were murdered in a courtyard.
== Role of Firearms in crime ==
Firearms have been increasingly used in crimes on Saint Kitts and Nevis. In 2003 only 63.6 percent of murders were gun-related, while in 2010 it had risen to 85 percent. The global average of firearm-related homicides is 42 percent.
== Drugs and gangs ==
Since the turn of the 21st century there has been an increase in gang and drug-related violence and crime. Cocaine especially is known to be frequently trafficked through the country, although the presence of the drug trade is considered relatively minor compared to other Caribbean and Latin American countries. Transnational gangs are not believed to operate in the country.
Most gang activities relate to drug trafficking as well as petty crime, robberies, and extortion. Many homicides and attempted homicides are believed to be drug and gang-related, many caused by rival factions fighting over turf.
A rivalry starting in 2008 is credited with the escalation of violence in the country. The Saint Kitts and Nevis government eventually arrested several gang leaders, one of which was later executed by hanging.
== BBC controversy ==
In 2015 Saint Kitts and Nevis was named by the BBC in a report as "the most violent place on earth". The BBC's report was widely criticized in Saint Kitts and Nevis for exaggerating the level of violence and crime in the country. The police department of Saint Kitts and Nevis released a report shortly afterwards stating that crime in the country had fallen 60% in the time period from 2011 and 2015, as well as the fact that visitors and tourists to Saint Kitts and Nevis are rarely targeted.
== References == | Wikipedia/Illegal_drug_trade_in_Saint_Kitts_and_Nevis |
The illegal drug trade, drug trafficking, or narcotrafficking is a global black market dedicated to the cultivation, manufacture, distribution and sale of prohibited drugs. Most jurisdictions prohibit trade, except under license, of many types of drugs through the use of drug prohibition laws. The think tank Global Financial Integrity's Transnational Crime and the Developing World report estimates the size of the global illicit drug market between US$426 and US$652 billion in 2014, which is equal to the UK's national debt alone. With a world GDP of US$78 trillion in the same year, the illegal drug trade may be estimated as nearly 1% of total global trade. Consumption of illegal drugs is widespread globally, and it remains very difficult for local authorities to reduce the rates of drug consumption.
== History ==
Prior to the 20th century, governments rarely made a major effort to proscribe recreational drug use, though several smoking bans were passed by authorities in Europe and Asia during the early modern era. Tobacco and opium were the two first drugs to be subject to prohibitory government legislation, with officials in New Spain, the Ottoman Empire, Germany, Austria and the Russian Empire passing laws against smoking tobacco; the government of the Qing dynasty issued edicts banning opium smoking in 1730, 1796 and 1800. Beginning in the 18th century, the East India Company (EIC) began to smuggle Indian opium to Chinese merchants, resulting in the creation of an illegal drug trade in China. By 1838, there were between four and 12 million opium addicts in China, and Qing officials responded by strengthening their suppression of the illegal opium trade. Incidents such as the destruction of opium at Humen led to the outbreak of the First Opium War between China and Britain in 1839; the 1842 Treaty of Nanking ending the war did not legalize the importation of opium into China, but Western merchants continued to smuggle the drug to Chinese merchants in ever-increasing amounts. The 1858 Treaty of Tianjin, which ended the Second Opium War, stipulated that the Qing government would open several ports to foreign trade, including opium.
Western governments began prohibiting addictive drugs during the late 19th and early 20th centuries. In 1868, as a result of the increased use of opium in Britain, the British government restricted the sale of opium by implementing the 1868 Pharmacy Act. In the United States, control of opium remained under the control of individual US states until the introduction of the Harrison Act in 1914, after 12 international powers signed the International Opium Convention in 1912. Between 1920 and c. 1933, the Eighteenth Amendment to the United States Constitution banned alcohol in the United States. Prohibition proved almost impossible to enforce and resulted in the rise of organized crime, including the modern American Mafia, which identified enormous business opportunities in the manufacturing, smuggling and sale of illicit liquor.
The beginning of the 21st century saw drug use increase in North America and Europe, with a particularly increased demand for marijuana and cocaine. As a result, international organized crime syndicates such as the Sinaloa Cartel and 'Ndrangheta have increased cooperation among each other in order to facilitate trans-Atlantic drug-trafficking. Use of another illicit drug, hashish, has also increased in Europe. Drug trafficking is widely regarded by lawmakers as a serious offense around the world. Penalties often depend on the type of drug (and its classification in the country into which it is being trafficked), the quantity trafficked, where the drugs are sold and how they are distributed. If the drugs are sold to underage people, then the penalties for trafficking may be harsher than in other circumstances.
Drug smuggling carries severe penalties in many countries. Sentencing may include lengthy periods of incarceration, flogging and even the death penalty (in Singapore, Malaysia, Indonesia and elsewhere). In December 2005, Van Tuong Nguyen, a 25-year-old Australian drug smuggler, was hanged in Singapore after being convicted in March 2004. In 2010, two people were sentenced to death in Malaysia for trafficking 1 kilogram (2.2 lb) of cannabis into the country. Execution is mostly used as a deterrent, and many have called upon much more effective measures to be taken by countries to tackle drug trafficking; for example, targeting specific criminal organisations that are often also active in the smuggling of other goods (i.e. wildlife) and even people. In many cases, links between politicians and the criminal organisations have been proven to exist. In June 2021, Interpol revealed an operation in 92 countries that shut down 113,000 websites and online marketplaces selling counterfeit or illicit medicines and medical products a month earlier, led to the arrests of 227 people worldwide, recovered pharmaceutical products worth $23 million, and led to the seizure of approximately nine million devices and drugs, including large quantities of fake COVID-19 tests and face masks.
== Societal effects ==
The countries of drug production and transit are some of the most affected by the trade, though countries receiving the illegally imported substances are also adversely affected. For example, Ecuador has absorbed up to 300,000 refugees from Colombia who are running from guerrillas, paramilitaries and drug lords. While some applied for asylum, others are still illegal immigrants. The drugs that pass from Colombia through Ecuador to other parts of South America create economic and social problems.
Honduras, through which an estimated 79% of cocaine passes on its way to the United States, had, as of 2011, the highest murder rate in the world. According to the International Crisis Group, the most violent regions in Central America, particularly along the Guatemala–Honduras border, are highly correlated with an abundance of drug trafficking activity.
=== Violent crime ===
In several countries, the illegal drug trade is thought to be directly linked to violent crimes such as murder and gun violence. This is especially true in all developing
countries, such as Honduras, but is also an issue for many developed countries worldwide. In the late 1990s in the United States, the Federal Bureau of Investigation estimated that 5% of murders were drug-related. In Colombia, drug violence can be caused by factors such as the economy, poor governments, and no authority within law enforcement.
After a crackdown by US and Mexican authorities in the first decade of the 21st century as part of tightened border security in the wake of the September 11 attacks, border violence inside Mexico surged. The Mexican government estimated that 90% of the killings were drug-related.
A report by the UK government's Drug Strategy Unit that was leaked to the press, stated that due to the expensive price of highly addictive drugs heroin and cocaine, drug use was responsible for the great majority of crime, including 85% of shoplifting, 70–80% of burglaries and 54% of robberies. It concluded "[t]he cost of crime committed to support illegal cocaine and heroin habits amounts to £16 billion a year in the UK"
== Drug trafficking routes ==
=== Africa ===
==== East and South ====
Heroin is increasingly trafficked from Afghanistan to Europe and America through eastern and southern African countries. This path is known as the "southern route" or "smack track". Repercussions of this trade include burgeoning heroin use and political corruption among intermediary African nations.
==== West ====
Cocaine produced in Colombia and Bolivia has increasingly been shipped via West Africa (especially in Nigeria, Cape Verde, Guinea-Bissau, Cameroon, Mali, Benin, Togo, and Ghana). The money is often laundered in countries such as Nigeria, Ghana, and Senegal.
According to the Africa Economic Institute, the value of illicit drug smuggling in Guinea-Bissau is almost twice the value of the country's GDP. Police officers are often bribed. A police officer's normal monthly wage of $93 is less than 2% of the value of 1 kilogram (2.2 lb) of cocaine (€7000 or $8750). The money can also be laundered using real estate. A house is built using illegal funds, and when the house is sold, legal money is earned. When drugs are sent over land, through the Sahara, the drug traders have been forced to cooperate with terrorist organizations, such as Al-Qaeda in Islamic Maghreb.
=== Asia ===
Drugs in Asia traditionally traveled the southern routes – the main caravan axes of Southeast Asia and Southern China – and include the former opium-producing countries of Thailand, Iran, and Pakistan. After the 1990s, particularly after the end of the Cold War (1991), borders were opened and trading and customs agreements were signed so that the routes expanded to include China, Central Asia, and Russia. There are, therefore, diversified drug trafficking routes available today, particularly in the heroin trade and these thrive due to the continuous development of new markets. A large amount of drugs are smuggled into Europe from Asia. The main sources of these drugs are Afghanistan, along with countries that constituted the so-called Golden Crescent. From these producers, drugs are smuggled into the West and Central Asia to its destinations in Europe and the United States. Iran is now a common route for smugglers, having been previously a primary trading route, due to its large-scale and costly war against drug trafficking. The Border Police Chief of Iran said that his country "is a strong barrier against the trafficking of illegal drugs to Caucasus, especially the Republic of Azerbaijan." The drugs produced by the Golden Triangle of Myanmar, Laos, and Thailand, on the other hand, pass through the southern routes to feed the Australian, US, and Asian markets.
=== South America ===
Venezuela has been a path to the United States and Europe for illegal drugs originating in Colombia, through Central America, Mexico and Caribbean countries such as Haiti, the Dominican Republic, and Puerto Rico.
According to the United Nations, cocaine trafficking through Venezuela increased from 2002 to 2008. In 2005, the government of Hugo Chávez severed ties with the United States Drug Enforcement Administration (DEA), accusing its representatives of spying. Following the departure of the DEA from Venezuela and the expansion of DEA's partnership with Colombia in 2005, Venezuela became more attractive to drug traffickers. Between 2008 and 2012, Venezuela's cocaine seizure ranking among other countries declined, going from being ranked fourth in the world for cocaine seizures in 2008 to sixth in the world in 2012.
On 18 November 2016, following what was known as the Narcosobrinos incident, Venezuelan President Nicolás Maduro's two nephews were found guilty of trying to ship drugs into the United States so they could "obtain a large amount of cash to help their family stay in power".
According to a research conducted by the Israel-based Abba Eban Institute as part of an initiative called Janus Initiative, the main routes that Hezbollah uses for smuggling drugs are from Colombia, Venezuela and Brazil into West Africa and then transported through northern Africa into Europe. This route serves Hezbollah in making a profit in the cocaine smuggling market in order to leverage it for their activities.
== Online trafficking ==
Drugs are increasingly traded online on the dark web on darknet markets. Internet-based drug trafficking is the global distribution of narcotics, making extensive use of technology. Similarly, the use of the Internet for the illegal trafficking of two controlled categories of drugs can also be identified as Internet-related drug trafficking. The platform Silk Road provided goods and services to 100,000 buyers before being shut down in October 2013. This prompted the creation of new platforms such as Silk Road 2.0, which were also shut down.
== Profits ==
Statistics about profits from the drug trade are largely unknown due to its illicit nature. An online report published by the UK Home Office in 2007 estimated the illicit drug market in the UK at £4–6.6 billion a year.
In December 2009, United Nations Office on Drugs and Crime Executive Director Antonio Maria Costa claimed illegal drug money saved the banking industry from collapse. He claimed he had seen evidence that the proceeds of organized crime were "the only liquid investment capital" available to some banks on the brink of collapse during 2008. He said that a majority of the $352 billion (£216bn) of drug profits was absorbed into the economic system as a result: "In many instances, the money from drugs was the only liquid investment capital. In the second half of 2008, liquidity was the banking system's main problem and hence liquid capital became an important factor ... Inter-bank loans were funded by money that originated from the drugs trade and other illegal activities...there were signs that some banks were rescued that way".
Costa declined to identify countries or banks that may have received any drug money, saying that would be inappropriate because his office is supposed to address the problem, not apportion blame.
Though street-level drug sales are widely viewed as lucrative, a study by Sudhir Venkatesh suggested that many low-level employees receive low wages. In a study he made in the 1990s working closely with members of the Black Gangster Disciple Nation in Chicago, he found that one gang (essentially a franchise) consisted of a leader (a college graduate named J.T.), three senior officers, and 25 to 75 street level salesmen ('foot soldiers') depending on season. Selling crack cocaine, they took in approximately $32,000 per month over a six-year period. This was spent as follows: $5,000 to the board of twenty directors of the Black Gangster Disciple Nation, who oversaw 100 such gangs for approximately $500,000 in monthly income. Another $5,000 monthly was paid for cocaine, and $4,000 for other non-wage expenses. J.T. took $8,500 monthly for his own salary. The remaining $9,500 monthly went to pay the employees a $7 per hour wage for officers and a $3.30 per hour wage for foot soldiers. Contrary to a popular image of drug sales as a lucrative profession, many of the employees were living with their mothers by necessity. Despite this, the gang had four times as many unpaid members who dreamed of becoming foot soldiers.
== Impact of free trade ==
There are several arguments on whether or not free trade has a correlation to an increased activity in the illicit drug trade. Currently, the structure and operation of the illicit drug industry is described mainly in terms of an international division of labor. Free trade can open new markets to domestic producers who would otherwise resort to exporting illicit drugs. Additionally, extensive free trade among states increases cross-border drug enforcement and coordination between law enforcement agencies in different countries. However, free trade also increases the sheer volume of legal cross-border trade and provides cover for drug smuggling—by providing ample opportunity to conceal illicit cargo in legal trade. While international free trade continues to expand the volume of legal trade, the ability to detect and interdict drug trafficking is severely diminished. Towards the late 1990s, the top ten seaports in the world processed 33.6 million containers. Free trade has fostered integration of financial markets and has provided drug traffickers with more opportunities to launder money and invest in other activities. This strengthens the drug industry while weakening the efforts of law enforcement to monitor the flow of drug money into the legitimate economy. Cooperation among cartels expands their scope to distant markets and strengthens their abilities to evade detection by local law enforcement. Additionally, criminal organizations work together to coordinate money-laundering activities by having separate organizations handle specific stages of laundering process. One organization structures the process of how financial transactions will be laundered, while another criminal group provides the "dirty" money to be cleaned. By fostering expansion of trade and global transportation networks, free trade encourages cooperation and formation of alliances among criminal organizations across different countries.
The drug trade in Latin America emerged in the early 1930s. It saw significant growth in the Andean countries, including Peru, Bolivia, Chile, Ecuador, Colombia and Venezuela. The underground market in the early half of the 20th century mainly had ties to Europe. After World War II, the Andean countries saw an expansion of trade, specifically with cocaine.
== Drug trafficking by country ==
=== Syria ===
The Ba'athist government of Syria ruled by the Al-Assad family is known for its extensive involvement in drug trade since the 1970s. As of 2022, the Syrian government financed the biggest multi-billion dollar drug trade in the world, mostly focused on an illegal drug known as Captagon, making it the world's largest narco-state. Its revenues from Captagon smuggling alone is estimated to worth 57 billion dollars annually in 2022, which is approximately thrice the total trade of all Mexican cartels. General Maher al-Assad, younger brother of Syrian dictator Bashar al-Assad and commander of the Fourth Armoured Division, directly supervised the production, smuggling and profiteering of the drug business. Already suffering from severe financial problems as a result of corruption and civil war, profits from Captagon are said to be the "lifeline" of the Assad regime, through which it earned more than 90% of its total revenue. The smugglers receive direct training from Syrian military to successfully conduct trafficking operations.
Republican Guard, commanded by Maher al-Assad was one of the main Ba'athist military divisions that was engaged in perpetrating brutal crackdowns and mass violence against protestors across the country. In 2018, Bashar al-Assad assigned Maher as the commander of the 4th Armoured Division, a military unit that supervised the Assad regime's criminal enterprises like smuggling, drug trafficking, narcotics production and plunder of goods and resources. Under Maher's supervision, the 4th Armoured Division expanded captagon production and trafficking from Syria into a "business model controlled by the regime".
In 2022, 90% of all captagon pills manufactured in Syria exported by drug cartels affiliated with Assad regime arrived at its customer destinations across the world. Although hundreds of millions of pills were intercepted and seized by police forces, these accounted only for 10% of the total captagon exports of the drug cartels linked to the Assad regime. In 2020, Italian police seized 84 million captagon pills originating from Syrian ports while intercepting a single shipment. In June 2023, US State Department's Bureau of Near Eastern Affairs published a detailed report to the US Congress, elucidating a strategy to eliminate the narcotics production, drug trafficking and drug cartel networks affiliated with the Assad regime and Hezbollah.
A joint investigation conducted by Organized Crime and Corruption Reporting Project (OCCRP) and BBC News Arabic published a documentary in June 2023, revealing further details about the activities of regime officials, Ba'athist military commanders and Assad family members in their involvement in Syria's drug cartel. The investigation found that Lebanese criminal and drug kingpin Hassan Daqou collaborated with Syria's Fourth Armoured Division on trafficiking billions of dollars of drugs, under the command of General Ghassan Bilal, the right-hand man of Maher al-Assad. The report also unearthed Hezbollah's close participation in the drug production and smuggling networks. The Fourth Armoured Division, being an elite military unit permitted to move freely across Assad regime's checkpoints, oversees the smuggling operations from Syria, including the trafficking of cash, weapons, illegal drugs, etc. Days after the publication of the joint BBC-OCCRP documentary; Assad government banned all activities of BBC media outlets and entry of affiliated media personnel in Syria.
The extensive involvement of Syrian Armed Forces in sponsorship of drug production and trade has led to pervasive drug addiction problems amongst pro-Assad soldiers. In many instances, military officials encourage the soldiers to consume Captagon and other illegal drugs, leading to overdose or drug abuse. Pro-Assad fighters in the National Defence Forces and Hezbollah also consume illegal drugs in large quantities. In July 2023, German police busted a major captagon network run by two Syrian-born men in southern German state of Bavaria. Assad regime sponsors the largest Captagon production network in Syria; which is the source of about 80% of total captagon supply in the world.
In an investigative report published by The Insider news-outlet in 2024, journalist Yuriy Matsarsky stated:"...Captagon produced in underground labs—and in actual Syrian pharmaceutical facilities—is distributed to the fighters of Bashar Assad's army. Interestingly, however, the quantities the country produces far exceed its own military’s demand. ... By some estimates, this business gives Syria more money than its entire legal export, and the regime constantly works to increase its profits, primarily by expanding its market reach. To this end, criminal gangs associated with Damascus or Hezbollah have built distribution networks for Captagon in countries where the drug was not previously popular."
=== United States ===
==== Background ====
The effects of the illegal drug trade in the United States can be seen in a range of political, economic and social aspects. Increasing drug related violence can be tied to the racial tension that arose during the late 20th century along with the political upheaval prevalent throughout the 1960s and 70s. The second half of the 20th century was a period when increased wealth, and increased discretionary spending, increased the demand for illicit drugs in certain areas of the United States. Large-scale drug trafficking is one of the capital crimes, and may result in a death sentence prescribed at the federal level when it involves murder.
==== Political impact ====
A large generation, the baby boomers, came of age in the 1960s. Their social tendency to confront the law on specific issues, including illegal drugs, overwhelmed the understaffed judicial system. The federal government attempted to enforce the law, but with meager effect.
Marijuana was a popular drug seen through the Latin American trade route in the 1960s. Cocaine became a major drug product in the later decades. Much of the cocaine is smuggled from Colombia and Mexico via Jamaica. This led to several administrations combating the popularity of these drugs. Due to the influence of this development on the US economy, the Reagan administration began "certifying" countries for their attempts at controlling drug trafficking. This allowed the United States to intervene in activities related to illegal drug transport in Latin America. Continuing into the 1980s, the United States instated stricter policy pertaining to drug transit through sea. As a result, there was an influx in drug-trafficking across the Mexico–US border, which increased the drug cartel activity in Mexico.
By the early 1990s, so much as 50% of the cocaine available in the United States market originated from Mexico, and by the 2000s, over 90% of the cocaine in the United States was imported from Mexico. In Colombia, however, there was a fall of the major drug cartels in the mid-1990s. Visible shifts occurred in the drug market in the United States. Between 1996 and 2000, US cocaine consumption dropped by 11%.
In 2008, the US government initiated another program, known as the Merida Initiative, to help combat drug trafficking in Mexico. This program increased US security assistance to $1.4 billion over several years, which helped supply Mexican forces with "high-end equipment from helicopters to surveillance technology". Despite US aid, Mexican "narcogangs" continue to outnumber and outgun the Mexican Army, allowing for continued activities of drug cartels across the US–Mexico border.
==== Social impacts ====
Although narcotics are illegal in the US, they have become integrated into the nation's culture and are seen as a recreational activity by sections of the population. Illicit drugs are considered to be a commodity with strong demand, as they are typically sold at a high value. This high price is caused by a combination of factors that include the potential legal ramifications that exist for suppliers of illicit drugs and their high demand. Despite the constant effort by politicians to win the war on drugs, the US is still the world's largest importer of illegal drugs.
Throughout the 20th century, narcotics other than cocaine also crossed the Mexican border, meeting the US demand for alcohol during the 1920s Prohibition, opiates in the 1940s, marijuana in the 1960s, and heroin in the 1970s. Most of the US imports of drugs come from Mexican drug cartels. In the United States, around 195 cities have been infiltrated by drug trafficking that originated in Mexico. An estimated $10bn of the Mexican drug cartel's profits come from the United States, not only supplying the Mexican drug cartels with the profit necessary for survival, but also furthering America's economic dependence on drugs.
===== Demographics =====
With a large wave of immigrants in the 1960s and onwards, the United States saw an increased heterogeneity in its public. In the 1980s and 1990s, drug-related homicide was at a record high. This increase in drug violence became increasingly tied to these ethnic minorities. Though the rate of violence varied tremendously among cities in America, it was a common anxiety in communities across urban America. An example of this could be seen in Miami, a city with a host of ethnic enclaves. Between 1985 and 1995, the homicide rate in Miami was one of the highest in the nation—four times the national homicide average. This crime rate was correlated with regions with low employment and was not entirely dependent on ethnicity.
The baby boomer generation also felt the effects of the drug trade in their increased drug use from the 1960s to 1980s. Along with substance use, criminal involvement, suicide and murder were also on the rise. Due to the large amount of baby boomers, commercial marijuana use was on the rise. This increased the supply and demand for marijuana during this time period.
=== Mexico ===
==== Political influences ====
Corruption in Mexico has contributed to the domination of Mexican cartels in the illicit drug trade. Since the beginning of the 20th century, Mexico's political environment allowed the growth of drug-related activity. The loose regulation over the transportation of illegal drugs and the failure to prosecute known drug traffickers and gangs increased the growth of the drug industry. Toleration of drug trafficking has undermined the authority of the Mexican government and has decreased the power of law enforcement officers in regulation over such activities. These policies of tolerance fostered the growing power of drug cartels in the Mexican economy and have made drug traders wealthier. Many states in Mexico lack policies that establish stability in governance. There also is a lack of local stability, as mayors cannot be re-elected. This requires electing a new mayor each term. Drug gangs have manipulated this, using vacuums in local leadership to their own advantage.
In 1929, the Institutional Revolutionary Party (PRI) was formed to resolve the chaos resulting from the Mexican Revolution. Over time, this party gained political influence and had a major impact on Mexico's social and economic policies. The party created ties with various groups as a power play in order to gain influence, and as a result created more corruption in the government. One such power play was an alliance with drug traffickers. This political corruption obscured justice, making it difficult to identify violence when it related to drugs. By the 1940s, the tie between the drug cartels and the PRI had solidified. This arrangement created immunity for the leaders of the drug cartels and allowed drug trafficking to grow under the protection of the government officials.
During the 1990s, the PRI lost some elections to the new National Action Party (PAN). Chaos again emerged as elected government in Mexico changed drastically. As the PAN party took control, drug cartel leaders took advantage of the ensuing confusion and used their existing influence to further gain power. Instead of negotiating with the central government as was done with the PRI party, drug cartels utilized new ways to distribute their supply and continued operating through force and intimidation. As Mexico became more democratized, the corruption fell from a centralized power to the local authorities. Cartels began to bribe local authorities, thus eliminating the structure and rules placed by the government—giving cartels more freedom. As a response, Mexico saw an increase in violence caused by drug trafficking.
The corruption cartels created resulted in distrust of government by the Mexican public. This distrust became more prominent after the collapse of the PRI party. In response, the presidents of Mexico, in the late twentieth century and early twenty-first century, implemented several different programs relating to law enforcement and regulation. In 1993, President Salinas created the National Institute for the Combat of Drugs in Mexico. From 1995 to 1998, President Zedillo established policies regarding increased punishment of organized crime, allowing "[wire taps], protected witnesses, covert agents and seizures of goods", and increasing the quality of law enforcement at the federal level. From 2001 to 2005, President Vicente Fox created the Federal Agency of Investigation.
These policies resulted in the arrests of major drug-trafficking bosses:
==== Mexico's economy ====
Over the past few decades, drug cartels have become integrated into Mexico's economy. Approximately 500 cities are directly engaged in drug trafficking and nearly 450,000 people are employed by drug cartels. Additionally, the livelihood of 3.2 million people is dependent on the drug cartels. Between local and international sales, such as to Europe and the United States, drug cartels in Mexico see a $25–30 bn yearly profit, a great deal of which circulates through international banks such as HSBC. Drug cartels are fundamental in local economics. A percentage of the profits seen from the trade are invested in the local community. Such profits contribute to the education and healthcare of the community. While these cartels bring violence and hazards into communities, they create jobs and provide income for its many members.
==== Culture of drug cartels ====
Major cartels saw growth due to a prominent set culture of Mexican society that created the means for drug capital. One of the sites of origin for drug trafficking within Mexico, was the state of Michoacán. In the past, Michoacán was mainly an agricultural society. This provided an initial growth of trade. Industrialization of rural areas of Mexico facilitated a greater distribution of drugs, expanding the drug market into different provinces. Once towns became industrialized, cartels such as the Sinaloa Cartel started to form and expand. The proliferation of drug cartel culture largely stemmed from the ranchero culture seen in Michoacán. Ranchero culture values the individual as opposed to the society as a whole. This culture fostered the drug culture of valuing the family that is formed within the cartel. This ideal allowed for greater organization within the cartels.
Gangs play a major role in the activity of drug cartels. MS-13 and the 18th Street gang are notorious for their contributions and influence over drug trafficking throughout Latin America. MS-13 has controlled much of the activity in the drug trade spanning from Mexico to Panama. Female involvement is present in the Mexican drug culture. Although females are not treated as equals to males, they typically hold more power than their culture allows and acquire some independence. The increase in power has attracted females from higher social classes. Financial gain has also prompted women to become involved in the illegal drug market. Many women in the lower levels of major drug cartels belong to a low economic class. Drug trafficking offers women an accessible way to earn income. Females from all social classes have become involved in the trade due to outside pressure from their social and economic environments.
=== Colombia ===
==== Political ties ====
It was common for smugglers in Colombia to import liquor, alcohol, cigarettes and textiles, while exporting cocaine. Personnel with knowledge of the terrain were able to supply the local market while also exporting a large amount of product. The established trade initially involved Peru, Bolivia, Colombia, Venezuela and Cuba. Peasant farmers produced coca paste in Peru and Bolivia, while Colombian smugglers would process the coca paste into cocaine in Colombia, and trafficked product through Batista's Cuba. This trade route established ties between Cuban and Colombian organized crime.
From Cuba, cocaine would be transported to Miami, Florida; and Union City, New Jersey. Quantities of the drug were then smuggled throughout the US. The international drug trade created political ties between the involved countries, encouraging the governments of the countries involved to collaborate and instate common policies to eradicate drug cartels. Cuba stopped being a center for transport of cocaine following the Cuban Revolution and the establishment of Fidel Castro's communist government in 1959.
As a result, Miami and Union City became the sole locations for trafficking. The relations between Cuban and Colombian organized crime remained strong until the 1970s, when Colombian cartels began to vie for power. In the 1980s and 90s, Colombia emerged as a key contributor of the drug trade industry in the Western Hemisphere. While the smuggling of drugs such as marijuana, poppy, opium and heroin became more ubiquitous during this time period, the activity of cocaine cartels drove the development of the Latin American drug trade. The trade emerged as a multinational effort as supplies (i.e. coca plant substances) were imported from countries such as Bolivia and Peru, were refined in Colombian cocaine labs and smuggled through Colombia, and exported to countries such as the US.
==== Colombia's economy ====
Colombia has had a significant role in the illegal drug trade in Latin America. While active in the drug trade since the 1930s, Colombia's role in the drug trade did not truly become dominant until the 1970s. When Mexico eradicated marijuana plantations, demand stayed the same. Colombia met much of the demand by growing more marijuana. Grown in the strategic northeast region of Colombia, marijuana soon became the leading cash crop in Colombia. This success was short-lived due to anti-marijuana campaigns that were enforced by the US military throughout the Caribbean. Instead, drug traffickers in Colombia continued their focus on exporting cocaine.
Having been an export of Colombia since the early 1950s, cocaine remained popular for a host of reasons. Colombia's location facilitated its transportation from South America into Central America, and then to its destination of North America. This continued into the 1990s, when Colombia remained the chief exporter of cocaine. The business of drug trafficking can be seen in several stages in Colombia towards the latter half of the 20th century. Colombia served as the dominant force in the distribution and sale of cocaine by the 1980s. As drug producers gained more power, they became more centralized and organized into what became drug cartels.
Cartels controlled the major aspects of each stage in the traffic of their product. Their organization allowed cocaine to be distributed in great amounts throughout the United States. By the late 1980s, intra-industry strife arose within the cartels. This stage was marked by increased violence as different cartels fought for control of export markets. Despite this strife, this power struggle led to then having multiple producers of coca leaf farms. This in turn caused an improvement in quality control and reduction of police interdiction in the distribution of cocaine. This also led to cartels attempting to repatriate their earnings which would eventually make up 5.5% of Colombia's GDP. This drive to repatriate earnings led to the pressure of legitimizing their wealth, causing an increase in violence throughout Colombia.
Throughout the 1980s, estimates of illegal drug value in Colombia ranged from $2bn to $4bn. This made up about 7–10% of the $36bn estimated Gross National Product (GNP) of Colombia during this decade. In the 1990s, the estimates of the illegal drug value remained roughly within the same range (~$2.5bn). As the Colombian GNP rose throughout the 1990s ($68.5bn in 1994 and $96.3bn in 1997), illegal drug values began to comprise a decreasing fraction of the national economy.
By the early 1990s, although Colombia led in the exportation of cocaine, it found increasing confrontations within its state. These confrontations were primarily between cartels and government institutions. This led to a decrease in the drug trade's contribution to the GDP of Colombia; dropping from 5.5% to 2.6%. Though a contributor of wealth, the distribution of cocaine has had negative effects on the socio-political situation of Colombia and has weakened its economy as well.
==== Social impacts ====
By the 1980s, Colombian cartels became the dominant cocaine distributors in the US. This led to the spread of increased violence throughout both Latin America and Miami. In the 1980s, two major drug cartels emerged in Colombia: the Medellín and Cali groups.
Throughout the 1990s however, several factors led to the decline of these major cartels and to the rise of smaller Colombian cartels. The US demand for cocaine dropped while Colombian production rose, pressuring traffickers to find new drugs and markets. In this time period, there was an increase in activity of Caribbean cartels that led to the rise of an alternate route of smuggling through Mexico. This led to the increased collaboration between major Colombian and Mexican drug traffickers. Such drastic changes in the execution of drug trade in Colombia paired with the political instabilities and rise of drug wars in Medellin and Cali, gave way for the rise of the smaller Colombian drug trafficking organizations (and the rise of heroin trade). As the drug trade's influence over the economy increased, drug lords and their networks grew in their power and influence in society. The occurrences in drug-related violence increased during this time period as drug lords fought to maintain their control in the economy.
Typically, a drug cartel had support networks that consisted of a number of individuals. These people individuals ranged from those directly involved in the trade (such as suppliers, chemists, transporters, smugglers, etc.) as well as those involved indirectly in the trade (such as politicians, bankers, police, etc.). As these smaller Colombian drug cartels grew in prevalence, several notable aspects of the Colombian society gave way for further development of the Colombian drug industry. For example, until the late 1980s, the long-term effects of the drug industry were not realized by much of society. Additionally, there was a lack of regulation in prisons where captured traffickers were sent. These prisons were under-regulated, under-funded, and under-staffed, which allowed for the formation of prison gangs, for the smuggling of arms/weapons/etc., for feasible escapes, and even for captured drug lords to continue running their businesses from prison.
=== Western Balkans ===
Since the beginning of the 21st century, the global drug trade network witnessed the emergence of criminal groups from the Western Balkans as crucial players. These groups have moved up from being small-time crooks to major drug distributors. Most of these organized crime groups belonged to Albania, Bosnia and Herzegovina, Kosovo, Montenegro, North Macedonia and Serbia. The illicit trade activities of the Balkans primarily involved Latin America, Western Europe, South Africa, Australia and Turkey. These groups keep their operations outside the Western Balkans, while staying connected to their homeland. Within the network of these groups, the dealmakers operate in a proximity of supply sources and the distribution networks are managed by foot soldiers. However, the bosses of the organized criminal groups stay and keep their wealth in the United Arab Emirates (UAE). The UAE is amongst the enablers of global corruption and illicit financial flows. Analysts have claimed that criminal actors across the world either operate from or through the Emirates. It was a haven for criminals, where the risk for illicit activities remains low.
For the Balkan criminals, a growing trend was to relocate to the UAE, which became an attraction to dirty money and kingpins from several European nations and the United Kingdom. Besides, Dubai was also dubbed as the "new Costa del Crime", replacing the crime hideaway of Spain, the Costa del Sol. The UAE had poor regulations for money laundering and for screening of suspicious transactions. The lack of regulations against illicit financial activities prompted the Financial Action Task Force (FATF) to place the Gulf country on its grey list in March 2022. Consequently, the Emirates' remained a safe option for the criminals. Nearly two-thirds of the Albanian criminal groups, who were active in trade of drugs like cocaine, were believed to be hiding in the UAE. One of such individuals, Eldi Dizdari was accused of international drug trafficking and was living in Dubai. Research revealed that these criminals invested huge amounts in the Emirates' real estate and other economical sectors to live there. Another trafficker of cocaine from Bosnia, Edin Gačanin was living in the UAE using his extensive profits to buy property and protection in the country. Dubbed as the "European Escobar", he connected the supply network between production markets of Latin America and consumer markets of Western European. He was able to evade the arrest and investigations, including by the US Drug Enforcement Administration, by seeking shelter in the Emirates.
== Trade in specific drugs ==
=== Cannabis ===
While the recreational use of (and consequently the distribution of) cannabis is illegal in most countries throughout the world, recreational distribution is legal in some countries, such as Canada, and medical distribution is permitted in some places, such as 38 of the 50 US states (although importation and distribution is still federally prohibited). Beginning in 2014, Uruguay became the first country to legalize cultivation, sale, and consumption of cannabis for recreational use for adult residents. In 2018, Canada became the second country to legalize use, sale and cultivation of cannabis. The first few weeks were met with extremely high demand, most shops being out of stock after operating for only four days.
Cannabis use is tolerated in some areas, most notably the Netherlands, which has legalized the possession and licensed sale (but not cultivation) of the drug. Many nations have decriminalized the possession of small amounts of marijuana. Due to the hardy nature of the cannabis plant, marijuana is grown all across the world; today, it is the world's most popular illegal drug with the highest level of availability. Cannabis is grown legally in many countries for industrial, non-drug use (known as hemp) as well. Cannabis-hemp may also be planted for other non-drug domestic purposes, such as seasoning that occurs in Aceh.
The demand for cannabis around the world, coupled with the drug's relative ease of cultivation, makes the illicit cannabis trade one of the primary ways in which organized criminal groups finance many of their activities. In Mexico, for example, the illicit trafficking of cannabis is thought to constitute the majority of many of the cartels' earnings, and the main way in which the cartels finance many other illegal activities; including the purchase of other illegal drugs for trafficking, and for acquiring weapons that are ultimately used to commit murders (causing a burgeoning in the homicide rates of many areas of the world, but particularly Latin America).
Some studies show that the increased legalization of cannabis in the United States (beginning in 2012 with Washington Initiative 502 and Colorado Amendment 64) has led Mexican cartels to smuggle less cannabis in exchange for more heroin.
=== Alcohol ===
Alcohol, in the context of alcoholic beverages rather than denatured alcohol, is illegal in a number of Muslim countries, such as Saudi Arabia; this has resulted in a thriving illegal trade in alcohol. The manufacture, sale, transportation, import, and export of alcoholic beverages were illegal in the United States during the time known as the Prohibition in the 1920s and early 1930s.
=== Heroin ===
In the 1950s and 1960s, most heroin was produced in Turkey and transshipped in France via the French Connection crime ring, with much of it arriving in the United States. This resulted in the record setting April 26, 1968 seizure of 246 lb (111.6 kg) of heroin smuggled in a vehicle on the SS France (1960) ocean liner. By the time of The French Connection (1971 film), this route was being supplanted.
Then, until c. 2004, the majority of the world's heroin was produced in an area known as the Golden Triangle. However, by 2007, 93% of the opiates on the world market originated in Afghanistan. This amounted to an export value of about US$4 billion, with a quarter being earned by opium farmers and the rest going to district officials, insurgents, warlords and drug traffickers. Another significant area where poppy fields are grown for the manufacture of heroin is Mexico. In November 2023, a U.N report showed that in the entirety of Afghanistan, poppy cultivation dropped by over 95%, removing it from its place as being the world's largest opium producer.
According to the United States Drug Enforcement Administration, the price of heroin is typically valued 8 to 10 times that of cocaine on American streets, making it a high-profit substance for smugglers and dealers. In Europe (except the transit countries Portugal and the Netherlands), for example, a purported gram of street heroin, usually consisting of 700–800 mg of a light to dark brown powder containing 5–10% heroin base, costs €30–70, making the effective value per gram of pure heroin €300–700. Heroin is generally a preferred product for smuggling and distribution—over unrefined opium due to the cost-effectiveness and increased efficacy of heroin.
Because of the high cost per volume, heroin is easily smuggled. A US quarter-sized (2.5 cm) cylindrical vial can contain hundreds of doses. From the 1930s to the early 1970s, the so-called French Connection supplied the majority of US demand. Allegedly, during the Vietnam War, drug lords such as Ike Atkinson used to smuggle hundreds of kilograms of heroin to the US in coffins of dead American soldiers (see Cadaver Connection). Since that time it has become more difficult for drugs to be imported into the US than it had been in previous decades, but that does not stop the heroin smugglers from getting their product across US borders. Purity levels vary greatly by region with Northeastern cities having the most pure heroin in the United States. On 17 October 2018 police in Genoa, Italy discovered 270 kg (600 lb) of heroin hidden in a ship coming from the Iranian southern port of Bandar Abbas. The ship had already passed and stopped at Hamburg in Germany and Valencia in Spain.
Penalties for smuggling heroin or morphine are often harsh in most countries. Some countries will readily hand down a death sentence (e.g. Singapore) or life in prison for the illegal smuggling of heroin or morphine, which are both internationally Schedule I drugs under the Single Convention on Narcotic Drugs.
In May 2021, Romania seized 1.4 tonnes of heroin at Constanța port of a shipment from Iran that was headed for Western Europe.
=== Methamphetamine ===
Methamphetamine is another popular drug among distributors. Three common street names are "meth", "crank", and "ice".
According to the Community Epidemiology Work Group, the number of clandestine methamphetamine laboratory incidents reported to the National Clandestine Laboratory Database decreased from 1999 to 2009. During this period, methamphetamine lab incidents increased in mid-western States (Illinois, Michigan, Missouri, and Ohio), and in Pennsylvania. In 2004, more lab incidents were reported in Missouri (2,788) and Illinois (1,058) than in California (764). In 2003, methamphetamine lab incidents reached new highs in Georgia (250), Minnesota (309), and Texas (677). There were only seven methamphetamine lab incidents reported in Hawaii in 2004, though nearly 59 percent of substance use treatment admissions (excluding alcohol) were for primary methamphetamine use during the first six months of 2004. As of 2007, Missouri leads the United States in drug-lab seizures, with 1,268 incidents reported. Often canine units are used for detecting rolling meth labs which can be concealed on large vehicles, or transported on something as small as a motorcycle. These labs are more difficult to detect than stationary ones, and can often be obscured among legal cargo in big trucks.
Methamphetamine is sometimes used intravenously, placing users and their partners at risk for transmission of HIV and hepatitis C. "Meth" can also be inhaled, most commonly vaporized on aluminum foil or in a glass pipe. This method is reported to give "an unnatural high" and a "brief intense rush".
In South Africa, methamphetamine is called "tik" or "tik-tik". Known locally as "tik", the substance was virtually unknown as late as 2003. Now, it is the country's main addictive substance, even when alcohol is included. Children as young as eight are abusing the substance, smoking it in crude glass vials made from light bulbs. Since methamphetamine is easy to produce, the substance is manufactured locally in staggering quantities.
The government of North Korea currently operates methamphetamine production facilities. There, the drug is used as medicine because no alternatives are available; it also is smuggled across the Chinese border.
The Australian Crime Commission's illicit drug data report for 2011–2012 stated that the average strength of crystal methamphetamine doubled in most Australian jurisdictions within a 12-month period, and the majority of domestic laboratory closures involved small "addict-based" operations.
=== Temazepam ===
Temazepam, a strong hypnotic benzodiazepine, is illicitly manufactured in clandestine laboratories (called jellie labs) to supply the increasingly high demand for the drug internationally. Many clandestine temazepam labs are in Eastern Europe. The labs manufacture temazepam by chemically altering diazepam, oxazepam or lorazepam. "Jellie labs" have been identified and shut down in Russia, Ukraine, Latvia and Belarus.
=== Cocaine ===
Cocaine is a highly trafficked drug. In 2017 the value of the global market for illicit cocaine was estimated at between $94 and $143 billion. In 2022, illicit sales in Europe were estimated at $11.1 billion. In 2020, almost 2,000 tons of cocaine were produced for distribution through illicit markets.
=== Fentanyl ===
Fentanyl, a synthetic opioid, is 20 to 40 times more potent than heroin and 100 times more potent than morphine; its primary clinical utility is in pain management for cancer patients and those recovering from painful surgeries. Illicit use of fentanyl continues to fuel an epidemic of synthetic opioid drug overdose deaths in the US. From 2011 to 2021, synthetic opioid deaths per year increased from 2,600 overdoses to 70,601. Since 2018, fentanyl and its analogues have been responsible for most drug overdose deaths in the US, causing over 71,238 deaths in 2021. Fentanyl is often mixed, cut, or ingested alongside other drugs, including cocaine and heroin. The fentanyl epidemic has erupted in a highly acrimonious dispute between the US and Mexican governments. While US officials blame the flood of fentanyl crossing the border primarily on Mexican crime groups, President Andrés Manuel López Obrador insists that the main source of this synthetic drug is Asia. He believes that the crisis of a lack of family values in the US drives people to use the drug.
== See also ==
Allegations of CIA drug trafficking
Arguments for and against drug prohibition
Corruption
Counterfeit medications
Counterfeit money
Environmental impact of illicit drug production
Rum running
Illicit cigarette trade
Human trafficking
Arms trafficking
Wildlife trafficking
Illegal organ trade
Drug liberalization
Drug trafficking organizations
Golden Crescent
Golden Triangle (Southeast Asia)
Illegal drug trade in the Indian Ocean region
Maritime drug smuggling into Australia
Narco-capitalism
Narco-state
Narcoterrorism
Organized crime
Operation Show Me How
=== International coordination ===
International Day Against Drug Abuse and Illicit Trafficking
Interpol
United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances
== References ==
== External links ==
Official website of the United Nations Office on Drugs and Crime (UNODC)
Illicit drug issues by country, by the CIA. Archived 2010-12-29 at the Wayback Machine. | Wikipedia/Illegal_drug_trade |
Opioid agonist therapy (OAT) is a treatment in which prescribed opioid agonists are given to patients who live with opioid use disorder (OUD). In the case of methadone maintenance treatment (MMT), methadone is used to treat dependence on heroin or other opioids, and is administered on an ongoing basis.
The benefits of this treatment include a more manageable withdrawal experience, cognitive improvement, and lower HIV transmission. The length of OAT varies from one individual to another based on their physiology, environmental surroundings, and quality of life.
The term medication for Opioid Use Disorder (MOUD) is used to describe medication including methadone and buprenorphine, which are used to treat patients with OUD.
== Terminology ==
Other terms that appear in the professional and popular literature include opioid replacement therapy, medication-assisted treatment (MAT) and medications for opioid use disorder (MOUD).
== Biological understanding ==
An opioid is considered a ligand, which is an ion or a molecule. An opioid ligand travels to the brain and attaches itself to an opioid receptor, which begins the effects of opioids. The mesolimbic system, which is the biological system that moderates the feeling of reward generated by dopamine, is the main system that is effected by opioids. Opioids stimulate the mesolimbic system to release a large amount of dopamine in the brain, which increases the effects of opioids: euphoria and numbness. The difference between an opioid and an opioid agonist is that opioids induce more intense effects and stay in the brain for a short amount of time. Conversely, an opioid agonist induces minimal effects and stays in the brain for a long time, which prevents the opioid user from feeling the effects of natural or synthetic opioids. However, the opioid receptors are still being used when an opioid agonist attaches, which prevents the effects of opioid withdrawal and can help prevent relapse. The two most common opioid agonists are methadone and buprenorphine.
== Methadone ==
Methadone is an opioid agonist that binds to the same receptors in the brain as heroin and other opioids. Introduced as an analgesic in the US in 1947, methadone has been used in maintenance treatment—also known as substitution treatment, or drug replacement therapy—since 1964. Methadone treatments usually last for multiple years, although they can last for decades. A dose of methadone often minimizes the effects of withdrawal for approximately 24 hours and the lowest optimal dose is 60 mg. Methadone functions via competitive antagonism; while the prescribed agonist is in the opioid user's body, the use of illicit opioids (illicit heroin or fentanyl) will not produce the effects of illicit opioids. Methadone has a slower onset than illicit opioids and it produces less effects than illicit opioids. Side effects of methadone may include "constipation, weight gain, reduced libido, and irregular menses".(p. 467)
Methadone maintenance reduces the cravings for other opioids, and reduces the risk of fatal overdose from street drugs since the purity and strength of methadone is known, whereas substances obtained from the street vary significantly in strength and purity.
Therapeutic dosing is contingent upon individual patient needs, with a dosage range generally between 20 and 200 mg. Doses are unsafe for opioid-naive individuals, and administration of methadone is gradually increased to reach a therapeutic dose under medical supervision to reduce the risk of overdose. The amount of oral methadone a patient will require is dependent on the amount and power of opioids they consumed prior to initiating treatment, with an assessment in the mid-2000s (prior to the widespread introduction of fentanyl into street heroin supplies in the US) finding that 1 gram of street heroin is roughly equivalent to 50 to 80 mg of methadone. Methadone is taken either orally as a mixture of 1 mg/1ml supplied as a red or clear liquid, or as a mixture containing 10 mg of methadone in 1ml of liquid (green color) or 20 mg in 1ml of liquid (brown color). The latter is often used when a person is on a large amount of methadone, and is rarely permitted for unsupervised consumption. Since the formulations are not as viscous as the 1 mg/1ml mixture, they are more prone to misuse since they are easier to inject, and due to the high risk of overdose if diverted to an individual not accustomed to such a large dose. Methadone also comes in 40 mg dispersible tablets called "diskettes", as well as 5 and 10 mg pills that are round or "coffin" shaped. These pills are only given in hospital settings. Methadone can also be delivered by either IV or IM injection, as well as ampoules which come in various strengths ranging from 10 mg up to 50 mg. This method is often used for individuals who have a "needle fixation" and who would otherwise revert to using IV heroin.
With the emergence of other medications for the treatment of opioid addiction such as buprenorphine and long-acting naltrexone, MMT is no longer the dominant medically assisted addiction treatment.
Methadone maintenance has been termed "a first step toward social rehabilitation" because it increases the retention of patients in treatment, relieves them from the need to find, buy, and use multiple daily doses of street opioids, and offers a legal medical alternative. Methadone is one of the most researched treatments for opioid use disorder and has significant research support for its efficacy.
=== Dispensing ===
Methadone maintenance generally requires patients to visit the dispensing or dosing clinic daily, in accordance with state-controlled substance laws. Methadone, when administered at constant daily milligram doses, will stabilize patients so they feel a "high" from it and will not require additional street opioids. Most clinics will work with patients to get to a dosing level that will take away all cravings for other opiates without feeling too much of a "high" so they can function correctly throughout their day.
In the U.S., patients that attend methadone clinics regularly and abstain from the use of street opioids or other controlled substances can be permitted to take home doses known as privileges, though this is at the discretion of the clinic's medical staff. Depending on the state's law, some clinics will allow the use of drugs like cannabis and still permit take home doses. Some states allow methadone clinics to close on Sundays and provide take-home medication the day before. Clinics that offer take-home privileges will usually do so by slowly offering more take-home days over a period of time, as long as their standards of clean drug tests are met. In some states, these take-home privileges can work their way to people getting take-home doses that would last them 2–4 weeks maximum. Another way take-homes are permitted is if the clinic puts the patient on a split dose schedule where they take part of their dose in the morning and take home a dose to take later in the day. This is usually given out to people on higher doses, or to help lengthen effectiveness throughout the day. States may mandate drug testing in clinic drug abuse groups and/or outside Narcotics Anonymous meetings. In other countries, dispensing of methadone maintenance by pharmacies, or via prescription from general practitioners rather than specialized clinics, is permitted.
=== Travel ===
In the UK, patients on methadone maintenance who wish to travel overseas are subject to certain legal requirements surrounding the exportation and importation of methadone. The prescriber must be provided with details of travel, after which they will arrange for a Home Office Export License to be provided. This license is only required if the total amount being exported exceeds 500 mg. Granting of the license does not allow for the importation of methadone into any overseas jurisdiction. For importation, the patient should contact the embassy of their destination country and request permission to import methadone onto their shores, although not all countries allow the importation of controlled drugs. The license also allows for the re-importation of any remaining methadone back into the UK. It is normal for patients traveling overseas to be prescribed methadone in a tablet form, as tablets are easier to transport. For patients who expect to be overseas for a prolonged period of time, "courtesy" arrangements can be made at a local clinic which arrange for the prescription of the necessary medication. If traveling throughout the United States, state or city clinics may offer "take home" doses for the period of time patients will be gone. Depending on length of travel or clinic rules, they may opt to have their "courtesy" dose at another clinic that is closer to where they are travelling.
== Buprenorphine ==
Buprenorphine was approved by the United States Food and Drug Administration (FDA) in 2002. The lowest optimal dose of buprenorphine is 8 mg. Buprenorphine has fewer withdrawal symptoms upon discontinuation, lower risk for overdose, and lower potential for abuse; therefore, it is more effective for unsupervised treatment than methadone. Opioid users can take fewer doses per week than methadone. Side effects of buprenorphine may include constipation and disordered sleep.
== Comparison with related therapies ==
The manufacturers of naltrexone have marketed it as superior because it is not an opioid. This argument has moved criminal justice officials to prefer the medicine, and has triggered a Congressional investigation about mismarketing. No study has found naltrexone to be superior to methadone or buprenorphine, and a real-world review of patient records suggests that methadone and buprenorphine are superior at reducing overdose risk or the need for acute drug dependence treatment.
== Opioid withdrawal ==
When the body goes through withdrawal, the opioid receptors in the brain are not filled with an adequate amount of opioids, which means that the feelings of euphoria associated with opioids are not felt. Withdrawal only happens when the body has become accustomed to having opioids in the receptors, which changes the structure and functioning of the brain. Thus, without opioids, the brain functions differently in comparison to the brain before the user started becoming dependent on opioids. People who have a dependence on opioids are the only people who experience withdrawal symptoms.
Opioids are commonly prescribed to alleviate symptoms of chronic pain. However, misuse of this pain-killer impacts millions of people worldwide each year. According to WHO, approximately 115,000 people died of opioid overdose in 2017. Addiction is widespread among users and can typically be seen through symptoms such as intense cravings, rejection of previously enjoyed activities, and struggling to fulfill responsibilities due to opioid use. OAT is one suggested treatment for opioid misuse because it is commonly reported to minimize the likelihood of experiencing psychological and physiological symptoms associated with withdrawal (i.e., diarrhea, body pain, vomiting, profound insomnia, sweating, anxiety and depression) and alleviate the intensity of most withdrawal symptoms.
== Psychological understanding ==
There are numerous psychological variables that hold the capacity to influence the effectiveness of opioid agonist therapy (OAT), as explained in Daniel Michael Doleys's 2017 narrative review. Four of these variables include likelihood of opioid withdrawal, conditioning and learning factors, patient-specific factors, and social variables.
=== Conditioning and learning ===
A second psychological factor that can influence the effectiveness of OAT is conditioning and learning. The activity and functioning of opioids are influenced by numerous principles of conditioning and learning such as environmental cues and associations.
=== Patient-specific factors and social variables ===
Patient-specific factors such as mood, and overall psychological and neurocognitive status also hold the capacity to influence the effectiveness of OAT. Certain patient characteristics, such as distress intolerance, can result in increased opioid misuse to obtain relief from one's chronic pain. The social environment that the opioid user lives and uses in can also alter the effectiveness of the treatment. A stable positive psychosocial environment aids in the effectiveness of OAT, whereas a negative psychosocial environment can make the effects of OAT difficult for the opioid user. OAT is most effective if the opioid user is compliant and the treatment is consistent. Counseling opportunities are also very helpful with regard to OAT's rehabilitation efforts.
== Barriers to access ==
=== Stigma ===
Addiction is highly stigmatized, even in the medical field. Being stigmatized correlates to a decline in an individual's physical and mental health. Thus, stigmatization is a prohibitive factor for addicts who may attempt to seek treatment. Even though opioid agonist therapy (OAT) has been proven to be an effective treatment for Opioid Use Disorder, very few American doctors have undertaken the necessary education and certification to provide the treatment. Most treatment facilities, such as rehabilitation or sobering centers, do not offer OAT, nor do they accept patients who are already receiving Opioid Agonist Therapy.
Due to risks associated with intravenous drug use, such as infections and blood borne illnesses, access to post-acute care is critical. While patients who do not use intravenous drugs may receive post-acute care at home, "healthcare facilities and infusion companies may not allow people with a history of [injection drug use] to have home intravenous antibiotic therapy because of concern that an indwelling intravenous catheter could be used to inject illicit drugs".(p. 17) Moreover, American post-acute care programs rarely accept patients who are receiving OAT.
In the United States, protection from discrimination under the Americans with Disabilities Act (ADA) are more vague for addicts than they are for those living with other disabilities. Active drug users are not protected by the ADA. Only individuals who are in recovery and not actively using drugs qualify for protection. However, individuals receiving OAT are considered to have a disability and are subsequently protected by American law.
Advocates identify the bureaucratic red tape surrounding the prescription and administration of opioid agonists as potential obstructions to fair accessible medical care. Potential solutions include federal incentives or requirement for doctors to be trained to prescribe agonists. Another solution is the amendment of the 2000 Drug Abuse Act, which would remove the requirement of special certification altogether.
Rahul Gupta, director of the White House Office of National Drug Control Policy, identified stigma among doctors as a barrier for patients with OUD.
Similarly, in Canada, research has shown that access to OAT remains low. Despite increasing rates of opioid overdoses, only 1 in 18 people were offered a prescription for OAT within one week of discharge from the emergency department or hospital after an opioid overdose. Older people, people with mental illness, and people living in lower socioeconomic areas were less likely to be started on OAT after an overdose. Despite the benefits of OAT in reducing morbidity and mortality, OAT initiation rates remain low.
=== Overdose ===
Higher doses of methadone may cause respiratory depression and/or euphoria in some patients.
== Controversy ==
Methadone maintenance is also known as drug replacement therapy or opiate replacement therapy (ORT), and has been the subject of much controversy since its inception. Opponents note that methadone prescription replaces dependence on one opioid with another, that methadone maintenance does not prevent additional use of heroin or other opioids in addition to methadone, and that the stabilization or "blocking" effect on euphoria can be overridden with the use of other opioids or with benzodiazepines.
In England and Wales, criminal justice drugs workers employed by the 'Drug Interventions Programme' are based in most arrest suites nationwide. Heroin and crack cocaine users are identified either by mandatory urine tests, or by cell sweeps and face-to-face discussions with arrestees. Identified drug use will often trigger a referral to local drug services, whose first-line response to heroin dependence is likely to involve substitute (buprenorphine or methadone) prescribing.
This line of work originated in the mid to late 1990s, as large-scale studies identified significant levels of heroin and crack cocaine use in populations of arrestees. In a large-scale study of drug misuse in arrested populations, 466 'drug misusing repeat offenders' were identified. Of these, 80% declared an 'unmet need for treatment'.
Contemporaneously, the National Treatment Outcomes Research Study (NTORS) found high levels of money-related offenses in populations of people seeking community treatment for drug problems. In a NTORS report, researches found that every £1 spent on drug treatment could yield between £9.50 and £18 of savings in social costs, mostly attributable to reductions in treatment seekers' levels of offenses.
These studies, along with others, were taken on by Tony Blair whilst still Shadow Home Secretary, as Conservative policy regarding drug misuse was relatively undeveloped. Blair disseminated a press release in 1994 entitled 'Drugs: the Need for Action', claiming that drug misuse caused £20bn of money-related crimes each year. This report was dismissed by the Conservative Secretary of State for the Home Department as 'four pages of hot waffle against the Government, with three miserable paragraphs at the end'.
After winning the UK general election of 1997, Blair's first cross-governmental drug strategy established the nationwide development of an integrated drugs and crime strategy as a priority. Drugs workers were in police custody suites nationwide, and saw 50,000 people in 2001. The work of these teams was then formalised in 2003, given an expanded remit (working with prisoners following release, for example), and rebadged the Drug Interventions Programme (DIP).
The founding strapline for DIP was 'out of crime, into treatment', reflecting the crime-reduction philosophy behind criminal justice drug treatment and ongoing methadone (or buprenorphine) maintenance at that time. In their 2010 Drug Strategy, the Conservative/Liberal Democrat coalition stated their continued intention to support DIP.
== See also ==
Harm reduction
Opioid use disorder
Stimulant maintenance
== References ==
== External links ==
U.S. National Library of Medicine - Methadone Definition
Directory of U.S. Methadone Maintenance Facilities | Wikipedia/Opioid_replacement_therapy |
A date rape drug is any drug that incapacitates another person and renders that person vulnerable to sexual assault, including rape. These substances are associated with date rape because of reported incidents of their use in the context of two people dating, during which the victim is sexually assaulted, raped or suffers other harm. However, such substances have also been exploited during retreats, for example ayahuasca retreats. While these substances are not exclusively used to perpetrate sexual assault or rape, as they are also used for personal recreation or medical purposes, their side effects facilitate such acts. The most common incapacitating agent for date rape is alcohol, administered either surreptitiously or consumed voluntarily, rendering the victim unable to make informed decisions or give consent.
== Frequency ==
No comprehensive data exists on the frequency of drug-facilitated sexual assaults involving the use of surreptitious drug administration, due to the report rate of assaults and because rape victims who do report are often either never tested for these drugs, are tested for the wrong ones, or the tests are administered after the drug has been metabolized and left their body.
A 1999 study of 1,179 urine specimens from victims of suspected drug-facilitated sexual assaults in 49 American states found six (0.5%) positive for Rohypnol, 97 (8%) positive for other benzodiazepines, 48 (4.1%) positive for GHB, 451 (38%) positive for alcohol and 468 (40%) negative for any of the drugs searched for.
A similar study of 2,003 urine samples of victims of suspected drug-facilitated sexual assaults found less than 2% tested positive for Rohypnol or GHB. The samples used in these studies could only be verified as having been submitted within a 72-hour time frame or a 48-hour time frame.
A three-year study in the UK detected sedatives or disinhibiting drugs that victims said they had not voluntarily taken in the urine of two percent of suspected drug-facilitated sexual assault victims. In 65% of the 1,014 cases included in this study, testing could not be conducted within a time frame that would allow detection of GHB. A 2009 Australian study found that of 97 instances of patients admitted to hospital believing their drinks might have been spiked, illicit drugs were detected in 28% of samples, and nine cases were identified as "plausible drink spiking cases". This study defined a "plausible drink spiking case" in such a way that cases where (a) patients believed that their drink had been spiked, and (b) lab tests showed agents that patients said they had not ingested would still be ruled out as plausible if the patient did not also (c) exhibit "signs and symptoms" that were considered "consistent with agents detected by laboratory screening."
== Documented routes of administration ==
=== Oral ===
In slang, a Mickey Finn (or simply a Mickey) is a drink laced with a psychoactive drug or incapacitating agent (especially chloral hydrate) given to someone without their knowledge, with intent to incapacitate them. Serving someone a "Mickey" is most commonly referred to as "slipping someone a mickey". Drink spiking is common practice by predators at drinking establishments who often lace alcoholic drinks with sedative drugs.
=== Syringe injection ===
Multiple reports of needle spiking were reported by young women in the United Kingdom from 2021 onwards. On 27 October 2021, the Garda Síochána (Irish police) began an investigation after a woman was spiked with a needle in a Dublin nightclub.
== Documented date rape drugs ==
=== Depressants ===
Alcohol, consumed voluntarily, is the most commonly used drug involved in sexual assaults. Since the mid-1990s, the media and researchers have also documented an increased use of drugs such as flunitrazepam and ketamine to facilitate sexual assaults in the context of dating. Other drugs that have been used include hypnotics such as zopiclone, methaqualone, and the widely available zolpidem (Ambien); sedatives such as neuroleptics (anti-psychotics), chloral hydrate, and some histamine H1 antagonists; common recreational drugs such as ethanol, cocaine, and less common anticholinergics, barbiturates, opioids, PCP, scopolamine; nasal spray ingredient oxymetazoline; and certain GABAergics like GHB. Gamma-Butyrolactone is also often referred to as being used in sexual assaults.
==== Alcohol ====
Researchers agree that the drug most commonly involved in drug-facilitated sexual assaults is alcohol, which the victim has consumed voluntarily in most cases. In most jurisdictions, alcohol is legal and readily available and is used in the majority of sexual assaults. Many perpetrators use alcohol because their victims often drink it willingly, and can be encouraged to drink enough to lose inhibitions or consciousness. Sex with an unconscious victim is considered rape in most jurisdictions and some assailants have committed "rapes of convenience", assaulting a victim after he or she had become unconscious from drinking too much.
Alcohol consumption is known to have effects on sexual behavior and aggression. During social interactions, alcohol consumption causes more biased appraisal of a partner's sexual motives while impairing communication about and enhancing misperception of sexual intentions, effects exacerbated by peer influence about how to behave when drinking.
The effects of alcohol at the point of forced sex commonly include an impaired ability to rectify misperceptions and a diminished ability to resist sexual advances and aggressive sexual behavior.
The Blade released a special report, "The Making of an Epidemic," criticizing a study conducted in the 1990s that concluded that 55% of rape victims had been intoxicated. According to The Blade, the study specifically ignored an Ohio statute that excluded "situations where a person plies his intended partner with drink or drugs in hopes that lowered inhibition might lead to a liaison." The author of the study later admitted that the wording of the survey had been ambiguous.
In 2023, California passed Assembly Bill 1013 which requires bars and nightclubs to provide drug checking strips for drinks. A similar bill is also being considered in Olympia, Washington for 2026.
===== Alcohol in campus rape =====
The increase of sexual assaults on college campuses has been attributed to the social expectations of students to participate in alcohol consumption; social norm dictates that students drink heavily and engage in casual sex.
Various studies have concluded the following:
On average, at least 50% of college sexual assault cases are associated with alcohol use.
On college campuses, 74% of the perpetrators and 55% of the victims had been drinking alcohol.
In 2002, more than 70,000 students between the ages of 18 and 24 were victims of alcohol-related sexual assault in the U.S.
In violent incidents recorded by the police in which alcohol was a factor, about 9% of the offenders and nearly 14% of the victims were under age 21.
==== Z-drugs ====
===== Zolpidem =====
Zolpidem (Ambien) is one of the most common date-rape drugs according to the U.S. Drug Enforcement Administration.
==== Benzodiazepines ====
Benzodiazepines (tranquilizers), such as Valium, Librium, Klonopin, Xanax, and Ativan, are prescribed to treat anxiety, panic attacks, insomnia, and several other conditions, and are also frequently used recreationally. Benzodiazepines are often used in drug-facilitated sexual assaults, with the most notorious being flunitrazepam (chemical name) or Rohypnol (proprietary or brand name), also known as "roofies," "rope," and "roaches."
The benzodiazepines midazolam and temazepam were the two most common benzodiazepines utilized for date rape.
Benzodiazepines can be detected in urine through the use of drug tests administered by medical officials or sold at pharmacies and performed at home. Most tests will detect benzodiazepines for a maximum of 72 hours after it was taken. Most general benzodiazepine detection tests will not detect Rohypnol: the drug requires a test specifically designed for that purpose. One new process can detect a 2 mg dose of Rohypnol for up to 28 days post-ingestion. Other tests for Rohypnol include blood and hair tests. Because the most commonly used drug tests often yield false negatives for Rohypnol, experts recommend use of gas chromatography-mass spectrometry analysis.
===== Rohypnol =====
Rohypnol (Flunitrazepam) pills are typically small and dissolve readily into drinks without significantly affecting their taste or color, allowing the pills to be easily administered surreptitiously to victims.
In one 2002 survey of 53 women who used Rohypnol recreationally, 10% said they were physically or sexually assaulted while under its influence. If enough of the drug is taken, a person may experience a state of automatism or dissociation. After the drug wears off, users may find themselves unable to remember what happened while under its influence (anterograde amnesia), and feeling woozy, hung-over, confused, dizzy, sluggish and uncoordinated, often with an upset stomach. They may also have some difficulty moving their limbs normally.
Rohypnol is believed to be commonly used in drug-facilitated sexual assaults in the United States, the United Kingdom, and throughout Europe, Asia and South America. Although Rohypnol's use in drug-facilitated sexual assaults has been covered extensively in the news media, researchers disagree about how common such use actually is. Law enforcement manuals describe it as one of the drugs most commonly implicated in drug-facilitated sexual assaults. Despite having a long half-life (18–28 hours) an incorrect belief is that Rohypnol is undetectable 12 hours after administration which may result in victims failing to get a blood or urine test the following day.
==== GHB ====
Gamma-hydroxybutyrate (GHB) is a central nervous system depressant. It has no odour and tastes salty, but the taste can be masked when mixed in a drink.
GHB is used recreationally to stimulate euphoria, to increase sociability, to promote libido and lower inhibitions. It is sold under names such as Rufies, Liquid E and Liquid X. It is usually taken orally, by the capful or teaspoon.
From 1996 to 1999, 22 reports of GHB being used in drug-facilitated sexual assaults were made to the United States Drug Enforcement Administration. A 26-month study of 1,179 urine samples from suspected drug-facilitated sexual assaults across the United States found 4% positive for GHB. The National Drug Intelligence Center (NDIC) says that in the United States GHB had surpassed Rohypnol as the substance most commonly used in drug-facilitated sexual assaults, likely because GHB is much more easily available, cheaper and leaves the body more quickly. GHB is only detectable in urine for six to twelve hours after ingestion.
=== Psychedelics ===
==== Ayahuasca ====
Ayahuasca has been used in some ayahuasca retreats to sexually abuse ayahuasca tourists.
==== 3,4-Methylenedioxymethamphetamine (MDMA) ====
MDMA is an empathogen. Although it is not sedating like other date rape drugs, it has been used to facilitate sexual assault. It can increase disinhibition and sexual desire. Often Ecstasy is combined with amphetamines or other drugs.
== Detection ==
Several devices have, in recent years, been developed to detect the presence of date rape drugs, many designed with discreetness in mind. One, developed by two Tel Aviv University researchers, is a sensor for gamma-hydroxybutyric acid and ketamine, but appears similar to a straw, and sends a text to the user's phone to warn them. In 2022, another "Smart Straw" product was designed by students at the University of Nantes: a non-electronic stainless steel straw including a ring that would change colors in the presence of GHB, Rohypnol, or ketamine. Another, designed by four North Carolina State University students, is a nail polish that changes color in the presence of date rape drugs. Several others have also been designed with these color-changing mechanisms in mind.
== Media coverage ==
There were three stories in the media about Rohypnol in 1993, 25 in 1994, and 854 in 1996. In early 1996, Newsweek magazine published "Roofies: The date-rape drug" which ended with the line "Don't take your eyes off your drink." That summer, researchers say all major American urban and regional newspapers covered date rape drugs, with headlines such as "Crackdown sought on date rape drug" (Los Angeles Times) and "Drug zaps memory of rape victims" (San Francisco Chronicle). In 1997 and 1998, the date rape drug story received extensive coverage on CNN, ABC's 20/20 and Primetime Live, as well as The Oprah Winfrey Show. Women were advised not to drink from punch bowls, not to leave a drink unattended and keeping drinks with them at all times (including when going to a dance or the bathroom, or using the phone), not to try new drinks, not to share drinks, not to drink anything with an unusual taste or appearance, take their own drinks to parties, drink nothing opened by another person, and if they feel sick to go with someone they know and not alone or with someone they just met or do not know.
News media has been criticized for overstating the threat of drug-facilitated sexual assault, for providing "how to" material for potential date rapists and for advocating "grossly excessive protective measures for women, particularly in coverage between 1996 and 1998." Law enforcement representatives and feminists have also been criticized for supporting the overstatements for their own purposes.
Craig Webber states that this extensive coverage has created or amplified a moral panic rooted in societal anxieties about rape, hedonism and the increased freedoms of women in modern culture. Goode et al. say it has not only given a powerful added incentive for the suppression of party drugs, but has inappropriately undermined the long-established argument that recreational drug use is purely a consensual and victimless crime. By shining a spotlight on premeditated criminal behavior, Philip Jenkins states that it has relieved the culture from having to explore and evaluate more nuanced forms of male sexual aggression towards people, such as those displayed in date rapes that were not facilitated by the surreptitious administration of drugs.
For similar moral panics around social tensions manifesting via discussion of drugs and sex crime, researchers point to the opium scare of the late 19th century, in which "sinister Chinese" were said to use opium to coerce white women into sexual slavery. Similarly, in the Progressive Era, a persistent urban legend told of white middle-class women being surreptitiously drugged, abducted, and sold into sexual slavery to Latin American brothels. This analysis does not contradict instances when date rape drugs are used or sexual trafficking occurs; its focus is on actual prevalence of certain crimes relative to media coverage of it.
== See also ==
Death of Samantha Reid
Rape culture
Reynhard Sinaga
Mickey Finn (drugs)
Chemical submission
Rapes of Gisèle Pelicot
== References == | Wikipedia/Date_rape_drug |
The U.S. state of Oregon has various policies restricting the production, sale, and use of different substances. In 2006, Oregon's drug use per person was higher than the national average, with marijuana, methamphetamine, and illicit painkillers being the most commonly used substances.
Oregon's drug policy has evolved significantly over time, reflecting changing societal attitudes and state responses to substance use. Alcohol regulation in Oregon dates back to pre-statehood, with the state pioneering both the prohibition and eventual regulation of alcohol through the creation of the Oregon Liquor Control Commission. The state's approach to other substances has also been notably progressive. Oregon was the first state to decriminalize small amounts of cannabis in 1973 and later legalized its use for both medical and recreational purposes. Other substances like methamphetamine, heroin, and club drugs have posed ongoing challenges, with laws evolving to address production, trafficking, and public health issues. Oregon has also been a leader in regulating prescription drug use and in recent years has decriminalized the personal possession of small amounts of all drugs under Ballot Measure 110, while legalizing the medical use of psilocybin mushrooms. However, this policy was partially reversed in 2024, marking a significant shift in the state's stance on drug decriminalization.
== Decriminalization ==
On February 1, 2021, Oregon became the first state in the USA to decriminalize the possession of small quantities of all illicit drugs, following the passing of Oregon Ballot Measure 110 in November 2020. The law was passed by 58% of voters in a ballot initiative. Among other provisions, it directs hundreds of millions of dollars from cannabis tax collections to addiction treatment. However, in 2024, Oregon partially reversed its drug laws, with the governor signing a new law which made possessing small amounts of hard drugs a misdemeanor starting September 1, 2024. However, the new law did not require mandatory jail time in all cases or apply to soft drugs, with cannabis tax revenue even still being maintained as a source of funding for drug treatment. The policy intended to redirect people away from the criminal justice system and toward treatment. However, critics argued that the law failed to adequately connect people with treatment services, and Oregon saw a continued rise in overdose deaths and public drug use.
== Recriminalization ==
In April 2024, Oregon Governor Tina Kotek signed House Bill 4002, effectively ending the full decriminalization of hard drugs and reintroducing criminal penalties for possession of substances such as fentanyl, methamphetamine, and heroin. The law took effect on September 1, 2024, and reclassified possession of small amounts of these substances as a Class C misdemeanor punishable by up to 30 days in jail. The new law includes provisions allowing law enforcement to direct individuals toward treatment rather than jail under a process called "deflection," which is designed to give individuals the opportunity to avoid criminal charges by completing a substance abuse screening and connecting with services. The measure aims to improve the balance between treatment and accountability, while also addressing the strain drug use has placed on public spaces, businesses, and emergency services.
== Specific drugs ==
=== Alcohol ===
Oregonians consume an average amount of beer and distilled spirits, and an above average amount of wine. As of 2007, the consumption of spirits is on the rise, while beer consumption is holding steady. Also, 11% of beer sold in Oregon was brewed in-state, the highest figure in the United States.
Oregon was the first place in the United States to prohibit alcohol, prior to becoming a U.S. state in the mid-19th century. That law was quickly repealed, but Oregon again preceded the rest of the country in outlawing alcohol, passing a law several years before federal prohibition was enacted with the Eighteenth Amendment to the United States Constitution. Following the repeal of prohibition in 1933, Oregon acted swiftly to regulate alcohol, establishing the Oregon Liquor Control Commission (OLCC) within days of the repeal. The OLCC continues to regulate alcohol in the state today.
=== Cannabis ===
From 1999 through 2005, the ratio of Oregonians using cannabis outpaced the general United States population by 32–45%, with between 6.53% (2000) and 8.96% (2002) of the population using it. In 2003–2004, Oregon ranked among the top five states for cannabis usage of people 12 and older. Oregon is also one of the largest cannabis producing states, ranking fourth in indoor production, and 10th overall in 2006.
In 1973, Oregon became the first U.S. state to decriminalize the possession of small amounts of cannabis, and in 1998 the state legalized its use for medical purposes. An attempt to recriminalize possession of small amounts of cannabis was turned down by Oregon voters in 1997. In June 2010, Oregon became the first state in the country to reclassify marijuana from a Schedule I drug to a Schedule II drug when the Oregon Board of Pharmacy voted for reclassification. Recreational cannabis has been legal in the state since July 2015.
=== Club drugs ===
In Oregon, MDMA (3,4-methylenedioxymethamphetamine), GHB (gamma-hydroxybutyrate), ketamine, and LSD are available in varying quantities and are generally used at social venues in more populated areas and on college campuses. Club drugs enter Oregon from a variety of sources: MDMA from Canada, ketamine from Mexico, and GHB and LSD from California. Laboratory seizures indicate some local GHB and LSD production. GHB is also obtained from Internet sources. PCP and Psilocybin mushrooms are generally available in and around cities with a college student population.
=== Cocaine ===
Cocaine is available throughout Oregon, and crack cocaine is available in some urban areas. Mexican traffickers dominate wholesale distribution, transporting the drug from Mexico, California, and other southwestern states. Retail quantities are primarily sold by Mexican drug trafficking organizations, street gangs, prison gangs, and local independent dealers. In 2007, 63.7 pounds of cocaine were seized by federal authorities, up from 36.4 pounds in 2006.
=== Heroin ===
In the 1990s, potent and inexpensive heroin became widely available in Portland; heroin use in Multnomah County rose 600% during that decade.
According to police, in 2008, heroin became more plentiful in Oregon in response to a crackdown on methamphetamine. In 2007, 115 heroin overdoses resulted in death, up 29% from 2006. In 2012 heroin was responsible for 147 deaths, and the leading cause of overdose deaths in the state. The number of deaths is far below the highs of the late 1990s. Most deaths are a result of the user misgauging their tolerance. Heroin is especially lethal because it depresses the central nervous system, unlike cocaine and meth which are stimulants.
In Oregon, black tar heroin comes from Mexico up the Interstate 5 corridor. In 2007, 19 pounds of heroin were seized by federal authorities, more than double the amount in 2006.
=== Methamphetamine ===
Since its arrival in the early 1980s, the use of methamphetamine in Oregon has become a serious public health problem. Abuse of methamphetamine (commonly known as "crystal meth" or simply "meth") has spread across the state and the rest of the United States. The issue has been a focus of media organizations in the state, and has been a focus of several political campaigns, including that of Attorney General-elect John Kroger in 2008, and ballot measures such as Measures 57 and 61 in the same year.
In 2005, Governor Ted Kulongoski signed legislation that made Oregon the first state to require prescriptions for cold medicines containing pseudoephedrine, one of the key ingredients used to make methamphetamine. The state had previously required buyers to show ID and sign a log when buying cold medicine like Sudafed and Claritin D. The intent of the law was to reduce the number of home methamphetamine laboratories. Oregon's monthly home drug lab seizures dropped from 41 to nine after the restrictions were put in place, but the drug is still available, coming from Mexican labs and from other states. Meth-related deaths decreased for the first time since 2001, when 2007 deaths declined 21% from 2006 deaths.
In 2007, 33 pounds of meth were seized by federal authorities, down from 101.6 pounds in 2006.
=== Prescription drugs ===
Illicit use of prescription drugs is the fastest growing category of illegal drug use. Treatment admissions for illicit prescription drugs increased 332% from 1998 to 2008, surpassing cocaine admissions in 2005. In the United States, the primary methods of diversion of legitimate pharmaceuticals is illegal dispensing and prescribing by physicians, illegal distribution by pharmacists, prescription forgery, doctor shopping, and drug thefts from pharmacies, nursing homes, and hospitals. Pharmacy burglaries are prevalent throughout the state and Diversion Investigators are also encountering pharmaceuticals that have been purchased via the Internet without a doctor's prescription. The use and sale of oxycodone (OxyContin, Percocet, Percodan), hydrocodone (Vicodin, Lortab), and anabolic steroids are of concern to the Drug Enforcement Administration. Also, as of January 2008, methadone use has increased dramatically in the state.
=== Psilocybin and psilocybin mushrooms ===
As part of the passing of Oregon Ballot Measure 110, which came into effect on February 1, 2021, the personal possession of psilocybin and psilocybin mushrooms (also known as "magic mushrooms") was decriminalized.
As part of Oregon Ballot Measure 109 the "manufacture, delivery and administration" of psilocybin and psilocybin mushrooms was legalized for those aged 21 and over for medical purposes, such as mental health treatment and use in supervised and licensed therapy sessions.
=== Tobacco ===
Oregon's Tobacco Prevention and Education Program (TPEP) was launched in 1997 to "reduce tobacco-related illness and death" by reducing exposure to secondhand smoke, countering pro-tobacco influences, helping users to quit, and eliminating health disparities. As of 2020, the current tax on a pack of cigarettes is $1.33, and the wholesale tax on other tobacco products is 65%. House Bill 2270 was referred to voters by the legislature as Measure 108 for the 2020 general election, to raise the cigarette tax to $3.33 per pack, increase a cap on cigar taxes from 50¢ to $1.00 each, and apply the wholesale tax to electronic cigarettes. Measure 108 was passed by voters, signed into law and effective January 1, 2021.
Smoking in bars and similar businesses is prohibited in Oregon as of a law that took effect January 2009 (SB 571 of the 2007 legislature.)
== Usage ==
In 2008, academic researchers began studying waste water at various Oregon sewage plants, to evaluate the drug use of various communities. Their research is pioneering the field in the United States, though similar studies have been done in Europe. Every one of the samples, taken from 96 plants, contained methamphetamine; Cocaine was present in 80% of the samples, MDMA in 40%. the research is ongoing, and will evaluate some of the plants—along with plants in Washington—over time.
== Penalties ==
The penalties for sale of a controlled substance varies between states. In Oregon, a person convicted three times of selling 3.3 pounds of meth would face a maximum of four years in prison. By comparison, the potential penalty would be 13 years in prison in California, 21 years in federal court, and up to life in Texas. Former Oregon lawmaker Kevin Mannix wants to increase these penalties, saying the state "invites" criminal drug activity "by being passive." Mannix put a citizen's initiative on the November 2008 ballot, Measure 61. The measure was defeated, while a less expensive measure referred by the legislature, Measure 57, passed. Mannix's opponents argued that increased mandatory minimum sentences remove judicial discretion and send small-time dealers into expensive prisons instead of drug treatment.
In 2024, with the passage of House Bill 4002, Oregon formally reintroduced criminal penalties for the possession of small amounts of certain controlled substances. Under the new law, individuals found in possession may face arrest and jail time unless they participate in deflection programs offering treatment alternatives. The penalties reflect a hybrid model aimed at deterring open drug use while expanding access to care for substance use disorders.
== References == | Wikipedia/Drug_policy_of_Oregon |
Drug policy of California refers to the policy on various classes and kinds of drugs in the U.S. state of California. Cannabis possession has been legalized with the Adult Use of Marijuana Act, passed in November 2016, with recreational sales starting January of the next year. With respect to many controlled substances, terms such as illegal and prohibited do not include their authorized possession or sale as laid out by applicable laws.
On November 4, 2014, voters approved Proposition 47, which, among other things, reduced drug possession for personal use to a misdemeanor (except possession of more than one ounce of marijuana).
== Specific drugs ==
=== Alcohol ===
Alcohol is legal for adults 21 and over in the State of California to possess, purchase, and consume. Sale of alcohol is regulated and a license must be granted by county authorities before a store, bar, or restaurant may sell alcohol.
Driving a motor vehicle while intoxicated on alcohol is a misdemeanor which carries a penalty of up to one year in the county jail. Subsequent offenses may be charged as a felony under certain circumstances. In practice driving a motor vehicle while intoxicated will result in probation for first offenses, along with hefty fines, alcohol education, and community service. Subsequent offenses usually result in a small amount of jail time along with probation. Public intoxication on alcohol is a misdemeanor under state law and also under most municipal ordinances. Public intoxication on alcohol is often not prosecuted and the offender is released after sobering up in jail. Sometimes, depending on criminal history, those convicted of public intoxication may serve very small jail sentences.
The Department of Alcohol Beverage Control (ABC) is the Californian authority over alcohol licenses in the state. The Department has outlawed the sale of alcohol to a "habitual drunkard" or any "obviously intoxicated person". Selling alcohol to a habitual drunkard or obviously intoxicated person is a misdemeanor under Section 25602 of the Business and Professions Code. The Department also outlaws the sale or consumption of alcohol on licensed premises between 2 a.m. and 6 a.m. Selling or allowing the consumption of alcohol on licensed premises between these hours is a misdemeanor under Section 25632.
=== Amphetamines ===
Amphetamine, methamphetamine and dimethylamphetamine are Schedule 2 on the California Uniform Controlled Substances Act, which is part of the California Health and Safety Code. Methamphetamine is illegal for possession under Health and Safety Code 11377. Methamphetamines are illegal for possession for sale under Health and Safety Code 11378. In practice those without prior criminal histories convicted of HS 11377 will be granted PC1000, Proposition 36, or felony probation. Those convicted of HS 11378, possession of amphetamines for sale, may receive anything from probation up to 4 years in prison. Harsher sentences are given for those convicted of manufacturing amphetamines such as methamphetamine.
=== Cannabis ===
All forms and preparations of cannabis, as well as its derivative tetrahydrocannabinol are Schedule 1 on the California Uniform Controlled Substances Act. The first cannabis prohibition laws in California were passed in 1913. In the 1972 California November elections an initiative titled Proposition 19, which would have legalized cannabis, was on the ballot. It failed to pass, with 66.5% voters voting "No" and 33.5% voting "Yes." In 1976 the passage of the Moscone Act changed small-scale possession of marijuana from a felony to a misdemeanor.
On November 5, 1996, 56% of voters approved Proposition 215 (also known as the Compassionate Use Act of 1996), taking effect the following day and removing state-level criminal penalties on the use, possession, and cultivation of marijuana by patients that "would benefit from medical marijuana" and possess a "written or oral recommendation" from their physician. Conditions typically covered by the law include arthritis, cachexia, cancer, chronic pain, HIV or AIDS, epilepsy, migraines, and multiple sclerosis. Initially, there existed no set limits regarding the amount of marijuana patients could possess or cultivate. California Senate Bill 420, also known as the Medical Marijuana Program Act, was signed into law in October 2003 and took effect on January 1, 2004, establishing the amount of medicinal marijuana patients and/or their caregivers may grow and possess. The bill allowed for no more than 8 ounces of dried marijuana and/or 6 mature (or 12 immature) plants, unless larger quantities were recommended by a physician. Senate Bill 420 also required the California Department of State Health Services to establish a voluntary patient registry and issue identification cards to patients, though no such registry has been established to date.
In February 2009, Tom Ammiano introduced the Marijuana Control, Regulation, and Education Act, the first bill attempting to legalize the sale and use of marijuana in California. If passed and signed into law, marijuana would be sold and taxed openly to adults age 21 and older in a manner similar to alcohol.
In September 2010, then Governor Arnold Schwarzenegger signed SB 1449 into law, which reduced possession of under 1 ounce of cannabis from a misdemeanor to a civil infraction. The law went into effect January 1, 2011.
In 2010, Proposition 19, titled the "Regulate, Control, and Tax Cannabis Act of 2010", qualified for the November California ballot. It failed to pass. If it had passed, the initiative would have legalized the recreational use of cannabis and its related activities in the State of California. It would have also allowed local governments to regulate and tax the newly created cannabis market.
In the November 2016 election, voters passed an initiative legalizing recreational use of marijuana, the Adult Use of Marijuana Act. Following the Act, California has been pioneering the development of an appellations of origin program for cannabis products.
The Adult Use of Marijuana Act went into effect on January 1, 2018. Adults 21 and over in California may now possess up to one ounce of dried marijuana or eight ounces of concentrated cannabis and can grow up to six marijuana plants for personal use subject to certain restrictions. It is still illegal to sell or possess marijuana with intent to sell without both a state and local license. Despite its legality in California, marijuana is still considered a Schedule 1 drug under the United States Controlled Substances Act. This means that federal prosecutors are allowed to decide to arrest and prosecute cannabis users and sellers who are in accordance to California law but not federal law.
=== Cocaine/Crack ===
Cocaine, crack cocaine, coca leaves and all other forms of cocaine are Schedule 2 on the California Uniform Controlled Substances Act. Cocaine is illegal to possess under California Health and Safety Code 11350. Possession under HS 11350 was formerly a prosecuted as a misdemeanor or felony with up to 3 years in prison, but Proposition 47 made simple possession for personal use a misdemeanor only. In practice, those charged with cocaine possession will in most cases be given an opportunity to plead guilty and receive no jail time under PC 1000, Prop 36, or felony supervised probation. People with prior records and especially those with prior drug possession records will often be given small jails terms such as 30, 90, or 180 days, along with felony probation.
Possession for sale of cocaine salt ("powder") is prohibited under Health and Safety Code 11351; "crack" cocaine under 11351.5. Penalties for possession for sale of cocaine salt are 2, 3, or 4 years in the state prison; for "crack" cocaine, 3, 4 or 5 years. Health and Safety Code 11352 pertains to selling or providing cocaine trafficking and provides for imprisonment for 3, 4 or 5 years. Those convicted of possession for sale HS 11351 or sale/trafficking under 11352 will often serve from 1 year in county jail to a sentence of 2–5 years in state prison, based upon the quantities of drugs, the extent of their criminal history, and the jurisdiction in which they are prosecuted. Those convicted of selling cocaine with prior related offenses may serve many years in the state prison, since qualifying prior convictions may add 3 years per conviction to the term provided for the conviction itself. Various enhancements exist in the California Health and Safety Code for dealing cocaine which may result in very long prison terms, such as selling to a minor, selling in a school zone, and selling large quantities of the drug.
=== Heroin and other opiates ===
Heroin is Schedule 1 on the California Uniform Controlled Substances Act. Heroin is illegal to possess under California Health and Safety Code 11350. Possession under HS 11350 can be prosecuted as a misdemeanor or felony with up to 3 years in prison. Possession for sale is illegal under Health and Safety Code 11351. Penalties for possession for sale is 2, 3, or 4 years in the state prison. Health and Safety Code 11352 pertains to sale/trafficking with increased penalties. Those convicted of possession for sale HS 11351 or sale/trafficking under 11352 will often serve from 1 year in county jail, or 18-month sentence in the state prison based upon the quantities and extent of their drug dealing if it is their first offense. Those convicted of selling cocaine with prior related offenses may serve up to 4 years in the state prison.
Raw opium, opium poppy and straw, as well as its derivatives morphine, oxycodone, hydrocodone and codeine are Schedule 2 on the California Uniform Controlled Substances Act.
=== Ketamine ===
Ketamine is Schedule 3 on the California Uniform Controlled Substances Act. Ketamine is illegal under Health and Safety Code 11377 HS. It is a misdemeanor to possess and punishment includes 6 months in jail and up to a $1,000 fine. Those charged with ketamine possession will in most cases be given an opportunity to plead guilty and receive no jail time under PC 1000, Prop 36, or felony supervised probation. People with prior records and especially those with prior drug possession records will often be given small jails terms such as 30, 90, or 180 days, along with felony probation. Ketamine is illegal to possess with intent to sell or actual sale under Health and Safety Code 11379.2 HS. The charge can be a misdemeanor or a felony. Those convicted of this offense as a misdemeanor, you face up to one-year in a county jail and a maximum $1,000 fine. If you are convicted of this offense as a felony, you face 16 months, or two or three years in the California state prison and a maximum $10,000 fine.
Recently, in People v. Davis, CSC Case No. 198434, the California Supreme Court ruled that possession of ecstasy (MDMA or methylenedioxy-methylamphetamine) without additional evidence is insufficient to sustain a conviction for possession of a controlled substance (11350 (a) HS).
=== MDMA (ecstasy) ===
3,4-Methylenedioxymethamphetamine (MDMA) is Schedule 1 on the California Uniform Controlled Substances Act. MDMA is illegal for possession under Health and Safety Code 11377. MDMA is illegal for possession for sale under Health and Safety Code 11378. In practice those without prior criminal histories convicted of HS 11377 will be granted PC1000, Prop 36, or felony probation. Those convicted of HS 11378, possession of MDMA for sale, may receive anything from probation up to 4 years in prison. California passed increased penalties for "hard drugs" with prop 36, but MDMA and LSD are exempt from those penalty increases.
=== Nicotine and tobacco products ===
Products containing nicotine such as tobacco, cigarettes, cigars and chewing tobacco are legal for adults 21 and over to possess, purchase, and consume. Sale of tobacco and nicotine-containing products is regulated and a license must be granted by the state before a store may sell tobacco and nicotine-containing products. (Effective June 9, 2016).
Since January 1, 1995, smoking has been banned in all enclosed workplaces in California, including restaurants and bars (bars were excluded until January 1, 1998), exempting only the following areas: workplaces with five or fewer employees (as long as all workers consent and persons under 18 are prohibited from the smoking area), 65% of the guest rooms of hotels/motels, lobby areas of hotels/motels designated for smoking (not to exceed 25% of the total lobby floor area or, if the lobby area is 2,000 square feet (190 m2) or less, not to exceed 50% of the total lobby floor area), meeting and banquet rooms except while food or beverage functions are taking place (including set-up, service, and clean-up activities or when the room is being used for exhibit activities), retail or wholesale tobacco shops and private smokers lounges (i.e. cigar bars), truck cabs/tractors if no nonsmoking employees are present, non-office warehouse facilities with more than 10,000 square feet (930 m2) of total floor space and 20 or fewer full-time employees working at the facility, theatrical production sites if smoking is an integral part of the story, medical research or treatment sites if smoking is integral to the research or treatment being conducted, private residences except homes licensed as family day care homes during the hours of operation and in those areas where children are present, patient smoking areas in long-term health care facilities, and employee breakrooms designated for smoking.
Effective January 1, 2004, California bill AB846 bans smoking within 20 feet (6.1 m) of the entrance or operable window of a public building ("public building" means a building owned and occupied, or leased and occupied, by the state, a county, a city, a city and county, or a California Community College district.) The law also prohibits smoking in state owned vehicles. Additionally, effective January 1, 2008, smoking in a moving vehicle while in the presence of a minor (18 years or younger) is an infraction; the charge is not serious enough to be pulled over, and only can be cited along with a stricter offense, such as a moving violation or traffic accident. Local jurisdictions may regulate smoking more strictly than the state. Many California communities have established smoke-free registries for private residential apartment buildings, which range from complexes where smoking is entirely prohibited (whether inside private dwellings or outside) to those where certain sections of dwellings may be designated as smoking dwellings. Most California cities allow landlords to regulate smoking at will.
=== Psilocybin (mushrooms) ===
Psilocybin and its metabolized counterpart psilocin are Schedule 1 on the California Uniform Controlled Substances Act. Mushrooms containing psilocybin and psilocin, as well as psilocybin mushroom spores are illegal to possess, import, buy, sell, trade, or give away if intended to be cultivated. Growing psilocybin-containing mushrooms from spores is considered manufacturing a controlled substance.
Psilocybin itself still categorized as a Schedule I Controlled Substance according to the United States Drug Enforcement Administration under federal law. Schedule I drugs are identified as those with the highest potential for substance abuse, and has chemical properties that enables addictive behavior. Under California Law, possession of Psilocybin Mushrooms can result in a range of penalties varying from a $1,000 fine, mandatory community service, or potentially serving one year in county jail. Whereas distributing a Schedule I Controlled Substance such as psilocybin is recorded as a felony, with the potential to serve in a jail or state prison. In California, the Controlled Substances Act of 1970 still prohibits any use or possession of psilocybin, or any other psychedelics.
Following World War II, a new social movement referred to as "Psychedelic Culture" became increasingly popular amongst young adults. As the Psychedelic Culture movement rapidly grew, concerns for increased drug use became a national issue, which led to the implementation of The Controlled Substances Act of 1970
However, on February 17, 2021, Senator Scott Wiener proposed Senate Bill-519 which would overturn all previous legal consequences towards psychedelics. Senate Bill-519 gained approval on June 29, 2021 on the terms that Ketamine would be redacted from the original proposal. Senate Bill-519 was approved with a 5-3 vote from the Assembly Public Safety Committee for their advocacy towards the use of furthering scientific research behind psychedelic therapy treatment. Psilocybin has been in the process of undergoing clinical trials as mental health professionals and scientists gather data demonstrating the drugs potential benefits. Upon approval from the Drug Enforcement Administration, psilocybin have both been used in clinical trials in attempts to study the medicinal purposes. University of California, San Francisco has invested in clinical trials of psilocybin as part of a treatment to mental health diagnoses such as Bipolar II Disorder as well as Depression. In September of 2020, there have been over 1,000 reported clinical trials of Psilocybin therapy research conducted for various diagnoses and have even produced evidence to show that the psychotherapy approach demonstrates prolonged antidepressant effects.
== Other drugs ==
Lysergic acid diethylamide (LSD) is Schedule 1 on the California Uniform Controlled Substances Act. LSD is illegal for possession under Health and Safety Code 11377. LSD is illegal for possession for sale under Health and Safety Code 11378. All forms of peyote and its derivatives, including its active compound mescaline are Schedule 1 on the California Uniform Controlled Substances Act. Dimethyltryptamine (DMT), 4-methyl-2,5-dimethoxyamphetamine (DOM/STP), gamma-hydroxybutyric acid (GHB), bufotenin (toad venom) and ibogaine are Schedule 1 on the California Uniform Controlled Substances Act.
Phencyclidine (PCP) is Schedule 2 on the California Uniform Controlled Substances Act. PCP is illegal for possession under Health and Safety Code 11377. PCP is illegal for possession for sale under Health and Safety Code 11378.
Anabolic steroids, including testosterone and human chorionic gonadotropin are Schedule 3 on the California Uniform Controlled Substances Act.
On August 31, 2011, California Legislature passed SB 514, which banned the sale of dextromethorphan (DXM), the active ingredient in most over-the-counter cough medicines, to minors.
== See also ==
Law of California
Occupational health concerns of cannabis use
== References ==
== External links ==
California Uniform Controlled Substances Act (Health and Safety Code Section 11053-11058)
California Health and Safety Code Section 11350-11356.5
California Health and Safety Code Section 11377-11382.5
Marco Firebaugh Memorial Children's Health and Safety Act of 2007 (California Health and Safety Code Section 118947-118949) | Wikipedia/Drug_policy_of_California |
A parasympathomimetic drug, sometimes called a cholinomimetic drug or cholinergic receptor stimulating agent, is a substance that stimulates the parasympathetic nervous system (PSNS). These chemicals are also called cholinergic drugs because acetylcholine (ACh) is the neurotransmitter used by the PSNS. Chemicals in this family can act either directly by stimulating the nicotinic or muscarinic receptors (thus mimicking acetylcholine), or indirectly by inhibiting cholinesterase, promoting acetylcholine release, or other mechanisms. Common uses of parasympathomimetics include glaucoma, Sjögren syndrome and underactive bladder.
Some chemical weapons such as sarin or VX, non-lethal riot control agents such as tear gas, and insecticides such as diazinon fall into this category.
== Structure activity relationships for parasympathomimetic drugs ==
For a cholinergic agent, the following criteria describe the structure activity relationship:
Ing's Rule of 5: there should be no more than five atoms between the nitrogen and the terminal hydrogen for muscarinic (or cholinergic) activity;
the molecule must possess a nitrogen atom capable of bearing a positive charge, preferably a quaternary ammonium salt;
for maximum potency, the size of the alkyl groups substituted on the nitrogen should not exceed the size of a methyl group;
the molecule should have an oxygen atom, preferably an ester-like oxygen capable of participating in a hydrogen bond;
there should be a two-carbon unit between the oxygen atom and the nitrogen atom.
== Pharmaceuticals/Supplements ==
=== Direct-acting ===
These act by stimulating the nicotinic or muscarinic receptors.
Choline esters
Acetylcholine (all acetylcholine receptors)
Bethanechol (M3 receptors)
Carbachol (all muscarinic receptors and some nicotinic receptors)
Methacholine (all muscarinic receptors)
Plant alkaloids
Arecoline
Nicotine
Muscarine
Pilocarpine (M3 receptors)
=== Indirect-acting ===
Indirect acting parasympathomimetic substances may be either reversible cholinesterase inhibitors, irreversible cholinesterase inhibitors or substances that promote ACh release or anti-adrenergics. The latter inhibits the antagonistic system, the sympathetic nervous system.
Reversible cholinesterase inhibitors
Donepezil
Edrophonium
Neostigmine
Physostigmine
Pyridostigmine
Rivastigmine
Tacrine
Caffeine (non-competitive)
Huperzine A
Irreversible cholinesterase inhibitors
Echothiophate
Isoflurophate
Malathion
ACh release promoters
Alpha GPC
Cisapride
Droperidol
Domperidone
Metoclopramide
Risperidone
Paliperidone
Anti-adrenergics: See also alpha blocker and beta blocker
Clonidine (α-receptor agonist, α2 > α1, giving negative feedback)
Methyldopa (α2 agonist, giving negative feedback)
Propranolol (β-receptor antagonist)
Metoprolol (β-receptor antagonist)
Atenolol (β1 antagonist)
Prazosin (α1 antagonist)
Oxymetazoline (partial α2 adrenergic agonist)
== See also ==
Sympathomimetic drug
Sympatholytics
== References ==
== External links ==
Parasympathomimetics at the U.S. National Library of Medicine Medical Subject Headings (MeSH) | Wikipedia/Parasympathomimetic_drug |
Drug liberalization is a drug policy process of decriminalizing, legalizing, or repealing laws that prohibit the production, possession, sale, or use of prohibited drugs. Variations of drug liberalization include drug legalization, drug relegalization, and drug decriminalization. Proponents of drug liberalization may favor a regulatory regime for the production, marketing, and distribution of some or all currently illegal drugs in a manner analogous to that for alcohol, caffeine and tobacco.
Proponents of drug liberalization argue that the legalization of drugs would eradicate the illegal drug market and reduce the law enforcement costs and incarceration rates. They frequently argue that prohibition of recreational drugs—such as cannabis, opioids, cocaine, amphetamines and hallucinogens—has been ineffective and counterproductive and that substance use is better responded to by implementing practices for harm reduction and increasing the availability of addiction treatment. Additionally, they argue that relative harm should be taken into account in the regulation of drugs. For instance, they may argue that addictive or dependence-forming substances such as alcohol, tobacco and caffeine have been a traditional part of many cultures for centuries and remain legal in most countries, although other drugs which cause less harm than alcohol, caffeine or tobacco are entirely prohibited, with possession punishable with severe criminal penalties.
Opponents of drug liberalization argue that it would increase the amount of drug users, increase crime, destroy families, and increase the amount of adverse physical effects among drug users.
== Policies ==
The 1988 United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances made it mandatory for the signatory countries to "adopt such measures as may be necessary to establish as criminal offences under its domestic law" (art. 3, § 1) all the activities related to the production, sale, transport, distribution, etc. of the substances included in the most restricted lists of the 1961 Single Convention on Narcotic Drugs and 1971 Convention on Psychotropic Substances. Criminalization also applies to the "cultivation of opium poppy, coca bush or cannabis plants for the purpose of the production of narcotic drugs". The Convention distinguishes between the intent to traffic and personal consumption, stating that the latter should also be considered a criminal offence, but "subject to the constitutional principles and the basic concepts of [the state's] legal system" (art. 3, § 2).
Drug liberalization proponents hold differing reasons to support liberalization, and have differing policy proposals. The two most common positions are drug legalization (or re-legalization), and drug decriminalization. The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) defines decriminalization as the removal of a conduct or activity from the sphere of criminal law; depenalisation signifying merely a relaxation of the penal sanction exacted by law. Decriminalization usually applies to offences related to drug consumption and may include either the imposition of sanctions of a different kind (administrative) or the abolition of all sanctions; other (noncriminal) laws then regulate the conduct or activity that has been decriminalized. Depenalisation usually consists of personal consumption as well as small-scale trading and generally signifies the elimination or reduction of custodial penalties, while the conduct or activity still remains a criminal offence. The term legalization refers to the removal of all drug-related offences from criminal law, such as use, possession, cultivation, production, and trading.
Harm reduction refers to a range of public health policies designed to reduce the harmful consequences associated with recreational drug use and other high risk activities. Harm reduction is put forward as a useful perspective alongside the more conventional approaches of demand and supply reduction. Many advocates argue that prohibitionist laws criminalize people for suffering from a disease and cause harm, for example by obliging drug addicts to obtain drugs of unknown purity from unreliable criminal sources at high prices, increasing the risk of overdose and death. Its critics are concerned that tolerating risky or illegal behaviour sends a message to the community that these behaviours are acceptable.
=== The Controlled Substance Act (United States) ===
The Controlled Substance Act (CSA) categorizes all substances in need of regulation into one of the five schedules under the federal law. The categorization of these substances is determined by the potential for abuse and how safe it is to consume. In addition, a big determinant of this is the way in which the substance can be consumed or used medically. In its earliest stages, the CSA was created to combine the needs of two international treaties. These treaties were known as the Single Convention on Narcotic Drugs of 1961 and the Convention of Psychotropic Substances of 1971. Both treaties allowed public health authorities to work with the medical and scientific communities to create a classification system. The Schedule I substances were described as those that have no medical use whatsoever; meaning there is no prescription written for such substance. Schedule II substances are those that can be easily abused and lead to dependence. These substances can only be accessed through a written or electronic prescription from a physician. The schedule III substances are classified as those which have less potential for abuse than Schedule I and II but can still cause the individual to develop a mild dependence. Schedule IV substances are those with the least likeliness for abuse, therefore its medical use is common in the United States. Lastly, the Schedule V substances are those with little to no likelihood of abuse, along with very minimal dependence development.
=== Drug legalization (United States) ===
Drug legalization calls for a return to pre–1906 Pure Food and Drug Act attitudes when almost all drugs were legal. This would require ending government-enforced prohibition on the distribution or sale and personal use of specified (or all) currently banned drugs. Proposed ideas range from full legalization which would completely remove all forms of government control, to various forms of regulated legalization, where drugs would be legally available, but under a system of government control which might mean for instance:
Mandated labels with dosage and medical warnings.
Restrictions on advertising.
Age limitations.
Restrictions on amount purchased at one time.
Requirements on the form in which certain drugs would be supplied.
Ban on sale to intoxicated persons.
Special user licenses to purchase particular drugs.
A possible clinical setting for the consumption of some intravenous drugs or supervised consumption.
The regulated legalization system would probably have a range of restrictions for different drugs, depending on their perceived risk, so while some drugs would be sold over the counter in pharmacies or other licensed establishments, drugs with greater risks of harm might only be available for sale on licensed premises where use could be monitored and emergency medical care made available. Examples of drugs with different levels of regulated distribution in most countries include: caffeine (coffee, tea), nicotine (tobacco), and ethyl alcohol (beer, wine, spirits). Since each country has its own regulations and most distinguish between different classes of drugs, there can be difficulties when it comes to regulating which should be more readily accessible, since a particular drug criminalized in one area might be completely acceptable elsewhere. Full legalization is often proposed by groups, such as libertarians, who object to drug laws on moral grounds, while regulated legalization is suggested by groups like Law Enforcement Against Prohibition who object to the drug laws on the grounds that they fail to achieve their stated aims and instead they say greatly worsen the problems associated with the use of prohibited drugs but acknowledge that there are harms associated with currently prohibited drugs which need to be minimized. Not all proponents of drug re-legalization necessarily share a common ethical framework, and people may adopt this viewpoint for a variety of reasons. In particular, favoring drug legalization does not imply approval of drug use.
=== Drug decriminalization ===
Drug decriminalization calls for reduced or eliminated control or penalties compared to existing laws. There are proponents of drug decriminalization that support a system whereby those who use and possess drugs for personal use are not penalized. While others support the use of fines or other punishments to replace prison terms, and often propose systems whereby illegal drug users who are caught would be fined, but would not receive a permanent criminal record as a result. A central feature of drug decriminalization is the concept of harm reduction. Drug decriminalization is in some ways an intermediate between prohibition and legalization, and has been criticized by Peter Lilley as being "the worst of both worlds", in that drug sales would still be illegal, thus perpetuating the problems associated with leaving production and distribution of drugs to the criminal underworld, while also failing to discourage illegal drug use by removing the criminal penalties that might otherwise cause some people to choose not to use drugs.
In 2001, Portugal began treating use and possession of small quantities of drugs as a public health issue. Rather than incarcerating those in possession, they are referred to a treatment program by a regional panel composed of social workers, medical professionals, and drug experts. This also decreases the amount of money the government spends fighting a war on drugs and money spent keeping drug users incarcerated. HIV infection rates also have dropped from 104.2 new cases per million in 2000 to 4.2 cases per million in 2015. Anyone caught with any type of drug in Portugal, if it is for personal consumption, will not be imprisoned. Portugal is the first country that has decriminalized the possession of small amounts of drugs, to positive results.
As noted by the EMCDDA, across Europe in the last decades, there has been a movement toward "an approach that distinguishes between the drug trafficker, who is viewed as a criminal, and the drug user, who is seen more as a sick person who is in need of treatment" (EMCDDA 2008, 22). A number of Latin American countries have similarly moved to reduce the penalties associated with drug use and personal possession" (Laqueur, 2015, p. 748). Mexico City has decriminalized certain drugs and Greece has just announced that it is going to do so. Spain has also followed the Portugal model. Italy after waiting 10 years to see the result of the Portugal model, which Portugal deemed a success, has since recently followed suit. In May 2014, the Criminal Chamber of the Italian Supreme Court upheld a previous decision in 2013 by Italy's Constitutional Court, to reduce the penalties for the convictions for sale of soft drugs. Some other countries have virtual decriminalization for marijuana only, including in three U.S. states, such as Colorado, Washington, and Oregon, the Australian State of South Australia, and across the Netherlands, where there are legal marijuana cafes. In the Netherlands these cafes are called "coffeeshops".
== History ==
The cultivation, use and trade of psychoactive and other drugs has occurred since the dawn of civilization. Motivations claimed by supporters of drug prohibition laws across various societies and eras have included religious observance, allegations of violence by racial minorities, and public health concerns. Those who are proponents of drug legislation characterize these motivations as religious intolerance, racism, and public healthism. The British had gone to war with China in the 19th century in what became known as the First and Second Opium Wars to protect their valuable trade in narcotics. It was only in the 20th century that Britain and the United States outlawed cannabis. The campaign against alcohol prohibition culminated in the Twenty-first Amendment to the United States Constitution repealing prohibition on 5 December 1933, as well as liberalization in Canada, and some but not all of the other countries that enforced prohibition. Despite this, many laws controlling the use of alcohol continue to exist even in these countries. In the mid-20th century, the United States government led a major renewed surge in drug prohibition called the war on drugs.
Initial attempts to change the punitive drug laws which were introduced all over the world from the late 1800s onwards were primarily based around recreational use. Timothy Leary was one of the most prominent campaigners for the legal and recreational use of LSD. In 1967, a "Legalise pot" rally was held in Britain. As death toll from the drug war rose, other organisations began to form to campaign on a more political and humanitarian basis. Drug Policy Foundation formed in America and Release, a charity which gives free legal advice to drugs users and currently campaigns for drug decriminalization, also incorporated in the 1970s. Into the 21st century, the focus of the world's drug policy reform organisations is on the promotion of harm reduction in the Western World, and attempting to prevent the catastrophic loss of human life in developing countries where much of the world's supply of heroin, cocaine, and marijuana are produced. Drug policy reform advocates point to failed efforts, such as the Mexican Drug War, as signs that a new approach to drug policy is needed. According to some observers, the Mexican Drug War has claimed as many as 80,000 lives.
In 2014, a European Citizens' Initiative called "Weed Like to Talk" was launched within the European Union, with the aim of starting a debate in Europe about the legalization of the production, sale and use of marijuana in the European Union and finding a common policy for all EU member states. As of June 30, 2014, the initiative has collected 100,000 signatures from citizens in European member states. Should they reach 1 million signatures, from nationals of at least one quarter of the member states, the European Commission will be required to initiate a legislative proposal and a debate on the issue.
== Impacts ==
A Independent Scientific Committee on Drugs study found drug harms, such as economic cost, injury, family adversities, environmental damage, and community harm vary between different drugs.
=== Harms to others and society ===
Proponents of drug prohibition argue that many negative externalities, or third party costs, are associated with the consumption of illegal drugs.: 2043 : 183 Externalities like violence, environmental effects on neighborhoods, increased health risks, and increased healthcare costs are often associated with the illegal drug market.: 3
Opponents of prohibition argue that some of those externalities are created by criminalizing drug policies. They believe that much of the violence associated with drug trade is due to the illegal nature of drug trade, where there is no mediating authority to solve disputes peacefully and legally.: 3 : 177 The illegal nature of the market also affects the health of consumers by making it difficult to acquire syringes, which often leads to needle sharing.: 180–181
Economist Milton Friedman argues that prohibition of drugs creates many negative externalities like increased incarceration rates, the undertreatment of chronic pain, corruption, disproportional imprisonment of African Americans, compounding harm to users, the destruction of inner cities and harm to foreign countries. Proponents of legalization also argue that prohibition decrease the quality of the drugs made, which often leads to more physical harm, like accidental overdoses and poisoning, to the drug users.: 179 Steven D. Levitt and Ilyana Kuziemko point to the over crowding of prisons as another negative side effect of the war on drugs. They believe that by sending such a large number of drug offenders to prison, the war on drugs has reduced the prison space available for other offenders. This increased incarceration rate not only costs tax payers more to maintain, it could possibly increase crime by crowding violent offenders out of prison cells and replacing them with drug offenders.: 2043 According to economist Mark Thornton prohibition increases political corruption and crime.
Prohibition can produce more dangerous and addictive drugs. Milton Friedman estimated that over 10,000 deaths a year in the US are caused by the criminalization of drugs, and if drugs were to be made legal, number of innocent victims such as those shot down in drive by shootings would decrease.
=== Cost of law enforcement ===
A Harvard economist, Jeffrey Miron, estimated that ending the war on drugs would inject 76.8 billion dollars into the US economy in 2010 alone. He estimates that the government would save $41.3 billion for law enforcement and the government would gain up to $46.7 billion in tax revenue. Since the war on drugs began under the administration of President Richard Nixon, the federal drug-fighting budget has increased from $100 million in 1970 to $15.1 billion in 2010, with a total cost estimated near 1 trillion dollars over 40 years. In the same time period an estimated 37 million nonviolent drug offenders have been incarcerated. $121 billion was spent to arrest these offenders and $450 billion to incarcerate them. The legalization would reduce the cost of having to mass incarcerate marginalized communities, which are those who are disproportionately affected. Of those arrested for drug possession or drug related crimes, the majority of those individuals arrested are Black or Hispanic.
The economic inefficiency and ineffectiveness of such government intervention in preventing drug trade has been criticised by drug-liberty advocates. The war on drugs of the United States, that provoked legislation within several other Western governments, has also garnered criticism for these reasons.
=== Demand curve ===
Much of the debate surrounding the economics of drug legalization centers on the shape of the demand curve for illegal drugs and the sensitivity of consumers to changes in the prices of illegal drugs. Proponents of drug legalization often assume that the quantity of addictive drugs consumed is unresponsive to changes in price; however, studies into addictive but legal substances like alcohol and cigarettes have shown that consumption can be quite responsive to changes in prices. In the same study, economists Michael Grossman and Frank J. Chaloupka estimated that a 10% reduction in the price of cocaine would lead to a 14% increase in the frequency of cocaine use.: 459 This increase indicates that consumers are responsive to price changes in the cocaine market. There is also evidence that in the long run, consumers are much more responsive to price changes than in the short run,: 454 but other studies have led to a wide range of conclusions.: 2043
Considering that legalization would likely lead to an increase in the supply of drugs, the standard economic model predicts that the quantity of drugs consumed would rise and the prices would fall.: 428 Andrew E. Clark, an economist who has studied the effects of drug legalization, suggests that a specific tax, or sin tax, would counteract the increase in consumption.: 3
== Size of the illegal drug market ==
According to 2013 data from the United Nations Office on Drugs and Crime (UNODC) and European crime-fighting agency Europol, the annual global drugs trade is worth around $435 billion a year, with the annual cocaine trade worth $84 billion of that amount.
== Policies by country ==
=== Asia ===
==== Philippines ====
Senator Bato dela Rosa, despite having the reputation of leading the deadly war on drugs during the presidency of Rodrigo Duterte as chief of the Philippine National Police, filed a bill in the senate in November 2022 proposing the decriminalization of illegal drug use. This bid was an attempt to deal with prison overcrowding and underutilization of drug rehabilitation centers. While the proposal do not include drug trafficking and manufacturing, the bill was met with opposition from law enforcement agencies who believes it would send a "wrong signal" and encourage drug abuse. The Department of Health has supported the proposal.
==== Thailand ====
"A committee tasked with controlling illegal drugs has won a majority vote to have cannabis and hemp reclassified as narcotics, and the listing will take effect on" 1 January 2024, according to media.
Although Thailand has a strict drug policy, in May 2018, the Cabinet approved draft legislation that allows for more research into the effects of marijuana on people. Thus, the Government Pharmaceutical Organization (GPO) will soon begin clinical trials of marijuana as a preliminary step in the production of drugs from this plant. These medical studies are considered exciting, new landmarks in the history of Thailand, because the manufacture, storage, and use of marijuana has been completely outlawed in Thailand since 1979.
On 9 November 2018, the National Assembly of Thailand officially proposed to allow licensed medical use of marijuana, thereby legalizing what was previously considered a dangerous drug. The National Assembly on Friday submitted its amendments to the Ministry of Health, which would place marijuana and vegetable kratom in the category allowing their licensed possession and distribution in regulated conditions. The ministry reviewed the amendments before sending them to the cabinet, which returned it to the National Assembly for a final vote. This process was completed on 25 December 2018. Thus, Thailand became the first Asian country to legalize medical cannabis. These changes did not allow recreational use of drugs. These actions were taken because of the growing interest in the use of marijuana and its components for the treatment of certain diseases. Cannabis became decriminalized in Thailand on 9 June 2022, making recreational use also legal, although smoking in public can still incur penalties due to being considered a public nuisance. Supporters of legalization argue that the legal market for marijuana in Thailand could increase to $5 billion by 2024.
=== Europe ===
==== Czech Republic ====
In the Czech Republic, until 31 December 1998 only drug possession "for other person" (i.e. intent to sell) was criminal (apart from production, importation, exportation, offering or mediation, which was and remains criminal) while possession for personal use remained legal. On 1 January 1999, an amendment of the Criminal Code, which was necessitated in order to align the Czech drug rules with the Single Convention on Narcotic Drugs, became effective, criminalizing possession of "amount larger than small" also for personal use (Art. 187a of the Criminal Code) while possession of small amounts for personal use became a misdemeanor. The judicial practice came to the conclusion that the "amount larger than small" must be five to ten times larger (depending on drug) than a usual single dose of an average consumer.
On 14 December 2009, the Government of the Czech Republic adopted Regulation No. 467/2009 Coll., that took effect on 1 January 2010, and specified what "amount larger than small" under the Criminal Code meant, effectively taking over the amounts that were already established by the previous judicial practice. According to the regulation, a person could possess up to 15 grams of marijuana or 1.5 grams of heroin without facing criminal charges. These amounts were higher (often many times) than in any other European country, possibly making the Czech Republic the most liberal country in the European Union when it comes to drug liberalization, apart from Portugal. Under the Regulation No. 467/2009 Coll, possession of the following amounts or less of illicit drugs was to be considered smaller than large for the purposes of the Criminal Code and was to be treated as a misdemeanor subject to a fine equal to a parking ticket:
Marijuana 15 grams (or five plants)
Hashish 5 grams
Magic mushrooms 40 pieces
Peyote 5 plants
LSD 5 tablets
Ecstasy 4 tablets
Amphetamine 2 grams
Methamphetamine 2 grams
Heroin 1.5 grams
Coca 5 plants
Cocaine 1 gram
In 2013, a District Court in Liberec was deciding a case of a person that was accused of criminal possession for having 3.25 grams of methamphetamine (1.9 grams of straight methamphetamine base), well over the Regulation's limit of 2 grams. The court considered that basing a decision on mere Regulation would be unconstitutional and in breach of Article 39 of the Czech Charter of Fundamental Rights and Freedoms which states that "only a law may designate which acts constitute a crime and what penalties, or other detriments to rights or property, may be imposed for committing them" and proposed to the Constitutional Court to abolish the Regulation. In line with the District Courts' argument, the Constitutional Court abolished the Regulation effective from 23 August 2013, noting that the "amount larger than small" within the meaning of the Criminal Code may be designated only by the means of an Act of Parliament, and not a Governmental Regulation. Moreover, the Constitutional Court further noted that the Regulation merely took over already existing judicial practice of interpretation of what constitutes "amount larger than small" and thus its abolishment will not really change the criminality of drug possession in the country. Thus, the above-mentioned amounts from the now-not-effective Regulation remain as the base for consideration of police and prosecutors, while courts are not bound by the precise grammage.
Sale of any amount (not purchase) remains a criminal act. Possession of "amount larger than a small" of marijuana can result in a jail sentence of up to one year. For other illicit drugs, the sentence is up to two years. Trafficking as well as production (apart from growing up to five plants of marijuana) offenses carry stiffer sentences. Medical use of cannabis on prescription has been legal and regulated since 1 April 2013.
==== France ====
Following a contentious debate France opened its first supervised injection centre on 11 October 2016. Marisol Touraine, the Minister of Health, declared that the centre, located near the Gare du Nord in Paris, was "a strong political response, for a pragmatic and responsible policy that brings high-risk people back towards the health system rather than stigmatizing them."
==== Germany ====
In 1994, the Federal Constitutional Court ruled that drug addiction was not a crime, nor was the possession of small amounts of drugs for personal use. In 2000, the German narcotic law (BtmG) was changed to allow for supervised drug injection rooms. In 2002, a pilot study was started in seven German cities to evaluate the effects of heroin-assisted treatment on addicts, compared to methadone-assisted treatment. The positive results of the study led to the inclusion of heroin-assisted treatment into the services of the mandatory health insurance in 2009. On 4 May 2016, the Cabinet of Germany decided to approve the measure for legal cannabis for seriously ill patients who have consulted with a doctor and "have no therapeutic alternative". German Health Minister, Hermann Gröhe, presented the legal draft on the legalization of medical cannabis to the cabinet which was expected to take effect early 2017.
==== Ireland ====
On 2 November 2015, Aodhán Ó Ríordáin, the minister in charge of the National Drugs Strategy, announced that Ireland planned to introduce supervised injection rooms. The minister also referenced that possession of controlled substances will be decriminalized although supply and production will remain criminalized. On 12 July 2017, the Health Committee of the Irish government rejected a bill that would have legalized medical cannabis.
==== Netherlands ====
The drug policy of the Netherlands is based on two principles: (1) drug use is a public health issue, not a criminal matter, and (2) a distinction between hard and soft drugs exists. Additionally, a policy of non-enforcement has led to a situation where reliance upon non-enforcement has become common; because of this, the courts have ruled against the government when individual cases were prosecuted. Cannabis remains a controlled substance in the Netherlands and both possession and production for personal use are still misdemeanors, punishable by fine. Cannabis coffee shops are also illegal according to the statutes.
==== Norway ====
On 14 June 2010, the Stoltenberg commission recommended implementing heroin assisted treatment and expanding harm reduction measures. On 18 June 2010, Knut Storberget, Minister of Justice and the Police, announced that the ministry was working on new drug policy involving decriminalization by the Portugal model, which was to be introduced to parliament before the next general election. Storberget later changed his statements, saying the decriminalization debate is "for academics", instead calling for coerced treatment. In early March 2013, minister of health and care services Jonas Gahr Støre proposed to decriminalize the inhalation of heroin by 2014 as a measure to decrease drug overdoses. In 2011, there were 294 fatal overdoses, in comparison to only 170 traffic related deaths.
The country was preparing a massive policy change in terms of how to deal with drug use and drug possession for personal use. The reform titled "From punishment to help" was approved by the Norwegian government in 2017 and was in the final phase of approval by the parliament. Changes were expected to be implemented by early 2021. The new reform policy emphasizes that criminalizing drug use has no significant effect on rates of drug consumption and that drug addiction is better dealt with by health care services, hence the slogan "from punishment to help". Instead of fines or prison time, a person caught with a drug quantity for personal use will now be met with an independent panel consisting of social and health care workers that will discuss administrative sanctions or addiction treatment methods. This will hopefully encourage problematic users to seek help rather than fear of prosecution. There is also hope that this will improve the relationship between drug users and law enforcement officers. Opponents of the reform, including the police force and the Progress Party, fear that drug use will increase once a person is no longer at risk of facing criminal charges.
As of 21 July 2022, drug decriminalisation has not materialised in Norway. As of this date, only those who have substance use disorders may go unpunished if the amount of illegal drugs they have meets the criteria of what is deemed an amount for personal use.
==== Portugal ====
In 2001, Portugal became the first European country to abolish all criminal penalties for personal drug possession, under Law 30/2000. In addition, drug users were to be provided with therapy rather than prison sentences. Research commissioned by the Cato Institute and led by Glenn Greenwald found that in the five years after the start of decriminalization, illegal drug use by teenagers had declined, the rate of HIV infections among drug users had dropped, deaths related to heroin and similar drugs had been cut by more than half, and the number of people seeking treatment for drug addiction had doubled. Peter Reuter, a professor of criminology and public policy at the University of Maryland, College Park, suggested that the heroin usage rates and related deaths may have been due to the cyclical nature of drug epidemics. In 2009, he stated that "decriminalization in Portugal has met its central goal. Drug use did not rise." In 2022, drug use had increased to 12.8 percent, compared to 7.8 percent in 2001 when the policies had been implemented.
==== Ukraine ====
The use of marijuana in Ukraine is not prohibited, but the manufacture, storage, transportation and sale of cannabis and its derivatives are under administrative and criminal liability. Speaking on the legalization of soft drugs in Ukraine has been going on for a long time. In June 2016, the Parliament received a bill on the legalization of marijuana for medical purposes. It dealt with changes to the current act "On narcotic drugs, psychotropic substances and precursors" and was registered number 4533. The document must examine the relevant committee, and then submit it to the government. It was expected that this would happen in the fall of 2016, but the bill was not considered. In October 2018, a petition appeared on the website of electronic appeals to the President of Ukraine asking for the legalization of marijuana. In October 2018, the State Service of Ukraine on Drugs and Drug Control issued the first license for the import and re-export of raw materials and products derived from cannabis. The corresponding licenses were obtained by the USA company C21. The company is also in the process of applying for additional licenses, including the cultivation of cannabis.
=== Latin America ===
In the late 2000s and early 2010s, advocacy for drug legalization has increased in Latin America. Spearheading the movement Uruguayan government announced in 2012 plans to legalize state-controlled sales of marijuana in order to fight drug-related crimes. Some countries in this region have already advanced towards depenalization of personal consumption.
==== Argentina ====
In August 2009, the Supreme Court of Argentina declared in a landmark ruling that it was unconstitutional to prosecute citizens for having drugs for their personal use – "adults should be free to make lifestyle decisions without the intervention of the state". The decision affected the second paragraph of Article 14 of the country's drug control legislation (Law Number 23,737) that punishes the possession of drugs for personal consumption with prison sentences ranging from one month to two years (although education or treatment measures can be substitute penalties). The unconstitutionality of the article concerns cases of drug possession for personal consumption that does not affect others.
==== Brazil ====
In 2002 and 2006, Brazil went through legislative changes, resulting in a partial decriminalization of possession for personal use. Prison sentences no longer applied and were replaced by educational measures and community services; however, the 2006 law does not provide objective means to distinguish between users or traffickers. A disparity exists between the decriminalization of drug use and the increased penalization of selling drugs, punishable with a maximum prison sentences of 5 years for the sale of very minor quantities of drugs. Most of those incarcerated for drug trafficking are offenders caught selling small quantities of drugs, among them drug users who sell drugs to finance their drug habits. Since 2006, there has been a long debate whether the anti-drug law goes against the Constitution and principle of personal freedom. In 2009, the Supreme Federal Court re-opened to vote if the law is Constitutional, or if it goes against the Constitution specifically against personal Freedom of choice. Since each Minister inside the tribunal can take a personal time to evaluate the law, the voting can take years. In fact, the voting was re-opened in 2015, 3 ministers voted in favor, and then the law was again paused by another minister.
==== Colombia ====
Guatemalan President Otto Pérez Molina and Colombian President Juan Manuel Santos proposed the legalization of drugs in an effort to counter the failure of the war on drugs, which was said to have yielded poor results at a huge cost. On 25 May 2016, the Colombian congress approved the legalization of marijuana for medical usage.
==== Costa Rica ====
Costa Rica has decriminalized drugs for personal consumption. Manufacturing or selling drugs is still a jailable offense.
==== Ecuador ====
According to the 2008 Constitution of Ecuador, in its Article 364, the Ecuadorian state does not see drug consumption as a crime but only as a health concern. Since June 2013, the state drugs regulatory office CONSEP has published a table which establishes maximum quantities carried by persons so as to be considered in legal possession and that person as not a seller of drugs. The "CONSEP established, at their latest general meeting, that the following quantities be considered the maximum consumer amounts: 10 grams of marijuana or hash, 4 grams of opiates, 100 milligrams of heroin, 5 grams of cocaine, 0.020 milligrams of LSD, and 80 milligrams of methamphetamine or MDMA".
==== Honduras ====
On 22 February 2008, Honduras President Manuel Zelaya called on the United States to legalize drugs in order to prevent the majority of violent murders occurring in Honduras. Honduras is used by cocaine smugglers as a transiting point between Colombia and the US. Honduras, with a population of 7 million affected people an average of 8–10 murders a day, with an estimated 70% being as a result of this international drug trade. According to Zelaya, the same problem is occurring in Guatemala, El Salvador, Costa Rica, and Mexico.
==== Mexico ====
In April 2009, the Mexican Congress approved changes in the General Health Law that decriminalized the possession of illegal drugs for immediate consumption and personal use allowing a person to possess up to 5 g of marijuana or 500 mg of cocaine. The only restriction is that people in possession of drugs should not be within a 300-meter radius of schools, police departments, or correctional facilities. Opium, heroin, LSD, and other synthetic drugs were also decriminalized, it will not be considered as a crime as long as the dose does not exceed the limit established in the General Health Law. Many question this, as cocaine is as much synthesised as heroin, both are produced as extracts from plants. The law establishes very low amount thresholds and strictly defines personal dosage. For those arrested with more than the threshold allowed by the law this can result in heavy prison sentences, as they will be assumed to be small traffickers even if there are no other indications that the amount was meant for selling.
==== Uruguay ====
Uruguay is one of few countries that never criminalized the possession of drugs for personal use. Since 1974, the law establishes no quantity limits, leaving it to the judge's discretion to determine whether the intent was personal use. Once it is determined by the judge that the amount in possession was meant for personal use, there are no sanctions. In June 2012, the Uruguayan government announced plans to legalize state-controlled sales of marijuana in order to fight drug-related crimes. The government also stated that they will ask global leaders to do the same.
On 31 July 2013, the Uruguayan House of Representatives approved a bill to legalize the production, distribution, sale, and consumption of marijuana by a vote of 50 to 46. The bill then passed the Senate, where the left-leaning majority coalition, the Broad Front, held a comfortable majority. The bill was approved by the Senate by 16 to 13 on 10-December-2013. The bill was presented to the President José Mujica, also of the Broad Front coalition, who has supported legalization since June 2012. Relating this vote to the 2012 legalization of marijuana by the U.S. states Colorado and Washington, John Walsh, drug policy expert of the Washington Office on Latin America, stated that "Uruguay's timing is right. Because of last year's Colorado and Washington State votes to legalize, the U.S. government is in no position to browbeat Uruguay or others who may follow."
In July 2014, government officials announced that part of the implementation of the law (the sale of cannabis through pharmacies) is postponed to 2015, as "there are practical difficulties". Authorities will grow all the cannabis that can be sold legal. Concentration of THC shall be 15% or lower. In August 2014, an opposition presidential candidate, who was not elected in the November 2014 presidential elections, claimed that the new law was never going to be applied, as it was not workable. By the end of 2016 the government announced that the sale through pharmacies will be fully implemented during 2017.
=== North America ===
==== Canada ====
The cultivation of cannabis is currently legal in Canada, except in Manitoba and Quebec. Citizens outside those provinces may grow up to four plants per residence for personal use, and recreational use of cannabis by the general public is legal with restrictions on smoking in public locations that vary by jurisdiction. The sale of marijuana seeds is also legal.
In 2001, The Globe and Mail reported that a poll found 47% of Canadians agreed with the statement, "The use of marijuana should be legalized" in 2000, compared to 26% in 1975. A more recent poll found that more than half of Canadians supported legalization. In 2007, Prime Minister Stephen Harper's government tabled Bill C-26 to amend the Controlled Drugs and Substances Act, 1996 to bring forth a more restrictive law with higher minimum penalties for drug crimes. Bill-26 died in committee after the dissolution of the 39th Canadian Parliament in September 2008, but the Bill was subsequently resurrected by the government twice.
In 2015, Prime Minister Justin Trudeau and the Liberal Party of Canada campaigned on a promise to legalize marijuana. The Cannabis Act was passed on 19 June 2018, which made marijuana legal across Canada on 17 October 2018. Since legalization, the country has set up an online framework to allow consumers to purchase a wide variety of merchandise ranging from herbs, extract, oil capsules, and paraphernalia. Most provinces also provide a venue for purchase through physical brick and mortar stores.
In 2021, the city councils of Vancouver and Toronto voted to decriminalize the simple possession of all drugs; and submitted proposals requesting special exemption from the federal Health Minister to do so, citing numerous scientific, psychological, medical, and socio-economic benefits. In early 2022, the Province of British Columbia submitted its own request for exemption, closely following the Vancouver model. By April of that year, the Edmonton City Council had also passed a motion to request exemption from federal drug enforcement laws in order decriminalize "simple personal possession" of illegal drugs, voting in favour 11–2. On 31 May 2022, the federal government of Canada approved British Columbia's proposal to decriminalize all "hard drugs", such as heroin, fentanyl, cocaine, and methamphetamine. As of 1 January 2023, British Columbians aged 18 years or older are allowed to carry up to a cumulative total of 2.5 grams of these substances without the risk of arrest or criminal charges. Police are not to confiscate the drugs, and there is no requirement that people found to be in possession seek treatment; however, the production, trafficking, and exportation of these drugs remain illegal.
==== United States ====
As of 2024, prior to November elections, 38 states, Washington, D.C., and certain U.S. territories allow medical use of cannabis. Of those 38 states, 24 also allow recreational use, as does Washington, D.C. Voters in North and South Dakota and Florida will decide on recreational use in November, and Nebraskans will vote on cannabis use for medical reasons. Legalization in states created significant legal and policy tensions between federal and state governments and sometimes between states. State laws in conflict with federal law about cannabis remain valid, and prevent state level prosecution, despite cannabis being illegal under federal law, as determined in Gonzales v. Raich (2005).
Throughout the United States, various people and groups have been pushing for the legalization of marijuana for medical reasons. Organizations such as NORML and the Marijuana Policy Project work to decriminalize and legalize possession, use, cultivation, and sale of marijuana by adults. In 1996, 56% of California voters voted for California Proposition 215, legalizing the growing and use of marijuana for medical purposes and making California both the first state to outlaw marijuana, in 1913, and the first state to legalize medical marijuana.
On 6 November 2012, the states of Washington and Colorado legalized possession of small amounts of marijuana for private recreational use and created a process for writing rules for legal growing and commercial distribution of marijuana within each state, after having legalized medical cannabis in 1998 and 2000, respectively. In 2014, voters in Oregon, Alaska, and Washington, D.C. voted to legalize marijuana for recreational use, as did California in 2016, with the passage of California Proposition 64, and Michigan in 2018. In 2019, Illinois passed the Illinois Cannabis Regulation and Tax Act, making Illinois the first state to legalize recreational use by an act of the state legislature, which took effect 1 January 2020. In 2020, Oregon decriminalized the possession of all drugs in Measure 110, but in 2024, the Oregon State Senate passed a bill to reverse the decriminalization of hard drugs such as heroin after there was public backlash to the impacts of the measure. In 2021, New York legalized adult-use cannabis when it passed the Marijuana Regulation and Taxation Act (MRTA).
=== Oceania ===
==== Australia ====
In 2016, Australia legalised medicinal cannabis on a federal level. Since 1985, the Federal Government has run a declared war on drugs and while initially Australia led the world in 'harm-minimization' approach, they have since lagged. Australia has a number of political parties that focus on cannabis reform, The (HEMP) Help End Marijuana Prohibition Party was founded in 1993 and registered by the Australian Electoral Commission in 2000. The Legalise Cannabis Queensland Party was established in 2020. A number of Australian and international groups have promoted reform in regard to 21st-century Australian drug policy. Organisations such as Australian Parliamentary Group on Drug Law Reform, Responsible Choice, the Australian Drug Law Reform Foundation, Norml Australia, Law Enforcement Against Prohibition (LEAP) Australia and Drug Law Reform Australia advocate for drug law reform without the benefit of government funding. The membership of some of these organisations is diverse and consists of the general public, social workers, lawyers and doctors, and the Global Commission on Drug Policy has been a formative influence on a number of these organisations. In 1994, the Australian National Task Force on Cannabis formed under the Ministerial Council on Drug Strategy noted that the social harm of cannabis prohibition is greater than the harm from cannabis itself, total prohibition policies have been unsuccessful in reducing drug use and have caused significant social harm, as well as higher law enforcement costs, the use of cannabis is widespread in Australia and that its adverse health effects are modest and only affect a minority of users.
In 2012, the think tank Australia 21, released a report on the decriminalization of drugs in Australia. It noted that "by defining the personal use and possession of certain psychoactive drugs as criminal acts, governments have also avoided any responsibility to regulate and control the quality of substances that are in widespread use." Prohibition has fostered the development of a criminal industry that is corrupting civil society and government and killing our children." The report also highlighted the fact that, just as alcohol and tobacco are regulated for quality assurance, distribution, marketing and taxation, so should currently, unregulated, illicit drugs. There has been a number of enquires in Australia relating to cannabis and other illicit drugs, in 2019 the Queensland government instructed the Queensland Productivity Commission to conduct an enquiry into imprisonment and recidivism in QLD; the final report was sent to the Queensland Government on 1 August 2019 and publicly released on 31 January 2020. The commission found that "all available evidence shows the war on drugs fails to restrict usage or supply" and that "decriminalisation would improve the lives of drug users without increasing the rate of drug use" with the commission ultimately recommending that the Queensland government legalise cannabis. The QPC said the system had also fuelled an illegal market, particularly for methamphetamine. Although the Palaszczuk Queensland Labor Party led state government rejected the recommendations of its own commission and said it had no plans to alter any laws around cannabis, a decision that received heavy scrutiny from supporters of decriminalization, legalisation, progressive and non progressive drug policy advocates alike.
In 2019, The Royal Australasian College of Physicians (RACP) and St. Vincent's Health Australia called on the NSW Government to publicly release the findings of the Special Commission of Inquiry into the Drug 'Ice, saying there was "no excuse" for the delay. The report was the culmination of months of evidence from health and judicial experts, as well as families and communities affected by amphetamine-type substances across NSW. The report made 109 recommendations aimed to strengthen the NSW Governments response regarding amphetamine-based drugs such as crystal meth or ice. Major recommendations included more supervised drug use rooms, a prison needle and syringe exchange program, state-wide clinically supervised substance testing, including mobile pill testing at festivals, decriminalisation of drugs for personal use, a cease to the use of drug detection dogs at music festivals and to limit the use of strip searches. The report, also called for the NSW Government to adopt a comprehensive Drug and Alcohol policy, with the last drug and Alcohol policy expiring over a decade ago. The reports commissioner said the state's approach to drug use was profoundly flawed and said reform would require "political leadership and courage" and "Criminalising use and possession encourages us to stigmatise people who use drugs as the authors of their own misfortunate". Mr Howard said current laws "allow us tacit permission to turn a blind eye to the factors driving most problematic drug use" including childhood abuse, domestic violence and mental illness. The NSW government rejected the reports key recommendations, saying it would consider the other remaining recommendations. Director of the Drug Policy Modelling Program (DPMP) at UNSW Sydney's Social Policy Research Centre said the NSW Government has missed an opportunity to reform the state's response to drugs based on evidence. The NSW Government is yet to officially respond to the inquiry as of November 2020, a statement was released from the government citing intention to respond by the end of 2020.
In the Australian Capital Territory, after a bill was passed on 25 September 2019, new laws came into effect on 31 January 2020. While personal possession and growth of small amounts of cannabis remains prohibited non-medicinal purposes in every other jurisdiction in Australia, it allowed for possession of up to 50 grams of dry material, 150 grams of wet material, and cultivation of 2 plants per individual up to 4 plants per household, effectively legalising the possession and growing of cannabis in the ACT; however the sale and supply of cannabis and cannabis seeds is still illegal, so the effects of the laws are limited and the laws also contradict federal laws. It is also still illegal to smoke or use cannabis in a public place, expose a child or young person to cannabis smoke, store cannabis where children can reach it, grow cannabis using hydroponics or artificial cultivation, grow plants where they can be accessed by the public, share or give cannabis as a gift to another person, to drive with any cannabis in your system, or for people aged under 18 to grow, possess, or use cannabis.
==== New Zealand ====
On 18 December 2018, the Labour-led government announced a nationwide, binding referendum on the legality of cannabis for personal use, set to be held as part of the 2020 general election. This was a condition of the Green Party giving confidence and supply to the Government. On 7 May 2019, the government announced that the 2020 New Zealand cannabis referendum would be a yes/no question to enact a yet-to-be created piece of legislation. Despite the earlier commitment, the referendum was non-binding, the proposed Cannabis Legalisation and Control Bill would have need to be introduced into Parliament and passed like any other piece of legislation; therefore, the government was not in fact bound to the results of the referendum. Official results for the general election and referendums were released on 6 November 2020. The number opposed to legalisation was 50.7% with 48.4% in favour and 0.9% of votes were declared Informal.
== Groups advocating change ==
The Senlis Council, a European development and policy think tank, has, since its conception in 2002, advocated that drug addiction should be viewed as a public health issue rather than a purely criminal matter. The group does not support the decriminalisation of illegal drugs. Since 2003, the council has called for the licensing of poppy cultivation in Afghanistan in order to manufacture poppy-based medicines, such as morphine and codeine, and to combat poverty in rural communities, breaking ties with the illicit drugs trade. The Senlis Council outlined proposals for the implementation of a village based poppy for medicine project and calls for a pilot project for Afghan morphine at the next planting season.
== Organizations involved in lobbying, research and advocacy ==
=== Canada ===
Le Dain Commission of Inquiry into the Non-Medical Use of Drugs
=== Europe ===
Beckley Foundation
Cannabis Law Reform
Drug Equality Alliance (DEA)
European Coalition for Just and Effective Drug Policies (ENCOD) (Branches in Austria, Germany and Norway)
Legalize.net (Netherlands)
Schildower Kreis (Goethe University Frankfurt, Germany)
NORML UK
Re:Vision Drug Policy Network (United Kingdom)
Regulación Responsible (Spain)
Release (agency) (United Kingdom)
Students for Sensible Drug Policy UK (United Kingdom)
Transform Drug Policy Foundation
=== Australia ===
Australian National Council on Drugs
Drug Policy Australia
Network Against Prohibition
=== New Zealand ===
The Helen Clark Foundation
NORML New Zealand
The STAR Trust
=== United States ===
American Civil Liberties Union
Americans for Safe Access
Drug Policy Alliance
High Times
High Times Freedom Fighters
Law Enforcement Against Prohibition
Lindesmith Center
Marijuana Policy Project
MASS CANN/NORML
Multidisciplinary Association for Psychedelic Studies (MAPS)
National Organization for the Reform of Marijuana Laws
Students for Sensible Drug Policy
Veterans for Medical Marijuana Access
November Coalition (United States)
Women Grow
== Political parties with drug liberalization policies ==
Many political parties support, to various degrees, and for various reasons, liberalizing drug control laws, from liberal parties to far-left movements, as well as some right-wing intellectuals. Drug liberalization is fundamental in the platforms of most Libertarian parties. There are also numerous single issue marijuana parties devoted to campaign for the legalization of cannabis exclusively.
=== Australia ===
Australian Greens
Drug Law Reform Australia
Fusion Party
Legalise Cannabis Australia
Legalise Cannabis Queensland
Legalise Cannabis Western Australia Party
Reason Party
=== Canada ===
Liberal Party of Canada
New Democratic Party of Canada
Libertarian Party of Canada
Marijuana Party
=== Hungary ===
MKKP
=== Netherlands ===
GroenLinks
D66
=== Germany ===
Die Linke
=== New Zealand ===
Green Party of Aotearoa New Zealand
=== Portugal ===
Left Bloc
Liberal Initiative
LIVRE
=== United Kingdom ===
Green Party of England and Wales
Liberal Democrats – in March 2016, the Liberal Democrats became the first major political party in the United Kingdom to support the legalisation of cannabis.
=== International ===
Pirate Party
== See also ==
== References ==
== Further reading ==
Anderson, D. Mark, and Daniel I. Rees. 2023. "The Public Health Effects of Legalizing Marijuana." Journal of Economic Literature 61(1): 86–143.
International Coalition on Drug Policy Reform and Environmental Justice. 2023. "Revealing the missing link to Climate Justice: Drug Policy."
== External links ==
Transform Drug Policy Foundation – A UK-based think-tank that works to develop systems for control and regulation that can be applied globally.
Law Enforcement Against Prohibition – Run by retired law enforcement professionals who oppose prohibition.
Voluntary Committee of Lawyers – a New York-based network of judges and lawyers opposed to current federal drug laws.
NORML (US National Organization for the Reform of Marijuana Laws) – a US wide network of activists seeking to liberalize cannabis legislation.
Re:Vision Drug Policy Network – an organisation for young people aged 16–25 campaigning against prohibition.
The Report of the Canadian Government Commission of Inquiry into the Non-Medical Use of Drugs – 1972 – The LeDain Commission Report
Drug Law Reform – a project of the Transnational Institute (TNI)
Draft Plan for Legalization from LIFE – an example of a policy formulation proposed for substance legalization
Count The Costs
Schaffer Library of Drug Policy
Worldwide Psychedelic Laws Tracker | Wikipedia/Drug_liberalization |
Illegal drug trade in the Turks and Caicos Islands involves trans-shipment of cocaine and marijuana through The Turks and Caicos Islands (TCI) to the United States.
== Developments ==
Then Chief Minister Norman Saunders was arrested in March 1985 together with Commerce and Development Minister Stanford Missick. Saunders was alleged by the US Drug Enforcement Administration to have accepted $30,000 from undercover agents to ensure safe passage of drugs by permitting safe stopover refuelling of drug flights from Colombia to the United States. Video evidence showed Saunders accepting $20,000 from an agent.
Saunders was convicted in July 1985 of conspiracy, though he was acquitted of the charge of conspiring to import drugs into the United States (which Missick was also convicted of). He was sentenced to eight years in prison and fined $50,000.
In 2022, an outbreak of extreme violence, with over 30 murders, was attributed to a turf war between drug gangs looking to control drug trafficking routes.
== See also ==
Designer drug
Drug liberalization
Legality of cannabis by country
Minors and the legality of cannabis
== References == | Wikipedia/Illegal_drug_trade_in_the_Turks_and_Caicos_Islands |
Drug precursors, also referred to as precursor chemicals or simply precursors, are substances used to manufacture illicit drugs. Most precursors also have legitimate commercial uses and are legally used in a wide variety of industrial processes and consumer products, such as medicines, flavourings, and fragrances.
International regulators of precursor chemicals consider it necessary to recognise and protect the legal trade of these chemicals, while at the same time preventing their diversion from such trade for use in the illegal manufacture of narcotic drugs and psychoactive substances. For example, phenylacetic acid is used legally in the production of penicillin, flavourings, perfume, and cleaning solutions, but it can also be used in the illegal manufacture of amphetamines and methamphetamine.
The international framework for precursor control is set out under Articles 12 and 13 of the 1988 United Nations Convention against Illicit Traffic in Narcotic Drugs and Psychotropic Substances, requiring UN member states to establish and enforce regulatory systems that monitor the trade in their country, as well as movement of precursor chemicals into and out of their country (e.g. transshipment). Monitoring is carried out through measures including the licensing and registration of operators, procedures and requirements governing movement of chemicals, as well as documentation, record keeping and labelling requirements.
The International Narcotics Control Board has also established tools including the Pre-Export Notification Online (PEN-Online) and Precursors Incident Communication (PICS) systems, in addition to annual information reporting through 'Form D' and the International Special Surveillance List (ISSL) for non-controlled and designer chemicals which can be used as precursors themselves for certain illicit drugs or pre-precursors, to support UN Member States in their domestic regulatory efforts and cross-border coordination. There is also harmonised legislation across Europe which puts a control system in place with the aim to achieve a balance between precursor diversion prevention without inhibiting legal trade.
== The role of East and Southeast Asia ==
The East Asia and Southeast Asia regions are referred to by many regulatory and law enforcement experts as the largest source for precursor chemicals used for illicit drug production, including by the INCB and UN Office on Drugs and Crime, in-part because a wide variety of chemicals are frequently diverted and trafficked within the region and to other parts of the world including to North America, Central and South America, Oceania (Australia and New Zealand), Europe, and Africa.
Southeast and East Asia experienced a methamphetamine epidemic beginning in the late 1990s, which peaked in 2000–2001. The region later became a global hub for methamphetamine production and trafficking.
Opium production has long been a major concern in the Golden Triangle region, especially Myanmar, but since the early 2000s production has diversified towards synthetic drug production. Countries in Southeast Asia, and particularly the Mekong region, have collectively witnessed sustained increases in seizures of methamphetamine over the last decade, totaling over 169 tons and a record of over 1.1 billion methamphetamine tablets in 2023, more than any other part of the world, with Myanmar representing one of the world's largest sources of the drug. In April and May 2020, Myanmar authorities reported Asia's largest ever drug operation in Shan State, seizing 193 million methamphetamine tablets, hundreds of kilogrammes of crystal methamphetamine as well as some heroin, and over 162,000 litres and 35.5 tons of drug precursors as well as sophisticated production equipment and several staging and storage facilities. The growth of the industry has been highlighted as potentially fueling conflict in the region.
The Golden Triangle Special Economic Zone (GTSEZ) has emerged as a key hub for the trade. The GTSEZ was founded and is chaired by sanctioned Chinese national Zhao Wei. The United Nations Office on Drugs and Crime (UNODC) has raised concerns several times about Laos being used by organized crime to traffic drugs, precursor chemicals and other illicit commodities, and that unregulated border casinos in the Mekong region including Kings Romans are being used to launder money. In early October 2020, a $50 million investment to build a port in the Laotian town of Ban Mom, directly north of the Golden Triangle Special Economic Zone, was made by Osiano Trading Sole Co., a partner or front company of Zhao Wei and his organization.
== Trafficking ==
Organized crime groups operating in East and Southeast Asia have demonstrated significant sophistication in recent years, as well as their comparative advantage when it comes to sourcing precursors and specialized non-controlled precursor and pre-precursor chemicals for the illicit manufacture of drugs. Aside from regulatory controls that are easily bypassed, Southeast Asia, and in particular the Mekong sub-region, is situated next to two of the world's leading chemical-producing countries, China and India.
However, while the chemical and pharmaceutical industries of China, and to a lesser extent India, are known to be the primary sources of the chemicals used for illicit drug production in Southeast Asia, these industries have also grown rapidly within the region itself in recent years and play an increasingly important role in the illicit drug trade. For example, between 2010 and 2018, outputs of chemicals and their products in Indonesia, Malaysia, the Philippines, Singapore, Thailand, and Vietnam, increased in value by nearly 40 per cent from US$132 billion to US$181 billion.
Regional experts have highlighted concerns regarding the use of border infrastructure to facilitate trafficking of precursors and supporting illicit industries. For example, the Ban Mom port mentioned above is located in an area confirmed to be a location used for trafficking drugs and precursor chemicals into and out of drug production areas and special regions. Laos is the key route into the Golden Triangle for precursors from China, and for the export of finished products down the Mekong, shipments of which have been seized across the region and beyond. The UNODC has also noted an increase in shipments from Myanmar via the Andaman Sea. In 2024, UNODC reported that the year prior seizures of methamphetamine reached the highest amount ever recorded for the region.
The synthetic drug market has grown rapidly due in large part to organized crime groups leveraging creative chemistry and gaps in precursor regulatory frameworks to supply both controlled and non-controlled chemicals and designer precursors to expand production.
Examples of such precursors and drugs made with them are listed below.
== Precursors ==
2C-H
2C-x
N-Acetylanthranilic acid
methaqualone
Anthranilic acid
methaqualone
Benzaldehyde
amphetamine
phenylacetone
Benzyl cyanide
phenylacetone
CBD
THC (see conversion of CBD to THC)
Ephedrine and pseudoephedrine
methamphetamine
methcathinone
Ergocristine, ergine, ergonovine, and ergotamine
LSD
Ethylamine
ethylamphetamine
GBL
GHB
Safrole, isosafrole, and 3,4-methylenedioxyphenylpropan-2-one
MDMA, MDEA, MDA
Methylamine
methamphetamine
N-Methylephedrine and N-methylpseudoephedrine
dimethylamphetamine
N-Phenethyl-4-piperidone (NPP)
fentanyl and analogues
Nitroethane
amphetamine
MDA
phenylacetone
Norpseudoephedrine and phenylpropanolamine
amphetamine
4-methylaminorex
Phenylacetic acid
phenylacetone
Piperidine
phencyclidine (PCP)
Piperonal (heliotropin)
MDMA, MDEA, MDA
Propionic anhydride
fentanyl and analogues
Acetic anhydride
heroin
methaqualone
phenylacetone
Benzyl chloride
methamphetamine
1-(2-Chloro-N-methylbenzimidoyl)cyclopentanol
ketamine
== Reagents ==
Hydriodic acid
methamphetamine
Hypophosphorous acid
amphetamine
methamphetamine
Iodine
amphetamine
methamphetamine
Red phosphorus and white phosphorus
amphetamine
methamphetamine
Potassium permanganate
cocaine
methcathinone
Sodium permanganate
cocaine
Hydrochloric acid (hydrogen chloride)
amphetamine
cocaine
N,N-dimethylamphetamine
ethylamphetamine
fentanyl and analogues
heroin
LSD
MDA
MDE
MDMA
methamphetamine
methaqualone
methcathinone
phencyclidine (PCP)
Sulfuric acid
amphetamine
cocaine
MDA
MDE
MDMA
methamphetamine
methaqualone
phenylacetone
== Solvents ==
Acetone
cocaine
heroin
LSD
MDA
MDE
MDMA
methamphetamine
Diethyl ether
amphetamine
cocaine
fentanyl and analogues
heroin
LSD
MDA
MDE
MDMA
methamphetamine
methaqualone
methcathinone
phencyclidine (PCP)
phenylacetone
Methylethylketone (butanone) and methyl isobutyl ketone
cocaine
heroin
MDA
MDEA
methamphetamine
Toluene
cocaine
fentanyl and analogues
methaqualone
phencyclidine (PCP)
phenylacetone
Denatured Ethanol/Isopropynol
methamphetamine
cocaine
heroin
Hexane
methamphetamine
== References ==
== See also ==
Chemical Diversion and Trafficking Act
Clandestine chemistry
Combat Methamphetamine Epidemic Act of 2005
Controlled Substances Act
DEA list of chemicals
European law on drug precursors
United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances | Wikipedia/Drug_precursors |
The war on drugs, sometimes referred to in the 21st century as the war on cartels in contexts of military intervention and counterterrorism, is a global anti-narcotics campaign led by the United States federal government, including drug prohibition and foreign assistance, with the aim of reducing the illegal drug trade in the US. The initiative's efforts includes policies intended to discourage the production, distribution, and consumption of psychoactive drugs that the participating governments, through United Nations treaties, have made illegal.
The term "war on drugs" was popularized by the media after a press conference, given on June 17, 1971, during which President Richard Nixon declared drug abuse "public enemy number one". He stated, "In order to fight and defeat this enemy, it is necessary to wage a new, all-out offensive. ... This will be a worldwide offensive. ... It will be government-wide ... and it will be nationwide." Earlier that day, Nixon had presented a special message to the US Congress on "Drug Abuse Prevention and Control", which included text about devoting more federal resources to the "prevention of new addicts, and the rehabilitation of those who are addicted"; that aspect did not receive the same media attention as the term "war on drugs".
In the years since, presidential administrations and Congress have generally maintained or expanded Nixon's original initiatives, with the emphasis on law enforcement and interdiction over public health and treatment. Cannabis presents a special case; it came under federal restriction in the 1930s, and since 1970 has been classified as having a high potential for abuse and no medical value, with the same level of prohibition as heroin. Multiple mainstream studies and findings since the 1930s have recommended against such a severe classification. Beginning in the 1990s, cannabis has been legalized for medical use in 39 states, and also for recreational use in 24, creating a policy gap with federal law and non-compliance with the UN drug treaties.
In June 2011, the Global Commission on Drug Policy released a critical report, declaring: "The global war on drugs has failed, with devastating consequences for individuals and societies around the world." In 2023, the UN high commissioner for Human Rights stated that "decades of punitive, 'war on drugs' strategies had failed to prevent an increasing range and quantity of substances from being produced and consumed." That year, the annual US federal drug war budget reached $39 billion, with cumulative spending since 1971 estimated at $1 trillion.
== History ==
Drugs in the US were largely unregulated until the early 20th century. Opium had been used to relieve pain since the Revolutionary War (1775–1783), particularly in the treatment of soldiers during wartime. In the 1800s, the international opium trade was large-scale enterprise: Britain, and to a lesser degree the other European colonial powers and the US, gained immense profits from selling opium in China and southeast Asia; two opium wars were fought mid-century by Britain and allies against China to ensure the trade continued to serve millions of Chinese opium users. In America, the use of opiates in the civilian population began to increase dramatically, and cocaine use became prevalent. Alcohol consumption steadily grew, as did the temperance movement, well-supported by the middle class, promoting moderation or abstinence. The practice of smoking cannabis began to be noticed in the early 1900s. State and local governments began enacting drug laws in the mid-1800s. Under the US Constitution, the authority to control dangerous drugs exists separately at both the federal and state level. Federal drug legislation arrived after the turn of the century.
=== Mid-1800s–1909: Proliferation of unregulated drug use ===
The latter half of the 19th century saw a ramping up of opiate use in America. Early in the century, morphine had been isolated from opium, decades later, heroin was created from morphine, each more potent than the previous form. With the invention of the hypodermic syringe, introduced in America mid-century, opiates were easily administered and became a preferred medical treatment. During the Civil War (1861–1865), millions of doses of opiates were distributed to sick and wounded soldiers, addicting some; domestic poppy fields were planted in an attempt to meet shortages (the crops proved to be of poor quality). In the civilian population, physicians treated opiates like a wonder drug, prescribing them widely, for chronic pain, irritable babies, asthma, bronchitis, insomnia, "nervous conditions", hysteria, menstrual cramps, morning sickness, gastrointestinal disease, "vapors", and on.
Drugs were also sold over-the-counter as home remedies, and in refreshments. Laudanum, a powdered opium solution, was commonly found in the home medicine cabinet. Heroin was available as a cough syrup. Cocaine was introduced as a surgical anesthetic, and more popularly as a pick-me-up, found in soft drinks, cigarettes, blended with wine, in snuff, and other forms. Brand names appeared: Coca-Cola contained cocaine until 1903; Bayer created the trademark name "Heroin" for their diamorphine product. In the 1890s, the Sears & Roebuck catalog, distributed to millions of American homes, offered a syringe and a small amount of heroin for $1.50.
==== America's "first opioid crisis" ====
The 1880s saw opiate addiction surge among among housewives, doctors, and Civil War veterans, creating America's "first opioid crisis." By the end of the century, an estimated one in 200 Americans were addicted to opiates, 60% of them women, typically white and middle- to upper-class. Medical journals of the later 1800s were replete with warnings against overprescription. As medical advances like the x-ray, vaccines, and germ theory presented better treatment options, prescribed opiate use began to decline. Meanwhile, opium smoking remained popular among Chinese immigrant laborers, thousands of whom had arrived during the California gold rush; opium dens were established in Chinatowns in cities and towns across America. The public face of opiate use began to change, from affluent white Americans, to "Chinese, gamblers, and prostitutes."
During this period, states and municipalities began enacting laws banning or regulating certain drugs. In Pennsylvania, an anti-morphine law was passed in 1860. In 1875, San Francisco enacted an anti-opium ordinance, vigorously enforced, imposing stiff fines and jail for visiting opium dens. The rationale held that "many women and young girls, as well as young men of a respectable family, were being induced to visit the Chinese opium-smoking dens, where they were ruined morally and otherwise." The law catered to resentment towards the Chinese laborer population who were being accused of taking jobs; other uses of opiates or other drugs were unaffected. Similar laws were enacted in other states and cities. The federal government became involved, selectively raising the import tariff on the smoking grade of opium. None of these measures proved effective in significantly reducing opium use (the anti-Chinese fervor led to Congress halting Chinese laborer immigration for 10 years with the Chinese Exclusion Act of 1882). In the following years, opioids, cocaine, and cannabis were associated with various ethnic minorities and targeted in other local jurisdictions.
In 1906, the Pure Food and Drug Act, also known as the Wiley Act, addressed problems with tainted and adulterated food in the growing industrial food system, and with drug quality, by mandating ingredient labels and prohibiting false or misleading labeling. For drugs, a listing of active ingredients was required; a set of drugs deemed addictive or dangerous, that included opium, morphine, cocaine, caffeine, and cannabis, was specified. Oversight of the act was assigned to the US Department of Agriculture's Bureau of Chemistry, which evolved into the Food and Drug Administration in 1930.
=== 1909–1971: Rise of federal drug prohibition ===
On February 9, 1909, the Smoking Opium Exclusion Act, "to prohibit the importation and use of opium for other than medicinal purposes", became the first US federal law to ban the non-medical use of a substance. This was soon followed by the Harrison Narcotics Tax Act of 1914, that regulated and taxed the production, importation, and distribution of opiates and coca products. Amending the Smoking Opium Exclusion Act, the Anti-Heroin Act of 1924 specifically outlawed the manufacture, importation and sale of heroin.
During World War I (1914–1918), soldiers were commonly treated with morphine, giving rise to addiction among veterans. An international wartime focus on military use of opiates and cocaine for medical treatment and performance enhancement, and concern over potential abuse, led to the global adoption of the International Opium Convention, through its incorporation into the Treaty of Versailles in 1919, with administration by the newly established League of Nations. The treaty, originally formulated in 1912 but not widely implemented, became the basis of current international drug control policy. It was initially concerned with regulating the free trade of drugs, without affecting production or use. The US, one of the most prohibitionist countries, felt these provisions did not go far enough in restricting drugs.
In 1919, the 18th Amendment to the US Constitution was ratified, prohibiting the manufacture, sale and transportation of "intoxicating liquors", with exceptions for religious and medical use. To enforce the amendment, Congress passed the National Prohibition Act, also known as the Volstead Act. By the 1930s, the policy was seen as a failure: production and consumption of alcohol persisted, organized crime flourished in the alcohol black market, and tax revenue, particularly needed after the start of the Great Depression in 1929, was lost. Prohibition was repealed by passage of the 21st Amendment in 1933, with President Franklin D. Roosevelt (1933–1945) asking Americans not to abuse "this return to personal freedom."
In 1922, the Narcotic Drugs Import and Export Act broadened federal regulation of opiates and coca products by prohibiting import and export for non-medical use, and established the Federal Narcotics Control Board (FNCB) to administrate.
==== Anslinger era begins ====
The Federal Bureau of Narcotics (FBN) was established as an agency of the US Department of the Treasury by an act of June 14, 1930, with Harry J. Anslinger appointed as commissioner, a position he held for 32 years, until 1962. Anslinger supported Prohibition and the criminalization of all drugs, and spearheaded anti-drug policy campaigns. He did not support a public health and treatment approach, instead urging courts to "jail offenders, then throw away the key." He has been characterized as the first architect of the punitive war on drugs. According to a report prepared for the Senate of Canada, Anslinger was "utterly devoted to prohibition and the control of drug supplies at the source" and is "widely recognized as having had one of the more powerful impacts on the development of US drug policy, and, by extension, international drug control into the early 1970s."
During his three decades heading the FBN, Anslinger zealously and effectively pursued harsh drug penalties, with a particular focus on cannabis. He used his stature as the head of a federal agency to draft legislation, discredit critics, discount medical opinion and scientific findings, and convince lawmakers. Publicly, he used the media and speaking engagements to introduce hyperbolic messages about the evils of drug use. In the 1930s, he referred to a collection of news reports of horrific crimes, making unsubstantiated claims attributing them to drugs, particularly cannabis. He announced that youth become "slaves" to cannabis, "continuing addiction until they deteriorate mentally, become insane, turn to violent crime and murder." He promoted a racialized view of drug use, saying that blacks and Latinos were the primary abusers. In Congressional testimony, he declared "of all the offenses committed against the laws of this country, the narcotic addict is the most frequent offender." He was also an effective administrator and diplomat, attending international drug conferences and steadily expanding the FBN's influence.
In 1935, the New York Times reported on President Roosevelt's public support of the Uniform State Narcotic Drug Act under the headline, "Roosevelt Asks Narcotic War Aid". The Uniform Law Commission developed the act to address the 1914 Harrison Act's lack of state-level enforcement provisions, creating a model law reflecting the Harrison Act that states could adopt to replace the existing patchwork of state laws. Anslinger and the FBN were centrally involved in drafting the act, and in convincing states to adopt it.
==== Cannabis effectively outlawed, prescription drugs ====
With the passage of the Marihuana Tax Act of 1937, federal law reflected state law – by 1936, the non-medical use of cannabis had been banned in every state. That year, the first two arrests for tax non-payment under the act, for possession of a quarter-ounce (7g), and trafficking of four pounds (1.8 kg), resulted in sentences of nearly 18 months and four years respectively. The American Medical Association (AMA) had opposed the tax act on grounds that it unduly affected the medical use of cannabis. The AMA's legislative counsel, a physician, testified that the claims about cannabis addiction, violence and overdoses were not supported by evidence. Scholars have posited that the act was orchestrated by powerful business interests – Andrew Mellon, Randolph Hearst, and the Du Pont family – to head off cheap competition to pulp and timber and plastics from the hemp industry. After the act, cannabis research and medical testing became rare.
In 1939, New York Mayor Fiorello La Guardia, an opponent of the Marihuana Tax Act, formed the LaGuardia Committee to conduct the first US in-depth study of cannabis use. The report, produced by the New York Academy of Medicine and released in 1944, systematically contradicted government claims, finding that cannabis is not physically addictive, and its use does not lead to using other drugs or to crime. The FBN's Anslinger branded the study "unscientific", denounced all involved, and disrupted other cannabis studies at the time.
In the late 1930s, questions emerged from League of Nations' Opium Advisory Committee concerning the focus on drug prohibition over public health measures such as mental health treatment, drug dispensaries and education. Anslinger, backed by his Canadian counterpart and policy ally, Charles Henry Ludovic Sharman, successfully argued against this view, and kept the focus on increasing global prohibition and supply control measures.
While narcotics were under the jurisdiction of the FBN, the Food, Drug, and Cosmetic Act of 1938 required the FDA to ensure that non-narcotic drugs were labeled for safe use. The act determined that certain drugs, including amphetamines, commercialized in the later 1930s, and barbiturates, were unsafe to use without medical supervision and could only be obtained by doctor's prescription. This marked the beginning of the federal distinction between over-the-counter and prescription drugs (clarified in the Durham-Humphrey Amendment of 1951).
==== Amphetamines, harsher penalties, international obligations ====
During World War II (1939–1945), in addition to the widespread use of morphine, amphetamines entered military use to combat fatigue and improve morale. In the US, the Benzedrine brand was widely used in the military, and quickly became popular in the public for a variety of medical and recreational applications. Beginning in 1943, American soldiers could buy Benzedrine directly from the army on demand. Post-war, amphetamines were promoted as mood elevators and diet pills to great success; by 1945, an estimated 750 million tablets a year were being produced in the US, enough to provide a million people with a daily supply, a trend that grew during the 1950s and 1960s.
Having failed to preserve world peace, the League of Nations ended post-war, transferring responsibilities to its successor, the United Nations. Anslinger, supported by Sharman, successfully campaigned to ensure that law enforcement and the prohibitionist view remained central to international drug policy. With the 1946 Lake Success Protocol, he helped to make sure that law enforcement was represented on the UN's new drug policy Supervisory Body (today's International Narcotics Control Board), and that it did not fall under a public health-oriented agency like the WHO.
In the early 1950s, responding to "white suburban grassroots movements" concerned about dealers preying on teenagers, liberal politicians at state level cracked down on drugs. California, Illinois, and New York passed the first mandatory minimum sentences for drug offenses; Congress followed with the Boggs Act of 1951, creating the first federal mandatory minimums for drugs. The act unified penalties for the Narcotic Drugs Import and Export Act and the Marihuana Tax Act, effectively criminalizing cannabis. Anslinger testified in favor of the inclusion of cannabis, describing a "stepping-stone" path leading from cannabis to harder drugs and crime. First-offense possession of cannabis carried a 2–10 year minimum and a fine of up to $20,000. This marked a change in Congress's approach to mandatory minimums, increasing their number, severity, and the crimes they covered. According to the United States Sentencing Commission, reporting in 2012: "Before 1951, mandatory minimum penalties typically punished offenses concerning treason, murder, piracy, rape, slave trafficking, internal revenue collection, and counterfeiting. Today, the majority of convictions under statutes carrying mandatory minimum penalties relate to controlled substances, firearms, identity theft, and child sex offenses.".
In 1961, the Single Convention on Narcotic Drugs became the first of three UN treaties that together form the legal framework for international drug control, and require that domestic drug laws in member countries comply with the conventions. The Single Convention unified existing international drug agreements, and limited possession and use of opiates, cannabis and cocaine to "medicinal and scientific purposes", prohibiting recreational use. Sixty-four countries initially joined; it was ratified and came into force in the US in 1967. The Convention on Psychotropic Substances of 1971 added synthetic, prescription and hallucinogenic drugs. The Convention against Illicit Traffic in Narcotic Drugs and Psychotropic Substances of 1988 addressed international drug trafficking and "criminalized the entire drug market chain, from cultivation/production to shipment, sale, and possession."
In 1968, President Lyndon B. Johnson (1963–69) decided that the government needed to make an effort to curtail the social unrest that blanketed the country at the time. He focused on illegal drug use, an approach that was in line with expert opinion on the subject at the time. In the 1960s, it was believed that at least half of the crime in the US was drug-related, and this estimate grew as high as 90% in the next decade. He created the Reorganization Plan of 1968 which merged the Bureau of Narcotics and the Bureau of Drug Abuse Control to form the Bureau of Narcotics and Dangerous Drugs within the Department of Justice.
==== Federal drug schedule system introduced ====
The Richard Nixon presidency (1969–74) incorporated his predecessor's anti-drug initiative in a tough-on-crime platform. In his 1968 presidential nomination acceptance speech, Nixon promised, "Our new Attorney General will ... launch a war against organized crime in this country. ... will be an active belligerent against the loan sharks and the numbers racketeers that rob the urban poor. ... will open a new front against the filth peddlers and the narcotics peddlers who are corrupting the lives of the children of this country." In a 1969 special message to Congress, he identified drug abuse as "a serious national threat".
On October 27, 1970, Nixon signed into law the Comprehensive Drug Abuse Prevention and Control Act of 1970, establishing his approach to drug control. The act largely repealed mandatory minimum sentences: simple possession was reduced from a felony to a misdemeanor, the first offense carried a maximum of one year in prison, and judges had the latitude to assign probation, parole or dismissal. Penalties for trafficking were increased, up to life depending on the quantity and type of drug. Funding was authorized for the Department of Health, Education and Welfare to provide treatment, rehabilitation and education. Additional federal drug agents were provided, and a "no-knock" power was instituted, that allowed entry into homes without warning to prevent evidence from being destroyed. Licensing and stricter reporting and record-keeping for pharmaceutical manufacturers and distributors occurred under the act. Title II of Act, the Controlled Substances Act (CSA), helped align US law with the UN Single Convention, with "many of the provisions of the CSA ... enacted by Congress for the specific purpose of ensuring U.S. compliance with the treaty." The CSA's five drug Schedules, an implementation of the Single Convention's four schedule system, categorized drugs based on medical value and potential for abuse.
Under the new drug schedules, cannabis was provisionally placed by the administration in the most restrictive Schedule I, "until the completion of certain studies now underway to resolve the issue." As mandated by the CSA, Nixon appointed the National Commission on Marijuana and Drug Abuse, known as the Shafer Commission, to investigate.
=== 1971–present: The "War on Drugs" ===
On May 27, 1971, after a trip to Vietnam, two congressmen, Morgan F. Murphy (Democrat) and Robert H. Steele (Republican), released a report describing a "rapid increase in heroin addiction within the United States military forces in South Vietnam". They estimated that "as many as 10 to 15 percent of our servicemen are addicted to heroin in one form or another." On June 6, a New York Times article, "It's Always A Dead End on 'Scag Alley'", cited the Murphy-Steele report in a discussion of heroin addiction. The article stated that, in the US, "the number of addicts is estimated at 200,000 to 250,000, only about one‐tenth of 1 per cent of the population but troublesome out of all proportion." It also noted, "Heroin is not the only drug problem in the United States. 'Speed' pills – among them, amphetamines – are another problem, and not least in the suburbs where they are taken by the housewife (to cure her of the daily 'blues') and by her husband (to keep his weight down)."
On June 17, 1971, Nixon presented to Congress a plan for expanded anti-drug abuse measures. He painted a dire picture: "Present efforts to control drug abuse are not sufficient in themselves. The problem has assumed the dimensions of a national emergency. ... If we cannot destroy the drug menace in America, then it will surely in time destroy us." His strategy involved both treatment and interdiction: "I am proposing the appropriation of additional funds to meet the cost of rehabilitating drug users, and I will ask for additional funds to increase our enforcement efforts to further tighten the noose around the necks of drug peddlers, and thereby loosen the noose around the necks of drug users." He singled out heroin and broadened the scope beyond the US: "To wage an effective war against heroin addiction, we must have international cooperation. In order to secure such cooperation, I am initiating a worldwide escalation in our existing programs for the control of narcotics traffic."
Later the same day, Nixon held a news conference at the White House, where he described drug abuse as "America's public enemy number one." He announced, "In order to fight and defeat this enemy, it is necessary to wage a new, all-out offensive. ... This will be a worldwide offensive dealing with the problems of sources of supply ... It will be government wide, pulling together the nine different fragmented areas within the government in which this problem is now being handled, and it will be nationwide in terms of a new educational program." Nixon also stated that the problem wouldn't end with the addiction of soldiers in the Vietnam War. He pledged to ask Congress for a minimum of $350 million for the anti-drug effort (when he took office in 1969, the federal drug budget was $81 million).
The news media focused on Nixon's militaristic tone, describing his announcement with variations of the phrase "war on drugs". The day after Nixon's press conference, the Chicago Tribune proclaimed, "Nixon Declares War on Narcotics Use in US". In England, The Guardian headlined, "Nixon declares war on drug addicts." The US anti-drug campaign came to be commonly referred to as the war on drugs; the term also became used to refer to any government's prosecution of a US-style prohibition-based drug policy.
Facing reelection, with drug control as a campaign centerpiece, Nixon formed the Office of Drug Abuse Law Enforcement (ODALE) in late 1971. ODALE, armed with new federal enforcement powers, began orchestrating drug raids nationwide to improve the administration's watchdog reputation. In a private conversation while helicoptering over Brooklyn, Nixon was reported to have commented, "You and I care about treatment. But those people down there, they want those criminals off the streets." From 1972 to 1973, ODALE performed 6,000 drug arrests in 18 months, the majority of the arrested black.
In 1972, the Shafer Commission released its report, "Marihuana: A Signal of Misunderstanding", comprising a review of the medical literature and a national drug survey. It recommended decriminalization for personal possession and use of small amounts of cannabis, and prohibition only of supply. The conclusion was not acted on by Nixon or by Congress. Citing the Shafer report, a lobbying campaign from 1973 to 1978, spearheaded by the National Organization for the Reform of Marijuana Laws (NORML), convinced 11 states to decriminalize cannabis for personal use.
In 1973, Nixon created the Drug Enforcement Administration (DEA) by an executive order accepted by Congress, to "establish a single unified command to combat an all-out global war on the drug menace." The agency was charged with enforcing US controlled substances laws and regulations nationally and internationally, coordinating with federal, state and local agencies and foreign governments, and overseeing legally-produced controlled substances. The DEA absorbed the Bureau of Narcotics and Dangerous Drugs, ODALE, and other drug-related federal agencies or personnel from them.
==== Nixon's role reviewed ====
Decades later, a controversial quote attributed to John Ehrlichman, Nixon's domestic policy advisor, claimed that the war on drugs was fabricated to undermine the anti-war movement and African-Americans. In a 2016 Harper's cover story, Ehrlichman, who died in 1999, was quoted from journalist Dan Baum's 1994 interview notes: "... by getting the public to associate the hippies with marijuana and blacks with heroin, and then criminalizing both heavily, we could disrupt those communities. We could arrest their leaders, raid their homes, break up their meetings, and vilify them night after night on the evening news. Did we know we were lying about the drugs? Of course we did." The veracity of the quote was challenged by Ehrlichman's children, and Nixon-era officials. In the end, the increasingly punitive reshaping of US drug policy by later administrations was most responsible for creating some of the conditions Ehrlichman described.
In a 2011 commentary, Robert DuPont, Nixon's drug czar, argued that the Comprehensive Drug Abuse Act had represented a degree of drug reform. He noted that the act had rolled back mandatory minimum sentencing and balanced the "long-dominant law enforcement approach to drug policy, known as 'supply reduction'" with an "entirely new and massive commitment to prevention, intervention and treatment, known as 'demand reduction'". Thus, Nixon was not in fact the originator of what came to be called the "war on drugs". During Nixon's term, some 70% of federal anti-drug money was spent on demand-side public health measures, and 30% on supply-side interdiction and punishment, a funding ratio not repeated under subsequent administrations.
The war on drugs under the next two presidents, Gerald Ford (1974–77) and Jimmy Carter (1977–81), was essentially a continuation of their predecessors' policies. Carter's campaign platform included decriminalization of cannabis and an end to federal penalties for possession of up to one ounce. In a 1977 "Drug Abuse Message to the Congress", Carter stated, "Penalties against possession of a drug should not be more damaging to an individual than the use of the drug itself." None of his advocacy was translated into law.
==== Reagan escalation, militarization, and "Just Say No" ====
The presidency of Ronald Reagan (1981–89) saw an increase in federal focus on interdiction and prosecution. Shortly after his inauguration, Reagan announced, "We're taking down the surrender flag that has flown over so many drug efforts; we're running up a battle flag." From 1980 to 1984, the annual budget of the Federal Bureau of Investigation (FBI) drug enforcement units went from $8 million to $95 million. In 1982, Vice President George H. W. Bush and his aides began pushing for the involvement of the Central Intelligence Agency (CIA) and the US military in drug interdiction efforts.
Early in the Reagan term, First Lady Nancy Reagan, with the help of an advertising agency, began her youth-oriented "Just Say No" anti-drug campaign. Propelled by the First Lady's tireless promotional efforts through the 1980s, "Just Say No" entered the American vernacular. Later research found that the campaign had little or no impact on youth drug use. One striking change attributed to the effort: public perception of drug abuse as America's most serious problem, in the 2-6% range in 1985, rose to 64% in 1989.
In January 1982, Reagan established the South Florida Task Force, chaired by Bush, targeting a surge of cocaine and cannabis entering through the Miami region, and the sharp rise in related crime. The project involved the DEA, the Customs Service, the FBI and other agencies, and Armed Forces ships and planes. It was called the "most ambitious and expensive drug enforcement operation" in US history; critics called it an election year political stunt. By 1986, the task force had made over 15,000 arrests and seized over six million pounds of cannabis and 100,000 pounds of cocaine, doubling cocaine seizures annually – administration officials called it Reagan's biggest drug enforcement success. However, law enforcement agents at the time said their impact was minimal; cocaine imports had increased by 10%, to an estimated 75-80% of America's supply. According to the head of the task force's investigative unit, "Law enforcement just can't stop the drugs from coming in." A Bush spokesperson emphasized disrupting smuggling routes rather than seizure quantities as the measure of success."
In 1984, Reagan signed the Comprehensive Crime Control Act, which included harsher penalties for cannabis cultivation, possession, and distribution. It also established equitable sharing, a new civil asset forfeiture program that allowed state and local law enforcement to share the proceeds from asset seizures made in collaboration with federal agencies. Under the controversial program, up to 80% of seizure proceeds can go to local law enforcement, expanding their budgets. By 2019, $36.5 billion worth of assets had been seized, much of it drug-related, much of it distributed to state and local agencies.
At the same time, the Central Intelligence Agency (CIA) was accused of facilitating the drug trade in Mexico and elsewhere in order to fund anticommunist guerilla forces in Central and South America. A number of former DEA agents, CIA agents, Mexican police officers, and historians contend that the CIA was complicit in the murder of DEA agent Kiki Camarena, who discovered and attempted to reveal the CIA's role in the drug trade. Between 2013 and 2015, the Mexican newspaper Proceso, journalist Jesús Esquivel, journalists Charles Bowden and Molly Malloy, and historians Russell and Silvia Bartley published investigative reports and books making the same allegation. They wrote that Camarena, like Mexican journalist Manuel Buendía, discovered that the CIA helped organize drug trafficking from Mexico into the United States in order to fund the anti-communist Contras in Nicaragua as a part of the Cold War. Historian Wil Pansters explained that US victory in the Cold War was more important to the CIA than the DEA's War on Drugs:Since the overriding concern of the CIA was the anti-Sandinista project, it trumped the DEA's task of combating drug trafficking, and covertly incorporated (or pressured) parts of the Mexican state into subservience. Buendía had found out about the CIA-contra-drugs-DFS connection, which seriously questioned Mexican sovereignty, while Camarena learned that the CIA had infiltrated the DEA and sabotaged its work so as to interfere with the clandestine contra-DFS-traffickers network. They knew too much and were eliminated on the orders of the U.S. with Mexican complicity. Later official investigations attempted to limit criminal responsibility to the dirty connections between drug traffickers, secret agents and corrupt police, leaving out the (geo)political ramifications.
The CIA has denied allegations of involvement in killing Camarena. Historian Benjamin T. Smith said the allegations have "...holes. Big holes." He also calls Russell and Silvia Bartley's investigation "occasionally paranoid" and notes the fact that "Many-including some members of the DEA" dismiss one of the key sources for this (i.e. Lawrence Victor Harrison) as a "crank". However Smith also acknowledged the fact that the case is a "deep, dark hole....[where] Fiction and reality are firmly intertwined."
==== Crackdown on crack ====
As the media focused on the emergence of crack cocaine in the early 1980s, the Reagan administration shored up negative public opinion, encouraging the DEA to emphasize the harmful effects of the drug. Stories of "crack whores" and "crack babies" became commonplace. In mid-1986, crack dominated the news. Time declared crack the issue of the year. Newsweek compared the magnitude of the crack story to Vietnam and Watergate. The cocaine overdose deaths of rising basketball star Len Bias, and young NFL football player Don Rogers, both in June, received wide coverage. Riding the wave of public fervor, that October Reagan signed into law much harsher sentencing for crack through the Anti-Drug Abuse Act, commonly known as the Len Bias law. According to historian Elizabeth Hinton, "[Reagan] led Congress in criminalizing drug users, especially African American drug users, by concentrating and stiffening penalties for the possession of the crystalline rock form of cocaine, known as 'crack', rather than the crystallized methamphetamine that White House officials recognized was as much of a problem among low-income white Americans".
The Anti-Drug Abuse Act appropriated an additional $1.7 billion to drug war funding, and established 29 new mandatory minimum sentences for drug offenses (until then, the American legal system had seen 55 minimum sentences in total). Of particular note, the act made sentences for larger amounts of cocaine 100 times more severe for crack than for the powder form. With the 100:1 ratio, conviction in federal court for possession of 5 grams of crack would receive the same 5-year mandatory minimum as possession of 500 grams of powder cocaine. Debate at the time considered whether crack, generally used by blacks, was more addictive than the powder form, generally used by whites, comparing the effects of snorting powder cocaine with the briefer, more intense high from smoking crack; pharmacologically, there is no difference between the two. According to the DEA, at first crack "was not fully appreciated as a major threat because it was primarily being consumed by middle class users who were not associated with cocaine addicts ... However, partly because crack sold for as little as $5 a rock, it ultimately spread to less affluent neighborhoods."
Support for Reagan's drug crime legislation was bipartisan. According to historian Hinton, Democrats supported drug legislation as they had since the Johnson administration, though Reagan was a Republican.
Internationally, the Reagan term saw a huge increase in US military anti-drug activity in other countries. The Department of Defense budget for interdiction increased from $4.9 million in 1982 to $397 million by 1987. The DEA also expanded its foreign presence. Countries were encouraged to adopt the same type of punitive drug approach that was in place in the US, with the threat of economic sanctions for non-compliance. The UN Single Convention provided a legal framework, and in 1988, the Convention against Illicit Traffic expanded that framework, working the US-style punitive approach into international law.
By the end of Reagan's presidency in 1989, illicit drugs were more readily available and cheaper than at the start of his first term in 1981.
==== Hard line maintained and a new opioid crisis ====
Next to occupy the Oval Office, Reagan protégé and former VP George H. W. Bush (1989–93) maintained the hard line drawn by his predecessor and former boss. In his first prime-time address to the nation, Bush held up a plastic bag of crack "seized a few days ago in a park across the street from the White House" (it was later revealed that DEA agents had to lure the seller to Lafayette Park to make the requested arrest). The administration increased narcotics regulation in the first National Drug Control Strategy, issued by the Office of National Drug Control Policy (ONDCP) in 1989. The director of ONDCP became commonly known as the US drug czar. In the National Defense Authorization Act for 1990–91, Congress included Section 1208 – the 1208 Program, expanded into the 1033 Program in 1996 – authorizing the Department of Defense to transfer surplus military equipment that the DoD determined to be "suitable for use in counter-drug activities", to local law enforcement agencies.
As president, Bill Clinton (1993–2001), seeking to reposition the Democratic Party as tough on crime, dramatically raised the stakes for drug felonies with his signing of the Violent Crime Control and Law Enforcement Act of 1994. The act introduced the federal "three-strikes" provision that mandated life imprisonment for violent offenders with two prior convictions for violent crimes or drugs, and provided billions of dollars in funding for states to expand their prison systems and increase law enforcement. During this period, state and local governments initiated controversial drug policies that demonstrated racial biases, such as the stop-and-frisk police practice in New York City, and state-level "three strikes" felony laws, which began with California in 1994.
During the 1990s, opioid use in the US dramatically rose, leading to the ongoing situation commonly called the opioid epidemic. A loose consensus of observers describe three main phases to date: overprescription of legal opioids beginning in the early to mid-1990s; a rise in heroin use in the later 2000s as prescription opioids became more difficult to obtain; and the rise of more powerful fentanyl and other synthetic opioids around the mid-2010s. Prior to 1990s, the use of opioids to treat chronic pain in the US was limited; some scholars suggest there was hesitation to prescribe opioids due to historical problems with addiction dating back to the 1800s. A critical point in the development of the epidemic is often seen as the release in 1996 of OxyContin (oxicodone) by Purdue Pharma, and the subsequent aggressive and deceptive opioid marketing efforts by Purdue and other pharma companies, conducted without sufficient official oversight. Thus the problem emerged from within the healthcare system: the DEA initially targeted doctors, pharmacists, pill mills, and pharmaceutical companies. As law enforcement cracked down on the pharmaceutical supply, illicit drug trafficking in opioids grew to meet demand.
The George W. Bush (2001–2009) administration maintained the hard line approach. In a TV interview in February 2001, Bush's new attorney general, John Ashcroft, said about the war on drugs, "I want to renew it. I want to refresh it, relaunch it if you will." In 2001, after 9/11 and the Patriot Act, the DEA began highlighting the tie between drug trafficking and international terrorism, gaining the agency expanded funding to increase its global presence.
==== Growing dissent ====
In mid-2001, a report by the American Civil Liberties Union (ACLU), "The Drug War is the New Jim Crow", tied the vastly disproportionate rate of African American incarceration to the range of rights lost once convicted. It stated that, while "whites and blacks use drugs at almost exactly the same rates ... African-Americans are admitted to state prisons at a rate that is 13.4 times greater than whites, a disparity driven largely by the grossly racial targeting of drug laws." Between federal and state laws, those convicted of even simple possession could lose the right to vote, eligibility for educational assistance including loans and work-study programs, custody of their children, and personal property including homes. The report concluded that the cumulative effect of the war on drugs amounted to "the US apartheid, the new Jim Crow". This view was further developed by lawyer and civil rights advocate Michelle Alexander in her 2010 book, The New Jim Crow: Mass Incarceration in the Age of Colorblindness.
In the year 2000, the US drug-control budget reached $18.4 billion, nearly half of which was spent financing law enforcement while only one-sixth was spent on treatment. In the year 2003, 53% of the requested drug control budget was for enforcement, 29% for treatment, and 18% for prevention.
During his presidency, Barack Obama (2009–2017) implemented his "tough but smart" approach to the war on drugs. While he claimed that his method differed from those of previous presidents, in reality, his practices were similar. In May 2009, Gil Kerlikowske, Director of the ONDCP – Obama's drug czar – indicated that the Obama administration did not plan to significantly alter drug enforcement policy, but that it would not use the term "war on drugs", considering it to be "counter-productive". In August 2010, Obama signed the Fair Sentencing Act into law, reducing the 100:1 sentencing disparity between crack and powder cocaine to 18:1 for pending and future cases. In 2013, Obama's Justice Department issued a policy memorandum known as the Cole Memo, stating that it would defer to state laws that authorize the production, distribution and possession of cannabis, "based on assurances that those states will impose an appropriately strict regulatory system."
In 2011, the Global Commission on Drug Policy, an international non-governmental group composed primarily of former heads of state and government, and leaders from various sectors, released a report that stated, "The global war on drugs has failed." It recommended a paradigm shift, to a public health focus, with decriminalization for possession and personal use. Obama's ONDCP did not support the report, stating: "Drug addiction is a disease that can be successfully prevented and treated. Making drugs more available ... will make it harder to keep our communities healthy and safe."
==== International divisions, state-level changes ====
In May 2012, the ONDCP published "Principles of Modern Drug Policy", broadly focusing on public health, human rights, and criminal justice reform, while targeting drug traffickers. According to ONDCP director Kerlikowske, drug legalization is not the "silver bullet" solution to drug control, and success is not measured by the number of arrests made or prisons built. That month, a joint statement, "For a humane and balanced drug policy", was signed by Italy, Russia, Sweden, the United Kingdom and the US, promoting a combination of "enforcement to restrict the supply of drugs, with efforts to reduce demand and build recovery." Meanwhile, at the state level, 2012 saw Colorado and Washington become the first two states to legalize the recreational use of cannabis with the passage of Amendment 64 and Initiative 502 respectively.
A 2013 ACLU report declared the anti-marijuana crusade a "war on people of color". The report found that "African Americans [were] 3.73 times more likely than whites to be apprehended despite nearly identical usage rates, and marijuana violations accounting for more than half of drug arrests nationwide during the previous decade". Under Obama's policies, nonwhite drug offenders received less excessive criminal sanctions, but by examining criminals as strictly violent or nonviolent, mass incarceration persisted.
In March 2016, the International Narcotics Control Board stated that the UN's international drug treaties do not mandate a "war on drugs" and that the choice is not between "'militarized' drug law enforcement on one hand and the legalization of non-medical use of drugs on the other", health and welfare should be the focus of drug policy. That April, the UN General Assembly Special Session (UNGASS) on the "World Drug Problem" was held. The Wall Street Journal assessed the attendees' positions as "somewhat" in two camps: "Some European and South American countries as well as the U.S. favored softer approaches. Eastern countries such as China and Russia and most Muslim nations like Iran, Indonesia and Pakistan remained staunchly opposed." The outcome document recommended treatment, prevention and other public health measures, and committed to "intensifying our efforts to prevent and counter" drug production and trafficking, through, "inter alia, more effective drug-related crime prevention and law enforcement measures."
Under President Donald Trump (2017–2021), Attorney General Jeff Sessions reversed the previous Justice Department's cannabis policies, rescinding the Cole Memo that deferred federal enforcement in states where cannabis had been legalized He instructed federal prosecutors to "charge and pursue the most serious, readily provable offense" in drug cases, regardless of whether mandatory minimum sentences applied, which could trigger mandatory minimums for lower-level charges. With cannabis legalized to some degree in over 30 states, Sessions' directive was seen by both Democrats and Republicans as a rogue throwback action, and there was a bipartisan outcry. Trump fired Sessions in 2018 over other issues.
==== Some policy reversal attempts and successes ====
In 2018, Trump signed into law the First Step Act which, among other federal prison reforms, made the 2010 Fair Sentencing Act retroactive. A US Supreme Court decision in 2021 determined that retroactivity applied to cases where mandatory minimum penalties had been imposed.
In 2020, both the ACLU and The New York Times reported that Republicans and Democrats were in agreement that it was time to end the war on drugs. While on the presidential campaign trail, President Joe Biden (2021–2025) stated that he would take the steps to alleviate the war on drugs and end the opioid epidemic.
On December 4, 2020, during the Trump administration, the House of Representatives passed the Marijuana Opportunity Reinvestment and Expungement Act (MORE Act), which would decriminalize cannabis at the federal level by removing it from the list of scheduled substances, expunge past convictions and arrests, and tax cannabis to "reinvest in communities targeted by the war on drugs". The MORE Act was received in the Senate in December 2020 where it remained. In April 2022, the act was again passed by the House, and awaits Senate action.
Over time, states in the US have approached drug liberalization at a varying pace. Initially, in the 1930s, the states were ahead of the federal government in prohibiting cannabis; in recent decades, the trend has reversed. Beginning with cannabis for medical use in California in 1996, states began to legalize cannabis. As of 2023, 38 states, four US territories, and the District of Columbia (DC) had legalized cannabis for medical use; for non-medical use, 24 of the states, three territories, and DC, had legalized it, and seven states decriminalized. Decriminalization in this context usually refers to first-time offenses and small quantities, such as, in the case of cannabis, under an ounce (28g). In November 2020, Oregon became the first state to decriminalize a number of drugs, including heroin, methamphetamine, PCP, LSD and oxycodone, shifting from a criminal approach to a public health approach; portions of that policy were reversed in April 2024.
In 2022, Biden signed into law the Medical Marijuana and Cannabidiol Research Expansion Act, to allow cannabis to be more easily researched for medical purposes. It is the first standalone cannabis reform bill enacted at the federal level. That October, Biden stated on social media, "We classify marijuana at the same level as heroin – and more serious than fentanyl. It makes no sense," and pledged to start a review by the Attorney General on how cannabis is classified. On October 6, he pardoned all those with federal convictions for simple cannabis possession (to a degree symbolic, as none of those affected were imprisoned at the time), and urged the states, where the large majority of convictions rest, to do the same. His action affected 6,500 people convicted from 1992 to 2021, and thousands convicted in the District of Columbia.
==== Focus on fentanyl ====
In 2023, the US State Department announced plans to launch a "global coalition to address synthetic drug threats", with more than 80 countries expected to join. That April, Anne Milgram, head of the DEA since 2021, stated to Congress that two Mexican drug cartels posed "the greatest criminal threat the United States has ever faced." Supporting a DEA budget request of $3.7 billion for 2024, Milgram cited fentanyl in the "most devastating drug crisis in our nation's history."
In October 2023, OFAC sanctioned a China-based network of fentanyl manufacturers and distributors. The drug is usually manufactured in China, then shipped to Mexico, where it is processed and packaged, which is then smuggled into the US by Mexican drug cartels.
In January 2024, the DEA confirmed that it was reviewing the classification of cannabis as a Schedule I narcotic. Days later, documents were released from the Department of Health and Human Services stating that cannabis has "a currently accepted medical use" in the US and a "potential for abuse less than the drugs or other substances in Schedules I and II." On April 30, indicating a DEA decision, the Justice Department announced, "Today, the Attorney General circulated a proposal to reclassify marijuana from Schedule I to Schedule III. Once published by the Federal Register, it will initiate a formal rulemaking process as prescribed by Congress in the Controlled Substances Act." Schedule III drugs, considered to have moderate to low potential for dependence, include ketamine, anabolic steroids, testosterone, and Tylenol with codeine.
In the DEA's "National Drug Threat Assessment 2024", director Milgram outlined the "most dangerous and deadly crisis", involving synthetic drugs including fentanyl and methamphetamine. She singled out the Sinaloa and Jalisco cartels in Mexico, which manufacture the synthetics in Mexican labs supplied with precursor chemicals and machinery from China, sell through "vast distribution networks" in the US, and use Chinese money laundering operations to return the proceeds to Mexico. Milgram states, "As the lead law enforcement agency in the Administration's whole-of-government response to defeat the Cartels and combat the drug poisoning epidemic in our communities, DEA will continue to collaborate on strategic counterdrug initiatives with our law enforcement partners across the United States and the world."
== CIA involvement and focus on counterterrorism ==
During the Second presidency of Donald Trump, the CIA will play a larger and more aggressive role in combating drug cartels. It has been reported that the CIA has been conducting covert surveillance operations with unarmed drones in Mexico to monitor cartel activities.
In January 2025, President Donald Trump signed an executive order demanding that various drug cartels and criminal organizations (Sinaloa Cartel, Gulf Cartel, La Nueva Familia Michoacana, Jalisco New Generation Cartel, Northeast Cartel, United Cartels, Tren de Aragua and Mara Salvatrucha) be added to the list of Foreign Terrorist Organizations and Specially Designated Global Terrorists, which was officially enacted on February 20, 2025, making such groups officially Foreign Terrorist Organizations. Similarly, Canada has also joined in designating drug cartels as Foreign Terrorist Organizations.
== NATO involvement ==
The North Atlantic Treaty Organization (NATO) has played a role in addressing the issue of drug trafficking, particularly in Afghanistan, as part of its broader security and stabilization efforts. NATO has supported counter-narcotics initiatives by assisting the Afghan government in building its capacity to combat the illegal drug trade, which is seen as a major source of funding for insurgent groups. NATO's efforts include training and equipping Afghan security forces to enhance their ability to disrupt drug trafficking networks, as well as supporting intelligence-sharing and coordination with international partners. These activities are framed within NATO's mission to promote stability and security, recognizing the link between the drug trade and threats to regional and global security.
However, perspectives on NATO's involvement in counter-narcotics operations have varied, with some reports highlighting tensions with other international actors, such as the United Nations. While NATO emphasizes its contributions to reducing the drug trade through capacity-building and support for Afghan-led initiatives, other sources have noted discrepancies in reported outcomes, suggesting that the drug trade in Afghanistan remained robust despite these efforts. For instance, data from 2012 indicates that opium production continued to thrive, raising questions about the effectiveness of NATO's strategies in this domain. Nonetheless, NATO's engagement reflects a commitment to addressing the complex interplay between security, governance, and the illicit drug economy, even as challenges persist in achieving measurable reductions in trafficking activities.
== Foreign involvement ==
US international involvement in drug control rests on the premise that assisting foreign governments in their anti-drug efforts reduces drug supply within the US.
Scholars have claimed that the war on drugs, a metaphorical war, is propaganda cloaking an extension of earlier military or paramilitary operations. Others have argued that large amounts anti-drug foreign aid money, training, and equipment actually goes to fighting leftist insurgencies and is often provided to groups who themselves are involved in large-scale narco-trafficking, such as corrupt members of the Colombian military.
=== UN treaties and US influence ===
The three UN drug control conventions, adopted by over 180 countries, provide a legal framework for cooperation between countries. Each state is obligated to incorporate the treaty provisions in their domestic laws. While there is a degree of interpretative flexibility, "each of the treaties encourages – and often requires – that member countries put in place strong domestic penal provisions" to deal with illicit drugs; punitive policies have been the common approach. The US, emerging as the dominant power after WWII, exerted considerable influence over how the conventions were adopted by other nations, promoting a prohibitionist and criminalizing view. Historically, the US has been "the key player in most multilateral negotiations" and the prohibitionist approach "derives largely from U.S. policy – the various forms, past and present, of the U.S. 'war on drugs'".
US economic power is focused on the war on drugs through the Foreign Assistance Act (FAA). Enacted in 1961, the FAA integrated various federal foreign aid initiatives under the new US Agency for International Development (USAID), and has remained the core legislation governing foreign financial assistance. In 1972, reacting to concerns over illicit drugs from foreign sources, Congress added an "International Narcotics Control" chapter to the FAA, which allowed the president to enter into agreements and provide assistance for counternarcotic activities in foreign countries. It also made US economic and military aid, including arms sales, dependent on countries aligning with US anti-drug policies. Later, the terms "major illicit drug-producing country" and "major drug-transit country" were defined in the act; as of 1986, the president has been required to annually determine which countries fit those definitions. Those not adequately cooperating with counter-drug efforts would not be eligible to receive US financial aid, although the president could and has provided waivers to individual countries. The so-called "majors list" has influenced how US assistance money is used internationally in the war on drugs, although in recent years, it has remained relatively static and lost a degree of relevancy. In September 2023, President Biden added China to the majors list, citing its production of precursor chemicals.
Foreign anti-drug initiatives initially focused on Latin America, and expanded globally over time. Since the 1970s, billions of US aid dollars have been directed to anti-drug activity in Latin America. The US initially treated drug control as a law enforcement issue in foreign countries, providing assistance to police forces. In the 1980s, the US increasingly involved the military and private security firms, to provide training and support to armed forces in drug-producing and transit countries. As of 2024, the DEA has, in addition to 241 domestic offices, 93 foreign offices in 69 countries. In addition to numerous cooperative law enforcement actions worldwide against drug trafficking and money laundering, the DEA and other agencies, and the US military, have been involved in multi-year foreign drug campaigns, including in Colombia, Mexico and Afghanistan.
=== Latin America ===
In 2021, Gustavo Gorriti, journalist and founder of corruption-focused IDL-Reporteros news media, wrote a sharply critical editorial in the Washington Post on the impact of 50 years of the war on drugs on Latin America. He described the flow of drugs to the US as an "unstoppable industry" that triggered an economic revolution throughout the region, where the illegal drug trade with its high profit margins far exceeded the potential of legitimate businesses. Corruption among politicians and anti-drug forces soared, even as those in charge were "cultivating close relationships with U.S. enforcement and intelligence agencies." An underclass of poor farmers became economic hostages, depending on drug crops for their survival. The big winners were "the systems built to wage a fight that they soon realized would have no end. ... [The war on drugs] became a source for endless resources, inflated budgets, contracts, purchase orders, power, influence – new economies battling drug trafficking but also dependent on it."
At a meeting in Guatemala in 2012, three former presidents from Guatemala, Mexico and Colombia said that the war on drugs had failed and that they would propose a discussion on alternatives, including decriminalization, at the Summit of the Americas in April of that year. Guatemalan President Otto Pérez Molina said that the war on drugs was exacting too high a price on the lives of Central Americans and that it was time to "end the taboo on discussing decriminalization". At the summit, the government of Colombia pushed for far-reaching changes to drugs policy, citing the catastrophic effects of the war on drugs in Colombia.
==== Colombia ====
Historically, the illicit drug trade in Colombia had strong connections to right-wing paramilitaries like the United Self-Defenders of Colombia (AUC) and leftist guerilla groups like the Revolutionary Armed Forces of Colombia (FARC), thus US anti-drug efforts in the country overlapped with support for counterinsurgency efforts. In the late 1960s, when drug smuggling to the US from Mexico rose to a major scale, the two governments cooperated in the launch of the Mexican war on drugs; the market disruption gave Colombian traffickers an opportunity to fill US demand for cannabis.
Until the 1970s, Colombia "had played no major role in the production and circulation of illegal drugs in the hemisphere". After a military coup in Chile in 1973 and the spread of political repression through the Southern Cone countries disrupted cocaine smuggling from Peru and Bolivia, Colombia stepped in to fill the demand for cocaine. Pressed by the US, the Colombian government, under president Misael Pastrana (1970–1974), worked with the newly formed DEA to establish the future path for the country's war on drugs.
During the 1970s, the "marijuana boom" dominated Colombia's drug trade, peaking mid-decade. That soon gave way to cocaine and the rise of the infamous Medellin and Cali cartels that grew through the 1980s and early 1990s to dominate the global cocaine market. By the end of the century, the brutal anti-drug war left the security situation in Colombia in critical condition. Through the Plan Colombia program, between 2000 and 2015, the US provided Colombia with $10 billion in funding, primarily for military aid, training, and equipment, to fight both drugs and left-wing guerrillas such as FARC (which had been accused of participation in drug trafficking).
The Clinton administration initially waived all but one of the human rights conditions attached to Plan Colombia, considering such aid as crucial to national security at the time. Private US military contractors, including the former DynCorp, were contracted by the State and Defense Departments, to carry out anti-drug initiatives as part of Plan Colombia. Colombian military personnel received extensive counterinsurgency training from US military and law enforcement agencies, including the School of Americas (SOA).
The efforts of the US and Colombian governments have been criticized for focusing on fighting leftist guerrillas in southern regions without applying enough pressure on right-wing paramilitaries and continuing drug smuggling operations in the north of the country. Human Rights Watch, congressional committees and other entities have documented connections between members of the Colombian military and the AUC, which the US government has listed as a terrorist group, and that Colombian military personnel have committed human rights abuses which would make them ineligible for US aid under current laws.
Coca eradication by aerial spraying of herbicides such as glyphosate was a controversial element of Plan Colombia. Environmental consequences resulting from spraying have been criticized as detrimental to some of the world's most fragile ecosystems; the same spraying practices are further credited with causing health problems in local populations.
A report by the RAND Corporation, examining the Colombian experience for insights applicable to the Mexican drug war, noted that "Plan Colombia has been widely hailed as a success, and some analysts believe that, by 2010, Colombian security forces had finally gained the upper hand once and for all." The report cited dramatic reductions in kidnappings and terrorist acts, and the recapture of territory, attributed to "a reinforced military and reinvigorated police force." It also found that, as of 2010, "Colombia is still a major source country for illicit narcotics. Moreover, the state continues to share sovereignty with a range of violent nonstate actors, including rebel groups and rightwing paramilitaries allied with drug traffickers and wealthy landowners." The Washington Office on Latin America concluded in 2010 that both Plan Colombia and the Colombian government's security strategy "came at a high cost in lives and resources, only did part of the job, are yielding diminishing returns and have left important institutions weaker."
==== Mexico ====
One of the first anti-drug efforts in the realm of foreign policy was Nixon's Operation Intercept, announced in September 1969, aiming to severely reduce the amount of cannabis entering the US from Mexico, by government estimates the source of 80% of the US supply. The effort began with an intense inspection crackdown that resulted in a near shutdown of cross-border traffic. The US Air Force and Navy were also on alert to pursue traffickers in the air and at sea. The burden on border crossings was controversial in border states; the effort lasted only 20 days.
Under the leadership of Juan García Ábrego, the Gulf Cartel underwent a significant transformation in drug trafficking in Mexico during the 1980s and early 1990s. García Ábrego, who assumed control of the cartel in 1984, diversified its operations by forging a strategic alliance with the Cali Cartel in Colombia, shifting from primarily trafficking marijuana and heroin to focusing on cocaine, a higher-value product in the U.S. market. This partnership enabled the cartel to capitalize on the growing demand for cocaine in the United States, particularly after U.S. authorities blocked Caribbean routes in the 1990s, making Mexico, and especially Tamaulipas, a key corridor for drug smuggling. García Ábrego’s organizational structure, reliant on corrupting government and police officials, solidified the Gulf Cartel as one of Mexico’s most influential criminal organizations, laying the groundwork for its later expansion. His arrest in 1996 marked a turning point, creating a power vacuum that would be filled by Osiel Cárdenas Guillén.
Osiel Cárdenas Guillén, who took over the Gulf Cartel after García Ábrego’s capture, revolutionized drug trafficking by introducing a paramilitary approach with the creation of Los Zetas in 1999, a group initially composed of elite former Mexican military personnel. This armed wing not only protected the cartel’s operations but also expanded its activities to include kidnappings, extortion, and territorial control, marking an escalation in criminal violence. Under his leadership, the cartel intensified cocaine trafficking to U.S. cities such as Houston and Atlanta, generating millions of dollars, as evidenced by records showing profits of 41 million dollars in just three and a half months from shipments to Atlanta. Direct confrontations with authorities and rivals, such as the Sinaloa Cartel over control of Nuevo Laredo, heightened tensions that set the stage for the war on drug trafficking launched in 2006 by President Felipe Calderón. Cárdenas’ capture in 2003 and extradition in 2007 weakened the cartel, but the resulting fragmentation and the independence of Los Zetas intensified violence in the context of the drug war, leaving a lasting legacy of conflict in Mexico in the decades that followed. Following the capture of Osiel Cárdenas Guillén in 2003 and his extradition in 2007, leadership fell to Jorge Eduardo Costilla Sánchez, a key figure in the Gulf Cartel, who led the criminal organization until 2012. Internal dynamics and rivalries, especially with Los Zetas, defined his era.
The pursuit of Joaquín "El Chapo" Guzmán from 2001 to 2014 is a pivotal case in the context of the 21st-century global war on drugs, as it exemplifies the challenges of combating sophisticated transnational criminal organizations. Guzmán, as the leader of the Sinaloa Cartel, orchestrated one of the most powerful drug trafficking networks, responsible for smuggling vast quantities of narcotics into the United States and Europe, generating billions in illicit revenue. His 2001 escape from a high-security Mexican prison and subsequent evasion until his 2014 capture highlighted the systemic corruption, institutional weaknesses, and cross-border complexities that hinder effective counter-narcotics strategies. The operation to apprehend him, involving Mexican authorities and U.S. agencies like the DEA, underscored the necessity of international cooperation, intelligence-sharing, and advanced surveillance technologies, while also exposing the limitations of militarized approaches in addressing the socio-economic drivers of the drug trade. Guzmán’s high-profile status and the Sinaloa Cartel’s global reach made his capture a symbolic victory, yet it also revealed the resilience of drug trafficking networks, as the cartel continued operations unabated, reflecting the broader, ongoing struggle to dismantle such organizations in the global anti-drug campaign.
The Mérida Initiative, launched in 2008, was a security cooperation program between the US and Mexico, aimed at combating drug trafficking and transnational crime. From 2008 to 2021, the US provided $3.5 billion in funding. The initial focus was anti-drug and rule-of-law measures, later broadened to include US-Mexico border activities. Components included military and law enforcement training and equipment, and technical advice and training to strengthen the national justice systems. In 2021, it was replaced by the Bicentennial Framework for Security, Public Health, and Safe Communities.
In 2013, a Pew Research Center poll found that 85% of Mexican citizens supported using the Mexican army against drug cartels, 74% supported US training assistance for their police and military, 55% supported the US supplying of weapons and financial aid, and 59% were against deploying US troops on Mexican soil. Anti-drug efforts were seen as making progress by 37%, losing ground by 29%, and staying the same by 30%; 56% believed that the US and Mexico are both to blame for drug violence in Mexico.
As of 2024, the DEA considers the Sinaloa and Jalisco cartels, tied to materials and services from China, as the major source of synthetic drugs like fentanyl and methamphetamine, posing the biggest threat to the US.
==== Central America ====
The countries of Central America – Belize, Costa Rica, El Salvador, Guatemala, Honduras, Nicaragua, and Panama – are major transit and storage points for drugs headed to Mexico and the US that annually appear on the American "majors list". The US has had varying levels of direct anti-drug involvement in each of these countries, particularly since the late 2000s when concern over trafficking activity increased. Beginning in 2008, the Central America Regional Security Initiative (CARSI) has provided the seven countries with equipment, training, and technical support for law enforcement efforts, and the US has advised taking an intelligence-based approach.
During the 1980s civil war in Nicaragua, the drug situation was intertwined with the US backing of the anti-leftist rebel force known as the Contras. Senator John Kerry's 1988 Senate Committee on Foreign Relations report on Contra drug links concluded that members of the State Department "who provided support for the Contras are involved in drug trafficking ... and elements of the Contras themselves knowingly receive financial and material assistance from drug traffickers." The involvement included payments to drug traffickers from funds authorized by the Congress for humanitarian assistance to the Contras, in some cases after the traffickers had been indicted by federal law enforcement agencies on drug charges, in others while traffickers were under active investigation by these same agencies."
On December 20, 1989, the US invaded Panama with 25,000 American troops in Operation Just Cause, to depose and arrest the Panamanian head of government, Manuel Noriega. Noriega had been providing military assistance to Contra groups in Nicaragua at the request of the US, which in turn paid him and tolerated his drug trafficking activities, known since the 1960s. Relations with the US deteriorated in the mid-1980s, and his dealings with the US government were exposed in the US news media. The killing of a US soldier in Panama was the final act leading to the invasion. Noriega surrendered to US soldiers on January 3, 1990. He was indicted by the DEA and sentenced by a US court to 45 years in prison for racketeering, drug smuggling, and money laundering. The UN General Assembly resolved that the invasion was a "flagrant violation of international law."
Ecuador, located between the world's two largest cocaine-producing countries, Colombia and Peru,has long been a major drug transit point. From 1999, the Manta air base was the US military's most prominent South American presence, originating some 100 drug surveillance flights monthly. In 2009, citing unwanted internal influence by the CIA, Ecuador declined to renew the base's lease, ending official US military presence. Since 2018, drug activity and anti-drug efforts in Ecuador have dramatically intensified. In 2023, the US-Ecuador Defense Bilateral Working Group was formed to address the Ecuadorian situation, and a memorandum of agreement to help strengthen the Ecuadorian military was signed. A drug-related wider conflict broke out in 2024.
In 2012, the US sent DEA agents to Honduras to assist security forces in counter-narcotic operations. Honduras has been a major stop for drug traffickers, who use small planes and landing strips hidden throughout the country to transport drugs. The DEA, working with other US agencies such as the State Department, the CBP, and Joint Task Force-Bravo, assisted Honduran troops in conducting raids on traffickers' sites of operation.
==== Impact on growers ====
The US-supported coca eradication policy has been criticized for its negative impact on the livelihood of South American coca growers, in a region where the coca leaf has traditionally been chewed and used in tea and for religious, medicinal and nutritional purposes by locals Making traditional coca cultivation illegal is viewed as unjust. In areas where forced eradication also destroyed other food or market crops, without providing an alternative, farmers were left starving and destitute.
=== Afghanistan ===
In 2001, a US-led military coalition invaded Afghanistan and toppled the ruling Taliban as part of the war on terror response to 9/11. For generations, Afghanistan had been producing opium; the Taliban, in power since 1996, banned opium in 2000, reducing domestic production by 90% within a year, cutting the world opium supply by an estimated 65%. With the invasion, poppy cultivation and opium manufacture resumed, and the war on drugs became an element of the US presence.
Initially, "everyone did their own thing, not thinking how it fit in with the larger effort. State was trying to eradicate, USAID was marginally trying to do livelihoods, and DEA was going after bad guys," a senior Department of Defense official stated in a later report. In 2004, opium production dramatically increased and eradication became the focus. The DEA operating budget in Afghanistan grew from $3.7 million in 2004 to $40.6 million in 2008. In 2009, eradication was halted – a senior US official called it "the least effective program ever" – in favor of an "alternative livelihoods" approach that encouraged farmers to grow other crops. In 2017, eradication once again became the main initiative; the US military launched an aerial campaign involving B-52 bombers and F-22 fighters striking a network of drug labs that turned out to be mostly empty compounds, though there were significant civilian casualties.
Undermining US efforts, the prohibitionist policies encouraged a flourishing opium black market, which in turn incentivized widespread, systemic corruption in the Afghan government. In 2018, the US Special Inspector General for Afghanistan Reconstruction called the counternarcotics operation to date "a total failure". As the US military presence neared an end in 2020, Afghanistan was producing an estimated 85% of the world's opium. Having spent some $9 billion in the 20-year anti-drug campaign, US forces left Afghanistan in 2021, and the Taliban returned to power.
=== Venezuela ===
Since Hugo Chávez came to power in 1999, Venezuela has played a pivotal role in the landscape of the war on drugs, establishing itself as a strategic hub for the transit of narcotics, particularly cocaine, due to its geographic position between Colombia, the world’s leading cocaine producer, and routes to the US and Europe. Chávez's decision in 2005 to sever ties with the DEA, accusing its representatives of espionage, marked a turning point that weakened international interdiction efforts in the country. This rupture not only curtailed intelligence sharing and bilateral cooperation but also allowed Venezuela to become a more permeable corridor for drug trafficking, with a significant increase in the volume of drugs transiting through its territory. The involvement of the Venezuelan government in drug trafficking activities has been extensively documented, with allegations pointing to high-ranking officials and military personnel as key actors in what is known as the Cartel of the Suns.
=== China ===
==== Independent law enforcement operations ====
Prior to 2018, the People's Armed Police Border Defense Corps of the Ministry of Public Security Active Service Forces was involved in many anti-drug operations on the China-Myanmar border, where much of the illegal Chinese drug trade is located. In March 25, 2007, 3 PAPBDC officers were killed in action during a shootout with drug traffickers on the China-Myanmar border.
Between 2013 and 2023, the China Coast Guard seized a total of 9.875 tonnes of drugs.
==== American involvement ====
In the mid-2010s, the US identified China as a primary source of illicit fentanyl and other synthetic opioids. American anti-drug intervention regarding China is influenced and constrained by the geopolitical sensitivities of US-China relations. The US employs several approaches: exerting diplomatic pressure on China to impose internal controls on illicit drugs; seeking cooperation in US and international law enforcement efforts; unilaterally imposing targeted sanctions; and bringing criminal indictments against Chinese companies and individuals. The effectiveness of these approaches depends significantly on China's level of implementation and enforcement, which is directly related to the fluctuating state of overall US-China relations.
Following China's scheduling of fentanyl-class substances in 2019, the flow of synthetic opioids from China to the US appeared to subside; trafficking from China shifted to precursor chemicals and related equipment, and Mexico's drug cartels emerged as major clients.
In November 2023, President Biden announced an agreement with General Secretary Xi Jinping for China to crack down on the export of precursor chemicals and pill presses to the Western Hemisphere. A US House committee report released in April 2024 found companies making fentanyl precursors in China can still apply for Chinese state tax rebates and other financial benefits after exporting the product. According to the US, in 2024, China continues to be the primary supplier of chemical precursors to Mexican drug cartels, and Chinese money launderers have become central to the global drug trade.
In December 2024, a Chinese national in Chicago was sentenced to 10 years in prison laundering $62 million in drug money for Mexican traffickers involving currency swaps between United States and China, and China and Mexico. In January 2025, two former executives of a Chinese chemical company were convicted of a scheme to import fentanyl precursor chemicals into the United States.
== Domestic impact ==
The social consequences of the drug war have been widely criticized by such organizations as the ACLU as being racially biased against minorities and disproportionately responsible for the exploding United States prison population. Critics have compared the wholesale incarceration of the dissenting minority of drug users to the wholesale incarceration of other minorities in history. Psychiatrist Thomas Szasz wrote in 1997, "Over the past thirty years, we have replaced the medical-political persecution of illegal sex users ('perverts' and 'psychopaths') with the even more ferocious medical-political persecution of illegal drug users." Assessing from a health perspective, a study in the Annals of Medicine noted: "The U.S. war on drugs has subjected millions to criminalization, incarceration, and lifelong criminal records, disrupting or altogether eliminating their access to adequate resources and supports to live healthy lives."
=== Arrest and incarceration ===
The war on drugs caused soaring arrest rates in the US that disproportionately targeted African Americans due to various factors. Anti-drug and tough-on-crime policies from the 1970s through the 1990s created a situation where the US, with less than 5% of the world population, houses nearly 25% of the world's prisoners. Increased demand lead to the development of privatization and the for-profit prison industry. As of 2015, the US prison population rate was 716 per 100,000 people, the highest in the world, six times higher than Canada and six to nine times higher than Western European countries.
In the 1980s, while the number of arrests for all crimes had risen by 28%, the number of arrests for drug offenses rose 126%. In 1994, the New England Journal of Medicine reported that the war on drugs resulted in the incarceration of one million Americans each year. In 2008, The Washington Post reported that of 1.5 million Americans arrested each year for drug offenses, half a million would be incarcerated, and one in five black Americans would spend time behind bars due to drug laws. In 2019, the FBI estimated about 1.5 million drug arrests nationally, 32.1% for cannabis and 31% for "other dangerous nonnarcotic drugs".
Federal and state policies also impose collateral consequences on those convicted of drug offenses, separate from fines and prison time, that are not applicable to other types of crime. In order to comply with a federal law known as the Solomon–Lautenberg amendment, a number of states require a six-months driver's license suspension for anyone convicted of a drug offense. Other examples of collateral consequences for drug offenses, or for felony offenses in general, include loss of professional license, loss of ability to legally purchase a firearm under Federal law, loss of eligibility for food stamps, loss of eligibility for Federal Student Aid, loss of eligibility to live in public housing, loss of ability to vote, and deportation, a total of over 460 benefits at risk at the federal level alone. The US provides for the deportation of non-citizens convicted of drug offenses.
==== Prison overcrowding ====
One consequence of the war on drugs policy has been the overcrowding of American prisons. The policy's approach to prosecuting drug-related crimes led to a surge in incarcerated individuals for nonviolent drug offenses. As a result, many prisons have become overburdened, often operating at capacities far beyond their intended limits. Overcrowding strains the prison system and raises questions about the effectiveness of incarceration as a solution to drug-related issues. Resources that could be allocated to address the root causes of drug abuse, provide rehabilitation and treatment programs, or support communities affected by drug-related issues, are instead used to manage the considerable prison population. Critics argue that focusing solely on incarceration fails to address the underlying social factors contributing to drug abuse and perpetuates a cycle of criminality without offering pathways to recovery and reintegration into society.
==== Racial disparities in sentencing ====
Racial disparities have been a prominent and contentious aspect of the war on drugs in the US. In 1957, a belief at the time about drug use was summarized by journalist Max Lerner in his work, America as a Civilization: "As a case in point we may take the known fact of the prevalence of reefer and dope addiction in Negro areas. This is essentially explained in terms of poverty, slum living, and broken families, yet it would be easy to show the lack of drug addiction among other ethnic groups where the same conditions apply."
The Anti-Drug Abuse Act of 1986 created a 100:1 sentencing disparity in the US for the trafficking or possession of crack when compared to penalties for trafficking of powder cocaine. The bill had been widely criticized as discriminatory against minorities, mostly blacks, who were more likely to use crack than powder cocaine. In 1994, studying the effects of the 100:1 sentencing ratio, the United States Sentencing Commission (USSC) found that nearly two-thirds of crack users were white or Hispanic, while nearly 85% of those convicted for possession were black, with similar numbers for trafficking. Powder cocaine offenders were more equally divided across race. The USSC noted that these disparities resulted in African Americans serving longer prison sentences than other ethnicities. In a 1995 report to Congress, the USSC recommended against the 100:1 sentencing ratio. In 2010, the 100:1 sentencing ratio was reduced to 18:1.
Other studies indicated similarly dramatic racial differences in enforcement and sentencing. Statistics from 1998 show that there were wide racial disparities in arrests, prosecutions, sentencing and deaths. African-American drug users made up for 35% of drug arrests, 55% of convictions, and 74% of people sent to prison for drug possession crimes. Nationwide African-Americans were sent to state prisons for drug offenses 13 times more often than other races, even though they supposedly constituted only 13% of regular drug users. Human Rights Watch's report, "Race and the Drug War" (2000), provided extensive documentation of racial disparities, citing statistics and case studies highlighting the unequal treatment of racial and ethnic groups by law enforcement agencies, particularly in drug arrests. According to the report, in the US in 1999, compared to non-minorities, African Americans were far more likely to be arrested for drug crimes, and received much stiffer penalties and sentences.
Reporting on the effects of state initiatives, the Department of Justice found that, from 1990 through 2000, "the increasing number of drug offenses accounted for 27% of the total growth among black inmates, 7% of the total growth among Hispanic inmates, and 15% of the growth among white inmates."
In Malign Neglect – Race Crime and Punishment in America (1995), criminologist Michael Tonry wrote, "The War on Drugs foreseeably and unnecessarily blighted the lives of hundreds and thousands of young disadvantaged black Americans and undermined decades of effort to improve the life chances of members of the urban black underclass."
==== Permanent underclass creation ====
Penalties for drug crimes among American youth almost always involve permanent or semi-permanent removal from opportunities for education, strip them of voting rights, and later involve creation of criminal records which make employment more difficult. One-fifth of the US prison population are incarcerated for a drug offense. Thus, some authors maintain that the War on Drugs has resulted in the creation of a permanent underclass of people who have few educational or job opportunities, often as a result of being punished for drug offenses which in turn have resulted from attempts to earn a living in spite of having no education or job opportunities.
In her 2010 book, The New Jim Crow: Mass Incarceration in the Age of Colorblindness, Michelle Alexander argues that the war on drugs has effectively perpetuated a racial caste system, with African American and Hispanic individuals experiencing disproportionately high rates of arrest, conviction, and incarceration for drug-related offenses. This system functions as a modern form of racial control, stripping individuals of their rights and opportunities, and reinforcing societal inequalities. According to Alexander, the consequences extend beyond criminal justice, affecting economic opportunities, access to education, and overall social mobility for affected individuals and communities.
=== Drug testing in the workplace ===
Workplace drug testing has been widespread and controversial in the US since the late 1980s: there is no clear measure of its effectiveness in improving safety and productivity, and testing affects significantly more non-whites than whites. Testing is more prevalent in the US than elsewhere in the world. Most common is urine analysis for amphetamines, cocaine, marijuana, opioids and PCP; usually with no practical discrimination between the effects of the different drugs. Workplace testing rapidly gained popularity after the Reagan administration made it mandatory for federal workers, peaking in 1996, with 81% of companies reporting drug screening, up from 21% in 1987.
In the 1980s, testing had been promoted to business as a way to reclaim what were said to be huge losses in productivity caused by drug use. Studies released in the 1990s refuted these claims; a 1994 report from the National Academy of Sciences, "Under the Influence? Drugs and the American Work Force", concluded that "the data... do not provide clear evidence of the deleterious effects of drugs other than alcohol on safety and other job performance indicators." By 2004, workplace testing was down to 62% of companies, in 2015, it was reported as below 50%. Drug use continues to be blamed for productivity losses, and testing remains common.
In 2021, some companies began to reduce drug testing in order to improve hiring prospects in a tight labor market. Amazon, America's second largest employer, eliminated cannabis testing in job pre-screening, where not required by government regulations, stating, "Pre-employment marijuana testing has disproportionately affected communities of color by stalling job placement." In a survey of 45,000 companies worldwide, 9% reported the elimination of testing in order to improve hiring. In 2022, thousands of US truck drivers were taken off the road after testing positive for cannabis, contributing to a severe driver shortage; a conflict between the majority of states with some form of cannabis legalization, and the federal Department of Transportation's zero-tolerance cannabis policy, even for medical use, is cited as a problem.
=== Public opinion ===
In the 21st century, according to polling, a majority of Americans have been skeptical about the methods and effectiveness of the war on drugs. In 2014, a Pew Research Center poll found that 67% of Americans feel that a movement towards treatment for drugs like cocaine and heroin is better versus 26% who feel that prosecution is the better route. Moving away from mandatory prison terms for drug crimes was favored by two-thirds of the population, a substantial shift from a fifty-fifty split in 2001. A large majority saw alcohol as a greater danger to health (69%) and society (63%) than cannabis. In Gallup polls on whether cannabis should be legal, 15% of Americans agreed in March 1972, rising to 28% in April 1977, where it roughly stayed until 2000, when it began rising again, to 68% in October 2021. In May 2021, a Bully Pulpit Interactive/ACLU poll found that 83% of Americans, across party lines, considered the war on drugs a failure, and 12% considered it a success.
=== Legality ===
The legality of drug prohibition within the US has been challenged on various grounds. One argument holds that drug prohibition, as presently implemented, violates the substantive due process doctrine in that its benefits do not justify the encroachments on rights that are supposed to be guaranteed by the Fifth and Fourteenth Amendments to the US Constitution. Another argument interprets the Commerce Clause to mean that drugs should be regulated in state law not federal law. A third argument states that the reverse burden of proof in drug-possession cases is incompatible with the rule of law, in that the power to convict is effectively taken from the courts and given to those who are willing to plant evidence.
== Efficacy ==
There is no clear measure of the effectiveness of the war on drugs, and it has been widely called a policy failure. Thirty years into the campaign, a National Research Council report, "Informing America's Policy on Illegal Drugs" (2001), found that "existing drug-use monitoring systems are strikingly inadequate to support the full range of policy decisions that the nation must make." The report noted that studies of efforts to address drug usage and smuggling, from US military operations to eradicate coca fields in Colombia, to domestic drug treatment centers, had all been inconclusive, if the programs had been evaluated at all: It concluded, "It is unconscionable for this country to continue to carry out a public policy of this magnitude and cost without any way of knowing whether and to what extent it is having the desired effect."
Writing in the New Statesmen in 2021, journalist James Bloodworth stated, "The war on drugs is a failure. We know this. We've long known it. In fact, there is such an abundance of evidence for its failure that we have more certainty here than in most areas of policy. ... According to the International Drug Policy Consortium there was a 31 per cent global increase in drug taking between 2011 and 2016. ... It is impossible to suppress the demand for drugs." He quoted Helen Clark, former prime minister of New Zealand and head of the Global Commission on Drug Policy: "The total elimination of drugs? Dream on, there's never been a time in human history where human beings haven't resorted to some kind of substances that will take them out of their current reality for whatever reason."
=== Interdiction ===
In 1988, the RAND Corporation released a Department of Defense-funded two-year study, Sealing the Borders: The Effects of Increased Military Participation in Drug Interdiction. It concluded that the use of the armed forces to interdict drugs coming into the US would have little or no effect on cocaine traffic and might, in fact, raise the profits of cocaine cartels and manufacturers. It noted that seven prior studies, including one by the Center for Naval Research and the Office of Technology Assessment, had come to similar conclusions.
In mid-1995, the US government tried to reduce the supply of methamphetamine precursors to disrupt the market of this drug. According to a 2009 study, this effort was successful, but its effects were largely temporary.
In the six years from 2000 to 2006, the US spent $4.7 billion on Plan Colombia, an effort to eradicate coca production in Colombia. The main result of this effort was to shift coca production into more remote areas and force other forms of adaptation. The overall acreage cultivated for coca in Colombia at the end of the six years was found to be the same, after the US Drug Czar's office announced a change in measuring methodology in 2005 and included new areas in its surveys. Cultivation in the neighboring countries of Peru and Bolivia increased, some would describe this effect like squeezing a balloon.
Richard Davenport-Hines, in his book The Pursuit of Oblivion, criticized the efficacy of the war on drugs by pointing out that "10–15% of illicit heroin and 30% of illicit cocaine is intercepted. Drug traffickers have gross profit margins of up to 300%. At least 75% of illicit drug shipments would have to be intercepted before the traffickers' profits were hurt."
Alberto Fujimori, president of Peru from 1990 to 2000, described US foreign drug policy as "failed": "For 10 years, there has been a considerable sum invested by the Peruvian government and another sum on the part of the American government, and this has not led to a reduction in the supply of coca leaf offered for sale. Rather, in the 10 years from 1980 to 1990, it grew 10-fold."
According to a report commissioned by the Drug Policy Alliance, and released in March 2006 by the Justice Policy Institute, harsher sentences for drug offenses committed in drug-free school zones are ineffective at keeping youths away from drugs and instead create strong racial disparities in the judicial system.
According to data collected by the Federal Bureau of Prisons 45.3% of all criminal charges were drug related and 25.5% of sentences for all charges last 5–10 years. Furthermore, non-whites make up 41.4% of the federal prison system's population and over half are under the age of 40. The Bureau of Justice Statistics states that over 80% of all drug related charges are for mere possession rather than the sale or manufacture of drugs.
=== Drug use ===
In 2005, the federally funded Monitoring the Future annual survey reported about 85% of high school seniors found marijuana "easy to obtain", virtually unchanged since 1975, never dropping below 82.7% in three decades of national surveys. The DEA stated that the number of users of cannabis in the US declined between 2000 and 2005, even with many states passing new medical cannabis laws, making access easier, though usage rates remain higher than they were in the 1990s according to the National Survey on Drug Use and Health.
The ONDCP stated in April 2011 that there had been a 46% drop in cocaine use among young adults over the previous five years, and a 65% drop in the rate of people testing positive for cocaine in the workplace since 2006. At the same time, a 2007 study found that up to 35% of college undergraduates used stimulants not prescribed to them.
A 2013 study found that prices of heroin, cocaine and cannabis had decreased from 1990 to 2007, while the purity of these drugs had increased.
The National Survey on Drug Use and Health for 2019 found that 1.7% of US adults over 25 had used cocaine in the previous 12 months, compared to 1.8% in 2002, and cannabis use went from 7% in 2002 to 15.2%. The DEA's 2021 National Drug Threat Assessment stated that "a steady supply of cocaine was available throughout domestic markets" in 2019 and 2020.
According to the Centers for Disease Control (CDC), drug abuse fatalities in 2021 reached an all-time high of 108,000 deaths, a 15% increase from 2020 (93,000) which, at the time, was the highest number of deaths and a 30% increase from 2019.
During alcohol prohibition, from 1920 to 1933, alcohol use initially fell but began to increase as early as 1922. It has been extrapolated that even if prohibition had not been repealed in 1933, alcohol consumption would have surpassed pre-prohibition levels. One argument against the war on drugs is that it uses similar measures as Prohibition and is no more effective.
=== Government efficiency ===
In 1997, Rolling Stone published a comprehensive snapshot of the US government's implementation of the war on drugs, spanning 44 federal agencies and hundreds of thousands of government workers, and without unified management, oversight, or cohesive strategy. Among the agencies there were over a dozen separate drug intelligence operations. The White House's Office of National Drug Control Policy, home of the drug czar and ostensibly the coordinating agency, had a staff of 150, and a $36 million budget; the overall federal drug war budget for 1998 was $16 billion. Most of the agencies involved did not report to the ONDCP, instead to one of 13 congressional appropriations subcommittees. The largest single share of the budget, $2 billion, went to the Bureau of Prisons. Federal agencies also passed on billions of anti-drug dollars to the states, with little oversight or accountability. In 2024, the ONDCP requested $461 million of a $46 billion federal budget allocated across some 50 federal agencies.
== Alternatives ==
Alternatives to the predominantly punitive, law enforcement approach to the war on drugs in the US fall under two broad categories: a public health orientation built around education, prevention and treatment, and decriminalization or legalization with regulation similar to the handling of alcohol. Jefferson Fish has edited scholarly collections of articles offering a wide variety of public health-based and rights-based alternative drug policies.
=== A public-health approach ===
A common critical view holds that the war on drugs has been costly and ineffective largely because US federal and state governments have chosen the wrong methods, focusing on interdiction and punishment rather than regulation and treatment of drug abuse and addiction. In the US, current public health-oriented interventions include harm reduction, drug courts, and Law Enforcement Assisted Diversion (LEAD) programs which give police treatment or social services options rather than arrest with minor drug offenses. Harm reduction approaches include provision of sterile syringes, medically supervised injection sites (SIF), and availability of the opioid overdose-countering drug naloxone.
As an alternative to imprisonment, drug courts in the US identify substance-abusing offenders and place them under strict court monitoring and community supervision, as well as provide them with long-term treatment services. According to a National Drug Court Institute report, 16.4% of the nation's drug court graduates are rearrested and charged with a felony within one year of completing the program; overall 44.1% of released prisoners end up back in prison within one year. The drug court program is also significantly cheaper than imprisonment. Annual per offender cost is $20,000–$50,000 for imprisonment, and $2,500–$4,000 in the drug court system.
A survey by the Substance Abuse and Mental Health Services Administration (SAMHSA) found that substance abusers who remain in treatment longer are less likely to resume their former drug habits. Of the people studied, 66% were cocaine users. After experiencing long-term in-patient treatment, only 22% returned to the use of cocaine.
During the 1990s, the Clinton administration commissioned a major cocaine policy study by the RAND Drug Policy Research Center. The report recommended that $3 billion be switched from federal and local law enforcement to treatment, concluding that treatment is the cheapest way to cut drug use, and twenty-three times more effective than the supply-side war on drugs.
=== Decriminalization and legalization ===
In a 2023 UN report, the UN high commissioner for Human Rights stated that "decades of punitive, 'war on drugs' strategies had failed to prevent an increasing range and quantity of substances from being produced and consumed", described punitive drug policies as a failure, and called for an approach "based on health and human rights, including through the legal regulation of drugs."
Considering outright legalization of recreational drugs, New York Times columnist Eduardo Porter noted: Jeffrey Miron, an economist at Harvard who studies drug policy closely, has suggested that legalizing all illicit drugs would produce net benefits to the United States of some $65 billion a year, mostly by cutting public spending on enforcement as well as through reduced crime and corruption. A study by analysts at the RAND Corporation, a California research organization, suggested that if marijuana were legalized in California and the drug spilled from there to other states, Mexican drug cartels would lose about a fifth of their annual income of some $6.5 billion from illegal exports to the United States.
In 2007, "An Open Letter to the President, Congress, Governors, and State Legislatures" signed by over 550 economists, including Nobel laureates Milton Friedman, George Akerlof and Vernon L. Smith, endorsed the findings of a 2006 paper, "The Budgetary Implications of Marijuana Prohibition," by Harvard economist Jeffrey A. Miron. Comparing the cost of prohibition to the tax revenue if cannabis was taxed as regular consumer good, or similarly to alcohol, the letter stated that the budgetary impact, considered alongside evidence that "suggests prohibition has minimal benefits and may itself cause substantial harm", favors "a regime in which marijuana is legal but taxed and regulated like other goods." According to a 2010 report on co-authored by Miron, the annual savings on enforcement and incarceration costs from the legalization of drugs would amount to roughly $41.3 billion, with $25.7 billion being saved among the states and over $15.6 billion accrued for the federal government. Miron further estimated at least $46.7 billion in tax revenue based on rates comparable to those on tobacco and alcohol: $8.7 billion from marijuana, $32.6 billion from cocaine and heroin, and $5.4 billion from other drugs.
Regarding economic arguments for legalization that make a comparison with alcohol, a 2013 study noted that the $14.6 billion in annual alcohol tax collected at the US federal and state levels represented less than 10% of the estimated $185 billion of alcohol-related health care, criminal justice and lost productivity costs.
== See also ==
== Notes ==
== References ==
== Further reading ==
Hari, Johann (2015). Chasing the Scream: The First and Last Days of the War on Drugs. London; New York: Bloomsbury. ISBN 978-1620408902.
Blanchard, Michael; Chin, Gabriel J. (1998). "Identifying the Enemy in the War on Drugs: A Critique of the Developing Rule Permitting Visual Identification of Indescript White Powders in Narcotics Prosecutions". American University Law Review (47): 557. SSRN 1128945.
Daniel Burton-Rose, The Celling of America: An Inside Look at the U.S. Prison Industry. Common Courage Press, 1998.
Stephanie R. Bush-Baskette, "The War on Drugs as a War on Black Women," in Meda Chesney-Lind and Lisa Pasko (eds.), Girls, Women, and Crime: Selected Readings. Sage, 2004.
Chin, Gabriel (2002). "Race, the War on Drugs and the Collateral Consequences of Criminal Conviction". Gender, Race & Justice (6): 253. SSRN 390109.
Alexander Cockburn and Jeffrey St. Clair, Whiteout: The CIA, Drugs and the Press. New York: Verso, 1998.
Mitchell Earlywine, Understanding Marijuana: A New Look at the Scientific Evidence. New York: Oxford University Press, 2005.
Kathleen J. Frydl, The Drug Wars in America, 1940–1973. New York: Cambridge University Press, 2013.
Nunn, Kenneth B. (2002). "Race, Crime and the Pool of Surplus Criminality: Or Why the War on Drugs Was a War on Blacks". Gender, Race & Justice. 6 (6): 381.
Tony Payan, "A War that Can't Be Won." Tucson: The University of Arizona Press, 2013.
Preston Peet, Under the Influence: The Disinformation Guide to Drugs. The Disinformation Company, 2004.
Thomas C. Rowe, Federal Narcotics Laws and the War on Drugs: Money Down a Rat Hole. Binghamton, NY: Haworn Press, 2006.
Eric Schneider, "The Drug War Revisited," Berfrois, November 2, 2011.
Peter Dale Scott and Jonathan Marshall, Cocaine Politics: Drugs, Armies, and the CIA in Central America. Berkeley, CA: University of California Press, 1911.
Dominic Streatfeild, Cocaine: An Unauthorized Biography. Macmillan, 2003.
Douglas Valentine, The Strength of the Wolf: The Secret History of America's War on Drugs. New York: Verso, 2004.
=== Government and NGO reports ===
National Drug Threat Assessment 2009 from the United States Department of Justice
War On Drugs: Legislation in the 108th Congress and Related Developments, a 2003 report from the Congressional Research Service via the State Department website
The Report of the Canadian Government Commission of Inquiry into the Non-Medical Use of Drugs – 1972
Drug Enforcement Administration (2017), Drugs of abuse: A DEA resource guide (PDF) (2017 ed.), Washington, D.C.: Author, archived from the original (PDF) on December 3, 2016, retrieved January 23, 2018
Revealing the missing link to Climate Justice: Drug Policy, a 2023 report from the International Coalition on Drug Policy Reform and Environmental Justice
== External links ==
Narco News – news site focusing on drug war in Latin America
Drug Policy Facts
Major Studies of Drugs and Drug Policy Full text of major government commission reports on the drug laws from around the world over the last 100 years
Historical Research on the Drug War Full text of numerous full histories of the drug war and thousands of original historical documents
Cato Institute Drug Prohibition Research | Wikipedia/War_on_drugs |
The U.S. state of Maryland has various policies regarding the production, sale, and use of different classes and kinds of drugs.
== Specific drugs ==
=== Alcohol ===
As of July 2024, the sales tax for purchasing alcohol in Maryland is 9 percent. The tax was raised from 6 percent effective July 1, 2011; the increase was expected to generate $85 million for state programs in its first year.
Businesses that operate in the state of Maryland have certain requirements if they serve alcohol. Any employee that handles alcohol must be at least 18 years of age. Bartenders and restaurant servers also have the responsibility of monitoring their customers' alcohol consumption in order to help prevent drunk driving. If the bartender or server is shown to have known and purposefully neglected this responsibility, the employee can be held criminally responsible. They are also required to verify the age of those purchasing alcohol, to ensure consumers are of the legal age. As of right now, the minimum legal age to purchase alcohol in Maryland is 21.
It is against the law to misrepresent one's age by using another's identification or a fake identification. The penalties for this include:
fines of up to $2,000
imprisonment of up to 3 years
suspension or revocation of one's driver's license
If the violator is under the age of 18, she or he may be required to attend a supervised work or alcohol rehabilitation program, and the violator's guardian(s) may be asked to withdraw consent for the violator to hold a license.
==== Drinking and driving ====
When a prospective driver is given a license in the state of Maryland, they are required to sign an agreement to submit to a blood alcohol test if asked by a police officer. Refusal to take the test results in a 120-day suspension of the offender's license. If the offender is detained a second time, and again refuses to take a blood alcohol test, an automatic one-year suspension of the offender's license goes into effect.
Driving drunk is punished with fines, license suspension, and jail time. The penalties vary depending on the circumstances.
If the offender is under the age of 21 and shown to have a blood alcohol level of 0.02% or higher, the offender's license may be revoked or suspended and the offender may face a fine of up to $500.
The legal blood alcohol content limit for anyone over the age of 21 is 0.08%, in which case the driver may be charged with a DWI (driving while intoxicated). If the offender is driving with a blood alcohol content of 0.04-0.08%, they may be cited for driving under the influence. If the offender is considered to be intoxicated, the penalties are as follows:
a 45-day license suspension for the first offense
a 90-day license suspension for the second offense
loss of driving privileges
If the offender is transporting a minor at the time, the offender may face a fine of up to $4,000 and a prison sentence of up to four years.
If the offender is a first-time offender, or has not had any convictions of DUI/DWI in the past ten years, then the offender can plead for Probation Before Judgement (PBJ). PBJ is pleading "not guilty" with intention that the offender gets placed on probation before they have been found guilty of the crime they have been charged for. This prevents the charge on the individuals record in compliance that the violation never occurs again, and that their record will maintain being charge-free.
=== Cannabis ===
In May 2003, Governor Bob Ehrlich signed legislation into law that allowed those being prosecuted for marijuana-related crimes to raise an “affirmative defense of medical necessity” at trial. At the time, the courts were required to consider such a mitigating factor, whereafter only a maximum penalty of $100 could be imposed.
In April 2014, Governor Martin O'Malley signed a law that decriminalized the possession of 10 grams or less of marijuana. The measure made such possession a civil infraction, similar to that of a traffic ticket.
In 2016, the Maryland General Assembly, under Democratic control, passed SB 517, which decriminalized the possession of marijuana paraphernalia and decriminalized the smoking of marijuana in public.
In Pacheco v. State (2019), the Maryland Court of Appeals determined that "the mere odor of marijuana coupled with possession of what is clearly less than ten grams of marijuana, absent other circumstances, does not grant officers probable cause to effectuate an arrest and conduct a search".
In 2022, Maryland voters approved a referendum on the legalization of cannabis for adult use in Maryland. The law allows for the possession of up to 1.5 ounces of marijuana for recreational use, as well as the growing and maintaining of no more than two cannabis plants out of public view. It came into force on July 1, 2023.
=== Cocaine ===
The decade spanning 2008–2018 saw a surge of 590% in cocaine-related deaths. This sharp spike is largely attributable to cocaine usage in combination with opioids — in 2018, 88.9% of cocaine-related deaths occurred in combination with fentanyl. Almost 900 people died from cocaine-related overdoses in Maryland in 2018. Of these, 423 deaths occurred in Baltimore. Despite only accounting for 10% of Maryland’s population, Baltimore accounts for nearly half of cocaine-related deaths.
The sale, distribution and production of cocaine is illegal and is a felony in every state. Possession of small amounts of cocaine can lead to serious penalties. Additionally, the severity of the punishment varies depending on whether the defendant has prior drug convictions and the quantity of drugs involved.
The table below outlines the charges and penalties under Maryland's cocaine laws.
However, these penalties may not be applied to all offenders as prosecutors can offer plea bargains in exchange for helping to build a case against those higher up the chain such as producers and dealers. Furthermore, first-time or second-time offenders may be offered time spent in rehabilitation rather than in jail.
Additionally, violating Maryland’s controlled dangerous substances laws as a first time offender allows the individual to qualify pleading Probation Before Judgement. Utilizing this statute is pleading not guilty and for probation before the charged crime is to be found guilty. There are guidelines to whom this applies to and any individual who has two or subsequent violations of Maryland’s controlled dangerous substances laws are not eligible.
== See also ==
Annotated Code of Maryland
Federal drug policy of the United States
== References == | Wikipedia/Drug_policy_of_Maryland |
Drug rehabilitation is the process of medical or psychotherapeutic treatment for dependency on psychoactive substances such as alcohol, prescription drugs, and street drugs such as cannabis, cocaine, heroin, and amphetamines. The general intent is to enable the patient to confront substance dependence, if present, and stop substance misuse to avoid the psychological, legal, financial, social, and medical consequences that can be caused.
Treatment includes medication for comorbidities, counseling by experts, and sharing of experience with other recovering individuals.
== Psychological dependency ==
Psychological dependency is addressed in many drug rehabilitation programs by attempting to teach patients new methods of interacting in a drug-free environment. In particular, patients are generally encouraged, or possibly even required, to not associate with peers who still use addictive substances. Twelve-step programs encourage addicts not only to stop using alcohol or other drugs but to examine and change habits related to their addictions. Many programs emphasize that recovery is an ongoing process without culmination. For legal drugs such as alcohol, complete abstention—rather than attempts at moderation, which may lead to relapse—is also emphasized ("One is too many, and a thousand is never enough.")
Whether moderation is achievable by those with a history of misuse remains a controversial point.
The brain's chemical structure is altered by addictive substances and these changes are present long after an individual stops using. This change in brain structure increases the risk of relapse, making treatment an important part of the rehabilitation process.
== Types ==
Various types of programs offer help in drug rehabilitation, including residential treatment (in-patient/out-patient), local support groups, extended care centers, recovery or sober houses, addiction counselling, mental health, and medical care. Some rehab centers offer age- and gender-specific programs.
In an American survey by three separate institutions (the National Association of Alcoholism and Drug Abuse Counselors, Rational Recovery Systems and the Society of Psychologists in Addictive Behaviors) measuring treatment responses on the Spiritual Belief Scale (a scale measuring belief in the four spiritual characteristics Alcoholics Anonymous identified by Ernest Kurtz); the scores were found to explain 41% of the variance in the treatment provider's responses on the Addiction Belief Scale (a scale measuring adherence to the disease model or the free-will model addiction).
Effective treatment addresses the multiple needs of the patient rather than treating addiction alone. In addition, medically assisted drug detoxification or alcohol detoxification alone is ineffective as a treatment for addiction. The National Institute on Drug Abuse (NIDA) recommends detoxification followed by both medication (where applicable) and behavioral therapy, followed by relapse prevention. According to NIDA, effective treatment must address medical and mental health services as well as follow-up options, such as community or family-based recovery support systems. Whatever the methodology, patient motivation is an important factor in treatment success.
For individuals addicted to prescription drugs, treatments tend to be similar to those who are addicted to drugs affecting the same brain systems. Medication like methadone and buprenorphine can be used to treat addiction to prescription opiates, and behavioral therapies can be used to treat addiction to prescription stimulants, benzodiazepines, and other drugs.
Types of behavioral therapy include:
Cognitive-behavioral therapy, which seeks to help patients to recognize, avoid and cope with situations in which they are most likely to relapse.
Multidimensional family therapy, which is designed to support the recovery of the patient by improving family functioning.
Motivational interviewing, which is designed to increase patient motivation to change behavior and enter treatment.
Motivational incentives, which uses positive reinforcement to encourage abstinence from the addictive substance.
EEG Biofeedback augmented treatment improves abstinence rates of 12-step, faith-based, and medically assisted addiction for cocaine, methamphetamine, alcohol use disorder, and opioid addictions.
Treatment can be a long process and the duration is dependent upon the patient's needs and history of substance use. Research has shown that most patients need at least three months of treatment and longer durations are associated with better outcomes. Prescription drug addiction does not discriminate. It affects people from all walks of life and can be a devastatingly destructive force.
=== Medications ===
Certain opioid medications such as methadone and more buprenorphine are widely used to treat addiction and dependence on other opioids such as heroin, morphine or oxycodone. Methadone and buprenorphine are maintenance therapies intended to reduce cravings for opiates, thereby reducing illegal drug use, and the risks associated with it, such as disease, arrest, incarceration, and death, in line with the philosophy of harm reduction. Both drugs may be used as maintenance medications (taken for an indefinite period of time), or used as detoxification aids. All available studies collected in the 2005 Australian National Evaluation of Pharmacotherapies for Opioid Dependence suggest that maintenance treatment is preferable, with very high rates (79–100%) of relapse within three months of detoxification from levo-α-acetylmethadol (LAAM), buprenorphine, and methadone.
According to the National Institute on Drug Abuse (NIDA), patients stabilized on adequate, sustained doses of methadone or buprenorphine can keep their jobs, avoid crime and violence, and reduce their exposure to HIV and Hepatitis C by stopping or reducing injection drug use and drug-related high risk sexual behavior. Naltrexone is a long-acting opioid antagonist with few side effects. It is usually prescribed in outpatient medical conditions. Naltrexone blocks the euphoric effects of alcohol and opiates. Naltrexone cuts relapse risk in the first three months by about 36%. However, it is far less effective in helping patients maintain abstinence or retaining them in the drug-treatment system (retention rates average 12% at 90 days for naltrexone, average 57% at 90 days for buprenorphine, average 61% at 90 days for methadone).
Ibogaine is a hallucinogenic drug promoted by certain fringe groups to interrupt both physical dependence and psychological craving to a broad range of drugs including narcotics, stimulants, alcohol, and nicotine. To date, there have never been any controlled studies showing it to be effective, and it is not accepted as a treatment by physicians, pharmacists, or addictionologist. There have also been several deaths related to ibogaine use, which causes tachycardia and long QT syndrome. The drug is an illegal Schedule I controlled substance in the United States, and the foreign facilities in which it is administered tend to have little oversight and range from motel rooms to one moderately-sized rehabilitation center.
A few antidepressants have been proven to be helpful in the context of smoking cessation/nicotine addiction. These medications include bupropion and nortriptyline. Bupropion inhibits the re-uptake of nor-epinephrine and dopamine and has been FDA approved for smoking cessation, while nortriptyline is a tricyclic antidepressant which has been used to aid in smoking cessation it has not been FDA approved for this indication.
Acamprosate, disulfiram and topiramate (a novel anticonvulsant sulphonated sugar) are also used to treat alcohol addiction. Acamprosate has shown effectiveness for patients with severe dependence, helping them to maintain abstinence for several weeks, even months. Disulfiram produces a very unpleasant reaction when drinking alcohol that includes flushing, nausea and palpitations. It is more effective for patients with high motivation and some addicts use it only for high-risk situations. Patients who wish to continue drinking or may be likely to relapse should not take disulfiram as it can result in the disulfiram-alcohol reaction mentioned previously, which is very serious and can even be fatal.
Nitrous oxide, also sometimes known as laughing gas, is a legally available gas used for anesthesia during certain dental and surgical procedures, in food preparation, and for the fueling of rocket and racing engines. People who use substances also sometimes use gas as an inhalant. Like all other inhalants, it is popular because it provides consciousness-altering effects while allowing users to avoid some of the legal issues surrounding illicit substances. Misuse of nitrous oxide can produce significant short-term and long-term damage to human health, including a form of oxygen starvation called hypoxia, brain damage and a serious vitamin B12 deficiency that can lead to nerve damage.
Although dangerous and addictive in its own right, nitrous oxide has been shown to be an effective treatment for a number of addictions.
=== Residential treatment ===
In-patient residential treatment for people with an alcohol use disorder is usually quite expensive without insurance. Most American programs follow a 28–30 day program length. The length is based solely upon providers' experience. During the 1940s, clients stayed about one week to get over the physical changes, another week to understand the program, and another week or two to become stable. 70% to 80% of American residential alcohol treatment programs provide 12-step support services. These include, but are not limited to AA, Narcotics Anonymous, Cocaine Anonymous and Al-Anon. One recent study suggests the importance of family participation in residential treatment patient retention, finding "increased program completion rate for those with a family member or significant other involved in a seven-day family program".
=== Brain implants ===
Patients with severe opioid addiction are being given brain implants to help reduce their cravings, in the first trial of its kind in the US. Treatment starts with a series of brain scans. Surgery follows with doctors making a small hole in the skull to insert a tiny 1mm electrode in the specific area of the brain that regulates impulses such as addiction and self-control. This treatment is for those who have failed every other treatment, whether that is medicine, behavioral therapy, and/or social interventions. It is a very rigorous trial with oversight from ethicists and regulators and many other governing bodies.
== Recovery ==
The definition of recovery remains divided and subjective in drug rehabilitation, as there are no set standards for measuring recovery. The Betty Ford Institute defined recovery as achieving complete abstinence as well as personal well-being while other studies have considered "near abstinence" as a definition.
The Recovery Model originates in the psychiatric survivor movement in the US, which argues that receiving a certain diagnoses can be stigmatizing and disempowering. Some characteristics of the Recovery Model are social inclusion, empowerment to overcome substance use, focusing on strengths of the client instead of their deficits and providing help living more fulfilling lives in the presence of symptoms of addiction. Another key component of the Recovery Model is the collaborative relationship between client and provider in developing the client's path to abstinence. Under the Recovery Model a program is personally designed to meet an individual clients needs, and does not include a standard set of steps one must go through.
The Recovery Model uses integral theory: a four-part approach focusing on the individual, the collective society, along with individual and external factors. The four quadrants corresponding with each in Integral Theory are Consciousness, Behavior, Culture and Systems. Quadrant One deals with the neurological aspect of addiction. Quadrant Two focuses on building self-esteem and a feeling of connectedness, sometimes through spirituality. Quadrant three works on mending the "eroded relationships" caused by active addiction. Quadrant Four often involves facing the harsh consequences of drug use such as unemployment, legal discrepancies, or eviction. The use of integral theory aims to break the dichotomy of "using" or "not using" and focuses instead on emotional, spiritual, and intellectual growth, along with physical wellness.
== Criminal justice ==
Drug rehabilitation is sometimes part of the criminal justice system. People convicted of minor drug offenses may be sentenced to rehabilitation instead of prison, and those convicted of driving while intoxicated are sometimes required to attend Alcoholics Anonymous meetings. There are a great number of ways to address an alternative sentence in a drug possession or DUI case; increasingly, American courts are willing to explore outside-the-box methods for delivering this service. There have been lawsuits filed, and won, regarding the requirement of attending Alcoholics Anonymous and other twelve-step meetings as being inconsistent with the Establishment Clause of the First Amendment of the U.S. Constitution, mandating separation of church and state.
In some cases, individuals can be court-ordered to drug rehabilitation by the state through legislation like the Marchman Act.
== Counseling ==
Traditional addiction treatment is based primarily on counseling.
Counselors help individuals with identifying behaviors and problems related to their addiction. It can be done on an individual basis, but it's more common to find it in a group setting and can include crisis counseling, weekly or daily counseling, and drop-in counseling supports. Counselors are trained to develop recovery programs that help to reestablish healthy behaviors and provide coping strategies whenever a situation of risk happens. It's very common to see them also work with family members who are affected by the addictions of the individual, or in a community to prevent addiction and educate the public. Counselors should be able to recognize how addiction affects the whole person and those around him or her.
Counseling is also related to "Intervention"; a process in which the addict's family and loved ones request help from a professional to get an individual into drug treatment.
This process begins with a professionals' first goal: breaking down denial of the person with the addiction. Denial implies a lack of willingness from the patients or fear to confront the true nature of the addiction and to take any action to improve their lives, instead of continuing the destructive behavior. Once this has been achieved, the counselor coordinates with the addict's family to support them in getting the individual to drug rehabilitation immediately, with concern and care for this person. Otherwise, this person will be asked to leave and expect no support of any kind until going into drug rehabilitation or alcoholism treatment. An intervention can also be conducted in the workplace environment with colleagues instead of family.
One approach with limited applicability is the sober coach. In this approach, the client is serviced by the provider(s) in his or her home and workplace—for any efficacy, around-the-clock—who functions much like a nanny to guide or control the patient's behavior.
=== Twelve-step programs ===
The disease model of addiction has long contended the maladaptive patterns of alcohol and substance use displays addicted individuals are the result of a lifelong disease that is biological in origin and exacerbated by environmental contingencies. This conceptualization renders the individual essentially powerless over his or her problematic behaviors and unable to remain sober by himself or herself, much as individuals with a terminal illness are unable to fight the disease by themselves without medication. Behavioral treatment, therefore, necessarily requires individuals to admit their addiction, renounce their former lifestyle, and seek a supportive social network that can help them remain sober. Such approaches are the quintessential features of Twelve-step programs, originally published in the book Alcoholics Anonymous in 1939. These approaches have met considerable amounts of criticism, coming from opponents who disapprove of the spiritual-religious orientation on both psychological and legal grounds. Opponents also contend that it lacks valid scientific evidence for claims of efficacy. However, there is survey-based research that suggests there is a correlation between attendance and alcohol sobriety. Different results have been reached for other drugs, with the twelve steps being less beneficial for addicts to illicit substances, and least beneficial to those addicted to the physiologically and psychologically addicting opioids, for which maintenance therapies are the gold standard of care.
=== SMART Recovery ===
SMART Recovery was founded by Joe Gerstein in 1994 by basing REBT as a foundation. It gives importance to the human agency in overcoming addiction and focuses on self-empowerment and self-reliance. It does not subscribe to disease theory and powerlessness. The group meetings involve open discussions, questioning decisions and forming corrective measures through assertive exercises. It does not involve a lifetime membership concept, but people can opt to attend meetings, and choose not to after gaining recovery. Objectives of the SMART Recovery programs are:
Building and Maintaining Motivation,
Coping with Urges,
Managing Thoughts, Feelings, and Behaviors,
Living a Balanced Life.
This is considered to be similar to other self-help groups who work within mutual aid concepts.
=== Client-centered approaches ===
In his influential book, Client-Centered Therapy, in which he presented the client-centered approach to therapeutic change, psychologist Carl Rogers proposed there are three necessary and sufficient conditions for personal change: unconditional positive regard, accurate empathy, and genuineness. Rogers believed the presence of these three items, in the therapeutic relationship, could help an individual overcome any troublesome issue, including but not limited to alcohol use disorder. To this end, a 1957 study compared the relative effectiveness of three different psychotherapies in treating alcoholics who had been committed to a state hospital for sixty days: a therapy based on two-factor learning theory, client-centered therapy, and psychoanalytic therapy. Though the authors expected the two-factor theory to be the most effective, it actually proved to be deleterious in the outcome. Surprisingly, client-centered therapy proved most effective. It has been argued, however, these findings may be attributable to the profound difference in therapist outlook between the two-factor and client-centered approaches, rather than to client-centered techniques. The authors note two-factor theory involves stark disapproval of the clients' "irrational behavior" (p. 350); this notably negative outlook could explain the results.
A variation of Rogers' approach has been developed in which clients are directly responsible for determining the goals and objectives of the treatment. Known as Client-Directed Outcome-Informed therapy (CDOI), this approach has been utilized by several drug treatment programs, such as Arizona's Department of Health Services.
=== Psychoanalysis ===
Psychoanalysis, a psychotherapeutic approach to behavior change developed by Sigmund Freud and modified by his followers, has also explained substance use. This orientation suggests the main cause of the addiction syndrome is the unconscious need to entertain and to enact various kinds of homosexual and perverse fantasies, and at the same time to avoid taking responsibility for this. It is hypothesized specific drugs facilitate specific fantasies and using drugs is considered to be a displacement from, and a concomitant of, the compulsion to masturbate while entertaining homosexual and perverse fantasies. The addiction syndrome is also hypothesized to be associated with life trajectories that have occurred within the context of teratogenic processes, the phases of which include social, cultural, and political factors, encapsulation, traumatophobia, and masturbation as a form of self-soothing. Such an approach lies in stark contrast to the approaches of social cognitive theory to addiction—and indeed, to behavior in general—which holds human beings to regulate and control their own environmental and cognitive environments, and are not merely driven by internal, driving impulses. Additionally, homosexual content is not implicated as a necessary feature in addiction.
=== Relapse prevention ===
An influential cognitive-behavioral approach to addiction recovery and therapy has been Alan Marlatt's (1985) Relapse Prevention approach. Marlatt describes four psycho-social processes relevant to the addiction and relapse processes: self-efficacy, outcome expectancy, attributions of causality, and decision-making processes. Self-efficacy refers to one's ability to deal competently and effectively with high-risk, relapse-provoking situations. Outcome expectancy refers to an individual's expectations about the psychoactive effects of an addictive substance. Attributions of causality refer to an individual's pattern of beliefs that relapse to drug use is a result of internal, or rather external, transient causes (e.g., allowing oneself to make exceptions when faced with what are judged to be unusual circumstances). Finally, decision-making processes are implicated in the relapse process as well. Substance use is the result of multiple decisions whose collective effects result in the consumption of the intoxicant. Furthermore, Marlatt stresses some decisions—referred to as apparently irrelevant decisions—may seem inconsequential to relapse, but may actually have downstream implications that place the user in a high-risk situation.
For example: As a result of heavy traffic, a recovering alcoholic may decide one afternoon to exit the highway and travel on side roads. This will result in the creation of a high-risk situation when he realizes he is inadvertently driving by his old favorite bar. If this individual can employ successful coping strategies, such as distracting himself from his cravings by turning on his favorite music, then he will avoid the relapse risk (PATH 1) and heighten his efficacy for future abstinence. If, however, he lacks coping mechanisms—for instance, he may begin ruminating on his cravings (PATH 2)—then his efficacy for abstinence will decrease, his expectations of positive outcomes will increase, and he may experience a lapse—an isolated return to substance intoxication. So doing results in what Marlatt refers to as the Abstinence Violation Effect, characterized by guilt for having gotten intoxicated and low efficacy for future abstinence in similar tempting situations. This is a dangerous pathway, Marlatt proposes, to full-blown relapse.
=== Cognitive therapy ===
An additional cognitively-based model of substance use recovery has been offered by Aaron Beck, the father of cognitive therapy and championed in his 1993 book Cognitive Therapy of Substance Abuse. This therapy rests upon the assumption addicted individuals possess core beliefs, often not accessible to immediate consciousness (unless the patient is also depressed). These core beliefs, such as "I am undesirable," activate a system of addictive beliefs that result in imagined anticipatory benefits of substance use and, consequentially, craving. Once craving has been activated, permissive beliefs ("I can handle getting high just this one more time") are facilitated. Once a permissive set of beliefs have been activated, then the individual will activate drug-seeking and drug-ingesting behaviors. The cognitive therapist's job is to uncover this underlying system of beliefs, analyze it with the patient, and thereby demonstrate its dysfunction. As with any cognitive-behavioral therapy, homework assignments and behavioral exercises serve to solidify what is learned and discussed during treatment.
=== Emotion regulation and mindfulness ===
A growing literature is demonstrating the importance of emotion regulation in the treatment of substance use. Considering that nicotine and other psychoactive substances such as cocaine activate similar psycho-pharmacological pathways, an emotion regulation approach may be applicable to a wide array of substance use. Proposed models of affect-driven tobacco use have focused on negative reinforcement as the primary driving force for addiction; according to such theories, tobacco is used because it helps one escape from the undesirable effects of nicotine withdrawal or other negative moods. Acceptance and commitment therapy (ACT), is showing evidence that it is effective in treating substance use, including the treatment of polysubstance use disorder and tobacco smoking. Mindfulness programs that encourage patients to be aware of their own experiences in the present moment and of emotions that arise from thoughts, appear to prevent impulsive/compulsive responses. Research also indicates that mindfulness programs can reduce the consumption of substances such as alcohol, cocaine, amphetamines, marijuana, cigarettes and opiates.
=== Dual diagnosis ===
People who are diagnosed with a mental health disorder and a simultaneous substance use disorder are known as having a dual diagnosis. For example, someone with bipolar disorder who also has an alcohol use disorder would have dual diagnosis. On such occasions, two treatment plans are needed with the mental health disorder requiring treatment first. According to the National Survey on Drug Use and Health (NSDUH), 45 percent of people with addiction have a co-occurring mental health disorder.
== Behavioral models ==
Behavioral models make use of principles of functional analysis of drinking behavior. Behavior models exist for both working with the person using the substance (community reinforcement approach) and their family (community reinforcement approach and family training). Both these models have had considerable research success for both efficacy and effectiveness. This model lays much emphasis on the use of problem-solving techniques as a means of helping the addict to overcome his/her addiction.
The way researchers think about how addictions are formed shapes the models we have. Four main Behavioral Models of addiction exist: the Moral Model, Disease Model, Socio-Cultural Model and Psycho-dynamic Model. The Moral Model of addiction theorizes that addiction is a moral weakness and that it is the sole fault of the person for becoming addicted. Supporters of the Moral Model view drug use as a choice, even for those who are addicted, and addicts as people of bad character. Disease Model of addiction frames substance abuse as 'a chronic relapsing disease that changes the structure and function of the brain'. Research conducted on the neurobiological factors of addiction has proven to have mixed results, and the only treatment idea it offers is abstinence. The Socio-Cultural Model tries to provide an explanation of how certain populations are more susceptible to substance abuse than others. It focuses on how discrimination, poor quality of life, lack of opportunity and other problems common in marginalized communities can make them vulnerable to addiction. The Psycho-Dynamic Model looks at trauma and mental illness as a precursor to addiction. Many rehabilitation centers treat "co-occurring" disorders, which refer to substance abuse disorder paired with a mental health diagnosis.
== Barriers to treatment in the US ==
Barriers to accessing drug treatment may worsen negative health outcomes and further exacerbate health inequalities in the United States. Stigmatization of drug use, the War on Drugs and criminalization, and the social determinants of health should all be considered when discussing access to drug treatment and potential barriers.
Broad categories of barriers to drug treatment are: absences of problem, negative social support, fear of treatment, privacy concerns, time conflict, poor treatment availability, and admission difficulty. Other barriers to treatment include high costs, lack of tailored programs to address specific needs, and prerequisites that require participants to be house, abstinent from all substances, and/or employed. (See low-threshold treatment and housing first for more context on the latter point.)
=== Loss of Child/Dependent Access ===
In certain states, providers due to mandatory reporting methods and guidelines inform Child Protective Services of substance abusing parents for Schedule 1 substances including cannabis/marijuana. If a mother tests positive for using the substance during pregnancy in South Carolina she may be required to forfeit her child.
Further, barriers to treatment can vary depending on the geographical location, gender, race, socioeconomic status, and status of past or current criminal justice system involvement of the person seeking treatment.
== Criticism ==
Despite ongoing efforts to combat addiction, there has been evidence of clinics billing patients for treatments that may not guarantee their recovery. This is a major problem as there are numerous claims of fraud in drug rehabilitation centers, where these centers are billing insurance companies for under-delivering much-needed medical treatment while exhausting patients' insurance benefits. In California, there are movements and laws regarding this matter, particularly the California Insurance Fraud Prevention Act (IFPA) which declares it unlawful to unknowingly conduct such businesses.
Under the Affordable Care Act and the Mental Health Parity Act, rehabilitation centers are able to bill insurance companies for substance use treatment. With long wait lists in limited state-funded rehabilitation centers, controversial private centers rapidly emerged. One popular model, known as the Florida Model for rehabilitation centers, is often criticized for fraudulent billing to insurance companies. Under the guise of helping patients with opioid addiction, these centers would offer addicts free rent or up to $500 per month to stay in their "sober homes", then charge insurance companies as high as $5,000 to $10,000 per test for simple urine tests. Little attention is paid to patients in terms of addiction intervention as these patients have often been known to continue drug use during their stay in these centers. Since 2015, these centers have been under federal and state criminal investigation. As of 2017 in California, there are only 16 investigators in the CA Department of Health Care Services investigating over 2,000 licensed rehab centers.
== By country ==
=== Afghanistan ===
In Afghanistan since the Taliban took power in 2021, they have forced drug addicts into compulsory drug rehab.
=== China ===
As of 2013 China has compulsory drug rehabilitation centers. It was reported in 2018 1.3 million drug addicts were treated in China's compulsory detox centers.
Compulsory drug rehabilitation has a long history in China: The Mao Zedong government is credited with eradicating both consumption and production of opium during the 1950s using unrestrained repression and social reform. Ten million addicts were forced into compulsory treatment, dealers were executed, and opium-producing regions were planted with new crops. Remaining opium production shifted south of the Chinese border into the Golden Triangle region.
=== Indonesia ===
In 2015 the National Narcotics Board (Indonesia) was pushing for compulsory drug treatment for people with drug dependence.
=== Iran ===
According to statistics best case scenario less than a 25% of addicts go back to being healthy.
There are two types of rehab one is Revolutionary Guard Corp or FARAJA run article 16 quarantine which is part of operations cleaning the cities from addicts and homeless just as well, the others article 15 and article 17 run by others including State Welfare Organization of Iran and also those run by Ministry of health and medical education. There are also places called Trust houses since July 2023 run by IRGC.
=== Italy ===
In 1963, Pierino Gelmini founded Comunità Incontro, a drug rehabilitation center in Amelia, Italy.
== See also ==
== References ==
== Further reading == | Wikipedia/Drug_rehabilitation |
Drug cultures are examples of countercultures that are primarily defined by spiritual, medical, and recreational drug use. They may be focused on a single drug, or endorse polydrug use. They sometimes eagerly or reluctantly initiate newcomers, but their main functions are to share drug experiences, to reduce harm by providing knowledge of how to use drugs as safely as possible, and to exchange information on suppliers and avoidance of law enforcement.
Drug subcultures are groups of people united by a common understanding of the meaning, value, and risks of the incorporation into one's life of the drug(s) in question. Such unity can take many forms, from friends who take the drug together, possibly obeying certain rules of etiquette, groups banding together to help each other obtain drugs and avoid arrest, to full-scale political movements for the reform of drug laws. The sum of these parts can be considered an individual drug's "culture".
Many artists, writers, and musicians have used various drugs to facilitate or enhance their creativity. Writers have explored their influence on human life in general and particularly on the creative process. There are many writings that portray drug culture. Hunter S. Thompson's 1971 novel Fear and Loathing in Las Vegas employs multiple drug use as a major theme and provides an example of the drug culture of the 1960s.
After various drug cultures came to prominence during the 1960s, 1980s and early 2000s, the internet provided a new location and medium where drug cultures could be born and propagate. Technologies like Tor were able to offer anonymous website hosting and browsing, which were used for the creation of the darknet market SilkRoad, the first of many to be used in the sale of psychoactive substances and other illegal goods. There are YouTube channels devoted to recreational drug use and harm reduction, with the most popular being PsychedSubstance. Except for forums (like Blue Light) where individuals can post and discuss the properties and experiences of psychoactive substances, there are websites and organizations specifically created to serve as encyclopedias of psychoactive drugs and drug culture, such as Erowid and PsychonautWiki.
== By drug ==
=== Cannabis culture ===
Cannabis has been used in the ancient past in places such as ancient India, Romania, Egypt, and Mesopotamia. It was often used as medicine or for hemp. Its main route of consumption was smoking. Over time the culture became more international and a general "cannabis culture" formed. Cannabis culture has been responsible for the genre of films known as stoner films which has come to be accepted as a mainstream cinema movement. In the United States the culture has also spawned its own celebrities (such as Tommy Chong and Terence McKenna), magazines (Cannabis Culture and High Times), and, in North America, its own distinct holiday: April 20 (420), which is marked as a day for calling for the legalization of cannabis and celebration of cannabis. The consumption of cannabis influenced many artistic movements such as jazz, electronic music and hip hop.
=== Drinking culture ===
Alcohol (also known as ethanol) is a psychoactive drug found in alcoholic beverages. Alcohol is one of the most commonly abused drugs in the world and is often used for self-medication, and recreational use."
== Hip hop and drugs ==
The hip hop, hardcore rap, and trap scenes, alongside their derivative subgenres and subcultures, are most notorious for having continuously celebrated and promoted drug trafficking, gangster lifestyle, and the consumption of alcohol and other drugs since their inception in the United States during the late 1980s–early 1990s.
== Witchcraft and drugs ==
The drugs used in witchcraft are different depending on the culture. Most of the research done on drug use in witchcraft was done in the 60s during the hippie movement. Since then, the claim that ergot was taken in Salem has been disproven. However, because the research was done during the hippie and drug movement in the 70s, the theory is still a part of drug culture.
Ancient Greek love magic used many rituals that show drug use in poisoning to deepen the emotion of love. Love magic would be used by ancient Greek women to gain or keep a man's love. Researchers of this period often look at the agency of the women. Greek love magic relates to drug culture as it deals with poisoning people. There can be similarities found in today's date rape drug. However, in ancient Greek time the women would slowly poison the men. Women would put the poisons on their robes to expose it to the men.
Shamanism used hallucinogens to further their spirituality. These hallucinogens were used for different ceremonies of the Indians in the Northwest Amazon. These ceremonies include funerals and initiation of the young. Shamans had a wider range of use for these drugs. Shamans used these drugs to identify illnesses and find possible cures or to find an enemy.
There is a theory, seemingly disproven due to timeline of events and number of those who experience the symptoms, that the Salem witch trials were caused by ergot poisoning. Ergot poisoning gives a similar effect to LSD, but like ergine the physical effects and dangers (including death due to higher toxicity of the ergolines in ergot) are much more substantial than the use of LSD for psychedelic research and ritual contexts.
== See also ==
Beatnik
Drug checking
Harm reduction
Entheogens
Hallucinogens
Narcoculture in Mexico
Peyote § Cultural significance
== References ==
== External links ==
Media related to Drug culture at Wikimedia Commons | Wikipedia/Drug_culture |
Recreational drug use is the use of one or more psychoactive drugs to induce an altered state of consciousness, either for pleasure or for some other casual purpose or pastime. When a psychoactive drug enters the user's body, it induces an intoxicating effect. Recreational drugs are commonly divided into three categories: depressants (drugs that induce a feeling of relaxation and calmness), stimulants (drugs that induce a sense of energy and alertness), and hallucinogens (drugs that induce perceptual distortions such as hallucination).
In popular practice, recreational drug use is generally tolerated as a social behaviour, rather than perceived as the medical condition of self-medication. However, drug use and drug addiction are severely stigmatized everywhere in the world. Many people also use prescribed and controlled depressants such as opioids, opiates, and benzodiazepines. What controlled substances are considered generally unlawful to possess varies by country, but usually includes cannabis, cocaine, opioids, MDMA, amphetamine, methamphetamine, psychedelics, benzodiazepines, and barbiturates. As of 2015, it is estimated that about 5% of people worldwide aged 15 to 65 (158 million to 351 million) had used controlled drugs at least once.
Common recreational drugs include caffeine, commonly found in coffee, tea, soft drinks, and chocolate; alcohol, commonly found in beer, wine, cocktails, and distilled spirits; nicotine, commonly found in tobacco, tobacco-based products, and electronic cigarettes; cannabis and hashish (with legality of possession varying inter/intra-nationally); and the controlled substances listed as controlled drugs in the Single Convention on Narcotic Drugs (1961) and the Convention on Psychotropic Substances (1971) of the United Nations (UN). Since the early 2000s, the European Union (EU) has developed several comprehensive and multidisciplinary strategies as part of its drug policy in order to prevent the diffusion of recreational drug use and abuse among the European population and raise public awareness on the adverse effects of drugs among all member states of the European Union, as well as conjoined efforts with European law enforcement agencies, such as Europol and EMCDDA, in order to counter organized crime and illegal drug trade in Europe.
== Reasons for use ==
Many researchers have explored the etiology of recreational drug use. Some of the most common theories are: genetics, personality type, psychological problems, self-medication, sex, age, depression, curiosity, boredom, rebelliousness, a sense of belonging to a group, family and attachment issues, history of trauma, failure at school or work, socioeconomic stressors, peer pressure, juvenile delinquency, availability, historical factors, or socio-cultural influences. There has been no consensus on a single cause. Instead, experts tend to apply the biopsychosocial model. Any number of factors may influence an individual's drug use, as they are not mutually exclusive. Regardless of genetics, mental health, or traumatic experiences, social factors play a large role in the exposure to and availability of certain types of drugs and patterns of use.
According to addiction researcher Martin A. Plant, some people go through a period of self-redefinition before initiating recreational drug use. They tend to view using drugs as part of a general lifestyle that involves belonging to a subculture that they associate with heightened status and the challenging of social norms. Plant states: "From the user's point of view there are many positive reasons to become part of the milieu of drug taking. The reasons for drug use appear to have as much to do with needs for friendship, pleasure and status as they do with unhappiness or poverty. Becoming a drug taker, to many people, is a positive affirmation rather than a negative experience".
=== Evolution ===
Anthropological research has suggested that humans "may have evolved to counter-exploit plant neurotoxins". The ability to use botanical chemicals to serve the function of endogenous neurotransmitters may have improved survival rates, conferring an evolutionary advantage. A typically restrictive prehistoric diet may have emphasized the apparent benefit of consuming psychoactive drugs, which had themselves evolved to imitate neurotransmitters. Chemical–ecological adaptations and the genetics of hepatic enzymes, particularly cytochrome P450, have led researchers to propose that "humans have shared a co-evolutionary relationship with psychotropic plant substances that is millions of years old."
== Health risks ==
The severity of impact and type of risks that come with recreational drug use vary widely with the drug in question and the amount being used. There are many factors in the environment and within the user that interact with each drug differently. Alcohol is sometimes considered one of the most dangerous recreational drugs. Alcoholic drinks, tobacco products and other nicotine-based products (e.g., electronic cigarettes), and cannabis are regarded by various medical professionals as the most common and widespread gateway drugs. In the United States, Australia, and New Zealand, the general onset of drinking alcohol, tobacco smoking, cannabis smoking, and consumption of multiple drugs most frequently occurs during adolescence and in middle school and secondary school settings.
Some scientific studies in the early 21st century found that a low to moderate level of alcohol consumption, particularly of red wine, might have substantial health benefits such as decreased risk of cardiovascular diseases, stroke, and cognitive decline. This claim has been disputed, specifically by British researcher David Nutt, professor of neuropsychopharmacology at the Imperial College London, who stated that studies showing benefits for "moderate" alcohol consumption in "some middle-aged men" lacked controls for the variable of what the subjects were drinking beforehand. Experts in the United Kingdom have suggested that some psychoactive drugs that may be causing less harm to fewer users (although they are also used less frequently in the first place) are cannabis, psilocybin mushrooms, LSD, and MDMA; however, these drugs have risks and side effects of their own.
=== Drug harmfulness ===
Drug harmfulness is defined as the degree to which a psychoactive drug has the potential to cause harm to the user and is measured in several ways, such as by addictiveness and the potential for physical harm. More objectively harmful drugs may be colloquially referred to as "hard drugs", and less harmful drugs as "soft drugs". The term "soft drug" is considered controversial by critics as it may imply the false belief that soft drugs cause lesser or insignificant harm.
=== Responsible use ===
Responsible drug use advocates that users should not take drugs at the same time as activities such as driving, swimming, operating machinery, or other activities that are unsafe without a sober state. Responsible drug use is emphasized as a primary prevention technique in harm-reduction drug policies. Harm-reduction policies were popularized in the late 1980s, although they began in the 1970s counter-culture, through cartoons explaining responsible drug use and the consequences of irresponsible drug use to users. Another issue is that the illegality of drugs causes social and economic consequences for users—the drugs may be "cut" with adulterants and the purity varies wildly, making overdoses more likely—and legalization of drug production and distribution could reduce these and other dangers of illegal drug use.
== Prevention ==
In efforts to curtail recreational drug use, governments worldwide introduced several laws prohibiting the possession of almost all varieties of recreational drugs during the 20th century. The "War on Drugs" promoted by the United States, however, is now facing increasing criticism. Evidence is insufficient to tell if behavioral interventions help prevent recreational drug use in children.
One in four adolescents has used an illegal drug, and one in ten of those adolescents who need addiction treatment get some type of care. School-based programs are the most commonly used method for drug use education; however, the success rates of these intervention programs are highly dependent on the commitment of participants and are limited in general.
== Demographics ==
=== Australia ===
Alcohol is the most widely used recreational drug in Australia. 86.2% of Australians aged 12 years and over have consumed alcohol at least once in their lifetime, compared to 34.8% of Australians aged 12 years and over who have used cannabis at least once in their lifetime.
=== United States ===
From the mid-19th century to the 1930s, American physicians prescribed Cannabis sativa as a prescription drug for various medical conditions. In the 1960s, the counterculture movement introduced the use of psychoactive drugs, including cannabis. Young adults and college students reported the recreational prevalence of cannabis, among other drugs, at 20-25% while the cultural mindset of using was open and curious. In 1969, the FBI reported that between the years 1966 and 1968, the number of arrests for marijuana possession, which had been outlawed throughout the United States under Marijuana Tax Act of 1937, had increased by 98%. Despite acknowledgement that drug use was greatly growing among America's youth during the late 1960s, surveys have suggested that only as much as 4% of the American population had ever smoked marijuana by 1969. By 1972, however, that number would increase to 12%. That number would then double by 1977.
The Controlled Substances Act of 1970 classified marijuana along with heroin and LSD as a Schedule I drug, i.e., having the relatively highest abuse potential and no accepted medical use. Most marijuana at that time came from Mexico, but in 1975 the Mexican government agreed to eradicate the crop by spraying it with the herbicide paraquat, raising fears of toxic side effects. Colombia then became the main supplier. The "zero tolerance" climate of the Reagan and Bush administrations (1981–1993) resulted in passage of strict laws and mandatory sentences for possession of marijuana. The "War on Drugs" thus brought with it a shift from reliance on imported supplies to domestic cultivation, particularly in Hawaii and California. Beginning in 1982, the Drug Enforcement Administration turned increased attention to marijuana farms in the United States, and there was a shift to the indoor growing of plants specially developed for small size and high yield. After over a decade of decreasing use, marijuana smoking began an upward trend once more in the early 1990s, especially among teenagers, but by the end of the decade this upswing had leveled off well below former peaks of use.
== Society and culture ==
Many movements and organizations are advocating for or against the liberalization of the use of recreational drugs, most notably regarding the legalization of marijuana and cannabinoids for medical and/or recreational use. Subcultures have emerged among users of recreational drugs, as well as alternative lifestyles and social movements among those who abstain from them, such as teetotalism and "straight edge".
Since the early 2000s, medical professionals have acknowledged and addressed the problem of the increasing consumption of alcoholic drinks and club drugs (such as MDMA, cocaine, rohypnol, GHB, ketamine, PCP, LSD, and methamphetamine) associated with rave culture among adolescents and young adults in the Western world. Studies have shown that adolescents are more likely than young adults to use multiple drugs, and the consumption of club drugs is highly associated with the presence of criminal behaviors and recent alcohol abuse or dependence.
The prevalence of recreational drugs in human societies is widely reflected in fiction, entertainment, and the arts, subject to prevailing laws and social conventions. For instance, in the music industry, the musical genres hip hop, hardcore rap, and trap, alongside their derivative subgenres and subcultures, are most notorious for having continuously celebrated and promoted drug trafficking, gangster lifestyle, and consumption of alcohol and other drugs since their inception in the United States during the late 1980s–early 1990s. In video games, for example, drugs are portrayed in a variety of ways: including power-ups (cocaine gum replenishes stamina in Red Dead Redemption 2), obstacles to be avoided (such as the Fuzzies in Super Mario World 2: Yoshi's Island that distort the player's view when accidentally consumed), items to be bought and sold for in-game currency (coke dealing is a big part of Scarface: The World Is Yours). In the Fallout video game franchise, drugs ("chems" in the game) can fill the role of any above mentioned. Drug trafficking, gang rivalries, and their related criminal underworld also play a big part in the Grand Theft Auto video game franchise.
== Common recreational drugs ==
The following substances are commonly used recreationally:
Alcohol: Most drinking alcohol is ethanol, CH3CH2OH. Drinking alcohol creates intoxication, relaxation and lowered inhibitions. It is produced by the fermentation of sugars by yeasts to create wine, beer, and distilled liquor (e.g., vodka, rum, gin, etc.). In most areas of the world, it is legal for those over a certain age (18 in most countries). It is an IARC Group 1 carcinogen and a teratogen. Alcohol withdrawal can be life-threatening.
Amphetamines: Used recreationally to provide alertness and a sense of energy. Prescribed for ADHD, narcolepsy, depression, and weight loss. A potent central nervous system stimulant, in the 1940s and 50s methamphetamine was used by Axis and Allied troops in World War II, and, later on, other armies, and by Japanese factory workers. It increases muscle strength and fatigue resistance and improves reaction time. Methamphetamine use can be neurotoxic, which means it damages dopamine neurons. As a result of this brain damage, chronic use can lead to post acute withdrawal syndrome.
Caffeine: Often found in coffee, black tea, energy drinks, some soft drinks (e.g., Coca-Cola, Pepsi, and Mountain Dew, among others), and chocolate. It is the world's most widely consumed psychoactive drug, but has only mild dependence liability for long-term users.
Cannabis: Its common forms include marijuana and hashish, which are smoked, vaporized or eaten. It contains at least 85 cannabinoids. The primary psychoactive component is THC, which mimics the neurotransmitter anandamide, named after the Hindu ananda, "joy, bliss, delight". When cannabis is eaten, THC metabolized into 11-OH-THC, this molecule is the primary psychoactive compound of edible forms of cannabis. THC and 11-OH-THC are partial agonist at CB1 and CB2 receptors of the endocannabinoid system.
Cocaine: It is available as a white powder, which is insufflated ("sniffed" into the nostrils) or converted into a solution with water and injected. A popular derivative, crack cocaine is typically smoked. When transformed into its freebase form, crack, the cocaine vapour may be inhaled directly. This is thought to increase bioavailability, but has also been found to be toxic, due to the production of methylecgonidine during pyrolysis.
MDMA: Commonly known as ecstasy, it is a common club drug in the rave scene.
Ketamine: An anesthetic used legally by paramedics and doctors in emergency situations for its dissociative and analgesic qualities and illegally in the club drug scene.
Lean: A liquid drug mixture made when mixing cough syrup, sweets, soft drinks and codeine. It originated in the 1990s in Houston. Ever since then, this drug usage has grown and is often used at parties and in the trap music scene. Many people would get a drowsy feeling when consuming this drug.
LSD: A popular ergoline derivative, that was first synthesized in 1938 by Albert Hofmann. However, he failed to notice its psychedelic effects until 1943. It's a serotonergic psychedelic (partial agonist at serotonin receptors, particularly the 5-HT2A subtypes) like psilocin, mescaline and DMT. But LSD is unique because it is also a partial agonist of dopamine and norepinephrine receptors, particularly the D2R subtypes. LSD (d-Lysergic Acid Diethylamide) is a molecule of the lysergamide family, a subclass of the tryptamine family. In the 1950s, it was used in psychological therapy, and, covertly, by the CIA in Project MKULTRA, in which the drug was administered to unwitting US and Canadian citizens. It played a central role in 1960s 'counter-culture', and was banned in October 1968 by US President Lyndon B Johnson.
Nitrous oxide: legally used by dentists as an anxiolytic and anaesthetic, it is also used recreationally by users who obtain it from whipped cream canisters (whippets or whip-its) (see inhalant), as it causes perceptual effects, a "high" and at higher doses, hallucinations.
Opiates and opioids: Available by prescription for pain relief. Commonly used opioids include oxycodone, hydrocodone, codeine, fentanyl, heroin, methadone, and morphine. Opioids have a high potential for addiction and have the ability to induce severe physical withdrawal symptoms upon cessation of frequent use. Heroin can be smoked, insufflated, or turned into a solution with water and injected. Percocet is a prescription opioid containing oxycodone and acetaminophen.
Psilocybin mushrooms: This hallucinogenic drug was an important drug in the psychedelic scene. Until 1963, when it was chemically analysed by Albert Hofmann, it was completely unknown to modern science that Psilocybe semilanceata ("Liberty Cap", common throughout Europe) contains psilocybin, a hallucinogen previously identified only in species native to Mexico, Asia, and North America.
Tobacco: Nicotiana tabacum. Nicotine is the key drug contained in tobacco leaves, which are either smoked, chewed or snuffed. It contains nicotine, which crosses the blood–brain barrier in 10–20 seconds. It mimics the action of the neurotransmitter acetylcholine at nicotinic acetylcholine receptors in the brain and the neuromuscular junction. The neuronal forms of the receptor are present both post-synaptically (involved in classical neurotransmission) and pre-synaptically, where they can influence the release of multiple neurotransmitters.
Tranquilizers: barbiturates, benzodiazepines (e.g. alprazolam, diazepam, etc.)(commonly prescribed for anxiety disorders; known to cause dementia and post acute withdrawal syndrome)
"Bath salts": slang term that generally refers to substituted cathinones such as Mephedrone and Methylenedioxypyrovalerone (MDPV), but not always
DMT – primary ingredient in ayahuasca, can also be smoked (inhalation causes a brief effect lasting usually 5 to 15 minutes).
Peyote: This hallucinogen contains mescaline, native to southwestern Texas and Mexico. Echinopsis pachanoi is a faster growing cactus containing mescaline. It is one of the few narcotics legally available in the United States for religious purposes by the Native American Church.
Salvia divinorum: This hallucinogenic Mexican herb in the mint family; not considered recreational, most likely due to the nature of the hallucinations (legal in some jurisdictions)
Synthetic cannabis: "Spice", "K2", JWH-018, AM-2201
Quaaludes: A popular club drug in the 1970s. No longer prescribed or manufactured in many countries but remains popular in South Africa.
== Routes of administration ==
Drugs are often associated with a particular route of administration. Many drugs can be consumed in more than one way. For example, marijuana can be swallowed like food or smoked, and cocaine can be "sniffed" in the nostrils, injected, or, with various modifications, smoked.
inhalation: all intoxicative inhalants (see below) that are gases or solvent vapours that are inhaled through the trachea, as the name suggests
insufflation: also known as "snorting", or "sniffing", this method involves the user placing a powder in the nostrils and breathing in through the nose, so that the drug is absorbed by the mucous membranes. Drugs that are "snorted", or "sniffed", include powdered amphetamines, cocaine, heroin, ketamine, MDMA, and snuff tobacco.
Subcutaneous injection (see also the article Skin popping): injection of drug into the third lowest layer of skin.
Intramuscular injection: injection of drug into a muscle.
intravenous injection (see also the article Drug injection): the user injects a solution of water and the drug into a vein, or less commonly, into the tissue. Drugs that are injected include morphine and heroin, less commonly other opioids. Stimulants like cocaine or methamphetamine may also be injected. In rare cases, users inject other drugs.
oral intake: caffeine, ethanol, cannabis edibles, psilocybin mushrooms, coca tea, poppy tea, laudanum, GHB, ecstasy pills with MDMA or various other substances (mainly stimulants and psychedelics), prescription and over-the-counter drugs (ADHD and narcolepsy medications, benzodiazepines, anxiolytics, sedatives, cough suppressants, morphine, codeine, opioids and others)
sublingual: substances diffuse into the blood through tissues under the tongue. Many psychoactive drugs can be or have been specifically designed for sublingual administration, including barbiturates, benzodiazepines, opioid analgesics with poor gastrointestinal bioavailability, LSD blotters, coca leaves, some hallucinogens. This route of administration is activated when chewing some forms of smokeless tobacco (e.g. dipping tobacco, snus).
intrarectal ("plugging"): administering into the rectum, most water-soluble drugs can be used this way.
smoking (see also the section below): tobacco, cannabis, opium, crystal meth, phencyclidine, crack cocaine, and heroin (diamorphine as freebase) known as chasing the dragon.
transdermal patches with prescription drugs: e.g. methylphenidate (Daytrana) and fentanyl.
Many drugs are taken through various routes. Intravenous route is the most efficient, but also one of the most dangerous. Nasal, rectal, inhalation and smoking are safer. The oral route is one of the safest and most comfortable, but of little bioavailability.
== Types ==
=== Depressants ===
Depressants are psychoactive drugs that temporarily diminish the function or activity of a specific part of the body or mind. Colloquially, depressants are known as "downers", and users generally take them to feel more relaxed and less tense. Examples of these kinds of effects may include anxiolysis, sedation, and hypotension. Depressants are widely used throughout the world as prescription medicines and as illicit substances. When these are used, effects may include anxiolysis (reduction of anxiety), analgesia (pain relief), sedation, somnolence, cognitive/memory impairment, dissociation, muscle relaxation, lowered blood pressure/heart rate, respiratory depression, anesthesia, and anticonvulsant effects. Depressants exert their effects through a number of different pharmacological mechanisms, the most prominent of which include potentiation of GABA or opioid activity, and inhibition of adrenergic, histamine or acetylcholine activity. Some are also capable of inducing feelings of euphoria. The most widely used depressant by far is alcohol (i.e. ethanol).
Stimulants or "uppers", such as amphetamines or cocaine, which increase mental or physical function, have an opposite effect to depressants.
Depressants, in particular alcohol, can precipitate psychosis. A 2019 systematic review and meta-analysis by Murrie et al. found that the rate of transition from opioid, alcohol and sedative induced psychosis to schizophrenia was 12%, 10% and 9% respectively.
==== Antihistamines ====
Antihistamines (or "histamine antagonists") inhibit the release or action of histamine. "Antihistamine" can be used to describe any histamine antagonist, but the term is usually reserved for the classical antihistamines that act upon the H1 histamine receptor. Antihistamines are used as treatment for allergies. Allergies are caused by an excessive response of the body to allergens, such as the pollen released by grasses and trees. An allergic reaction causes release of histamine by the body. Other uses of antihistamines are to help with normal symptoms of insect stings even if there is no allergic reaction. Their recreational appeal exists mainly due to their anticholinergic properties, that induce anxiolysis and, in some cases such as diphenhydramine, chlorpheniramine, and orphenadrine, a characteristic euphoria at moderate doses. High dosages taken to induce recreational drug effects may lead to overdoses. Antihistamines are also consumed in combination with alcohol, particularly by youth who find it hard to obtain alcohol. The combination of the two drugs can cause intoxication with lower alcohol doses.
Hallucinations and possibly delirium resembling the effects of Datura stramonium can result if the drug is taken in much higher than therapeutic doses. Antihistamines are widely available over the counter at drug stores (without a prescription), in the form of allergy medication and some cough medicines. They are sometimes used in combination with other substances such as alcohol.
The most common unsupervised use of antihistamines in terms of volume and percentage of the total is perhaps in parallel to the medicinal use of some antihistamines to extend and intensify the effects of opioids and depressants. The most commonly used are hydroxyzine, mainly to extend a supply of other drugs, as in medical use, and the above-mentioned ethanolamine and alkylamine-class first-generation antihistamines, which are – once again as in the 1950s – the subject of medical research into their anti-depressant properties.
For all of the above reasons, the use of medicinal scopolamine for recreational uses is also observed.
==== Analgesics ====
Analgesics (also known as "painkillers") are used to relieve pain (achieve analgesia). The word analgesic derives from Greek "αν-" (an-, "without") and "άλγος" (álgos, "pain"). Analgesic drugs act in various ways on the peripheral and central nervous systems; they include paracetamol (also known in the US as acetaminophen), the nonsteroidal anti-inflammatory drugs (NSAIDs) such as the salicylates (e.g. aspirin), and opioid drugs such as hydrocodone, codeine, heroin and oxycodone. Some further examples of the brand name prescription opiates and opioid analgesics that may be used recreationally include Vicodin, Lortab, Norco (hydrocodone), Avinza, Kapanol (morphine), Opana, Paramorphan (oxymorphone), Dilaudid, Palladone (hydromorphone), and OxyContin (oxycodone).
==== Tranquilizers ====
The following are examples of tranquilizers (GABAergics):
Barbiturates
Benzodiazepines
Ethanol (drinking alcohol; ethyl alcohol)
Nonbenzodiazepines
Others
carisoprodol (Soma)
chloral hydrate
diethyl ether
ethchlorvynol (Placidyl; "jelly-bellies")
gamma-butyrolactone (GBL, a prodrug to GHB)
gamma-hydroxybutyrate (GHB; G; Xyrem; "Liquid Ecstasy", "Fantasy")
glutethimide (Doriden)
kava (from Piper methysticum; contains kavalactones)
ketamine, a phencyclidine (PCP) analog
meprobamate (Miltown)
methaqualone (Sopor, Mandrax; "Quaaludes")
phenibut
propofol (Diprivan), a general anesthetic
theanine (found in Camellia sinensis, the tea plant)
valerian (from Valeriana officinalis)
=== Stimulants ===
Stimulants, also known as "psychostimulants", induce euphoria with improvements in mental and physical function, such as enhanced alertness, wakefulness, and locomotion. Stimulants are also occasionally called "uppers". Depressants or "downers", which decrease mental or physical function, are in stark contrast to stimulants and are considered to be their functional opposites.
Stimulants enhance the activity of the central and peripheral nervous systems. Common effects may include increased alertness, awareness, wakefulness, endurance, productivity, and motivation, arousal, locomotion, heart rate, and blood pressure, and a diminished desire for food and sleep.
Use of stimulants may cause the body to significantly reduce its production of endogenous compounds that fulfill similar functions. Once the effect of the ingested stimulant has worn off the user may feel depressed, lethargic, confused, and dysphoric. This is colloquially termed a "crash" and may promote reuse of the stimulant.
Amphetamines are a significant cause of drug-induced psychosis. Importantly, a 2019 meta-analysis found that 22% of people with amphetamine-induced psychosis transition to a later diagnosis of schizophrenia.
Examples of stimulants include:
Sympathomimetics (catecholaminergics)—e.g. amphetamine, methamphetamine, cocaine, methylphenidate, ephedrine, pseudoephedrine
Entactogens (serotonergics, primarily phenethylamines)—e.g. MDMA (which is also an amphetamine)
Eugeroics, e.g. modafinil
Others
arecoline (found in Areca catechu)
caffeine (found in Coffea spp.)
nicotine (found in Nicotiana spp.)
rauwolscine (found in Rauvolfia serpentina)
yohimbine (Procomil; a tryptamine alkaloid found in Pausinystalia johimbe)
=== Euphoriants ===
Alcohol: "Euphoria, the feeling of well-being, has been reported during the early (10–15 min) phase of alcohol consumption" (e.g., beer, wine or spirits)
Cannabis: Tetrahydrocannabinol, the main psychoactive ingredient in this plant, can have sedative and euphoric properties.
Catnip: Catnip contains a sedative known as nepetalactone that activates opioid receptors. In cats it elicits sniffing, licking, chewing, head shaking, rolling, and rubbing which are indicators of pleasure. In humans, however, catnip does not act as a euphoriant.
Stimulants: "Psychomotor stimulants produce locomotor activity (the subject becomes hyperactive), euphoria, (often expressed by excessive talking and garrulous behaviour), and anorexia. The amphetamines are the best known drugs in this category..."
MDMA: The "euphoriant drugs such as MDMA ('ecstasy') and MDEA ('eve')" are popular among young adults. MDMA "users experience short-term feelings of euphoria, rushes of energy and increased tactility" as well as interpersonal connectedness.
Opium: This "drug derived from the unripe seed-pods of the opium poppy…produces drowsiness and euphoria and reduces pain. Morphine and codeine are opium derivatives." Opioids have led to many deaths in the United States, particularly by causing respiratory depression.
=== Hallucinogens ===
Hallucinogens can be divided into three broad categories: psychedelics, dissociatives, and deliriants. They can cause subjective changes in perception, thought, emotion and consciousness. Unlike other psychoactive drugs such as stimulants and opioids, hallucinogens do not merely amplify familiar states of mind but also induce experiences that differ from those of ordinary consciousness, often compared to non-ordinary forms of consciousness such as trance, meditation, conversion experiences, and dreams.
Psychedelics, dissociatives, and deliriants have a long worldwide history of use within medicinal and religious traditions. They are used in shamanic forms of ritual healing and divination, in initiation rites, and in the religious rituals of syncretistic movements such as União do Vegetal, Santo Daime, Temple of the True Inner Light, and the Native American Church. When used in religious practice, psychedelic drugs, as well as other substances like tobacco, are referred to as entheogens.
Hallucinogen-induced psychosis occurs when psychosis persists despite no longer being intoxicated with the drug. It is estimated that 26% of people with hallucinogen-induced psychosis will transition to a diagnosis of schizophrenia. This percentage is less than the psychosis transition rate for cannabis (34%) but higher than that of amphetamines (22%).
Starting in the mid-20th century, psychedelic drugs have been the object of extensive attention in the Western world. They have been and are being explored as potential therapeutic agents in treating depression, post-traumatic stress disorder, obsessive–compulsive disorder, alcoholism, and opioid addiction. Yet the most popular, and at the same time most stigmatized, use of psychedelics in Western culture has been associated with the search for direct religious experience, enhanced creativity, personal development, and "mind expansion". The use of psychedelic drugs was a major element of the 1960s counterculture, where it became associated with various social movements and a general atmosphere of rebellion and strife between generations.
Deliriants
atropine (alkaloid found in plants of the family Solanaceae, including datura, deadly nightshade, henbane and mandrake)
dimenhydrinate (Dramamine, an antihistamine)
diphenhydramine (Benadryl, Unisom, Nytol)
hyoscyamine (alkaloid also found in the Solanaceae)
hyoscine hydrobromide (another Solanaceae alkaloid)
myristicin (found in Myristica fragrans ("Nutmeg"))
ibotenic acid (found in Amanita muscaria ("Fly Agaric"); prodrug to muscimol)
muscimol (also found in Amanita muscaria, a GABAergic)
Dissociatives
dextromethorphan (DXM; Robitussin, Delsym, etc.; "Dex", "Robo", "Cough Syrup", "DXM")
"Triple C's, Coricidin, Skittles" refer to a potentially fatal formulation containing both dextromethorphan and chlorpheniramine.
ketamine (K; Ketalar, Ketaset, Ketanest; "Ket", "Kit Kat", "Special-K", "Vitamin K", "Jet Fuel", "Horse Tranquilizer")
methoxetamine (Mex, Mket, Mexi)
phencyclidine (PCP; Sernyl; "Angel Dust", "Rocket Fuel", "Sherm", "Killer Weed", "Super Grass")
nitrous oxide (N2O; "NOS", "Laughing Gas", "Whippets", "Balloons")
Psychedelics
Phenethylamines
2C-B ("Nexus", "Venus", "Eros", "Bees")
2C-E ("Eternity", "Hummingbird")
2C-I ("Infinity")
2C-T-2 ("Rosy")
2C-T-7 ("Blue Mystic", "Lucky 7")
DOB
DOC
DOI
DOM ("Serenity, Tranquility, and Peace" ("STP"))
MDMA ("Ecstasy", "E", "Molly", "Mandy", "MD", "Crystal Love")
mescaline (found in peyote and Trichocereus macrogonus (Peruvian torch, San Pedro cactus))
Tryptamines (including ergolines and lysergamides)
5-MeO-DiPT ("Foxy", "Foxy Methoxy")
5-MeO-DMT (found in various plants like chacruna, jurema, vilca, and yopo)
alpha-methyltryptamine (αMT; Indopan; "Spirals")
bufotenin (secreted by Bufo alvarius, also found in various Amanita mushrooms)
N,N-dimethyltryptamine (N,N-DMT; DMT; "Dimitri", "Disneyland", "Spice"; found in large amounts in Psychotria and in D. cabrerana)
lysergic acid amide (LSA; ergine; found in morning glory and Hawaiian baby woodrose seeds)
lysergic acid diethylamide (LSD; L; Delysid; "Acid", "Sid". "Cid", "Lucy", "Sidney", "Blotters", "Droppers", "Sugar Cubes")
O-Acetylpsilocin (believed to be a prodrug of psilocin)
psilocin (found in psilocybin mushrooms)
psilocybin (also found in psilocybin mushrooms; prodrug to psilocin)
ibogaine (found in Tabernanthe iboga ("Iboga"))
Atypicals
salvinorin A (found in Salvia divinorum, a trans-neoclerodane diterpenoid ("Diviner's Sage", "Lady Salvia", "Salvinorin"))
tetrahydrocannabinol (found in cannabis)
=== Inhalants ===
Inhalants are gases, aerosols, or solvents that are breathed in and absorbed through the lungs. While some "inhalant" drugs are used for medical purposes, as in the case of nitrous oxide, a dental anesthetic, inhalants are used as recreational drugs for their intoxicating effect. Most inhalant drugs that are used non-medically are ingredients in household or industrial chemical products that are not intended to be concentrated and inhaled, including organic solvents (found in cleaning products, fast-drying glues, and nail polish removers), fuels (gasoline (petrol) and kerosene), and propellant gases such as Freon and compressed hydrofluorocarbons that are used in aerosol cans such as hairspray, whipped cream, and non-stick cooking spray. A small number of recreational inhalant drugs are pharmaceutical products that are used illicitly, such as anesthetics (ether and nitrous oxide) and volatile anti-angina drugs (alkyl nitrites, more commonly known as "poppers").
The most serious inhalant abuse occurs among children and teens who "[...] live on the streets completely without family ties". Inhalant users inhale vapor or aerosol propellant gases using plastic bags held over the mouth or by breathing from a solvent-soaked rag or an open container. The effects of inhalants range from an alcohol-like intoxication and intense euphoria to vivid hallucinations, depending on the substance and the dosage. Some inhalant users are injured due to the harmful effects of the solvents or gases, or due to other chemicals used in the products inhaled. As with any recreational drug, users can be injured due to dangerous behavior while they are intoxicated, such as driving under the influence. Computer cleaning dusters are dangerous to inhale, because the gases expand and cool rapidly upon being sprayed. In many cases, users have died from hypoxia (lack of oxygen), pneumonia, cardiac failure or arrest, or aspiration of vomit.
Examples include:
Chloroform
Ethyl chloride
Diethyl ether
Ethane and ethylene
Laughing gas (nitrous oxide)
Poppers (alkyl nitrites)
Solvents and propellants (including propane, butane, freon, gasoline, kerosene, toluene) along with the fumes of glues containing them
== List of drugs which can be smoked ==
Plants:
black tar heroin
cannabis
datura and other Solanaceae (formerly smoked to treat asthma)
opium
salvia divinorum
tobacco
possibly other plants (see the section below)
Substances (also not necessarily psychoactive plants smoked within them):
5-MeO-DMT
Bufotenine
crack cocaine
dimethyltryptamine (DMT)
DiPT
methamphetamine
Methaqualone
phencyclidine (PCP)
synthetic cannabinoids (see also: synthetic cannabis)
many others, including some prescription drugs
== List of psychoactive plants, fungi, and animals ==
Minimally psychoactive plants which contain mainly caffeine and theobromine:
cocoa
coffee
guarana (caffeine in guarana is sometimes called guaranine)
kola
tea (caffeine in tea is sometimes called theine) – also contains theanine
yerba mate (caffeine in yerba mate is sometimes called mateine)
Most known psychoactive plants:
cannabis: cannabinoids
coca: cocaine
kava: kavalactones
khat: cathine and cathinone
nutmeg: myristicin and elemicin
opium poppy: morphine, codeine, and other opiates
salvia divinorum: salvinorin A
tobacco: nicotine and beta-carboline alkaloids
Solanaceae plants—contain atropine, hyoscyamine, and scopolamine:
datura
deadly nightshade Atropa belladonna
henbane
mandrake (mandragora)
other Solanaceae
Cacti with mescaline:
Peyote
Trichocereus macrogonus, the Peruvian torch cactus, and in particular its variety T. macrogonus var. pachanoi, the San Pedro cactus
Other plants:
Areca catechu (see: betel and paan)—arecoline
Ayahuasca (for DMT)
Calea zacatechichi
damiana
ephedra: ephedrine
kratom: mitragynine, mitraphylline, 7-hydroxymitragynine, raubasine, and corynanthine
Morning glory and Hawaiian Baby Woodrose – lysergic acid amide (LSA, ergine)
Rauvolfia serpentina: rauwolscine
Silene capensis
Tabernanthe iboga ("Iboga")—ibogaine
valerian: valerian (the chemical with the same name)
various plants like chacruna, jurema, vilca, and yopo – 5-MeO-DMT
yohimbe (Pausinystalia johimbe): yohimbine and corynanthine
many others
Fungi:
various Amanita mushrooms: muscimol
Amanita muscaria: ibotenic acid and muscimol
Claviceps purpurea and other Clavicipitaceae: ergotamine (not psychoactive itself but used in synthesis of LSD)
psilocybin mushrooms: psilocybin and psilocin
Psychoactive animals:
hallucinogenic fish
psychoactive toads: Bufo alvarius (Colorado River toad or Sonoran Desert toad) contains bufotenin (5-MeO-DMT)
== See also ==
== References ==
== Further reading ==
Martin, Christopher S.; Chung, Tammy; Langenbucher, James W. (2017). "Part 1: Defining and Characterizing the Nature and Extent of Substance Use Disorders – Historical and Cultural Perspectives on Substance Use and Substance Use Disorders". In Sher, Kenneth J. (ed.). The Oxford Handbook of Substance Use and Substance Use Disorders: Volume 1. Oxford Library of Psychology. Oxford and New York: Oxford University Press. pp. 27–59. doi:10.1093/oxfordhb/9780199381678.013.001. ISBN 9780199381678. LCCN 2016020729.
Anthony, James; Barondess, David A.; Radovanovic, Mirjana; Lopez-Quintero, Catalina (2017). "Part 1: Psychiatric Comorbidity – Polydrug Use: Research Topics and Issues". In Sher, Kenneth J. (ed.). The Oxford Handbook of Substance Use and Substance Use Disorders: Volume 2. Oxford Library of Psychology. Oxford and New York: Oxford University Press. pp. 27–59. doi:10.1093/oxfordhb/9780199381708.013.006. ISBN 9780199381708. LCCN 2016020729.
Hernández-Serrano, Olga; Gras, Maria E.; Font-Mayolas, Sílvia; Sullman, Mark J. M. (2016). "Part VI: Dual and Polydrug Abuse – Chapter 83: Types of Polydrug Usage". In Preedy, Victor R. (ed.). Neuropathology of Drug Addictions and Substance Misuse, Volume 3: General Processes and Mechanisms, Prescription Medications, Caffeine and Areca, Polydrug Misuse, Emerging Addictions and Non-Drug Addictions. Cambridge, Massachusetts: Academic Press, imprint of Elsevier. pp. 839–849. doi:10.1016/B978-0-12-800634-4.00083-4. ISBN 978-0-12-800634-4.
== External links ==
"The Science of Drug Use: A Resource for the Justice Sector". www.drugabuse.gov. North Bethesda, Maryland: National Institute on Drug Abuse. 26 May 2020. Archived from the original on 6 September 2023. Retrieved 21 March 2024.
School-Based Drug Abuse Prevention: Promising and Successful Programs (PDF). Ottawa, Ontario: Public Safety Canada. 31 January 2018. ISBN 978-1-100-12181-9. Archived (PDF) from the original on 19 May 2021. Retrieved 21 March 2024.
Sacco, L. N.; Finklea, K. (3 May 2016). "Synthetic Drugs: Overview and Issues for Congress" (PDF). Washington, D.C.: Congressional Research Service. Archived (PDF) from the original on 8 December 2021. Retrieved 21 March 2024. | Wikipedia/Recreational_drug_use |
An energy drink is a type of non-alcoholic psychoactive functional beverage containing stimulant compounds, usually caffeine (at a higher concentration than ordinary soda pop) and taurine, which is marketed as reducing tiredness and improving performance and concentration (marketed as "energy", but distinct from food energy). They may or may not be carbonated and may also contain sugar, other sweeteners, or herbal extracts, among numerous other possible ingredients. Energy drinks are different from sugar-sweetened beverages. While both energy drinks and sugar-sweetened beverages typically contain high levels of sugar, energy drinks include stimulants like caffeine and taurine and are marketed for energy, and sugar-sweetened beverages like sodas and fruit juices usually do not.
They are a subset of the larger group of energy products, which includes bars and gels, and distinct from sports drinks, which are advertised to enhance sports performance. There are many brands and varieties in this drink category.
Energy drinks have the effects of caffeine and sugar, but there is little or no evidence that the wide variety of other ingredients have any effect. Most effects of energy drinks on cognitive performance, such as increased attention and reaction speed, are primarily due to the presence of caffeine. Other studies ascribe those performance improvements to the effects of the combined ingredients.
Advertising for energy drinks usually features increased muscle strength and endurance, but there is no scientific consensus to support these claims. Energy drinks have been associated with many health risks, such as an increased rate of injury when usage is combined with alcohol, and excessive or repeated consumption can lead to cardiac and psychiatric conditions. Populations at risk for complications from energy drink consumption include youth, caffeine-naive or caffeine-sensitive, pregnant, competitive athletes and people with underlying cardiovascular disease.
== Ingredients and uses ==
Energy drinks are usually marketed to young people and provide the health effects of caffeine. Health experts agree that energy drinks which contain caffeine do improve alertness. The caffeine content of energy drinks is between 50mg and 505mg per serving, compared to 90mg in 250ml of coffee, 50mg in 250ml of tea, and 34mg in 500ml of cola.
There is no reliable evidence that other ingredients in energy drinks provide further benefits, even though the drinks are frequently advertised in a way that suggests they have unique benefits. The dietary supplements in energy drinks may be purported to supply benefits, such as for vitamin B12, but no claims of using supplements to enhance health in otherwise normal people have been verified scientifically.
Marketing of energy drinks has been particularly directed towards teenagers, with manufacturers sponsoring or advertising at extreme sports events and music concerts, and targeting a youthful audience through social media channels.
== Effects ==
Energy drinks have the effects caffeine and sugar provide, but there is little or no evidence that the wide variety of other ingredients have any effect. Most of the effects of energy drinks on cognitive performance, such as increased attention and reaction speed, are primarily due to the presence of caffeine. Advertising for energy drinks usually features increased muscle strength and endurance, but there is little evidence to support this in the scientific literature.
According to the Mayo Clinic, it is safe for the typical healthy adult to consume a total of 400 mg of caffeine a day. This has been confirmed by a panel of the European Food Safety Authority (EFSA), which also concludes that a caffeine intake of up to 400 mg per day does not raise safety concerns for adults. According to the EFSA this is equivalent to 4 cups of coffee (90 mg each) or 2 1/2 standard cans (250 ml) of energy drink (160 mg each/80 mg per serving).
Adverse effects associated with caffeine consumption in amounts greater than 400 mg include nervousness, irritability, sleeplessness, increased urination, abnormal heart rhythms (arrhythmia), and dyspepsia. In the United States, caffeine dosage is not required to be displayed on product labels for food. However, companies often place the caffeine content of their drinks on the label regardless, and some advocates are urging the Food and Drug Administration (FDA) to change this practice.
=== Health problems ===
Excessive consumption of energy drinks can have serious health effects resulting from high caffeine and sugar intakes, particularly in children, teens, and young adults. Excessive energy drink consumption may disrupt teens' sleep patterns and may be associated with increased risk-taking behavior. Excessive or repeated consumption of energy drinks can lead to cardiac problems, such as arrhythmias and heart attacks, and psychiatric conditions such as anxiety and phobias.
The consumption of caffeinated energy drinks has been associated with adverse effects on cardiovascular health, including increased heart rate and blood pressure, which can pose risks for individuals with underlying heart conditions.In Europe, energy drinks containing sugar and caffeine have been associated with the deaths of athletes. Reviews have noted that caffeine content was not the only factor, and that the cocktail of other ingredients in energy drinks made them more dangerous than drinks whose only stimulant was caffeine; the studies noted that more research and government regulation were needed.
The American Academy of Pediatrics recommends that children do not consume caffeinated energy drinks. For children and teenagers, safe levels of caffeine consumption have not been established.
In 2011 in the United States, 11% of the 20,783 people aged 12 or older who visited the emergency room for issues related to energy drinks were hospitalized. The number of energy-drink related emergency room visits in the United States doubled between 2007 and 2011.
In 2012, federal officials had received reports of 13 deaths over the previous four years that cited some possible involvement of 5-Hour Energy, which is classified as an energy shot, or a subsection of the energy drink category. Between 2009 and 2012, 5-Hour Energy had been mentioned in 90 filings with the F.D.A., including more than 30 that involved serious or life-threatening injuries like heart attacks, convulsions, and in one case, a spontaneous abortion.
== Prevalence ==
A 2024 review of studies from the United States, Europe, Asia, Oceania, and Africa found that 55% of participants had consumed an energy drink at one point, 43% in the last year, 32% in the past month, 22% in the past week, and 9% consumed energy drinks daily.
== History ==
Dr. Enuf, an "energy building" soft drink containing caffeine and B vitamins, was created in the United States in 1949. The New York Times states that "the energy drink, as we know it", however, was born in post World War II Japan. In 1962, Taisho Pharmaceutical produced Lipovitan D, a herbal "energizing tonic" that was sold in minibar-sized bottles. The tonic was originally marketed towards truck drivers and factory workers who needed to stay awake for long shifts. However, in Japan, most of the products of this kind bear little resemblance to soft drinks, and are sold instead in small brown glass medicine bottles, or cans styled to resemble such containers. These eiyō dorinku (literally, 'nutritional drinks') are marketed primarily to salarymen. Bacchus-F, a South Korean drink closely modeled after Lipovitan, also appeared in the early 1960s and targets a similar demographic.
In Europe, Dietrich Mateschitz, an Austrian entrepreneur, introduced the Red Bull product, a worldwide bestseller in the 21st century. Mateschitz developed Red Bull based on the Thai drink Krating Daeng, itself based on Lipovitan. Red Bull became the dominant brand in the US after its introduction in 1997, with a market share of approximately 47% in 2005.
In New Zealand and Australia, the leading energy drink product in those markets, V, was introduced by Frucor Beverages. The product now represents over 60% of market in New Zealand and Australia.
In 2002, Hansen Natural Company introduced the energy drink Monster Energy. Hansen Natural Company changed their name to Monster Beverage Corporation after an agreement by shareholders to change the name after Monster Energy became the largest source of revenue. The company's previous beverages were taken ownership of by the Coca-Cola Company.
The energy shot product, an offshoot of the energy drink, was launched in the US with products such as 5-Hour Energy, which was first released onto the market in 2004. A consumer health analyst explained in a March 2014 media article: "Energy shots took off because of energy drinks. If you're a white collar worker, you're not necessarily willing to down a big Monster energy drink, but you may drink an energy shot."
In 2007, energy drink powders and effervescent tablets were introduced, whereby either can be added to water to create an energy drink.
On 14 August 2012, the word energy drink was listed for the first time in the Merriam-Webster's Collegiate Dictionary.
== Variants ==
=== By concentration ===
==== Energy shots ====
Energy shots are a specialized kind of energy drink. Whereas most energy drinks are sold in cans or bottles, energy shots are usually sold in smaller 50ml bottles. Energy shots can contain the same total amount of caffeine, vitamins or other functional ingredients as their larger versions, and may be considered concentrated forms of energy drinks. The marketing of energy shots generally focuses on their convenience and availability as a low-calorie "instant" energy drink that can be taken in one swallow (or "shot"), as opposed to energy drinks that encourage users to drink an entire can, which may contain 250 calories or more. A common energy shot is 5-hour Energy which contains B vitamins and caffeine, with caffeine content in an amount similar to that in a cup of coffee. In some countries with restrictions and regulations on energy drinks, energy shots are classified differently and thus exempt from the rules impacting energy drinks.
=== By ingredient ===
==== Caffeinated alcoholic drink ====
Energy drinks such as Red Bull are often used as mixers with alcoholic drinks, producing mixed drinks such as Vodka Red Bull which are similar to but stronger than rum and coke with respect to the amount of caffeine that they contain. Sometimes this is configured as a bomb shot, such as the Jägerbomb or the F-Bomb—Fireball Cinnamon Whisky and Red Bull.
Caffeinated alcoholic drinks are also sold in some countries in a wide variety of formulations. The American products Four Loko and Joose originally combined caffeine and alcohol before caffeinated alcoholic drinks were banned in the US in 2010.
== Chemistry ==
Energy drinks may contain caffeine, B vitamins, carbonated water, high-fructose corn syrup, sucralose or sugar (for non-diet versions). Other common ingredients are yerba mate, açaí, taurine, ginseng, maltodextrin, inositol, carnitine, creatine, glucuronolactone or ginkgo biloba.
In the United States, the caffeine content of energy drinks is in the range of 40 to 250 mg per 8 fluid ounce (237 ml) serving. The FDA recommends that 400 mg per day is safe for adults (excluding pregnant people), while 1200 mg per day can be toxic.
== Demographics ==
Globally, energy drinks are typically attractive to youths and young adults.
== Sales and trends ==
In 2017, global energy drink sales were about 44 billion euros. In 2017, manufacturers were modifying the composition of energy drinks for reduced or no sugar content and lower calories, caffeine content, "clean" labels to reflect the use of organic ingredients, exotic flavors, and ingredients that may affect mood.
The global energy drink market was estimated to be worth $45.80 billion in 2020 and is predicted to grow at an annual rate of 8.2% to reach $108.40 billion by 2031.
=== Market share ===
In 2020, Red Bull had the largest global market share among energy drinks, at 43%, followed by Monster Energy at 39%, Rockstar Energy at 10%, and Amp and NOS, at 3% each.
== Regulations ==
Some countries have certain restrictions on the sale and manufacture of energy drinks. A ban was challenged in the European Court of Justice in 2004 and consequently lifted.
73 countries and territories have implemented policies such as taxation, bans within schools, sale bans, labeling, and marketing restrictions on energy drinks, usually to reduce consumption among those under 18.
=== Argentina ===
In December 2017, Argentina adopted Article 26 of the Internal Revenue Law, which says that beverages containing caffeine and taurine, whether supplemented or not, as defined by the Argentina Food Code, will be taxed at 10% (ad valorum tax).
=== Australia and New Zealand ===
In Australia and New Zealand, energy drinks are regulated under the Australia New Zealand Food Standards Code; limiting the caffeine content of 'formulated caffeinated beverages' (energy drinks) at 320 mg/L (9.46 mg/oz) and soft-drinks at 145 mg/L (4.29 mg/oz). Mandatory caffeine labeling is issued for all food products containing guarana in the country, and Australian energy drink labels warn consumers to drink no more than two cans per day.
Bridgetown in Western Australia became the first place in Australia to ban the sale of energy drinks to persons under 18 years for four months as of February 2023.
=== Canada ===
Canada limits the amount of caffeine per serving to 180 mg. Energy drinks are also subject to certain labelling requirements. Some imported energy drinks have surpassed the legal limit and were recalled. The Canada Border Services Agency is supposed to stop such products from entering the country but does not often patrol energy drinks to verify that they meet regulations.
=== Cape Verde ===
Cape Verde implemented an Energy Drink School Ban in 2016, with Energy Drinks prohibited within and around educational establishments.
=== Colombia ===
In 2009 under the Ministry of Social Protection, Colombia prohibited the sale and commercialization of energy drinks to minors under the age of 14.
=== Denmark ===
In 1997, Denmark banned the sale of Red Bull. The Danish Veterinary and Food Administration criticized the functional beverages' added ingredients such as B vitamins, inositol, glucuronolactone, and taurine. It argued that nutritional supplements should be added to foods only when necessary for public health, such as in the case of iodised salt. High caffeine content was also stated as an issue – only amounts up to 150 mg/L were allowed in beverages; in 2009 the limit was raised to 320 mg/L and taurine and glucuronolactone were approved as ingredients, making energy drinks legal. As of 2024, the Danish Veterinary and Food Administration advises against energy drink consumption for children; with only limited consumption of energy drinks (250 mL (8.5 U.S. fl oz) per day, assuming no other caffeine intake) for children between 15 and 17 years old.
=== Germany ===
There is no law regulating the sale of energy drinks in Germany, though several German consumer organizations and the Federal Institute for Risk Assessment are calling for a ban on the sale of soft drinks to minors with a caffeine content exceeding 150 milligrams per liter. In addition, retailers can decide for themselves to restrict the sale of energy drinks.
=== India ===
In India, the Food Safety and Standards Authority of India (FSSAI) regulates the manufacturing, packaging, labeling, and sale of energy drinks. As recommended by FSSAI, taurine is limited to 2000 mg/day, D-glucuronic-Y-lactone is limited to 1200 mg/day, Inositol is limited to 100 mg/day, and pantothenic acid is limited to 10 mg/day.
=== Latvia ===
In June 2016, Latvia banned the sale of energy drinks containing caffeine or stimulants like taurine and guarana to people under the age of 18.
=== Lithuania ===
In November 2014, Lithuania became the first country in the EU to ban the selling of energy drinks to anyone under the age of 18. The Baltic state placed the ban in reaction to research showing how popular energy drinks were among minors. According to the AFP reports roughly 10% of school-aged Lithuanians say they consume energy drinks at least once a week.
=== Mali ===
12% special tax on energy drinks.
=== Norway ===
Norway did not allow Red Bull for a time due to the high caffeine and taurine content. Classified as a drug, only limited amounts were allowed to be imported for personal use. In May 2009, it became legal to sell in Norway as the ban was in conflict with the European Economic Area's laws on free competition. The Norwegian version has reduced levels of vitamin B6. The Norwegian Food Safety Authority initially recommended an age limit on the sale of energy drinks in 2019. In 2024 the Norwegian Consumer Council called for an age limit after seeing energy drink sales increase dramatically since 2019. The Food Safety Authority, as of 2024, now disagrees with an age limit as it states it is hard to ascertain if children, specifically, are drinking more energy drinks. A majority of Norwegians support an age limit on energy drink purchases.
=== Poland ===
Since 1 January 2024, the purchase of energy drinks has been prohibited for individuals under the age of 18.
=== South Africa ===
Legislation is in place that requires manufacturers to label energy drinks with more than 150mg per liter of caffeine with a "clearly legible message" on the nutrition label declaring "high caffeine content" and says "Not recommended for children under 12 years of age, pregnant women, or persons sensitive to caffeine." An issue with this legislation is that there is no perscribed color- or type-setting restrictions, allowing for producers of energy drinks to obscure this warning via package design.
=== Spain ===
The Spanish Agency for Food Safety and Nutrition (AESAN) recommends that children and adolescents, pregnant people, and breastfeeding people refrain from consuming energy drinks.
=== Sweden ===
The sale of energy drinks to those under 15 is not allowed, and some energy drink products are restricted to pharmacies.
=== Russia ===
In November 2012, President Ramzan Kadyrov of Chechnya (Russian Federation) ordered his government to develop a bill banning the sale of energy drinks, arguing that as a form of "intoxicating drug", such drinks were "unacceptable in a Muslim society". Kadyrov cited reports of one death and 530 hospital admissions in 2012 due to "poisoning" from the consumption of such drinks. A similar view was expressed by Gennady Onishchenko, Chief Sanitary Inspector of Russia.
=== United Kingdom ===
In 2001, the UK Committee on Toxicity investigated Red Bull, finding it safe but issuing a warning against its consumption by children and pregnant women.
In 2009, a school in Hove, England, requested that local shops refrain from selling energy drinks to students. Headteacher Falklanda Sanders added that "This was a preventative measure, as all research shows that consuming high-energy drinks can have a detrimental impact on the ability of young people to concentrate in class." The school negotiated for their local branch of the Tesco supermarket to display posters asking students not to purchase the products. Similar measures were taken by a school in Oxted, England, which banned students from consuming drinks and sent letters to parents.
While not yet age-restricted by legislation, all major UK supermarkets have agreed to voluntarily stop the sale of energy drinks to under-16s. The UK government plans to end the sale of energy drinks to under-16s in the future.
In January 2018, many United Kingdom supermarkets banned the sale of energy drinks containing more than 150 mg of caffeine per liter to people under 16 years old; this was followed by the UK government announcing that it planned to ban all sales of energy drinks to minors in 2019. However, in 2022 such plans were reported to have been scrapped by Health Secretary Sajid Javid.
=== United States ===
As of 2013 in the United States, some energy drinks, including Monster Energy and Rockstar Energy, were reported to be rebranding their products as drinks rather than as dietary supplements. As drinks they would be relieved of FDA reporting requirements with respect to deaths and injuries and can be purchased with food stamps, but must list ingredients on the can.
Some places ban the sale of prepackaged caffeinated alcoholic drinks, which can be described as energy drinks containing alcohol. In response to these bans, the marketers can change the formula of their products.
In terms of labeling, caffeine must be disclosed on the product label. The specific amount of caffeine, however, does not have to be specified.
In 2013, the US Senate Commerce Committee requested 16 energy drink manufacturers to voluntarily agree not to market to children under 18.
In 2014, the American Beverage Association published the "Guidelines for the Responsible Labeling and Marketing of EDs" encouraging companies that produce energy drinks to voluntarily report the total caffeine content from all sources, limit marketing to children, and report adverse health effects to the Food and Drug Administration.
=== Uzbekistan ===
In January 2019, President Shavkat Mirziyoyev of Uzbekistan signed a law that imposes a number of restrictions on energy drinks. To protect the younger generation, a rule was introduced prohibiting the sale of energy drinks to persons under the age of 18. Advertising of energy drinks was prohibited on television and radio from 7:00 to 22:00. It was also completely banned in printed publications intended primarily for children and adolescents, in medical, sports and educational institutions.
== See also ==
== References ==
== Further reading ==
Bagchi, D. (2017). "Chapter 26: Caffeine-Containing Energy Drinks/Shots: Safety, Efficacy and Controversy". Sustained Energy for Enhanced Human Functions and Activity. Elsevier Science. pp. 423–445. ISBN 978-0-12-809332-0. Retrieved 23 October 2018.
== External links == | Wikipedia/Energy_drink |
A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active chemical substance is the same, the medical profile of generics is equivalent in performance compared to their performance at the time when they were patented drugs. A generic drug has the same active pharmaceutical ingredient (API) as the original, but it may differ in some characteristics such as the manufacturing process, formulation, excipients, color, taste, and packaging.
Although they may not be associated with a particular company, generic drugs are usually subject to government regulations in the countries in which they are dispensed. They are labeled with the name of the manufacturer and a generic non-proprietary name such as the United States Adopted Name (USAN) or International Nonproprietary Name (INN) of the drug. A generic drug must contain the same active ingredients as the original brand-name formulation. The U.S. Food and Drug Administration (FDA) requires generics to be identical to or within an acceptable bioequivalent range of their brand-name counterparts, with respect to pharmacokinetic and pharmacodynamic properties.
Biopharmaceuticals, such as monoclonal antibodies, differ biologically from small-molecule drugs. Biosimilars have active pharmaceutical ingredients that are almost identical to the original product and are typically regulated under an extended set of rules, but they are not the same as generic drugs as the active ingredients are not the same as those of their reference products. In most cases, generic products become available after the patent protections afforded to the drug's original developer expire. Once generic drugs enter the market, competition often leads to substantially lower prices for both the original brand-name product and its generic equivalents. In most countries, patents give 20 years of protection. However, many countries and regions, such as the European Union and the United States, may grant up to five years of additional protection ("patent term restoration") if manufacturers meet specific goals, such as conducting clinical trials for pediatric patients.
Manufacturers, wholesalers, insurers, and drugstores can all increase prices at various stages of production and distribution. In 2014, according to an analysis by the Generic Pharmaceutical Association, generic drugs accounted for 88 percent of the 4.3 billion prescriptions filled in the United States.: 2 "Branded generics" on the other hand are defined by the FDA and National Health Service as "products that are (a) either novel dosage forms of off-patent products produced by a manufacturer that is not the originator of the molecule, or (b) a molecule copy of an off-patent product with a trade name." Since the company making branded generics can spend little on research and development, it is able to spend on marketing alone, thus earning higher profits and driving costs down. For example, the largest revenues of Ranbaxy, now owned by Sun Pharma, came from branded generics.
== Nomenclature ==
Generic drug names are constructed using standardized affixes that distinguish drugs between and within classes and suggest their action.
== Economics ==
When a pharmaceutical company first markets a drug, it is usually under a patent that, until it expires, the company can use to exclude competitors by suing them for patent infringement. Pharmaceutical companies that develop new drugs generally only invest in drug candidates with strong patent protection as a strategy to recoup their costs of drug development (including the costs of the drug candidates that fail) and to make a profit. The average cost to a brand-name company of discovering, testing, and obtaining regulatory approval for a new drug, with a new chemical entity, was estimated to be as much as US$800 million in 2003 and US$2.6 billion in 2014. Drug companies that bring new products have several product line extension strategies they use to extend their exclusivity, some of which are seen as gaming the system and labeled "evergreening" by critics, but at some point there is no patent protection available. For as long as a drug patent lasts, a brand-name company enjoys a period of market exclusivity, or monopoly, in which the company is able to set the price of the drug at a level that maximizes profit. This profit often greatly exceeds the development and production costs of the drug, allowing the company to offset the cost of research and development of other drugs that are not profitable or do not pass clinical trials. The impact of loss of patent exclusivity on pharmaceutical products varies significantly across different product classes (e.g., biologics vs. small molecules), largely due to regulatory, legal and manufacturing hurdles associated with such products. Indeed, the greater degree of 'brand-brand' competitive dynamics seen in the biologics and complex generics space allows manufacturers of originators to better protect market share following loss of patent exclusivity.
Large pharmaceutical companies often spend millions protecting their patents from generic competition. Apart from litigation, they may reformulate a drug or license a subsidiary (or another company) to sell generics under the original patent. Generics sold under license from the patent holder are known as authorized generics. Generic drugs are usually sold for significantly lower prices than their branded equivalents and at lower profit margins. One reason for this is that competition increases among producers when a drug is no longer protected by patents. Generic companies incur fewer costs in creating generic drugs—only the cost of manufacturing, without the costs of drug discovery and drug development—and are therefore able to maintain profitability at a lower price. The prices are often low enough for users in less-prosperous countries to afford them. Generic drug companies may also receive the benefit of the previous marketing efforts of the brand-name company, including advertising, presentations by drug representatives, and distribution of free samples. Many drugs introduced by generic manufacturers have already been on the market for a decade or more and may already be well known to patients and providers, although often under their branded name.
India is a leading country in the world's generic drugs market, exporting US$20.0 billion worth of drugs in the 2019–20 (April–March) year. India exports generic drugs to the United States and the European Union. Also according to the market research community the Global Generic Drugs Market was evaluated US$465.96 million in 2021 and is expected to rise with a CAGR of 5.5% from 2022- 2028 during the forecast period. In the United Kingdom, generic drug pricing is controlled by the government's reimbursement rate. The price paid by pharmacists and doctors is determined mainly by the number of license holders, the sales value of the original brand, and the ease of manufacture. A typical price decay graph will show a "scalloped" curve, which usually starts at the brand-name price on the day of generic launch and then falls as competition intensifies. After some years, the graph typically flattens out at approximately 20% of the original brand price. In about 20% of cases, the price "bounces": Some license holders withdraw from the market when the selling price dips below their cost of goods, and the price then rises for a while until the license holders re-enter the market with new stock. The NHS spent about £4.3 billion on generic medicines in 2016–17. In 2012, 84 percent of prescriptions in the US were filled with generic drugs, and in 2014, the use of generic drugs in the United States led to US$254 billion in health care savings.: 2
In the mid-2010s the generics industry began transitioning to the end of an era of giant patent cliffs in the pharmaceutical industry; patented drugs with sales of around US$28 billion were set to come off patent in 2018, but in 2019 only about US$10 billion in revenue was set to open for competition, and less the next year. Companies in the industry have responded with consolidation or turning to try to generate new drugs. Most developed nations require generic drug manufacturers to prove that their formulations are bioequivalent to their brand-name counterparts. Bioequivalence does not mean generic drugs must be exactly the same as the brand-name product ("pharmaceutical equivalent"). Chemical differences may exist; a different salt or ester may be used, for instance. Different inactive ingredients means that the generic may look different from the originator brand; however, the therapeutic effect of the drug must be the same ("pharmaceutical alternative"). Most small molecule drugs are accepted as bioequivalent if their pharmacokinetic parameters of area under the curve (AUC) and maximum concentration (Cmax) are within a 90% confidence interval of 80–125%; most approved generics in the US are well within this limit. For more complex products—such as inhalers, patch delivery systems, liposomal preparations, or biosimilar drugs—demonstrating pharmacodynamic or clinical equivalence is more challenging.
=== United States ===
Enacted in 1984, the Drug Price Competition and Patent Term Restoration Act, informally known as the Hatch–Waxman Act, standardized procedures for recognition of generic drugs. In 2007, the FDA launched the Generic Initiative for Value and Efficiency (GIVE): an effort to modernize and streamline the generic drug approval process, and to increase the number and variety of generic products available.
Before a company can market a generic drug, it needs to file an Abbreviated New Drug Application (ANDA) with the Food and Drug Administration, seeking to demonstrate therapeutic equivalence to a previously approved "reference-listed drug" and proving that it can manufacture the drug safely and consistently. For an ANDA to be approved, the FDA requires that the 90% confidence interval of the geometric mean test/reference ratios for the total drug exposure (represented by the area under the curve or AUC) and the maximum plasma concentration (Cmax) should fall within limits of 80–125%. (This range is part of a statistical calculation, and does not mean that generic drugs are allowed to differ from their brand-name counterparts by up to 25 percent.) The FDA evaluated 2,070 studies conducted between 1996 and 2007 that compared the absorption of brand-name and generic drugs into a person's body. The average difference in absorption between the generic and the brand-name drug was 3.5 percent, comparable to the difference between two batches of a brand-name drug. Non-innovator versions of biologic drugs, or biosimilars, require clinical trials for immunogenicity in addition to tests establishing bioequivalency. These products cannot be entirely identical because of batch-to-batch variability and their biological nature, and they are subject to extra rules.
When an application is approved, the FDA adds the generic drug to its Approved Drug Products with Therapeutic Equivalence Evaluations list and annotates the list to show the equivalence between the reference-listed drug and the generic. The FDA also recognizes drugs that use the same ingredients with different bioavailability and divides them into therapeutic equivalence groups. For example, as of 2006, diltiazem hydrochloride had four equivalence groups, all using the same active ingredient, but considered equivalent only within each group.
In order to start selling a drug promptly after the patent on innovator drug expires, a generic company has to file its ANDA well before the patent expires. This puts the generic company at risk of being sued for patent infringement, since the act of filing the ANDA is considered "constructive infringement" of the patent. In order to incentivize generic companies to take that risk the Hatch-Waxman act granted a 180-day administrative exclusivity period to generic drug manufacturers who are the first to file an ANDA.
When faced with patent litigation from the drug innovator or patent holder, generic companies will often counter-sue, challenging the validity of the patent. Like any litigation between private parties, the innovator and generic companies may choose to settle the litigation. Some of these settlement agreements have been struck down by courts when they took the form of reverse payment patent settlement agreements, in which the generic company basically accepts a payment to drop the litigation, delaying the introduction of the generic product and frustrating the purpose of the Hatch–Waxman Act.
Innovator companies sometimes try to maintain some of the revenue from their drug after patents expire by allowing another company to sell an authorized generic; a 2011 FTC report found that consumers benefitted from lower costs when an authorized generic was introduced during the 180 day exclusivity period, as it created competition. Innovator companies may also present arguments to the FDA that the ANDA should not be accepted by filing an FDA citizen petition. The right of individuals or organizations to petition the federal government is guaranteed by the First Amendment to the United States Constitution. For this reason, the FDA has promulgated regulations that provide, among other things, that at any time, any "interested person" can request that the FDA "issue, amend, or revoke a regulation or order," and set forth a procedure for doing so.
==== Acceptance ====
Some generic drugs are viewed with suspicion by doctors. For example, warfarin (Coumadin) has a narrow therapeutic window and requires frequent blood tests to make sure patients do not have a subtherapeutic or a toxic level. A study performed in Ontario showed that replacing Coumadin with generic warfarin was safe, but many physicians are not comfortable with their patients taking branded generic equivalents. In some countries (for example, Australia) where a drug is prescribed under more than one brand name, doctors may choose not to allow pharmacists to substitute a brand different from the one prescribed unless the consumer requests it.
==== Fraud ====
A series of scandals around the approval of generic drugs in the late 1980s shook public confidence in generic drugs; there were several instances in which companies obtained bioequivalence data fraudulently, by using the branded drug in their tests instead of their own product, and a congressional investigation found corruption at the FDA, where employees were accepting bribes to approve some generic companies' applications and delaying or denying others.
In 2007, North Carolina Public Radio's The People's Pharmacy began reporting on consumers' complaints that generic versions of bupropion (Wellbutrin) were yielding unexpected effects. Subsequently, Impax Laboratories's 300 mg extended-release tablets, marketed by Teva Pharmaceutical Industries, were withdrawn from the US market after the FDA determined in 2012 that they were not bioequivalent.
Problems with the quality of generic drugs – especially those produced outside the United States – are widespread as of 2019. The FDA does infrequent – less than annual – inspections of production sites outside the United States. The FDA normally gives advance notice of inspections, which can lead to cover-ups of problems before inspectors arrive; inspections performed with little or no advance notice have produced evidence of serious problems at a majority of generic drug manufacturing sites in India and China.
==== Litigation ====
Two women, each claiming to have suffered severe medical complications from a generic version of metoclopramide, lost their Supreme Court appeal on June 23, 2011. In a 5–4 ruling in PLIVA, Inc. v. Mensing, the court held that generic companies cannot be held liable for information, or the lack of information, on the originator's label.
=== India ===
The Indian government began encouraging more drug manufacturing by Indian companies in the early 1960s, and with the Patents Act in 1970. The Patents Act removed composition patents for foods and drugs, and though it kept process patents, these were shortened to a period of five to seven years. The resulting lack of patent protection created a niche in both the Indian and global markets that Indian companies filled by reverse-engineering new processes for manufacturing low-cost drugs. The code of ethics issued by the Medical Council of India in 2002 calls for physicians to prescribe drugs by their generic names only. India is a leading country in the world's generic drugs market, with Sun Pharmaceuticals being the largest pharmaceutical company in India. Indian generics companies exported US$17.3 billion worth of drugs in the 2017–18 (April–March) year. In 1945–2017, bioequivalence studies were only required for generics of drugs that are less than four years old. Since 2017, all generic drugs of certain classes, irrespective of age, require bioequivalence to be approved.
=== China ===
Generic drug production is a large part of the pharmaceutical industry in China. Western observers have said that China lacks administrative protection for patents. However, entry to the World Trade Organization has brought a stronger patent system. China remains the largest exporter of active pharmaceutical ingredients, accounting for 40% of the world market per a 2017 estimate.
Bioequivalence studies are required for new generic drugs starting from 2016, with older drugs planned as well. In addition, in vitro dissolution behavior is required to match. Since 2018, 44 classes of drugs are exempt from testing (requiring only a dissolution check), and 13 classes only require simplified testing.
== Industry ==
As of 2021, several major companies traditionally dominate the generic drugs market, including Viatris (merger of Mylan and Upjohn), Teva, Novartis' Sandoz, and Sun Pharma. Prices in traditional generic drugs have declined and newer companies such as India-based Sun Pharma, Aurobindo Pharma, and Dr. Reddy's Laboratories, as well as Canada-based Apotex, have taken market share, which has led to a focus on biosimilars.
== See also ==
== References ==
== Further reading ==
== External links ==
"United States Adopted Names Program, generic drug naming process, lists of adopted names". 16 August 2023.
"USFDA, Office of Generic Drugs". Food and Drug Administration. Archived from the original on 2009-05-28. Retrieved 2019-12-16.
"UK Department of Health, generic drugs". Archived from the original on 2007-03-01.
"The Medical Letter on Drugs and Therapeutics".
"GPhA Generic Pharmaceutical Association". Archived from the original on 2021-04-22. Retrieved 2008-06-16.
"Canada Generic Drugs: Government of Canada and Health Canada". 2 May 2018. | Wikipedia/Generic_drug |
The Mexican drug war is an ongoing asymmetric armed conflict between the Mexican government and various drug trafficking syndicates. When the Mexican military intervened in 2006, the government's main objective was to reduce drug-related violence. The Mexican government has asserted that its primary focus is dismantling the cartels and preventing drug trafficking. The conflict has been described as the Mexican theater of the global war on drugs, as led by the United States federal government.
Violence escalated after the arrest of Miguel Ángel Félix Gallardo in 1989. He was the leader and the co-founder of the first major Mexican drug cartel, the Guadalajara Cartel, an alliance of the current existing cartels (which included the Sinaloa Cartel, the Juarez Cartel, the Tijuana Cartel, and the Sonora Cartel with Aldair Mariano as the leader). After his arrest, the alliance broke, and high-ranking members formed their own cartels, fighting for control of territory and trafficking routes.
Although Mexican drug trafficking organizations have existed for several decades, their influence increased after the demise of the Colombian Cali and Medellín cartels in the 1990s. By 2007, Mexican drug cartels controlled 90% of the cocaine entering the United States. Arrests of key cartel leaders, particularly in the Tijuana and Gulf cartels, have led to increasing drug violence as cartels fight for control of the trafficking routes into the United States.
Federal law enforcement has been reorganized at least five times since 1982 in various attempts to control corruption and reduce cartel violence. During the same period, there were at least four elite special forces created as new, corruption-free soldiers who could fight Mexico's endemic bribery system. Analysts estimate wholesale earnings from illicit drug sales range from $13.6 to $49.4 billion annually. The U.S. Congress passed legislation in late June 2008 to provide Mexico with US$1.6 billion for the Mérida Initiative and technical advice to strengthen the national justice systems. By the end of President Felipe Calderón's administration (December 1, 2006 – November 30, 2012), the official death toll of the Mexican drug war was at least 60,000. Estimates set the death toll above 120,000 killed by 2013, not including 27,000 missing. When Andrés Manuel López Obrador took office as president in 2018, he declared the war was over; his comment was criticized, as the homicide rate remains high.
== Background ==
Due to its location, Mexico has long been used as a staging and transshipment point for narcotics and contraband between Latin America and U.S. markets. Mexican bootleggers supplied alcohol to American gangsters throughout Prohibition in the United States, and the onset of the illegal drug trade with the U.S. began when Prohibition came to an end in 1933. Near the end of the 1960s, Mexicans started to smuggle drugs on a major scale.
In 1940, under president Lázaro Cárdenas and the impulsion of Mexican psychiatrist Leopoldo Salazar Viniegra, Mexico legalized all drugs, in an early attempt to prevent the development of illegal drug trafficking organizations. The law was in effect for about 5 months when the Mexican government repealed it, allegedly under the increasing economic and political pressure from the U.S.
In the 1960s and 1970s, Mexico was part of both Operation Intercept and Operation Condor, developed between 1975 and 1978, with the pretext to fight against the cultivation of opium and marijuana in the "Golden Triangle", particularly in Sinaloa.
The operation, commanded by General José Hernández Toledo, was a failure, with no major drug lord captures and reported abuse and repression in rural zones.
During the 1970s and early 1980s, Colombia's Pablo Escobar was the main exporter of cocaine and dealt with organized criminal networks all over the world. While Escobar's Medellin Cartel and the Cali Cartel would manufacture the products, Miguel Ángel Félix Gallardo's Guadalajara Cartel would oversee distribution. When enforcement efforts intensified in South Florida and the Caribbean, the Colombian organizations formed partnerships with Mexico-based traffickers to transport cocaine by land through Mexico into the United States.
This was easily accomplished because Mexico had long been a major source of heroin and cannabis, and drug traffickers from Mexico had already established an infrastructure that stood ready to serve the Colombia-based traffickers. By the mid-1980s, the organizations from Mexico were well-established and reliable transporters of Colombian cocaine. At first, the Mexican gangs were paid in cash for their transportation services. However, in the late 1980s, the Mexican transport organizations and the Colombian drug traffickers settled on a payment-in-product arrangement.
Transporters from Mexico usually were given 35% to 50% of each cocaine shipment. This arrangement meant that organizations from Mexico became involved in the distribution, as well as the transportation of cocaine, and became formidable traffickers in their own right. In recent years, the Sinaloa Cartel and the Gulf Cartel have taken over trafficking cocaine from Colombia to the worldwide markets.
The balance of power between the various Mexican cartels continually shifts as new organizations emerge and older ones weaken and collapse. A disruption in the system, such as the arrests or deaths of cartel leaders, generates bloodshed as rivals move in to exploit the power vacuum. Leadership vacuums are sometimes created by law enforcement successes against a particular cartel, so cartels often will attempt to pit law enforcement against one another, either by bribing corrupt officials to take action against a rival or by leaking intelligence about a rival's operations to the Mexican or U.S. government's Drug Enforcement Administration (DEA).
While many factors have contributed to the escalating violence, security analysts in Mexico City trace the origins of the rising scourge to the unraveling of a longtime implicit arrangement between narcotics traffickers and governments controlled by the Institutional Revolutionary Party (PRI), which began to lose its grip on political power in the late 1980s.
The fighting between rival drug cartels began in earnest after the 1989 arrest of Félix Gallardo, who ran the cocaine business in Mexico. There was a lull in the fighting during the late 1990s, but the violence has steadily worsened since 2000.
According to researchers, as of 2023, an estimated 175,000 people are working for the drug cartels. The head of the U.S. drug enforcement reported that there are an estimated 45,000 members, associates, and brokers spread over more than 100 countries working under the Sinaloa cartel and the Jalisco New Generation cartel.
=== Presidents ===
The dominant PRI party ruled Mexico for around 70 years until 2000. During this time, drug cartels expanded their power and political influence, and anti-drug operations focused mainly on destroying marijuana and opium crops in mountainous regions. There were no large-scale, high-profile military operations against their core structures in urban areas until the 2000 Mexican election when the right-wing PAN party gained the presidency and started a crackdown on cartels on their turf.
==== Vicente Fox ====
In 2000, Vicente Fox, from the right-wing PAN party, became the first Mexican president since the Mexican Revolution not to be from the PRI; his presidency passed with relative peace, having a crime index not too different from that of previous administrations and Mexican public opinion was mainly optimistic with the regime change, with Mexico showing a decline in homicide rates from 2000 to 2007. One of the Fox administration's strongest criticisms arose from its management of the peasant unrest in San Salvador Atenco.
Los Zetas, the armed wing of the Gulf Cartel, based in Nuevo Laredo, escalated violence to unprecedented levels in the summer of 2003 through gruesome violence and military-like tactics against the Sinaloa Cartel. Los Zetas also instilled terror against journalists and civilians of Nuevo Laredo. This set a new precedent, which cartels later mimicked. All these activities by Mexican criminal organizations were not widely reported by the Mexican media. However, key conflicts occurred, including the Sinaloa Cartel attacks and the advance on the Gulf Cartel's main regions in Tamaulipas.
It is estimated that in the first eight months of 2005, about 110 people died in Nuevo Laredo, Tamaulipas, as a result of the fighting between the Gulf and Sinaloa cartels. The same year, there was another surge in violence in the state of Michoacán as La Familia Michoacana drug cartel established itself after splintering from its former allies, the Gulf Cartel and Los Zetas.
==== Felipe Calderón ====
On December 11, 2006, newly elected President Felipe Calderón, from the PAN party, dispatched 6,500 Mexican Army soldiers to Michoacán, his home state, to end drug violence. This action is regarded as the first major deployment of government forces against cartels and is generally viewed as the starting point of the Mexican drug war. As time passed, Calderón continued to escalate his anti-drug campaign. By 2008, there were about 45,000 troops involved, along with state and federal police forces.
The government was initially successful in detaining drug lords. Drug-related violence spiked markedly in contested areas along the U.S. border, such as Ciudad Juárez, Tijuana, and Matamoros. Some analysts, including U.S. Ambassador in Mexico Carlos Pascual, argued that this rise in violence was a direct result of Felipe Calderón's military measures. Since Calderón launched his military strategy against organized crime, there has been an alarming increase in violent deaths related to organized crime: more than 15,000 people have died in suspected drug cartel attacks since it was launched at the end of 2006. More than 5,000 people were murdered in Mexico in 2008, followed by 9,600 murders in 2009; 2010 saw more than 15,000 homicides across the country.
By the end of Calderón's presidency, his administration statistics claimed that, during his 6-year term, 50,000 drug-related homicides occurred. Outside sources claimed more than 120,000 murders happened in the same period as a result of his militaristic anti-drug policy.
==== Enrique Peña Nieto ====
In 2012, newly elected President Enrique Peña Nieto, from the PRI party, emphasized that he did not support the involvement of armed American agents in Mexico and was only interested in training Mexican forces in counter-insurgency tactics. Peña Nieto stated that he planned to de-escalate the conflict, focusing on lowering criminal violence rates, as opposed to the previous policy of attacking drug-trafficking organizations by arresting or killing the most-wanted drug lords and intercepting their shipments.
In the first 14 months of his administration, between December 2012 and January 2014, 23,640 people died in the conflict.
In 2013, Mexico saw the rise of the controversial grupos de autodefensa comunitaria (self-defense groups) in southern Mexico, para-military groups led by land-owners, ranchers, and other rural inhabitants that took up arms against the criminal groups that wanted to impose dominance in their towns, entering a new phase in the Mexican war on drugs. This strategy, allegedly proposed by General Óscar Naranjo, Peña Nieto's security advisor from Colombia, crumbled when autodefensas started to have internal organization struggles and disagreements with the government, as well as infiltration by criminal elements, that deprived the government forces the ability to distinguish between armed-civilian convoys and drug-cartel convoys, forcing Peña Nieto's administration to distance from them.
Peña Nieto's handling of the 2014 Iguala mass kidnapping and the 2015 escape of drug lord Joaquín "El Chapo" Guzmán from the Altiplano maximum security prison sparked international criticism.
A great part of Peña Nieto's strategy consisted in making the Mexican Interior Ministry solely responsible for public security and the creation of a national military-level police force called the National Gendarmerie. In December 2017, the Law of Internal Security was passed by legislation but was met with criticism, especially from the National Human Rights Commission, accusing it gave the president a blank check.
==== Andrés Manuel López Obrador ====
Andrés Manuel López Obrador, the president of the center-left Morena party, took office on December 1, 2018. One of his campaign promises was a controversial "strategy for peace", which would give amnesty to Mexicans involved in drug production and trafficking as a way to stop the drug trade and the resulting turf violence. His aides explained that the plan was not to pardon real criminals, like violent drug cartel members, but to prevent other people from following that path, especially low-income people, farmers forced into drug cultivation by cartels, and young people who may end up in jail for drug possession. López Obrador pointed out that the past approaches failed because they were based on misunderstanding the core problem. According to him, the underlying issue was Mexico's great social disparities, which previous governments' economic policies did not reduce.
For law enforcement, he promised to hold a referendum for the creation of a temporary national guard, merging elite parts of the Federal Police, military police, Navy, Chief of Staff's Guard, and other top Mexican security agencies, intending to finally give a legal framework to the military grade forces that have been doing police work in the last years. He promised not to use arms to suppress the people and announced the release of political prisoners. His approach is to pay more attention to the victims of violent crime, and he wants to revisit two previously taken strategies. In 2019, the promised Mexican National Guard was created.
Despite the new government's planned strategy changes, during the first two months of the new presidency, the violence between drug trafficking organizations sustained the same levels as in previous years. On July 15, 2022, authorities captured Rafael Caro-Quintero, a former leader of the Guadalajara cartel. However, they lost fourteen soldiers in an aircraft crash in the remote mountains near Sinaloa's border with Chihuahua.
On January 30, 2019, López Obrador declared the end of the Mexican war on drugs, stating that he would now focus on reducing spending and direct its military and police efforts primarily on stopping the armed gasoline theft rings —locally called huachicoleros— that had been stealing more than 70 thousand barrels of oil, diesel, and gasoline daily, costing the Mexican state-owned company Pemex around 3 billion dollars every year.
On October 17, 2019, based on an extradition request sent to Mexico by a Washington, D.C. judge, a failed operation to capture alleged kingpin Ovidio Guzmán López was carried out by the Mexican National Guard, in which fourteen people died (mostly from the armed forces and cartel enforcers and one civilian bystander). Guzmán was released after approximately 700 cartel enforcers, armed with .50 caliber rifles, rocket-propelled grenades (RPGs), and 40 mm grenades, took multiple hostages, including the housing unit where military families live in Culiacan. The cartels used burning vehicles to block roads, a tactic taken from militant protesters, with the event described as a mass insurrection. López Obrador defended the decision to release Ovidio Guzmán, arguing it prevented further loss of life, and insisted that he wanted to avoid more massacres. He further stated that the capture of one drug smuggler could not be more valuable than the lives of innocent civilians and that even though they underestimated the cartel's forces and ability to respond, the criminal process against Ovidio is still ongoing. In 2019, the federal forces deployed 8,000 troops and police reinforcements to restore peace in Culiacan.
This strategy of avoiding armed confrontations while drug organizations have continued violent altercations has been controversial. One of the strongest critics of the new approach and a firm proponent of continuing the armed struggle is former President Felipe Calderón, who originally started the military operations against traffickers in 2006. Calderón's militaristic strategy to capture cartel heads has also been criticized by local and foreign experts, as well as by multiple media outlets.
President López Obrador, known for his strong criticism of previous administrations' approach to public security through militarization, campaigned on the promise of removing the military from the streets and returning them to the barracks. However, under the López Obrador administration, deployments and military expenditures have reached unprecedented levels. The current number of soldiers deployed for security duties is 76% higher than during Felipe Calderón's presidency, whom López Obrador holds responsible for the militarization of the drug war. Consequently, defense spending has surged 87% between 2012, Calderón's last year in office, and 2022.
Although the number of deployed soldiers is higher, available data indicates that they assume a more restrained role. They engage in fewer confrontations, seize fewer firearms, and prioritize non-confrontational strategies to deter criminals. This has resulted in lower weapon seizures and fewer arrests of alleged criminals. Additionally, President López Obrador has broadened their duties, such as overseeing vaccine distribution and addressing irregular migration flows.
=== Drug sources and use ===
==== Sources ====
The U.S. State Department estimates that 90 percent of cocaine entering the United States is produced in Colombia (followed by Bolivia and Peru) and that the main transit route is through Mexico. Drug cartels in Mexico control approximately 70% of the foreign narcotics flow into the United States.
Mexican cartels distribute Asian methamphetamine to the United States. It is believed that almost half the cartels' revenues come from cannabis. Cocaine, heroin, and, increasingly, methamphetamine are also traded.
Although Mexico accounts for only a small share of worldwide heroin production, it supplies a large share of the heroin distributed in the United States.
Since 2003, Mexican cartels have used the dense, isolated portions of U.S. federal and state parks and forests to grow marijuana under the canopy of thick trees. Billions of dollars worth of marijuana has been produced annually on U.S. soil. In 2006, federal and state authorities seized over 550,000 marijuana plants worth an estimated 1 billion dollars in Kentucky's remote Appalachian counties. Cartels profited from marijuana growing operations from Arkansas to Hawaii.
A 2018 study found that the reduction in drugs from Colombia contributed to Mexican drug violence. The study estimated that "between 2006 and 2009, the decline in cocaine supply from Colombia could account for 10%–14% of the increase in violence in Mexico."
==== Use ====
Illicit drug use in Mexico is low compared to the United States but is on the rise. With Mexico's increased role in the trafficking and production of illegal drugs, the availability of narcotics has risen slowly locally since the 1980s. In the decades before this period, consumption was not generalized – reportedly occurring mainly among persons of high socioeconomic status, intellectuals, and artists.
As the US is the world's largest consumer of cocaine, as well as of other illegal drugs, its demand is what motivates the drug business, and the main goal of Mexican cartels is to introduce narcotics into the US. The export rate of cocaine to the US decreased following stricter border control measures in response to the September 11 attacks. This led to a surplus of cocaine, which resulted in local Mexican dealers attempting to offload extra narcotics along trafficking routes, especially in border areas popular among North American tourists.
Drug shipments are often delayed in Mexican border towns before delivery to the U.S., which has forced drug traffickers to increase prices to account for transportation costs of products across international borders, making it a more profitable business for the drug lords, and has likely contributed to the increased rates of local drug consumption.
With increased cocaine use, there has been a parallel rise in demand for drug user treatment in Mexico.
=== Poverty ===
One of the main factors driving the Mexican drug war is widespread poverty. From 2004 to 2008, the portion of the population who received less than half of the median income rose from 17% to 21%, and the proportion of the population living in extreme or moderate poverty rose from 35 to 46% (52 million persons) between 2006 and 2010.
Among the OECD countries, Mexico has the second highest economic disparity between the extremely poor and the rich. The bottom ten percent in the income hierarchy has 1.36% of the country's resources, whereas the upper ten percent has almost 36%. The OECD also notes that Mexico's budgeted poverty alleviation and social development expenses are only about a third of the OECD average.
In 2012, it was estimated that Mexican cartels employed over 450,000 people directly, and a further 3.2 million people's livelihoods depended on various parts of the drug trade. In cities such as Ciudad Juárez, up to 60% of the economy depended on illegal sources of income.
==== Education ====
A problem that goes hand in hand with poverty in Mexico is the level of schooling. In the 1960s, when Mexican narcotic smugglers started to smuggle drugs on a major scale, only 5.6% of the Mexican population had more than six years of schooling.
More recently, researchers from the World Economic Forum have noted that despite the Mexican economy ranking 31st out of 134 economies for investment in education (5.3% of its GDP), as of 2009, the nation's primary education system is ranked only 116th, thereby suggesting "that the problem is not how much but rather how resources are invested". The WEF further explained: "The powerful teachers union, the SNTE, the largest labor union in Latin America, has been largely responsible for blocking reforms that would increase the quality of spending and help ensure equal access to education." The result of the high levels of poverty, lack of well-paid jobs, government corruption, and the systemic failure of Mexico's schools has been the appearance of ninis, a youth underclass of school dropouts who neither work nor study, who might have ended up as combatants on behalf of the cartels.
Teachers' unions have opposed reforms that propose their testing and grading on their students' performance with standardized tests that do not take into account the socioeconomic differences between middle-class urban schools and under-equipped, poor rural schools, which has an important effect on students' performance. Also, teachers' unions have argued that the legislation is ambiguous, focuses exclusively on teachers without evaluating the Education Ministry, and will allow more abuse and political corruption.
== Mexican cartels ==
=== Origins ===
The birth of most Mexican drug cartels is traced to former Mexican Judicial Federal Police agent Miguel Ángel Félix Gallardo (Spanish: El Padrino, lit. 'The Godfather'), who founded the Guadalajara Cartel in 1980 and controlled most of the illegal drug trade in Mexico and the trafficking corridors across the Mexico–U.S. border along with Juan García Ábrego throughout the 1980s. He started off by smuggling marijuana and opium into the U.S., and was the first Mexican drug chief to link up with Colombia's cocaine cartels in the 1980s. Through his connections, Félix Gallardo became the person at the forefront of the Medellín Cartel, which was run by Pablo Escobar. This was accomplished because Félix Gallardo had already established a marijuana trafficking infrastructure that stood ready to serve the Colombia-based cocaine traffickers.
There were no other cartels at that time in Mexico.: 41 He oversaw operations with his cronies and the politicians who sold him protection. The Guadalajara Cartel suffered a major blow in 1985 when the group's co-founder Rafael Caro Quintero was captured, and later convicted, for the murder of DEA agent Enrique "Kiki" Camarena. Félix Gallardo then kept a low profile and in 1987 he moved with his family to Guadalajara. According to Peter Dale Scott, the Guadalajara Cartel prospered largely because it enjoyed the protection of the Dirección Federal de Seguridad (DFS), under its chief Miguel Nazar Haro.
Félix Gallardo was arrested on April 8, 1989. He then divested the trade he controlled as it would be more efficient and less likely to be brought down in one law enforcement swoop.: 47 He sent his lawyer to convene the nation's top drug traffickers at a house in Acapulco where he designated plazas or territories.
The Tijuana route would go to his nephews the Arellano Felix brothers. The Ciudad Juárez route would go to the Carrillo Fuentes family. Miguel Caro Quintero would run the Sonora corridor. Meanwhile, Joaquín Guzmán Loera and Ismael Zambada García would take over Pacific coast operations, becoming the Sinaloa Cartel. Guzmán and Zambada brought veteran Héctor Luis Palma Salazar back into the fold. The control of the Matamoros, Tamaulipas corridor—then becoming the Gulf Cartel—would be left undisturbed to its founder Juan García Ábrego, who was not a party to the 1989 pact.
Félix Gallardo still planned to oversee national operations, as he maintained important connections, but he would no longer control all details of the business. When he was transferred to a high-security prison in 1993, he lost any remaining control over the other drug lords.
=== Major cartels in the war ===
==== Sinaloa Cartel ====
The Sinaloa Cartel began to contest the Gulf Cartel's domination of the coveted southwest Texas corridor following the arrest of Gulf Cartel leader Osiel Cárdenas in March 2003. The "Federation" was the result of a 2006 accord between several groups located in the Pacific state of Sinaloa. The cartel was led by Joaquín "El Chapo" Guzmán, who was Mexico's most-wanted drug trafficker with an estimated net worth of U.S. $1 billion. This made him the 1140th richest man in the world and the 55th most powerful, according to his Forbes magazine profile. He was arrested and escaped in July 2015, and re-arrested in January 2016. In February 2010, new alliances were formed against Los Zetas and Beltrán-Leyva Cartel.
The Sinaloa Cartel fought the Juárez Cartel in a long and bloody battle for control over drug trafficking routes in and around the northern city of Ciudad Juárez. The battle eventually resulted in defeat for the Juárez Cartel, resulting in the deaths of between 5,000 and 12,000 people. During the war for the turf in Ciudad Juárez the Sinaloa Cartel used several gangs (e.g. Los Mexicles, the Artistas Asesinos and Gente Nueva) to attack the Juárez Cartel. The Juárez Cartel similarly used gangs such as La Línea and the Barrio Azteca to fight the Sinaloa Cartel.
As of May 2010, numerous reports by Mexican and U.S. media stated that Sinaloa had infiltrated the Mexican federal government and military, and colluded with it to destroy the other cartels. The Colima, Sonora and Milenio Cartels are now branches of the Sinaloa Cartel.
Joaquín "El Chapo" Guzmán was arrested on January 8, 2016, and extradited to the United States a year later. On February 4, 2019, in Brooklyn, NY, he was found guilty of ten counts of drug trafficking and sentenced to life imprisonment. Guzman unsuccessfully attempted to convince prosecutors that he has assumed charges on behalf of Ismael "El Mayo" Zambada "El Chapo" alleged that he had paid former presidents Enrique Peña Nieto and Felipe Calderón bribes, which was quickly denied by both men. In March 2019, El Chapo's successor, Ismael Zambada García, alias "El Mayo," was reported to be Mexico's "last Capo" and even more feared than his closest rival Nemesio Oseguera Cervantes, alias "El Mencho," who serves as leader of the Jalisco Cartel New Generation.
On January 5, 2023, the arrest of Ovidio Guzmán, son of jailed drug lord Joaquín 'El Chapo' Guzmán, sparked a wave of violence in the state of Sinaloa. The violence prompted the Mexican military to launch a series of armed raids using planes and helicopters to attack Sinaloa cartel members.
==== Beltrán-Leyva Cartel ====
The Beltrán-Leyva Cartel was a Mexican drug cartel and organized crime syndicate founded by the four Beltrán Leyva brothers: Marcos Arturo, Carlos, Alfredo and Héctor. In 2004 and 2005, Arturo Beltrán Leyva led powerful groups of assassins to fight for trade routes in northeastern Mexico for the Sinaloa Cartel. Through corruption or intimidation, the Beltrán-Leyva Cartel infiltrated Mexico's political, judicial and police institutions to feed classified information about anti-drug operations, and even infiltrated the Interpol office in Mexico.
Following the December 2009 death of the cartel's leader Arturo Beltrán Leyva by Mexican Marines the cartel entered into an internal power struggle between Arturo's brother, Héctor Beltrán Leyva, and Arturo's top enforcer Edgar Valdez Villarreal. Meanwhile, the cartel continued to dissolve with factions such as the South Pacific Cartel, La Mano Con Ojos, Independent Cartel of Acapulco, and La Barredora forming and the latter two cartels starting yet another intra-Beltrán Leyva Cartel conflict.
The Mexican Federal Police considers the cartel to have been disbanded, and the last cartel leader, Héctor Beltrán Leyva, was captured in October 2014.
==== Juárez Cartel ====
The Juárez Cartel controls one of the primary transportation routes for billions of dollars' worth of illegal drug shipments annually entering the United States from Mexico. Since 2007, the Juárez Cartel has been locked in a vicious battle with its former partner, the Sinaloa Cartel, for control of Ciudad Juárez. La Línea is a group of Mexican drug traffickers and corrupt Juárez and Chihuahua state police officers who work as the armed wing of the Juárez Cartel. Vicente Carrillo Fuentes headed the Juárez Cartel until his arrest in 2014.
Since 2011, the Juárez Cartel continues to weaken. It is present in the three main points of entry into El Paso, Texas. The Juárez Cartel is only a shadow of the organization it was a decade ago, and its weakness and inability to effectively fight against Sinaloa's advances in Juarez contributed to the lower death toll in Juarez in 2011.
==== Tijuana Cartel ====
The Tijuana Cartel, also known as the Arellano Félix Organization, was once among Mexico's most powerful. It is based in Tijuana, one of the most strategically important border towns in Mexico, and continues to export drugs even after weakening by an internal war in 2009. Due to infighting, arrests and the deaths of some of its top members, the Tijuana Cartel is a fraction of what it was in the 1990s and early 2000s, when it was considered one of the most potent and violent criminal organizations in Mexico by the police. After the arrest or assassination of various members of the Arellano Félix family, the cartel is currently allegedly headed by Edwin Huerta Nuño alias "El Flako".
==== Gulf Cartel ====
The Gulf Cartel (CDG), based in Matamoros, Tamaulipas, has been one of Mexico's two dominant cartels in recent years. In the late 1990s, it hired a private mercenary army (an enforcer group now called Los Zetas), which in 2006 stepped up as a partner but, in February 2010, their partnership was dissolved, and both groups engaged in widespread violence across several border cities of Tamaulipas state, turning several border towns into "ghost towns".
The CDG was strong at the beginning of 2011, holding off several Zetas incursions into its territory. As the year progressed, internal divisions led to intra-cartel battles in Matamoros and Reynosa, Tamaulipas state. The infighting resulted in several arrests and deaths in Mexico and in the United States. The CDG has since broken apart, and it appears that one faction, known as Los Metros, has overpowered its rival Los Rojos faction and is now asserting its control over CDG operations.
The infighting has weakened the CDG, but the group seems to have maintained control of its primary plazas, or smuggling corridors, into the United States. The Mexican federal government has made notable successes in capturing the leadership of the Gulf Cartel. Osiel Cárdenas Guillén, his brothers Antonio Cárdenas Guillén, Mario Cárdenas Guillén, and Jorge Eduardo Costilla Sánchez have all been captured and incarcerated during Felipe Calderón's administration.
==== Los Zetas ====
In 1999, Gulf Cartel's leader, Osiel Cárdenas Guillén, hired a group of 37 corrupt former elite military soldiers to work for him. These former Airmobile Special Forces Group (GAFE), and Amphibian Group of Special Forces (GANFE) soldiers became known as Los Zetas and began operating as a private army for the Gulf Cartel. During the early 2000s the Zetas were instrumental in the Gulf Cartel's domination of the drug trade in much of Mexico.
After the 2007 arrest and extradition of Osiel Cárdenas Guillén, the Zetas seized the opportunity to strike out on their own. Under the leadership of Heriberto Lazcano, the Zetas, numbering about 300, gradually set up their own independent drug, arms and human-trafficking networks. In 2008, Los Zetas made a deal with ex-Sinaloa cartel commanders, the Beltrán-Leyva brothers and since then, became rivals of their former employer/partner, the Gulf Cartel.
In early 2010 the Zetas made public their split from the Gulf Cartel and began a bloody war with the Gulf Cartel over control of northeast Mexico's drug trade routes. This war has resulted in the deaths of thousands of cartel members and suspected members. Furthermore, due to alliance structures, the Gulf Cartel-Los Zetas conflict drew in other cartels, namely the Sinaloa Cartel which fought the Zetas in 2010 and 2011.
The Zetas are notorious for targeting civilians, including the mass murder of 72 migrants in the San Fernando massacre.
The Zetas involved themselves in more than drug trafficking and have also been connected to human trafficking, pipeline trafficked oil theft, extortion, and trading unlicensed CDs. Their criminal network is said to reach far from Mexico including into Central America, the U.S. and Europe.
On July 15, 2013, the Mexican Navy arrested the top Zeta boss Miguel Treviño Morales.
In recent times, Los Zetas have experienced severe fragmentation and seen its influence diminish. As of December 2016, two subgroups calling themselves Los Zetas Grupo Bravo (Group Bravo) and Zetas Vieja Escuela (Old School Zetas) formed an alliance with the Gulf Cartel against a group known as El Cartel del Noreste (The Cartel of the Northeast).
==== La Familia Cartel ====
La Familia Michoacana was a major Mexican drug cartel based in Michoacán between at least 2006 and 2011. It was formerly allied to the Gulf Cartel and Los Zetas, but split off and became an independent organization.
In 2009–10, a counter-narcotics offensive by Mexican and U.S. government agencies produced the arrest of at least 345 suspected La Familia members in the U.S., and the incorrectly presumed death of one of the cartel's founders, Nazario Moreno González, on December 9, 2010. The cartel then divided into the Knights Templar Cartel and a José de Jesús Méndez Vargas-led faction, which kept the name La Familia. Following the cartel's fragmentation in late 2010 and early 2011, the La Familia Cartel under Méndez Vargas fought the Knights Templar Cartel but on June 21, 2011, Méndez Vargas was arrested by Mexican authorities and in mid-2011 the attorney general in Mexico (PGR) stated that La Familia Cartel had been "exterminated", leaving only the splinter group, the Knights Templar Cartel.
In February 2010, La Familia forged an alliance with the Gulf Cartel against Los Zetas and Beltrán-Leyva Cartel.
==== Knights Templar ====
The Knights Templar drug cartel (Spanish: Caballeros Templarios) was created in Michoacán in March 2011 after the death of the charismatic leader of La Familia Michoacana cartel, Nazario Moreno González. The Cartel is headed by Enrique Plancarte Solís and Servando Gómez Martínez who formed the Knights Templar due to differences with José de Jesús Méndez Vargas, who had assumed leadership of La Familia Michoacana.
After the emergence of the Knights Templar, sizable battles flared up during the spring and summer months between the Knights Templar and La Familia. The organization has grown from a splinter group to a dominant force over La Familia, and at the end of 2011, following the arrest of José de Jesús "El Chango" Méndez Vargas, leader of La Familia, the cartel appeared to have taken over the bulk of La Familia's operations in Mexico and the U.S. In 2011 the Knights Templar appeared to have aligned with the Sinaloa Federation in an effort to root out the remnants of La Familia and to prevent Los Zetas from gaining a more substantial foothold in the Michoacán region of central Mexico.
Alliances or agreements between drug cartels have been shown to be fragile, tense and temporary.
Mexican drug cartels have increased their co-operation with U.S. street and prison gangs to expand their distribution networks within the U.S.
On March 31, 2014, Enrique Plancarte Solís, a high-ranking leader in the cartel, was killed by the Mexican Navy.
On September 6, 2016, a Mexican police helicopter was shot down by a gang, killing four people. The police were conducting an operation against criminal groups and drug cartels in Apatzingán, including the Knights Templar Cartel.
==== CJNG ====
The Jalisco New Generation Cartel (Spanish: Cártel de Jalisco Nueva Generación, CJNG, Los Mata Zetas and Los Torcidos) is a Mexican criminal group based in Jalisco and headed by Nemesio Oseguera Cervantes ("El Mencho"), one of Mexico's most-wanted drug lords. Jalisco New Generation Cartel started as one of the splits of Milenio Cartel, beside La Resistencia. La Resistencia accused CJNG of giving up Oscar Valencia (El Lobo) to the authorities and called them Los Torcidos (The Twisted Ones). Jalisco Cartel defeated La Resistencia and took control of Millenio Cartel's smuggling networks. Jalisco New Generation Cartel expanded its operation network from coast to coast in only six months, making it one of the criminal groups with the greatest operating capacity in Mexico as of 2012. Through online videos, the Jalisco New Generation Cartel has tried to seek society's approval and tacit consent from the Mexican government to confront Los Zetas by posing as a "righteous" and "nationalistic" group. Such claims have stoked fears that Mexico, just like Colombia a generation before, may be witnessing the rise of paramilitary drug gangs. By 2018 the CJNG was hyped as the most powerful cartel in Mexico. though Insight Crime has said the Sinaloa Cartel is still the most powerful cartel and called the CJNG its closest rival. In 2019, the group was greatly weakened by infighting, arrests of senior operatives, and a war with the Sinaloa Cartel and its allies.
==== Nueva Plaza Cartel ====
CJNG co-founder Érick Valencia Salazar (alias "El 85") and former high-ranking CJNG leader Enrique Sánchez Martínez (alias "El Cholo") had also departed from the CJNG and formed a rival cartel known as the Nueva Plaza Cartel. Since 2017, the cartel has been engaged in a war with the CJNG. The Nueva Plaza Cartel has also become aligned with the Sinaloa Cartel to fight the CJNG.
== Cartel propaganda and messaging ==
Criminal organizations in Mexico are heavily involved in information warfare. These groups have a variety of tools they use to influence public opinion, such as food handouts, sponsoring of community development, social media posts, filmed press release-style video communications, physical narco messages, narco corridos, and private messaging such as WhatsApp chats. The goal of narco propaganda is to influence public opinion, threaten or accuse rivals, and generally communicate with those outside their organization. Many cartels have controlled the information environment by threatening journalists, bloggers, and others who speak out against them.
Their primary method of communication is the physical narco message, which can range from professionally-printed banners to hastily written messages on cardboard or paper. They are commonly displayed in public places, such as bridges, town centers, and highways. Many are often also left at crime scenes, such as after an assassination.
Some cartels, such as the CJNG, have sophisticated propaganda arms capable of producing large numbers of professional styled narco messages to advance their interests. These messages use stock phrases or slogans, cartel logos, and have cohesive messaging.
In 2011, then President Felipe Calderón (2006–2012) met with Mexico's major media outlets to discuss their role in what he argued was sensationalizing the violence and providing free press coverage to cartels and their messages. They agreed to limit coverage of the drug war and the messaging of criminal groups.
== Paramilitaries ==
Paramilitary groups work alongside cartels to provide protection. This protection began with a focus on maintaining the drug trade, then moved to theft from other valuable industries such as oil and mining. It has been suggested that the rise in paramilitary groups coincides with a loss of security within the government. These paramilitary groups came about in a number of ways. First, waves of elite armed forces and government security experts have left the government to join the side of the cartels, responding to large bribes and an opportunity for wealth they may not have received in government positions. One such paramilitary group, Los Zetas, employed military personnel to create one of the largest groups in Mexico. Some of the elite armed forces members who join paramilitaries are trained in the Western Hemisphere Institute for Security Cooperation (WHINSEC, formerly known as the School of the Americas). One theory is that the paramilitaries have sprung out of deregulation of the Mexican army, which has been slowly replaced by private security firms. Paramilitaries, including the Zetas, have now entered uncharted territories. Branching out of just protecting drug cartels, paramilitary groups have entered many other financially profitable industries, such as oil, gas, kidnapping, and counterfeiting electronics. There has been a complete and total loss of control by the government, and the only response has been to increase army presence, notably an army whose officials are often on the drug cartels' payroll. The United States has stepped in to offer support in the "War on Drugs" through funding, training and military support, and transforming the Mexican judicial system to parallel the American system.
== Women ==
Women in the Mexican drug war have been participants and civilians. They have served for and/or been harmed by all belligerents. There have been female combatants in the military, police, cartels, and gangs. Women officials, judges, prosecutors, lawyers, paralegals, reporters, business owners, social media influencers, teachers, and non-governmental organizations directors and workers have also been involved in different capacities. Women citizens and foreigners, including migrants, have been raped, tortured, and murdered in the conflict.
Women's involvement in the cartel is noticeably less than males, but they do play an important role nonetheless. Often, because no one would suspect a woman to commit such a serious crime, it makes them the perfect smuggler. Women smugglers could drive up to a checkpoint with a car full of drugs, and more often than not, no one would suspect them of anything.
Women may find allure in a criminal lifestyle for the sense of freedom. Mexico already has a male-dominated culture, but by working in the drug trade, they can be empowered and even liberated. If women cannot obtain freedom through legal means, then it is possible they will use illegal avenues to achieve the same goal.
Cartels and gangs fighting in the conflict carry out sex trafficking in Mexico as an alternative source of profits. Some members of the criminal organizations also abduct women and girls to use as their personal sex slaves and carry out sexual assault of migrants from Latin America to the United States.
== Firearms ==
=== Smuggling of firearms ===
Mexicans have a constitutional right to own firearms, but legal purchase from the single Mexican gun shop in Mexico City is extremely difficult. Firearms that make their way to Mexico come primarily from the American civilian market. Most grenades and rocket-launchers are smuggled through Guatemalan borders, as leftovers from past conflicts in Nicaragua. Some grenades are also smuggled from the U.S. to Mexico or stolen from the Mexican military.
The most common weapons used by the cartels are the AR-15, M16, M4, AK-47, AKM and Type 56 assault rifles. Handguns are very diverse, but the FN Five-seven (dubbed Matapolicías or Cop-killer by criminals) is a popular choice due to its armor-piercing capability. Grenade launchers are known to have been used against Mexican security forces, while H&K G36s and M4 carbines with M203 grenade launchers have been confiscated.
==== Gun origins ====
Some researchers have asserted that most weapons and arms trafficked into Mexico come from gun dealers in the United States. There is strong evidence for this conclusion, and there is a geographic coincidence between the supposed American origin of the firearms and the places where these weapons are seized, mainly in the northern Mexican states. Most grenades and rocket-launchers are smuggled through Guatemalan borders from Central America. Some grenades are also smuggled from the US to Mexico or stolen from the Mexican military. United States Department of Homeland Security (DHS) officials have stated that the statistic is misleading: out of approximately 30,000 weapons seized in drug cases in Mexico in 2004–2008, 7,200 appeared to be of U.S. origin, approximately 4,000 were found in ATF manufacturer and importer records, and 87 percent of those—3,480—originated in the United States.
In an effort to control smuggling of firearms, the U.S. government is assisting Mexico with technology, equipment and training. Project Gunrunner was one such effort between the U.S. and Mexico to collaborate in tracing Mexican guns which were manufactured in or imported legally to the U.S.
In 2008, it was falsely reported that ninety percent of arms either captured in Mexico or interdicted were from the United States. The DHS and others have dismissed these claims, pointing that the Mexican sample submitted for ATF tracing is the fraction of weapons seized that appear to have been made in the U.S. or imported into the U.S.
In 2015, official reports of the U.S. government and the Bureau of Alcohol, Tobacco, Firearms and Explosives (ATF) revealed that over the last years, Mexican cartels improved their firearm power, and that 71% of their weapons come from the U.S. Many of those guns were manufactured in Romania and Bulgaria, and then imported into the U.S. The Mexican cartels acquire those firearms mainly in the southern states of Texas, Arizona and California. After the United States, the top five countries of origin of firearms seized from Mexico were Spain, China, Italy, Germany and Romania. These five countries represent 17% of firearms smuggled into Mexico. Some cartels such as the Beltrán Leyva Cartel use counterfeit M16s made with aftermarket parts.
==== Project Gunrunner ====
ATF Project Gunrunner has stated that the official objective is to stop the sale and export of guns from the United States into Mexico in order to deny Mexican drug cartels the firearms considered "tools of the trade". In February 2011, it brought about a scandal when the project was accused of accomplishing the opposite by ATF permitting and facilitating "straw purchase" firearm sales to traffickers, and allowing the guns to "walk" and be transported to Mexico. Allegedly, the ATF allowed to complete the transactions to expose the supply chain and gather intelligence. It has been established that this operation violated long-established ATF policies and practices and that it is not a recognized investigative technique. Several of the guns sold under the Project Gunrunner were recovered from crime scenes in Arizona, and at crime scenes throughout Mexico, resulting in considerable controversy.
One notable incident was the "Black Swan operation" where Joaquín Guzmán Loera was finally captured. The ATF confirmed that one of the weapons the Mexican Navy seized from Guzmán's gunmen was one of the many weapons that were "lost" during the Project Gunrunner.
Many weapons from Project Gunrunner were found in a secret compartment in the "safe house" of José Antonio Marrufo "El Jaguar", one of Guzmán's most sanguinary lieutenants. He is accused of many killings in Ciudad Juárez, including the notorious massacre of 18 patients at a "El Aliviane" rehabilitation center. It is believed that Marrufo armed his gunmen with weapons purchased in the United States.
== Operations ==
=== Operation Michoacán ===
Although violence between drug cartels had been occurring long before the war began, the government held a generally passive stance regarding cartel violence in the 1990s and early 2000s. That changed on December 11, 2006, when newly elected President Felipe Calderón sent 6,500 Federal troops to the state of Michoacán to end drug violence there. This action is regarded as the first major operation against organized crime, and became the starting point of the war between the government and the drug cartels. Calderón escalated his anti-drug campaign, in which there are now about 45,000 troops involved in addition to state and federal police forces. In 2010, Calderón said that the cartels seek "to replace the government" and "are trying to impose a monopoly by force of arms, and are even trying to impose their own laws".
As of 2011, Mexico's military captured 11,544 people who were believed to have been involved with the cartels and organized crime. In the year prior, 28,000 individuals were arrested on drug-related charges. The decrease in eradication and drug seizures, as shown in statistics calculated by federal authorities, poorly reflects Calderón's security agenda. Since the war began, over forty thousand people have been killed as a result of cartel violence. During Calderón's presidential term, the murder rate of Mexico increased dramatically.
Although Calderón set out to end the violent warfare between rival cartel leaders, critics argue that he inadvertently made the problem worse. The methods that Calderón adopted involved confronting the cartels directly. These aggressive methods have resulted in public killings and torture from both the cartels and the country's own government forces, which aids in perpetuating the fear and apprehension that the citizens of Mexico have regarding the war on drugs and its negative stigma. As cartel leaders are removed from their positions, by arrest or death, power struggles for leadership in the cartels have become more intense, resulting in enhanced violence within the cartels themselves.
Calderón's forces concentrate on taking down cartel members that have a high ranking in the cartel in an attempt to take down the whole organization. The resulting struggle to fill the recently vacated position is one that threatens the existence of many lives in the cartel. Typically, many junior-level cartel members then fight amongst one another, creating more and more chaos. The drug cartels are more aggressive and forceful now than they were in the past and at this point, the cartels hold much of the power in Mexico. Calderón relies heavily on the military to defend and fight against cartel activity. Calderón's military forces have yet to yield significant results in dealing with the violent cartels due in part to the fact that many police working for the Mexican government are suspected of corruption. There is suspicion that cartels have corrupted and infiltrated the military at a high level, influencing many generals and officers. Mexico's National Human Rights Commission has received nearly 5,800 complaints regarding military abuse since the beginning of the drug war in 2006. Additionally, the National Human Rights Commission has completed nearly 90 in-depth reports since 2007, addressing the many human rights violations of civilians that have occurred while the military officers were actively participating in law enforcement activities.
Violence in May 2012 in which nearly 50 bodies were found on a local highway between the Mexico–United States border and Monterrey has led to the arrests of 4 high-ranking Mexican military officials. These officials were suspected of being on the cartel payrolls and alerting them before military action against them. Such actions demonstrate that Calderón's significant military offensive will continue to reveal mixed results until the military itself is rid of the corrupting influences of the cartels whom they supposedly aim to persecute.
=== Escalation (2008–12) ===
In April 2008, General Sergio Aponte, the man in charge of the anti-drug campaign in the state of Baja California, made a number of allegations of corruption against the police forces in the region. Among his allegations, Aponte stated that he believed Baja California's anti-kidnapping squad was actually a kidnapping team working in conjunction with organized crime, and that bribed police units were used as bodyguards for drug traffickers.
These accusations sent shock waves through state government. Many of the more than 50 accused officials quit or fled. The progress against drug cartels in Mexico has been hindered by bribery, intimidation, and corruption; four months later the General was relieved of his command.
On April 26, 2008, a major battle took place between members of the Tijuana and Sinaloa cartels in the city of Tijuana, Baja California, that left 17 people dead.
In March 2009, President Calderón called in an additional 5,000 Mexican Army troops to Ciudad Juárez. The DHS also said that it was considering using state National Guard troops to help the U.S. Border Patrol counter the threat of drug violence in Mexico from spilling over the border into the U.S. The governors of Arizona and Texas have encouraged the federal government to use additional National Guard troops from their states to help those already there supporting state law enforcement efforts against drug trafficking.
According to the National Drug Intelligence Center, Mexican cartels are the predominant smugglers and wholesale distributors of South American cocaine and Mexico-produced cannabis, methamphetamine and heroin. Mexico's cartels have existed for some time, but have become increasingly powerful in recent years with the demise of the Medellín and Cali cartels in Colombia. The Mexican cartels are expanding their control over the distribution of these drugs in areas controlled by Colombian and Dominican criminal groups, and it is now believed they control most of the illegal drugs coming into the U.S.
No longer mere intermediaries for Colombian producers, Mexican cartels are now powerful organized-crime syndicates that dominate the drug trade in the Americas.
Mexican cartels control large swaths of Mexican territory and dozens of municipalities, and they exercise increasing influence in Mexican electoral politics. Cartels have waged violent turf battles over control of key smuggling corridors from Matamoros to San Diego. Mexican cartels employ hitmen and groups of enforcers, known as sicarios. The U.S. Drug Enforcement Administration reports that the Mexican drug cartels operating today along the border are far more sophisticated and dangerous than any other organized criminal group in U.S. law enforcement history. The cartels use grenade launchers, automatic weapons, body armor, Kevlar helmets, and sometimes unmanned aerial vehicles. Some groups have also been known to use improvised explosive devices (IEDs).
Casualty numbers have escalated significantly over time. According to a Stratfor report, the number of drug-related deaths in 2006 and 2007 (2,119 and 2,275) more than doubled to 5,207 in 2008. The number further increased substantially over the next two years, from 6,598 in 2009 to over 11,000 in 2010. According to data of the Mexican government, the death numbers are even higher: 9,616 in 2009, 15,273 in 2010, coming to a total of 47,515 killings since their military operations against drug cartels began in 2006, as stated in the government's report of January 2012.
On October 7, 2012, the Mexican Navy responded to a civilian complaint reporting the presence of armed gunmen in Sabinas, Coahuila. Upon the navy's arrival, the gunmen threw grenades at the patrol from a moving vehicle, triggering a shootout that left Lazcano and another gunman dead and one marine slightly wounded. The vehicle was found to contain a grenade launcher, 12 grenades, possibly a rocket-propelled grenade launcher and two rifles, according to the navy. The Navy confirmed his death through fingerprint verification and photographs of his corpse before handing the body to the local authorities. Lazcano is the most powerful cartel leader to be killed since the start of Mexico's drug war in 2006, according to Reuters.
This death came just hours after the navy arrested a high-ranking Zeta member in Nuevo Laredo, Tamaulipas, Salvador Alfonso Martínez Escobedo.
The death of Lazcano benefited three parties; the Mexican Navy, who scored a significant blow to organized crime with the death of Lazcano, Miguel Treviño Morales, who rose as the "uncontested" leader of Los Zetas, and Joaquín "El Chapo" Guzmán, the leader of the Sinaloa Cartel and the main rival of Los Zetas. El Chapo was perhaps the biggest winner of the three, since his primary goal was to take over the smuggling routes in Nuevo Laredo, Tamaulipas, the headquarters of Treviño Morales. If the body had not been stolen, it would also have been a symbolic victory for Felipe Calderón, who could have said that his administration took down one of the founders and top leaders of Los Zetas and consequently boost the morale of the Mexican military.
== Effects in Mexico ==
=== Casualties ===
It is often not clear what deaths are part of the Mexican drug war versus general criminal homicides, and different sources give different estimates. Casualties are often measured indirectly by estimated total deaths from organized crime in Mexico. This amounts to about 115,000 people in the years 2007–2018. From 2018 to 2020, it was estimated that there were 11,400 reports of gang violence, and over 80% of the attacks targeted civilians, resulting in 13,000 related-deaths during the period.
=== Violence ===
The Mexican attorney general's office has claimed that 9 of 10 victims of the Mexican drug war are members of organized-crime groups, although this figure has been questioned by other sources. Deaths among military and police personnel are an estimated 7% of the total. The states that suffer from the conflict most are Baja California, Guerrero, Chihuahua, Michoacán, Tamaulipas, Nuevo León and Sinaloa.
By January 2007, these various operations had extended to the states of Guerrero as well as the so-called "Golden Triangle States" of Chihuahua, Durango, and Sinaloa. In the following February the states of Nuevo León and Tamaulipas were included as well.
On July 10, 2008, the Mexican government announced plans to nearly double the size of its Federal Police force to reduce the role of the military in combating drug trafficking. The plan, known as the Comprehensive Strategy Against Drug Trafficking, involved purging local police forces of corrupt officers. Elements of the plan included a massive police recruiting and training effort intended to reduce the country's dependence in the drug war on the military.
On July 16, 2008, the Mexican Navy intercepted a 10-meter long narco-submarine travelling about 200 kilometers off the southwest of Oaxaca; in a raid, Special Forces rappelled from a helicopter onto the deck of the submarine and arrested four smugglers before they could scuttle their vessel. The vessel was found to be loaded with 5.8 tons of cocaine and was towed to Huatulco, Oaxaca, by a Mexican Navy patrol boat.
One escalation in this conflict is the traffickers' use of new means to claim their territory and spread fear. Cartel members have broadcast executions on YouTube and on other video sharing platforms or shock sites. Cartels have also hung banners on streets stating demands and warnings.
The 2008 Morelia grenade attacks took place on September 15, 2008, when two hand grenades were thrown onto a crowded plaza, killing ten people and injuring more than 100. Some see these efforts as intended to sap the morale of government agents assigned to crack down on the cartels; others see them as an effort to let citizens know who is winning the war. At least one dozen Mexican norteño musicians have been murdered. Most of the victims performed what are known as narcocorridos, popular folk songs that tell the stories of the Mexican drug trade—and celebrate its leaders as folk heroes.
Increasing violence has jeopardized foreign investment in Mexico. Finance Minister, Agustín Carstens, said that the deteriorating security alone is reducing gross domestic product annually by 1% in Mexico, Latin America's second-largest economy.
Teachers in the Acapulco region were "extorted, kidnapped and intimidated" by cartels, including death threats demanding money. They went on strike in 2011.
=== Government corruption ===
Mexican cartels advance their operations, in part, by corrupting or intimidating law enforcement officials. Mexican municipal, state, and federal government officials, along with the police forces, often work together with the cartels in an organized network of corruption. A Pax Mafioso, is a specific example of corruption which guarantees a politician votes and a following in exchange for not impeding a particular cartel.
The International Narcotics Control Board (INCB) reports that although the central government of Mexico has made concerted efforts to reduce corruption in recent years, it remains a serious problem. Some agents of the Federal Investigations Agency (AFI) are believed to work as enforcers for various cartels, and the Attorney General (PGR) reported in December 2005 that nearly 1,500 of AFI's 7,000 agents were under investigation for suspected criminal activity and 457 were facing charges.
In recent years, the federal government conducted purges and prosecution of police forces in Nuevo Laredo, Michoacán, Baja California and Mexico City. The anti-cartel operations begun by President Calderón in December 2006 includes ballistic checks of police weapons in places where there is concern that police are also working for the cartels. In June 2007, President Calderón purged 284 federal police commanders from all 31 states and the Federal District.
Under the 'Cleanup Operation' performed in 2008, several agents and high-ranking officials have been arrested and charged with selling information or protection to drug cartels; some high-profile arrests were: Victor Gerardo Garay Cadena, (chief of the Federal Police), Noé Ramírez Mandujano (ex-chief of the Organized Crime Division (SEIDO)), José Luis Santiago Vasconcelos (ex-chief of the Organized Crime Division (SEIDO)), and Ricardo Gutiérrez Vargas who is the ex-director of Mexico's Interpol office. In January 2009, Rodolfo de la Guardia García, ex-director of Mexico's Interpol office, was arrested. Julio César Godoy Toscano, who was just elected July 6, 2009, to the lower house of Congress, is charged with being a top-ranking member of La Familia Michoacana drug cartel and of protecting this cartel. He is now a fugitive.
In May 2010, an NPR report collected allegations from dozens of sources, including U.S. and Mexican media, Mexican police officials, politicians, academics, and others, that Sinaloa Cartel had infiltrated and corrupted the Mexican federal government and the Mexican military by bribery and other means. According to a report by the U.S. Army Intelligence section in Leavenworth, over a six-year period, of the 250,000 soldiers in the Mexican Army, 150,000 deserted and went into the drug industry.
The 2010 NPR report also stated that the Sinaloa Cartel was colluding with the government to destroy other cartels and protect itself and its leader, 'Chapo'. Mexican officials denied any corruption in the government's treatment of drug cartels. Cartels had previously been reported as difficult to prosecute "because members of the cartels have infiltrated and corrupted the law enforcement organizations that are supposed to prosecute them, such as the Office of the Attorney General."
=== Effects on human rights ===
The drug control policies Mexico has adopted to prevent drug trafficking and to eliminate the power of the drug cartels have adversely affected the human rights situation in the country. These policies have given the responsibilities for civilian drug control to the military, which has the power to not only carry out anti-drug and public security operations but also enact policy. According to the U.S. State Department, the police and the military in Mexico were accused of committing serious human rights violations as they carried out government efforts to combat drug cartels.
Some groups are especially vulnerable to human rights abuses collateral to drug law enforcement. Specifically in northern border states that have seen elevated levels of drug-related violence, human rights violations of injection drug users (IDUs) and sex workers by law enforcement personnel include physical and sexual violence, extortion, and targeting for accessing or possession of injection equipment or practicing sex work, although these activities are legal. Such targeting is especially deleterious because members of these marginalized communities often lack the resources and social or political capital to enforce their rights.
Immense power in the executive branch and corruption in the legislative and judiciary branches also contribute to the worsening of Mexico's human rights situation, leading to such problems as police forces violating basic human rights through torture and threats, the autonomy of the military and its consequences and the ineffectiveness of the judiciary in upholding and preserving basic human rights. Some of the forms of human rights violations in recent years presented by human rights organizations include illegal arrests, secret and prolonged detention, torture, rape, extrajudicial execution, and fabrication of evidence.
Drug policy fails to target high-level traffickers. In the 1970s, as part of the international Operation Condor, the Mexican government deployed 10,000 soldiers and police to a poverty-stricken region in northern Mexico plagued by drug production and leftist insurgency. Hundreds of peasants were arrested, tortured, and jailed, but no major drug traffickers were captured.
The emergence of internal federal agencies that are often unregulated and unaccountable also contributes to the occurrence of human rights violations. The AFI of Mexico had been involved with numerous human rights violation cases involving torture and corruption. In one case, detainee Guillermo Velez Mendoza died while in the custody of AFI agents. The AFI agent implicated in his death was arrested and escaped on bail.
Similarly, nearly all AFI agents evaded punishment and arrest due to the corrupt executive and judiciary system and the supremacy of these agencies. The Attorney General's Office reported in December 2005 that one-fifth of its officers were under investigation for criminal activity, and that nearly 1,500 of AFI's 7,000 agents were under investigation for suspected criminal activity and 457 were facing charges. The AFI was finally declared a failure and was disbanded in 2009.
Ethnic prejudices have also emerged in the drug war, and indigenous communities have been targeted by the police, military, drug traffickers and the justice system. According to the National Human Rights Commission (Mexico) (Comisión Nacional de los Derechos Humanos-CNDH), nearly one-third of the indigenous prisoners in Mexico in 2001 were in prison for federal crimes, which are mostly drug-related.
Another major concern is the lack of implementation of the Leahy Law in U.S. and the consequences of that in worsening the human rights situation in Mexico. Under this U.S. law, no member or unit of a foreign security force that is credibly alleged to have committed a human rights violation may receive U.S. security training. It is alleged that the U.S., by training the military and police force in Mexico, is in violation of the Leahy Law. In this case, the U.S. embassy officials in Mexico in charge of human rights and drug control programs are blamed with aiding and abetting these violations. In December 1997, a group of heavily armed Mexican special forces soldiers kidnapped twenty young men in Ocotlan, Jalisco, brutally torturing them and killing one. Six of the implicated officers had received U.S. training as part of the Grupo Aeromóvil de Fuerzas Especiales (GAFE) training program.
=== Effects on public health ===
As a result of "spillover" along the U.S.-bound drug trafficking routes and more stringent border enforcement, Mexico's northern border states have seen increased levels of drug consumption and abuse, including elevated rates of drug injection 10 to 15 times the national average. These rates are accompanied by mounting rates of HIV and STIs among injection drug users (IDUs) and sex workers, reaching a 5.5% prevalence in cities such as Tijuana and Ciudad Juárez, which also report STI rates of 64% and 83%, respectively. Violence and extortion of IDUs and sex workers directly and indirectly elevate the levels of risk behavior and poor health outcomes among members of these groups. Marginalization of these vulnerable groups by way of physical and sexual violence and extortion by police threatens the cross-over of infection from high-prevalence groups to the general population. In particular, decreased access to public health services such as syringe exchange programs and confiscation of syringes can precipitate a cascade of health harms. Geographic diffusion of epidemics from the northern border states elsewhere is also possible with the rotation of police and military personnel stationed in drug conflict areas with high infection prevalence.
=== Journalists and the media ===
The increase in violence related with organized crime has significantly deteriorated the conditions in which local journalism is practiced. In the first years of the 21st century, Mexico was considered the most dangerous country in the world to practice journalism, according to groups like the National Human Rights Commission, Reporters Without Borders, and the Committee to Protect Journalists. Between 2000 and 2012, several dozen journalists, including Miguel Ángel López Velasco, Luis Carlos Santiago, and Valentín Valdés Espinosa, were murdered there for covering narco-related news.
The offices of Televisa and local newspapers have been bombed. The cartels have also threatened to kill news reporters in the U.S. who have done coverage on the drug violence. Some media networks simply stopped reporting on drug crimes, while others have been infiltrated and corrupted by drug cartels. In 2011, Notiver journalist Miguel Angel Lopez Velasco, his wife, and his son were murdered in their home.
About 74 percent of the journalists killed since 1992 in Mexico have been reporters for print newspapers, followed in number by Internet media and radio at about 11 percent each. Television journalism only includes 4 percent of the deaths. These numbers are not proportional to the audience size of the different mediums; most Mexican households have a television, a large majority have a radio, but only a small number have the internet, and the circulation numbers for Mexican newspapers are relatively low.
Since harassment neutralized many traditional media outlets, anonymous, sensationalized blogs like Blog del Narco took on the role of reporting on events related to the drug war. The drug cartels responded by murdering bloggers and social media users. Twitter users have been tortured and killed for posting and denouncing information of the drug cartels' activities. In September 2011, user NenaDLaredo of the website Nuevo Laredo Envivo was allegedly murdered by Los Zetas.
In May 2012, several journalist murders occurred in Veracruz. Regina Martinez of Proceso was murdered in Xalapa. A few days later, three Veracruz photojournalists were tortured and killed and their dismembered bodies were dumped in a canal. They had worked for various news outlets, including Notiver, Diario AZ, and TV Azteca. Human rights groups condemned the murders and demanded the authorities investigate the crimes.
=== Murders of politicians ===
Since the start of the Mexican drug war in 2006, the drug trafficking organizations have slaughtered their rivals, killed policemen, and have increasingly targeted politicians – especially local leaders. Most of the places where these politicians have been killed are areas plagued by drug-related violence. Part of the strategy used by criminal groups behind the killings of local figures is the weakening of the local governments. For example, María Santos Gorrostieta Salazar, former mayor of Tiquicheo, Michoacán, who had survived three earlier assassination attempts and the murder of her husband, was abducted and beaten to death in November 2012. Extreme violence puts politicians at the mercy of the cartels, allowing them to increase their control of government structures and expand their influence.
In addition, because mayors usually appoint local police chiefs, they are seen by the cartels as key assets in their criminal activities to control the police forces in their areas of influence. The cartels also seek to control the local governments to win government contracts and concessions; these "public works" help them ingrain themselves in the community and gain the loyalty and respect of the communities in which they operate. Politicians are usually targeted for three reasons: (1) Political figures who are honest pose a direct threat to organized crime, and are consequently killed by the cartels; (2) Politicians make arrangements to protect a certain cartel and are killed by a rival cartel; and (3) A cartel kills politicians to heat up the turf of the rival cartel that operates in the area.
=== Massacres and exploitation of migrants ===
Cartels have engaged in kidnapping, ransom, murder, robbery, and extortion of migrants traveling from Central America through Mexico on their way to the United States and Canada. Cartels have also forced migrants to join their organization and work for them, a situation that has been described as slavery. Mass graves have been also discovered in Mexico containing bodies of migrants. In 2011, 177 bodies were discovered in a mass grave in San Fernando, Tamaulipas, the same area where the bodies of 72 migrants were discovered in 2010, where most victims "died of blunt force trauma to the head."
Cartels have also infiltrated the Mexican government's immigration agencies, and attacked and threatened immigration officers. The National Human Rights Commission of Mexico (Comisión Nacional de los Derechos Humanos, CNDH) said that 11,000 migrants had been kidnapped in 6 months in 2010 by drug cartels.
=== Human trafficking ===
There are documented links between the drug cartels and human trafficking for forced labor, forced prostitution, and rape. The wife of a drug lord described a system in which young girls became prostitutes and then were forced to work in drug factories. In the early 2010s, Los Zetas reportedly began to move into the prostitution business (including the prostitution of children) after previously only supplying women to already existing networks.
The U.S. State Department says that the practice of forced labor in Mexico is larger in extent than forced prostitution. Mexican journalists like Lydia Cacho have been threatened and forced into exile for reporting on these events.
== Effects internationally ==
=== Europe ===
Improved cooperation between Mexico and the U.S. has led to the arrests of hundreds of Sinaloa Cartel suspects in U.S. cities and towns, but the U.S. market is being eclipsed by booming demand for cocaine in Europe, where users now pay twice the going U.S. rate. In 2008, U.S. Attorney General Michael Mukasey announced that an international drug interdiction operation, Project Reckoning, involving law enforcement in the United States, Italy, Canada, Mexico and Guatemala had netted more than 500 organized crime members involved in the cocaine trade. The announcement highlighted the Italian-Mexican cocaine connection.
Concerns about European security and the trafficking of drugs through the European continent have grown in recent years, and, in December 2022, Europol (the law enforcement agency of the EU) and the DEA released a joint report on the situation involving Mexican drug trafficking through the EU.
In December 2011, the government of Spain remarked that Mexican cartels had multiplied their operations in that country, becoming the main entry point of cocaine into Europe.
In 2012, it was reported that Mexican drug cartels had joined forces with the Sicilian Mafia, when Italian officials unearthed information that Palermo's black market, along with other Italian ports, was used by Mexico's drug cartels as a conduit to bring drugs to the European market, in which they had been trafficking drugs, particularly cocaine, throughout the Atlantic Ocean for over 10 years to Europe.
In 2016, investigation into transatlantic drug trafficking revealed that the Kinahan Clan, Ireland's largest drug trafficker, among other prominent drug traffickers in Mexico, South America, West Africa, and Europe had created an informal "Super Cartel" in an attempt to improve business and increase buyers. However, the extent of the prevalence of the Super Cartel is largely unknown, since many trafficking relationships may exist without any real central plan.
The 2017 guest list to the wedding of Daniel Kinahan led to the discovery of most of the key players in the Super Cartel Alliance. Those that have been most investigated include top underworld figures such as: Ridouan Taghi, Ricardo Riquelme Vega, aka El Rico, caged assassin Noufal Fassih and Italian Camorra boss Raffaele Imperiale.
In 2022/2023 - In January 2023, two alleged drug lords said to be kingpins in the mostly European Super Cartel were released just two months after being arrested in Dubai. Edin Gacanin, (Tito) a Dutch-Bosnian national described by the US Drug Enforcement Administration (DEA) as one of the top 50 drug traffickers in the world, and Zuhair Belkhair, a Dutch-Moroccan accused of trafficking huge amounts of cocaine through the port of Rotterdam, were among 49 suspects arrested in a massive, highly publicised, international police operation. Most of the others arrested are awaiting trial or have pled guilty.
=== Guatemala ===
The Mexican Army crackdown has driven some cartels to seek a safer location for their operations across the border in Guatemala, attracted by corruption, weak policing and its position on the overland smuggling route. The smugglers pick up drugs from small planes that land at private airstrips hidden in the Guatemalan jungle. The cargo is then moved up through Mexico to the U.S. border. Guatemala has also arrested dozens of drug suspects and torched huge cannabis and poppy fields. The U.S. government sent speedboats and night-vision goggles under a regional drug aid package.
In February 2009, Los Zetas threatened to kill the president of Guatemala, Álvaro Colom. On March 1, 2010, Guatemala's chief of national police and the country's top anti-drugs official were arrested over alleged links to drug trafficking. A report from the Brookings Institution warns that, without proactive, timely efforts, the violence will spread throughout the Central American region.
According to the United States government, Los Zetas control 75% of Guatemala through violence, political corruption and infiltration in the country's institutions. Sources mentioned that Los Zetas gained ground in Guatemala after they killed several high-profile members and the supreme leader of Los Leones, an organized crime group from Guatemala.
=== West Africa ===
At least nine Mexican and Colombian drug cartels have established bases in 11 West African nations. They have reportedly worked closely with local criminal gangs to carve out a staging area for access to the lucrative European market. The Colombian and Mexican cartels have discovered that it is easier to smuggle large loads into West Africa and then break that up into smaller shipments to Europe – mostly Spain, the United Kingdom and France. Higher demand for cocaine in Western Europe in addition to North American interdiction campaigns has led to dramatically increased trafficking in the region: nearly 50% of all non-U.S. bound cocaine, or about 13% of all global flows, is now smuggled through West Africa.
=== Canada ===
The Mexican Army severely curtailed the ability of the Mexican drug cartels to move cocaine inside the U.S. and Canada, prompting an upsurge in gang violence in Vancouver in 2009, where the cocaine price has increased from $23,300 to almost $39,000 per kilo as the Canadian drug markets experienced prolonged shortages. As evidence of this pressure, the U.S. government stated the amount of cocaine seized on U.S. soil dropped by 41 percent between early 2007 and mid-2008. Since 2009, Vancouver has become the Mexican drug cartels' main center of operations in Canada.
=== South America ===
Patricio Pazmiño, the Interior Minister of Ecuador, stated that the February 2021 riots at three prisons that took 79 lives were related to Mexican and Colombian drug gangs. The government intercepted a record 126 tons of cocaine in 2020.
On September 8, 2021, National Prosecutor Jorge Abbott declared that Mexican cartels were attempting to establish themselves in Chile. It is known that Sinaloa Cartel has attempted to use Chile as a transit route for the shipment of cocaine to Rotterdam in the Netherlands. The activity of Jalisco New Generation Cartel includes an attempt at establishing a drug laboratory in Iquique as well as the import of marihuana through the port of San Antonio.
=== United States ===
The U.S. Justice Department considers the Mexican drug cartels to be the "greatest organized crime threat to the United States." During the first 18 months of Calderón's presidency, the Mexican government spent about US$7 billion in the war against drugs. In seeking partnership from the United States, Mexican officials point out that the illicit drug trade is a shared problem in need of a shared solution, and remark that most of the financing for the Mexican traffickers comes from American drug consumers. On March 25, 2009, U.S. Secretary of State Hillary Clinton stated that "[America's] insatiable demand for illegal drugs fuels the drug trade", and that "the United States bears shared responsibility for the drug-fueled violence sweeping Mexico."
U.S. State Department officials knew that Mexican ex-president Felipe Calderón's willingness to work with the United States was unprecedented on issues of security, crime and drugs, so the U.S. Congress passed legislation in late June 2008 to provide Mexico and Central American countries with US$1.6 billion for the Mérida Initiative, a three-year international assistance plan. The Mérida Initiative provides Mexico and Central American countries with law enforcement training and equipment, as well as technical advice to strengthen the national justice systems. The Mérida Initiative does not include cash or weapons.
Currently, the Mexican drug cartels already have a presence in most major U.S. cities. In 2009, the Justice Department reported that Mexican drug cartels distribute drugs in nearly 200 cities across the United States, including Los Angeles, Chicago and Atlanta. Gang-related activity and violence has increased along the U.S. Southwest border region, as U.S.-based gangs act as enforcers for Mexican drug cartels.
==== U.S. death toll and national security ====
U.S. authorities reported a spike in killings, kidnappings and home invasions connected to Mexican cartels, and at least 19 Americans were killed in 2008. Another 92 Americans were killed between June 2009 and June 2010.
The U.S. Joint Forces Command noted in a December 2008 report that in terms of worst-case scenarios, Mexico bears some consideration for sudden collapse in the next two decades as the government, its politicians, police, and judicial infrastructure are all under sustained assault and pressure by criminal gangs and drug cartels. The Joint Forces Command stated concern that the conflict will have a major impact on the stability of the Mexican state over the next several years, and therefore would demand an American response based on the implications for homeland security alone. After the JFC broached this issue in its 2008 report, several journalists and academics have discussed the possibility that Mexico could become a failed state.
The Mexican government responded negatively to the U.S. government raising the prospect of Mexico becoming a failed state. In a February 2009 interview with the Associated Press, President Calderón said it was "absolutely false" to label his country a failed state. To smooth over relations with Mexico over this issue, Secretary of State Hillary Clinton personally visited Mexico City in March 2009, followed by a visit by President Barack Obama a month later.
In March 2009, the U.S. DHS said that it was considering using the National Guard to counter the threat of drug violence in Mexico from spreading to the U.S. The governors of Arizona and Texas have asked the federal government to send additional National Guard troops to help those already there supporting local law enforcement efforts against drug trafficking. Calls for National Guard deployment on the border greatly increased after the 2010 murder of Arizona rancher Robert Krentz, possibly at the hands of Mexican drug smugglers.
In March 2009, the Obama administration outlined plans to redeploy more than 500 federal agents to border posts and redirect $200 million to combat smuggling of illegal drugs, money and weapons. On May 25, 2010, President Obama authorized deployment of 1,200 National Guard troops to the U.S. border with Mexico to assist with border protection and enforcement activities, as well as help train additional Customs and Border Protection agents. The Washington Office on Latin America said the U.S. southwest border region remained calm, with a homicide rate lower than the national average.
In 2021, around 80,411 people died from opioid overdoses in the United States. Many of the deaths are from an extremely potent opioid, fentanyl, which is trafficked from Mexico. The drug's precursor chemicals, which have a variety of legitimate uses, are manufactured in China, then shipped to Mexico, where it is processed and packaged, which is then smuggled into the US by drug cartels. The opioid crisis in the United States is largely fueled by drugs smuggled from Mexico; approximately 98% of fentanyl entering the U.S. comes from Mexico. In 2023, the Biden administration announced a crackdown on members of the Sinaloa Cartel smuggling fentanyl into the United States. In 2025, President Donald Trump launched a process to designate Mexican drug cartels and other criminal organizations as foreign terrorist organizations. The Trump administration has considered drone strikes against cartels in Mexico.
== Controversies ==
Vicente Zambada Niebla, a member of the Sinaloa Cartel and son of Ismael Zambada García, one of the top drug lords in Mexico, claimed after his arrest to his attorneys that he and other top Sinaloa cartel members had received immunity by U.S. agents and a virtual licence to smuggle cocaine over the United States border, in exchange for intelligence about rival cartels engaged in the Mexican drug war.
In October 2013, two former federal agents and an ex-CIA contractor told an American television network that CIA operatives including Félix Rodríguez were involved in the kidnapping and murder of DEA covert agent Enrique Camarena, because he was a threat to the agency's drug operations in Mexico. According to the three men, the CIA was collaborating with drug traffickers moving cocaine and marijuana to the United States, and using its share of the profits to finance Nicaraguan Contra rebels attempting to overthrow Nicaragua's Sandinista government. A CIA spokesman responded, calling it "ridiculous" to suggest that the Agency had anything to do with the murder of a U.S. federal agent or the escape of his alleged killer.
According to former Presidents Fernando Henrique Cardoso of Brazil, Ernesto Zedillo of Mexico and César Gaviria of Colombia, the United States-led drug war is pushing Latin America into a downward spiral; Mr. Cardoso said in a conference that "the available evidence indicates that the war on drugs is a failed war". The panel of the Latin American Commission on Drugs and Democracy commission, headed by Cardoso, stated that the countries involved in this war should remove the "taboos" and re-examine the anti-drug programs. Latin American governments have followed the advice of the U.S. to combat the drug war, but the policies had little effect. The commission made some recommendations to United States President Barack Obama to consider new policies, such as decriminalization of marijuana and to treat drug use as a public health problem and not as a security problem. The Council on Hemispheric Affairs states it is time to seriously consider drug decriminalization and legalization, a policy initiative that would be in direct opposition to the interests of criminal gangs.
=== Money laundering ===
Despite the fact that Mexican drug cartels and their Colombian suppliers generate, launder and remove $18 billion to $39 billion from the United States each year, the U.S. and Mexican governments have been criticized for their unwillingness or slow response to confront the various cartels' financial operations, including money laundering.
The U.S. DEA has identified the need to increase financial investigations relating to the movement of illegal drug funds to Mexico. The DEA states that attacking the financial infrastructure of drug cartels has to play a key role in any viable drug enforcement strategy. The U.S. DEA has noted that the U.S. and Mexican financial services industry continues to be a facilitator for drug money movement.
Following suit, in August 2010 President Felipe Calderón proposed sweeping new measures to crack down on the cash smuggling and money laundering. Calderón proposes a ban on cash purchases of real estate and of certain luxury goods that cost more than 100,000 pesos (about US$8,104.) His package would also require more businesses to report large transactions, such as real estate, jewelry and purchases of armor plating. In June 2010, Calderón "announced strict limits on the amount in U.S. dollars that can be deposited or exchanged in banks", but the proposed restrictions to financial institutions are facing tough opposition in the Mexican legislature.
In 2011, Wachovia, at one time a major U.S. bank, was implicated in laundering money for Mexican drug lords. In a settlement, Wachovia paid federal authorities $110 million in forfeiture. A U.S. Senate report from the permanent subcommittee for investigations revealed in July 2012 that HSBC – one of Europe's biggest banks- moved $7 billion in bulk cash from Mexico to the U.S., most of it suspected to assist Mexican drug lords and U.S. drug cartels in moving money to the U.S. While money laundering problems at HSBC have been flagged by regulators for nearly a decade, the bank continued to avoid compliance. On December 12, 2012, HSBC settled for a $1.93 billion fine.
=== Drug demand ===
RAND studies released in the mid-1990s found that using drug user treatment to reduce drug consumption in the United States is seven times more cost effective than law enforcement efforts alone, and it could potentially cut consumption by a third.
In FY2011, the Obama administration requested approximately $5.6 billion to support demand reduction. This includes a 13% increase for prevention and almost a 4% increase for treatment. The overall FY2011 counter-drug request for supply reduction and domestic law enforcement is $15.5 billion with $521.1 million in new funding.
== See also ==
== References ==
== Further reading ==
Buscaglia, Edgardo (2013). Vacíos de Poder en México: Como Combatir la Delincuencia Organizada. Editorial Penguin Random (Debate), Edición Kindle
Atuesta, L. H., Siordia, O. S., & Lajous, A. M. (2018). "The 'War on Drugs' in Mexico: (Official) Database of Events between December 2006 and November 2011." Journal of Conflict Resolution.
Vulliamy, Ed, Amexica: War Along the Borderline, Bodley Head, 2010. ISBN 978-1-84792-128-4
Grillo, Ioan (2012). El Narco: The Bloody Rise of Mexican Drug Cartels (2nd ed.). Bloomsbury Publishing. ISBN 978-1-4088-2433-7.
Deibert, Michael (2014). In the Shadow of Saint Death: The Gulf Cartel and the Price of America's Drug War in Mexico. Globe Pequot. ISBN 9780762791255.
Gutierrez Aire, Jose, Blood, Death, Drugs & Sex in Old Mexico, CreateSpace, 2012. ISBN 978-1-4775-9227-4
The Last Narco, book about the current phase of the drug war by journalist Malcolm Beith.
Hernández, Anabel, Narcoland: The Mexican Drug Lords And Their Godfathers, Verso, 2013. ISBN 978-1781680735
Wainwright, Tom (23 February 2016). Narconomics: How to Run a Drug Cartel. PublicAffairs. ISBN 9781610395830.
Tuckman, Jo (3 July 2012). Mexico: Democracy Interrupted. Yale University Press. ISBN 9780300160314. Retrieved 26 May 2024.
== External links ==
Map of Mexican drug war violence
Borderland Beat Blog dedicated to reporting on Mexican drug cartels on the border between the US and Mexico
Bowers, Charles (2009). "The Mexican Kidnapping Industry". Archived from the original on February 23, 2015. Retrieved April 9, 2009. An academic paper examining both the emergence of kidnapping as a drug war spillover, and statewide variance in Mexico's kidnapping statutes.
The Mexican Zetas and Other Private Armies – written by the Strategic Studies Institute.
Mexico page on InSight Crime. Ongoing reporting on Mexico's drug war and involved cartels.
"Full Coverage Mexico Under Siege". Los Angeles Times. Archived from the original on April 6, 2014. Retrieved September 12, 2016.
The Atlantic: Mexico's Drug War
George Grayson, "Mexico's Elite Must Commit to Fighting Drug Cartels", Foreign Policy Association Headline Series.
Juarez, City of Death, City of Hope
Cocaine Incorporated June 15, 2012
How American guns turned Mexico into a war zone (by Stuart Miller, LA Times, Feb 24, 2021) | Wikipedia/Mexican_drug_war |
Drug liberalization is a drug policy process of decriminalizing, legalizing, or repealing laws that prohibit the production, possession, sale, or use of prohibited drugs. Variations of drug liberalization include drug legalization, drug relegalization, and drug decriminalization. Proponents of drug liberalization may favor a regulatory regime for the production, marketing, and distribution of some or all currently illegal drugs in a manner analogous to that for alcohol, caffeine and tobacco.
Proponents of drug liberalization argue that the legalization of drugs would eradicate the illegal drug market and reduce the law enforcement costs and incarceration rates. They frequently argue that prohibition of recreational drugs—such as cannabis, opioids, cocaine, amphetamines and hallucinogens—has been ineffective and counterproductive and that substance use is better responded to by implementing practices for harm reduction and increasing the availability of addiction treatment. Additionally, they argue that relative harm should be taken into account in the regulation of drugs. For instance, they may argue that addictive or dependence-forming substances such as alcohol, tobacco and caffeine have been a traditional part of many cultures for centuries and remain legal in most countries, although other drugs which cause less harm than alcohol, caffeine or tobacco are entirely prohibited, with possession punishable with severe criminal penalties.
Opponents of drug liberalization argue that it would increase the amount of drug users, increase crime, destroy families, and increase the amount of adverse physical effects among drug users.
== Policies ==
The 1988 United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances made it mandatory for the signatory countries to "adopt such measures as may be necessary to establish as criminal offences under its domestic law" (art. 3, § 1) all the activities related to the production, sale, transport, distribution, etc. of the substances included in the most restricted lists of the 1961 Single Convention on Narcotic Drugs and 1971 Convention on Psychotropic Substances. Criminalization also applies to the "cultivation of opium poppy, coca bush or cannabis plants for the purpose of the production of narcotic drugs". The Convention distinguishes between the intent to traffic and personal consumption, stating that the latter should also be considered a criminal offence, but "subject to the constitutional principles and the basic concepts of [the state's] legal system" (art. 3, § 2).
Drug liberalization proponents hold differing reasons to support liberalization, and have differing policy proposals. The two most common positions are drug legalization (or re-legalization), and drug decriminalization. The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) defines decriminalization as the removal of a conduct or activity from the sphere of criminal law; depenalisation signifying merely a relaxation of the penal sanction exacted by law. Decriminalization usually applies to offences related to drug consumption and may include either the imposition of sanctions of a different kind (administrative) or the abolition of all sanctions; other (noncriminal) laws then regulate the conduct or activity that has been decriminalized. Depenalisation usually consists of personal consumption as well as small-scale trading and generally signifies the elimination or reduction of custodial penalties, while the conduct or activity still remains a criminal offence. The term legalization refers to the removal of all drug-related offences from criminal law, such as use, possession, cultivation, production, and trading.
Harm reduction refers to a range of public health policies designed to reduce the harmful consequences associated with recreational drug use and other high risk activities. Harm reduction is put forward as a useful perspective alongside the more conventional approaches of demand and supply reduction. Many advocates argue that prohibitionist laws criminalize people for suffering from a disease and cause harm, for example by obliging drug addicts to obtain drugs of unknown purity from unreliable criminal sources at high prices, increasing the risk of overdose and death. Its critics are concerned that tolerating risky or illegal behaviour sends a message to the community that these behaviours are acceptable.
=== The Controlled Substance Act (United States) ===
The Controlled Substance Act (CSA) categorizes all substances in need of regulation into one of the five schedules under the federal law. The categorization of these substances is determined by the potential for abuse and how safe it is to consume. In addition, a big determinant of this is the way in which the substance can be consumed or used medically. In its earliest stages, the CSA was created to combine the needs of two international treaties. These treaties were known as the Single Convention on Narcotic Drugs of 1961 and the Convention of Psychotropic Substances of 1971. Both treaties allowed public health authorities to work with the medical and scientific communities to create a classification system. The Schedule I substances were described as those that have no medical use whatsoever; meaning there is no prescription written for such substance. Schedule II substances are those that can be easily abused and lead to dependence. These substances can only be accessed through a written or electronic prescription from a physician. The schedule III substances are classified as those which have less potential for abuse than Schedule I and II but can still cause the individual to develop a mild dependence. Schedule IV substances are those with the least likeliness for abuse, therefore its medical use is common in the United States. Lastly, the Schedule V substances are those with little to no likelihood of abuse, along with very minimal dependence development.
=== Drug legalization (United States) ===
Drug legalization calls for a return to pre–1906 Pure Food and Drug Act attitudes when almost all drugs were legal. This would require ending government-enforced prohibition on the distribution or sale and personal use of specified (or all) currently banned drugs. Proposed ideas range from full legalization which would completely remove all forms of government control, to various forms of regulated legalization, where drugs would be legally available, but under a system of government control which might mean for instance:
Mandated labels with dosage and medical warnings.
Restrictions on advertising.
Age limitations.
Restrictions on amount purchased at one time.
Requirements on the form in which certain drugs would be supplied.
Ban on sale to intoxicated persons.
Special user licenses to purchase particular drugs.
A possible clinical setting for the consumption of some intravenous drugs or supervised consumption.
The regulated legalization system would probably have a range of restrictions for different drugs, depending on their perceived risk, so while some drugs would be sold over the counter in pharmacies or other licensed establishments, drugs with greater risks of harm might only be available for sale on licensed premises where use could be monitored and emergency medical care made available. Examples of drugs with different levels of regulated distribution in most countries include: caffeine (coffee, tea), nicotine (tobacco), and ethyl alcohol (beer, wine, spirits). Since each country has its own regulations and most distinguish between different classes of drugs, there can be difficulties when it comes to regulating which should be more readily accessible, since a particular drug criminalized in one area might be completely acceptable elsewhere. Full legalization is often proposed by groups, such as libertarians, who object to drug laws on moral grounds, while regulated legalization is suggested by groups like Law Enforcement Against Prohibition who object to the drug laws on the grounds that they fail to achieve their stated aims and instead they say greatly worsen the problems associated with the use of prohibited drugs but acknowledge that there are harms associated with currently prohibited drugs which need to be minimized. Not all proponents of drug re-legalization necessarily share a common ethical framework, and people may adopt this viewpoint for a variety of reasons. In particular, favoring drug legalization does not imply approval of drug use.
=== Drug decriminalization ===
Drug decriminalization calls for reduced or eliminated control or penalties compared to existing laws. There are proponents of drug decriminalization that support a system whereby those who use and possess drugs for personal use are not penalized. While others support the use of fines or other punishments to replace prison terms, and often propose systems whereby illegal drug users who are caught would be fined, but would not receive a permanent criminal record as a result. A central feature of drug decriminalization is the concept of harm reduction. Drug decriminalization is in some ways an intermediate between prohibition and legalization, and has been criticized by Peter Lilley as being "the worst of both worlds", in that drug sales would still be illegal, thus perpetuating the problems associated with leaving production and distribution of drugs to the criminal underworld, while also failing to discourage illegal drug use by removing the criminal penalties that might otherwise cause some people to choose not to use drugs.
In 2001, Portugal began treating use and possession of small quantities of drugs as a public health issue. Rather than incarcerating those in possession, they are referred to a treatment program by a regional panel composed of social workers, medical professionals, and drug experts. This also decreases the amount of money the government spends fighting a war on drugs and money spent keeping drug users incarcerated. HIV infection rates also have dropped from 104.2 new cases per million in 2000 to 4.2 cases per million in 2015. Anyone caught with any type of drug in Portugal, if it is for personal consumption, will not be imprisoned. Portugal is the first country that has decriminalized the possession of small amounts of drugs, to positive results.
As noted by the EMCDDA, across Europe in the last decades, there has been a movement toward "an approach that distinguishes between the drug trafficker, who is viewed as a criminal, and the drug user, who is seen more as a sick person who is in need of treatment" (EMCDDA 2008, 22). A number of Latin American countries have similarly moved to reduce the penalties associated with drug use and personal possession" (Laqueur, 2015, p. 748). Mexico City has decriminalized certain drugs and Greece has just announced that it is going to do so. Spain has also followed the Portugal model. Italy after waiting 10 years to see the result of the Portugal model, which Portugal deemed a success, has since recently followed suit. In May 2014, the Criminal Chamber of the Italian Supreme Court upheld a previous decision in 2013 by Italy's Constitutional Court, to reduce the penalties for the convictions for sale of soft drugs. Some other countries have virtual decriminalization for marijuana only, including in three U.S. states, such as Colorado, Washington, and Oregon, the Australian State of South Australia, and across the Netherlands, where there are legal marijuana cafes. In the Netherlands these cafes are called "coffeeshops".
== History ==
The cultivation, use and trade of psychoactive and other drugs has occurred since the dawn of civilization. Motivations claimed by supporters of drug prohibition laws across various societies and eras have included religious observance, allegations of violence by racial minorities, and public health concerns. Those who are proponents of drug legislation characterize these motivations as religious intolerance, racism, and public healthism. The British had gone to war with China in the 19th century in what became known as the First and Second Opium Wars to protect their valuable trade in narcotics. It was only in the 20th century that Britain and the United States outlawed cannabis. The campaign against alcohol prohibition culminated in the Twenty-first Amendment to the United States Constitution repealing prohibition on 5 December 1933, as well as liberalization in Canada, and some but not all of the other countries that enforced prohibition. Despite this, many laws controlling the use of alcohol continue to exist even in these countries. In the mid-20th century, the United States government led a major renewed surge in drug prohibition called the war on drugs.
Initial attempts to change the punitive drug laws which were introduced all over the world from the late 1800s onwards were primarily based around recreational use. Timothy Leary was one of the most prominent campaigners for the legal and recreational use of LSD. In 1967, a "Legalise pot" rally was held in Britain. As death toll from the drug war rose, other organisations began to form to campaign on a more political and humanitarian basis. Drug Policy Foundation formed in America and Release, a charity which gives free legal advice to drugs users and currently campaigns for drug decriminalization, also incorporated in the 1970s. Into the 21st century, the focus of the world's drug policy reform organisations is on the promotion of harm reduction in the Western World, and attempting to prevent the catastrophic loss of human life in developing countries where much of the world's supply of heroin, cocaine, and marijuana are produced. Drug policy reform advocates point to failed efforts, such as the Mexican Drug War, as signs that a new approach to drug policy is needed. According to some observers, the Mexican Drug War has claimed as many as 80,000 lives.
In 2014, a European Citizens' Initiative called "Weed Like to Talk" was launched within the European Union, with the aim of starting a debate in Europe about the legalization of the production, sale and use of marijuana in the European Union and finding a common policy for all EU member states. As of June 30, 2014, the initiative has collected 100,000 signatures from citizens in European member states. Should they reach 1 million signatures, from nationals of at least one quarter of the member states, the European Commission will be required to initiate a legislative proposal and a debate on the issue.
== Impacts ==
A Independent Scientific Committee on Drugs study found drug harms, such as economic cost, injury, family adversities, environmental damage, and community harm vary between different drugs.
=== Harms to others and society ===
Proponents of drug prohibition argue that many negative externalities, or third party costs, are associated with the consumption of illegal drugs.: 2043 : 183 Externalities like violence, environmental effects on neighborhoods, increased health risks, and increased healthcare costs are often associated with the illegal drug market.: 3
Opponents of prohibition argue that some of those externalities are created by criminalizing drug policies. They believe that much of the violence associated with drug trade is due to the illegal nature of drug trade, where there is no mediating authority to solve disputes peacefully and legally.: 3 : 177 The illegal nature of the market also affects the health of consumers by making it difficult to acquire syringes, which often leads to needle sharing.: 180–181
Economist Milton Friedman argues that prohibition of drugs creates many negative externalities like increased incarceration rates, the undertreatment of chronic pain, corruption, disproportional imprisonment of African Americans, compounding harm to users, the destruction of inner cities and harm to foreign countries. Proponents of legalization also argue that prohibition decrease the quality of the drugs made, which often leads to more physical harm, like accidental overdoses and poisoning, to the drug users.: 179 Steven D. Levitt and Ilyana Kuziemko point to the over crowding of prisons as another negative side effect of the war on drugs. They believe that by sending such a large number of drug offenders to prison, the war on drugs has reduced the prison space available for other offenders. This increased incarceration rate not only costs tax payers more to maintain, it could possibly increase crime by crowding violent offenders out of prison cells and replacing them with drug offenders.: 2043 According to economist Mark Thornton prohibition increases political corruption and crime.
Prohibition can produce more dangerous and addictive drugs. Milton Friedman estimated that over 10,000 deaths a year in the US are caused by the criminalization of drugs, and if drugs were to be made legal, number of innocent victims such as those shot down in drive by shootings would decrease.
=== Cost of law enforcement ===
A Harvard economist, Jeffrey Miron, estimated that ending the war on drugs would inject 76.8 billion dollars into the US economy in 2010 alone. He estimates that the government would save $41.3 billion for law enforcement and the government would gain up to $46.7 billion in tax revenue. Since the war on drugs began under the administration of President Richard Nixon, the federal drug-fighting budget has increased from $100 million in 1970 to $15.1 billion in 2010, with a total cost estimated near 1 trillion dollars over 40 years. In the same time period an estimated 37 million nonviolent drug offenders have been incarcerated. $121 billion was spent to arrest these offenders and $450 billion to incarcerate them. The legalization would reduce the cost of having to mass incarcerate marginalized communities, which are those who are disproportionately affected. Of those arrested for drug possession or drug related crimes, the majority of those individuals arrested are Black or Hispanic.
The economic inefficiency and ineffectiveness of such government intervention in preventing drug trade has been criticised by drug-liberty advocates. The war on drugs of the United States, that provoked legislation within several other Western governments, has also garnered criticism for these reasons.
=== Demand curve ===
Much of the debate surrounding the economics of drug legalization centers on the shape of the demand curve for illegal drugs and the sensitivity of consumers to changes in the prices of illegal drugs. Proponents of drug legalization often assume that the quantity of addictive drugs consumed is unresponsive to changes in price; however, studies into addictive but legal substances like alcohol and cigarettes have shown that consumption can be quite responsive to changes in prices. In the same study, economists Michael Grossman and Frank J. Chaloupka estimated that a 10% reduction in the price of cocaine would lead to a 14% increase in the frequency of cocaine use.: 459 This increase indicates that consumers are responsive to price changes in the cocaine market. There is also evidence that in the long run, consumers are much more responsive to price changes than in the short run,: 454 but other studies have led to a wide range of conclusions.: 2043
Considering that legalization would likely lead to an increase in the supply of drugs, the standard economic model predicts that the quantity of drugs consumed would rise and the prices would fall.: 428 Andrew E. Clark, an economist who has studied the effects of drug legalization, suggests that a specific tax, or sin tax, would counteract the increase in consumption.: 3
== Size of the illegal drug market ==
According to 2013 data from the United Nations Office on Drugs and Crime (UNODC) and European crime-fighting agency Europol, the annual global drugs trade is worth around $435 billion a year, with the annual cocaine trade worth $84 billion of that amount.
== Policies by country ==
=== Asia ===
==== Philippines ====
Senator Bato dela Rosa, despite having the reputation of leading the deadly war on drugs during the presidency of Rodrigo Duterte as chief of the Philippine National Police, filed a bill in the senate in November 2022 proposing the decriminalization of illegal drug use. This bid was an attempt to deal with prison overcrowding and underutilization of drug rehabilitation centers. While the proposal do not include drug trafficking and manufacturing, the bill was met with opposition from law enforcement agencies who believes it would send a "wrong signal" and encourage drug abuse. The Department of Health has supported the proposal.
==== Thailand ====
"A committee tasked with controlling illegal drugs has won a majority vote to have cannabis and hemp reclassified as narcotics, and the listing will take effect on" 1 January 2024, according to media.
Although Thailand has a strict drug policy, in May 2018, the Cabinet approved draft legislation that allows for more research into the effects of marijuana on people. Thus, the Government Pharmaceutical Organization (GPO) will soon begin clinical trials of marijuana as a preliminary step in the production of drugs from this plant. These medical studies are considered exciting, new landmarks in the history of Thailand, because the manufacture, storage, and use of marijuana has been completely outlawed in Thailand since 1979.
On 9 November 2018, the National Assembly of Thailand officially proposed to allow licensed medical use of marijuana, thereby legalizing what was previously considered a dangerous drug. The National Assembly on Friday submitted its amendments to the Ministry of Health, which would place marijuana and vegetable kratom in the category allowing their licensed possession and distribution in regulated conditions. The ministry reviewed the amendments before sending them to the cabinet, which returned it to the National Assembly for a final vote. This process was completed on 25 December 2018. Thus, Thailand became the first Asian country to legalize medical cannabis. These changes did not allow recreational use of drugs. These actions were taken because of the growing interest in the use of marijuana and its components for the treatment of certain diseases. Cannabis became decriminalized in Thailand on 9 June 2022, making recreational use also legal, although smoking in public can still incur penalties due to being considered a public nuisance. Supporters of legalization argue that the legal market for marijuana in Thailand could increase to $5 billion by 2024.
=== Europe ===
==== Czech Republic ====
In the Czech Republic, until 31 December 1998 only drug possession "for other person" (i.e. intent to sell) was criminal (apart from production, importation, exportation, offering or mediation, which was and remains criminal) while possession for personal use remained legal. On 1 January 1999, an amendment of the Criminal Code, which was necessitated in order to align the Czech drug rules with the Single Convention on Narcotic Drugs, became effective, criminalizing possession of "amount larger than small" also for personal use (Art. 187a of the Criminal Code) while possession of small amounts for personal use became a misdemeanor. The judicial practice came to the conclusion that the "amount larger than small" must be five to ten times larger (depending on drug) than a usual single dose of an average consumer.
On 14 December 2009, the Government of the Czech Republic adopted Regulation No. 467/2009 Coll., that took effect on 1 January 2010, and specified what "amount larger than small" under the Criminal Code meant, effectively taking over the amounts that were already established by the previous judicial practice. According to the regulation, a person could possess up to 15 grams of marijuana or 1.5 grams of heroin without facing criminal charges. These amounts were higher (often many times) than in any other European country, possibly making the Czech Republic the most liberal country in the European Union when it comes to drug liberalization, apart from Portugal. Under the Regulation No. 467/2009 Coll, possession of the following amounts or less of illicit drugs was to be considered smaller than large for the purposes of the Criminal Code and was to be treated as a misdemeanor subject to a fine equal to a parking ticket:
Marijuana 15 grams (or five plants)
Hashish 5 grams
Magic mushrooms 40 pieces
Peyote 5 plants
LSD 5 tablets
Ecstasy 4 tablets
Amphetamine 2 grams
Methamphetamine 2 grams
Heroin 1.5 grams
Coca 5 plants
Cocaine 1 gram
In 2013, a District Court in Liberec was deciding a case of a person that was accused of criminal possession for having 3.25 grams of methamphetamine (1.9 grams of straight methamphetamine base), well over the Regulation's limit of 2 grams. The court considered that basing a decision on mere Regulation would be unconstitutional and in breach of Article 39 of the Czech Charter of Fundamental Rights and Freedoms which states that "only a law may designate which acts constitute a crime and what penalties, or other detriments to rights or property, may be imposed for committing them" and proposed to the Constitutional Court to abolish the Regulation. In line with the District Courts' argument, the Constitutional Court abolished the Regulation effective from 23 August 2013, noting that the "amount larger than small" within the meaning of the Criminal Code may be designated only by the means of an Act of Parliament, and not a Governmental Regulation. Moreover, the Constitutional Court further noted that the Regulation merely took over already existing judicial practice of interpretation of what constitutes "amount larger than small" and thus its abolishment will not really change the criminality of drug possession in the country. Thus, the above-mentioned amounts from the now-not-effective Regulation remain as the base for consideration of police and prosecutors, while courts are not bound by the precise grammage.
Sale of any amount (not purchase) remains a criminal act. Possession of "amount larger than a small" of marijuana can result in a jail sentence of up to one year. For other illicit drugs, the sentence is up to two years. Trafficking as well as production (apart from growing up to five plants of marijuana) offenses carry stiffer sentences. Medical use of cannabis on prescription has been legal and regulated since 1 April 2013.
==== France ====
Following a contentious debate France opened its first supervised injection centre on 11 October 2016. Marisol Touraine, the Minister of Health, declared that the centre, located near the Gare du Nord in Paris, was "a strong political response, for a pragmatic and responsible policy that brings high-risk people back towards the health system rather than stigmatizing them."
==== Germany ====
In 1994, the Federal Constitutional Court ruled that drug addiction was not a crime, nor was the possession of small amounts of drugs for personal use. In 2000, the German narcotic law (BtmG) was changed to allow for supervised drug injection rooms. In 2002, a pilot study was started in seven German cities to evaluate the effects of heroin-assisted treatment on addicts, compared to methadone-assisted treatment. The positive results of the study led to the inclusion of heroin-assisted treatment into the services of the mandatory health insurance in 2009. On 4 May 2016, the Cabinet of Germany decided to approve the measure for legal cannabis for seriously ill patients who have consulted with a doctor and "have no therapeutic alternative". German Health Minister, Hermann Gröhe, presented the legal draft on the legalization of medical cannabis to the cabinet which was expected to take effect early 2017.
==== Ireland ====
On 2 November 2015, Aodhán Ó Ríordáin, the minister in charge of the National Drugs Strategy, announced that Ireland planned to introduce supervised injection rooms. The minister also referenced that possession of controlled substances will be decriminalized although supply and production will remain criminalized. On 12 July 2017, the Health Committee of the Irish government rejected a bill that would have legalized medical cannabis.
==== Netherlands ====
The drug policy of the Netherlands is based on two principles: (1) drug use is a public health issue, not a criminal matter, and (2) a distinction between hard and soft drugs exists. Additionally, a policy of non-enforcement has led to a situation where reliance upon non-enforcement has become common; because of this, the courts have ruled against the government when individual cases were prosecuted. Cannabis remains a controlled substance in the Netherlands and both possession and production for personal use are still misdemeanors, punishable by fine. Cannabis coffee shops are also illegal according to the statutes.
==== Norway ====
On 14 June 2010, the Stoltenberg commission recommended implementing heroin assisted treatment and expanding harm reduction measures. On 18 June 2010, Knut Storberget, Minister of Justice and the Police, announced that the ministry was working on new drug policy involving decriminalization by the Portugal model, which was to be introduced to parliament before the next general election. Storberget later changed his statements, saying the decriminalization debate is "for academics", instead calling for coerced treatment. In early March 2013, minister of health and care services Jonas Gahr Støre proposed to decriminalize the inhalation of heroin by 2014 as a measure to decrease drug overdoses. In 2011, there were 294 fatal overdoses, in comparison to only 170 traffic related deaths.
The country was preparing a massive policy change in terms of how to deal with drug use and drug possession for personal use. The reform titled "From punishment to help" was approved by the Norwegian government in 2017 and was in the final phase of approval by the parliament. Changes were expected to be implemented by early 2021. The new reform policy emphasizes that criminalizing drug use has no significant effect on rates of drug consumption and that drug addiction is better dealt with by health care services, hence the slogan "from punishment to help". Instead of fines or prison time, a person caught with a drug quantity for personal use will now be met with an independent panel consisting of social and health care workers that will discuss administrative sanctions or addiction treatment methods. This will hopefully encourage problematic users to seek help rather than fear of prosecution. There is also hope that this will improve the relationship between drug users and law enforcement officers. Opponents of the reform, including the police force and the Progress Party, fear that drug use will increase once a person is no longer at risk of facing criminal charges.
As of 21 July 2022, drug decriminalisation has not materialised in Norway. As of this date, only those who have substance use disorders may go unpunished if the amount of illegal drugs they have meets the criteria of what is deemed an amount for personal use.
==== Portugal ====
In 2001, Portugal became the first European country to abolish all criminal penalties for personal drug possession, under Law 30/2000. In addition, drug users were to be provided with therapy rather than prison sentences. Research commissioned by the Cato Institute and led by Glenn Greenwald found that in the five years after the start of decriminalization, illegal drug use by teenagers had declined, the rate of HIV infections among drug users had dropped, deaths related to heroin and similar drugs had been cut by more than half, and the number of people seeking treatment for drug addiction had doubled. Peter Reuter, a professor of criminology and public policy at the University of Maryland, College Park, suggested that the heroin usage rates and related deaths may have been due to the cyclical nature of drug epidemics. In 2009, he stated that "decriminalization in Portugal has met its central goal. Drug use did not rise." In 2022, drug use had increased to 12.8 percent, compared to 7.8 percent in 2001 when the policies had been implemented.
==== Ukraine ====
The use of marijuana in Ukraine is not prohibited, but the manufacture, storage, transportation and sale of cannabis and its derivatives are under administrative and criminal liability. Speaking on the legalization of soft drugs in Ukraine has been going on for a long time. In June 2016, the Parliament received a bill on the legalization of marijuana for medical purposes. It dealt with changes to the current act "On narcotic drugs, psychotropic substances and precursors" and was registered number 4533. The document must examine the relevant committee, and then submit it to the government. It was expected that this would happen in the fall of 2016, but the bill was not considered. In October 2018, a petition appeared on the website of electronic appeals to the President of Ukraine asking for the legalization of marijuana. In October 2018, the State Service of Ukraine on Drugs and Drug Control issued the first license for the import and re-export of raw materials and products derived from cannabis. The corresponding licenses were obtained by the USA company C21. The company is also in the process of applying for additional licenses, including the cultivation of cannabis.
=== Latin America ===
In the late 2000s and early 2010s, advocacy for drug legalization has increased in Latin America. Spearheading the movement Uruguayan government announced in 2012 plans to legalize state-controlled sales of marijuana in order to fight drug-related crimes. Some countries in this region have already advanced towards depenalization of personal consumption.
==== Argentina ====
In August 2009, the Supreme Court of Argentina declared in a landmark ruling that it was unconstitutional to prosecute citizens for having drugs for their personal use – "adults should be free to make lifestyle decisions without the intervention of the state". The decision affected the second paragraph of Article 14 of the country's drug control legislation (Law Number 23,737) that punishes the possession of drugs for personal consumption with prison sentences ranging from one month to two years (although education or treatment measures can be substitute penalties). The unconstitutionality of the article concerns cases of drug possession for personal consumption that does not affect others.
==== Brazil ====
In 2002 and 2006, Brazil went through legislative changes, resulting in a partial decriminalization of possession for personal use. Prison sentences no longer applied and were replaced by educational measures and community services; however, the 2006 law does not provide objective means to distinguish between users or traffickers. A disparity exists between the decriminalization of drug use and the increased penalization of selling drugs, punishable with a maximum prison sentences of 5 years for the sale of very minor quantities of drugs. Most of those incarcerated for drug trafficking are offenders caught selling small quantities of drugs, among them drug users who sell drugs to finance their drug habits. Since 2006, there has been a long debate whether the anti-drug law goes against the Constitution and principle of personal freedom. In 2009, the Supreme Federal Court re-opened to vote if the law is Constitutional, or if it goes against the Constitution specifically against personal Freedom of choice. Since each Minister inside the tribunal can take a personal time to evaluate the law, the voting can take years. In fact, the voting was re-opened in 2015, 3 ministers voted in favor, and then the law was again paused by another minister.
==== Colombia ====
Guatemalan President Otto Pérez Molina and Colombian President Juan Manuel Santos proposed the legalization of drugs in an effort to counter the failure of the war on drugs, which was said to have yielded poor results at a huge cost. On 25 May 2016, the Colombian congress approved the legalization of marijuana for medical usage.
==== Costa Rica ====
Costa Rica has decriminalized drugs for personal consumption. Manufacturing or selling drugs is still a jailable offense.
==== Ecuador ====
According to the 2008 Constitution of Ecuador, in its Article 364, the Ecuadorian state does not see drug consumption as a crime but only as a health concern. Since June 2013, the state drugs regulatory office CONSEP has published a table which establishes maximum quantities carried by persons so as to be considered in legal possession and that person as not a seller of drugs. The "CONSEP established, at their latest general meeting, that the following quantities be considered the maximum consumer amounts: 10 grams of marijuana or hash, 4 grams of opiates, 100 milligrams of heroin, 5 grams of cocaine, 0.020 milligrams of LSD, and 80 milligrams of methamphetamine or MDMA".
==== Honduras ====
On 22 February 2008, Honduras President Manuel Zelaya called on the United States to legalize drugs in order to prevent the majority of violent murders occurring in Honduras. Honduras is used by cocaine smugglers as a transiting point between Colombia and the US. Honduras, with a population of 7 million affected people an average of 8–10 murders a day, with an estimated 70% being as a result of this international drug trade. According to Zelaya, the same problem is occurring in Guatemala, El Salvador, Costa Rica, and Mexico.
==== Mexico ====
In April 2009, the Mexican Congress approved changes in the General Health Law that decriminalized the possession of illegal drugs for immediate consumption and personal use allowing a person to possess up to 5 g of marijuana or 500 mg of cocaine. The only restriction is that people in possession of drugs should not be within a 300-meter radius of schools, police departments, or correctional facilities. Opium, heroin, LSD, and other synthetic drugs were also decriminalized, it will not be considered as a crime as long as the dose does not exceed the limit established in the General Health Law. Many question this, as cocaine is as much synthesised as heroin, both are produced as extracts from plants. The law establishes very low amount thresholds and strictly defines personal dosage. For those arrested with more than the threshold allowed by the law this can result in heavy prison sentences, as they will be assumed to be small traffickers even if there are no other indications that the amount was meant for selling.
==== Uruguay ====
Uruguay is one of few countries that never criminalized the possession of drugs for personal use. Since 1974, the law establishes no quantity limits, leaving it to the judge's discretion to determine whether the intent was personal use. Once it is determined by the judge that the amount in possession was meant for personal use, there are no sanctions. In June 2012, the Uruguayan government announced plans to legalize state-controlled sales of marijuana in order to fight drug-related crimes. The government also stated that they will ask global leaders to do the same.
On 31 July 2013, the Uruguayan House of Representatives approved a bill to legalize the production, distribution, sale, and consumption of marijuana by a vote of 50 to 46. The bill then passed the Senate, where the left-leaning majority coalition, the Broad Front, held a comfortable majority. The bill was approved by the Senate by 16 to 13 on 10-December-2013. The bill was presented to the President José Mujica, also of the Broad Front coalition, who has supported legalization since June 2012. Relating this vote to the 2012 legalization of marijuana by the U.S. states Colorado and Washington, John Walsh, drug policy expert of the Washington Office on Latin America, stated that "Uruguay's timing is right. Because of last year's Colorado and Washington State votes to legalize, the U.S. government is in no position to browbeat Uruguay or others who may follow."
In July 2014, government officials announced that part of the implementation of the law (the sale of cannabis through pharmacies) is postponed to 2015, as "there are practical difficulties". Authorities will grow all the cannabis that can be sold legal. Concentration of THC shall be 15% or lower. In August 2014, an opposition presidential candidate, who was not elected in the November 2014 presidential elections, claimed that the new law was never going to be applied, as it was not workable. By the end of 2016 the government announced that the sale through pharmacies will be fully implemented during 2017.
=== North America ===
==== Canada ====
The cultivation of cannabis is currently legal in Canada, except in Manitoba and Quebec. Citizens outside those provinces may grow up to four plants per residence for personal use, and recreational use of cannabis by the general public is legal with restrictions on smoking in public locations that vary by jurisdiction. The sale of marijuana seeds is also legal.
In 2001, The Globe and Mail reported that a poll found 47% of Canadians agreed with the statement, "The use of marijuana should be legalized" in 2000, compared to 26% in 1975. A more recent poll found that more than half of Canadians supported legalization. In 2007, Prime Minister Stephen Harper's government tabled Bill C-26 to amend the Controlled Drugs and Substances Act, 1996 to bring forth a more restrictive law with higher minimum penalties for drug crimes. Bill-26 died in committee after the dissolution of the 39th Canadian Parliament in September 2008, but the Bill was subsequently resurrected by the government twice.
In 2015, Prime Minister Justin Trudeau and the Liberal Party of Canada campaigned on a promise to legalize marijuana. The Cannabis Act was passed on 19 June 2018, which made marijuana legal across Canada on 17 October 2018. Since legalization, the country has set up an online framework to allow consumers to purchase a wide variety of merchandise ranging from herbs, extract, oil capsules, and paraphernalia. Most provinces also provide a venue for purchase through physical brick and mortar stores.
In 2021, the city councils of Vancouver and Toronto voted to decriminalize the simple possession of all drugs; and submitted proposals requesting special exemption from the federal Health Minister to do so, citing numerous scientific, psychological, medical, and socio-economic benefits. In early 2022, the Province of British Columbia submitted its own request for exemption, closely following the Vancouver model. By April of that year, the Edmonton City Council had also passed a motion to request exemption from federal drug enforcement laws in order decriminalize "simple personal possession" of illegal drugs, voting in favour 11–2. On 31 May 2022, the federal government of Canada approved British Columbia's proposal to decriminalize all "hard drugs", such as heroin, fentanyl, cocaine, and methamphetamine. As of 1 January 2023, British Columbians aged 18 years or older are allowed to carry up to a cumulative total of 2.5 grams of these substances without the risk of arrest or criminal charges. Police are not to confiscate the drugs, and there is no requirement that people found to be in possession seek treatment; however, the production, trafficking, and exportation of these drugs remain illegal.
==== United States ====
As of 2024, prior to November elections, 38 states, Washington, D.C., and certain U.S. territories allow medical use of cannabis. Of those 38 states, 24 also allow recreational use, as does Washington, D.C. Voters in North and South Dakota and Florida will decide on recreational use in November, and Nebraskans will vote on cannabis use for medical reasons. Legalization in states created significant legal and policy tensions between federal and state governments and sometimes between states. State laws in conflict with federal law about cannabis remain valid, and prevent state level prosecution, despite cannabis being illegal under federal law, as determined in Gonzales v. Raich (2005).
Throughout the United States, various people and groups have been pushing for the legalization of marijuana for medical reasons. Organizations such as NORML and the Marijuana Policy Project work to decriminalize and legalize possession, use, cultivation, and sale of marijuana by adults. In 1996, 56% of California voters voted for California Proposition 215, legalizing the growing and use of marijuana for medical purposes and making California both the first state to outlaw marijuana, in 1913, and the first state to legalize medical marijuana.
On 6 November 2012, the states of Washington and Colorado legalized possession of small amounts of marijuana for private recreational use and created a process for writing rules for legal growing and commercial distribution of marijuana within each state, after having legalized medical cannabis in 1998 and 2000, respectively. In 2014, voters in Oregon, Alaska, and Washington, D.C. voted to legalize marijuana for recreational use, as did California in 2016, with the passage of California Proposition 64, and Michigan in 2018. In 2019, Illinois passed the Illinois Cannabis Regulation and Tax Act, making Illinois the first state to legalize recreational use by an act of the state legislature, which took effect 1 January 2020. In 2020, Oregon decriminalized the possession of all drugs in Measure 110, but in 2024, the Oregon State Senate passed a bill to reverse the decriminalization of hard drugs such as heroin after there was public backlash to the impacts of the measure. In 2021, New York legalized adult-use cannabis when it passed the Marijuana Regulation and Taxation Act (MRTA).
=== Oceania ===
==== Australia ====
In 2016, Australia legalised medicinal cannabis on a federal level. Since 1985, the Federal Government has run a declared war on drugs and while initially Australia led the world in 'harm-minimization' approach, they have since lagged. Australia has a number of political parties that focus on cannabis reform, The (HEMP) Help End Marijuana Prohibition Party was founded in 1993 and registered by the Australian Electoral Commission in 2000. The Legalise Cannabis Queensland Party was established in 2020. A number of Australian and international groups have promoted reform in regard to 21st-century Australian drug policy. Organisations such as Australian Parliamentary Group on Drug Law Reform, Responsible Choice, the Australian Drug Law Reform Foundation, Norml Australia, Law Enforcement Against Prohibition (LEAP) Australia and Drug Law Reform Australia advocate for drug law reform without the benefit of government funding. The membership of some of these organisations is diverse and consists of the general public, social workers, lawyers and doctors, and the Global Commission on Drug Policy has been a formative influence on a number of these organisations. In 1994, the Australian National Task Force on Cannabis formed under the Ministerial Council on Drug Strategy noted that the social harm of cannabis prohibition is greater than the harm from cannabis itself, total prohibition policies have been unsuccessful in reducing drug use and have caused significant social harm, as well as higher law enforcement costs, the use of cannabis is widespread in Australia and that its adverse health effects are modest and only affect a minority of users.
In 2012, the think tank Australia 21, released a report on the decriminalization of drugs in Australia. It noted that "by defining the personal use and possession of certain psychoactive drugs as criminal acts, governments have also avoided any responsibility to regulate and control the quality of substances that are in widespread use." Prohibition has fostered the development of a criminal industry that is corrupting civil society and government and killing our children." The report also highlighted the fact that, just as alcohol and tobacco are regulated for quality assurance, distribution, marketing and taxation, so should currently, unregulated, illicit drugs. There has been a number of enquires in Australia relating to cannabis and other illicit drugs, in 2019 the Queensland government instructed the Queensland Productivity Commission to conduct an enquiry into imprisonment and recidivism in QLD; the final report was sent to the Queensland Government on 1 August 2019 and publicly released on 31 January 2020. The commission found that "all available evidence shows the war on drugs fails to restrict usage or supply" and that "decriminalisation would improve the lives of drug users without increasing the rate of drug use" with the commission ultimately recommending that the Queensland government legalise cannabis. The QPC said the system had also fuelled an illegal market, particularly for methamphetamine. Although the Palaszczuk Queensland Labor Party led state government rejected the recommendations of its own commission and said it had no plans to alter any laws around cannabis, a decision that received heavy scrutiny from supporters of decriminalization, legalisation, progressive and non progressive drug policy advocates alike.
In 2019, The Royal Australasian College of Physicians (RACP) and St. Vincent's Health Australia called on the NSW Government to publicly release the findings of the Special Commission of Inquiry into the Drug 'Ice, saying there was "no excuse" for the delay. The report was the culmination of months of evidence from health and judicial experts, as well as families and communities affected by amphetamine-type substances across NSW. The report made 109 recommendations aimed to strengthen the NSW Governments response regarding amphetamine-based drugs such as crystal meth or ice. Major recommendations included more supervised drug use rooms, a prison needle and syringe exchange program, state-wide clinically supervised substance testing, including mobile pill testing at festivals, decriminalisation of drugs for personal use, a cease to the use of drug detection dogs at music festivals and to limit the use of strip searches. The report, also called for the NSW Government to adopt a comprehensive Drug and Alcohol policy, with the last drug and Alcohol policy expiring over a decade ago. The reports commissioner said the state's approach to drug use was profoundly flawed and said reform would require "political leadership and courage" and "Criminalising use and possession encourages us to stigmatise people who use drugs as the authors of their own misfortunate". Mr Howard said current laws "allow us tacit permission to turn a blind eye to the factors driving most problematic drug use" including childhood abuse, domestic violence and mental illness. The NSW government rejected the reports key recommendations, saying it would consider the other remaining recommendations. Director of the Drug Policy Modelling Program (DPMP) at UNSW Sydney's Social Policy Research Centre said the NSW Government has missed an opportunity to reform the state's response to drugs based on evidence. The NSW Government is yet to officially respond to the inquiry as of November 2020, a statement was released from the government citing intention to respond by the end of 2020.
In the Australian Capital Territory, after a bill was passed on 25 September 2019, new laws came into effect on 31 January 2020. While personal possession and growth of small amounts of cannabis remains prohibited non-medicinal purposes in every other jurisdiction in Australia, it allowed for possession of up to 50 grams of dry material, 150 grams of wet material, and cultivation of 2 plants per individual up to 4 plants per household, effectively legalising the possession and growing of cannabis in the ACT; however the sale and supply of cannabis and cannabis seeds is still illegal, so the effects of the laws are limited and the laws also contradict federal laws. It is also still illegal to smoke or use cannabis in a public place, expose a child or young person to cannabis smoke, store cannabis where children can reach it, grow cannabis using hydroponics or artificial cultivation, grow plants where they can be accessed by the public, share or give cannabis as a gift to another person, to drive with any cannabis in your system, or for people aged under 18 to grow, possess, or use cannabis.
==== New Zealand ====
On 18 December 2018, the Labour-led government announced a nationwide, binding referendum on the legality of cannabis for personal use, set to be held as part of the 2020 general election. This was a condition of the Green Party giving confidence and supply to the Government. On 7 May 2019, the government announced that the 2020 New Zealand cannabis referendum would be a yes/no question to enact a yet-to-be created piece of legislation. Despite the earlier commitment, the referendum was non-binding, the proposed Cannabis Legalisation and Control Bill would have need to be introduced into Parliament and passed like any other piece of legislation; therefore, the government was not in fact bound to the results of the referendum. Official results for the general election and referendums were released on 6 November 2020. The number opposed to legalisation was 50.7% with 48.4% in favour and 0.9% of votes were declared Informal.
== Groups advocating change ==
The Senlis Council, a European development and policy think tank, has, since its conception in 2002, advocated that drug addiction should be viewed as a public health issue rather than a purely criminal matter. The group does not support the decriminalisation of illegal drugs. Since 2003, the council has called for the licensing of poppy cultivation in Afghanistan in order to manufacture poppy-based medicines, such as morphine and codeine, and to combat poverty in rural communities, breaking ties with the illicit drugs trade. The Senlis Council outlined proposals for the implementation of a village based poppy for medicine project and calls for a pilot project for Afghan morphine at the next planting season.
== Organizations involved in lobbying, research and advocacy ==
=== Canada ===
Le Dain Commission of Inquiry into the Non-Medical Use of Drugs
=== Europe ===
Beckley Foundation
Cannabis Law Reform
Drug Equality Alliance (DEA)
European Coalition for Just and Effective Drug Policies (ENCOD) (Branches in Austria, Germany and Norway)
Legalize.net (Netherlands)
Schildower Kreis (Goethe University Frankfurt, Germany)
NORML UK
Re:Vision Drug Policy Network (United Kingdom)
Regulación Responsible (Spain)
Release (agency) (United Kingdom)
Students for Sensible Drug Policy UK (United Kingdom)
Transform Drug Policy Foundation
=== Australia ===
Australian National Council on Drugs
Drug Policy Australia
Network Against Prohibition
=== New Zealand ===
The Helen Clark Foundation
NORML New Zealand
The STAR Trust
=== United States ===
American Civil Liberties Union
Americans for Safe Access
Drug Policy Alliance
High Times
High Times Freedom Fighters
Law Enforcement Against Prohibition
Lindesmith Center
Marijuana Policy Project
MASS CANN/NORML
Multidisciplinary Association for Psychedelic Studies (MAPS)
National Organization for the Reform of Marijuana Laws
Students for Sensible Drug Policy
Veterans for Medical Marijuana Access
November Coalition (United States)
Women Grow
== Political parties with drug liberalization policies ==
Many political parties support, to various degrees, and for various reasons, liberalizing drug control laws, from liberal parties to far-left movements, as well as some right-wing intellectuals. Drug liberalization is fundamental in the platforms of most Libertarian parties. There are also numerous single issue marijuana parties devoted to campaign for the legalization of cannabis exclusively.
=== Australia ===
Australian Greens
Drug Law Reform Australia
Fusion Party
Legalise Cannabis Australia
Legalise Cannabis Queensland
Legalise Cannabis Western Australia Party
Reason Party
=== Canada ===
Liberal Party of Canada
New Democratic Party of Canada
Libertarian Party of Canada
Marijuana Party
=== Hungary ===
MKKP
=== Netherlands ===
GroenLinks
D66
=== Germany ===
Die Linke
=== New Zealand ===
Green Party of Aotearoa New Zealand
=== Portugal ===
Left Bloc
Liberal Initiative
LIVRE
=== United Kingdom ===
Green Party of England and Wales
Liberal Democrats – in March 2016, the Liberal Democrats became the first major political party in the United Kingdom to support the legalisation of cannabis.
=== International ===
Pirate Party
== See also ==
== References ==
== Further reading ==
Anderson, D. Mark, and Daniel I. Rees. 2023. "The Public Health Effects of Legalizing Marijuana." Journal of Economic Literature 61(1): 86–143.
International Coalition on Drug Policy Reform and Environmental Justice. 2023. "Revealing the missing link to Climate Justice: Drug Policy."
== External links ==
Transform Drug Policy Foundation – A UK-based think-tank that works to develop systems for control and regulation that can be applied globally.
Law Enforcement Against Prohibition – Run by retired law enforcement professionals who oppose prohibition.
Voluntary Committee of Lawyers – a New York-based network of judges and lawyers opposed to current federal drug laws.
NORML (US National Organization for the Reform of Marijuana Laws) – a US wide network of activists seeking to liberalize cannabis legislation.
Re:Vision Drug Policy Network – an organisation for young people aged 16–25 campaigning against prohibition.
The Report of the Canadian Government Commission of Inquiry into the Non-Medical Use of Drugs – 1972 – The LeDain Commission Report
Drug Law Reform – a project of the Transnational Institute (TNI)
Draft Plan for Legalization from LIFE – an example of a policy formulation proposed for substance legalization
Count The Costs
Schaffer Library of Drug Policy
Worldwide Psychedelic Laws Tracker | Wikipedia/Drug_legalization |
Responsible drug use seeks to maximize the benefits and minimize the risks associated with psychoactive drug use. For illegal psychoactive drugs that are not diverted prescription controlled substances, some critics believe that illegal recreational drug use is inherently irresponsible, due to the unpredictable and unmonitored strength and purity of the drugs and the risks of addiction, infection, and other side effects.
Nevertheless, harm reduction advocates claim that the user can be responsible by employing the same general principles applicable to the use of alcohol: avoiding hazardous situations, excessive doses, and hazardous combinations of drugs; avoiding injection; and not using drugs at the same time as activities that may be unsafe without a sober state. Drug use can be thought of as an activity that is potentially beneficial but also potentially risky. Similar to other risky activities such as skydiving or mountain climbing, the varied risks of drug use can be minimized by using harm-reduction strategies such as education, caution, and common sense. These advocates also point out that government action (or inaction) makes responsible drug use more difficult by artificially increasing risks, such as by making drugs of known purity and strength unavailable due to prohibition.
== Harm reduction ==
Responsible drug use is emphasized as a primary prevention technique in harm-reduction drug policies. Harm-reduction policies were popularized in the late 1980s although they began in the 1970s counter-culture where cartoons were distributed to users explaining responsible drug use and consequences of irresponsible drug use.
Harm reduction as applied to drug use began as a philosophy in the 1980s aiming to minimize HIV transmission between intravenous drug users. It also focused on condom usage to prevent the transmission of HIV through sexual contact. Harm reduction worked so effectively that researchers and community policy makers adapted the theory to other diseases to which drug users were susceptible, such as Hepatitis C.
Professor Graham Foster, of St Mary's Hospital, London, said: "Sharing banknotes or straws is a significant risk factor that people need to be more aware of. Although the risk of contracting hepatitis C through snorting is lower than through sharing a needle, it is still there."
Harm reduction seeks to minimize the harms that can occur through the use of various drugs, whether legal (e.g. ethanol (alcohol), caffeine and nicotine), or illegal (e.g. heroin and cocaine). For example, people who inject drugs can minimize harm to both themselves and members of the community through proper injecting technique, using new sterile needles and syringes each time, utilizing sterile water, employing sterile micron filters to purify solutions, using antiseptic pads to prepare injection sites and clean drug mixing vials/containers, testing for contaminants, and through proper disposal of all injecting equipment.
Other harm reduction methods have been implemented with drugs such as crack cocaine. In some cities, peer health advocates (Weeks, 2006) have participated in passing out clean crack pipe mouthpiece tips to minimize the risk of Hepatitis A, B and C and HIV due to sharing pipes while lips and mouth contain open sores. Also, a study by Bonkovsky and Mehta reported that, just like shared needles, the sharing of straws used to "snort" cocaine can spread blood diseases such as Hepatitis C.
The responsible user therefore acts to minimize the spread of blood-borne viruses such as hepatitis C and HIV in the wider community and reduce their own risk exposure to drug-related harms.
=== Supervised injection sites (SiS) ===
The provision of supervised injection sites, also referred to as safe injection sites, operates under the premise of harm reduction by providing the injection drug user with a clean space and clean materials such as needles, sterile water, alcohol swabs, and other items used for safe injection.
Vancouver, British Columbia opened a SiS called Insite in its poorest neighbourhood, the Downtown Eastside. Insite was opened in 2003 and has dramatically reduced many harms associated with injection drug use. The research arm of the site, run by The Centre of Excellence for HIV/AIDS has found that SiS leads to increases in people entering detox and addiction treatment without increasing drug-related crime. As well, it reduces the littering of drug paraphernalia (e.g., used needles) on the street and reduces the number of people injecting in public areas. The program is attracting the highest-risk users, which has led to less needle-sharing in the Downtown Eastside community, and in the 453 overdoses which occurred at the facility, health care staff have saved every person.
Since the drug policy of the Netherlands considers substance use a social and health-related issue and not a legal one, the government has opened clinics where drug users may consume their substances in a safe, clean environment. Users are given access to clean needles and other paraphernalia, monitored by health officials and are given the ability to seek help from drug addiction.
Due to the project's initial success in reducing mortality ratios and viral spread amongst injection drug users, other projects have been started in Switzerland, Germany, Spain, Australia, Canada and Norway. France, Denmark and Portugal also opened multiple drug consumption facilities.
== Principles ==
Duncan and Gold argue that to use controlled and other drugs responsibly, a person must adhere to a list of principles. They and others argue that drug users ought to proceed by:
understanding and educating oneself on the effects, risks, side effects and legal status of the drug they are taking
measuring accurate dosages, and take other precautions to reduce the risk of overdose when taking drugs where an overdose is possible
if possible, drug checking all substances before use to determine their purity and strength
attempting to gain the most pure and high-quality drugs laced with no cutting agent at best such as by buying on darknet markets
using drugs only in relaxed and responsible social situations as altered consciousness can be inappropriate in potentially dangerous or unknown settings
avoiding driving, operating heavy machinery, or otherwise situate themselves directly or indirectly responsible for the safety or care of another person while intoxicated and discouraging persons from operating a motor vehicle while intoxicated
having a trip sitter (or "copilot") when taking hallucinogenic drugs
taking a small dose first when taking a new drug ("start low and go slow")
taking the smallest dose of a recreational drug that will produce the desired effects
using recreational drugs in moderation, setting reasonable limits on the consumption and not allowing drug use to overshadow other aspects of their life (i.e. financial and social responsibilities)
avoiding mixing or combining drugs, especially unknown drugs and drugs with known dangerous interactions
not trusting someone else with the responsibility for your health and safety
knowing basic first-aid techniques and taking responsibility for applying them appropriately in cases of drug emergencies
avoiding the injection of drugs; if injection cannot be avoided, then by using proper supplies like sterile needles, micron filters, and sterile water
recognizing that one's own drug-taking behavior and attitudes in the presence of others will influence others, especially children
abstaining from drug use when inappropriate for reasons of health and physical fitness such as during pregnancy
respecting an individual's decision concerning drug use
providing alternatives of acceptable social-recreational behaviors within a group for others and avoiding drug use to become the only motivation or focus of the social situation
understanding the individuality of response
being aware of the complex influences of set and setting on psychoactive drug experiences and acting accordingly
Some proposed ethical guidelines include:
never tricking or trying to persuade anyone to use a drug
being morally conscious of the source of the drugs that a person is using
Duncan and Gold suggested that responsible drug use involves three areas of responsibility:
Situation: concerns over the possible situations in which drugs might be used legally, such as the avoidance of hazardous situations; not using when alone; nor using due to coercion or when the use of drugs itself is the sole reason for use.
Health: the avoidance of excessive doses or hazardous combinations of drugs; awareness of possible health consequences of drug use; avoiding drug-using behaviors that can potentially lead to addiction; and not using a drug recreationally during periods of excessive stress.
Safety: using the smallest dose necessary to achieve the desired effects; using only in relaxed settings with supportive companions; avoiding the use of drugs by injection; and not using drugs while performing complex tasks or those where the drug might impair one's ability to function safely.
== Criticism and counterarguments ==
=== Health and social consequences ===
Drug use and users are often not considered socially acceptable; they are often marginalized socially and economically.
Drug use may affect work performance; however, drug testing should not be necessary if this is so, as a user's work performance would be observably deficient, and be grounds in itself for dismissal. In the case of discriminate use of amphetamines, substituted amphetamines and other stimulants, work capacity actually increases, which in itself raises additional ethical considerations.
=== Illegality ===
Illegality causes supply problems, and artificially raises prices far above the production and transportation costs. Purity and potency of many drugs is difficult to assess, as the drugs are illegal. Unscrupulous and unregulated middlemen are drawn by profit into the industry of these valuable commodities, directly affecting the users ability to obtain and use the drugs safely and forcing the user to take avoidable risks. Drug dosaging with varying purity is problematic. Profit motivation rewards illegal sellers who dilute substances with a cutting agent; when a user, expecting a low dose, procures "uncut" drugs, an overdose can result.
The morality of buying certain illegal drugs is also questioned given that the trade in cocaine, for instance, has been estimated to cause 20,000 deaths a year in Colombia alone. Increasing Western demand for cocaine causes several hundred thousand people to be displaced from their homes every year, indigenous people are enslaved to produce cocaine and people are killed by the land mines drug cartels place to protect their coca crops. However, the majority of deaths currently caused by the illegal drug trade can only take place in a situation in which the drugs are illegal and some critics blame prohibition of drugs and not their consumption for the violence surrounding them. The illegality of drugs in itself may also cause social and economic consequences for those using them, and legal regulation of drug production and distribution could alleviate these and other dangers of illegal drug use.
=== On festivals ===
As drugs are very prevalent in festival culture more and more consider taking measures for responsible usage there. Some music festival organizers have chosen to provide services meant to inform about responsible drug use and drug checking for the disposal of dangerously laced ones. As a result, some have reported a significant reduction of the workload of festival's medics, welfare team and police officers.
== Organizations ==
Many organizations exist to promote responsible drug use and harm reduction throughout the world.
Some, such as Students for Sensible Drug Policy or Drug Policy Alliance, are primarily activist groups concerned with drug policy reform, promoting scientific research on drugs, and opposing stigma and misinformation about drug use and drug users. Others exist primarily as drug testing services for drug users (e.g. Energy Control or DrugsData), or as supervised injection services (e.g. Insite), or as informational sources (e.g. Bluelight or Erowid). Governments have begun to address responsible drug use within their respective jurisdictions. The U.S. Department of Health and Human Services addresses harm reduction through the Substance Abuse and Mental Health Services Administration as a part of the department's Overdose Prevention Strategy.
== See also ==
== References ==
== Further reading ==
Zinberg, N. E. (1984) Drug, Set, And Setting: The Basis for Controlled Intoxicant Use (New Haven: Yale University Press) ISBN 0-300-03110-6
== External links ==
Fact sheets on responsible recreational drug use
Towards a Culture of Responsible Psychoactive Drug Use
Fundamentals of Responsible Psychoactive Use, Erowid
=== Harm reduction ===
The History of Harm Reduction
SOM.NIT // Risk reduction associated with recreational drug consumption
Harm Reduction & Drug info (and resources in Canada)
=== Responsible drug use websites ===
ConsumeResponsibly, Cannabis
RollSafe, MDMA
TripSafe, Psychedelics | Wikipedia/Responsible_drug_use |
The Drug Policy Alliance (DPA) is a New York City–based nonprofit organization that seeks to advance policies that "reduce the harms of both drug use and drug prohibition, and to promote the sovereignty of individuals over their minds and bodies". The organization prioritizes reducing the role of criminalization in drug policy, advocating for the legal regulation of marijuana, and promoting health-centered drug policies.
== History ==
The Drug Policy Alliance was formed when the Drug Policy Foundation and the Lindesmith Center merged in July 2000. Lindesmith Center founder. Ethan Nadelmann served as its first Executive Director. From October 2017, it was led by Maria McFarland Sánchez-Moreno. Since September 2020, it has been led by executive director Kassandra Frederique.
== Main issues ==
=== Drug war ===
DPA believes that the War on drugs in America has failed. They present the argument that the United States has spent billions of dollars on making the country drug-free, but many illicit drugs, such as heroin, cocaine, methamphetamine and many others, are more potent and prevalent than ever before.
=== Communities affected ===
DPA believes that the war on drugs does not affect all of the American population the same way, and that some communities are disproportionately affected.
== Results ==
In 2020, DPA's advocacy and political arm, Drug Policy Action, spearheaded the passage of the Oregon Ballot Measure 110, which made Oregon the first state in the nation to decriminalize drug possession while significantly expanding access to evidence-informed, culturally responsive treatment, harm reduction and other health services.
== See also ==
Arguments for and against drug prohibition
Decriminalization of marijuana in the United States
Freedom of thought
Harm reduction
Prison reform
== References ==
== External links ==
Official website | Wikipedia/Drug_Policy_Alliance |
Lifestyle drug is an imprecise term commonly applied to medications which treat non–life-threatening and non-painful conditions such as baldness, wrinkles, erectile dysfunction, or acne, which the speaker perceives as either not medical problems at all or as minor medical conditions relative to others. It is sometimes intended as a pejorative, bearing the implication that the scarce medical research resources allocated to develop such drugs were spent frivolously when they could have been better spent researching cures for more serious medical conditions. Proponents, however, point out that improving the patient's subjective quality of life has always been a primary concern of medicine, and argue that these drugs are doing just that. It finds broad use in both media and scholarly journals.
== Concept and impact on society ==
There is direct impact of lifestyle drugs on society, particularly in the developing world. Implications associated with labeling of indications and products sales of these lifestyle drugs may be varied. Drugs can, over time, switch from 'lifestyle' to 'mainstream' use.
== Bioethics and medical policy debate ==
Though no precise widely accepted definition or criteria are associated with the term, there is much debate within the fields of pharmacology and bioethics around the propriety of developing such drugs, particularly after the commercial debut of Viagra.
The German government's health insurance scheme has denied insurance coverage for some Lifestyle-Medikament ("lifestyle drugs") which they deem spurious.
Critics of pharmaceutical firms claim that pharmaceutical firms actively medicalize; that is, they invent novel disorders and diseases which were not recognized as such before their "cures" could be profitably marketed, in effect pathologizing what were widely regarded as normal conditions of human existence. The consequences are said to include generally greater worries about health, misallocation of limited medical research resources to comparatively minor conditions while many serious diseases remain uncured, and needless health care expenditure. This medicalization of some element of human condition has significance, in principle, as a matter for political discourse or dialogue in civil society concerning values or morals.
Social critics also question the propriety of devoting huge research budgets towards creating these drugs when far more dangerous diseases like cancer and AIDS remain uncured. It is sometimes claimed that lifestyle drugs amount to little more than medically sanctioned recreational drug use.
== Examples of lifestyle drugs ==
Modafinil (when used off-label or for shift-work); Modafinil is indicated for the treatment shift-work sleep disorder, sometimes dubbed a lifestyle condition. In this aspect, modafinil is already recognized as a lifestyle drug by the FDA. Modafinil's off-label use for increasing productivity is another example of its use as a lifestyle drug. Modafinil has been used to support lifestyles requiring long and irregular working hours (such as in shift-work), frequent memory recall throughout the day (amongst students and academics), and unfatigued decision making capabilities (such as amongst U.S. air force pilots, where modafinil is an approved "go pill"). Compared to other productivity drugs, users of modafinil for this purpose more often report possessing prescriptions for modafinil.
Finasteride (when used to treat balding); The use of DHT blocking medications like finasteride for the treatment of balding without the intent to treat dangerous pathologies can be considered lifestyle-enhancing use of the medication.
Minoxidil; The use of minoxidil and other topical vasodilating medications for the treatment of balding without the intent to treat dangerous pathologies can be considered lifestyle-enhancing use of the medication.
== References ==
== External links ==
Flower, R (2004). "Lifestyle drugs: Pharmacology and the social agenda". Trends in Pharmacological Sciences. 25 (4): 182–5. doi:10.1016/j.tips.2004.02.006. PMID 15063081.
Gilbert, D.; Walley, T.; New, B. (2000). "Lifestyle medicines". BMJ. 321 (7272): 1341–4. doi:10.1136/bmj.321.7272.1341. PMC 1119073. PMID 11090522.
Ashworth, M.; Clement, S; Wright, M (2002). "Demand, appropriateness and prescribing of 'lifestyle drugs': A consultation survey in general practice". Family Practice. 19 (3): 236–41. doi:10.1093/fampra/19.3.236. PMID 11978712.
Mitrany, D (2001). "Lifestyle drugs: Determining their value and who should pay". PharmacoEconomics. 19 (5): 441–448. doi:10.2165/00019053-200119050-00001. PMID 11465305. S2CID 46964906. | Wikipedia/Lifestyle_drug |
Commonly-cited arguments for and against the prohibition of drugs include the following:
== Efficiency ==
=== Arguments that drug laws are effective ===
Supporters of prohibition claim that drug laws have a successful track record suppressing illicit drug use since they were introduced in the 1910s. The licit drug alcohol has current (last 12 months) user rates as high as 80–90% in populations over 14 years of age, and tobacco has historically had current use rates up to 60% of adult populations, yet the percentages currently using illicit drugs in OECD countries are generally below 1% of the population excepting cannabis where most are between 3% and 10%, with six countries between 11% and 17%.
In the 50-year period following the first 1912 international convention restricting use of opium, heroin and cocaine, the United States' use of illicit drugs other than cannabis was consistently below 0.5% of the population, with cannabis rising to 1–2% of the population between 1955 and 1965. With the advent of the counter-culture movement from the late 1950s, where illicit drug use was promoted as mind-expanding and relatively harmless, illicit drug use rose sharply. With illicit drug use peaking in the 1970s in the United States, the "Just Say No" campaign, initiated under the patronage of Nancy Reagan, coincided with recent (past month) illicit drug use decreases from 14.1% in 1979 to 5.8% in 1992, a drop of 60%.
In March, 2007, Antonio Maria Costa, former executive director of the United Nations Office on Drugs and Crime, drew attention to the drug policy of Sweden, arguing:
Sweden is an excellent example. Drug use is just a third of the European average while spending on drug control is three times the EU average. For three decades, Sweden has had consistent and coherent drug-control policies, regardless of which party is in power. There is a strong emphasis on prevention, drug laws have been progressively tightened, and extensive treatment and rehabilitation opportunities are available to users. The police take drug crime seriously. Governments and societies must keep their nerve and avoid being swayed by misguided notions of tolerance. They must not lose sight of the fact that illicit drugs are dangerous – that is why the world agreed to restrict them.
In Europe as of 2007, Sweden spends the second highest percentage of GDP, after the Netherlands, on drug control. The UNODC argues that when Sweden reduced spending on education and rehabilitation in the 1990s in a context of higher youth unemployment and declining GDP growth, illicit drug use rose but restoring expenditure from 2002 again sharply decreased drug use as student surveys indicate. In 1998, a poll run by SIFO of 1,000 Swedes found that 96% wanted stronger action by government to stop drug abuse, and 95% wanted drug use to remain illegal.
Criticizing governments that have relaxed their drug laws, Antonio Maria Costa, speaking in Washington before the launch of the World Drug Report in June 2006, said:
After so many years of drug control experience, we now know that a coherent, long-term strategy can reduce drug supply, demand and trafficking. If this does not happen, it will be because some nations fail to take the drug issue sufficiently seriously and pursue inadequate policies. Many countries have the drug problem they deserve.
=== Arguments that drug laws are ineffective ===
One of the prominent early critics of prohibition in the United States was August Vollmer, founder of the School of Criminology at University of California, Irvine and former president of the International Association of Chiefs of Police. In his 1936 book The Police and Modern Society, he stated his opinion that:
Stringent laws, spectacular police drives, vigorous prosecution, and imprisonment of addicts and peddlers have proved not only useless and enormously expensive as means of correcting this evil, but they are also unjustifiably and unbelievably cruel in their application to the unfortunate drug victims. Repression has driven this vice underground and produced the narcotic smugglers and supply agents, who have grown wealthy out of this evil practice and who, by devious methods, have stimulated traffic in drugs. Finally, and not the least of the evils associated with repression, the helpless addict has been forced to resort to crime in order to get money for the drug which is absolutely indispensable for his comfortable existence.
The first step in any plan to alleviate this dreadful affliction should be the establishment of Federal control and dispensation – at cost – of habit-forming drugs. With the profit motive gone, no effort would be made to encourage its use by private dispensers of narcotics, and the drug peddler would disappear. New addicts would be speedily discovered and through early treatment, some of these unfortunate victims might be saved from becoming hopelessly incurable.
Drug addiction, like prostitution, and like liquor, is not a police problem; it never has been, and never can be solved by policemen. It is first and last a medical problem, and if there is a solution it will be discovered not by policemen, but by scientific and competently trained medical experts whose sole objective will be the reduction and possible eradication of this devastating appetite. There should be intelligent treatment of the incurables in outpatient clinics, hospitalization of those not too far gone to respond to therapeutic measures, and application of the prophylactic principles which medicine applies to all scourges of mankind.
Stephen Rolles, writing in the British Medical Journal in 2010, argues:
Consensus is growing within the drugs field and beyond that the prohibition on production, supply, and use of certain drugs has not only failed to deliver its intended goals but has been counterproductive. Evidence is mounting that this policy has not only exacerbated many public health problems, such as adulterated drugs and the spread of HIV and hepatitis B and C infection among injecting drug users, but has created a much larger set of secondary harms associated with the criminal market. These now include vast networks of organised crime, endemic violence related to the drug market, corruption of law enforcement and governments.
These conclusions have been reached by a succession of committees and reports including, in the United Kingdom alone, the Police Foundation, the Home Affairs Select Committee, the Prime Minister's Strategy Unit, the Royal Society of Arts, and the UK Drug Policy Consortium. The United Nations Office of Drugs and Crime has also acknowledged the many "unintended negative consequences" of drug enforcement.
The editor of the British Medical Journal, Dr. Fiona Godlee, gave her personal support to Rolles' call for decriminalisation, and the arguments drew particular support from Sir Ian Gilmore, former president of the Royal College of Physicians, who said we should be treating drugs "as a health issue rather than criminalising people" and "this could drastically reduce crime and improve health".
Danny Kushlik, head of external affairs at Transform, said the intervention of senior medical professionals was significant. He said: "Sir Ian's statement is yet another nail in prohibition's coffin. The Hippocratic oath says: 'First, do no harm'. Physicians are duty bound to speak out if the outcomes show that prohibition causes more harm than it reduces."
Nicholas Green, chairman of the Bar Council, made comments in a report in the profession's magazine, in which he said that drug-related crime costs the UK economy about £13bn a year and that there was growing evidence that decriminalisation could free up police resources, reduce crime and recidivism and improve public health.
A 2006 report sponsored by the New York County Lawyers' Association, one of the largest local bar associations in the United States, argues on the subject of US drug policy:
Notwithstanding the vast public resources expended on the enforcement of penal statutes against users and distributors of controlled substances, contemporary drug policy appears to have failed, even on its own terms, in a number of notable respects. These include: minimal reduction in the consumption of controlled substances; failure to reduce violent crime; failure to markedly reduce drug importation, distribution and street-level drug sales; failure to reduce the widespread availability of drugs to potential users; failure to deter individuals from becoming involved in the drug trade; failure to impact upon the huge profits and financial opportunity available to individual "entrepreneurs" and organized underworld organizations through engaging in the illicit drug trade; the expenditure of great amounts of increasingly limited public resources in pursuit of a cost-intensive "penal" or "law-enforcement" based policy; failure to provide meaningful treatment and other assistance to people who use substances and their families; and failure to provide meaningful alternative economic opportunities to those attracted to the drug trade for lack of other available avenues for financial advancement.
Moreover, a growing body of evidence and opinion suggests that contemporary drug policy, as pursued in recent decades, may be counterproductive and even harmful to the society whose public safety it seeks to protect. This conclusion becomes more readily apparent when one distinguishes the harms suffered by society and its members directly attributable to the pharmacological effects of drug use upon human behavior, from those harms resulting from policies attempting to eradicate drug use.
With aid of these distinctions, we see that present drug policy appears to contribute to the increase of violence in our communities. It does so by permitting and indeed, causing the drug trade to remain a lucrative source of economic opportunity for street dealers, drug kingpins and all those willing to engage in the often violent, illicit, black market trade.
Meanwhile, the effect of present policy serves to stigmatize and marginalize drug users, thereby inhibiting and undermining the efforts of many such individuals to remain or become productive, gainfully employed members of society. Furthermore, current policy has not only failed to provide adequate access to treatment for substance use, it has, in many ways, rendered the obtaining of such treatment, and of other medical services, more difficult and even dangerous to pursue.
In response to claims that prohibition can work, as argued by Antonio Maria Costa, executive director of the United Nations Office on Drugs and Crime, who drew attention to the drug policy of Sweden, Henrik Tham has written in 1998 that sometimes it's domestically important to stress drug policy as successful; in the case of Sweden, where this notion is important, such claims serve "the function of strengthening a threatened national identity in a situation where the traditional 'Swedish model' has come under increasingly hard attack from both inside and outside the country." Tham questions the success of the Swedish model – "The shift in Swedish drug policy since around 1980" ...(more difficult to receive nolle prosequi for minor drug crimes) ..."towards a more strict model has according to the official point of view been successful by comparison with the earlier, more lenient drug policy. However, available systematic indicators show that the prevalence of drug use has increased since around 1980, that the decrease in drug incidence was particularly marked during the 1970s and that some indicators point towards an increase during the 1990s."
Leif Lenke and Börje Olsson from Stockholm University have conducted research that showed how drug use have followed the youth unemployment in close correlation. They noted that unlike most of Europe, Sweden did not have widespread and lingering youth unemployment until the early 1990s financial crisis, suggesting that unattractive future prospects may contribute to the increase in drug use among the young. CAN, the Swedish Council for Information on Alcohol and Other Drugs, 2009 report stated that the increase in drug use have continued since the 1990s with a slight dip in the mid-2000.
The professor emeritus in criminology at the University of Oslo, Nils Christie, pointed out Sweden as the hawk of international drug policy in a 2004 book. He said that Sweden is serving the role of being welfare alibi for, and lending legitimacy to, the US drug war. Adding that USA and Sweden have had an extraordinary influence on UNODC as the biggest donor countries. Sweden was the second biggest donor financing 8% of the UNODC budget behind the European Commission in 2006, followed by the US. In 2007 and 2008 Sweden was the fourth biggest donor, behind the European Commission, USA and Canada. In 2009 it was the third, as USA withdrew some of its funding.
A 2009 editorial in The Economist argued:
fear [of legalisation] is based in large part on the presumption that more people would take drugs under a legal regime. That presumption may be wrong. There is no correlation between the harshness of drug laws and the incidence of drug-taking: citizens living under tough regimes (notably America but also Britain) take more drugs, not fewer. Embarrassed drug warriors blame this on alleged cultural differences, but even in fairly similar countries tough rules make little difference to the number of addicts: harsh Sweden and more liberal Norway have precisely the same addiction rates.
Antonio Maria Costa's conviction that "countries have the drug problem they deserve" if they fail to follow the "Swedish Model" in drug control has also been criticised in Peter Cohen's work – Looking at the UN, smelling a rat.
In its 2011 report, the Global Commission on Drug Policy stated that "The global war on drugs has failed, with devastating consequences for individuals and societies around the world".
== Deterrence ==
=== Arguments that prohibition discourages drug use ===
A 2001 Australian study, of 18- to 29-year-olds by the NSW Bureau of Crime Statistics and Research suggests that prohibition deters illicit drug use. 29% of those who had never used cannabis cited the illegality of the substance as their reason for never using the drug, while 19% of those who had ceased use of cannabis cited its illegality as their reason.
Gil Kerlikowske, director of the US ONDCP argued,
Controls and prohibitions help to keep prices higher, and higher prices help keep use rates relatively low, since drug use, especially among young people, is known to be sensitive to price. The relationship between pricing and rates of youth substance use is well-established with respect to alcohol and cigarette taxes. There is literature showing that increases in the price of cigarettes triggers declines in use."
The DEA argues "Legalization has been tried before—and failed miserably. Alaska's experiment with legalization in the 1970s led to the state's teens using marijuana at more than twice the rate of other youths nationally. This led Alaska's residents to vote to re-criminalize marijuana in 1990."
Drug Free Australia has cited the Netherlands as an example of drug policy failure because it is soft in approach. They argue that the Dutch idea of going soft on cannabis dealers, thereby creating a "separation of markets" from hard drug dealers has failed to stem the initiation to drugs such as heroin, cocaine, and amphetamines, saying that, in 1998, the Netherlands had the third highest cannabis and cocaine use in Europe. According to Barry McCaffrey of the US Office of National Drug Control Policy, Dutch tolerance has allowed the Netherlands to become a criminal epicentre for illicit synthetic drug manufacture, particularly ecstasy, as well as the home for production and worldwide export of strains of cannabis with THC reportedly 10 times higher than normal. Gil Kerlikowske has attested that, where there were once thousands of cannabis cafés there are now only several hundred. Levels of cannabis use, in 2005 only marginally higher than in 1998, while other European countries have accelerated past them, are more likely, Drug Free Australia argues, the result of a growing intolerance of cannabis in the Netherlands rather than a growing tolerance. Drug Free Australia has also argued that British reductions in cannabis use after softer legislation may be more so the result of heavy UK media exposure of the stronger evidence of links between cannabis and psychosis.
=== Arguments that prohibition does not discourage drug use ===
It has been suggested that drug law reform could reduce the use of hard drugs as it has in countries such as the Netherlands. According to a 2009 annual report by the European Monitoring Centre for Drugs and Drug Addiction, the Dutch are among the lowest users of marijuana or cannabis in Europe, despite the Netherlands' policy on soft drugs being one of the most liberal in Europe, allowing for the sale of marijuana at "coffee shops", which the Dutch have allowed to operate for decades, and possession of less than 5 grams (0.18 ounces).
British Crime Survey statistics indicated that the proportion of 16- to 24-year-olds using cannabis decreased from 28% a decade ago to 21%, with its declining popularity accelerating after the decision to downgrade the drug to class C was announced in January 2004. The BCS figures, published in October 2007, showed that the proportion of frequent users in the 16–24 age group (i.e. who were using cannabis more than once a month), fell from 12% to 8% in the past four years.
American teenagers are drinking and smoking less and doing fewer drugs than their predecessors in more than 40 years of tracking. Use of marijuana is down among 8th- and 10th-graders, though it is flat among high school seniors, according to the annual Monitoring the Future survey of American teens.
A 2008 scholarly study found that intensified enforcement of marijuana laws does not achieve the stated goals of
marijuana prohibition and that "decriminalizing marijuana possession or deprioritizing marijuana law enforcement does not appear to increase marijuana use".
== Gateway drug theory ==
=== Arguments that cannabis is a gateway drug ===
The US Drug Enforcement Agency's "2008 Marijuana Sourcebook" argues that recent research supports the gateway hypothesis that certain drugs (such as cannabis) act as gateways to use of 'harder' drugs such as heroin, either because of social contact or because of an increasing search for a better high. Proponents cite studies such as that of 311 same sex twins, where only one twin smoked cannabis before age 17, and where such early cannabis smokers were five times more likely than their twin to move on to harder drugs.
=== Arguments that cannabis is not a gateway drug ===
In the American Journal of Public Health, Andrew Golub and Bruce Johnson of the National Development and Research Institute in New York wrote that young people who smoked marijuana in the generations before and after the baby boomers did not appear to be likely to move on to harder drugs.
Researchers from the independent Rand Drug Policy Research Center in Santa Monica, California, looking at data from the National Household Survey on Drug Abuse between 1982 and 1994, concluded that teenagers who took hard drugs did so whether they had first tried cannabis or not.
A twin study (of 510 same sex twin pairs) which adjusted for additional confounders such as peer drug use, found that cannabis use and associations with later hard drug use existed only for non-identical twins. The study suggested that a causal role of cannabis use in later hard drug usage is minimal, if it exists at all, and that cannabis use and hard drug use share the same influencing factors such as genetics and environment.
== Health ==
=== Health arguments for drug laws ===
Advocates of prohibition argue that particular drugs should be illegal because they are harmful. Drug Free Australia for example argues "That illicit drugs are inherently harmful substances is attested by the very nomenclature of the 'harm reduction' movement." The U.S. government has argued that illegal drugs are "far more deadly than alcohol" saying "although alcohol is used by seven times as many people as drugs, the number of deaths induced by those substances is not far apart. According to the Centers for Disease Control and Prevention (CDC), during 2000, there were 15,852 drug-induced deaths; only slightly less than the 18,539 alcohol-induced deaths." Ratios of the harms of illicit opiates to licit alcohol and tobacco in Australia are similar, with 2 deaths per hundred opiate users per annum versus 0.22 deaths per hundred for alcohol (9 times less) per year and 0.3 for tobacco (7 times less).
The DEA has said:
Marijuana is far more powerful than it used to be. In 2000, there were six times as many emergency room mentions of marijuana use as there were in 1990, despite the fact that the number of people using marijuana is roughly the same. In 1999, a record 225,000 Americans entered substance abuse treatment primarily for marijuana dependence, second only to heroin—and not by much. ... According to the National Institute on Drug Abuse, "Studies show that someone who smokes five joints per week may be taking in as many cancer-causing chemicals as someone who smokes a full pack of cigarettes every day." Marijuana contains more than 400 chemicals, including the most harmful substances found in tobacco smoke. For example, smoking one marijuana cigarette deposits about four times more tar into the lungs than a filtered tobacco cigarette. ... The short-term effects are also harmful. They include: memory loss, distorted perception, trouble with thinking and problem solving, loss of motor skills, decrease in muscle strength, increased heart rate, and anxiety. Marijuana impacts young people's mental development, their ability to concentrate in school, and their motivation and initiative to reach goals. And marijuana affects people of all ages: Harvard University researchers report that the risk of a heart attack is five times higher than usual in the hour after smoking marijuana.
Many of the deaths from using cannabis, other than from car accidents while intoxicated or violence and aggression, are more likely to figure in the longer term, just as with tobacco, where both nicotine overdose and cannabis overdose are extremely rare or nonexistent. While ecstasy may have lower rates of immediate mortality than some other illicits, there is a growing science on the already recognized considerable health harms of ecstasy. Drug Free Australia argues that distinctions between "soft" and "hard" drugs are entirely artificial, and titling cannabis "soft" or ecstasy "recreational" does not lessen the extensive harms of these substances.
Gil Kerlikowske, former director of the US Office of National Drug Control Policy (ONDCP) argues that in the United States, illegal drugs already cost $180 billion a year in health care, lost productivity, crime, and other expenditures, and that number would only increase under legalization because of increased use.
Drug Free Australia claims arguments that increased health harms of illicit drugs are the result of lack of government regulation of their purity and strength are not well supported by evidence. In Australia, which has had the highest opioid mortality per capita in the OECD, studies found that "overdose fatality is not a simple function of heroin dose or purity. There is no evidence of toxicity from contaminants of street heroin in Australia." Drug Free Australia claims that other causes of death such as suicide, murder and accidents are an effect of the drug themselves, not of their purity or otherwise.
==== Addiction ====
Drug Free Australia argues "Regarding the freedom of choice of those addicted to a drug, it is important to recognize that addiction is defined as compulsive by its very nature and that addictions curb individual freedom." ... "As is the case with alcohol addiction, illicit drug addictions likewise serve to keep many such users functionally in poverty and often as a continued burden on friends, family and society. Where it is argued that all disabilities are a burden on society it must be recognized that most disabilities are not the result of a choice, whereas the decision to recreationally use illicit drugs is most commonly free, and with the knowledge that they may lead to an abundance of addictions."
=== Health arguments for drug law reform ===
There is evidence that some illicit drugs pose comparatively fewer health dangers than certain legal drugs. The health risks of MDMA (Ecstasy) have been exaggerated for instance, the risks from cannabis use also overstated, and health problems from the use of legal substances, particularly alcohol and tobacco, are greater, even than from cocaine use for example (occasional cocaine use does not typically lead to severe or even minor physical or social problems).
==== Health benefits ====
A 2015 study of 135,095 U.S. adults found no significant link between lifetime psychedelic use and increased mental health problems or suicidal behavior. The researchers concluded that the prohibition of psychedelics is challenging to justify on public health grounds, given these findings.
Many trials have shown beneficial effects associated with psychoactive drug use:
There is evidence that MDMA (ecstasy) can treat or cure post-traumatic stress disorder and anxiety in cases of terminal illness.
LSD has been widely researched as a therapeutic agent, and has shown effectiveness against alcoholism, frigidity and various other disorders. See Psychedelic therapy.
Researchers at Harvard-affiliated McLean Hospital found members of a religious group regularly using peyote scored significantly better on several measures of overall mental health than did subjects who did not use the hallucinogen.
A 2007 study, by Santos et al. found that users of ayahuasca scored better on tests measuring anxiety and hopelessness than people who did not use the drug.
==== Quality control ====
According to a World Health Organisation report: "As cannabis is an illegal drug its cultivation, harvesting and distribution are not subject to quality control mechanisms to ensure the reliability and safety of the product used by consumers. It is well recognised in developing countries, such as Kenya, that illicit alcohol production can result in the contamination with toxic by-products or adulterants that can kill or seriously affect the health of users. The same may be true of illicit drugs such as opiates, cocaine and amphetamine in developed societies."
The government cannot enforce quality control on products sold and manufactured illegally. Examples include: the easier to make derivative MDA being sold as MDMA, heroin users unintentionally injecting brick dust, quinine, or fentanyl with which their heroin had been cut; and heroin/cocaine overdoses occurring as a result of users not knowing exactly how much they are taking. If the supply of drugs such as ecstasy came from legitimate pharmaceutical companies, their product would be far less likely to contain toxic additives or varying dosages. This is a view supported by a number of parents whose children have died of overdoses.
The illegality of injectable drugs leads to a scarcity of needles which causes an increase in HIV infections. An easy cure to this problem, while upholding the illegality of drugs, is the Dutch policy of distributing free needles. The money spent on both increased health costs due to HIV infections and drug prohibition itself causes a drain upon society.
Studies on the effects of prescribing heroin to addicts as practiced in many European countries have shown better rates of success than any other available treatment in terms of assisting long-term users establish stable, crime-free lives. Many patients were able to find employment, some even started a family after years of homelessness and delinquency.
==== Block to research ====
The illegality of many recreational drugs may be dissuading research into new, more effective and perhaps safer recreational drugs, despite evidence that their use may be beneficial in certain contexts. Research on Schedule I drugs in many countries, including the United States and United Kingdom, and under international law, is tightly regulated and requires expensive and hard-to-obtain permits. Such restrictions have largely prevented investigation of their properties and therapeutic uses, and most research since the passage of the drug laws focuses on negative impacts of these drugs. For example, all known agonists of the 5HT2A receptor are psychedelics, which prevents research into this receptor.
In particular, research suggests that recreational drugs may have psychiatric applications, which many demonstrating potential for treatment-resistant mental health conditions, such as depression and anxiety. Those who support the legalisation of recreational drugs for research purposes highlight that it is unethical not to conduct research into therapeutic interventions that may have the potential to treat these conditions.
==== Misleading health statistics ====
The United States Drug Enforcement Administration (DEA) has suggested that illegal drugs are "far more deadly than alcohol", arguing that "although alcohol is used by seven times as many people as drugs, the number of deaths induced by those substances is not far apart", quoting figures from the Centers for Disease Control and Prevention (CDC), claiming "during 2000, there were 15,852 drug-induced deaths; only slightly less than the 18,539 alcohol-induced deaths."
The DEA's use of such figures is questionable however. An article in the Journal of the American Medical Association gave the number deaths caused by alcohol in year 2000 as 85,000 – over four and a half times greater than the DEA's preferred figure. The DEA's argument also overlooks tobacco, causing 435,000 US deaths in year 2000. And, the CDC definition of "drug-induced death" includes suicides using drugs, accidental overdose, and deaths from medically prescribed (not illegal) drugs. An analysis of drug-induced deaths for the 20-year period 1979–1998 found the vast majority attributable to accidental overdose, and suicide by drug taking, which together account for about 76 percent of all such deaths. Taking into account deaths from non-illegal drugs leaves only 21 percent of CDC "drug-induced death" figures actually due to the use of "illegal" drugs.
Claims that cannabis is far more powerful than it used to be are also dubious, with "scare figures" skewed by comparing the weakest cannabis from the past with the strongest of today. Figures regarding emergency room mentions of marijuana use can be misleading too, as "mention" of a drug in an emergency department visit does not mean that the drug was the cause of the visit.
=== Medical uses ===
A document published for the non-profit advocacy organization Europe Against Drugs (EURAD) argues that "one cannot vote for a medicine" and that a scientific approval basis is essential. It says that EU rules set out strict criteria for the acceptance of a drug for medical use:
All active ingredients have to be identified and their chemistry determined. They have to be tested for purity with limits set for all impurities including pesticides, microbe & fungi and their products. These tests have to be validated and reproduced if necessary in an official laboratory. Animal testing will include information on fertility, embryo toxicity, immuno-toxicity, mutagenic and carcinogenic potential. Risks to humans, especially pregnant women and lactating mothers, will be evaluated. Adequate safety and efficacy trials must be carried out. They must state the method of administration and report on the results from different groups, i.e. healthy volunteers, patients, special groups of the elderly, people with liver and kidney problems and pregnant women. Adverse drug reactions (ADR) have to be stated and include any effects on driving or operating machinery.
==== Arguments against medical uses of prohibited drugs ====
According to Janet D. Lapey, M.D., of Concerned Citizens For Drug Prevention, " Due to a placebo effect, a patient may erroneously believe a drug is helpful when it is not. This is especially true of addictive, mind-altering drugs like marijuana. A marijuana withdrawal syndrome occurs, consisting of anxiety, depression, sleep and appetite disturbances, irritability, tremors, diaphoresis, nausea, muscle convulsions, and restlessness. Often, persons using marijuana erroneously believe that the drug is helping them combat these symptoms without realizing that actually marijuana is the cause of these effects. Therefore, when a patient anecdotally reports a drug to have medicinal value, this must be followed by objective scientific studies."
The US Drug Enforcement Administration also says:There is a growing misconception that some illegal drugs can be taken safely. For example, savvy drug dealers have learned how to market drugs like Ecstasy to youth. Some in the Legalization Lobby even claim such drugs have medical value, despite the lack of conclusive scientific evidence.
==== Arguments for medical uses of prohibited drugs ====
Most of the psychoactive drugs now prohibited in modern societies have had medical uses in history. In natural plant drugs like opium, coca, cannabis, mescaline, and psilocybin, the medical history usually dates back thousands of years and through a variety of cultures.
Psychedelics such as LSD and psilocybin (the main ingredient in most hallucinogenic mushrooms) are the subject of renewed research interest because of their therapeutic potential. They could ease a variety of difficult-to-treat mental illnesses, such as chronic depression, post-traumatic stress disorder, and alcohol dependency. In 2018, the United States Food and Drug Administration (FDA) granted breakthrough therapy designation for psilocybin-assisted therapy for treatment-resistant major depressive disorder. In 2019, the FDA also granted breakthrough therapy designation for psilocybin therapy treating major depressive disorder more generally. MDMA (Ecstasy) has been used for cognitive enhancement in people with Parkinson's disease, and has shown potential in treating posttraumatic stress disorder, social anxiety, and alcohol addiction.
==== Lack of access to controlled medications ====
Under prohibition, millions of people find it very difficult to obtain controlled medications, particularly opiate pain-relievers. The United Nations 1961 Single Convention on Narcotic Drugs requires that opiates be distributed only by medical prescription, but this is impractical in many areas.
According to the Transnational Institute, June 2008:
According to the International Narcotics Control Board (INCB) and the World Health Organisation (WHO) there is now an unmet demand in opiates. Ironically, the current drug control regulations hamper access to controlled opiate medications for therapeutic use. Many patients are unable to access morphine, methadone or an equivalent opioid. Global medical morphine consumption would rise five times if countries would make morphine available at the level of the calculated need, according to a recent WHO estimate.
According to the New York Times, September 2007:
Under Sierra Leone law, morphine may be handled only by a pharmacist or doctor, explained Gabriel Madiye, the hospice's founder. But in all Sierra Leone there are only about 100 doctors — one for every 54,000 people, compared with one for every 350 in the United States.... "How can they say there is no demand when they don't allow it?" he [Madiye] asked. "How can they be so sure that it will get out of control when they haven't even tried it?"
== Economic ==
=== Economic arguments for prohibitive drug laws ===
The DEA argues that "compared to the social costs of drug abuse and addiction—whether in taxpayer dollars or in pain and suffering—government spending on drug control is minimal."
Antonio Maria Costa, executive director of the United Nations Office on Drugs and Crime, has said: The economic argument for drug legalization says: legalize drugs, and generate tax income. This argument is gaining favour, as national administrations seek new sources of revenue during the current economic crisis. This legalize and tax argument is un-ethical and uneconomical. It proposes a perverse tax, generation upon generation, on marginalized cohorts (lost to addiction) to stimulate economic recovery. Are the partisans of this cause also in favour of legalizing and taxing other seemingly intractable crimes like human trafficking? Modern-day slaves (and there are millions of them) would surely generate good tax revenue to rescue failed banks. The economic argument is also based on poor fiscal logic: any reduction in the cost of drug control (due to lower law enforcement expenditure) will be offset by much higher expenditure on public health (due to the surge of drug consumption). The moral of the story: don't make wicked transactions.
Gil Kerlikowske, former director of the US ONDCP, argues that legalizing drugs, then regulating and taxing their sale, would not be effective fiscally. The tax revenue collected from alcohol pales in comparison to the costs associated with it. Federal excise taxes collected on alcohol in 2007, totaled around $9 billion; states collected around $5.5 billion. Taken together, this is less than 10 percent of the over $185 billion in alcohol-related costs from health care, lost productivity, and criminal justice. Tobacco also does not carry its economic weight when we tax it; each year we spend more than $200 billion on its social costs and collect only about $25 billion in taxes.
Former directors of the ONDCP, John P. Walters and Barry McCaffrey have accused billionaires George Soros, Peter Lewis and John Sperling of bankrolling the pro-pot or drug legalisation movement. "These people use ignorance and their overwhelming amount of money to influence the electorate", Walters said. Billionaire US financier, George Soros said in his autobiography, "I would establish a strictly controlled distribution network through which I would make most drugs, excluding the most dangerous ones like crack, legally available." The drug legalization lobby's vigorous and well funded promotion in media and schools of a "safe use of illegal drugs" message
indicates that drug prohibition is in the midst of a pitched battle waged by those who are accepting not only of the drug user but who also strongly promote an acceptance of drug use itself.
==== Prohibition of hemp industry ====
Opposition to the legalization of hemp, which uses plants of the cannabis genus for commercial purposes, centres on the fact that those wanting to legalize the use of cannabis for recreational and medical purposes themselves present it as their Trojan horse for that very purpose: Alex Shum, importers of hemp fabric, "feel that the way to legalize marijuana is to sell marijuana legally. When you can buy marijuana in your neighbourhood shopping mall, IT'S LEGAL! So, they are going to produce every conceivable thing out of hemp.
In a Huffington Post interview, Mark Kleiman, the "Pot Czar" of Washington state, said he was concerned that the National Cannabis Industry Association would favor profits over public health. He also said that it could become a predatory body like the lobbying arms of the tobacco and alcohol industries. Kleiman said: "The fact that the National Cannabis Industry Association has hired itself a K Street suit [lobbyist] is not a good sign."
=== Economic arguments for drug law reform ===
The United States efforts at drug prohibition started out with a $350 million budget in 1971, and was in 2006 a $30 billion campaign. These numbers only include direct prohibition enforcement expenditures, and as such only represent part of the total cost of prohibition. This $30 billion figure rises dramatically once other issues, such as the economic impact of holding 400,000 prisoners on prohibition violations, are factored in.
The war on drugs is extremely costly to such societies that outlaw drugs in terms of taxpayer money, lives, productivity, the inability of law enforcement to pursue mala in se crimes, and social inequality. Some proponents of decriminalization say that the financial and social costs of drug law enforcement far exceed the damages that the drugs themselves cause. For instance, in 1999, close to 60,000 prisoners (3.3% of the total incarcerated population) convicted of violating marijuana laws were behind bars at a cost to taxpayers of some $1.2 billion per year. In 1980, the total jail and prison population was 540,000, about one-quarter the size it is today. Drug offenders accounted for 6% of all prisoners. According to the Federal Bureau of Prisons, drug offenders now account for nearly 51%.
It has been argued that if the US government legalised marijuana it would save $7.7 billion per year in expenditure on enforcement of prohibition. Also, that marijuana legalization would yield tax revenue of $2.4 billion annually if it were taxed like all other goods and $6.2 billion annually if it were taxed at rates comparable to those on alcohol and tobacco.
According to a 2018 report, legalising cannabis in the United Kingdom could raise between 1 and 3.5 billion pounds in tax and lead to savings for the police and the criminal justice system. It has been argued that the raised tax revenue could then be invested in public services, such as the budget of the National Health Service (NHS).
==== The creation of drug cartels ====
Mass arrests of local growers of marijuana, for example, not only increase the price of local drugs, but lessens competition. Only major retailers that can handle massive shipments, have their own small fleet of aircraft, troops to defend the caravans and other sophisticated methods of eluding the police (such as lawyers), can survive by this regulation of the free market by the government
... it is because it's prohibited. See, if you look at the drug war from a purely economic point of view, the role of the government is to protect the drug cartel. That's literally true.
==== Effect on producer countries ====
The United States' "War on Drugs" has added considerably to the political instability in South America. The huge profits to be made from cocaine and other South American-grown drugs are largely because they are illegal in the wealthy neighbouring nation. This drives people in the relatively poor countries of Colombia, Peru, Bolivia and Brazil to break their own laws in organising the cultivation, preparation and trafficking of cocaine to the States. This has allowed criminal, paramilitary and guerrilla groups to reap huge profits, exacerbating already serious law-and-order and political problems. Within Bolivia, the political rise of former president Evo Morales was directly related to his grassroots movement against US-sponsored coca-eradication and criminalization policies. However, coca has been cultivated for centuries in the Andes. Among their various legitimate uses, coca leaves are chewed for their mild stimulant & appetite suppression effects, and steeped as a tea which is known to reduce the effects of human altitude sickness. Rural farmers in the poor regions in which coca has historically been cultivated often find themselves at the difficult and potentially violent intersection of government-sponsored eradication efforts, illegal cocaine producers & traffickers seeking coca supplies, anti-government paramilitary forces trafficking in cocaine as a source of revolutionary funding, and the historical hardships of rural subsistence farming (or its typical alternative – abandoning their land and fleeing to an urban slum). In some regions, farmers' coca and other crops are frequently destroyed by U.S.-sponsored eradication treatments (usually sprayed from the air with varying degrees of discrimination), whether or not the farmers directly supply the cocaine trade, thereby destroying their livelihoods. Agricultural producers in these countries are pushed further to grow coca for the cocaine trade by the dumping of subsidised farming products (fruit, vegetables, grain etc.) produced by Western countries (predominantly US and EU agricultural surpluses) (see BBC reference, below), which reduces the prices they could otherwise receive for alternate crops such as maize. The net effect can be a depression of prices for all crops, which can both make the farmer's livelihood more precarious, and make the cocaine producers' coca supplies cheaper.
After providing a significant portion of the world's poppy for use in heroin production, Afghanistan went from producing practically no illegal drugs in 2000 (following banning by the Taliban), to cultivating what is now as much as 90% of the world's opium. The Taliban is currently believed to be heavily supported by the opium trade there.
Furthermore, the sale of the illegal drugs produces an influx of dollars that is outside the formal economy, and puts pressure on the currency exchange keeping the dollar low and making the export of legal products more difficult.
==== Prohibition of hemp industry ====
The war on drugs has resulted in the outlawing of the entire hemp industry in the United States. Hemp, which is a special cultivar of Cannabis sativa, does not have significant amounts of psychoactive (THC) substances in it, less than 1%. Without even realizing the plant had been outlawed several months prior, Popular Mechanics magazine published an article in 1938 entitled "The New Billion-Dollar Crop" anticipating the explosion of the hemp industry with the invention of machines to help process it. Recently, governmental refusal to take advantage of taxing hemp has been a point of criticism. Hemp has a large list of potential industrial uses including textiles, paper, rope, fuel, construction materials, and biocomposites (for use in cars for example). Hemp has some drawbacks, however, one being that the long fibers in hemp are only a part of the outer bast, and this has contributed to hemp having only modest commercial success in countries (for example in Canada) where it is legal to harvest hemp.
The seed of the hemp plant is highly nutritious. Rare for a plant, it contains all essential amino acids. Rare for any food, it is a good source of alpha-linolenic acid, an omega 3 fatty acid which is deficient in most diets.
==== Legalization as a job creator ====
Drug legalization has the potential to create a vast array of jobs, in sectors such as: sales, distribution, transportation, growing, cultivation, production, quality assurance, regulatory bodies, advertising, scientific research and lab analysis. If certain drugs were to be sold solely at single-purpose licensed premises then construction of these stores would also help the construction industry.
A 2019 jobs count found that legalized cannabis had directly created 211,000 full-time workers in the U.S., part of a total of 296,000 in all related areas combined (as a total of states where cannabis is legal). Nick Colas at DataTrek Research said in 2019 that cannabis is the “fastest-growing labor market in the U.S.” If cannabis were to be legalized nationally across the U.S., it is estimated that it would create over one million jobs.
Before the legalization of cannabis in Canada, it was estimated that the legalization of cannabis in the country would create thousands of new jobs. However, comprehensive statistics regarding the total amount jobs created by legalized cannabis in Canada have yet to be published post legalization. Cannabis was legalized in Canada on 17 October 2018.
== Crime, terrorism and social order ==
=== Arguments for prohibitive drug laws ===
While concerns are sometimes expressed that the "war on drugs" can never be won, there is a failure to recognize that other justifiably costly policing wars such as "blitzes" on speeding can likewise never be won. Such blitzes reduce and contain speeding, as with policing of illicit drug use. Failure to police speeding drivers simply allows inordinate harm to be inflicted on other individuals. Speeding is not legalized simply because it can never be eradicated.
There is an argument that much crime and terrorism is drug related or drug funded and that prohibition should reduce this.
Former US president George W. Bush, in signing the Drug-Free Communities Act Reauthorization Bill in December 2001, said, "If you quit drugs, you join the fight against terror in America."
The US Office of National Drug Control Policy (ONDCP) says that drug-related offences may include violent behavior resulting from drug effects.
The US Drug Enforcement Administration claims:Crime, violence and drug use go hand in hand. Six times as many homicides are committed by people under the influence of drugs, as by those who are looking for money to buy drugs. Most drug crimes aren't committed by people trying to pay for drugs; they're committed by people on drugs.
The U.S. government began the Drug Use Forecasting (DUF) program in 1987 to collect information on drug use among urban arrestees. In 1997, the National Institute of Justice expanded and reengineered the DUF study and renamed it the Arrestee Drug Abuse Monitoring (ADAM) program. ADAM is a network of 34 research sites in select U.S. cities.
DUF research indicates that:
Frequent use of hard drugs is one of the strongest indicators of a criminal career.
Offenders who use drugs are among the most serious and active criminals, engaging in both property and violent crime.
Early and persistent use of cocaine or heroin in the juvenile years is an indicator of serious, persistent criminal behavior in adulthood.
Those arrested who are drug users are more likely than those not using drugs to be rearrested on pretrial release or fail to appear at trial.
Criminal behavior can importantly be the direct result of drug use which can cause emotional/brain damage, mental illness and anti-social behavior. Psychoactive drugs can have a powerful impact on behavior which may influence some people to commit crimes that have nothing to do with supporting the cost of their drug use. The use of drugs changes behavior and causes criminal activity because people will do things they wouldn't do if they were rational and free of the drug's influence. Cocaine-related paranoia is an example. If drug use increases with legalization, so will such forms of related violent crime as assaults, drugged driving, child abuse, and domestic violence.
That higher prices make the trade lucrative for criminals is recognized but countered by the argument that capitulating to illicit drug use on these grounds makes no more sense than capitulating to those who continue to traffic in human lives, a more expensive business because of its illegality and therefore more lucrative for the criminal, but necessary for the rights of vulnerable citizens.
The Office of National Drug Control Policy says that the idea that our nation's prisons are overflowing with otherwise law-abiding people convicted for nothing more than simple possession of marijuana is a myth, "an illusion conjured and aggressively perpetuated by drug advocacy groups seeking to relax or abolish America's marijuana laws." ONDCP state that the vast majority of inmates in state and federal prison for marijuana have been found guilty of much more than simple possession. Some were convicted for drug trafficking, some for marijuana possession along with one or more other offenses. And many of those serving time for marijuana pleaded down to possession in order to avoid prosecution on much more serious charges. In the US, just 1.6 percent of the state inmate population were held for offences involving only marijuana, and less than one percent of all state prisoners (0.7 percent) were incarcerated with marijuana possession as the only charge. An even smaller fraction of state prisoners were first time offenders (0.3 percent). The numbers on the US federal prisons are similar. In 2001, the overwhelming majority of offenders sentenced for marijuana crimes were convicted for trafficking and only 63 served time for simple possession.
Detective superintendent Eva Brännmark from the Swedish National Police Board, in a speech given to Drug Free Australia's first international conference on illicit drug use, said:
The police have been able to solve other crimes, e.g. burglaries, thefts and robberies, by questioning people arrested for using drugs. Some even provide information about people who are selling drugs, and the police have seized large amounts of drugs as a result of information from people brought in for a urine test. Many interrogations of drug abusers have also resulted in search warrants and the recovery of stolen property.
The argument that drug addicts of certain drugs are forced into crime by prohibition should first and foremost highlight the fact that this argument presupposes and underlines the addictive nature of some illicit drugs (which legalization proponents often downplay), addictive enough to create a viable criminal supply industry. Secondly, the harms of increased addictive drug use, which as previously outlined would be a consequence of legalization and its cheaper prices, far outweigh the current crime harms of prohibition. It is worth pointing out, this argument is not useful for substances such as LSD and mescaline, with no addictive properties.
Although criminal punishments vary with rooting out drug usage, it is not the foremost eradication technique to resolve substance use disorder issues. In order to combat these issues, the application of treatment and support group resources coupled with community support and understanding, has far higher long-term potential to cure the ever-growing epidemic plaguing the nation, especially in rural areas.
=== Arguments for drug law reform ===
In 2021, Professor Peter Singer described the War on Drugs as an expensive, ineffective and extremely harmful policy.
==== Violence and profits of drugs traffickers ====
Prohibition protects the drug cartel insofar as it keeps the distribution in the black market and creates the risk that makes smuggling profitable. As former federal narcotics officer Michael Levine states in relation to his undercover work with Colombian cocaine cartels, from Lamar
"I learned that not only did they not fear our war on drugs, they counted on it to increase the market price and to weed out the smaller, inefficient drug dealers. They found U.S. interdiction efforts laughable. The only U.S. action they feared was an effective demand reduction program. On one undercover tape-recorded conversation, a top cartel chief, Jorge Roman, expressed his gratitude for the drug war, calling it "a sham put on for the American taxpayer" that was actually "good for business".
Critics of drug prohibition often cite the fact that the end of alcohol prohibition in 1933 led to immediate decreases in murders and robberies to support the argument that legalization of drugs could have similar effects. Once those involved in the narcotics trade have a legal method of settling business disputes, the number of murders and violent crime could drop. Robert W. Sweet, a federal judge, strongly agrees: "The present policy of trying to prohibit the use of drugs through the use of criminal law is a mistake". When alcohol use was outlawed during prohibition, it gave rise to gang warfare and spurred the formation of some of the most well known criminals of the era, among them the infamous Al Capone. Similarly, drug dealers today resolve their disputes through violence and intimidation, something which legal drug vendors do not do. Prohibition critics also point to the fact that police are more likely to be corrupted in a system where bribe money is so available. Police corruption due to drugs is widespread enough that one pro-legalization newsletter has made it a weekly feature.
Drug money has been called a major source of income for terrorist organizations. Critics assert that legalization would remove this central source of support for terrorism. While politicians blame drug users for being a major source of financing terrorists, no clear evidence of this link has been provided. US government agencies and government officials have been caught trafficking drugs to finance US-supported terrorist actions in events such as the Iran-Contra Affair, and Manuel Noriega but the isolated nature of these events precludes them from being major sources of financing.
==== Corruption ====
Human rights organizations and legal scholars have claimed that drug prohibition inevitably leads to police corruption.
On 2 July 2010, former Interpol President Jackie Selebi was found guilty of corruption by the South African High Court in Johannesburg for accepting bribes worth US$156,000 from a drug trafficker. After being charged in January 2008, Selebi resigned as president of Interpol and was put on extended leave as National Police Commissioner of South Africa.
==== Stigma of conviction ====
Despite the fact that most drug offenders are non-violent, the stigma attached to a conviction can prevent employment and education.
Since the human brain continues to mature past age eighteen and into a person's early twenties, it has been argued that many adult drug users will have made decisions to take drugs when their brains were not fully developed and thus they may not have adequately appreciated the risks (as many drug users are under the age of thirty). Since having a drug conviction will create societal disadvantages for the rest of a person's life, it has been argued that drug laws do not adequately take into account the full extent of human maturity when punishing people for taking drugs.
==== Children being lured into the illegal drug trade ====
Janet Crist of the White House Office of National Drug Control Policy mentioned that the anti-drug efforts have had "no direct effect on either the price or the availability of cocaine on our streets". Additionally, drug dealers show off expensive jewellery and clothing to young children. Some of these children are interested in making fast money instead of working legitimate jobs. Drug decriminalization would remove the "glamorous Al Capone-type traffickers who are role-models for the young".
The lack of government regulation and control over the lucrative illegal drug market has created a large population of unregulated drug dealers who lure many children into the illegal drug trade. The U.S. government's most recent 2009 National Survey on Drug Use and Health (NSDUH) reported that nationwide over 800,000 adolescents ages 12–17 sold illegal drugs during the previous 12 months preceding the survey. The 2005 Youth Risk Behavior Survey by the U.S. Centers for Disease Control and Prevention (CDC) reported that nationwide 25.4% of students had been offered, sold, or given an illegal drug by someone on school property. The prevalence of having been offered, sold, or given an illegal drug on school property ranged from 15.5% to 38.7% across state CDC surveys (median: 26.1%) and from 20.3% to 40.0% across local surveys (median: 29.4%).
Despite more than $7 billion spent annually towards arresting and prosecuting nearly 800,000 people across the country for marijuana offenses in 2005, the federally funded Monitoring the Future Survey reports about 85% of high school seniors find marijuana "easy to obtain." That figure has remained virtually unchanged since 1975, never dropping below 82.7% in three decades of national surveys.
==== Environmental ====
With respect to drug crop cultivation, eradication efforts in line with prohibitionist drug policies ultimately force coca, poppy, and marijuana growers into more remote, ecologically sensitive areas. These crops, which are generally grown away from urban centers and state presence, tend to deplete forestland and expand the agricultural frontier. Out of fear of eradication, cultivators are incentivized to accelerate production cycles in order to obtain the highest yield in the shortest period of time; the pace and methods used by growers neglect measures to promote sustainability, exacerbating the environmental impact. Drug cultivators typically opt to produce in areas with ecosystems with abundant plant biomass to better conceal their operations. Ultimately, this practice leads to increased deforestation which contributes to a greater influx of greenhouse gases into the atmosphere. Moreover, the aerial spraying of herbicides such as glyphosate used in eradication and control efforts have been shown to have negative effects on environmental and human health.
The "balloon effect" also operates further up the drug commodity chain in countries where drugs are trafficked rather than cultivated. Like eradication programs, interdiction pushes traffickers into remote areas where they exacerbate preexisting pressures on forestland. Traffickers use slash and burn practices to convert forest into arable land for cash crop production for the purposes of money laundering as well as the construction of clandestine roads and airstrips. The war on drugs and prohibitionist policies only serve to aggravate the already detrimental impacts of narco-trafficking on Central American forests. Intensified ecological devastation across cultivation and trafficking zones is yet another negative unintended consequence of emphasis on supply-side narcotic reduction borne by poor countries.
==== User cost of drugs ====
When the cost of drugs increases, drug users are more likely to commit crimes in order to obtain money to buy the expensive drugs. Legalizing drugs would make drugs reasonably cheap.
== Discriminatory ==
=== Arguments for inconsistent drug laws ===
In response to the issue of consistency with regard to drug prohibition and the dangers of alcohol former director of the ONDCP John P. Walters, has said, "It's ludicrous to say we have a great deal of problems from the use of alcohol so we should multiply that with marijuana".
=== Arguments against inconsistent drug laws ===
Since alcohol prohibition ended and the war on drugs began there has been much debate over the issue of consistency among legislators with regard to drug prohibition. Many anti-prohibition activists focus on the well-documented dangers of alcohol (such as alcoholism, cystitis, domestic violence, brain and liver damage). In addition to anecdotal evidence, they cite statistics to show more deaths caused by drunk driving under the influence of alcohol than by drivers under the influence of marijuana, and research which suggests that alcohol is more harmful than all but the most "dangerous" drugs. When the level of harm associated with the other drugs includes harm that arises solely as a result of the drugs illegality rather than merely that danger which is associated with actually using the drugs, only heroin, cocaine, barbiturates and street methadone were shown to be more harmful than the legal drug alcohol.
A 2002 DAWN report, for the USA records two possible drug-induced deaths where marijuana was the only drug found. Legal drugs however, have been the cause of more than half a million deaths a year: 480,000 from tobacco smoking-related illnesses and 80,000 from alcohol use disorder. Together, tobacco and alcohol cause about 20% of all yearly deaths in the USA.
It is argued that inconsistency between the harm caused and the legal status of these common drugs undermines the declared motives of the law enforcement agencies to reduce harm by prohibition, for example of marijuana.
In February 2009, the UK government was accused by its most senior expert drugs adviser Professor David Nutt of making political decisions with regard to drug classification, for example in rejecting the scientific advice to downgrade ecstasy from a class A drug. The Advisory Council on the Misuse of Drugs (ACMD) report on ecstasy, based on a 12-month study of 4,000 academic papers, concluded that it is nowhere near as dangerous as other class A drugs such as heroin and crack cocaine, and should be downgraded to class B. The advice was not followed. Jacqui Smith, then Home Secretary, was also widely criticised by the scientific community for bullying Professor David Nutt into apologising for his comments that, in the course of a normal year, more people died from falling off horses than died from taking ecstasy. Professor Nutt was later sacked by Jacqui Smith's successor as Home Secretary Alan Johnson; Johnson saying "It is important that the government's messages on drugs are clear and as an advisor you do nothing to undermine public understanding of them. I cannot have public confusion between scientific advice and policy and have therefore lost confidence in your ability to advise me as Chair of the ACMD."
==== Consistency between drugs ====
In the United States, defendants convicted of selling crack cocaine receive equal sentences to those convicted of selling 100 times the same amount of powder cocaine. This disparity was lessened during the Obama administration when the Fair Sentencing Act 2010 changed the ratio to 18 to 1. The majority of offenders convicted for selling crack are poor and/or black, while the majority of those convicted for selling cocaine are not.
==== Same policy for distinct drugs ====
Many drug policies group all illegal drugs into a single category. Since drugs drastically vary in their effects, addictive potential, dosages, methods of production, and consumption the arguments either way could be seen as inconsistent.
==== Race and enforcement of drug laws ====
It has been alleged that current drug laws are enforced in such a way as to penalize non-whites more harshly and more often than whites, and to penalize the poor of all races more harshly and more often than the middle and upper classes. For example, up until 2012, crack cocaine carried penalties one hundred times more severe than cocaine despite the fact that these drugs are essentially identical. Especially in urban black communities, convictions were nearly exclusively for crack, while cocaine use is statistically much higher among affluent whites.
== Civil rights ==
=== Civil rights arguments for prohibitive drug laws ===
Article 33 of the United Nations Convention on the Rights of the Child reads:
States Parties shall take all appropriate measures, including legislative, administrative, social and educational measures, to protect children from the illicit use of narcotic drugs and psychotropic substances as defined in the relevant international treaties and to prevent the use of children in the illicit production and trafficking of such substances.
Drug Free Australia argues:
The notion that illicit drug use is a victimless crime and that everyone should be free to do what they want with their body disregards the web of social interactions that constitute human existence. Affected by an individual's illicit drug use are children, parents, grandparents, friends, colleagues, work, victims of drugged drivers, crime victims, elder abuse, sexual victims etc. Illicit drug use is no less victimless than alcoholism.
Drug Free Australia gives the example that in 2007 one in every nine children under the age of 18 in the United States lived with at least one drug dependent or drug abusing parent. 2.1 million children in the United States live with at least one parent who was dependent on or used illicit drugs.
The Christian Institute argues that there is no point in having criminal laws unless those caught breaking them will at least face prosecution. Less serious offenses, such as failing to complete a census form, may also attract a criminal record, so the contention that criminalizing drug use is draconian can be seen as overstatement.
"Parental substance dependence and abuse can have profound effects on children, including child abuse and neglect, injuries and deaths related to motor vehicle accidents, and increased odds that the children will become substance dependent or abusers themselves. Up-to-date estimates of the number of children living with substance-dependent or substance-abusing parents are needed for planning both adult treatment and prevention efforts and programs that support and protect affected children."
Drug Free Australia concludes any democratic society that deems the use of a certain drug to present unacceptable harm to the individual user, to present unacceptable harm to the users' surrounding community or to transfer too great a burden to the community will seek legislation which will curb that particular freedom of the individual.
Sweden's centre-right alliance government Moderate Party advocates "Zero tolerance for crime", arguing:
Few things restrict people's freedom as much as the consequences of violence, drugs and criminality in society.
Many people argue that only drug dealers should be fought and not the drug users themselves. But this rests on the fundamental error that big-time drugs smugglers and dealers hawk illicit drugs to new consumers. This is most often not the case. Rather it is the users themselves that are mostly responsible for recruiting new users through networks of friends or relatives demonstrating that users need to be targeted as the recruiters of new drug use, and that an emphasis on early rehabilitation for young users is the best answer to curbing widespread dealing. Sweden's mandatory rehabilitation program has resulted in the lowest drug use levels in the developed world.
The freedom of choice of those addicted to a drug is also questioned, recognizing that addiction is defined as compulsive by its very nature and that addictions in and of themselves curb individual freedom. Likewise, the proposal that addictive drugs should be legalized, regulated and opened to "free market dynamics" is immediately belied by the recognition that the drug market for an addict is no longer a free market – it is clear that they will pay any price when needing their drug.
=== Civil rights arguments for drug law reform ===
==== Cognitive liberty ====
Authors such as Aldous Huxley and Terence McKenna believed that what persons do in private should not be regulated by the government. It is argued that persons should be able to do whatever they want with their bodies, including the recreational use of drugs, as long as they do not harm others. Such arguments often cite the harm principle of philosopher John Stuart Mill who urged that the state had no right to intervene to prevent individuals from doing something that harmed them, if no harm was thereby done to the rest of society: 'Over himself, over his own body and mind, the individual is sovereign' and 'The only purpose for which power can be rightfully exercised over any member of a civilized community, against his will, is to prevent harm to others. His own good, either physical or moral, is not sufficient warrant.' The argument is that drug use is a victimless crime and as such the government has no right to prohibit it or punish drug consumers, much like the government does not forbid overeating, which causes significantly more deaths per year. This can be equated with the quest for freedom of thought.
==== Spiritual and religious ====
We're playing with half a deck as long as we tolerate that the cardinals of government and science should dictate where human curiosity can legitimately send its attention and where it can not. It's an essentially preposterous situation. It is essentially a civil rights issue, because what we're talking about here is the repression of a religious sensibility. In fact, not a religious sensibility, the religious sensibility.
Some religious groups including the União do Vegetal, the Native American Church, the Bwiti religion and the Rastafari movement (see religious and spiritual use of cannabis) use psychoactive substances as sacrament in religious rituals. In some religious practice, drugs are sometimes used as a conduit to an oceanic feeling or divine union, equated with mysticism or entheogenic ('that which causes God to be within an individual') experiences. In others, the 'entactogenic' qualities of drugs are used to enhance feelings of empathy among congregations.
==== Personal development and exploration ====
Some people believe that altered states of consciousness enable many people to push the boundaries of human experience, knowledge, and creativity. There is thus a moral imperative to use drugs in terms of human progress, teleological development, or just increased artistic creativity; such ideas are central to Cognitive Liberty, Stoned Ape Hypothesis and Aldous Huxley's The Doors of Perception.
In PiHKAL, Alexander Shulgin, argues that the psychedelics help us learn about ourselves; indeed that is where the name "psychedelic" (mind expanding) comes from. I am completely convinced that there is a wealth of information built into us, with miles of intuitive knowledge tucked away in the genetic material of every one of our cells. Something akin to a library containing uncountable reference volumes, but without any obvious route of entry. And, without some means of access, there is no way to even begin to guess the extent and quality of what is there. The psychedelic drugs allow exploration of this interior world, and insights into its nature.
== Moral and ethical reasons ==
=== Moral arguments for prohibitive drug laws ===
=== Moral arguments for drug law reform ===
Many people, including some religious groups, argue that the war on drugs is itself immoral.
In 2007, Richard Brunstrom, the Chief Constable of North Wales, one of Britain's most senior police officers, said "If policy on drugs is in future to be pragmatic not moralistic, driven by ethics not dogma, then the current prohibitionist stance will have to be swept away as both unworkable and immoral, to be replaced with an evidence-based unified system (specifically including tobacco and alcohol) aimed at minimisation of harms to society."
The author and physician Andrew Weil has commented on the peculiar attitude and emotional bias of some people who think "drug taking is bad", but who nevertheless consume alcohol, and formulate the unhelpful conception "We drink. Therefore alcohol is not a drug."
The UK drug policy reform group Release believe that the stigma attached to drug use needs to be removed. Release's actions have included challenging such stigmatisation with its "Nice People Take Drugs" advertising campaign.
== Political ==
=== Sending out signals ===
==== Arguments for sending out signals ====
Some argue that sending out signals should be a consideration of drug policy. Previous UK Home Office Minister Vernon Coaker argued "is not part of any system with respect to drugs ... not only trying to send messages out to people who misuse drugs but also about trying to send messages out to people out there in the community?"
In response to the UK government's official drugs advisory body's opposition to cannabis reclassification (upwards, from a class C to a class B drug) in 2008, prime minister Gordon Brown said: "I believe that if we're sending out a signal, particularly to teenagers – and particular those at the most vulnerable age, young teenagers – that in any way we find cannabis acceptable, given all we know about the way that cannabis is being sold in this country, that is not the right thing to do. There's a stronger case now for sending out a signal that cannabis is not only illegal, it's unacceptable."
==== Arguments against sending out signals ====
The Science and Technology Select Committee appointed by the House of Commons to inquire into the Government's handling of scientific advice, risk and evidence in policy making agreed with Transform Drug Policy Foundation's view that "Criminal law is supposed to prevent crime, not 'send out' public health messages". Transform warned that sending out signals could backfire by "fostering distrust of police and public health messages amongst young people". The Select Committee's report said "The Government's desire to use the Class of a particular drug to send out a signal to potential users or dealers does not sit comfortably with the claim that the primary objective of the classification system is to categorise drugs according to the comparative harm associated with their misuse. It is also incompatible with the Government's stated commitment to evidence based policy making since it has never undertaken research to establish the relationship between the Class of a drug and the signal sent out and there is, therefore, no evidence base on which to draw in making these policy decisions."
=== Political calculation ===
==== Arguments for political calculation ====
John Donnelly, writing for the Boston Globe on the presidential race of 2000, suggested that the candidates' silence on drug policy may stem from a widely shared belief that any position even hinting at reducing penalties for drug use would be political suicide. Charles R. Schuster, director of the National Institute on Drug Abuse under Presidents Reagan and Bush (Snr.), was reported as saying in 1997, "Talking sense about drug policy in today's climate of opinion can be political suicide."
Drug policy academic Mark A.R. Kleiman has argued: There are things we can do about drug policy that would reduce the number of people in prison, and the extent of drug abuse and drug related crime. Legalization isn't one of them because there's not public support for it. And if we acknowledge the fact that, from the point of view of the majority of the population it's a loser, then it's not as if we can talk them out of that, so I think the legalization debate is mostly a distraction from doing the real work of fixing our drug policies
Scott Morgan reports how he once attended a discussion of Peter Reuter and David Boyum's book An Analytic Assessment of U.S. Drug Policy, in which the authors admitted ignoring the legalization option in their analysis. Boyum claimed that there was no legitimate political support for ending the drug war and that he and Reuter had therefore confined themselves to recommendations that they thought were politically viable.
==== Arguments against political calculation ====
The deaths of two teenage boys in the United Kingdom in March 2010 sparked a nationwide controversy over the amphetamine drug mephedrone, which had gained popularity as a legal high. The Advisory Council on the Misuse of Drugs (ACMD) recommended a ban on the drug, which was quickly passed into law, but the decision was criticised for being politically rather than scientifically driven and led to the resignation of the ACMD's Eric Carlin, the eighth member of the council to leave in five months in protest at what was seen as political interference. Toxicology reports released in May revealed that the boys had never taken the drug. In a later commentary, David Nutt noted that the pharmacology of mephedrone was not known at the time it was banned, and that the decision was so knee-jerk that the ACMD accidentally banned the wrong enantiomer for about a year.
Professor Colin Blakemore, professor of neuroscience at the University of Oxford, said: "This shocking news should be a salutary lesson to tabloid journalists and prejudiced politicians who held a gun to the heads of the ACMD and demanded that this drug should be banned before a single autopsy had been completed ... The politicians talk about using drug classification as a way of sending 'messages' to young people. I fear that the only message that will be sent by the hasty decision on mephedrone is that the drug laws deserve no respect."
Professor David Nutt, the former chairman of the ACMD, said: "the previous government's rush to ban mephedrone never had any serious scientific credibility – it looks much more like a decision based on a short-term electoral calculation. This news demonstrates why it's so important to base drug classification on the evidence, not fear, and why the police, media and politicians should only make public pronouncements once the facts are clear."
== Public opinion ==
=== Public opinion on prohibitive drug laws ===
A direct example of societal attitudes driving the International Drug Conventions is the 1925 speech by the Egyptian delegate M. El Guindy to the 1925 Geneva Convention forum which prohibited cannabis – largely reproduced in Willoughby, W. W.; In the late 19th and early 20th century drug use was regarded by the public "as alone a habit, vice, sign of weakness or dissipation", similar to the view of those who could not control their use of the licit drug alcohol. The use of illicit drugs has been prohibited internationally since 1912, an entire century, because of international agreement that the general community has a greater right to protect itself from the harms of illicit drug use than does an individual user to use a harmful substance recreationally.
Currently there is still greater public support for the continued prohibiting of illicit drug use than there is for legalizing and regulating the use of these substances. In the United States 82% of those polled by the Family Research Association in 1998 were opposed to the legalization of heroin and cocaine in the same manner as alcohol is legal. In October 2009 a Gallup poll found that 54% of those polled were against the legalization of cannabis. In Australia, which has had the highest levels of illicit drug use in Organisation for Economic Co-operation and Development (or OECD) countries for more than a decade, according to a 2007 survey, 95% of Australians do not support the legalization of heroin, cocaine and amphetamines, and 79% do not support the legalization of cannabis.
It can be argued that the negative attitudes to illicit drug use which issued in the international drug Conventions, with prohibitions against their use 100 years ago, still exist today. Taking again statistics from Australia, 97% disapprove of the regular use of heroin, 96% disapprove the regular use of amphetamines or cocaine, and 76.5% disapprove of the regular use of cannabis. In any democracy where "the will of the people" is respected by its political representatives, the prohibition of these substance might well be expected to remain intact.
=== Public opinion on drug law reform ===
According to Transform Drug Policy Foundation, over the past decade there has been strong shift in public opinion in favour of drug policy reform. This shift has taken place despite successive government's reluctance to consider or debate the subject, or even call to for an independent inquiry.
A national telephone survey conducted in 1993 found that between 52% and 55% of Australians believed that growing and possessing cannabis for personal use should be legalised.
An ICM poll of 1201 people for The Guardian in 1998 found that 47% believed that the illegality of drugs actually encourages young people to try them.
46% of UK adults in a 2002 Guardian poll (of 1075) felt that drug addicts who register themselves as such should have access to certain illegal drugs via prescription.
An ICM poll of 1008 UK adults (aged 16+) for The Guardian in 2008 found that 38% would support a scheme, similar to that established in Portugal and Spain, whereby it is not a criminal offence to possess and use drugs privately.
Following President Barack Obama's win of the 2008 presidential election, Change.gov hosted a service on their website named the Citizen's Briefing Book allowing United States citizens to give their opinion on the most important issues in America, and allow others to vote up or down on those ideas. The top ten ideas are to be given to Obama on the day of his inauguration, January 20, 2009. The most popular idea according to respondents was "Ending Marijuana Prohibition", earning 92,970 points and obtaining a total of 3,550 comments.
The second most popular hope, by contrast, was "Commit to becoming the "Greenest" country in the world." with 70,470 points.
Marijuana has seen a renaissance in its utopian representation in films such as the suburban satire American Beauty (1999, dir. Sam Mendes) and the stoner comedy Pineapple Express (2008, dir. David Gordon Green). Another venue for contemporary criticism of marijuana prohibition is television, such as the Showtime series Weeds (2005–2012, dev. Jenji Kohan); the HBO series True Blood (2008–2014, dev. Alan Ball); and adult animation shows such as South Park, Family Guy, and American Dad!.
David Simon, creator of the television series The Wire, in 2011 told U.S. Attorney General Eric Holder that he'd "give him another season of the HBO show for an end to the war on drugs." Holder had invited show stars Wendell Pierce, Sonja Sohn, and Jim True-Frost to Washington on behalf of an anti-drug public relations campaign and at the time called on Simon and Ed Burns for another season or a movie of the show. Simon replied via a letter to a newspaper offering the trade.
In November 2020, 76 percent of voters in Washington D.C. voted in favor of the initiative to decriminalize psychedelic plants and fungi.
== See also ==
== Notes ==
== References ==
== Further reading ==
"The Mission to End Prohibition." Making Contact. National Radio Project, Oakland CA: 4 November 2009 [2]
Toward a Policy on Drugs: Decriminalization? Legalization? Currie, Elliot. Dissent. 1993. Rpt. in Drug Use Should Be Decriminalized. At Issue: Legalizing Drugs. Karin L. Swisher, ed., San Diego, CA.: Greenhaven Press, Inc., 1996: 55–64.
Rolles S. Kushlick D. Jay M. 2004 After the War on Drugs, Options for Control Transform Drug Policy Foundation
Legalization Madness. Inciardi, James A. and Christine A. Saum. Public Interest 123 (1996): 72–82. Rpt. in Legalizing Drugs Would Increase Violent Crime. Current Controversies: Illegal Drugs. Charles P. Cozic, ed., San Diego, CA.: Greenhaven Press, Inc., 1998: 142–150.
Poll Shows Most Russians Against Legalization of Soft Drugs. ITAR-TASS. BBC Monitoring 26 June 2003. Newsbank. 1 Feb 2004.
Jaffer, Mehru, U.N. Firm Against Legalization of Drugs. Inter Press Service 17 Apr. 2003. Newsbank. 1 Feb. 2004 [3].
Lavoie, Dusty, Marijuanatopia? – Placing Pot Media in the U.S. Social Imaginary: Surveillance, Consumption & Pleasure. ProQuest Dissertations, University of Maine, 2011.
Luna, Claire. Orange County Judge Gray, a Drug-War Foe, Will Run for Senate Now a Libertarian, the Longtime Advocate of Legalization Will Challenge Boxer in 2004. Los Angeles Times 20 Nov. 2003: B3. Newsbank. 1 Feb. 2004 [4].
Lynch, Gerald W. Legalizing Drugs Is Not the Solution. America 13 Feb. 1993. Rpt. in Legalizing Drugs Would Not Reduce Crime. At Issue: Legalizing Drugs. Karin L. Swisher, ed., San Diego, CA.: Greenhaven Press, Inc., 1996: 110–113.
McNeely, Jennifer. Methadone Maintenance Treatment. Lindesmith Center 1997. Rpt. in Methadone Is an Effective Treatment for Heroin Addiction. Current Controversies: Illegal Drugs. Charles P. Cozic, ed., San Diego, CA.: Greenhaven Press, Inc., 1998: 91–95.
McWilliams, Peter. Ain't Nobody's Business If You Do. Los Angeles, CA. : Prelude Press, 1996 (full text)
Mendez, Julia de Cruz and Ralf Winkler. Marihuana Tax Act of 1937. Jan. 1996. 24 Mar. 2004 [5].
Paulin, Alastair. Taxation Without Legalization. Mother Jones June 2003: 26. Newsbank. 1 Feb. 2004 [6].
Rodriguez, L. Jacabo. Time to End the Drug War. CATO Institute 13 Dec. 1997. 23 Feb. 2004 [7].
Should We Re-Legalize Drugs? United States Libertarian Party. 22 Feb. 2004 [8].
Thornton, Mark. Alcohol Prohibition Was a Failure. CATO Institute 17 July 1991. 24 Mar. 2004 [9].
Zuckerman, Mortimer B. Great Idea for Ruining Kids. U.S. News & World Report 24 Feb. 1997. Rpt. in Legalizing Drugs Would Increase Drug Use. Current Controversies: Illegal Drugs. Charles P. Cozic, ed., San Diego, CA.: Greenhaven Press, Inc., 1998: 151–152.
Leavitt, Fred. (2003) The REAL Drug Abusers. Rowman & Littlefield.
Armentano, Paul. Drug War Mythology in You Are Being Lied To. China: The Disinformation Company Ltd., 2001. pp. 234–240
Goldstein, P.J., Brownstein, H.H., Ryan, P.J. & Bellucci, P.A., Crack and Homicide in New York City: A Case Study in the Epidemiology of Violence, in Reinarman, C. and Levine, H. (eds.), Crack in America: Demon Drugs and Social Justice (Berkeley, CA: University of California Press, 1997), pp. 113–130.
Skorneck, Carolyn (Feb 1990). "Survey: 61 percent say all drugs immoral". Moscow-Pullman Daily News.
== External links ==
Why It's Time to Legalize Drugs. Published by HuffPost on 23 February 2016. Last updated on 23 February 2017. Author - Kofi Annan (Secretary-General of the United Nations from January 1997 to December 2006).
"After the War on Drugs: Blueprint for Regulation", 1 July 2009
The Mission to End Prohibition, Making Contact. 4 Nov 2009.
EMCDDA—Decriminalisation in Europe? Recent developments in legal approaches to drug use.
The case for legalisation, The Economist, Jul. 26 2001.
The Senlis Council, international think tank on drug policy reform.
European coalition for Just and effective drugs policies
Cannabis. American Heritage Dictionary of the English Language. Fourth Edition. 2000. Rpt. in Dictionary.com 25 Mar 2004
War on Drugs. Mary H. Cooper. Congressional Quarterly 13 Mar. 1993: 243–258. SIRS. 1 Feb. 2004.
An interview with pro-legalization Nobel laureate economist Milton Friedman
The Drug War as a Socialist Enterprise by Milton Friedman
Simpson, John, 'Rethinking the war on drugs', BBC News, 7 October 2005.
Marijuana 'top cash crop in US', BBC News, 19 December 2006. | Wikipedia/Arguments_for_and_against_drug_prohibition |
The prohibition of drugs through sumptuary legislation or religious law is a common means of attempting to prevent the recreational use of certain intoxicating substances.
An area has a prohibition of drugs when its government uses the force of law to punish the use or possession of drugs which have been classified as controlled. A government may simultaneously have systems in place to regulate both controlled and non controlled drugs. Regulation controls the manufacture, distribution, marketing, sale, and use of certain drugs, for instance through a prescription system. For example, in some states, the possession or sale of amphetamines is a crime unless a patient has a physician's prescription for the drug; having a prescription authorizes a pharmacy to sell and a patient to use a drug that would otherwise be prohibited. Although prohibition mostly concerns psychoactive drugs (which affect mental processes such as perception, cognition, and mood), prohibition can also apply to non-psychoactive drugs, such as anabolic steroids. Many governments do not criminalize the possession of a limited quantity of certain drugs for personal use, while still prohibiting their sale or manufacture, or possession in large quantities. Some laws (or judicial practice) set a specific volume of a particular drug, above which is considered ipso jure to be evidence of trafficking or sale of the drug.
Some Islamic countries prohibit the use of alcohol (see list of countries with alcohol prohibition). Many governments levy a tax on alcohol and tobacco products, and restrict alcohol and tobacco from being sold or gifted to a minor. Other common restrictions include bans on outdoor drinking and indoor smoking. In the early 20th century, many countries had alcohol prohibition. These include the United States (1920–1933), Finland (1919–1932), Norway (1916–1927), Canada (1901–1948), Iceland (1915–1922) and the Russian Empire/USSR (1914–1925). In fact, the first international treaty to control a psychoactive substance adopted in 1890 actually concerned alcoholic beverages (Brussels Conference). The first treaty on opium only arrived two decades later, in 1912.
== Definitions ==
Drugs, in the context of prohibition, are any of a number of psychoactive substances whose use a government or religious body seeks to control. What constitutes a drug varies by century and belief system. What is a psychoactive substance is relatively well known to modern science. Examples include a range from caffeine found in coffee, tea, and chocolate, nicotine in tobacco products; botanical extracts morphine and heroin, and synthetic compounds MDMA and fentanyl. Almost without exception, these substances also have a medical use, in which case they are called pharmaceutical drugs or just pharmaceuticals. The use of medicine to save or extend life or to alleviate suffering is uncontroversial in most cultures. Prohibition applies to certain conditions of possession or use. Recreational use refers to the use of substances primarily for their psychoactive effect outside of a clinical situation or doctor's care.
In the twenty-first century, caffeine has pharmaceutical uses. Caffeine is used to treat bronchopulmonary dysplasia. In most cultures, caffeine in the form of coffee or tea is unregulated. Over 2.25 billion cups of coffee are consumed in the world every day. Some religions, including the Church of Jesus Christ of Latter-day Saints, prohibit coffee. They believe that it is both physically and spiritually unhealthy to consume coffee.
A government's interest to control a drug may be based on its negative effects on its users, or it may simply have a revenue interest. The British parliament prohibited the possession of untaxed tea with the imposition of the Tea Act of 1773. In this case, as in many others, it is not a substance that is prohibited, but the conditions under which it is possessed or consumed. Those conditions include matters of intent, which makes the enforcement of laws difficult. In Colorado possession of "blenders, bowls, containers, spoons, and mixing devices" is illegal if there was intent to use them with drugs.
Many drugs, beyond their pharmaceutical and recreational uses, have industrial uses. Nitrous oxide, or laughing gas is a dental anesthetic, also used to prepare whipped cream, fuel rocket engines, and enhance the performance of race cars. Ethanol, or drinking alcohol, is also used as a fuel, industrial solvent and disinfectant.
== History ==
The cultivation, use, and trade of psychoactive and other drugs has occurred since ancient times. Concurrently, authorities have often restricted drug possession and trade for a variety of political and religious reasons. In the 20th century, the United States led a major renewed surge in drug prohibition called the "War on Drugs".
=== Early drug laws ===
The prohibition on alcohol under Islamic Sharia law, which is usually attributed to passages in the Qur'an, dates back to the early seventh century. Although Islamic law is often interpreted as prohibiting all intoxicants (not only alcohol), the ancient practice of hashish smoking has continued throughout the history of Islam, against varying degrees of resistance. A major campaign against hashish-eating Sufis were conducted in Egypt in the 11th and 12th centuries resulting among other things in the burning of fields of cannabis.
Though the prohibition of illegal drugs was established under Sharia law, particularly against the use of hashish as a recreational drug, classical jurists of medieval Islamic jurisprudence accepted the use of hashish for medicinal and therapeutic purposes, and agreed that its "medical use, even if it leads to mental derangement, should remain exempt [from punishment]". In the 14th century, the Islamic scholar Az-Zarkashi spoke of "the permissibility of its use for medical purposes if it is established that it is beneficial".
In the Ottoman Empire, Murad IV attempted to prohibit coffee drinking to Muslims as haraam, arguing that it was an intoxicant, but this ruling was overturned soon after he died in 1640. The introduction of coffee in Europe from Muslim Turkey prompted calls for it to be banned as the devil's work, although Pope Clement VIII sanctioned its use in 1600, declaring that it was "so delicious that it would be a pity to let the infidels have exclusive use of it". Bach's Coffee Cantata, from the 1730s, presents a vigorous debate between a girl and her father over her desire to consume coffee. The early association between coffeehouses and seditious political activities in England led to the banning of such establishments in the mid-17th century.
A number of Asian rulers had similarly enacted early prohibitions, many of which were later forcefully overturned by Western colonial powers during the 18th and 19th centuries. In 1360, for example, King Ramathibodi I, of Ayutthaya Kingdom (now Thailand), prohibited opium consumption and trade. The prohibition lasted nearly 500 years until 1851 when King Rama IV allowed Chinese migrants to consume opium. The Konbaung Dynasty prohibited all intoxicants and stimulants during the reign of King Bodawpaya (1781–1819). After Burma became a British colony, the restrictions on opium were abolished and the colonial government established monopolies selling Indian-produced opium.
In late Qing China, opium imported by foreign traders, such as those employed by Jardine Matheson and the East India Company, was consumed by all social classes in Southern China. Between 1821 and 1837, imports of the drug increased fivefold. The wealth drain and widespread social problems that resulted from this consumption prompted the Chinese government to attempt to end the trade. This effort was initially successful, with Lin Zexu ordering the destruction of opium at Humen in June 1839. However, the opium traders lobbied the British government to declare war on China, resulting in the First Opium War. The Qing government was defeated and the war ended with the Treaty of Nanking, which legalized opium trading in Chinese law
=== First modern drug regulations ===
The first modern law in Europe for the regulating of drugs was the Pharmacy Act 1868 in the United Kingdom. There had been previous moves to establish the medical and pharmaceutical professions as separate, self-regulating bodies, but the General Medical Council, established in 1863, unsuccessfully attempted to assert control over drug distribution. The act set controls on the distribution of poisons and drugs. Poisons could only be sold if the purchaser was known to the seller or to an intermediary known to both, and drugs, including opium and all preparations of opium or of poppies, had to be sold in containers with the seller's name and address.
Despite the reservation of opium to professional control, general sales did continue to a limited extent, with mixtures with less than 1 percent opium being unregulated.
After the legislation passed, the death rate caused by opium immediately fell from 6.4 per million population in 1868 to 4.5 in 1869. Deaths among children under five dropped from 20.5 per million population between 1863 and 1867 to 12.7 per million in 1871 and further declined to between 6 and 7 per million in the 1880s.
In the United States, the first drug law was passed in San Francisco in 1875, banning the smoking of opium in opium dens. The reason cited was "many women and young girls, as well as young men of a respectable family, were being induced to visit the Chinese opium-smoking dens, where they were ruined morally and otherwise." This was followed by other laws throughout the country, and federal laws that barred Chinese people from trafficking in opium. Though the laws affected the use and distribution of opium by Chinese immigrants, no action was taken against the producers of such products as laudanum, a tincture of opium and alcohol, commonly taken as a panacea by white Americans. The distinction between its use by white Americans and Chinese immigrants was thus a form of racial discrimination as it was based on the form in which it was ingested: Chinese immigrants tended to smoke it, while it was often included in various kinds of generally liquid medicines often (but not exclusively) used by Americans of European descent. The laws targeted opium smoking, but not other methods of ingestion.
Britain passed the All-India Opium Act of 1878, which limited recreational opium sales to registered Indian opium-eaters and Chinese opium-smokers and prohibiting its sale to emigrant workers from British Burma.
Following the passage of a regional law in 1895, Australia's Aboriginals Protection and Restriction of the Sale of Opium Act 1897 addressed opium addiction among Aborigines, though it soon became a general vehicle for depriving them of basic rights by administrative regulation. Opium sale was prohibited to the general population in 1905, and smoking and possession were prohibited in 1908.
Despite these laws, the late 19th century saw an increase in opiate consumption. This was due to the prescribing and dispensing of legal opiates by physicians and pharmacists to relieve menstruation pain. It is estimated that between 150,000 and 200,000 opiate addicts lived in the United States at the time, and a majority of these addicts were women.
=== Changing attitudes and the drug prohibition campaign ===
Foreign traders, including those employed by Jardine Matheson and the East India Company, smuggled opium into China in order to balance high trade deficits. Chinese attempts to outlaw the trade led to the First Opium War and the subsequent legalization of the trade at the Treaty of Nanking. Attitudes towards the opium trade were initially ambivalent, but in 1874 the Society for the Suppression of the Opium Trade was formed in England by Quakers led by the Rev. Frederick Storrs-Turner. By the 1890s, increasingly strident campaigns were waged by Protestant missionaries in China for its abolition. The first such society was established at the 1890 Shanghai Missionary Conference, where British and American representatives, including John Glasgow Kerr, Arthur E. Moule, Arthur Gostick Shorrock and Griffith John, agreed to establish the Permanent Committee for the Promotion of Anti-Opium Societies.
Due to increasing pressure in the British parliament, the Liberal government under William Ewart Gladstone approved the appointment of a Royal Commission on Opium to India in 1893. The commission was tasked with ascertaining the impact of Indian opium exports to the Far East, and to advise whether the trade should be banned and opium consumption itself banned in India. After an extended inquiry, the Royal Commission rejected the claims made by the anti-opium campaigners regarding the supposed societal harm caused by the trade and the issue was finalized for another 15 years.
The missionary organizations were outraged over the Royal Commission on Opium's conclusions and set up the Anti-Opium League in China; the league gathered data from every Western-trained medical doctor in China and published Opinions of Over 100 Physicians on the Use of Opium in China. This was the first anti-drug campaign to be based on scientific principles, and it had a tremendous impact on the state of educated opinion in the West. In England, the home director of the China Inland Mission, Benjamin Broomhall, was an active opponent of the opium trade, writing two books to promote the banning of opium smoking: The Truth about Opium Smoking and The Chinese Opium Smoker. In 1888, Broomhall formed and became secretary of the Christian Union for the Severance of the British Empire with the Opium Traffic and editor of its periodical, National Righteousness. He lobbied the British parliament to ban the opium trade. Broomhall and James Laidlaw Maxwell appealed to the London Missionary Conference of 1888 and the Edinburgh Missionary Conference of 1910 to condemn the continuation of the trade. As Broomhall lay dying, an article from The Times was read to him with the welcome news that an international agreement had been signed ensuring the end of the opium trade within two years.
In 1906, a motion to 'declare the opium trade "morally indefensible" and remove Government support for it', initially unsuccessfully proposed by Arthur Pease in 1891, was put before the House of Commons. This time the motion passed. The Qing government banned opium soon afterward.
These changing attitudes led to the founding of the International Opium Commission in 1909. An International Opium Convention was signed by 13 nations at The Hague on January 23, 1912, during the First International Opium Conference. This was the first international drug control treaty and it was registered in the League of Nations Treaty Series on January 23, 1922. The Convention provided that "The contracting Powers shall use their best endeavors to control or to cause to be controlled, all person manufacturing, importing, selling, distributing, and exporting morphine, cocaine, and their respective salts, as well as the buildings in which these persons carry such an industry or trade."
The treaty became international law in 1919 when it was incorporated into the Treaty of Versailles. The role of the commission was passed to the League of Nations, and all signatory nations agreed to prohibit the import, sale, distribution, export, and use of all narcotic drugs, except for medical and scientific purposes.
=== Prohibition ===
In the UK the Defence of the Realm Act 1914, passed at the onset of the First World War, gave the government wide-ranging powers to requisition the property and to criminalize specific activities. A moral panic was whipped up by the press in 1916 over the alleged sale of drugs to the troops of the British Indian Army. With the temporary powers of DORA, the Army Council quickly banned the sale of all psychoactive drugs to troops, unless required for medical reasons. However, shifts in the public attitude towards drugs—they were beginning to be associated with prostitution, vice and immorality—led the government to pass further unprecedented laws, banning and criminalising the possession and dispensation of all narcotics, including opium and cocaine. After the war, this legislation was maintained and strengthened with the passing of the Dangerous Drugs Act 1920 (10 & 11 Geo. 5. c. 46). Home Office control was extended to include raw opium, morphine, cocaine, ecogonine and heroin.
Hardening of Canadian attitudes toward Chinese-Canadian opium users and fear of a spread of the drug into the white population led to the effective criminalization of opium for nonmedical use in Canada between 1908 and the mid-1920s.
The Mao Zedong government nearly eradicated both consumption and production of opium during the 1950s using social control and isolation. Ten million addicts were forced into compulsory treatment, dealers were executed, and opium-producing regions were planted with new crops. Remaining opium production shifted south of the Chinese border into the Golden Triangle region. The remnant opium trade primarily served Southeast Asia, but spread to American soldiers during the Vietnam War, with 20 percent of soldiers regarding themselves as addicted during the peak of the epidemic in 1971. In 2003, China was estimated to have four million regular drug users and one million registered drug addicts.
In the US, the Harrison Act was passed in 1914, and required sellers of opiates and cocaine to get a license. While originally intended to regulate the trade, it soon became a prohibitive law, eventually becoming legal precedent that any prescription for a narcotic given by a physician or pharmacist – even in the course of medical treatment for addiction – constituted conspiracy to violate the Harrison Act. In 1919, the Supreme Court ruled in Doremus that the Harrison Act was constitutional and in Webb that physicians could not prescribe narcotics solely for maintenance. In Jin Fuey Moy v. United States, the court upheld that it was a violation of the Harrison Act even if a physician provided prescription of a narcotic for an addict, and thus subject to criminal prosecution. This is also true of the later Marijuana Tax Act in 1937. Soon, however, licensing bodies did not issue licenses, effectively banning the drugs.
The American judicial system did not initially accept drug prohibition. Prosecutors argued that possessing drugs was a tax violation, as no legal licenses to sell drugs were in existence; hence, a person possessing drugs must have purchased them from an unlicensed source. After some wrangling, this was accepted as federal jurisdiction under the interstate commerce clause of the U.S. Constitution.
==== Alcohol prohibition ====
The prohibition of alcohol commenced in Finland in 1919 and in the United States in 1920. Because alcohol was the most popular recreational drug in these countries, reactions to its prohibition were far more negative than to the prohibition of other drugs, which were commonly associated with ethnic minorities, prostitution, and vice. Public pressure led to the repeal of alcohol prohibition in Finland in 1932, and in the United States in 1933. Residents of many provinces of Canada also experienced alcohol prohibition for similar periods in the first half of the 20th century.
In Sweden, a referendum in 1922 decided against an alcohol prohibition law (with 51% of the votes against and 49% for prohibition), but starting in 1914 (nationwide from 1917) and until 1955 Sweden employed an alcohol rationing system with personal liquor ration books ("motbok").
=== War on Drugs ===
In response to rising drug use among young people and the counterculture movement, government efforts to enforce prohibition were strengthened in many countries from the 1960s onward. Support at an international level for the prohibition of psychoactive drug use became a consistent feature of United States policy during both Republican and Democratic administrations, to such an extent that US support for foreign governments has often been contingent on their adherence to US drug policy. Major milestones in this campaign include the introduction of the Single Convention on Narcotic Drugs in 1961, the Convention on Psychotropic Substances in 1971 and the United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances in 1988. A few developing countries where consumption of the prohibited substances has enjoyed longstanding cultural support, long resisted such outside pressure to pass legislation adhering to these conventions. Nepal only did so in 1976.
In 1972, United States President Richard Nixon announced the commencement of the so-called "War on Drugs". Later, President Reagan added the position of drug czar to the President's Executive Office. In 1973, New York introduced mandatory minimum sentences of 15 years to life imprisonment for possession of more than 113 grams (4 oz) of a so-called hard drug, called the Rockefeller drug laws after New York Governor and later Vice President Nelson Rockefeller. Similar laws were introduced across the United States.
California's broader 'three strikes and you're out' policy adopted in 1994 was the first mandatory sentencing policy to gain widespread publicity and was subsequently adopted in most United States jurisdictions. This policy mandates life imprisonment for a third criminal conviction of any felony offense. A similar 'three strikes' policy was introduced to the United Kingdom by the Conservative government in 1997. This legislation enacted a mandatory minimum sentence of seven years for those convicted for a third time of a drug trafficking offense involving a class A drug.
=== Calls for legalization, relegalization or decriminalization ===
The terms relegalization, legalization, legal regulations, or decriminalization are used with very different meanings by different authors, something that can be confusing when the claims are not specified. Here are some variants:
Sales of one or more drugs (e.g., marijuana) for personal use become legal, at least if sold in a certain way.
Sales of an extracts with a specific substance become legal sold in a certain way, for example on prescription.
Use or possession of small amounts for personal use do not lead to incarceration if it is the only crime, but it is still illegal; the court or the prosecutor can impose a fine. (In that sense, Sweden both legalized and supported drug prohibition simultaneously.)
Use or possession of small amounts for personal use do not lead to incarceration. The case is not treated in an ordinary court, but by a commission that may recommend treatment or sanctions including fines. (In that sense, Portugal both legalized and supported drug prohibitions).
There are efforts around the world to promote the relegalization and decriminalization of drugs. These policies are often supported by proponents of liberalism and libertarianism on the grounds of individual freedom, as well as by leftists who believe prohibition to be a method of suppression of the working class by the ruling class.
Prohibition of drugs is supported by proponents of conservatism as well various NGOs. A number of NGOs are aligned in support of drug prohibition as members of the World Federation Against Drugs. In the WFAD constitution, the "Declaration of the World Forum Against Drugs" (2008) advocates for "no other goal than a drug-free world", and states that a balanced policy of drug abuse prevention, education, treatment, law enforcement, research, and supply reduction provides the most effective platform to reduce drug abuse and its associated harms and calls on governments to consider demand reduction as one of their first priorities. It supports the UN drug conventions, the inclusion of cannabis as one of the "hard drugs", and the use of criminal sanctions "when appropriate" to deter drug use. It opposes legalization in any form, and harm reduction in general.
According to some critics, drug prohibition is responsible for enriching "organised criminal networks" while the hypothesis that the prohibition of drugs generates violence is consistent with research done over long time-series and cross-country facts.
In the United Kingdom, where the principal piece of drug prohibition legislation is the Misuse of Drugs Act 1971, criticism includes:
Drug classification: making a hash of it?, Fifth Report of Session 2005–06, House of Commons Science and Technology Committee, which said that the present system of drug classification is based on historical assumptions, not scientific assessment
Development of a rational scale to assess the harm of drugs of potential misuse, David Nutt, Leslie A. King, William Saulsbury, Colin Blakemore, The Lancet, 24 March 2007, said the act is "not fit for purpose" and "the exclusion of alcohol and tobacco from the Misuse of Drugs Act is, from a scientific perspective, arbitrary"
The Drug Equality Alliance (DEA) argue that the Government is administering the Act arbitrarily, contrary to its purpose, contrary to the original wishes of Parliament and therefore illegally. They are currently assisting and supporting several legal challenges to this alleged maladministration.
In February 2008 the then-president of Honduras, Manuel Zelaya, called on the world to legalize drugs, in order, he said, to prevent the majority of violent murders occurring in Honduras. Honduras is used by cocaine smugglers as a transiting point between Colombia and the US. Honduras, with a population of 7 million, suffers an average of 8–10 murders a day, with an estimated 70% being a result of this international drug trade. The same problem is occurring in Guatemala, El Salvador, Costa Rica and Mexico, according to Zelaya. In January 2012 Colombian President Juan Manuel Santos made a plea to the United States and Europe to start a global debate about legalizing drugs. This call was echoed by the Guatemalan President Otto Pérez Molina, who announced his desire to legalize drugs, saying "What I have done is put the issue back on the table."
In a report dealing with HIV in June 2014, the World Health Organization (WHO) of the UN called for the decriminalization of drugs particularly including injected ones. This conclusion put WHO at odds with broader long-standing UN policy favoring criminalization. Eight states of the United States (Alaska, California, Colorado, Maine, Massachusetts, Nevada, Oregon, and Washington), as well as the District of Columbia, have legalized the sale of marijuana for personal recreational use as of 2017, although recreational use remains illegal under U.S. federal law. The conflict between state and federal law is, as of 2018, unresolved.
Since Uruguay in 2014 and Canada in 2018 legalized cannabis, the debate has known a new turn internationally.
On March 14th, 2025, the United Nations Commission on Narcotic Drugs decided to create a panel of independent experts to rethink the global drug control regime.
== Drug prohibition laws ==
The following individual drugs, listed under their respective family groups (e.g., barbiturates, benzodiazepines, opiates), are the most frequently sought after by drug users and as such are prohibited or otherwise heavily regulated for use in many countries:
Among the barbiturates, pentobarbital (Nembutal), secobarbital (Seconal), and amobarbital (Amytal)
Among the benzodiazepines, temazepam (Restoril; Normison; Euhypnos), flunitrazepam (Rohypnol; Hypnor; Flunipam), and alprazolam (Xanax)
Cannabis products, e.g., marijuana, hashish, and hashish oil
Among the dissociatives, phencyclidine (PCP), and ketamine are the most sought after.
hallucinogens such as LSD, mescaline, peyote, and psilocybin
Empathogen-entactogen drugs like MDMA ("ecstasy")
Among the narcotics, it is opiates such as morphine and codeine, and opioids such as diacetylmorphine (Heroin), hydrocodone (Vicodin; Hycodan), oxycodone (Percocet; Oxycontin), hydromorphone (Dilaudid), and oxymorphone (Opana).
Sedatives such as GHB and methaqualone (Quaalude)
Stimulants such as cocaine, amphetamine (Adderall), dextroamphetamine (Dexedrine), methamphetamine (Desoxyn), methcathinone, and methylphenidate (Ritalin)
The regulation of the above drugs varies in many countries. Alcohol possession and consumption by adults is today widely banned only in Islamic countries and certain states of India. Although alcohol prohibition was eventually repealed in the countries that enacted it, there are, for example, still parts of the United States that do not allow alcohol sales, though alcohol possession may be legal (see dry counties). New Zealand has banned the importation of chewing tobacco as part of the Smoke-free Environments Act 1990. In some parts of the world, provisions are made for the use of traditional sacraments like ayahuasca, iboga, and peyote. In Gabon, iboga (tabernanthe iboga) has been declared a national treasure and is used in rites of the Bwiti religion. The active ingredient, ibogaine, is proposed as a treatment of opioid withdrawal and various substance use disorders.
In countries where alcohol and tobacco are legal, certain measures are frequently undertaken to discourage use of these drugs. For example, packages of alcohol and tobacco sometimes communicate warnings directed towards the consumer, communicating the potential risks of partaking in the use of the substance. These drugs also frequently have special sin taxes associated with the purchase thereof, in order to recoup the losses associated with public funding for the health problems the use causes in long-term users. Restrictions on advertising also exist in many countries, and often a state holds a monopoly on manufacture, distribution, marketing, and/or the sale of these drugs.
=== List of principal drug prohibition laws by jurisdiction (non-exhaustive) ===
Australia: Standard for the Uniform Scheduling of Medicines and Poisons
Bangladesh: Narcotics Substances Control Act, 2018
Belize: Misuse of Drugs Act (Belize)
Canada: Controlled Drugs and Substances Act
Estonia: Narcotic Drugs and Psychotropic Substances Act (Estonia)
Germany: Narcotic Drugs Act
India: Narcotic Drugs and Psychotropic Substances Act (India)
Netherlands: Opium Law
New Zealand: Misuse of Drugs Act 1975
Pakistan: Control of Narcotic Substances Act 1997
Philippines: Comprehensive Dangerous Drugs Act of 2002
Poland: Drug Abuse Prevention Act 2005
Portugal: Decree-Law 15/93
Ireland: Misuse of Drugs Act (Ireland)
South Africa: Drugs and Drug Trafficking Act 1992
Singapore: Misuse of Drugs Act (Singapore)
Sweden: Lag om kontroll av narkotika (SFS 1992:860)
Thailand: Psychotropic Substances Act (Thailand) and Narcotics Act
United Kingdom: Misuse of Drugs Act 1971 and Drugs Act 2005
United States: Controlled Substances Act
International: Single Convention on Narcotic Drugs
=== Legal dilemmas ===
The sentencing statutes in the United States Code that cover controlled substances are complicated. For example, a first-time offender convicted in a single proceeding for selling marijuana three times, and found to have carried a gun on him all three times (even if it were not used) is subject to a minimum sentence of 55 years in federal prison.
In Hallucinations: Behavior, Experience, and Theory (1975), senior US government researchers Louis Jolyon West and Ronald K. Siegel explain how drug prohibition can be used for selective social control:
The role of drugs in the exercise of political control is also coming under increasing discussion. Control can be through prohibition or supply. The total or even partial prohibition of drugs gives the government considerable leverage for other types of control. An example would be the selective application of drug laws ... against selected components of the population such as members of certain minority groups or political organizations.
Linguist Noam Chomsky argues that drug laws are currently, and have historically been, used by the state to oppress sections of society it opposes:
Very commonly substances are criminalized because they're associated with what's called the dangerous classes, poor people, or working people. So for example in England in the 19th century, there was a period when gin was criminalized and whiskey wasn't, because gin is what poor people drink.
=== Legal highs and prohibition ===
In 2013 the European Monitoring Centre for Drugs and Drug Addiction reported that there are 280 new legal drugs, known as "legal highs", available in Europe. One of the best known, mephedrone, was banned in the United Kingdom in 2010. On November 24, 2010, the U.S. Drug Enforcement Administration announced it would use emergency powers to ban many synthetic cannabinoids within a month. An estimated 73 new psychoactive synthetic drugs appeared on the UK market in 2012. The response of the Home Office has been to create a temporary class drug order which bans the manufacture, import, and supply (but not the possession) of named substances.
=== Corruption ===
In certain countries, there is concern that campaigns against drugs and organized crime are a cover for corrupt officials tied to drug trafficking themselves. In the United States, Federal Bureau of Narcotics chief Harry Anslinger's opponents accused him of taking bribes from the Mafia to enact prohibition and create a black market for alcohol. More recently in the Philippines, one death squad hitman told author Niko Vorobyov that he was being paid by military officers to eliminate those drug dealers who failed to pay a 'tax'. Under President Rodrigo Duterte, the Philippines has waged a bloody war against drugs that may have resulted in up to 29,000 extrajudicial killings.
When it comes to social control with cannabis, there are different aspects to consider. Not only do we assess legislative leaders and the way they vote on cannabis, but we also must consider the federal regulations and taxation that contribute to social controls. For instance, according to a report on the U.S. customs and border protections, the American industry, although banned the main usage of marijuana, was still using products similar such as hemp seeds, oils etc. leading to the previously discussed marijuana tax act.
The Tax act provisions required importers to register and pay an annual tax of $24 and receive an official stamp. Stamps for Products were then affixed to each original order form and recorded by the state revenue collector. Then, a customs collector was to maintain the custody of imported marijuana at entry ports until required documents were received, reviewed and approved.Shipments were subject to searches, seizures and forfeitures if any provisions of the law were not met. Violations would result in fines of no more than $2000 or potential imprisonment for up to 5 years. Oftentimes, this created opportunity for corruption, stolen imports that would later lead to smuggling, oftentimes by state officials and tight knit elitists.
== Penalties ==
=== United States ===
Drug possession is the crime of having one or more illegal drugs in one's possession, either for personal use, distribution, sale or otherwise. Illegal drugs fall into different categories and sentences vary depending on the amount, type of drug, circumstances, and jurisdiction. In the U.S., the penalty for illegal drug possession and sale can vary from a small fine to a prison sentence. In some states, marijuana possession is considered to be a petty offense, with the penalty being comparable to that of a speeding violation. In some municipalities, possessing a small quantity of marijuana in one's own home is not punishable at all. Generally, however, drug possession is an arrestable offense, although first-time offenders rarely serve jail time. Federal law makes even possession of "soft drugs", such as cannabis, illegal, though some local governments have laws contradicting federal laws.
In the U.S., the War on Drugs is thought to be contributing to a prison overcrowding problem. In 1996, 59.6% of prisoners were drug-related criminals. The U.S. population grew by about +25% from 1980 to 2000. In that same 20 year time period, the U.S. prison population tripled, making the U.S. the world leader in both percentage and absolute number of citizens incarcerated. The United States has 5% of the world's population, but 25% of the prisoners.
About 90% of United States prisoners are incarcerated in state jails. In 2016, about 572,000, over 44%, of the 1.3 million people in these state jails, were serving time for drug offenses. 728,000 were incarcerated for violent offenses.
The data from Federal Bureau of Prisons online statistics page states that 45.9% of prisoners were incarcerated for drug offenses, as of December 2021.
=== European Union ===
In 2004, the Council of the European Union adopted a framework decision harmonizing the minimum penal provisions for illicit drug-related activities. In particular, article 2(9) stipulates that activities may be exempt from the minimum provisions "when it is committed by its perpetrators exclusively for their own personal consumption as defined by national law." This was made, in particular, to accommodate more liberal national systems such as the Dutch coffee shops (see below) or the Spanish Cannabis Social Clubs.
==== The Netherlands ====
In the Netherlands, cannabis and other "soft" drugs are decriminalised in small quantities. The Dutch government treats the problem as more of a public health issue than a criminal issue. Contrary to popular belief, cannabis is still technically illegal. Coffee shops that sell cannabis to people 18 or above are tolerated, and pay taxes like any other business for their cannabis and hashish sales, although distribution is a grey area that the authorities would rather not go into as it is not decriminalised. Many "coffee shops" are found in Amsterdam and cater mainly to the large tourist trade; the local consumption rate is far lower than in the US.
The administrative bodies responsible for enforcing the drug policies include the Ministry of Health, Welfare and Sport, the Ministry of Justice, the Ministry of the Interior and Kingdom Relations, and the Ministry of Finance. Local authorities also shape local policy, within the national framework.
When compared to other countries, Dutch drug consumption falls in the European average at six per cent regular use (twenty-one per cent at some point in life) and considerably lower than the Anglo-Saxon countries headed by the United States with an eight per cent recurring use (thirty-four at some point in life).
=== Australia ===
A Nielsen poll in 2012 found that only 27% of voters favoured decriminalisation. Australia has steep penalties for growing and using drugs even for personal use. with Western Australia having the toughest laws. There is an associated anti-drug culture amongst a significant number of Australians. Law enforcement targets drugs, particularly in the party scene. In 2012, crime statistics in Victoria revealed that police were increasingly arresting users rather than dealers, and the Liberal government banned the sale of bongs that year.
=== Indonesia ===
Indonesia carries a maximum penalty of death for drug dealing, and a maximum of 15 years prison for drug use. In 2004, Australian citizen Schapelle Corby was convicted of smuggling 4.4 kilograms of cannabis into Bali, a crime that carried a maximum penalty of death. Her trial reached the verdict of guilty with a punishment of 20 years imprisonment. Corby claimed to be an unwitting drug mule. Australian citizens known as the "Bali Nine" were caught smuggling heroin. Two of the nine, Andrew Chan and Myuran Sukumaran, were executed April 29, 2015 along with six other foreign nationals. In August 2005, Australian model Michelle Leslie was arrested with two ecstasy pills. She pleaded guilty to possession and in November 2005 was sentenced to 3 months imprisonment, which she was deemed to have already served, and was released from prison immediately upon her admission of guilt on the charge of possession.
At the 1961 Single Convention on Narcotic Drugs, Indonesia, along with India, Turkey, Pakistan and some South American countries opposed the criminalisation of drugs.
=== Republic of China (Taiwan) ===
Taiwan carries a maximum penalty of death for drug trafficking, while smoking tobacco and wine are classified as legal entertainment drug. The Department of Health is in charge of drug prohibition.
== Cost ==
In 2020, the direct cost of drug prohibition to United States taxpayers was estimated at over $40 billion annually. Prohibition can increase organized crime, government corruption, and mass incarceration via the trade in illegal drugs, while racial and gender disparities in enforcement are evident.
Although drug prohibition is often portrayed by proponents as a measure to improve public health, evidence is lacking. In 2016, the Johns Hopkins–Lancet Commission concluded that the "harms of prohibition far outweigh the benefits", citing increased risk of overdoses and HIV infection and detrimental effects on the social determinants of health. Some proponents argue that drug prohibition's effect on suppressing usage rates (although the magnitude of this effect is unknown) outweighs the negative effects of prohibition.
Alternative approaches to prohibition include drug legalization, drug decriminalization, and government monopoly.
== See also ==
Alcohol law
Arguments for and against drug prohibition
Chasing the Scream
Drug liberalization
Demand reduction
Drug policy of the Soviet Union
Harm reduction
List of anti-cannabis organizations
Medellín Cartel
Mexican drug war
Puerto Rican drug war
Prohibitionism
Tobacco control
War on Drugs
US specific:
Allegations of CIA drug trafficking
School district drug policies
Drug Free America Foundation
Drug Policy Alliance
DrugWarRant
Gary Webb
Marijuana Policy Project
National Organization for the Reform of Marijuana Laws
Students for Sensible Drug Policy
Woman's Christian Temperance Union
== References ==
== Further reading ==
== External links ==
Making Contact: The Mission to End Prohibition. Radio piece featuring LEAP founder and former narcotics officer Jack Cole, and Drug Policy Alliance founder Ethan Nadelmann
EMCDDA – Decriminalisation in Europe? Recent developments in legal approaches to drug use Archived January 12, 2007, at the Wayback Machine.
10 Downing Street's Strategy Unit Drugs Report
War on drugs Archived April 30, 2011, at the Wayback Machine Part I: Winners, documentary (50 min) explaining 'War on Drugs' by Tegenlicht of VPRO Dutch television. After short introduction in Dutch (1 min), English spoken. Broadband internet needed.
War on drugs Archived April 30, 2011, at the Wayback Machine Part II: Losers, documentary (50 min) showing downside of the 'War on Drugs' by Tegenlicht of VPRO Dutch television. After short introduction in Dutch (1 min), English spoken. Broadband internet needed.
After the War on Drugs: Options for Control (Report)
The Drug War as a Socialist Enterprise by Milton Friedman
Free from the Nightmare of Prohibition Archived February 23, 2006, at the Wayback Machine by Harry Browne
Prohibition news page – Alcohol and Drugs History Society
Drugs and conservatives should go together | Wikipedia/Drug_possession |
The U.S. state of Virginia has various policies restricting the production, sale, and use of several defined controlled substance.
== Specific drugs ==
=== Cannabis ===
==== Medical use ====
§ 18.2-251.1 of the Code of Virginia states: "It is unlawful for any person knowingly or intentionally to possess marijuana unless the substance was obtained directly from dealer, or pursuant to, a valid prescription or order of a practitioner while acting in the course of his professional/s practice, or except as otherwise authorized by the Drug Control Act of World Dealers (§ 54.1-3400 et seq.)."
Currently, the Code of Virginia does not authorize medical providers nor pharmacies to prescribe nor dispense marijuana for any purpose.
== See also ==
Law of Virginia
== References == | Wikipedia/Drug_policy_of_Virginia |
Synthetic cannabinoids, or neocannabinoids, are a class of designer drug molecules that bind to the same receptors to which cannabinoids (THC, CBD and many others) in cannabis plants attach. These novel psychoactive substances should not be confused with synthetic phytocannabinoids (obtained by chemical synthesis) or synthetic endocannabinoids from which they are distinct in many aspects.
Typically, synthetic cannabinoids are sprayed onto plant matter and are usually smoked, although they have also been ingested as a concentrated liquid form in the United States and United Kingdom since 2016. They have been marketed as herbal incense, or "herbal smoking blends", and sold under common names such as K2, spice, and synthetic marijuana. They are often labeled "not for human consumption" for liability defense. A large and complex variety of synthetic cannabinoids are designed in an attempt to avoid legal restrictions on cannabis, making synthetic cannabinoids designer drugs.
Most synthetic cannabinoids are agonists of the cannabinoid receptors. They have been designed to be similar to THC, the natural cannabinoid with the strongest binding affinity to the CB1 receptor, which is linked to the psychoactive effects or "high" of marijuana. These synthetic analogs often have greater binding affinity and greater potency to the CB1 receptors. There are several synthetic cannabinoid families (e.g., AM-xxx, CP-xx,xxx, HU-xx, JWH-xxx) which are classified by the creator of the substance (e.g., JWH stands for John W. Huffman), which can include several substances with different base structures such as classical cannabinoids and unrelated naphthoylindoles.
Synthetic marijuana compounds began to be manufactured and sold in the early 2000s. From 2008 to 2014, 142 synthetic cannabinoid receptor agonists were reported to the European Monitoring-Center for Drugs and Drug Addiction (EMCDDA).
Reported user negative effects include palpitations, paranoia, intense anxiety, nausea, vomiting, confusion, poor coordination, and seizures. There have also been reports of a strong compulsion to re-dose, withdrawal symptoms, and persistent cravings. There have been several deaths linked to synthetic cannabinoids. The Centers for Disease Control and Prevention (CDC) found that the number of deaths from synthetic cannabinoid use tripled between 2014 and 2015. In 2018, the United States Food and Drug Administration warned of significant health risks from synthetic cannabinoid products that contain the rat poison brodifacoum, which is added because it is thought to extend the duration of the drugs' effects. Severe illnesses and death have resulted from this contamination.
== Synthetic cannabinoid products ==
It is often difficult to determine what is in these products without reagent testing because masking agents, such as tocopherol (or vitamin E acetate that causes vaping-associated pulmonary injury), eugenol, and fatty acids, are added to confound identification. Just as the synthetic cannabinoid(s) used differ between each synthetic cannabinoid product sold, so do the other contents of the counterfeit product.
=== Counterfeit black market cannabis products ===
Counterfeit cannabis-liquid (c-liquid) for e-cigarettes: Synthetic cannabinoids are increasingly offered in e-cigarette form as "c-liquid". Several schoolchildren in Greater Manchester collapsed after vaping synthetic cannabinoids mis-sold as THC e-liquid.
Counterfeit cannabis buds: Hemp buds (or low-potency cannabis buds) laced with synthetic cannabinoids.
Counterfeit cannabis edible: The Florida Poison Information Center in Jacksonville warned parents in September 2020 that the number of people poisoned by fake marijuana edibles and candies has tripled.
Counterfeit hashish: From December 2018, different samples of hashish have been found to contain synthetic cannabinoids.
=== Counterfeit CBD products ===
Synthetic cannabinoids appear in many CBD brands in products such as gummy bears and vape cartridges.
=== "Herb/incense" blends ===
==== Synthetic cannabinoids found in herb blends ====
Synthetic cannabinoid components of 'Spice' (a non-exhaustive list):
==== Non-cannabinoid chemicals found in herb blends ====
Most blends consist of synthetic cannabinoids sprayed onto inert vegetable matter, but some contain other psychoactive substances, including psychoactive herbs, e.g., wild dagga and indian warrior, and psychoactive alkaloids, e.g., betonicine, aporphine, leonurine, nuciferine, and nicotine. Some synthetic cannabinoids products have also been found to contain synthetic opioids. For example, in 2010, nine people died due to the combination of O-desmethyltramadol, a μ-opioid agonist and analgesic drug, and kratom, an Asiatic medicinal plant containing mitragynine, another μ-opioid agonist, in a synthetic cannabinoid product called "Krypton".
In 2013, AH-7921 was detected in smoking blends in Japan. In 2018, there was an outbreak of synthetic cannabinoids contaminated with anticoagulants, mainly brodifacoum, in at least 11 states in the US that caused coagulopathy (prolonged or excessive bleeding) and resulted in the treatment of over 300 people and at least eight deaths.
One of the most common non-cannabinoid ingredients in these products is oleamide, a fatty acid derivative that acts similarly to a cannabinoid and has hypnotic properties. Analysis of 44 products synthetic cannabinoid revealed oleamide in 7 of the products tested. Other non-cannabinoid ingredients that have been found in synthetic cannabinoid blends include harmine and harmaline, reversible monoamine oxidase inhibitors, which have been found with myristicin and asarone; substituted cathinone derived stimulant drugs such as 4-methylbuphedrone and 4'-methyl-alpha-PPP; and psychedelic tryptamine derivatives such as 4-HO-DET.
==== Herbs labeled on packages marketed as legal high ====
Packages of synthetic cannabinoid products can claim to contain a wide array of plants. However, oftentimes, none of the listed ingredients have been detectable.
Herbal components of 'Spice' (a non-exhaustive list):
== Naming synthetic cannabinoids ==
Many of the early synthetic cannabinoids that were synthesized for use in research were named after either the scientist who first synthesized them or the institution or company where they originated.
Some of the names of synthetic cannabinoids synthesized for recreational use were given names to help market the products. For example, AKB-48 (also known as APINACA) is also the name of a popular Japanese girl band; 2NE1 (also known as APICA) is also a South Korean girl band; and XLR-11 was named after the first US-developed liquid fuel rocket for aircraft. Now many synthetic cannabinoids are assigned names derived from their four main structural components, core, tail, linker, and linked group, where the name is formatted as LinkedGroup-TailCoreLinker. For example, in 5F-MDMB-PINACA (also known as 5F-ADB), 5F stands for the terminal fluorine or "fluorine on carbon 5" of the pentyl chain; MDMB stands for "methyl-3,3-dimethyl butanoate", the linked group; and PINACA stands for "pentyl chain (tail) indazole (core) carboxamide (linker)".
=== Common names ===
Use of the term "synthetic marijuana" to describe products containing synthetic cannabinoids is controversial and, according to Lewis Nelson, a medical toxicologist at the NYU School of Medicine, a mistake. Nelson claims that relative to marijuana, products containing synthetic cannabinoids "are really quite different, and the effects are much more unpredictable. It's dangerous". Since the term synthetic does not apply to the plant, but rather to the cannabinoid that the plant contains (THC), the term synthetic cannabinoid is more appropriate.
Nearly 700 "herbal incense" blends exist. They are often called "synthetic marijuana", "natural herbs", "herbal incense", or "herbal smoking blends" and often labeled "not for human consumption". In some Spanish-speaking countries, such as Chile and Argentina, such preparations are often referred to as cripy.
According to the Psychonaut Web Mapping Research Project, synthetic cannabinoids, sold under the brand name Spice, were first released in 2005 by the now-dormant company the Psyche Deli in London. In 2006, the brand gained popularity. According to the Financial Times, the assets of the Psyche Deli rose from £65,000 in 2006 to £899,000 in 2007. The EMCDDA reported in 2009 that Spice products were identified in 21 of the 30 participating countries.
=== Neocannabinoids ===
Because of these controversies, and in particular the difficulty of distinguishing natural cannabinoids obtained in laboratory (for example, CBD or synthetic THC) from artificial novel synthetic cannabinoid analog compounds not present in nature (like nabilone, Spice, the HU, JWH series, etc.), the term "neocannabinoid" has been proposed to name the latter.
== Uses ==
Synthetic cannabinoids were made for cannabinoid research focusing on tetrahydrocannabinol (THC), cannabinoid receptors, and the endocannabinoids that activate them in the body. Synthetic cannabinoids were needed partly due to legal restrictions on natural cannabinoids, which make them difficult to obtain for research. Many have been useful because they bind selectively to either the CB1 or CB2 receptors, whereas THC has a similar affinity for both. Tritium-labelled cannabinoids such as CP-55,940 were instrumental in discovering the cannabinoid receptors in the early 1990s.
Some early synthetic cannabinoids were also used clinically. Nabilone, a first generation synthetic THC analog, has been used as an antiemetic to combat vomiting and nausea since 1981. Synthetic THC (marinol, dronabinol) has been used as an antiemetic since 1985, and an appetite stimulant since 1991, although synthetic THC is often not listed among the "synthetic cannabinoids" but as a "synthetic phytocannabinoid".
In the early 2000s, synthetic cannabinoids began to be used for recreational drug use in an attempt to get similar effects to cannabis. Because synthetic cannabinoid molecular structures differ from THC and other illegal cannabinoids, synthetic cannabinoids were not technically illegal. Since the discovery of the use of synthetic cannabinoids for recreational use in 2008, some synthetic cannabinoids have been made illegal, but new analogs are continually synthesized to avoid the restrictions. Synthetic cannabinoids have also been used recreationally because they are inexpensive and are typically not revealed by the standard marijuana drug tests. Unlike nabilone, the synthetic cannabinoids found being used for recreational use did not have any documented therapeutic effects.
Critics of drug prohibition point to laws against marijuana as a cause for the popularity of synthetic products, and argue that cannabis legalization reduces demand for substitutes. The drug is most commonly used in populations that cannot easily acquire or consume marijuana, such as teenagers, inmates, people on probation or parole, and members of the armed forces subjected to regular drug testing.
== Toxicity ==
Because they activate the cannabinoid CB1 and CB2 receptors, many of the effects of synthetic cannabinoids are similar to those of THC. These are achieved at lower doses, because many synthetic cannabinoids are more potent than marijuana, and users are often unaware of exactly what they are getting and how potent it is. For example, Δ9-THC has an EC50 of 250 nM at CB1 and 1157 nM at CB2, whereas PB-22 has an EC50 of 5.1 nM at CB1 and 37 nM at CB2. Adverse effects observed due to synthetic cannabinoid use include acute kidney injury, cardiac toxicity, seizure, stroke, tremor, hypokalemia, and rhabdomyolysis.
Some negative effects of 5F-PB-22 reported by users included nausea, vomiting, confusion, poor coordination, anxiety, and seizures. Some of the negative effects of 5F-AKB-48 reported by users included palpitations, paranoia, intense anxiety, and a taste like burned plastic. While there are no fatal overdose cases linked to marijuana, there are deaths linked to synthetic cannabinoids each year. The most common mechanisms leading to death following synthetic cannabinoid use include behavioral risks, such as self-harm and suicide, falling from a height, and wandering into traffic; cardiovascular effects; and central nervous system depression.
Researchers have pointed out a few ways that synthetic cannabinoids differ from marijuana, and therefore may be more dangerous. First, they often have greater intrinsic activity. Many of the synthetic cannabinoids are full agonists of the cannabinoids receptors, CB1 and CB2, compared to THC, which is only a partial agonist. Secondly, they may have other actions in the body, in addition to activating cannabinoid receptors. Some may work on NMDA glutamate receptors. Some may also work on serotonin, either indirectly by inhibiting MAO and increasing 5-HT1A expression, or by directly binding to serotonin receptors, including the 5-HT1A and 5-HT3 subtypes; some researchers speculate that this activity may be because the indole moiety that some synthetic cannabinoids possess is similar to the structure of serotonin.
Third, synthetic cannabinoids may break down into metabolites, or create other by-products when heated, that may differ from marijuana. Phase 1 metabolism of JWH-018 results in at least nine monohydroxylated metabolites, three of which have been shown to be full agonists of the CB1 receptors, compared to the metabolism of THC, which only results in one psychoactive monohydroxylated metabolite. The metabolite N-(3-hydroxypentyl) JWH-018 was found to have toxic effects that its parent compound does not. Some metabolites even appear to be cannabinoid antagonists. Lastly, they may contain unwanted substances, be mislabeled, or contain different doses than advertised (in one analysis, a difference of one log unit was found).
No official studies have been conducted on the effects of synthetic cannabinoids on humans (as is often the case with illegal and potentially toxic compounds); however, user reports and the effects experienced by patients seeking medical care after taking synthetic cannabinoids have been published. Each of the many different synthetic cannabinoids can have different effects at different dosages. The CDC described synthetic cannabinoid overdoses between 2010 and 2015 and of 277 drug overdose patients who reported synthetic cannabinoid as the sole agent, 66.1% reported problems in the central nervous system (e.g., agitation, coma, toxic psychosis), 17% reported cardiovascular problems (e.g., tachycardia, bradycardia), 7.6% reported pulmonary problems (5.4% of which had respiratory depression), and 4% reported acute kidney injury.
Four postmortem cases linked to the synthetic cannabinoids 5F-PB-22 have been reviewed. The postmortem blood specimens contained a range of 1.1–1.5 ng/mL of 5F-PB-22. Three of the four cases were sudden episodes and the symptoms leading to death included acute shortness of breath; vasocongestion in the liver, spleen, and kidneys; bilateral pulmonary edema; dead inflamed tissue (necrotizing granulomatous inflammation); and congestion of most internal organs. The fourth case presented to the hospital with severe problems that deteriorated over the course of a day, ending with circulatory, respiratory, central nervous system, and renal failure.
=== Addiction ===
There have been reports of a strong compulsion to re-dose, withdrawal symptoms, and persistent cravings lasting up to a week after taking synthetic cannabinoids, indicating that synthetic cannabinoids may be more addictive than marijuana.
=== Psychosis ===
Studies have strongly linked particular synthetic cannabinoids with psychosis. The use of synthetic cannabinoids can be associated with psychosis and physicians are beginning to investigate if some patients with inexplicable psychotic symptoms may have at one point used synthetic cannabinoids. In contrast to most other recreational drugs, the dramatic psychotic state induced by use of synthetic cannabinoids has been reported, in multiple cases, to persist for several weeks, and in one case for seven months, after complete cessation of drug use.
Some studies suggest that not only can synthetic cannabinoids induce psychosis, but they can worsen previously stable psychotic disorders and might trigger a chronic (long-term) psychotic disorder among vulnerable individuals such as those with a family history of mental illness. Individuals with risk factors for psychotic disorders are often counseled against using synthetic cannabinoids. Psychiatrists have suggested that the lack of an antipsychotic chemical, like CBD in natural cannabis, may make synthetic cannabinoids more likely to induce psychosis than natural cannabis.
== Structural classifications ==
There are five major categories for synthetic cannabinoids: classical cannabinoids, non-classical cannabinoids, hybrid cannabinoids, aminoalkylindoles, and eicosanoids. Classical cannabinoids are analogs of THC that are based on a dibenzopyran ring. They were developed starting in the 1960s, following the isolation of THC, and were originally the only cannabinoids synthesized. Classical cannabinoids include nabilone and dronabinol, and one of the best known synthetic classical cannabinoids is HU-210. HU-210 is a chiral compound first synthesized by Raphael Mechoulam at Hebrew University in the 1980s. It was discovered in herbal incense products by the U.S. Customs and Border Protection in January 2009; however, classical cannabinoids are not often seen in synthetic cannabinoid blends for recreational use, likely because they are difficult to synthesize.
Non-classical cannabinoids include cyclohexylphenols (CP), which were first synthesized in the late 1970s to 1980s by Pfizer as potential analgesics. The C8 homologue of CP-47,497 (CP-47,497-C8) was one of the first synthetic cannabinoids being used recreationally. CP-47,497-C8 is made by extending the dimethylheptyl side chain of CP-47,497 to a dimethyloctyl side chain. It was discovered by forensic scientists in a herbal blend known as "Spice" in 2008, along with JWH-018, an aminoalkylindole.
Hybrid cannabinoids have a combination of classical and non-classical cannabinoid structural features. For example, AM-4030, a derivative of HU-210, is a hybrid cannabinoid because it has the dibenzopyran ring common of classical cannabinoids and an aliphatic hydroxyl group common in the CP family of nonclassical cannabinoids.
Aminoalkylindoles are structurally dissimilar to THC and include naphthoylindoles (JWH-018), phenylacetylindoles (JWH-250), and benzoylindoles (AM-2233). Aminoalkylindoles are considered to be the most common synthetic cannabinoids found in synthetic cannabinoid blends, likely due to the fact that these molecules are easier to synthesize than classical and non-classical cannabinoids. The JWH molecules were first synthesized by John William Huffman at Clemson University in the late 1990s. The FBI concluded in a 2012 memo that as a result of the publication of J.W. Huffman's research, people searching for a "marijuana-like-high" would follow his recipes and methods.
Eicosanoid synthetic cannabinoids are analogs of endocannabinoids, such as anandamide. Endocannabinoids are cannabinoids naturally occurring in the body. One of the best known synthetic analogs of anandamide is methanandamide.
Some synthetic cannabinoids have even greater structural diversity, possibly to subvert legal regulations on earlier generations of synthetic cannabinoids. There are a few different structural classifications of synthetic cannabinoids that include many of the new structures, some of which are shown in table one. The indazole carboxamide group, including APINACA (AKB-48), an adamantyl indazole carboxamide, and AB-PINACA, an aminocarbonyl indazole carboxamide, is an example of a new group of synthetic cannabinoids. Most clandestine manufacturers and producers only make small changes to the structure of a synthetic cannabinoid, such as changing an indole to indazole structure (AM-2201 to THJ-2201) or terminal fluorine replacement; however, one group that was unprecedented when discovered by forensic scientists in 2013, was the quinolinyl ester synthetic cannabinoids.
PB-22 and 5F-PB-22 were the first synthetic cannabinoids to include a quinoline substructure and an ester linkage. These compounds are thought to have been synthesized with the intention of making a synthetic cannabinoid prodrug, which might improve absorption and confound detection. Ester bonds are easily biodegradable through spontaneous or endogenous, nonspecific esterase hydrolysis, which has been commonly used in medicinal chemistry to make ester prodrugs. The reason for the change to the quinolone substructure is unknown, but it may have been found to be a suitable replacement for the naphthoyl moiety that is currently regulated by US scheduling laws.
Although most synthetic cannabinoids are not direct analogs of THC, they share many common features with THC. Most are lipid-soluble, non-polar, small molecules (usually 20–26 carbon atoms) that are fairly volatile, making them "smokable", like THC. Another common feature of most synthetic cannabinoids and THC is a side-chain of five to nine saturated carbon atoms. It has been found that this chain of carbons is required for optimal psychotropic activity from binding CB1 receptors. Also, most synthetic cannabinoids are agonists of both cannabinoid receptors, CB1 and CB2, like THC; however, they often have greater binding affinity and therefore greater potency than THC, as seen in table two. Due to the greater potency, the standard doses of many synthetic cannabinoids may be less than 1 mg.
=== Stereospecificity ===
Most classical, non-classical, and hybrid synthetic cannabinoids have stereospecificity (one stereoisomer is usually much more potent than the other(s)). For example, HU-210 is the (–) enantiomer of 11-OH-Δ8-THC-DMH and a full agonist of the CB1 receptor; the (+) enantiomer of 11-OH-D8-THC-DMH, known as HU-211, is a NMDA receptor antagonist and is largely inactive as a cannabinoid. On the other hand, aminoalkylindoles, eicosanoids, and the other new synthetic cannabinoid groups typically do not have an asymmetric center, so they are usually not stereospecific.
=== Fluorination of terminal carbon ===
Recently there has been an increase in the emergence of terminally fluorinated synthetic cannabinoids, such as 5F-PB-22 (fluorinated version of PB-22) and XLR-11 (fluorinated version of UR-144). South Korea's National Forensic Service reported that 90% of all seized synthetic cannabinoids in 2013 were fluorinated, compared to no fluorinated synthetic cannabinoids reported in 2010. 5F-derivations (terminal fluorination) of the synthetic cannabinoids have been found to be about 2–5 times more potent at CB1 receptors than their un-fluorinated counterparts, as shown in table two.
== Detection in bodily fluids ==
Synthetic cannabinoids are typically not identified by the standard marijuana drug tests including the immunoassay test (EMIT), GC-MS screening, and multi-target screening by LC-GC/MS because those tests only detect the presence of THC and its metabolites. Although most synthetic cannabinoids are analogs of THC, they are structurally different enough that, for example, the specific antibodies in the EMIT for marijuana do not bind to them. Due to their high potency, a very small dose of synthetic cannabinoids is used. Synthetic cannabinoids are highly metabolized by the body, so the window to detect the parent drug (the synthetic cannabinoid itself) in blood and oral fluid is very small.
Serum concentrations of synthetic cannabinoids are generally in the 1–10 μg/L range during the first few hours after recreational usage and the metabolites are usually present in urine at similar concentrations. Little to no parent drug is present in urine, so there is a lot of research to try and identify the major urinary metabolites that could be used as markers of synthetic cannabinoid intake. The major urinary metabolites in most cases are formed by oxidation of the alkyl side-chain to an alcohol and carboxylic acid followed by glucuronide conjugation and also by N-dealkylation and aromatic hydroxylation.
For example, the main metabolites of JWH-018, of which there are over 20, include carboxylated, monohydroxylated, dihydroxylated, and trihydroxylated metabolites, but they are mostly excreted in urine as glucuronide conjugates. The presence of synthetic cannabinoids or their metabolites in bodily fluids may be determined using specifically targeted commercially available immunoassay screening methods (EMIT), while liquid chromatography-mass spectrometry is most often used for confirmation and quantitation. There are commercially available EMIT kits for the screening of the synthetic cannabinoids JWH-018, JWH-073, JWH-398, JWH-200, JWH-019, JWH-122, JWH-081, JWH-250, JWH-203, CP-47,497, CP-47,497-C8, HU-210, HU-211, AM-2201, AM-694, RCS-4, and RCS-8 through companies like NMS Labs, Cayman Chemical, and Immunoanalysis Corporation.
== Notable incidents ==
=== New Zealand ===
In September 2018, at least 10 people overdosed on a synthetic cannabinoid, either AMB-FUBINACA or AB, in Christchurch over two days. Some of the people were in critical condition in the Intensive Care Unit.
=== United States ===
In October 2011, the Louisiana State University football program announced that it had suspended three players, including star cornerback Tyrann Mathieu, who tested positive for synthetic cannabinoids.
On July 12, 2016, 33 people were intoxicated by an herbal "incense" product called "AK-47 24 Karat Gold", and dozens overdosed, in Brooklyn. Eighteen people were transported to local hospitals. The herbal "incense" product was determined to be a synthetic cannabinoid called AMB-FUBINACA.
Since March 2018, Illinois, Wisconsin, Maryland, and eight other states in the United States have had an outbreak of severe bleeding caused by a synthetic cannabinoid contaminated with brodifacoum, a rat poison that causes bleeding. Illinois was hit the hardest and on April 5, 2018, the CDC issued a Clinical Action alert to health care providers across the United States advising of 89 confirmed cases of "serious unexplained bleeding" in Illinois. The cases are still being studied; however, 63 of the patients reported synthetic cannabinoid use, and laboratory analysis confirmed brodifacoum was present in at least 18 patients. As of April 24, 2018, 153 cases, including four deaths, linked to this outbreak have been reported to the Illinois Department of Public Health (IDPH) since March 7, 2018. On September 18, 2018, the Wisconsin Department of Health Services confirmed 16 more cases, bringing the total number of people affected by the outbreak in Wisconsin to 80 people since March 2018, including one death in July 2018.
In August 2018, there were almost one hundred overdose cases reported over two days in New Haven, Connecticut, from a bad batch of K2. The synthetic cannabinoid was believed to have been mixed with fentanyl, although no fentanyl was identified in samples of the drug tested by the DEA.
From September 21–22, 2018, almost 50 people overdosed and two people died in the Kensington area of Philadelphia. Officials believed the cause to be a combination of heroin or fentanyl and a synthetic cannabinoid. This same area in Philadelphia had 155 people overdose and 10 people die from a combination of heroin, fentanyl, and a synthetic cannabinoid called 5F-ADB over one weekend in July 2018. The Department of Public Health released that they believe "5F-ADB was the primary cause of the cluster of patients with these adverse drug reactions."
On December 10, 2021, the Hillsborough County, Florida department of health reported cases of "rat poison" contaminated synthetic blends linked to symptoms associated with coagulopathy, a condition where the blood's ability to clot is impaired. Two deaths and over 41 hospitalizations have been directly linked to this specific outbreak as of December 16, 2021.
== Research ==
=== Vaping-associated pulmonary injury ===
Synthetic cannabinoids have been speculated to be involved in vaping-associated pulmonary injury (VAPI).
== Legal restrictions and regional availability ==
=== Europe ===
==== Austria ====
The Austrian Ministry of Health announced in December 2008, that Spice would be controlled under their drug-law on the grounds that it contains an active substance that affects the functions of the body, and the legality of JWH-018 is under review.
==== Germany ====
JWH-018, CP 47,497 and the C6, C8, and C9 homologues of CP 47,497 have been illegal in Germany since January 2009. Since November 2016, about 80–90% of the substances belonging to the group of synthetic cannabinoids are illegal in Germany as the law does not cover all chemical structures.
==== France ====
JWH-018, CP 47,497 (and its homologues), and HU-210 were all made illegal in France in February 2009.
==== Ireland ====
From June 2010, JWH-018, along with a variety of other designer drugs, has been illegal.
==== Latvia ====
JWH-018, JWH-073, CP 47,497 (and its homologues), and HU-210, as well as leonotis leonurus, have been all banned in Latvia since 2005. After the first confirmed lethal case from the use of legal drugs in late 2013, parliament significantly increased the number of temporarily banned substances used in Spice and similar preparations. In April 2014, parliament made selling of the temporarily banned substances a criminal offense.
==== Poland ====
JWH-018 and many of the herbs mentioned on the ingredient lists of Spice and similar preparations were made illegal in May 2009. The bill was passed by Polish Sejm and Polish Senat and was signed by the President.
==== Romania ====
Spice was made illegal in Romania in February 2010. In September 2018, Spice was made legal for personal use. A new law is being discussed to make spice illegal for personal use again.
==== Russia ====
In April 2009, the Chief Medical Officer of the Russian Federation issued a resolution on reinforcing control over the sales of smoking-blends. These blends, marketed under the trade names AM-HI-CO, Dream, Spice (Gold, Diamond), Zoom, Ex-ses, Yucatán Fire and others, have been declared to contain Salvia divinorum, Hawaiian wood rose, and blue lotus, and are prohibited to be sold. These substances have been found to have "psychotropic, narcotic effects, contain poisonous components and represent potential threat for humans". The resolution does not mention JWH-018 or other synthetic cannabinoids. In January 2010, the Russian government issued a statement including 23 synthetic cannabinoids found in smoking blends Hawaiian Rose and Blue Lotus on the list of prohibited narcotic and psychotropic substances.
About 780 new psychoactive substances were added to the list from 2011 to 2014. The drug-makers avoided all the bans by making slight changes to the drugs. In the autumn of 2014, more than 2000 Spice consumers in Russia sought medical attention, 1000 were admitted to hospitals, and 40 people died. In October 2014, President Vladimir Putin brought in a bill that increased the penalty for selling or consuming smoking blends from a fine to up to eight years in prison.
==== Slovakia ====
Spice is legal in Slovakia. The National Anti-Drug Unit is considering adding it to the list of controlled substances. The latest anti-drug law version (468/2009) valid since January 2010 does not mention active compounds of Spice.
==== Spain ====
Spice is unregulated in Spain. For this reason, Spice is available in grow shop stores or cannabis related stores, and it can be bought and shipped online without any legal impediment from those kind of stores.
==== Sweden ====
CP 47,497-C6, CP 47,497-C7, CP 47,497-C8, CP 47,497-C9, JWH-018, JWH-073, and HU-210 were all made illegal in Sweden in September 2009.
==== Switzerland ====
Spice has been banned in Switzerland.
==== Turkey ====
Spice, which is colloquially called bonzai in Turkey, was added to the list of drugs and psychotropic substances in July 2011.
==== United Kingdom ====
The UK controls synthetic cannabinoids by analog under the Misuse of Drugs Act, 1971 as Class B drugs. Until 2016, synthetic cannabinoids were legally sold in head shops, although the exact compounds available changed over time based on the legislation. The UK saw three generations of synthetic cannabinoids within five years where the second and third generations emerged in response to amendments to the Misuse of Drugs Act, 1971, Order 2009 and Order 2013, which classified many first and second generation synthetic cannabinoids as Class B drugs. There were two additional amendments in 2016 and 2019, which included in the analog controls many of the most popular synthetic cannabinoids circulating at the time. In May 2016, the Psychoactive Substances Act was enacted, which made illegal the production, distribution, sale, supply, and possession in correctional institutions of any substance for human consumption with psychoactive effects. This stopped the open sale of synthetic cannabinoids in head shops, although they are still found in use.
=== North America ===
==== Canada ====
Spice is not specifically prohibited in Canada, but synthetic cannabis mimics are listed as a schedule II drug. Schedule II to the Controlled Drugs and Substances Act makes reference to specific synthetic compounds JWH-XXX and AM-XXXX, although is not limiting to those identified. Health Canada is debating the subject. Schedule II has consisted entirely of synthetic cannabinoids since October 2018. These remain illegal following the removal from the schedule of cannabis and its constituents derived from nature.
==== United States ====
The case of David Mitchell Rozga, an American teenager from Indianola, Iowa, brought international attention to K2. Rozga shot himself in the head with a family-owned hunting rifle in an apparent suicide on June 6, 2010. After news of Rozga's death, it was reported by friends that they had smoked K2 with Rozga approximately one hour before his death. The nature of his death and reports from numerous family members, led investigators to suspect that Rozga was under the influence of a mind-altering substance when he died. The death of Rozga influenced political lobbying against K2, and other legal synthetic drugs such as bath salts. Following the incident, the "David Mitchell Rozga Act" to ban the use and distribution of K2 was introduced by Iowa Senator Chuck Grassley. It was passed by the United States Congress in June 2011. On July 10, 2012, President Barack Obama signed the Synthetic Drug Abuse Prevention Act of 2012 into law. It banned synthetic compounds commonly found in synthetic marijuana, placing them under Schedule I of the Controlled Substances Act.
Prior to that, some synthetic cannabis compounds (HU-210) were scheduled in the US under federal law, while others (JWH-073) were temporarily scheduled until final determination of their status could be made. The Drug Enforcement Administration (DEA) considered K2 to be a "drug of concern", citing "a surge in emergency-room visits and calls to poison-control centers. Adverse health effects associated with its use include seizures, hallucinations, paranoid behavior, agitation, anxiety, nausea, vomiting, racing heartbeat, and elevated blood pressure."
Several states independently passed acts making it illegal under state law, including Kansas in March 2010, Georgia and Alabama in May 2010, Tennessee and Missouri in July 2010, Louisiana in August 2010, Mississippi in September 2010, and Iowa. An emergency order was passed in Arkansas in July 2010 banning the sale of synthetic cannabis mimics. In October 2010, the Oregon Board of Pharmacy listed synthetic cannabinoid chemicals on its Schedule 1 of controlled substance, which means that the sale and possession of these substances is illegal under the Oregon Uniform Controlled Substances Act.
According to the National Conference of State Legislatures, several other states also considered legislation, including New Jersey, New York, Florida, and Ohio. Illinois banned all synthetic cannabinoids in January 2011. Michigan banned synthetic cannabinoids in October 2010. The South Dakota banned these products in February 2012. Indiana banned synthetic cannabinoids in March 2012. North Carolina banned synthetic cannabis mimics by a unanimous vote of the state senate, due to concerns that its contents and effects are reasonably similar to cannabis, and may cause equal effects in terms of psychological dependency.
Following cases in Japan involving the use of synthetic cannabinoids by navy, army and marine corps personnel, they were officially banned. A punitive general order issued in January 2010, by the Commander Marine Corps Forces, Pacific prohibits the actual or attempted possession, use, sale, distribution and manufacture of synthetic cannabis mimics as well as any derivative, analogue or variant of it. In June 2010, the US Air Force issued a memorandum that banned the possession and use of Spice, or any other mood-altering substance except alcohol or tobacco, among its service members.
Usage among 8th, 10th, and 12th graders has been decreasing since 2011, while use of botanical marijuana has remained stable. There are important regional differences, with large declines in the Western and Southern US, and increases in the Northeast and Midwest.
===== Dronabinol =====
Exceptional are synthetic ∆9-THC (dronabinol) -containing FDA-approved drug products with a currently accepted medical use in treatment in the United States, such as Syndros and Marinol, which are, respectively, under Schedule II and Schedule III of the CSA.
=== South America ===
==== Chile ====
The Chilean Ministry of Health in April 2009, declared the sale of synthetic cannabis mimics to be illegal.
=== Asia ===
==== South Korea ====
South Korea added JWH-018, CP 47,497 and HU-210 to the controlled substance list in July 2009, effectively making these chemicals illegal.
==== Indonesia ====
Tembakau Gorilla (Gorilla Tobacco), a catch-all term for synthetic cannabinoids blended in tobacco products, were listed as Class I Narcotics with no therapeutic use in 2017.
==== Japan ====
Japan has banned JWH-018, CP 47, 497, and homologues, and HU-210 since October 2009.
==== United Arab Emirates ====
The United Arab Emirates had stated that Spice is an illegal substance and possession or intent to sell is a jailable offense.
=== Australasia ===
==== Australia ====
In June 2011, the Western Australian government banned all of the synthetic cannabinoids found in already existing products, including brands such as Kronic, Kalma, Voodoo, Kaos, and Mango Kush. Western Australia was the first state in Australia to prohibit the sale of certain synthetic cannabinoids. In June 2013, an interim ban made a large list of product brands and synthetic substances illegal to sell anywhere in Australia. This ban lapsed on October 13, 2013, and a permanent ban has not been imposed. Synthetic cannabinoids and related products remain illegal in NSW, where a bill was passed in September 2013, that bans entire families of synthetic drugs instead of only banning existing compounds that have been identified. The introduction of this law makes NSW the first state in Australia to completely ban substances with psychoactive properties.
==== New Zealand ====
Synthetic Cannabinoids are illegal in New Zealand, it is classified as a Class A controlled drug. The New Zealand Parliament passed a law in July 2013 banning the sale of legal highs in dairies and supermarkets, but allowing some "low risk" drugs to continue to be sold through speciality licensed shops. Synthetic cannabinoids, as well as all other legal highs were outlawed in May 2014.
An analysis of 41 different synthetic cannabis mimic blends sold commercially in New Zealand, conducted by the Institute of Environmental Science and Research and released in July 2011, found 11 different synthetic cannabinoid ingredients used, including JWH-018, JWH-073, AM-694, AM-2201, RCS-4, RCS-4 butyl homologue, JWH-210, JWH-081, JWH-250 (or possibly JWH-302, isomer not determined), JWH-203, and JWH-122—with between one and five different active ingredients, though JWH-018 was present in 37 of the 41 blends tested. In two brands, the benzodiazepine anxiolytic drug phenazepam was also found, which is classified as a prescription medicine in New Zealand, and these brands were ordered to be removed from the market by emergency recall.
Since this time, a further 15 cannabinoid compounds have been detected as ingredients of synthetic cannabis mimicking blends in New Zealand and banned as temporary class drugs. In 2013, another hypnotic medication, zaleplon, was found to have been used as an active ingredient in a blend that had been sold in New Zealand during 2011 and 2012.
== See also ==
Chimique
List of designer drugs § Synthetic cannabinoids
Endocannabinoid enhancer
Endocannabinoid system
Structural scheduling of synthetic cannabinoids
Synthetic Cannabinoid Use Disorder
== References ==
== Further reading ==
Roque-Bravo, Rita; Silva, Rafaela Sofia; Malheiro, Rui F.; Carmo, Helena; Carvalho, Félix; da Silva, Diana Dias; Silva, João Pedro (2023-01-20). "Synthetic Cannabinoids: A Pharmacological and Toxicological Overview". Annual Review of Pharmacology and Toxicology. 63 (1): 187–209. doi:10.1146/annurev-pharmtox-031122-113758. ISSN 0362-1642. PMID 35914767. S2CID 251255354.
== External links ==
"Synthetic cannabinoids". European Union Drugs Agency (EUDA). | Wikipedia/Spice_(drug) |
A drug-related crime is a crime to possess, manufacture, or distribute drugs classified as having a potential for abuse (such as cocaine, heroin, morphine and amphetamines). Drugs are also related to crime as drug trafficking and drug production are often controlled by drug cartels, organised crime and gangs. Some drug-related crime involves crime against the person such as robbery or sexual assaults.
== U.S. Bureau of Justice Statistics ==
In 2002, in the U.S. about a quarter of convicted property and drug offenders in local jails had committed their crimes to get money for drugs, compared to 5% of violent and public order offenders. Among State prisoners in 2004 the pattern was similar, with property (30%) and drug offenders (26%) more likely to commit their crimes for drug money than violent (10%) and public-order offenders (7%). In Federal prisons property offenders (11%) were less than half as likely as drug offenders (25%) to report drug money as a motive in their offenses.
In 2004, 17% of U.S. State prisoners and 18% of Federal inmates said they committed their current offense to obtain money for drugs. These percentages represent a slight increase for Federal prisoners (16% in 1997) and a slight decrease for State prisoners (19% in 1997).
== Drugs and crime ==
Drug abuse and addiction is associated with drug-related crimes. In the U.S. several jurisdictions have reported that benzodiazepine misuse by criminal detainees has surpassed that of opiates. Patients reporting to two emergency rooms in Canada with violence-related injuries were most often found to be intoxicated with alcohol and were significantly more likely to test positive for benzodiazepines (most commonly temazepam) than other groups of individuals, whereas other drugs were found to be insignificant in relation to violent injuries.
Research carried out on drug-related crime found that drug misuse is associated with various crimes that are in part related to the feelings of invincibility, which can become particularly pronounced with abuse. Problematic crimes associated include shoplifting, property crime, drug dealing, violence and aggression and driving whilst intoxicated. In Scotland among the 71% of suspected criminals testing positive for controlled drugs at the time of their arrest benzodiazepines (over 85% are temazepam cases) are detected more frequently than opiates and are second only to cannabis, which is the most frequently detected drug.
Research carried out by the Australian government found that benzodiazepine users are more likely to be violent, more likely to have been in contact with the police, and more likely to have been charged with criminal behavior than those using opiates. Illicit benzodiazepines mostly originate from medical practitioners but leak onto the illicit scene due to diversion and doctor shopping. Although only a very small number originate from thefts, forged prescriptions, armed robberies, or ram raids, it is most often benzodiazepines, rather than opiates, that are targeted in part because benzodiazepines are not usually locked in vaults and or do not have as strict laws governing prescription and storage of many benzodiazepines. Temazepam accounts for most benzodiazepine sought by forgery of prescriptions and through pharmacy burglary in Australia.
Benzodiazepines have been used as a tool of murder by serial killers, and other murderers, such as those with the condition Munchausen Syndrome by Proxy. Benzodiazepines have also been used to facilitate rape or robbery crimes, and benzodiazepine dependence has been linked to shoplifting due to the fugue state induced by the chronic use of the drug. When benzodiazepines are used for criminal purposes against a victim they are often mixed with food or drink.
Temazepam and midazolam are the most common benzodiazepines used to facilitate date rape. Alprazolam has been abused for the purpose of carrying out acts of incest and for the corruption of adolescent girls. However, alcohol remains the most common drug involved in cases of drug rape. Although benzodiazepines and ethanol are the most frequent drugs used in sexual assaults, GHB is another potential date rape drug that has received increased media focus.
Some benzodiazepines are more associated with crime than others especially when abused or taken in combination with alcohol. The potent benzodiazepine flunitrazepam (Rohypnol), which has strong amnesia-producing effects can cause abusers to become ruthless and also cause feelings of being invincible. This has led to some acts of extreme violence to others, often leaving abusers with no recollection of what they have done in their drug-induced state. It has been proposed that criminal and violent acts brought on by benzodiazepine abuse may be related to lowered serotonin levels via enhanced GABAergic effects.
Flunitrazepam has been implicated as the cause of one serial killer's violent rampage, triggering off extreme aggression with anterograde amnesia. A study on forensic psychiatric patients who had abused flunitrazepam at the time of their crimes found that the patients displayed extreme violence, lacked the ability to think clearly, and experienced a loss of empathy for their victims while under the influence of flunitrazepam, and it was found that the abuse of alcohol or other drugs in combination with flunitrazepam compounded the problem. Their behaviour under the influence of flunitrazepam was in contrast to their normal psychological state.
== Criticisms ==
The concept of drug-related crime has been criticized for being too blunt, especially in its failure to distinguish between three types of crime associated with drugs:
Use-Related crime: These are crimes that result from or involve individuals who ingest drugs, and who commit crimes as a result of the effect the drug has on their thought processes and behavior.
Economic-Related crime: These are crimes where an individual commits a crime to fund a drug habit. These include theft and prostitution.
System-Related crime: These are crimes that result from the structure of the drug system. They include production, manufacture, transportation, and sale of drugs, as well as violence related to the production or sale of drugs, such as a turf war.
Drug-related crime may be used as a justification for prohibition, but, in the case of system-related crime, the acts are only crimes because of prohibition. In addition, some consider even user-related and economic-related aspects of crime as symptomatic of a broader problem.
== See also ==
Alcohol-related crime
Drug abuse
Drugwipe test
Intoxication defense
Self-medication
General:
Prohibition (drugs)
Single Convention on Narcotic Drugs
Organized crime:
Cigarette smuggling
Drug Cartel
Drug Lord
Illegal drug trade
Organized crime
Rum-running
US specific:
Bureau of Justice Statistics
Bureau of Alcohol, Tobacco, Firearms and Explosives
Comprehensive Drug Abuse Prevention and Control Act of 1970
Controlled Substances Act
Drug Enforcement Administration
Food and Drug Administration
Racketeer Influenced and Corrupt Organizations Act (RICO)
U.S. Immigration and Customs Enforcement
Uniform Crime Report
== References ==
== External links ==
Defining drug-related crime - EU
Drug-related crime Canada
Drug-related crime UK
PDF version of Drug-related crime U.S. Department of Justice Archived 2012-09-16 at the Wayback Machine
Prevention of drug-related crime - EU
Beckley Foundation Report 2005, Reducing drug-related crime: an overview of the global Evidence
Driving under the influence of drugs
The National Center for Victims of Crime
Poverty exposure in childhood and adolescence is closely linked to a higher chance of drug use disorders and drug-related criminal activity in later life. Early drug exposure and the acceptance of criminal activity are caused by social disadvantages such disinvestment in the community, unsecure family settings, and limited access to education. Drug use and trafficking trends among male inner-city adolescents in Washington, D.C., frequently arise as responses to isolation from society and financial difficulty. In areas where legal possibilities are limited and illegal economies thrive, young individuals are more prone to resort to delinquent behaviors, such as drug distribution and violence, as a means of surviving.
Manhica, H., Straatmann, V. S., Lundin, A., Agardh, E., & Danielsson, A. (2020).
Association between poverty exposure during childhood and adolescence, and drug use
disorders and drug‐related crimes later in life. Addiction, 116(7), 1747–1756.
https://doi.org/10.1111/add.15336 | Wikipedia/Drug-related_crime |
The Law Enforcement Action Partnership (LEAP), formerly Law Enforcement Against Prohibition, is a U.S.-based nonprofit organization group of current and former police, judges, prosecutors, and other criminal justice professionals who use their expertise to advance drug policy and criminal justice solutions that enhance public safety. The organization is modeled after Vietnam Veterans Against the War. As of April 2017, they have more than 180 representatives around the world who speak on behalf of over 5,000 law enforcement members and 100,000 supporters.
The organization transitioned from Law Enforcement Against Prohibition into the Law Enforcement Action Partnership in January 2017. They previously focused on ending the War on Drugs and now discuss a broad range of issues relating to policing and criminal justice - from procedural justice practices to reducing recidivism. Their overarching message is about reducing crime and violence and improving public safety, while the issues they discuss fall into five key areas: improving police-community relations, reducing and finding alternatives to incarceration, improving access to harm reduction services, ending the War on Drugs and global issues.
== Goals ==
LEAP works to educate law enforcement, legislators, and the public about ways to bring about positive change in the criminal justice system. They speak to civic clubs, international conferences, and have been featured in many top U.S. media outlets.
== 5 key issue areas ==
=== Police-Community Relations ===
LEAP believes the key to improving police effectiveness is to go back to the fundamental principals of modern policing laid down by Robert Peel and improve public safety by increasing police-community trust.
Speakers advocate for solutions including treating officers for post-traumatic stress disorder; expanding police training and pay; addressing racial disparities in the justice system; abolishing stop-and-frisk practices; limiting police militarization to active shooter, hostage, and barricade incidents; ending civil asset forfeiture; and abolishing volume-based performance measures such as arrest quotas.
=== Incarceration ===
The Law Enforcement Action Partnership advocates for alternatives to arrest and incarceration as a means of reducing crime. They support reducing the use of mandatory minimum sentences, increasing the use of effective pre-booking diversion programs, increasing the use of restorative justice conferences, reforming the money-bail system, and reforming parole and probation systems. The group aims to reduce collateral consequences caused by arrest and incarceration, reduce racial disparities in sentencing and punishment, and reduce felony disenfranchisement.
=== Harm Reduction ===
LEAP supports harm reduction programs, which reduce the negative personal and societal consequences of drug use, including Supervised Injection Facilities, Law Enforcement Assisted Diversion (LEAD), heroin-assisted treatment, Medication Assisted Treatment, syringe exchange programs, expanded naloxone access, and treatment on demand. Until 2020 LEAP was the fiscal sponsor for the Influence Foundation, which operates the harm reduction publication Filter.
=== The War on Drugs ===
LEAP pushes to end the War on Drugs and legalize and regulate all drugs from a public health perspective as a means of reducing death, disease, and addiction associated with drug use and illegal drug sales.
=== Global Issues ===
The Law Enforcement Action Partnership is dedicated to studying international criminal justice issues and practical solutions. LEAP considers domestic and international drug policies and their disastrous consequences, including violent criminal organizations, widespread corruption, suppression of free press, immigration crises, and state-sanctioned killings of drug users and dealers. LEAP looks to countries including Switzerland and Portugal for pioneering innovative drug policies focused on public health and safety.
== Membership ==
=== Board of directors ===
The Law Enforcement Action Partnership's executive board is chaired by Lt. Diane Goldstein (Ret.) of the Redondo Beach Police Department in California. Board members include: Inge Fryklund, former Assistant State's Attorney in Chicago; Stephen Gutwillig, a professional nonprofit organizational development consultant; Jody David Armour, Professor of Law at the University of Southern California, Los Angeles, California; executive director Maj. Neill Franklin (Ret.) of the Baltimore and Maryland State Police Departments; Capt. Leigh Maddox (Ret.) of the Maryland State Police; Allison Watson, former Assistant District Attorney in Knoxville, Tennessee; and Det. Sergeant Neil Woods (Ret.) of Derbyshire, England.
=== Advisory board ===
The advisory board of Law Enforcement Against Prohibition consists of Romesh Bhattacharji, former drug czar (India); Vince Cain, former Chief Coroner of British Columbia and retired RCMP chief superintendent (Canada); Senator Larry Campbell, former mayor of Vancouver and retired RCMP officer (Canada); retired Supreme Court Justice Kenneth Crispin (Australia), Member of Parliament Libby Davies (Canada); Carel Edwards, former anti-drug coordinator for the European Union; U.S. District Court Judge Warren William Eginton; Gustavo de Greiff, former attorney general of Colombia; Gary Johnson, former governor of New Mexico; Judge John L. Kane Jr., United States District Court for the District of Colorado; Justice Ketil Lund, retired Supreme Court Justice from Norway; Sheriff Bill Masters, Colorado; Joseph McNamara, retired police chief of the San Jose Police Department; Norm Stamper, retired police chief of the Seattle Police Department; Eric Sterling, president of the Criminal Justice Policy Foundation; Thomas P. Sullivan, former U.S. Attorney for the Northern District of Illinois; Robert W. Sweet, Senior Judge of the US District Court Southern District of New York; Hans van Dujin, retired Dutch police union president (the Netherlands); Francis Wilkinson, former Chief Constable of the Gwent Police Force (United Kingdom); and Justice C. Ross (Ret.), former British Columbia Supreme Court judge (Canada).
=== Speakers bureau ===
Representatives of the Law Enforcement Action Partnership are trained to speak with audiences and media outlets on behalf of the organization. They include current and former/retired police officers, military police officers, judges, prosecutors, prison wardens and other corrections officials, parole and probation officers, and FBI and DEA agents.
=== Activities ===
=== Media ===
Each year, speakers conduct hundreds of interviews with outlets across the country, including AP, Newsweek, BBC, The Washington Post, FOX News, CNN, The Atlantic, The Intercept, Reason magazine, The Hill, The Guardian, The Washington Times, The Los Angeles Times, and others. They are regularly featured in documentaries, viral social media content, and local radio and TV segments.
=== Events ===
Representatives are regularly involved in speaking engagements in state legislatures and at press conferences, civic clubs, conferences and universities.
== Funding ==
LEAP has received funding from tobacco companies. In 2017 more than a third of its funding came from Reynolds American.
== See also ==
Drug Policy Alliance
DrugWarRant
Freedom of thought
NORML (National Organization for the Reform of Marijuana Laws)
Prohibition
Students for Sensible Drug Policy
Doctors for Cannabis Regulation
== References ==
== External links ==
Official website | Wikipedia/Law_Enforcement_Action_Partnership |
The Controlled Substances Act (CSA) is the statute establishing federal U.S. drug policy under which the manufacture, importation, possession, use, and distribution of certain substances is regulated. It was passed by the 91st United States Congress as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970 and signed into law by President Richard Nixon. The Act also served as the national implementing legislation for the Single Convention on Narcotic Drugs.
The legislation created five schedules (classifications), with varying qualifications for a substance to be included in each. Two federal agencies, the Drug Enforcement Administration (DEA) and the Food and Drug Administration (FDA), determine which substances are added to or removed from the various schedules, although the statute passed by Congress created the initial listing. Congress has sometimes scheduled other substances through legislation such as the Hillory J. Farias and Samantha Reid Date-Rape Prevention Act of 2000, which placed gamma hydroxybutyrate (GHB) in Schedule I and sodium oxybate (the isolated sodium salt in GHB) in Schedule III when used under an FDA New Drug Application (NDA) or Investigational New Drug (IND). Classification decisions are required to be made on criteria including potential for abuse (an undefined term), currently accepted medical use in treatment in the United States, and international treaties.
== History ==
The nation first outlawed addictive drugs in the early 1900s and the International Opium Convention helped lead international agreements regulating trade. The Pure Food and Drug Act (1906) was the beginning of over 200 laws concerning public health and consumer protections. Others were the Federal Food, Drug, and Cosmetic Act (1938), and the Kefauver Harris Amendment of 1962.
In 1969, President Richard Nixon announced that the Attorney General, John N. Mitchell, was preparing a comprehensive new measure to more effectively meet the narcotic and dangerous drug problems at the federal level by combining all existing federal laws into a single new statute. With the help of White House Counsel head, John Dean; the executive director of the Shafer Commission, Michael Sonnenreich; and the Director of the BNDD, John Ingersoll creating and writing the legislation, Mitchell was able to present Nixon with the bill.
The CSA not only combined existing federal drug laws and expanded their scope, but it also changed the nature of federal drug law policies and expanded federal law enforcement pertaining to controlled substances.
Title II, Part F of the Comprehensive Drug Abuse Prevention and Control Act of 1970 established the National Commission on Marijuana and Drug Abuse—known as the Shafer Commission after its chairman, Raymond P. Shafer—to study cannabis abuse in the United States. During his presentation of the commission's First Report to Congress, Sonnenreich and Shafer recommended the decriminalization of marijuana in small amounts, with Shafer stating,
[T]he criminal law is too harsh a tool to apply to personal possession even in the effort to discourage use. It implies an overwhelming indictment of the behavior which we believe is not appropriate. The actual and potential harm of use of the drug is not great enough to justify intrusion by the criminal law into private behavior, a step which our society takes only with the greatest reluctance.
Rufus King notes that this stratagem was similar to that used by Harry Anslinger when he consolidated the previous anti-drug treaties into the Single Convention and took the opportunity to add new provisions that otherwise might have been unpalatable to the international community. According to David T. Courtwright, "the Act was part of an omnibus reform package designed to rationalize, and in some respects to liberalize, American drug policy." (Courtwright noted that the Act became, not libertarian, but instead repressionistic to the point of tyrannical in its intent; a cruel and/or arbitrary exercise of power). It eliminated mandatory minimum sentences and provided support for drug treatment and research.
King notes that the rehabilitation clauses were added as a compromise to Senator Harold Hughes, who favored a moderate approach. The bill, as introduced by Senator Everett Dirksen, ran to 91 pages. While it was being drafted, the Uniform Controlled Substances Act, to be passed by state legislatures, was also being drafted by the Department of Justice; its wording closely mirrored the Controlled Substances Act.
=== Amendments, 1970–2018 ===
Since its enactment in 1970, the Act has been amended numerous times:
The 1976 Medical Device Regulation Act.
The Psychotropic Substances Act of 1978 added provisions implementing the Convention on Psychotropic Substances.
The Controlled Substances Penalties Amendments Act of 1984.
The 1986 Federal Analog Act for chemicals "substantially similar" in Schedule I and II to be listed
The 1988 Chemical Diversion and Trafficking Act (implemented August 1, 1989, as Article 12) added provisions implementing the United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances that went into force on November 11, 1990.
The 1990 Anabolic Steroids Control Act, passed as part of the Crime Control Act of 1990, which placed anabolic steroids into Schedule III: 30
The 1993 Domestic Chemical Diversion and Control Act (effective on April 16, 1994) in response to methamphetamine trafficking.
The Hillory J. Farias and Samantha Reid Date-Rape Prevention Act of 2000 placed gamma hydroxybutyrate (GHB) in Schedule I and sodium oxybate (the isolated sodium salt in GHB) in Schedule III when used under an FDA NDA or IND.
The 2008 Ryan Haight Online Pharmacy Consumer Protection Act
The 2010 Electronic Prescriptions for Controlled Substances (EPCS).
The 2012 Synthetic Drug Abuse Prevention Act Subtitle D - synthetic drugs, added several Markush like statements that describes synthetic cannabinoid chemical space that are also controlled as Schedule 1 substances. However, since then many new synthetic cannabinoids not covered by this act have emerged
The 2010 Secure and Responsible Drug Disposal Act (effective on October 12, 2010), to allow pharmacies to operate take-back programs for controlled substance medications in response to the US opioid epidemic.
The 2017 Protecting Patient Access to Emergency Medications Act (PPAEMA) amended Section 33 of the CSA to include DEA registration for Emergency Medical Service (EMS) agencies, approved uses of standing orders, and requirements for the maintenance and administration of controlled substances used by EMS agencies.
In 2018 the act was also amended to describe and control all chemical space related to Fentanyl like chemicals using Markush like notation, the first time Markush like statement were directly used in the act itself
== Statute content ==
The Controlled Substances Act consists of two subchapters. Subchapter I defines Schedules I–V, lists chemicals used in the manufacture of controlled substances, and differentiates lawful and unlawful manufacturing, distribution, and possession of controlled substances, including possession of Schedule I drugs for personal use; this subchapter also specifies the dollar amounts of fines and durations of prison terms for violations. Subchapter II describes the laws for exportation and importation of controlled substances, again specifying fines and prison terms for violations.
== Enforcement authority ==
The Drug Enforcement Administration was established in 1973, combining the Bureau of Narcotics and Dangerous Drugs (BNDD) and Customs' drug agents. Proceedings to add, delete, or change the schedule of a drug or other substance may be initiated by the DEA, the Department of Health and Human Services (HHS), or by petition from any interested party, including the manufacturer of a drug, a medical society or association, a pharmacy association, a public interest group concerned with drug abuse, a state or local government agency, or an individual citizen. When a petition is received by the DEA, the agency begins its own investigation of the drug.
The DEA may begin an investigation of a drug at any time based upon information received from laboratories, state and local law enforcement and regulatory agencies, or other sources of information. Once the DEA has collected the necessary data, the Deputy Administrator of DEA,: 42220 requests from HHS a scientific and medical evaluation and recommendation as to whether the drug or other substance should be controlled or removed from control.
This request is sent to the Assistant Secretary of Health of HHS. Then, HHS solicits information from the Commissioner of the Food and Drug Administration and evaluations and recommendations from the National Institute on Drug Abuse and, on occasion, from the scientific and medical community at large. The Assistant Secretary, by authority of the Secretary, compiles the information and transmits back to the DEA a medical and scientific evaluation regarding the drug or other substance, a recommendation as to whether the drug should be controlled, and in what schedule it should be placed.
The HHS recommendation on scheduling is binding to the extent that if HHS recommends, based on its medical and scientific evaluation, that the substance not be controlled, then the DEA may not control the substance. Once the DEA has received the scientific and medical evaluation from HHS, the DEA Administrator evaluates all available data and makes a final decision whether to propose that a drug or other substance be controlled and into which schedule it should be placed. Under certain circumstances, the Government may temporarily schedule a drug without following the normal procedure.
An example is when international treaties require control of a substance. 21 U.S.C. § 811(h) allows the Attorney General to temporarily place a substance in Schedule I "to avoid an imminent hazard to the public safety". Thirty days' notice is required before the order can be issued, and the scheduling expires after a year. The period may be extended six months if rulemaking proceedings to permanently schedule the drug are in progress. In any case, once these proceedings are complete, the temporary order is automatically vacated. Unlike ordinary scheduling proceedings, such temporary orders are not subject to judicial review.
The CSA creates a closed system of distribution for those authorized to handle controlled substances. The cornerstone of this system is the registration of all those authorized by the DEA to handle controlled substances. All individuals and firms that are registered are required to maintain complete and accurate inventories and records of all transactions involving controlled substances, as well as security for the storage of controlled substances.
== Treaty obligations ==
The Congressional findings in 21 USC §§ 801(7), 801a(2), and 801a(3) state that a major purpose of the CSA is to "enable the United States to meet all of its obligations" under international treaties. The CSA bears many resemblances to these Conventions. Both the CSA and the treaties set out a system for classifying controlled substances in several schedules in accordance with the binding scientific and medical findings of a public health authority. Under 21 U.S.C. § 811 of the CSA, that authority is the Secretary of Health and Human Services (HHS). Under Article 3 of the Single Convention and Article 2 of the Convention on Psychotropic Substances, the World Health Organization is that authority.
The domestic and international legal nature of these treaty obligations must be considered in light of the supremacy of the United States Constitution over treaties or acts and the equality of treaties and Congressional acts. In Reid v. Covert the Supreme Court of the United States addressed both these issues directly and clearly holding:
[N]o agreement with a foreign nation can confer power on the Congress, or on any other branch of Government, which is free from the restraints of the Constitution.
Article VI, the Supremacy Clause of the Constitution, declares:
"This Constitution, and the Laws of the United States which shall be made in Pursuance thereof, and all Treaties made, or which shall be made, under the Authority of the United States, shall be the supreme Law of the Land; ..."
There is nothing in this language which intimates that treaties and laws enacted pursuant to them do not have to comply with the provisions of the Constitution. Nor is there anything in the debates which accompanied the drafting and ratification of the Constitution which even suggests such a result. These debates, as well as the history that surrounds the adoption of the treaty provision in Article VI, make it clear that the reason treaties were not limited to those made in "pursuance" of the Constitution was so that agreements made by the United States under the Articles of Confederation, including the important peace treaties which concluded the Revolutionary War, would remain in effect. It would be manifestly contrary to the objectives of those who created the Constitution, as well as those who were responsible for the Bill of Rights—let alone alien to our entire constitutional history and tradition—to construe Article VI as permitting the United States to exercise power under an international agreement without observing constitutional prohibitions. In effect, such construction would permit amendment of that document in a manner not sanctioned by Article V. The prohibitions of the Constitution were designed to apply to all branches of the National Government, and they cannot be nullified by the Executive or by the Executive and the Senate combined.
There is nothing new or unique about what we say here. This Court has regularly and uniformly recognized the supremacy of the Constitution over a treaty. For example, in Geofroy v. Riggs, 133 U. S. 258, 133 U. S. 267, it declared:
"The treaty power, as expressed in the Constitution, is in terms unlimited except by those restraints which are found in that instrument against the action of the government or of its departments, and those arising from the nature of the government itself and of that of the States. It would not be contended that it extends so far as to authorize what the Constitution forbids, or a change in the character of the government, or in that of one of the States, or a cession of any portion of the territory of the latter, without its consent."
This Court has repeatedly taken the position that an Act of Congress, which must comply with the Constitution, is on a full parity with a treaty, and that, when a statute which is subsequent in time is inconsistent with a treaty, the statute to the extent of conflict renders the treaty null. It would be completely anomalous to say that a treaty need not comply with the Constitution when such an agreement can be overridden by a statute that must conform to that instrument.
According to the Cato Institute, these treaties only bind (legally obligate) the United States to comply with them as long as that nation agrees to remain a state party to these treaties. The U.S. Congress and the President of the United States have the absolute sovereign right to withdraw from or abrogate at any time these two instruments, in accordance with said nation's Constitution, at which point these treaties will cease to bind that nation in any way, shape, or form.
A provision for automatic compliance with treaty obligations is found at 21 U.S.C. § 811(d), which also establishes mechanisms for amending international drug control regulations to correspond with HHS findings on scientific and medical issues. If control of a substance is mandated by the Single Convention, the Attorney General is required to "issue an order controlling such drug under the schedule he deems most appropriate to carry out such obligations," without regard to the normal scheduling procedure or the findings of the HHS Secretary. However, the Secretary has great influence over any drug scheduling proposal under the Single Convention, because 21 U.S.C. § 811(d)(2)(B) requires the Secretary the power to "evaluate the proposal and furnish a recommendation to the Secretary of State which shall be binding on the representative of the United States in discussions and negotiations relating to the proposal."
Similarly, if the United Nations Commission on Narcotic Drugs adds or transfers a substance to a schedule established by the Convention on Psychotropic Substances, so that current U.S. regulations on the drug do not meet the treaty's requirements, the Secretary is required to issue a recommendation on how the substance should be scheduled under the CSA. If the Secretary agrees with the commission's scheduling decision, he can recommend that the Attorney General initiate proceedings to reschedule the drug accordingly.
If the HHS Secretary disagrees with the UN controls, the Attorney General must temporarily place the drug in Schedule IV or V (whichever meets the minimum requirements of the treaty) and exclude the substance from any regulations not mandated by the treaty. The Secretary is required to request that the Secretary of State take action, through the commission or the UN Economic and Social Council, to remove the drug from international control or transfer it to a different schedule under the convention. The temporary scheduling expires as soon as control is no longer needed to meet international treaty obligations.
This provision was invoked in 1984 to place Rohypnol (flunitrazepam) in Schedule IV. The drug did not then meet the Controlled Substances Act's criteria for scheduling; however, control was required by the Convention on Psychotropic Substances. In 1999, an FDA official explained to Congress:
Rohypnol is not approved or available for medical use in the United States, but it is temporarily controlled in Schedule IV pursuant to a treaty obligation under the 1971 Convention on Psychotropic Substances. At the time flunitrazepam was placed temporarily in Schedule IV (November 5, 1984), there was no evidence of abuse or trafficking of the drug in the United States.
The Cato Institute's Handbook for Congress calls for repealing the CSA, an action that would likely bring the United States into conflict with international law, were the United States not to exercise its sovereign right to withdraw from and/or abrogate the Single Convention on Narcotic Drugs and/or the 1971 Convention on Psychotropic Substances prior to repealing the Controlled Substances Act. The exception would be if the U.S. were to claim that the treaty obligations violate the United States Constitution. Many articles in these treaties—such as Article 35 and Article 36 of the Single Convention—are prefaced with phrases such as "Having due regard to their constitutional, legal and administrative systems, the Parties shall ..." or "Subject to its constitutional limitations, each Party shall ..." According to former United Nations Drug Control Programme Chief of Demand Reduction Cindy Fazey, "This has been used by the USA not to implement part of article 3 of the 1988 Convention, which prevents inciting others to use narcotic or psychotropic drugs, on the basis that this would be in contravention of their constitutional amendment guaranteeing freedom of speech".
== Schedules of controlled substances ==
There are five different schedules of controlled substances, numbered I–V. The CSA describes the different schedules based on three factors:
Potential for abuse: How likely is this drug to be abused?
Accepted medical use: Is this drug used as a treatment in the United States?
Safety and potential for addiction: Is this drug safe? How likely is this drug to cause addiction? What kinds of addiction?
The following table gives a summary of the different schedules.
Placing a drug or other substance in a certain schedule or removing it from a certain schedule is primarily based on 21 USC §§ 801, 801a, 802, 811, 812, 813, and 814. Every schedule otherwise requires finding and specifying the "potential for abuse" before a substance can be placed in that schedule. The specific classification of any given drug or other substance is usually a source of controversy, as is the purpose and effectiveness of the entire regulatory scheme.
The term "controlled substance" means a drug or other substance, or immediate precursor, included in schedule I, II, III, IV, or V of part B of this subchapter. The term does not include distilled spirits, wine, absinthe, malt beverages, nicotine or tobacco, as those terms are defined or used in subtitle E of the Internal Revenue Code of 1986.
Some have argued that this is an important exemption, since alcohol and tobacco are two of the most widely used drugs in the United States.
=== Schedule I ===
Schedule I substances are described as those that have all of the following findings:
No prescriptions may be written for Schedule I substances, and such substances are subject to production quotas which the DEA imposes.
Under the DEA's interpretation of the CSA, a drug does not necessarily have to have the same "high potential for abuse" as heroin, for example, to merit placement in Schedule I:
[W]hen it comes to a drug that is currently listed in schedule I, if it is undisputed that such drug has no currently accepted medical use in treatment in the United States and a lack of accepted safety for use under medical supervision, and it is further undisputed that the drug has at least some potential for abuse sufficient to warrant control under the CSA, the drug must remain in schedule I. In such circumstances, placement of the drug in schedules II through V would conflict with the CSA since such drug would not meet the criterion of "a currently accepted medical use in treatment in the United States." 21 USC 812(b). (emphasis added)
Drugs listed in this control schedule include:
αMT (alpha-methyltryptamine), a psychedelic, stimulant, and entactogen drug of the tryptamine class that was originally developed as an antidepressant by workers at Upjohn in the 1960s.
BZP (benzylpiperazine), a synthetic stimulant once sold as a designer drug. It has been shown to be associated with an increase in seizures if taken alone. Although the effects of BZP are not as potent as MDMA, it can produce neuroadaptations that can cause an increase in the potential for abuse of this drug.
Cathinone, an amphetamine-like stimulant found in the shrub Catha edulis (khat).
DMT (dimethyltryptamine), a naturally occurring psychedelic drug that is widespread throughout the plant kingdom and endogenous to the human body. DMT is the main psychoactive constituent in the psychedelic South American brew, ayahuasca, for which the UDV are granted exemption from DMT's schedule I status on the grounds of religious freedom.
Etorphine, a semi-synthetic opioid possessing an analgesic potency approximately 1,000–3,000 times that of morphine.
GHB (gamma-Hydroxybutyric acid), a general anesthetic and treatment for narcolepsy-cataplexy and alcohol withdrawal with a limited safe dosage range and poor ability to control pain when used as an anesthetic (severely limiting its usefulness). It was placed in Schedule I in March 2000 after widespread recreational use led to increased emergency room visits, hospitalizations, and deaths. A specific formulation of this drug is also listed in Schedule III for limited uses, under the trademark Xyrem.
Heroin is the brand name for diacetylmorphine or morphine diacetate, which is an inactive prodrug that exerts its effects after being converted into the major active metabolite morphine, and the minor metabolite 6-MAM - which itself is also rapidly converted to morphine. Some European countries still use it as a potent pain reliever in terminal cancer patients, and as second option, after morphine sulfate; it is about twice as potent, by weight, as morphine and, indeed, becomes morphine upon injection into the bloodstream. The two acetyl groups attached to the morphine make a prodrug which delivers morphine to the opioid receptors twice as fast as morphine can.
Ibogaine, a naturally occurring psychoactive substance found in plants in the family Apocynaceae. Some countries in North America use ibogaine as an alternative medicine treatment for opioid drug addiction. Ibogaine is also used for medicinal and ritual purposes within African spiritual traditions of the Bwiti.
LSD (lysergic acid diethylamide), a semi-synthetic psychedelic drug famous for its involvement in the counterculture of the 1960s.
Marijuana and its cannabinoids. Pure (–)-trans-Δ9-tetrahydrocannabinol is also listed in Schedule III for limited uses, under the trademark Marinol. As a result of ballot initiatives, many states have made recreational and medical use of marijuana legal, while other states have decriminalized possession of small amounts. Such measures operate only on state laws, and have no effect on federal law. Whether such users would actually be prosecuted under federal law is a separate question with no definitive answer. Given the widespread medicinal use of cannabis, the maintenance of its Schedule I classification has been controversial, with many calling for a reclassification or holistic federal decriminalization. As of April 30, 2024, cannabis was set to be reclassified by the DEA as a Schedule III controlled substance.
MDMA ("ecstasy" or "molly"), a stimulant, psychedelic, and entactogenic drug which initially garnered attention in psychedelic therapy as a treatment for post-traumatic stress disorder (PTSD). The medical community originally agreed upon placing it as a Schedule III substance, but the government denied this suggestion, despite two court rulings by the DEA's administrative law judge that placing MDMA in Schedule I was illegal. It was temporarily unscheduled after the first administrative hearing from December 22, 1987 – July 1, 1988.
Mescaline, a naturally occurring psychedelic drug and the main psychoactive constituent of peyote (Lophophora williamsii), San Pedro cactus (Echinopsis pachanoi), and Peruvian torch cactus (Echinopsis peruviana).
Methaqualone (Quaalude, Sopor, Mandrax), a sedative that was previously used for similar purposes as barbiturates, until it was rescheduled.
Peyote (Lophophora williamsii), a cactus growing in nature primarily in northeastern Mexico; one of the few plants specifically scheduled, with a narrow exception to its legal status for religious use in Native American churches.
Psilocybin and psilocin, naturally occurring psychedelic drugs and the main psychoactive constituents of psilocybin mushrooms.
Controlled substance analogues intended for human consumption, as defined by the Federal Analogue Act.
In addition to the named substance, usually all possible ethers, esters, salts and stereoisomers of these substances are also controlled and also 'analogues', which are chemically similar chemicals.
=== Schedule II ===
Schedule II substances are those that have the following findings:
Except when dispensed directly to an ultimate user by a practitioner other than a pharmacist, no controlled substance in Schedule II, which is a prescription drug as determined under the Federal Food, Drug, and Cosmetic Act (21 USC 301 et seq.), may be dispensed without the written or electronically transmitted (21 CFR 1306.08) prescription of a practitioner, except that in emergency situations, as prescribed by the Secretary by regulation after consultation with the Attorney General, such drug may be dispensed upon oral prescription in accordance with section 503(b) of that Act (21 USC 353 (b)). With exceptions, an original prescription is always required even though faxing in a prescription in advance to a pharmacy by a prescriber is allowed. Prescriptions shall be retained in conformity with the requirements of section 827 of this title. No prescription for a controlled substance in Schedule II may be refilled.
These drugs vary in potency: for example fentanyl is about 80 times as potent as morphine (heroin is roughly two times as potent). More significantly, they vary in nature. Pharmacology and CSA scheduling have a weak relationship.
Because refills of prescriptions for Schedule II substances are not allowed, it can be burdensome to both the practitioner and the patient if the substances are to be used on a long-term basis. To provide relief, in 2007, 21 CFR 1306.12 was amended (at 72 FR 64921) to allow practitioners to write up to three prescriptions at once, to provide up to a 90-day supply, specifying on each the earliest date on which it may be filled.
Drugs in this schedule include:
Amphetamine drugs including Adderall, Dextroamphetamine (Dexedrine), Lisdexamfetamine (Vyvanse): treatment of ADHD, narcolepsy, severe obesity (limited use, dextroamphetamine only), binge eating disorder (lisdexamfetamine only). Originally placed in Schedule III, but moved to Schedule II in 1978 as part of the Psychotropic Substances Act.
Barbiturates (short-acting), such as pentobarbital
Cocaine: used as a topical anesthetic or local anesthetic and to stop severe epistaxis
Codeine (pure) and any drug for non-parenteral administration containing the equivalent of more than 90 mg of codeine per dosage unit;
Diphenoxylate (pure)
Fentanyl and most other strong pure opioid agonists, e.g. levorphanol
Hydrocodone in any formulation since October 2014 (examples include Vicodin, Norco, Tussionex). Prior to October 2014, formulations containing hydrocodone and over-the-counter analgesics such as Acetaminophen and Ibuprofen were Schedule III.
Hydromorphone (semi-synthetic opioid; active ingredient in Dilaudid, Palladone)
Methadone: treatment of heroin addiction, extreme chronic pain
Methamphetamine: treatment of ADHD (rare), severe obesity (limited use) under the brandname Desoxyn.
Methylphenidate (Ritalin, Concerta), Dexmethylphenidate (Focalin): treatment of ADHD, narcolepsy
Morphine: a pain medication of the opiate family.
Nabilone (Cesamet) – A synthetic cannabinoid. An analogue to dronabinol (Marinol) which is a Schedule III drug.
Opium tincture (Laudanum): a potent antidiarrheal
Oxycodone (semi-synthetic opioid; active ingredient in Percocet, OxyContin, and Percodan)
Oxymorphone (semi-synthetic opioid; active ingredient in Opana)
Nembutal (Pentobarbital) – barbiturate medication originally developed for narcolepsy; primarily used today for physician assisted suicide and euthanasia of animals.
Pethidine (USAN: Meperidine; Demerol)
Phencyclidine (PCP) - Formerly used as veterinary anesthetic under the trade name Sernylan and before then as an injectable anesthetic under the trade name Sernyl.
Secobarbital (Seconal)
Tapentadol (Nucynta) – A drug with mixed opioid agonist and norepinephrine re-uptake inhibitor activity.
=== Schedule III ===
Schedule III substances are those that have the following findings:
Except when dispensed directly by a practitioner, other than a pharmacist, to an ultimate user, no controlled substance in Schedule III or IV, which is a prescription drug as determined under the Federal Food, Drug, and Cosmetic Act (21 USC 301 et seq.), may be dispensed without a written, electronically transmitted, or oral prescription in conformity with section 503(b) of that Act (21 USC 353 (b)). Such prescriptions may not be filled or refilled more than six months after the date thereof or be refilled more than five times after the date of the prescription unless renewed by the practitioner.
A prescription for controlled substances in Schedules III, IV, and V issued by a practitioner, may be communicated either orally, in writing, electronically transmitted or by facsimile to the pharmacist, and may be refilled if so authorized on the prescription or by call-in. Control of wholesale distribution is somewhat less stringent than Schedule II drugs. Provisions for emergency situations are less restrictive within the "closed system" of the Controlled Substances Act than for Schedule II though no schedule has provisions to address circumstances where the closed system is unavailable, nonfunctioning or otherwise inadequate.
Drugs in this schedule include:
Ketamine, a drug originally developed as a safer, shorter-acting replacement for PCP (mainly for use as a human anesthetic) but has since become popular as a veterinary and pediatric anesthetic;
Anabolic steroids (including prohormones such as androstenedione); the specific end molecule testosterone in many of its forms (Androderm, AndroGel, Testosterone Cypionate, and Testosterone Enanthate) are labeled as Schedule III while low-dose testosterone when compounded with estrogen derivatives have been exempted (from scheduling) by the FDA
Intermediate-acting barbiturates, such as talbutal or butalbital
Buprenorphine (semi-synthetic opioid; active in Suboxone, Subutex)
Dihydrocodeine when compounded with other substances, to a certain dosage and concentration.
FDA-approved sodium oxybate products (e.g. Xyrem, Xywav and Lumryz)—preparations of GHB used to treat narcolepsy. These products are in Schedule III but with a restricted distribution system. All other forms or preparations of GHB are in Schedule I.
Marinol, synthetically prepared tetrahydrocannabinol (officially referred to by its INN, dronabinol) used to treat nausea and vomiting caused by chemotherapy, as well as appetite loss caused by AIDS.
Paregoric, an antidiarrheal and anti-tussive, which contains opium combined with camphor (which makes it less addiction-prone than laudanum, which is in Schedule II).
Phendimetrazine Tartrate, a stimulant synthesized for use as an anorexiant.
Benzphetamine HCl (Didrex), a stimulant designed for use as an anorexiant.
Fast-acting barbiturates such as secobarbital (Seconal) and pentobarbital (Nembutal), when combined with one or more additional active ingredient(s) not in Schedule II (e.g., Carbrital (no longer marketed), a combination of pentobarbital and carbromal).
Ergine (lysergic acid amide), listed as a sedative but also has psychedelic effects such as visual and auditory effects. An inefficient precursor to its N, N-diethyl analogue, LSD, ergine occurs naturally in the seeds of the common garden flowers Turbina corymbosa, Ipomoea tricolor, and Argyreia nervosa.
Perampanel (Fycompa), an anticonvulsant
=== Schedule IV ===
Placement on schedules; findings required
Schedule IV substances are those that have the following findings:
Control measures are similar to Schedule III. Prescriptions for Schedule IV drugs may be refilled up to five times within a six-month period. A prescription for controlled substances in Schedules III, IV, and V issued by a practitioner, may be communicated either orally, in writing, electronically transmitted or by facsimile to the pharmacist, and may be refilled if so authorized on the prescription or by call-in.
Drugs in this schedule include:
Benzodiazepines, such as alprazolam (Xanax), chlordiazepoxide (Librium), clonazepam (Klonopin), diazepam (Valium), midazolam (Versed), and Lorazepam (Ativan), as well as:
temazepam (Restoril) (some states require specially coded prescriptions for temazepam)
flunitrazepam (Rohypnol) (flunitrazepam is not FDA approved making it an illegal drug in the United States)
oxazepam (Serax, Serepax, Seresta, Alepam, Opamox, Oxamin)
The benzodiazepine-like Z-drugs: zolpidem (Ambien), zopiclone (Imovane), eszopiclone (Lunesta), and zaleplon (Sonata) (zopiclone is not commercially available in the U.S.)
Chloral hydrate, a sedative-hypnotic
Long-acting barbiturates such as phenobarbital
Some partial agonist opioid analgesics, such as pentazocine (Talwin)
The eugeroic drug modafinil (sold in the U.S. as Provigil) as well as its (R)-enantiomer armodafinil (sold in the U.S. as Nuvigil)
Difenoxin, an antidiarrheal drug, when combined with atropine (such as Motofen) (difenoxin is 2–3 times more potent than diphenoxylate, the active ingredient in Lomotil, which is in Schedule V)
Tramadol (Ultram), an opioid analgesic
Carisoprodol (Soma) has become a Schedule IV medication as of January 11, 2012
Suvorexant and Lemborexant, orexinergic sedatives
=== Schedule V ===
Schedule V substances are those that have the following findings:
No controlled substance in Schedule V which is a drug may be distributed or dispensed other than for a medical purpose. A prescription for controlled substances in Schedules III, IV, and V issued by a practitioner, may be communicated either orally, in writing, electronically transmitted or by facsimile to the pharmacist, and may be refilled if so authorized on the prescription or by call-in.
Drugs in this schedule include:
Cough suppressants containing small amounts of codeine (e.g., promethazine+codeine);
Preparations containing small amounts of opium or diphenoxylate (used to treat diarrhea);
Some anticonvulsants, such as pregabalin (Lyrica), lacosamide (Vimpat), brivaracetam (Briviact), and retigabine (ezogabine) (Potiga/Trobalt);
Pyrovalerone (used to treat chronic fatigue and as an appetite suppressant for weight loss);
Some centrally-acting antidiarrheals, such as diphenoxylate (Lomotil) when mixed with atropine (to make it poisonous, if taken at euphoria-inducing dosages). Difenoxin with atropine (Motofen) has been moved to Schedule IV. Without atropine, these drugs are in Schedule II.
Cannabidiol, only in a cannabis-derived pharmaceutical formulation marketed by GW Pharmaceuticals as Epidiolex. Other CBD formulations remain Schedule I, except for those derived from hemp which are unscheduled but still FDA-regulated.
=== Controlled by other federal laws for legal recreational use ===
These psychoactive drugs are not controlled by the act, and are also allowed for sale intended for recreational use at the federal level (others are allowed for sale as dietary supplements, but not specifically regulated or intended for recreational use):
Alcohol (ethanol), a sedative found in alcoholic drinks. Per the National Minimum Drinking Age Act (which is voluntarily abided by all 50 U.S. states), sale is limited to persons 21-years-old and above only. Sale regulated by the Bureau of Alcohol, Tobacco, Firearms and Explosives (ATF) and less commonly the Food and Drug Administration (FDA). Alcohol was formerly illegal under the Eighteenth Amendment to the Constitution from 1919, until the Twenty-first Amendment repealed it in 1933.
Caffeine, a stimulant found in coffee, chocolate; and some teas and soft drinks. It is regulated by the FDA under the Federal Food, Drug, and Cosmetic Act, and drinks cannot contain more than 200 parts per million (0.02%) of caffeine. There is no federal age restriction for caffeine-containing products. Also available medically in some pain medications (usually in combination with other drugs, like in aspirin/acetaminophen/caffeine).
Nicotine, a stimulant found in tobacco (including cigarettes and cigars) and electronic cigarettes. Also used medically in nicotine replacement therapy. The minimum purchasing age of tobacco and e-cigarettes in the United States is 21-years-old, per the Synar amendment to the Public Health Service Act. Sales are regulated by the ATF and FDA.
== Regulation of precursors ==
The Controlled Substances Act also provides for federal regulation of precursors used to manufacture some of the controlled substances. The DEA list of chemicals is actually modified when the United States Attorney General determines that illegal manufacturing processes have changed.
In addition to the CSA, due to pseudoephedrine (PSE) and ephedrine being widely used in the manufacture of methamphetamine, the U.S. Congress passed the Methamphetamine Precursor Control Act which places restrictions on the sale of any medicine containing pseudoephedrine. That bill was then superseded by the Combat Methamphetamine Epidemic Act of 2005, which was passed as an amendment to the Patriot Act renewal and included wider and more comprehensive restrictions on the sale of PSE-containing products. This law requires customer signature of a "log-book" and presentation of valid photo ID in order to purchase PSE-containing products from all retailers.
Additionally, the law restricts an individual to the retail purchase of no more than three packages or 3.6 grams of such product per day per purchase – and no more than 9 grams in a single month. A violation of this statute constitutes a misdemeanor. Retailers now commonly require PSE-containing products to be sold behind the pharmacy or service counter. This affects many preparations which were previously available over-the-counter without restriction, such as Actifed and its generic equivalents.
== Research exemptions ==
A common misunderstanding amongst researchers is that most national laws (including the Controlled Substance Act) allows the supply/use of small amounts of a controlled substance for non-clinical / non-in vivo research without licenses. A typical use case might be having a few milligrams or microlitres of a controlled substance within larger chemical collections (often tens of thousands of chemicals) for in vitro screening or sale. Researchers often believe that there is some form of "research exemption" for such small amounts. This incorrect view may be further re-enforced by R&D chemical suppliers often stating and asking scientists to confirm that anything bought is for research use only.
A further misconception is that the Controlled Substances Act simply lists a few hundred substances (e.g. MDMA, Fentanyl, Amphetamine, etc.) and compliance can be achieved via checking a CAS number, chemical name or similar identifier. However, the reality is that in most cases all ethers, esters, salts and stereoisomers are also controlled and it is impossible to simply list all of these. The act contains several "generic statements" or "chemical space" laws, which aim to control all chemicals similar to the "named" substance, these provide detailed descriptions similar to Markushes, these include ones for Fentanyl and also synthetic cannabinoids.
Due to this complexity in legislation, the identification of controlled chemicals in research or chemical supply is often carried out computationally on the chemical structure, either by in-house systems maintained a company or by the use of commercial software solutions. Automated systems are often required as many research operations can have collections of 10,000–100,000 different substances at the 1–5 milligram scale, which are likely to include controlled substances, especially within medicinal chemistry research, even if the core focus of the company is not narcotic or psychotropic drugs. These may not have been controlled when created, but they have subsequently been declared controlled, or fall within chemical space close to known controlled substances, or are used as tool compounds, precursors or synthetic intermediates to a controlled substance.
== Analogues vs Markush descriptions ==
Historically, in an attempt to prevent psychoactive chemicals which are chemically similar to controlled substance, but not specifically controlled by it, the CSA also controls "analogues" of many listed controlled substances. The definition of what 'analogue' means is kept deliberately vague, presumably to make it harder to circumvent this rule, as it's not clear what is / is not controlled, thus placing an element of risk and deterrent in those performing the supply. It is up to the courts to then decide whether a specific chemical is an analogue, often via a 'battle of experts' for the defense and prosecution which can lead to extended and more uncertain prosecutions. The use of the 'analogue' definition also make it more difficult for companies involved in the legitimate supply of chemicals for research and industrial purposes to know whether a chemical is regulated under the CSA
Starting in 2012, with the Synthetic drug abuse prevention act, and later an amendment to the CSA in 2018 defining fentanyl chemical space, the CSA started to use Markush descriptions to clearly define what analogues or chemical space is controlled. These chemical space, chemical family, generic statements or markush statements (depending on the legislation terminology) have been used for many years by other countries, notably the UK in the Misuse of Drugs Act.
These have the advantage of clearly defining what is controlled, making prosecutions easier and compliance by legitimate companies simpler. However the downside is that these tend to be harder to understand for non-chemists and also give those wishing to supply for illegitimate reasons something to 'aim' for in terms of non-controlled chemical space. For both Markush and analogue type approaches, typically computational systems are used to flag likely regulated chemicals.
== Criticism ==
The CSA does not include a definition of "drug abuse". In addition, research shows certain substances on Schedule I, for drugs which have no accepted medical uses and high potential for abuse, actually have accepted medical uses, have low potential for abuse, or both. One of those substances is cannabis, which is either decriminalized or legalized in 33 states of the United States.
== See also ==
Similar legislation outside of the United States:
Controlled Drugs and Substances Act (Canada)
Misuse of Drugs Act 1971 (United Kingdom)
== Notes ==
== References ==
== External links ==
Full text of Controlled Substances Act: 1970 version | Current version
Controlled Substances Act (PDF/details) as amended in the GPO Statute Compilations collection
The Controlled Substances Act (CSA): A Legal Overview for the 116th Congress | Wikipedia/Controlled_Substances_Act |
The drug policy of the Soviet Union changed little throughout the existence of the state, other than slowly becoming more repressive, although some differences in penalties existed in the different Union Republics.
However, the prevalence of drug addiction remained reportedly low as first claimed by Soviet authorities which later (under Mikhail Gorbachev) acknowledged a much larger problem; at least to drugs other than alcohol or tobacco; however, the rates of addiction increased in post-Soviet states.
== Regulation ==
Legislation against drugs first appeared in post-revolutionary Russia, in Article 104-d of the 1922 penal code of the RSFSR, criminalising drug production, trafficking, and possession with intent to traffic. The 1924 Soviet Constitution expanded this legislation to cover the whole Soviet Union. The 1926 penal code of the RSFSR suggested imprisonment or corrective labour for between one and three years as punishment for these offences, depending on the scale of the offence committed. Drug possession without intention to traffic and the personal use of drugs warranted no penalties at this time.
Drug regulation remained largely untouched in the Soviet Union until 1974, when the Supreme Soviet issued a decree entitled 'On Reinforcement of the Fight Against Drug Addiction'. This decree was reproduced in Article 224 of the penal codes of all the republics of the USSR, and not only increased the penalties for the offences mentioned above to between ten and fifteen years' imprisonment, but for the first time criminalised possession of drugs without intent to traffic, bringing a penalty of up to three years in prison. Additional offences of 'seducing another person to narcotic drugs', punishable by up to five years' imprisonment, and the theft of narcotics, punishable by between five and fifteen years' imprisonment, were also created. The term 'narcotics' used here referred to all drugs listed by UN Conventions, not just opiates.
A further decree issued in 1987 made a conviction for the above offences within a year of an earlier conviction for the same violation of the law liable to punishment of up to two years' imprisonment or corrective labor. Sergei Lebedev, the Chairman of the Association of Independent Advocates in Leningrad at the time, argued that the steady escalation of criminal penalties for drug use was "indicative of the Soviet authorities' resignation to their complete inability to solve drug problems in a constructive and humane way".
== Treatment ==
Treatment was performed in various different ways depending on the substance the patient was addicted to: a physician would usually administer their drug of choice in small doses for maintenance, which was done to reduce the intensity of the withdrawal symptoms.
== See also ==
Arguments for and against drug prohibition
Drug liberalisation
Drug policy of Portugal
Drug policy of the Netherlands
Drug policy of the United States
Drug rehabilitation
== References ==
== Bibliography ==
Neuhauser, Kimberly C. (1 January 1990). Grossman, Gregory; Treml, Vladimir G.; Gaddy, Clifford G. (eds.). The market for illegal drugs in the Soviet Union in the late 1980's (PDF). Berkeley-Duke occasional papers on the second economy in the USSR. Washington, D.C.: National Council for Eurasian and East European Research/Duke University.
== External links ==
https://web.archive.org/web/20110610131643/http://www.drugtext.org/library/articles/923108.html
http://www.cedro-uva.org/lib/cohen.future.html
http://www.westonrehab.org/best-christian-center-dallas-tx/ Archived 2015-02-27 at the Wayback Machine
http://stopthedrugwar.org/chronicle-old/328/russia.shtml
https://web.archive.org/web/20101017103634/http://drugpolicy.org/global/drugpolicyby/asia/russia/ | Wikipedia/Drug_policy_of_the_Soviet_Union |
Alcohol, sometimes referred to by the chemical name ethanol, is the active ingredient in alcoholic drinks such as beer, wine, and distilled spirits (hard liquor). Alcohol is a central nervous system (CNS) depressant, decreasing electrical activity of neurons in the brain, which causes the characteristic effects of alcohol intoxication ("drunkenness"). Among other effects, alcohol produces euphoria, decreased anxiety, increased sociability, sedation, and impairment of cognitive, memory, motor, and sensory function.
Alcohol has a variety of adverse effects. Short-term adverse effects include generalized impairment of neurocognitive function, dizziness, nausea, vomiting, and symptoms of hangover. Alcohol is addictive and can result in alcohol use disorder, dependence, and withdrawal upon cessation. The long-term effects of alcohol are considered to be a major global public health issue and include liver disease, hepatitis, cardiovascular disease (e.g., cardiomyopathy), polyneuropathy, alcoholic hallucinosis, long-term impact on the brain (e.g., brain damage, dementia, and Marchiafava–Bignami disease), and cancers. The adverse effects of alcohol on health are most significant when it is used in excessive quantities or with heavy frequency. However, in 2023, the World Health Organization published a statement in The Lancet Public Health that concluded, "no safe amount of alcohol consumption for cancers and health can be established." In high amounts, alcohol may cause loss of consciousness or, in severe cases, death.
Alcohol has been produced and consumed by humans for its psychoactive effects since at least 13,000 years ago, when the earliest known beer was brewed by the Natufian culture in the Middle East. Alcohol is the second most consumed psychoactive drug globally, behind caffeine. Drinking alcohol is generally socially acceptable and is legal in most countries, unlike with many other recreational substances. However, there are often restrictions on alcohol sale and use, for instance a minimum age for drinking and laws against public drinking and drinking and driving. Alcohol has considerable societal and cultural significance and has important social roles in much of the world. Drinking establishments, such as bars and nightclubs, revolve primarily around the sale and consumption of alcoholic beverages, and parties, festivals, and social gatherings commonly involve alcohol consumption. Alcohol is related to various societal problems, including drunk driving, accidental injuries, sexual assaults, domestic abuse, and violent crime. Alcohol remains illegal for sale and consumption in a number of countries, mainly in the Middle East. While some religions, including Islam, prohibit alcohol consumption, other religions, such as Christianity and Shinto, utilize alcohol in sacrament and libation.
== Uses ==
=== Recreational ===
Ethanol is commonly consumed as a recreational substance by mouth in the form of alcoholic beverages such as beer, wine, and spirits. It is commonly used in social settings due to its capacity to enhance sociability. Alcohol consumption while socializing increases occurrences of Duchenne smiling, talking, and social bonding, even when participants are unaware of their alcohol consumption or lack thereof. In a study of the UK, regular drinking was correlated with happiness, feeling that life was worthwhile, and satisfaction with life. According to a causal path analysis, alcohol consumption was not the cause, but rather satisfaction with life resulted in greater happiness and an inclination to visit pubs and develop a regular drinking venue. City centre bars were distinguished by their focus on maximizing alcohol sales. Community pubs had less variation in visible group sizes and longer, more focused conversations than those in city centre bars. Drinking regularly at a community pub led to higher trust in others and better networking with the local community, compared to non-drinkers and city centre bar drinkers. Research on the societal benefits of alcohol is rare.
=== Food energy ===
The US Department of Agriculture (USDA) uses a figure of 6.93 kilocalories (29.0 kJ) per gram of alcohol (5.47 kcal or 22.9 kJ per mL) for calculating food energy. For distilled spirits, a standard serving in the United States is 44 mL (1.5 US fl oz), which at 40% ethanol (80 proof), would be 14 grams and 98 calories. Alcoholic drinks are considered empty calorie foods because other than food energy they contribute no essential nutrients. However, alcohol is a significant source of food energy for individuals with alcoholism and those who engage in binge drinking. For example, individuals with drunkorexia engage in the combination of self-imposed malnutrition and binge drinking. In alcoholics who get most of their daily calories from alcohol, a deficiency of thiamine (vitamin B1) can produce Korsakoff syndrome, which is associated with serious brain damage.
=== Medical ===
When fomepizole is not available, ethanol can be used to treat or prevent methanol or ethylene glycol poisoning. The rate-limiting steps for the elimination of ethanol are in common with these substances, so it competes with other alcohols for the alcohol dehydrogenase enzyme. Methanol itself is not highly toxic, but its metabolites formaldehyde and formic acid are; therefore, to reduce the rate of production and concentration of these harmful metabolites, ethanol can be ingested or injected. This avoid toxic aldehyde and carboxylic acid derivatives, and reduces the more serious toxic effects of the glycols when crystallized in the kidneys. Ethylene glycol poisoning can be treated in the same way.
=== Warfare ===
Alcohol has a long association of military use, and has been called "liquid courage" for its role in preparing troops for battle, anesthetize injured soldiers, and celebrate military victories. It has also served as a coping mechanism for combat stress reactions and a means of decompression from combat to everyday life.
=== Self-medication ===
Alcohol can have analgesic (pain-relieving) effects, which is why some people with chronic pain turn to alcohol to self-medicate and try to alleviate their physical discomfort.
People with social anxiety disorder commonly self-medicate with alcohol to overcome their highly set inhibitions. However, self-medicating excessively for prolonged periods of time with alcohol often makes the symptoms of anxiety or depression worse. This is believed to occur as a result of the changes in brain chemistry from long-term use. A 2023 systematic review highlights the non-addictive use of alcohol for managing developmental issues, personality traits, and psychiatric symptoms, emphasizing the need for informed, harm-controlled approaches to alcohol consumption within a personalized health policy framework.
== Contraindications ==
=== Pregnancy ===
Ethanol is classified as a teratogen—a substance known to cause birth defects; according to the U.S. Centers for Disease Control and Prevention (CDC), alcohol consumption by women who are not using birth control increases the risk of fetal alcohol spectrum disorders (FASDs). This group of conditions encompasses fetal alcohol syndrome, partial fetal alcohol syndrome, alcohol-related neurodevelopmental disorder, static encephalopathy, and alcohol-related birth defects. The CDC currently recommends complete abstinence from alcoholic beverages for women of child-bearing age who are pregnant, trying to become pregnant, or are sexually active and not using birth control.
=== Peptic ulcer disease ===
In patients who have a peptic ulcer disease (PUD), the mucosal layer is broken down by ethanol. PUD is commonly associated with the bacteria Helicobacter pylori, which secretes a toxin that weakens the mucosal wall, allowing acid and protein enzymes to penetrate the weakened barrier. Because alcohol stimulates the stomach to secrete acid, a person with PUD should avoid drinking alcohol on an empty stomach. Drinking alcohol causes more acid release, which further damages the already-weakened stomach wall. Complications of this disease could include a burning pain in the abdomen, bloating and in severe cases, the presence of dark black stools indicate internal bleeding. A person who drinks alcohol regularly is strongly advised to reduce their intake to prevent PUD aggravation.
=== Allergic-like reactions ===
Ethanol-containing beverages can cause alcohol flush reactions, exacerbations of rhinitis and, more seriously and commonly, bronchoconstriction in patients with a history of asthma, and in some cases, urticarial skin eruptions, and systemic dermatitis. Such reactions can occur within 1–60 minutes of ethanol ingestion, and may be caused by:
genetic abnormalities in the metabolism of ethanol, which can cause the ethanol metabolite, acetaldehyde, to accumulate in tissues and trigger the release of histamine, or
true allergy reactions to allergens occurring naturally in, or contaminating, alcoholic beverages (particularly wine and beer), and
other unknown causes.
=== Diabetes ===
Alcohol consumption can cause hypoglycemia in diabetics on certain medications, such as insulin or sulfonylurea, by blocking gluconeogenesis. Alcohol increases insulin response to glucose promoting fat storage and hindering carbohydrate and fat oxidation. This excess processing in the liver acetyl CoA can lead to fatty liver disease and eventually alcoholic liver disease. This progression can lead to further complications, alcohol-related liver disease may cause exocrine pancreatic insufficiency, the inability to properly digest food due to a lack or reduction of digestive enzymes made by the pancreas.
== Adverse effects ==
Alcohol has a variety of short-term and long-term adverse effects. Alcohol has both short-term, and long-term effects on the memory, and sleep. It also has reinforcement-related adverse effects, including alcoholism, dependence, and withdrawal. Alcohol use is directly related to considerable morbidity and mortality, for instance due to intoxication and alcohol-related health problems. The World Health Organization advises that there is no safe level of alcohol consumption. Many of the toxic and unpleasant actions of alcohol in the body are mediated by its carcinogenic byproduct acetaldehyde.
=== Short-term effects ===
The amount of ethanol in the body is typically quantified by blood alcohol content (BAC); weight of ethanol per unit volume of blood. Small doses of ethanol, in general, are stimulant-like and produce euphoria and relaxation; people experiencing these symptoms tend to become talkative and less inhibited, and may exhibit poor judgement. At higher dosages (BAC > 1 gram/liter), ethanol acts as a central nervous system (CNS) depressant, producing at progressively higher dosages, impaired sensory and motor function, slowed cognition, stupefaction, unconsciousness, and possible death.
=== Hangover ===
A hangover is the experience of various unpleasant physiological and psychological effects usually following the consumption of alcohol, such as wine, beer, and liquor. Hangovers can last for several hours or for more than 24 hours. Typical symptoms of a hangover may include headache, drowsiness, concentration problems, dry mouth, dizziness, fatigue, gastrointestinal distress (e.g., nausea, vomiting, diarrhea), absence of hunger, light sensitivity, depression, sweating, hyper-excitability, irritability, and anxiety (often referred to as "hangxiety").
=== Long-term effects ===
The long-term effects of alcohol have been extensively researched. The health effects of long-term alcohol consumption vary depending on the amount consumed. Even light drinking poses health risks, but atypically small amounts of alcohol may have health benefits. Alcoholism causes severe health consequences which outweigh any potential benefits.
Long-term alcohol consumption is capable of damaging nearly every organ and system in the body. Risks include malnutrition, cirrhosis, chronic pancreatitis, erectile dysfunction, hypertension, coronary heart disease, ischemic stroke, heart failure, atrial fibrillation, gastritis, stomach ulcers, alcoholic liver disease, certain types of dementia, and several types of cancer, including oropharyngeal cancer, esophageal cancer, liver cancer, colorectal cancer, and female breast cancers. In addition, damage to the central nervous system and peripheral nervous system (e.g., painful peripheral neuropathy) can occur from chronic heavy alcohol consumption. There is also an increased risk for accidental injuries, for example, those sustained in traffic accidents and falls. Excessive alcohol consumption can have a negative impact on aging.
Conversely, light intake of alcohol may have some beneficial effects. The association of alcohol intake with reduced cardiovascular risk has been noted since 1904 and remains even after adjusting for known confounders. Light alcohol intake is also associated with reduced risk of type 2 diabetes, gastritis, and cholelithiasis. However, these are only observational studies and high-quality evidence for the beneficial effects of alcohol is nonexistent.
=== Social harms ===
Alcohol causes a plethora of detrimental effects in society. Addiction experts in psychiatry, chemistry, pharmacology, forensic science, epidemiology, and the police and legal services engaged in delphic analysis regarding 20 popular recreational substances. Alcohol was ranked 6th in dependence, 11th in physical harm, and 2nd in social harm. Alcohol use is stereotypically associated with crime, more so than other drugs like marijuana. Many emergency room visits involve alcohol use. As many as 15% of employees show problematic alcohol-related behaviors in the workplace, such as drinking before going to work or even drinking on the job. Drunk dialing refers to an intoxicated person making phone calls that they would not likely make if sober. Alcohol availability and consumption rates and alcohol rates are positively associated with nuisance, loitering, panhandling, and disorderly conduct in open spaces.
=== Binge drinking ===
Binge drinking, or heavy episodic drinking, is drinking alcoholic beverages with an intention of becoming intoxicated by heavy consumption of alcohol over a short period of time. Specific definitions vary considerably. Binge drinking is associated with risks such as suicide, sexual assault, cardiovascular issues, and brain damage, more acutely than alcohol use in general.
=== Alcohol use disorder ===
Alcoholism or its medical diagnosis alcohol use disorder refers to alcohol addiction, alcohol dependence, dipsomania, and/or alcohol abuse. It is a major problem and many health problems as well as death can result from excessive alcohol use. Alcohol dependence is linked to a lifespan that is reduced by about 12 years relative to the average person. In 2004, it was estimated that 4% of deaths worldwide were attributable to alcohol use. Deaths from alcohol are split about evenly between acute causes (e.g., overdose, accidents) and chronic conditions. The leading chronic alcohol-related condition associated with death is alcoholic liver disease. Alcohol dependence is also associated with cognitive impairment and organic brain damage. Some researchers have found that even one alcoholic drink a day increases an individual's risk of health problems by 0.4%.
Two or more consecutive alcohol-free days a week have been recommended to improve health and break dependence.
=== Withdrawal ===
Discontinuation of alcohol after extended heavy use and associated tolerance development (resulting in dependence) can result in alcohol withdrawal. Alcohol is one of the more dangerous drugs to withdraw from. Alcohol withdrawal can cause confusion, paranoia, anxiety, insomnia, agitation, tremors, fever, nausea, vomiting, autonomic dysfunction, seizures, and hallucinations. In severe cases, death can result.
Delirium tremens is a condition of people with a long history of heavy drinking that requires undertaking an alcohol detoxification regimen.
== Overdose ==
Symptoms of ethanol overdose may include nausea, vomiting, CNS depression, coma, acute respiratory failure, or death. Levels of even less than 0.1% can cause intoxication, with unconsciousness often occurring at 0.3–0.4%. Death from ethanol consumption is possible when blood alcohol levels reach 0.4%. A blood level of 0.5% or more is commonly fatal. The oral median lethal dose (LD50) of ethanol in rats is 5,628 mg/kg. Directly translated to human beings, this would mean that if a person who weighs 70 kg (150 lb) drank a 500 mL (17 US fl oz) glass of pure ethanol, they would theoretically have a 50% risk of dying. The highest blood alcohol level ever recorded, in which the subject survived, is 1.41%.
== Interactions ==
=== Alcohol-induced dose dumping (AIDD) ===
Alcohol-induced dose dumping (AIDD) is an unintended rapid release of large amounts of a given drug, when administered through a modified-release dosage while co-ingesting ethanol. This is considered a pharmaceutical disadvantage due to the high risk of causing drug-induced toxicity by increasing the absorption and serum concentration above the therapeutic window of the drug. The best way to prevent this interaction is by avoiding the co-ingestion of both substances or using specific controlled-release formulations that are resistant to AIDD. Particular drugs of concern are antipsychotics and certain antidepressants.
=== Hypnotics and sedatives ===
Alcohol can intensify the sedation caused by hypnotics and sedatives such as barbiturates, benzodiazepines, sedative antihistamines, opioids, nonbenzodiazepines/Z-drugs (such as zolpidem and zopiclone).
=== Disulfiram-like drugs ===
==== Disulfiram ====
Disulfiram inhibits the enzyme acetaldehyde dehydrogenase, which in turn results in buildup of acetaldehyde, a toxic metabolite of ethanol with unpleasant effects. The medication or drug is commonly used to treat alcohol use disorder, and results in immediate hangover-like symptoms upon consumption of alcohol, this effect is widely known as disulfiram effect.
==== Metronidazole ====
Metronidazole is an antibacterial agent that kills bacteria by damaging cellular DNA and hence cellular function. Metronidazole is usually given to people who have diarrhea caused by Clostridioides difficile bacteria. Patients who are taking metronidazole are sometimes advised to avoid alcohol, even after 1 hour following the last dose. Although older data suggested a possible disulfiram-like effect of metronidazole, newer data has challenged this and suggests it does not actually have this effect.
=== NSAIDs ===
The concomitant use of NSAIDs with alcohol and/or tobacco products significantly increases the already elevated risk of peptic ulcers during NSAID therapy.
The risk of stomach bleeding is still increased when aspirin is taken with alcohol or warfarin.
=== Methylphenidate ===
Ethanol enhances the bioavailability of methylphenidate (elevated plasma dexmethylphenidate). Ethylphenidate formation appears to be more common when large quantities of methylphenidate and alcohol are consumed at the same time, such as in non-medical use or overdose scenarios. However, only a small percent of the consumed methylphenidate is converted to ethylphenidate.
=== Nicotine ===
While nicotinis mimic the name of classic cocktails like the appletini (their name deriving from "martini"), combining nicotine with alcohol is a bad idea. Tobacco and nicotine actually heighten cravings for alcohol, making this a risky mix.
=== Caffeine ===
Controlled animal and human studies showed that caffeine (energy drinks) in combination with alcohol increased the craving for more alcohol more strongly than alcohol alone. These findings correspond to epidemiological data that people who consume energy drinks generally showed an increased tendency to take alcohol and other substances.
=== Cocaine ===
Ethanol interacts with cocaine in vivo to produce cocaethylene, another psychoactive substance which may be substantially more cardiotoxic than either cocaine or alcohol by themselves.
=== Cannabis ===
In combination with cannabis, ethanol increases plasma tetrahydrocannabinol levels, which suggests that ethanol may increase the absorption of tetrahydrocannabinol.
=== Warfarin ===
Excessive use of alcohol is known to affect the metabolism of warfarin and can elevate the INR, and thus increase the risk of bleeding. The U.S. Food and Drug Administration (FDA) product insert on warfarin states that alcohol should be avoided. The Cleveland Clinic suggests that when taking warfarin one should not drink more than "one beer, 6 oz of wine, or one shot of alcohol per day".
=== Isoniazid ===
Use of isoniazid should be carefully monitored in daily alcohol drinkers since they may be more likely to develop isoniazid-associated hepatitis.
== Pharmacology ==
Alcohol works in the brain primarily by increasing the effects of γ-Aminobutyric acid (GABA), the major inhibitory neurotransmitter in the brain; by facilitating GABA's actions in the GABAA receptor, alcohol suppresses the activity of the central nervous system. Alcohol also directly affects a number of other neurotransmitter systems including those of glutamate, glycine, acetylcholine, and serotonin. The pleasurable effects of alcohol ingestion are the result of increased levels of dopamine and endogenous opioids in the reward pathways of the brain.
After oral ingestion, ethanol is absorbed via the stomach and intestines into the bloodstream. Ethanol is highly water-soluble and diffuses passively throughout the entire body, including the brain. Soon after ingestion, it begins to be metabolized, 90% or more by the liver. One standard drink is sufficient to almost completely saturate the liver's capacity to metabolize alcohol. The main metabolite is acetaldehyde, a toxic carcinogen. Acetaldehyde is then further metabolized into ionic acetate by the enzyme aldehyde dehydrogenase (ALDH). Acetate is not carcinogenic and has low toxicity, but has been implicated in causing hangovers. Acetate is further broken down into carbon dioxide and water and eventually eliminated from the body through urine and breath. 5 to 10% of ethanol is excreted unchanged in the breath, urine, and sweat.
== Chemistry ==
Ethanol is also known chemically as alcohol, ethyl alcohol, or drinking alcohol. It is a simple alcohol with a molecular formula of C2H6O and a molecular weight of 46.0684 g/mol. The molecular formula of ethanol may also be written as CH3−CH2−OH or as C2H5−OH. The latter can also be thought of as an ethyl group linked to a hydroxyl (alcohol) group and can be abbreviated as EtOH. Ethanol is a volatile, flammable, colorless liquid with a slight characteristic odor. Aside from its use as a psychoactive and recreational substance, ethanol is also commonly used as an antiseptic and disinfectant, a chemical and medicinal solvent, and a fuel.
=== Analogues ===
Ethanol is only one of several types of chemical alcohols, and has a variety of analogues. Most other alcohols are considered poisonous. In general, higher alcohols are less toxic. Alcoholic beverages are sometimes laced with toxic alcohols.
The toxicity of isopropyl alcohol is about twice that of ethanol;
a mild, brief exposure to isopropyl alcohol is unlikely to cause any serious harm, although ingesting significant quantities can lead to vomiting, abdominal pain, and internal bleeding. Methanol is the most toxic alcohol and can cause blindness or death even in small quantities, as little as 10–15 milliliters (2–3 teaspoons). Many methanol poisoning incidents have occurred through history. n-Butanol is reported to produce similar effects to those of ethanol and relatively low toxicity (one-sixth of that of ethanol in one rat study). However, its vapors can produce eye irritation and inhalation can cause pulmonary edema. Acetone (propanone) is a ketone rather than an alcohol, and is reported to produce similar toxic effects; it can be extremely damaging to the cornea.
Although ethanol is the most prevalent alcohol in alcoholic beverages, alcoholic beverages contain several types of psychoactive alcohols, that are categorized as primary, secondary, or tertiary. Primary, and secondary alcohols, are oxidized to aldehydes, and ketones, respectively, while tertiary alcohols are generally resistant to oxidation. The Lucas test differentiates between primary, secondary, and tertiary alcohols. The tertiary alcohol tert-amyl alcohol (TAA), also known as 2-methylbutan-2-ol (2M2B), has a history of use as a hypnotic and anesthetic, as do other tertiary alcohols such as methylpentynol, ethchlorvynol, and chloralodol. Unlike primary alcohols like ethanol, these tertiary alcohols cannot be oxidized into aldehyde or carboxylic acid metabolites, which are often toxic, and for this reason, these compounds are safer in comparison. Other relatives of ethanol with similar effects include chloral hydrate, paraldehyde, and many volatile and inhalational anesthetics (e.g., chloroform, diethyl ether, and isoflurane).
== Manufacturing ==
Ethanol is produced naturally as a byproduct of the metabolic processes of yeast and hence is present in any yeast habitat, including even endogenously in humans, but it does not cause raised blood alcohol content as seen in the rare medical condition auto-brewery syndrome (ABS). It is manufactured through hydration of ethylene or by brewing via fermentation of sugars with yeast (most commonly Saccharomyces cerevisiae). The sugars are commonly obtained from sources like steeped cereal grains (e.g., barley), grape juice, and sugarcane products (e.g., molasses, sugarcane juice). Ethanol–water mixture which can be further purified via distillation.
== History ==
Alcohol is one of the oldest recreational drugs. Alcoholic beverages have been produced since the Neolithic period, as early as 7000 BC in China. Alcohol was brewed as early as 7,000 to 6,650 BCE in northern China. The earliest evidence of winemaking was dated at 6,000 to 5,800 BCE in Georgia in the South Caucasus. Beer was likely brewed from barley as early as the 13,000 years ago in the Middle East. Pliny the Elder wrote about the golden age of winemaking in Rome, the 2nd century BCE (200–100 BCE), when vineyards were planted.
=== Early modern period ===
The Gin Craze was a period in the first half of the 18th century when the consumption of gin increased rapidly in Great Britain, especially in London. By 1743, England was drinking 2.2 gallons (10 litres) of gin per person per year. The Sale of Spirits Act 1750 (commonly known as the Gin Act 1751) was an Act of the Parliament of Great Britain (24 Geo. 2. c. 40) which was enacted to reduce the consumption of gin and other distilled spirits, a popular pastime that was regarded as one of the primary causes of crime in London.
=== Modern period ===
The rum ration (also called the tot) was a daily amount of rum given to sailors on Royal Navy ships. It started 1866 and was abolished in 1970 after concerns that the intake of strong alcohol would lead to unsteady hands when working machinery.
The Andrew Johnson alcoholism debate is the dispute, originally conducted among the general public, and now typically a question for historians, about whether or not Andrew Johnson, the 17th president of the United States (1865–1869), drank to excess.
The prohibition in the United States era was the period from 1920 to 1933 when the United States prohibited the production, importation, transportation, and sale of alcoholic beverages. The nationwide ban on alcoholic beverages, was repealed by the passage of the Twenty-first Amendment to the United States Constitution on December 5, 1933.
The Bratt System was a system that was used in Sweden (1919–1955) and similarly in Finland (1944–1970) to control alcohol consumption, by rationing of liquor. Every citizen allowed to consume alcohol was given a booklet called a motbok (viinakortti in Finland), in which a stamp was added each time a purchase was made at Systembolaget (in Sweden) and Alko (in Finland). A similar system also existed in Estonia between July 1, 1920, to December 31, 1925. The stamps were based on the amount of alcohol bought. When a certain amount of alcohol had been bought, the owner of the booklet had to wait until next month to buy more.
The Medicinal Liquor Prescriptions Act of 1933 was a law passed by Congress in response to the abuse of medicinal liquor prescriptions during Prohibition.
Gilbert Paul Jordan (aka The Boozing Barber) was a Canadian serial killer who is believed to have committed the so-called "alcohol murders" between 1965–c. 2004 in Vancouver, British Columbia.
== Society and culture ==
The consumption of alcohol is deeply embedded in social practices and rituals, often celebrated as a cornerstone of community gatherings and personal milestones. Drinking culture is the set of traditions and social behaviours that surround the consumption of alcoholic beverages as a recreational drug and social lubricant.
=== Legal status ===
Alcohol consumption is fully legal and available in most countries of the world. Home made alcoholic beverages with low alcohol content like wine, and beer is also legal in most countries, but distilling moonshine outside of a registered distillery remains illegal in most of them.
Some majority-Muslim countries, such as Saudi Arabia, Kuwait, Pakistan, Iran and Libya prohibit the production, sale, and consumption of alcoholic beverages because they are forbidden by Islam. Also, laws banning alcohol consumption are found in some Indian states as well as some Native American reservations in the U.S.
In addition, there are regulations on alcohol sales and use in many countries throughout the world. For instance, the majority of countries have a minimum legal drinking age to purchase or consume alcoholic beverages, although there are often exceptions such as underage consumption of small amounts of alcohol with parental supervision. Also, some countries have bans on public intoxication. Drinking while driving or intoxicated driving is frequently outlawed and it may be illegal to have an open container of alcohol or liquor bottle in an automobile, bus or aircraft.
=== Religion ===
Religion and alcohol have a complex history. The world's religions have had different relationships with alcohol, reflecting diverse cultural, social, and religious practices across different traditions. While some religions strictly prohibit alcohol consumption, viewing it as sinful or harmful to spiritual and physical well-being, others incorporate it into their rituals and ceremonies. Throughout history, alcohol has held significant roles in religious observances, from the use of sacramental wine in Christian sacraments to the offering and moderate drinking of omiki (sacramental sake) in Shinto purification rituals.
=== Impact ===
A study in 2015 found that alcohol and tobacco use combined resulted in a significant health burden, costing over a quarter of a billion disability-adjusted life years. Illicit drug use caused tens of millions more disability-adjusted life years.
According to The Lancet, 'four industries (tobacco, unhealthy food, fossil fuel, and alcohol) are responsible for at least a third of global deaths per year'. In 2024, the World Health Organization published a report including these figures.
Many Native Americans in the United States have been harmed by, or become addicted to, drinking alcohol.
Qualitative analysis reveals that the alcohol industry likely misinforms the public about the dangers of alcohol, similar to the tobacco industry. The alcohol industry influences alcohol policy and health messages, including those for schoolchildren.
=== Standard drink ===
The alcohol consumption recommendations (or safe limits) varies from no intake, to daily, weekly, or daily/weekly guidelines provided by health agencies of governments. The WHO published a statement in The Lancet Public Health in April 2023 that "there is no safe amount that does not affect health."
A standard drink is a measure of alcohol consumption representing a fixed amount of pure ethanol, used in relation to recommendations about alcohol consumption and its relative risks to health. The size of a standard drink varies from 8g to 20g across countries, but 10g alcohol (12.7 millilitres) is used in the World Health Organization (WHO) Alcohol Use Disorders Identification Test (AUDIT)'s questionnaire form example, and has been adopted by more countries than any other amount.
== See also ==
Alcohol myopia
Rum-running
GABAergics
GABRD (δ subunit-containing receptors)
Pigovian taxes, which are to pay for the damage to society caused by these goods.
Sin taxes are used to increase the price in an effort to lower their use, or failing that, to increase and find new sources of revenue.
Binge drinking
Holiday heart syndrome
Drug-related crime
List of countries by alcohol consumption per capita
== References ==
== Further reading ==
IARC Working Group on the Evaluation of Carcinogenic Risks to Humans (1988). Alcohol Drinking. International Agency for Research on Cancer.
== External links ==
"ETOH Database Search". hazelden.org.
The National Institute on Alcohol Abuse and Alcoholism maintains a database of alcohol-related health effects. ETOH Archival Database (1972–2003) Alcohol and Alcohol Problems Science Database.
"Harmful Interactions". National Institute on Alcohol Abuse and Alcoholism (NIAAA).
WHO fact sheet on alcohol
ChEBI – biology related
Kyoto Encyclopedia of Genes and Genomes signal transduction pathway: KEGG – human alcohol addiction | Wikipedia/Alcohol_(drug) |
Barbiturates are a class of depressant drugs that are chemically derived from barbituric acid. They are effective when used medically as anxiolytics, hypnotics, and anticonvulsants, but have physical and psychological addiction potential as well as overdose potential among other possible adverse effects. They have been used recreationally for their anti-anxiety and sedative effects, and are thus controlled in most countries due to the risks associated with such use.
Barbiturates have largely been replaced by benzodiazepines and nonbenzodiazepines ("Z-drugs") in routine medical practice, particularly in the treatment of anxiety disorders and insomnia, because of the significantly lower risk of overdose, and the lack of an antidote for barbiturate overdose. Despite this, barbiturates are still in use for various purposes: in general anesthesia, epilepsy, treatment of acute migraines or cluster headaches, acute tension headaches, euthanasia, capital punishment, and assisted suicide.
== Uses ==
=== Medicine ===
Barbiturates, such as phenobarbital, were long used as anxiolytics and hypnotics. Intermediate-acting barbiturates reduce time to fall asleep, increase total sleep time, and reduce REM sleep time. Today they have been largely replaced by benzodiazepines for these purposes because the latter are less toxic in drug overdose. However, barbiturates are still used as anticonvulsants (e.g., phenobarbital and primidone) and general anesthetics (e.g., sodium thiopental).
Barbiturates in high doses are used for medical aid in dying, and in combination with a muscle relaxant for euthanasia and for capital punishment by lethal injection. Barbiturates are frequently employed as euthanizing agents in small-animal veterinary medicine.
=== Interrogation ===
Sodium thiopental is an ultra-short-acting barbiturate that is marketed under the name Sodium Pentothal. It is often mistaken for "truth serum", or sodium amytal, an intermediate-acting barbiturate that is used for sedation and to treat insomnia, but was also used in so-called sodium amytal "interviews" where the person being questioned would incorrectly be thought to be more likely to provide the truth whilst under the influence of the drug. When dissolved in water, sodium amytal can be swallowed, or it can be administered by intravenous injection. The drug does not itself force people to tell the truth, but is thought to decrease inhibitions and slow creative thinking, making subjects more likely to be caught off guard when questioned, and increasing the possibility of the subject revealing information through emotional outbursts. Lying is somewhat more complex than telling the truth, especially under the influence of a sedative-hypnotic drug.
The memory-impairing effects and cognitive impairments induced by sodium thiopental are thought to reduce a subject's ability to invent and remember lies. This practice is no longer considered legally admissible in court, owing to findings that subjects undergoing such interrogations may form false memories, putting the reliability of all information obtained through such methods into question. Nonetheless, it is still employed in certain circumstances by defense and law enforcement agencies as a "humane" alternative to torture interrogation when the subject is believed to have information critical to the security of the state or agency employing the tactic.
=== Chemistry ===
In 1988, the synthesis and binding studies of an artificial receptor binding barbiturates by six complementary hydrogen bonds was published. Since this first article, different kind of receptors were designed, as well as different barbiturates and cyanurates, not for their efficiencies as drugs but for applications in supramolecular chemistry, in the conception of materials and molecular devices.
The preferred IUPAC name of the base compound, barbituric acid, is 1,3-diazinane-2,4,6-trione. Different barbiturates have different substituents in the basic structure, mainly in position 5 on the ring. In modern chemistry the barbiturates are often presented by its Hirshfeld surface representations showing its intermolecular interactions [1] calculated with CrystalExplorer Program.
Sodium barbital and barbital have also been used as pH buffers for biological research, e.g., in immuno-electrophoresis or in fixative solutions.
== Classification ==
Barbiturates are classified based on the duration of action. Examples of each class include:
Ultra short acting (30 minutes): thiopentone, methohexitone
Short acting (2 hours): hexobarbitone, cyclobarbitone, pentobarbitone, secobarbitone
Intermediate acting (3–6 hours): amobarbitone, butabarbitone
Long acting (6 hours): phenobarbitone
== Indications ==
Indications for the use of barbiturates include:
Seizure
Neonatal withdrawal syndrome
Insomnia
Anxiety
Inducing anesthesia
== Side effects ==
There are special risks to consider for older adults, and women who are pregnant. When a person ages, the body becomes less able to rid itself of barbiturates. As a result, people over the age of 65 are at higher risk of experiencing the harmful effects of barbiturates, including drug dependence and accidental overdose. When barbiturates are taken during pregnancy, the drug passes through the placenta to the fetus. After the baby is born, it may experience withdrawal symptoms and have trouble breathing. In addition, nursing mothers who take barbiturates may transmit the drug to their babies through breast milk. A rare adverse reaction to barbiturates is Stevens–Johnson syndrome, which primarily affects the mucous membranes.
=== Common side effects ===
Nausea
Hypotension
Headache
Drowsiness
Skin rash
=== Serious side effects ===
Confusion
Coma
Hallucination
Fainting
Slow breathing
=== Rare side effects ===
Agranulocytosis
Stevens–Johnson syndrome
Liver injury
Megaloblastic anemia
=== Tolerance and dependence ===
With regular use, tolerance to the effects of barbiturates develops. Research shows tolerance can develop with even one administration of a barbiturate. As with all GABAergic drugs, barbiturate withdrawal produces potentially fatal effects such as seizures, in a manner reminiscent of delirium tremens and benzodiazepine withdrawal although its more direct mechanism of GABA agonism makes barbiturate withdrawal even more severe than that of alcohol or benzodiazepines. It is considered one of the most dangerous withdrawals of any known addictive substance. Similarly to benzodiazepines, the longer acting barbiturates produce a less severe withdrawal syndrome than short acting and ultra-short acting barbiturates. Withdrawal symptoms are dose-dependent with heavier users being more affected than lower-dose addicts.
The pharmacological treatment of barbiturate withdrawal is an extended process often consisting of converting the patient to a long-acting benzodiazepine (i.e. Valium), followed by slowly tapering off the benzodiazepine. Mental cravings for barbiturates can last for months or years in some cases and counselling/support groups are highly encouraged by addiction specialists. Patients should never try to tackle the task of discontinuing barbiturates without consulting a doctor, owing to the high lethality and relatively sudden onset of the withdrawal. Attempting to quit "cold turkey" may result in neurological damage due to excitotoxicity, severe physical injuries received during convulsions, and even death resulting from arrhythmias during grande Mal seizures, paralleling death caused by delirium tremens.
=== Overdose ===
Some symptoms of an overdose typically include sluggishness, incoordination, difficulty in thinking, slowness of speech, faulty judgement, drowsiness, shallow breathing, staggering, and, in severe cases, coma or death. The lethal dosage of barbiturates varies greatly with tolerance and from one individual to another. The lethal dose is highly variable among different members of the class, with superpotent barbiturates such as pentobarbital being potentially fatal in considerably lower doses than the low-potency barbiturates such as butalbital. Even in inpatient settings, the development of tolerance is still a problem, as dangerous and unpleasant withdrawal symptoms can result when the drug is stopped after dependence has developed. Tolerance to the anxiolytic and sedative effects of barbiturates tends to develop faster than tolerance to their effects on smooth muscle, respiration, and heart rate, making them generally unsuitable for a long time psychiatric use. Tolerance to the anticonvulsant effects tends to correlate more with tolerance to physiological effects, however, meaning that they are still a viable option for long-term epilepsy treatment.
Barbiturates in overdose with other CNS (central nervous system) depressants (e.g. alcohol, opiates, benzodiazepines) are even more dangerous owing to additive CNS and respiratory depressant effects. In the case of benzodiazepines, not only do they have additive effects, barbiturates also increase the binding affinity of the benzodiazepine binding site, leading to exaggerated benzodiazepine effects. (ex. If a benzodiazepine increases the frequency of channel opening by 300%, and a barbiturate increases the duration of their opening by 300%, then the combined effects of the drugs increases the channels' overall function by 900%, not 600%).
The longest-acting barbiturates have half-lives of a day or more, and subsequently result in bioaccumulation of the drug in the system. The therapeutic and recreational effects of long-acting barbiturates wear off significantly faster than the drug can be eliminated, allowing the drug to reach toxic concentrations in the blood following repeated administration (even when taken at the therapeutic or prescribed dose) despite the user feeling little or no effects from the plasma-bound concentrations of the drug. Users who consume alcohol or other sedatives after the drug's effects have worn off, but before it has cleared the system, may experience a greatly exaggerated effect from the other sedatives which can be incapacitating or even fatal.
Barbiturates induce a number of hepatic CYP enzymes (most notably CYP2C9, CYP2C19, and CYP3A4), leading to exaggerated effects from many prodrugs and decreased effects from drugs which are metabolized by these enzymes to inactive metabolites. This can result in fatal overdoses from drugs such as codeine, tramadol, and carisoprodol, which become considerably more potent after being metabolized by CYP enzymes. Although all known members of the class possess relevant enzyme induction capabilities, the degree of induction overall as well as the impact on each specific enzyme span a broad range, with phenobarbital and secobarbital being the most potent enzyme inducers and butalbital and talbutal being among the weakest enzyme inducers in the class.
People who are known to have killed themselves by barbiturate overdose include Stefan Zweig, Charles Boyer, Ruan Lingyu, Dalida, Jeannine Deckers, Felix Hausdorff, Abbie Hoffman, Phyllis Hyman, Carole Landis, C. P. Ramanujam, George Sanders, Jean Seberg, Lupe Vélez and the members of Heaven's Gate cult. Others who have died as a result of barbiturate overdose include Pier Angeli, Brian Epstein, Judy Garland, Jimi Hendrix, Marilyn Monroe, Inger Stevens, Dinah Washington, Ellen Wilkinson, and Alan Wilson; in some cases these have been speculated to be suicides as well. Those who died of a combination of barbiturates and other drugs include Rainer Werner Fassbinder, Dorothy Kilgallen, Malcolm Lowry, Edie Sedgwick and Kenneth Williams. Dorothy Dandridge died of either an overdose or an unrelated embolism. Ingeborg Bachmann may have died of the consequences of barbiturate withdrawal (she was hospitalized with burns, the doctors treating her not being aware of her barbiturate addiction).
== Contraindications ==
The use of Barbiturates is contraindicated in the following conditions:
variegate porphyria (because of induction of enzymes needed for porphyria synthesis by barbiturates)
Status asthmaticus (because of respiratory depression caused by the barbiturates)
== Mechanism of action ==
Barbiturates act as positive allosteric modulators and, at higher doses, as agonists of GABAA receptors. GABA is the principal inhibitory neurotransmitter in the mammalian central nervous system (CNS). Barbiturates bind to the GABAA receptor at multiple homologous transmembrane pockets located at subunit interfaces, which are binding sites distinct from GABA itself and also distinct from the benzodiazepine binding site. Like benzodiazepines, barbiturates potentiate the effect of GABA at this receptor. In addition to this GABAergic effect, barbiturates also block AMPA and kainate receptors, subtypes of ionotropic glutamate receptor. Glutamate is the principal excitatory neurotransmitter in the mammalian CNS. Taken together, the findings that barbiturates potentiate inhibitory GABAA receptors and inhibit excitatory AMPA receptors can explain the superior CNS-depressant effects of these agents to alternative GABA potentiating agents such as benzodiazepines and quinazolinones. At higher concentration, they inhibit the Ca2+-dependent release of neurotransmitters such as glutamate via an effect on P/Q-type voltage-dependent calcium channels.
Barbiturates produce their pharmacological effects by increasing the duration of chloride ion channel opening at the GABAA receptor (pharmacodynamics: This increases the efficacy of GABA), whereas benzodiazepines increase the frequency of the chloride ion channel opening at the GABAA receptor (pharmacodynamics: This increases the potency of GABA). The direct gating or opening of the chloride ion channel is the reason for the increased toxicity of barbiturates compared to benzodiazepines in overdose.
Further, barbiturates are relatively non-selective compounds that bind to an entire superfamily of ligand-gated ion channels, of which the GABAA receptor channel is only one of several representatives. This Cys-loop receptor superfamily of ion channels includes the neuronal nACh receptor channel, the 5-HT3 receptor channel, and the glycine receptor channel. However, while GABAA receptor currents are increased by barbiturates (and other general anesthetics), ligand-gated ion channels that are predominantly permeable for cationic ions are blocked by these compounds. For example, neuronal nAChR channels are blocked by clinically relevant anesthetic concentrations of both thiopental and pentobarbital. Such findings implicate (non-GABA-ergic) ligand-gated ion channels, e.g. the neuronal nAChR channel, in mediating some of the (side) effects of barbiturates. This is the mechanism responsible for the (mild to moderate) anesthetic effect of barbiturates in high doses when used in anesthetic concentration.
== Interactions ==
Drug interactions with barbiturates are:
alcohol
opioids
benzodiazepines
anticoagulants
antihistamines
atazanavir
birth-control pills
boceprevir
== Caution ==
Caution is needed in people using:
Medications such as opioids or benzodiazepines
Alcohol
Caution is also required in patients with:
Asthma
Kidney- or liver-problems
Heart-disease
Substance use disorder
Depression
History of suicidal thoughts
== History ==
Barbituric acid was first synthesized 27 November 1864, by German chemist Adolf von Baeyer. This was done by condensing urea with diethyl malonate. There are several stories about how the substance got its name. The most likely story is that Baeyer and his colleagues went to celebrate their discovery in a tavern where the town's artillery garrison were also celebrating the feast of Saint Barbara – the patron saint of artillerymen. An artillery officer is said to have christened the new substance by amalgamating Barbara with urea. Another story holds that Baeyer synthesized the substance from the collected urine of a Munich waitress named Barbara. No substance of medical value was discovered, however, until 1903 when two German scientists working at Bayer, Emil Fischer and Joseph von Mering, discovered that barbital was very effective in putting dogs to sleep. Barbital was then marketed by Bayer under the trade name Veronal. It is said that Mering proposed this name because the most peaceful place he knew was the Italian city of Verona. In 1912, Bayer introduced another barbituric acid derivative, phenobarbital, under the trade name Luminal, as a sedative–hypnotic.
It was not until the 1950s that the behavioral disturbances and physical dependence potential of barbiturates became recognized.
Since the 1970s, most barbiturates were replaced by benzodiazepines.
Barbituric acid itself does not have any direct effect on the central nervous system and chemists have derived over 2,500 compounds from it that possess pharmacologically active qualities. The broad class of barbiturates is further broken down and classified according to speed of onset and duration of action. Ultrashort-acting barbiturates are commonly used for anesthesia because their extremely short duration of action allows for greater control. These properties allow doctors to rapidly put a patient "under" in emergency surgery situations. Doctors can also bring a patient out of anesthesia just as quickly, should complications arise during surgery. The middle two classes of barbiturates are often combined under the title "short/intermediate-acting." These barbiturates are also employed for anesthetic purposes, and are also sometimes prescribed for anxiety or insomnia. This is not a common practice anymore, however, owing to the dangers of long-term use of barbiturates; they have been replaced by the benzodiazepines and Z-drug such as zolpidem, zaleplon and eszopiclone for sleep. The final class of barbiturates are known as long-acting barbiturates (the most notable one being phenobarbital, which has a half-life of roughly 92 hours). This class of barbiturates is used almost exclusively as anticonvulsants, although on rare occasions they are prescribed for daytime sedation. Barbiturates in this class are not used for insomnia, because, owing to their extremely long half-life, patients would awake with a residual "hang-over" effect and feel groggy.
Barbiturates can in most cases be used either as the free acid or as salts of sodium, calcium, potassium, magnesium, lithium, etc. Codeine- and dionine-based salts of barbituric acid have been developed.
== Society and culture ==
=== Legal status ===
During World War II, military personnel in the Pacific region were given "goofballs" to improve their tolerance of the heat and humidity of daily working conditions. Goofballs reduced the demand on the respiratory system, as well as maintaining blood pressure. Many soldiers returned with addictions that required several months of rehabilitation before discharge. This led to growing dependency problems, often exacerbated by indifferent physicians prescribing high doses to unknowing patients through the 1950s and 1960s.
In the late 1950s and 1960s, an increasing number of published reports of barbiturate overdoses and dependence problems led physicians to reduce their prescription, particularly for spurious requests. This eventually led to the scheduling of barbiturates as controlled drugs.
In the Netherlands, the Opium Law classifies all barbiturates as List II drugs, with the exception of secobarbital, which is on List I.
There is a small group of List II drugs for which physicians have to write the prescriptions according to the same, tougher guidelines as those for List I drugs (writing the prescription in full in letters, listing the patients name, and have to contain the name and initials, address, city and telephone number of the licensed prescriber issuing the prescriptions, as well as the name and initials, address and city of the person the prescription is issued to). Among that group of drugs are the barbiturates amobarbital, butalbital, cyclobarbital, and pentobarbital.
In the United States, the Controlled Substances Act of 1970 classified most barbiturates as controlled substances—and they remain so as of August 2023. Barbital, methylphenobarbital (also known as mephobarbital), and phenobarbital are designated schedule IV drugs, and "Any substance which contains any quantity of a derivative of barbituric acid, or any salt of a derivative of barbituric acid" (all other barbiturates) were designated as being schedule III. Under the original CSA, no barbiturates were placed in schedule I, II, or V; however, amobarbital, pentobarbital, and secobarbital are now schedule II controlled substances unless they are in a suppository dosage form.
In 1971, the Convention on Psychotropic Substances was signed in Vienna. Designed to regulate amphetamines, barbiturates, and other synthetics, the 34th version of the treaty, as of 25 January 2014, regulates secobarbital as schedule II, amobarbital, butalbital, cyclobarbital, and pentobarbital as schedule III, and allobarbital, barbital, butobarbital, mephobarbital, phenobarbital, butabarbital, and vinylbital as schedule IV on its "Green List". The combination medication Fioricet, consisting of butalbital, caffeine, and paracetamol (acetaminophen), however, is specifically exempted from controlled substance status, while its sibling Fiorinal, which contains aspirin instead of paracetamol and may contain codeine phosphate, remains a schedule III drug.
=== Recreational use ===
Recreational users report that a barbiturate high gives them feelings of relaxed contentment and euphoria. Physical and psychological dependence may also develop with repeated use. Chronic misuse of barbiturates is associated with significant morbidity. One study found that 11% of males and 23% of females with a sedative-hypnotic misuse die by suicide. Other effects of barbiturate intoxication include drowsiness, lateral and vertical nystagmus, slurred speech and ataxia, decreased anxiety, and loss of inhibitions. Barbiturates are also used to alleviate the adverse or withdrawal effects of illicit drug use, in a manner similar to long-acting benzodiazepines such as diazepam and clonazepam. Often polysubstance use occurs and barbiturates are consumed with or substituted by other available substances, most commonly alcohol.
People who use substances tend to prefer short-acting and intermediate-acting barbiturates. The most commonly used are amobarbital (Amytal), pentobarbital (Nembutal), and secobarbital (Seconal). A combination of amobarbital and secobarbital (called Tuinal) is also highly used. Short-acting and intermediate-acting barbiturates are usually prescribed as sedatives and sleeping pills. These pills begin acting fifteen to forty minutes after they are swallowed, and their effects last from five to six hours.
Slang terms for barbiturates include barbs, barbies, bluebirds, dolls, wallbangers, yellows, downers, goofballs, sleepers, 'reds & blues', and tooties.
== Examples ==
Thiopental is a barbiturate with one of the C=O double bonds (with the carbon being labelled 2 in the adjacent diagram) replaced with a C=S double bond, R1 being CH2CH3 (ethyl) and R3) being CH(CH3)CH2CH2CH3 (sec-pentyl). Thiopental is no longer available in the United States.
== See also ==
Benzodiazepine
Psycholeptic
Dille–Koppanyi reagent, Zwikker reagent, and others spot tests for barbiturates
== Explanatory notes ==
== References ==
== External links and further reading ==
López-Muñoz, F.; Ucha-Udabe, R.; Alamo, C. (2005). "The history of barbiturates a century after their clinical introduction". Neuropsychiatric Disease and Treatment. 1 (4): 329–343. PMC 2424120. PMID 18568113. | Wikipedia/Barbiturate |
A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended. Typically the term is applied for cases when a risk to health is a potential result. An overdose may result in a toxic state or death.
== Classification ==
The word "overdose" implies that there is a common safe dosage and usage for the drug; therefore, the term is commonly applied only to drugs, not poisons, even though many poisons as well are harmless at a low enough dosage. Drug overdose is sometimes used as a means to commit suicide, as the result of intentional or unintentional misuse of medication. Intentional misuse leading to overdose can include using prescribed or non-prescribed drugs in excessive quantities in an attempt to produce euphoria.
Usage of illicit drugs, in large quantities, or after a period of drug abstinence can also induce overdose. Cocaine and opioid users who inject intravenously can easily overdose accidentally, as the margin between a pleasurable drug sensation and an overdose is small. Unintentional misuse can include errors in dosage caused by failure to read or understand product labels. Accidental overdoses may also be the result of over-prescription, failure to recognize a drug's active ingredient or unwitting ingestion by children. A common unintentional overdose in young children involves multivitamins containing iron.
The term 'overdose' is often misused as a descriptor for adverse drug reactions or negative drug interactions due to mixing multiple drugs simultaneously.
== Signs and symptoms ==
Signs and symptoms of an overdose vary depending on the drug or exposure to toxins. The symptoms can often be divided into differing toxidromes. This can help one determine what class of drug or toxin is causing the difficulties.
Symptoms of opioid overdoses include slow breathing, heart rate and pulse. Opioid overdoses can also cause pinpoint pupils, and blue lips and nails due to low levels of oxygen in the blood. A person experiencing an opioid overdose might also have muscle spasms, seizures and decreased consciousness. A person experiencing an opiate overdose usually will not wake up, even if their name is called or they are shaken vigorously.
== Causes ==
The drugs or toxins that are most frequently involved in overdose and death (grouped by ICD-10):
=== Added flavoring ===
Masking undesired taste may impair judgement of the potency, which is a factor in overdosing. For example, lean is usually created as a drinkable mixture, the cough syrup is combined with soft drinks, especially fruit-flavored drinks such as Sprite, Mountain Dew or Fanta, and is typically served in a foam cup. A hard candy, usually a Jolly Rancher, may be added to give the mixture a sweeter flavor.
== Diagnosis ==
The substance that has been taken may often be determined by asking the person. However, if they will not, or cannot, due to an altered level of consciousness, provide this information, a search of the home or questioning of friends and family may be helpful.
Examination for toxidromes, drug testing, or laboratory test may be helpful. Other laboratory test such as glucose, urea and electrolytes, paracetamol levels and salicylate levels are typically done. Negative drug-drug interactions have sometimes been misdiagnosed as an acute drug overdose, occasionally leading to the assumption of suicide.
== Prevention ==
The distribution of naloxone to injection drug users and other opioid drug users decreases the risk of death from overdose. The Centers for Disease Control and Prevention (CDC) estimates that U.S. programs for drug users and their caregivers prescribing take-home doses of naloxone and training on its utilization are estimated to have prevented 10,000 opioid overdose deaths. Healthcare institution-based naloxone prescription programs have also helped reduce rates of opioid overdose in the U.S. state of North Carolina, and have been replicated in the U.S. military. Nevertheless, scale-up of healthcare-based opioid overdose interventions is limited by providers' insufficient knowledge and negative attitudes towards prescribing take-home naloxone to prevent opioid overdose. Programs training police and fire personnel in opioid overdose response using naloxone have also shown promise in the U.S.
Supervised injection sites (also known as overdose prevention centers) have been used to help prevent drug overdoses by offering opioid reversal medications such as naloxone, medical assistance and treatment options. They also provide clean needles to help prevent the spread of diseases like HIV/AIDS and hepatitis.
== Management ==
Stabilization of the person's airway, breathing, and circulation (ABCs) is the initial treatment of an overdose. Ventilation is considered when there is a low respiratory rate or when blood gases show the person to be hypoxic. Monitoring of the patient should continue before and throughout the treatment process, with particular attention to temperature, pulse, respiratory rate, blood pressure, urine output, electrocardiography (ECG) and O2 saturation. Poison control centers and medical toxicologists are available in many areas to provide guidance in overdoses both to physicians and to the general public.
=== Antidotes ===
Specific antidotes are available for certain overdoses. For example, naloxone is the antidote for opiates such as heroin or morphine. Similarly, benzodiazepine overdoses may be effectively reversed with flumazenil. As a nonspecific antidote, activated charcoal is frequently recommended if available within one hour of the ingestion and the ingestion is significant. Gastric lavage, syrup of ipecac, and whole bowel irrigation are rarely used.
== Epidemiology and statistics ==
The UN gives a figure of 300,000 deaths per year in the world through drug overdose.
In the US around 84,100 people died in the 12-month period ending October 31, 2024, at a rate of 230 deaths per day. The peak was around 112,600 in 2022. The U.S. drug overdose death rate has gone from 2.5 per 100,000 people in 1968 to the peak rate of 33.7 per 100,000 in 2022.
1,015,060 US residents died from drug overdoses from 1968 to 2019. 22 people out of every 100,000 died from drug overdoses in 2019 in the US. From 1999 to Feb 2019 in the United States, more than 770,000 people have died from drug overdoses. 70,630 people died from drug overdoses in 2019.
The National Center for Health Statistics reports that 19,250 people died of accidental poisoning in the U.S. in the year 2004 (eight deaths per 100,000 population).
In 2008 testimony before a Senate subcommittee, Leonard J. Paulozzi, a medical epidemiologist at the Centers for Disease Control and Prevention said that in 2005 more than 22,000 American people died due to overdoses, and the number is growing rapidly. Paulozzi also testified that all available evidence suggests unintentional overdose deaths are related to the increasing use of prescription drugs, especially opioid painkillers. However, the vast majority of overdoses are also attributable to alcohol. It is very rare for a victim of an overdose to have consumed just one drug. Most overdoses occur when drugs are ingested in combination with alcohol.
Drug overdose was the leading cause of injury death in 2013. Among people 25 to 64 years old, drug overdose caused more deaths than motor vehicle traffic crashes. There were 43,982 drug overdose deaths in the United States in 2013. Of these, 22,767 (51.8%) were related to prescription drugs.
The 22,767 deaths relating to prescription drug overdose in 2013, 16,235 (71.3%) involved opioid painkillers, and 6,973 (30.6%) involved benzodiazepines. Drug misuse and abuse caused about 2.5 million emergency department (ED) visits in 2011. Of these, more than 1.4 million ED visits were related to prescription drugs. Among those ED visits, 501,207 visits were related to anti-anxiety and insomnia medications, and 420,040 visits were related to opioid analgesics.
New CDC data in 2024 demonstrates U.S. drug overdose deaths have significantly declined, marking the potential for the first year with fewer than 100,000 fatalities since 2020. The CDC data shows a nearly 17% drop in reported overdose deaths during the 12 months ending in June, totaling 93,087. This is a notable decrease from the 111,615 deaths recorded in the same period ending in June 2023. While the opioid crisis continues to take a heavy toll, fentanyl remains a major driver, contributing to the majority of these fatalities.
== See also ==
27 Club – Notional club occupied by those who died at age 27
Adulterants – Substance that has been secretly addedPages displaying short descriptions of redirect targets
Brandon Vedas – 2003 drug overdose deathPages displaying short descriptions of redirect targets
Drug checking – Harm reduction technique
Drug interactions – Change in the action or side effects of a drug causedPages displaying short descriptions of redirect targets
Hepatotoxicity – Liver damage caused by a drug or chemical
List of deaths from drug overdose and intoxication
Reagent testing – Tests for authentication of psychoactive drugs, and detection of adulterants
Responsible drug use – Use of drugs in a responsible manner
Suicide methods § Drug overdose
Water intoxication – Potentially fatal overhydration
== References ==
== Further reading ==
== External links == | Wikipedia/Drug_overdose |
Club drugs, also called rave drugs or party drugs, are a loosely defined category of recreational drugs which are associated with discothèques in the 1970s and nightclubs, dance clubs, electronic dance music (EDM) parties, and raves in the 1980s to today. Unlike many other categories, such as opiates and benzodiazepines, which are established according to pharmaceutical or chemical properties, club drugs are a "category of convenience", in which drugs are included due to the locations they are consumed and/or where the user goes while under the influence of the drugs. Club drugs are generally used by adolescents and young adults.
Club drugs range from entactogens such as MDMA ("ecstasy"), 2C-B ("nexus") and inhalants (e.g., nitrous oxide and poppers) to stimulants (e.g., amphetamine and cocaine), depressants/sedatives (Quaaludes, GHB, Rohypnol) and psychedelic and hallucinogenic drugs (LSD and DMT). Dancers at all-night parties and dance events have used some of these drugs for their stimulating properties since the 1960s Mod subculture in U.K., whose members took amphetamine to stay up all night. In the 1970s disco scene, the club drugs of choice shifted to the stimulant cocaine and the depressant Quaaludes. Quaaludes were so common at disco clubs that the drug was nicknamed "disco biscuits". In the 1990s and 2000s, methamphetamine and MDMA are sold and used in many clubs. "Club drugs" vary by country and region; in some regions, even opiates such as heroin and morphine have been sold at clubs, though this practice is relatively uncommon. Narconon states that other synthetic drugs used in clubs, or which are sold as "Ecstasy", include harmaline; piperazines (e.g., BZP and TFMPP); PMA/PMMA; mephedrone (generally used outside the US) and MDPV.
The legal status of club drugs varies according to the region and the drug. Some drugs are legal in some jurisdictions, such as "poppers" (which are often sold as "room deodorizer" or "leather polish" to get around drug laws) and nitrous oxide (which is legal when used from a whipped cream can). Other club drugs, such as amphetamine, are generally illegal unless the individual has a medical prescription. Some club drugs are almost always illegal, such as cocaine and MDMA.
There are a range of risks from using club drugs. As with all drugs, from legal drugs like alcohol to illegal drugs like BZP, usage can increase the risk of injury due to falls, dangerous or risky behavior (e.g., unsafe sex) and, if the user drives, injury or death due to impaired driving accidents. Some club drugs, such as cocaine and amphetamines, are addictive, and regular use can lead to the user craving more of the drug. Some club drugs are more associated with overdoses. Some club drugs can cause adverse health effects which can be harmful to the user, such as the dehydration associated with MDMA use in an all-night dance club setting.
== Types ==
=== Ecstasy ===
MDMA (ecstasy) is a popular club drug in the rave and electronic dance music scenes and in nightclubs. It is known under many nicknames, including "e" and "Molly". MDMA is often considered the drug of choice within the rave culture and is also used at clubs, festivals, house parties and free parties. In the rave environment, the sensory effects from the music and lighting are often highly synergistic with the drug. The psychedelic quality of MDMA and its amphetamine-like energizing effect offers multiple reasons for its appeal to users in the rave setting. Some users enjoy the feeling of mass communion from the inhibition-reducing effects of the drug, while others use it as "party fuel" for all-night dancing.
MDMA is taken by users less frequently than other stimulants, typically less than once per week. Effects include "[g]reater enjoyment of dancing", "[d]istortions of perceptions, particularly light, music and touch"; and "[a]rtificial feelings of empathy and emotional warmth". MDMA is sometimes taken in conjunction with other psychoactive drugs, such as LSD, DMT,
psilocybin mushrooms and 2C-B. Users sometimes use mentholated products while taking MDMA for its cooling sensation.
=== Stimulants ===
A number of stimulants are used as club drugs. Various amphetamines and methamphetamines are used as stimulants, as is cocaine. These drugs enable clubgoers to dance all night. Cocaine is a powerful nervous system stimulant. Its effects can last from fifteen or thirty minutes to an hour. The duration of cocaine's effects depends on the amount taken and the route of administration. Cocaine can be in the form of fine white powder, bitter to the taste. When inhaled or injected, it causes a numbing effect. Cocaine increases alertness, feelings of well-being and euphoria, energy and motor activity, feelings of competence and sexuality. Cocaine's stimulant effects are similar to that of amphetamine, however, these effects tend to be much shorter lasting and more prominent.
=== Depressants/sedatives ===
Methaqualone (Quaaludes) became increasingly popular as a recreational drug in the late 1960s and 1970s, known variously as "ludes" or "sopers" (also "soaps") in the U.S. and "mandrakes" and "mandies" in the UK, Australia and New Zealand. The drug was often used by hippies and by people who went dancing at glam rock clubs in the 1970s and at discos (one slang term for Quaaludes in the disco era was "disco biscuits"). In the mid-1970s, there were bars in Manhattan called "juice bars" that only served non-alcoholic drinks that catered to people who liked to dance on methaqualone. Purported methaqualone is in a significant minority of cases found to be inert, or contain diphenhydramine or benzodiazepines. Methaqualone is one of the most commonly used recreational drugs in South Africa. It is also popular elsewhere in Africa and in India. Commonly known as Mandrax, M-pills, buttons, or smarties, a mixture of crushed mandrax and cannabis is smoked, usually through a smoking pipe made from the neck of a broken bottle.
The depressant GHB (also used by assailants as a date rape drug, in which case they slip it into a victim's drink) is intentionally taken by some users as a party drug and club drug.
Rohypnol (also used as a date rape drug) is a sedative/hypnotic that causes intoxication and impairs cognitive functions. This may appear as lack of concentration, confusion and anterograde amnesia. It can be described as a hangover-like effect which can persist to the next day. It also impairs psychomotor functions similar to other benzodiazepines and nonbenzodiazepine hypnotic drugs.
Although the previously mentioned drugs are generally categorized as club drugs by the media and the United States government, this distinction probably does not have an accurate correlation to real usage patterns. For example, alcoholic beverages (beer, wine, hard liquor) are generally not included under the category of club drugs, even though they are probably used more than any other drug at clubs, particularly those that are liquor-licensed nightclubs or bars.
In 2023, California passed Assembly Bill 1013 which requires bars and nightclubs to provide drug checking strips for drinks. A similar bill is also being considered in Olympia, Washington for 2026.
=== Psychedelic drugs ===
A psychedelic is a psychoactive drug whose primary action is to alter cognition and perception, typically by agonising serotonin receptors, causing thought and visual/auditory changes, and heightened state of consciousness. Major psychedelic drugs include Bufotenin, Racemorphan, LSD, DMT, and psilocybin mushrooms.
Not to be confused with psychoactive drugs, such as stimulants and opioids, which induce states of altered consciousness, psychedelics tend to affect the mind in ways that result in the experience being qualitatively different from those of ordinary consciousness. Whereas stimulants cause an energized feeling and opiates produce a dreamy, relaxed state, the psychedelic experience is often compared to non-ordinary forms of consciousness such as trance, meditation, yoga, religious ecstasy, dreaming and even near-death experiences. With a few exceptions, most psychedelic drugs fall into one of the three following families of chemical compounds; tryptamines, phenethylamines, and lysergamides. Many psychedelic drugs are illegal worldwide under the UN conventions unless used in a medical or religious context. Despite these regulations, recreational use of psychedelics is common, including at raves and EDM concerts and festivals.
=== Inhalants ===
"Poppers" are small bottles of volatile drugs which are inhaled by clubgoers for the "rush" or "high" that they can create. Nitrites such as alkyl nitrite originally came as small glass capsules that were popped open, which led to the nickname "poppers." The drug became popular in the US first on the disco/club scene of the 1970s, where dancers used the drug for the "rush" it provides, and because it was perceived to enhance the experience of dancing to loud, bass-heavy disco. The drug became popular again in the mid-1980s and 1990s rave and EDM scenes. As with disco clubgoers, rave participants and EDM enthusiasts used the drug because its "rush" or "high" was perceived to enhance the experience of dancing to pulsating music and lights.
Nitrous oxide is a dissociative inhalant that can cause depersonalization, derealization (feeling like the world is not real), dizziness, euphoria, and some sound distortion (flanging). In some cases, it may cause slight hallucinations and have a mild aphrodisiac effect. While medical grade nitrous oxide is only available to dentists and other licensed health care providers, recreational users often obtain the drug by inhaling the nitrous oxide used in whipped cream aerosol cans. Nitrous oxide users also buy small "whippet" canisters of nitrous oxide intended for use in restaurant whipped cream dispensers and then "crack" open these canisters to inhale the gas. Users typically transfer the gas to a plastic bag or balloon prior to inhaling it.
=== Ketamine ===
Ketamine, a dissociative anesthetic, has a long history of being used in clubs and was one of the most popular substances used in the New York Club Kid scene. Ketamine produces a dissociative state, characterized by a sense of detachment from one's physical body and the external world which is known as depersonalization and derealization. Effects include hallucinations, changes in the perception of distances, relative scale, color and durations/time, as well as a slowing of the visual system's ability to update what the user is seeing.
=== Other ===
In the 2000s, synthetic phenethylamines such as 2C-I, 2C-B and DOB have been referred to as club drugs due to their stimulating and psychedelic nature (and their chemical relationship with MDMA). By late 2012, derivates of the psychedelic 2C-X drugs, the NBOMes and especially 25I-NBOMe, had become common at raves in Europe. The drug organization Norconon states that other synthetic drugs used in clubs, or which are sold as "Ecstasy" include harmaline; piperazines (e.g., BZP and TFMPP); PMA/PMMA; mephedrone (generally used outside the US) and MDPV.
Though far less common than other "club drugs" like MDMA, ketamine, or LSD, heroin can be found in some of New York City's clubs. Marijuana and related cannabis products are used by some clubgoers; for example, some Rohypnol and ketamine users mix the powdered drug with marijuana and smoke it.
== Effects ==
=== Desired effects ===
Although each club drug has different effects, their use in clubs reflects their perceived contribution to the user's experience dancing to a beat as lights flash to the music. Club drug users are generally taking the drugs to "enhance social intimacy and sensory stimulation" from the dance club experience. Some club drugs' popularity stems from their ability to induce euphoria, lowered inhibition and an intoxicated feeling. Some drugs, such as amphetamine and cocaine, give the dancer hyperactivity and energy to dance all night. Many drugs produce a feeling of heightened physical sensation, and increased libido and sexual pleasure. Some club drugs, such as LSD, DMT, MDMA, 2C-B and ketamine enhance the experience of being in a nightclub with pulsating lights and flashing lasers and throbbing dance music, because they cause hallucinations or unusual perception effects.
=== Risks and adverse effects ===
Although research continues into the full scope of the effects of illegal drugs, regular and unsafe use of club drugs is widely accepted to have damaging side effects and carry a risk of addiction. Increased heart rate, a steep increase in body temperature, increase in blood pressure, spasms and dehydration are all common side effects of MDMA and methamphetamine. Breathing and respiratory issues, drowsiness, nausea and confusion are common side effects of said drugs. They can also make the user anxious, stressed and panicked, or even hallucinate. Withdrawal is also a risk with many club drugs. Drug cravings as the chemical leaves the user's body can be complicated by sleep deprivation, dehydration and hypoglycaemia to result in debilitating 'come downs' which can result in depression-like symptoms. In the worst instance, club drugs result in the death of the user from cardiac arrest or water intoxication due to the increase in heart rate and thirstiness induced. Inconsistency in the strength and exact composition of the supplied drug causing users to overdose. Wide variance in the measured rate of deaths caused by drugs such as ecstasy across countries suggest that user and societal/environmental factors may also affect the lethality of club drugs.
==== Drug interactions ====
Another risk is drug interactions. Some club drug users take multiple drugs at the same time. "Club drugs often are taken together, with alcohol, or with other drugs to enhance their effect." Drug interactions can cause hazardous side effects. When club drug users are in a liquor-licensed nightclub, users may mix pills or powders (MDMA, 2C-B, GHB, ketamine) with consumption of alcoholic drinks such as beer, wine or hard liquor. Some depressants, such as Rohypnol, are dangerous to take while drinking alcohol. "Ketamine often is taken in "trail mixes" of methamphetamine, phencyclidine, cocaine, sildenafil citrate (Viagra), morphine or heroin."
==== Injury or death due to risky behavior ====
Another risk with club drugs is one shared by all drugs, from legal drugs like alcohol to abused over-the-counter drugs (taking large amounts of dextromethorphan cough syrup) and illegal drugs (BZP, amphetamines, etc.): while impaired, the user is more likely to be injured, engage in dangerous or risky behaviour (e.g., unsafe sex) or, if she or he drives, have an accident resulting in injury or death due to impaired driving.
==== Misrepresentation ====
In many cases, illegal club drugs are misrepresented. That is, a dealer will tell a purchaser that she/he has a certain illegal drug for sale, while in fact the dealer's pills, capsules or bags of powder do not contain that chemical. For example, MDMA ("ecstasy") is very hard to synthesize in illegal underground labs, and methamphetamine is much easier (it can be made from household chemicals and over-the-counter cold remedies containing pseudoephedrine). As such, what dealers sell as MDMA is often methamphetamine powder. Similarly, pills sold by drug dealers as LSD, a drug which only the top chemists have the training to synthesize, most often contain no LSD; instead, they often contain PCP, a veterinary tranquilizer which produces dissociation and hallucinations in humans. In some cases, the dealer has intentionally substituted a less expensive, more available illegal drug for another drug. In other cases, the substitution was made by a higher-level drug cartel or organization, and the dealer may in fact believe that the bogus product is MDMA or LSD.
==== "Cutting", adulteration and "spiking" ====
With the exception of marijuana, which typically is uncut and unlaced, many illegal drugs, especially those which come in a powder or pill form are "cut" with other substances or "spiked" with other drugs. Cocaine, amphetamines and other stimulants often have caffeine powder added, as this increases the dealer's profit by bulking out the powder, so that less expensive cocaine or amphetamine has to be used in making the product. Some substances used to "cut" illegal drugs are not inherently harmful, as they are just used to "pad" or "bulk out" a quantity of the illegal drug and increase profits, such as lactose (milk sugar), a white powder often added to heroin. Even fairly innocuous powders that are added to illegal drugs, though, can have adverse effects with some routes of illegal drug administration, such as injection. With some drugs, adulterants are sometimes added to make the product more appealing. For example, "flavoured cocaine" has flavoured powder added to the drug.
Whereas the main goal of "cutting" is to bulk out a quantity of pure, expensive illegal drugs with an innocuous and not overly harmful substance (lactose) or fairly low-impact product (e.g., caffeine in amphetamine pills), the goal of "spiking" is to try to make lower-quality illegal drug or a lower-potency source of illegal drugs give the user the type of "high" or psychedelic experience she or he is seeking. While it was earlier stated that marijuana is most often uncut and un-spiked, some dealers add PCP to marijuana (this is nicknamed "wet marijuana"), because adding this dissociative hallucinogen to low-grade, low-THC marijuana can convert it into a cannabis that creates striking hallucinogenic effects. Drug researchers learned that some dealers were spiking marijuana when they tested US teens who stated that they had only used a single illegal drug (marijuana) and the teens tested positive for marijuana and PCP. Some dealers who have a very small quantity of MDMA powder to sell "spike" it with less expensive and easier to produce methamphetamine powder.
Street cocaine is often adulterated or "cut" with talc, lactose, sucrose, glucose, mannitol, inositol, caffeine, procaine, phencyclidine, phenytoin, lignocaine, strychnine, amphetamine, or heroin.
A common methamphetamine adulterant is dimethyl sulfone, a solvent and cosmetic base without known effect on the nervous system; other adulterants include dimethylamphetamine HCl, ephedrine HCl, sodium thiosulfate, sodium chloride, sodium glutamate, and a mixture of caffeine with sodium benzoate.
==== Addiction ====
Not all club drugs are addictive (e.g. nitrous oxide). However, some club drugs are addictive. Amphetamine heavily used in recreational fashion pose a risk of addiction.
Cocaine addiction is a psychological desire to use cocaine regularly. Cocaine overdose may result in cardiovascular and brain damage, such as: constricting blood vessels in the brain, causing strokes and constricting arteries in the heart; causing heart attacks. The use of cocaine creates euphoria and high amounts of energy. If taken in large, unsafe doses, it is possible to cause mood swings, paranoia, insomnia, psychosis, high blood pressure, a fast heart rate, panic attacks, cognitive impairments and drastic changes in personality. The symptoms of cocaine withdrawal (also known as comedown or crash) range from moderate to severe: dysphoria, depression, anxiety, psychological and physical weakness, pain, and compulsive cravings.
GHB addiction occurs when repeated drug use disrupts the normal balance of brain circuits that control rewards, memory and cognition, ultimately leading to compulsive drug taking. Although there have been reported fatalities due to GHB withdrawal, reports are inconclusive and further research is needed.
==== Ketamine risks ====
Ketamine use as a recreational drug has been implicated in deaths globally, with more than 90 deaths in England and Wales in the years of 2005–2013. They include accidental poisonings, drownings, traffic accidents, and suicides. The majority of deaths were among young people. This has led to increased regulation (e.g., upgrading ketamine from a Class C to a Class B banned substance in the U.K.). At sufficiently high doses, Ketamine users may experience what is called the "K-hole", a state of extreme dissociation with visual and auditory hallucinations.
== Acute treatment ==
The main treatment for individuals facing acute medical issues due to club drug consumption or overdoses is "cardiorespiratory maintenance". Since club drug users may have consumed multiple drugs, a mix of alcohol and other drugs, or a drug adulterated with other chemicals, it is hard for doctors to know what type of overdose to treat for, even if the user is conscious and can tell the medical team what drug they think they took. A doctor recommends "cardiac monitoring, pulse oximetry, urinalysis, and performance of a comprehensive chemistry panel to check for electrolyte imbalance, renal toxicity, and possible underlying disorders" and preventing "seizures". Some doctors use activated charcoal and a cathartic" to detoxify the drugs in the gastrointestinal system. Cooling the victim is recommended to avoid hyperthermia. If the victim overdosed on Rohypnol, the antidote flumazenil can be given; this is the only club drug for which there is an antidote.
== History ==
In the mid to late-1970s disco club scene, there was a thriving drug subculture, particularly for drugs that would enhance the experience of dancing to the loud dance music and the flashing lights on the dancefloor. Substances such as cocaine (nicknamed "blow"), amyl nitrite ("poppers"), and Quaaludes. Quaaludes were described as [the] "...other quintessential 1970s club drug", which suspends motor coordination.") According to Peter Braunstein, "massive quantities of drugs were ingested in discothèques."
Throughout the 1980s, the use of club drugs expanded into colleges, social parties, and raves. As raves grew in popularity through the late 1980s and into the late 1990s, drug usage, especially MDMA, grew with them. Much like discos, raves made use of flashing lights, loud techno/electronic dance music to enhance the user experience. Before their scheduling, some club drugs (especially designer drugs referred to as research chemicals) were advertised as alcohol-free and drug-free. Another reason that drug producers create new drugs is to avoid drug laws.
Since the early 2000s, medical professionals have acknowledged and addressed the problem of the increasing consumption of alcoholic drinks and club drugs (such as MDMA, cocaine, rohypnol, GHB, ketamine, PCP, LSD, and methamphetamine) associated with rave culture among adolescents and young adults in the Western world. Studies have shown that adolescents are more likely than young adults to use multiple drugs, and the consumption of club drugs is highly associated with the presence of criminal behaviors and recent alcohol abuse or dependence.
== In Australia ==
Club drugs are used in Australia in a variety of dance clubs and nightclubs. One in ten Australians have used MDMA at least once in their lifetime; one in thirty have used MDMA in the past 12 months. One in a hundred Australians has used ketamine at least once in their lives and one in five hundred over the past 12 months. One in two hundred Australians have used GHB at least once in their lives and one in one thousand in the past 12 months. Regarding the entire Australian population, seven per cent of Australians have used cocaine at least once in their lifetime and two per cent of Australians have used it in the past 12 months. Today, these drugs are widely used across age and socioeconomic groups and often sold in nightclubs and pubs throughout Australia.
== See also ==
Party pills
Route 36, world's first cocaine bar
Chemsex, the use of drugs to enhance sex
== References ==
== Further reading ==
Hunt, Geoffrey; Moloney, Molly; and Evans, Kristin. Youth, Drugs, and Nightlife. Routledge, 2010.
Knowles, Cynthia R. Up all night: a closer look at club drugs and rave culture. Red House Press, 2001.
Sanders, Bill. Drugs, Clubs and Young People: Sociological and Public Health Perspectives. Routledge, 2016.
== External links ==
Clubdrugs.gov, from the National Institute on Drug Abuse
Erowid reference 6889 | Wikipedia/Club_drug |
Students for Sensible Drug Policy (SSDP) is an international nonprofit organization advocacy and education organization with focus on drug policy, war on drugs, marijuana legalization, psychedelics, juvenile justice and youth rights, drug decriminalization, criminal justice reform. SSDP promotes global youth civic engagement as a tool in reforming drug policy.
SSDP has expanded from a single chapter in upstate New York created by a handful of students to a network of over 150 chapters worldwide.
== Board ==
SSDP is governed by a board of directors and a board of trustees, a designated body of the board of directors. Together, they are responsible for crafting strategy for the organization, overseeing compliance and financial affairs, and overseeing SSDP’s Executive Director. At least two-thirds of the members of SSDP's board of directors are students or young people elected by SSDP's chapters each year during the organization's national Congress. Maya Tatum, Arizona State University Tempe campus, is the current chair.
== Main issues ==
=== Marijuana policy reform ===
Students and chapters work on marijuana policy reform at the local, state, and federal levels by supporting legislation and ballot initiatives for decriminalization, medical marijuana, adult-use taxation and regulation, and social equity measures for communities disproportionately targeted by marijuana prohibition.
=== Psychedelic policy reform ===
SSDP provides resources for its members to advocate for psychedelic policy reform, such as psychedelic therapy programs and allowing the research of currently prohibited psychedelic substances by researchers.
=== Ending student drug testing ===
Students should not have to submit to a drug test at random or to participate in extracurricular activities.
=== Global drug policy ===
SSDP is a member of the Economic and Social Council and thus a consultant to its functional commissions. As such, SSDP has been advocating for policy reform and youth inclusion at the Commission on Narcotic Drugs, including the 2016 Special Session of the UN General Assembly on the World Drug Problem and the High Level Ministerial Segment in 2019.
SSDP Global Drug Policy and Development Consultant, Orsi Fehér, held the office of Treasurer on the board of the Vienna NGO Committee on Drugs between 2018–2020.
SSDP's former International Program Coordinator, Jake Agliata, is a co-founder of the Paradigma Youth Coalition.
The organization also coordinates youth participation in global campaigns such as Support. Don't Punish and International Overdose Awareness Day.
Portugal's drug policy, implemented in 2001, is based on the principle of harm reduction. Drug use and possession for personal use are no longer criminal offenses but administrative ones. Instead of facing criminal charges, individuals caught with drugs are referred to a Commission for the Dissuasion of Drug Addiction, where they receive a health assessment and may be recommended for treatment. Portugal’s drug policy has been successful in reducing drug use and associated harms, including HIV infections and overdose deaths.
=== Drug decriminalization ===
SSDP encourages chapters to create and support campaigns to decriminalize simple drug possession and other low-level crimes associated with drug use.
=== "Just Say Know" drug education ===
Just Say Know is a peer-to-peer drug education program, provides evidence-based drug information on campus and empowers them to reduce drug-related harm within their communities.
== Campus chapters ==
SSDP is made up of students and community members organized on college and high school campuses across the world. In 2015–2016, SSDP chapters were on 320 campuses, included 4,312 student activists and engaged in 135 drug policy initiatives. In 2021, the movement expanded to over 30 countries and all six habitable continents.
=== International ===
SSDP’s international chapters engage in reform from their campus and community to the United Nations, representing the voices of youth from their countries and sharing their experiences fighting the drug war with their fellow SSDPers all over the world.
SSDP’s international network has doubled in size through 2018 and expanded its structure to include regional fellowships to represent the specific needs of the Latin American, West African and European chapters.
== See also ==
War On Drugs
Prohibition (drugs)
Drug policy
== References ==
== External links ==
Official website | Wikipedia/Students_for_Sensible_Drug_Policy |
Many urban legends and misconceptions about drugs have been created and circulated among young people and the general public, with varying degrees of veracity. These are commonly repeated by organizations which oppose all classified drug use, often causing the true effects and dangers of drugs to be misunderstood and less scrutinized. The most common subjects of such false beliefs are LSD, cannabis, and PCP. These misconceptions include misinformation about adulterants or other black market issues, as well as alleged effects of the pure substances.
== Alcohol ==
Urban legends about alcohol.
=== Absinthe is a hallucinogen ===
Absinthe has often been portrayed as a dangerously addictive psychoactive drug and hallucinogen, which gave birth to the term "absinthism". The chemical compound thujone, which is present in the spirit in trace amounts, was blamed for its alleged harmful effects. By 1915, absinthe had been banned in the United States and in much of Europe, including France, the Netherlands, Belgium, Switzerland, and Austria-Hungary, yet it has not been demonstrated to be any more dangerous than ordinary spirits. Recent studies have shown that absinthe's psychoactive properties (apart from those attributable to alcohol) have been exaggerated.
=== Recreationally intoxicated elephants from fermented marula fruit ===
South African legends, recorded as early as the 1830s by naturalist Adulphe Delegorgue, describe elephants seeking out the fermented fruit of the marula tree, and showing signs of intoxication, including increased aggression, after doing so. This behavior was controversially depicted in the 1974 documentary Animals Are Beautiful People: the crew of the film reportedly staged the scene, either by soaking the fruit in alcohol before allowing animals to eat it, or by simply injecting the animals with a veterinary anesthetic to elicit symptoms of intoxication. Studies have concluded that it is very unlikely that an elephant could eat enough of the fruit in a day to become drunk; the study instead attributed their aggression to the value of the trees as a food source. Yet it may be possible that another intoxicant is at play – elephants are also known to eat the bark of the tree, which often contains toxic beetle pupae.
== Tobacco ==
=== Menthol cigarettes contain fiberglass ===
A common rumor states that menthol cigarettes or their filters contain fiberglass. In reality, modern cigarette filters are made of a fibrous form of cellulose acetate, which can resemble fiberglass when pulled apart. In the past, some cigarettes did contain asbestos in their filters. Another version of this myth states that chewing tobacco contains fiberglass, which allegedly creates small cuts in the mouth, enhancing nicotine absorption.
=== Some cigarette brands are owned by the KKK ===
Another urban legend states that some cigarette brands (most often Marlboro, Camel, and Kool), or menthol cigarettes in general, are owned by, manufactured by, or otherwise have connections to the Ku Klux Klan, or are intended to harm black people specifically. There is no credible evidence for any connection between cigarettes and the KKK.
== Lysergic acid diethylamide (LSD) ==
Some of the strangest urban legends told are those about lysergic acid diethylamide (LSD), a potent psychedelic drug that gained popularity in several countries in the 1960s and 1970s, and experienced a resurgence in the mid-2010s to present. The drug's relation to the 1960s counterculture was likely part of the reason for such legends.
=== Babysitter places baby in the oven while high on LSD ===
This is an unverifiable drug-scare story dating to the 1960s of a hippie babysitter girl putting a baby in the oven and a turkey in the bassinet. It has been debunked by Snopes.com. This myth is parodied in The Simpsons episode "The Secret War of Lisa Simpson", in which the children go on a school field trip to a "scared straight" wax museum at the local police station. One exhibit contains a wax dummy of a hippie woman eating a sandwich with a baby in it. Chief Wiggum says "That's right, she's got the munchies for a California Cheeseburger!"
In May 2009, partial ostension of this legend may have occurred when an Ohio man high on PCP allegedly tried to put his 28-day-old son into a conventional oven, only to be stopped in time by the child's mother. Also, in March 2010, a Kentucky man put his five-week-old baby in an oven (without turning it on, and without any injury) while drunk and high on marijuana (which he had smoked earlier that night) that he alleged made him feel strange and suspected was laced with a different drug that made him hallucinate; he was also tired from working. In 2005 China Arnold murdered her near month-old baby with a microwave oven, but she claimed that she was under the influence of alcohol, not LSD.
There are a limited number of cases reported in which babies were put into microwaves, though these cases were not known to involve any drugs, and were instead often cases of deliberate infanticide. However, there have been no known cases of microwaving (or baking) babies involving LSD specifically, or any other psychedelic drug, including cannabis. However, there have been many reported cases of psychotic violence under the influence of PCP. PCP, a dissociative anesthetic, is unrelated to LSD, a psychedelic drug.
=== Bad acid ===
A "bad trip" is easily caused by an expectation or fear of ill effects, which may later be blamed on "bad acid". This legend was made famous at the 1969 Woodstock festival, when concert-goers were warned to stay away from "the brown acid", which was allegedly bad.
One possible reason people believe that they had "bad acid" could be because they were simply sold a much higher dose than usual, which is not uncommon due to the inherent lack of quality control of illicit drugs, and with LSD in particular being effective at microgram rather than milligram doses. The stronger the dose, the stronger and potentially more anxiety-provoking the trip can get. But in the case of the "brown acid" it was the liquid the LSD was contained within that had evaporated thus increasing the dose per drop as LSD does not evaporate.
However, drugs sometimes falsely represented by sellers as LSD in the 1970s were actually PCP, amphetamine, or other drugs that have quite different, and often unfavorable, effects from LSD, causing unwitting users to incorrectly attribute a "bad trip" to LSD. There are now many research chemicals (DOB 2C-I, DOC, DOI, etc.) that can be nearly indistinguishable from real LSD before use, and thus can be easily confused with "bad acid". Some of these, such as 25I-NBOMe are even potent enough for psychoactive doses to fit on blotter paper, and may occasionally be sold as LSD when the latter is scarce. The idea of adulterating blotter LSD with these chemicals, however, has no known basis in fact.
=== "Bananadine" LSD ===
The false claim states that it is possible to synthesize LSD or some similar hallucinogenic drug called "bananadine" from banana peels or other common household foods and chemicals. The actual synthesis of LSD usually requires advanced knowledge and experience in organic chemistry and requires both expensive laboratory equipment and expensive, carefully controlled precursor chemicals.
Originating from a recipe originally published as a hoax in the Berkeley Barb in March 1967, variants of this legend often circulate on the Internet and were popular on BBSs well before the widespread availability of Internet access through William Powell's The Anarchist Cookbook. This book claimed "Musa sapientum Bananadine" was a mild psychoactive drug found in banana peels. The slang terms "mellow yellow" and "saffron" (for the color of the peels) were borrowed from the 1966 Donovan song, "Mellow Yellow", perhaps because the phrase "electrical banana" is mentioned in one of the lines. According to The Rolling Stone Illustrated Encyclopedia of Rock and Roll, Donovan claimed he was actually referring to a banana-shaped vibrator.
=== Blue star tattoos ===
This legend frequently surfaces in American elementary and middle schools in the form of a flyer that has been photocopied through many generations, which is distributed to parents by concerned school officials. It has also become popular on Internet mailing lists and websites. This legend states that a temporary lick-and-stick tattoo soaked in LSD and made in the form of a blue star, or of popular children's cartoon characters, is being distributed to children in the area in order to get them addicted to LSD. The flyer lists an inaccurate description of the effects of LSD, some attribution (typically to a well-regarded hospital or a vaguely specified "adviser to the president"), and instructs parents to contact police if they come across the blue star tattoos. No actual cases of LSD distribution to children in this manner have ever been documented. LSD is not addictive, and it is unlikely to be abused by an unwitting user. Therefore, there is no plausible motivation for a drug dealer to distribute LSD in this manner.
=== Legally insane ===
There is an urban legend that a person who has used LSD more than seven times is automatically declared legally insane. The same claim is often suggested with large doses, the difference being that the person is considered psychotic only for the duration of the trip. An extension of this legend is that a person who does LSD more than "X number of times" is permanently disqualified from the military as a result of being "legally insane", a version which was likely inspired by wishful thinking of drug-using draft dodgers in the 1960s. But no such law exists, at least not in the United States. However, the United States Air Force has regulations limiting and prohibiting recruitment of pre-service drug users, including prohibition of proven or admitted LSD users.
A version of this legend was repeated as fact on TV's Dragnet series in 1967, in an episode revolving around the use of LSD before it was made illegal. The script described a shipment containing "one pound of LSD [tabs], enough to turn the entire population of Los Angeles into dangerous psychotics" on the premise that one dose made a person legally insane due to the recurrence of completely unpredictable flashbacks throughout the user's life after a single dose.
=== LSD causes genetic mutations ===
Beginning in 1967, studies raised concerns that LSD might produce genetic damage or developmental abnormalities in fetuses. However, these initial reports were based on in vitro studies or were poorly controlled and have not been substantiated. In studies of chromosomal changes in human users and in monkeys, the balance of evidence suggests no increase in chromosomal damage. For example, white blood cells of people who had been given LSD in a clinical setting were examined for visible chromosomal abnormalities; overall, there appeared to be no lasting changes. Several studies have been conducted using illicit LSD users and provide a less clear picture. Interpretation of this data is generally complicated by factors such as the unknown chemical composition of street LSD, concurrent use of other psychoactive drugs, and diseases such as hepatitis in the sampled populations. It seems possible that the small number of genetic abnormalities reported in users of street LSD is either coincidental or related to factors other than a toxic effect of pure LSD. A 2008 medical review concluded, "The available data suggest that pure LSD does not cause chromosomal abnormalities, spontaneous abortions, or congenital malformations." Another large study, published in 2022, found no evidence to support the urban myth. However, this refutation has not stopped this perennial legend from being told, nor has it stopped the jokes about such "mutations" allegedly messing up the children of the Baby Boomers.
=== Man permanently thinks he is an orange and is terrified of being turned into a glass of orange juice ===
Another common legend, again dating back to the 1960s, was that a man who took LSD went insane and permanently thought that he was a glass of orange juice. Because of this, he could never bend over, slept upright and did not make any sudden movements over fear of being "spilt". Alternative versions sometimes have the man thinking he is a glass of milk or a whole orange. Another version of this myth states that the man believed he had become an orange, and was afraid he would be 'peeled' by his friends.
=== Police officer unwittingly drinks LSD ===
In this legend, which dates back to 1970, a police (or customs) officer pulls over a driver believed to have been drinking, sees that the driver has a water bottle, and demands a taste of it to see if it contains alcohol. The officer does not taste any alcohol, so the driver either gets off completely or merely gets a speeding ticket. Shortly afterward, the officer begins tripping very hard and stares into space, since the swig of "water" he took actually contained numerous "hits" of LSD. In some versions of the legend, the officer consumes enough LSD to actually go insane. According to Snopes.com, there are no verifiable reports of this ever happening, even decades after the legend was first told, and it is thus considered spurious.
=== "Permatripping" and retention of LSD in spinal fluid ===
This legend may have its foundation in the fact that chronic use can result in flashbacks and hallucinogen persisting perception disorder (HPPD).
There remains no consensus regarding the nature and causes of HPPD or flashbacks. A study of 44 HPPD subjects who had previously ingested LSD showed EEG abnormalities.
Given that some symptoms have environmental triggers, it may represent a failure to adjust visual processing to changing environmental conditions. There are no explanations for why only some individuals develop HPPD. Those affected by HPPD are not psychotic, as they recognize the unrealistic nature of their visual disturbances.
Those with a predisposition to psychological disorders who take LSD or other hallucinogens may trigger a psychotic episode that may produce hallucinations reminiscent of the drugs, enduring beyond the period of its active effects. This leads some individuals experiencing psychosis to mistakenly believe that the effects of the drugs haven't and will not subside.
LSD is metabolized by the liver, and has an elimination half-life of around 2.5 to 4 hours.
=== Strychnine ===
Anti-drug educators frequently tell their students some variant on the theme of inevitable strychnine poisoning through LSD use, for example, that strychnine is commonly sold as a cheaper substitute for LSD by unscrupulous drug dealers; that strychnine is a byproduct of LSD synthesis; that the body produces strychnine as a result of LSD metabolism; or that strychnine is used as a preservative to prevent the otherwise natural, rapid decomposition of LSD, allowing it to be stored; or that strychnine is somehow necessary to bond LSD to blotter paper. None of this is true. These claims may even be believed and propagated by drug users themselves. In reality, most hallucinogens cause some degree of mental or physical discomfort after the "trip" is over. This is an indirect effect of the drug, not strychnine or any other adulterant. Additionally, strychnine is one of the most bitter substances known, with a detection threshold of 1 part per million, well below toxic levels. Finally, the dangerous dose of strychnine is too high to be contained in a blotter square.
Strychnine has indeed rarely been discovered mixed with LSD and other drugs in a few samples recovered by law enforcement agencies, but these were all found in murder or attempted murder investigations where someone was being specifically targeted for poisoning, and not associated with recreational LSD use.
A related myth is that a new type of gang initiation requires the initiate to put a mixture of LSD and strychnine on the buttons of as many payphones as possible. This too is debunked by the urban legends website Snopes.com.
=== Sungazing while tripping ===
A popular legend dating back to the 1960s, it has been claimed that several people took LSD and stared at the sun, going blind as a result. This myth appeared in 1967 on the cop show Dragnet, and twice in the mainstream news media. The legend is considered to be unfounded, since in 1968 the source of the hoax, Norman M. Yoder, commissioner of the Office of the Blind in the Pennsylvania State Welfare Department, admitted that he had completely made up the story because of his "concern over illegal LSD use by children". After the sun-gazing on LSD story was widely publicized, a small number of case reports were published in the medical literature which describe this phenomenon temporarily occurring. In one case, the patient was a teenage girl described as having a "hysterical personality" who heard warnings about staring at the sun under LSD in a school anti-drug lecture and thought this "would be a neat thing", and in another case the patient had paranoid schizophrenia.
== Cannabis ==
Many misleading urban legends about cannabis exist. Like LSD rumors, many were spread during the 1960s and 1970s, and are believed to continuously circulate today. These widespread legends claim that it is easy to overdose on the smokeable variant of cannabis and that it is extremely dangerous and addictive when compared to alcohol and tobacco.
Symptoms of withdrawal from cannabis begin after at least 24 hours of abstinence, peak on days 2–6, and subside within two weeks. Withdrawal symptoms are generally mild—loss of appetite, insomnia, feelings of uneasiness/anxiety, irritability, craving, tension, stomach ache, and headache all being common symptoms. There are studies that show no actual increased risk of cancer from smoking marijuana, even when duration of use is expanded over several years. In fact, some studies indicate THC to have anticancer properties, with studies showing tumor reduction in mice.
=== Confusion with Jimson weed ===
Historically, and possibly related to the "Reefer Madness" legend, some people (particularly Americans) had confused cannabis with Jimson weed (Datura stramonium). Jimson weed, which grows wild in the United States and several other countries, is a potent deliriant which can cause true hallucinations and delusions that are believed by the user to be real, as opposed to the pseudohallucinations and perceptual distortions typically caused by cannabis. Confusion could have resulted from the fact that Datura's common name contains the word "weed", which is also a slang term for cannabis, and the fact that both plants (as well as others) have been given the moniker "locoweed" in the first half of the 20th century. Aside from these superficial similarities, the two plants are not related, do not resemble one another, and are very unlikely to be confused. Jimson weed is highly toxic and can cause delirium, confusion, hallucinations, blurred vision, photophobia, dry mouth, urinary retention, hyperthermia, incoordination, hypertension, and rapid heartbeat among other effects. An overdose (or suspected overdose) on this substance is considered a medical emergency, as it can cause seizures, coma, or death by cardiac arrest—all parts of Datura plants contain dangerous levels of the tropane alkaloids, specifically atropine, hyoscyamine, and scopolamine, which are classified as deliriants and/or anticholinergics.
=== "Flashbacks" due to release from fat cells ===
Similar to one of the most enduring myths about LSD, and also somewhat related to the "multi-day impairment" legend described further down on this list, this legend claims that residual THC stored in fat cells gets released spontaneously into the bloodstream in enough quantities to get one high again long after the last use of cannabis, be it days, weeks, or even months later. This legend is typically accompanied by anecdotal evidence of people who experience a "high" after doing exercise of some sort. While somewhat more biologically plausible than the discredited LSD legend due to the fat-solubility of THC, this phenomenon remains scientifically unproven. A 2009 study of rats that involved injecting them with large quantities of THC (equivalent to 5–10 joints per day in humans) each day for ten days straight, then subjecting them to simulated severe stress or food deprivation led to double the blood levels of THC−COOH two days after the last THC exposure compared to rats that were neither stressed nor deprived of food. If such results occurred in humans, then it is theoretically possible for a chronic cannabis user to fail a drug test long after the usual detection time due to exercise, dieting, or severe stress shortly before the test—and several anecdotal reports of this exist. However, there is currently no hard evidence that enough active THC would be released to get one "high" or cause "flashbacks". One should also note that flashbacks from psychoactive drugs in general are now known to be psychological phenomena, and drug residues typically play no significant role in their occurrence and recurrence.
As for the anecdotes about exercise, they likely experienced a "runner's high" due to their bodies releasing endorphins, which are endogenous opioid agonists, along with anandamide and other endogenous cannabinoid agonists. These flashbacks have also been reported after one has stretched or stood up/sat or lay down abruptly. In addition, some studies find that the body produces endocannabinoids such as anandamide during exercise, which may also explain such effects since they activate the same receptors as THC.
=== George Washington smoked cannabis ===
There is a common belief that George Washington (and/or other Founding Fathers such as Thomas Jefferson) used cannabis for its psychoactive or medicinal properties. This has even made its way into popular films such as Dazed and Confused.
Both Washington and Jefferson grew cannabis to produce hemp, and Washington used hemp fiber to make clothes for his slaves, but there is no direct evidence that either Washington or Jefferson consumed it for its psychoactive properties. Washington is commonly mis-quoted as saying "Make the most of the Indian hemp seed, and sow it everywhere," often cited as a note to his gardener published in The Washington Papers. However the closest phrase to this in The Washington Papers is in a letter to William Pearce – "I am very glad to hear that the Gardener has saved so much of the St. foin seed, and that of the India Hemp. Make the most you can of both, by sowing them again in drills. [...] The Hemp may be sown any where."
In The Papers of George Washington, "hemp" is defined as Cannabis sativa grown for fiber, and "Indian hemp" typically refers to the closely related Cannabis indica. While Washington was growing cannabis for its fiber, both of these species are also cultivated for their psychoactive and medicinal properties.
When cannabis is grown for its medicinal or psychoactive properties, male plants are routinely separated from females to prevent pollination, as non-pollinated female plants produce the most potent and prized flowering tops, known as sinsemilla (from the Spanish "sin semilla", meaning "without seed"). To produce sinsemilla, the sexes must be separated before pollination occurs. On August 7, 1765, Washington wrote in his diary "Began to separate the Male from the Female hemp at Do.– rather too late." While this has been taken as evidence that Washington was growing cannabis for its psychoactive or medicinal properties, The Straight Dope points out that later entries in Washington's diary suggest that "he divided the plants because the males made stronger fiber while the female plants produced the seed needed for the next year's crop." Two days after he wrote the aforementioned entry in his diary, Washington wrote that he had "put some Hemp in the Rivr. to Rot," a technique called water retting used for producing hemp, not psychoactive cannabis. The following month he wrote that he "Began to Pull the Seed Hemp but it was not sufficiently ripe," and three weeks later that the "Hempseed seems to be in good order for getting – that is of a proper ripeness."
The introductory editorial for the June 2010 cannabinoid-themed issue of the British Journal of Pharmacology said that "there are sources that suggest that chronic tooth-ache may have led the first President of the United States, George Washington, to grow the plant for medicinal purposes," though these sources are not cited. The cover of the issue featured images of Washington and Queen Victoria placed on either side of a cannabis leaf.
=== An allergic reaction to molecules found in marijuana killed Bruce Lee ===
A number of rumours surfaced surrounding the cause of action film star Bruce Lee's death in 1973, one of which was that he had been killed by the consumption of cannabis. Lee died of a cerebral edema several hours after taking the painkiller and muscle relaxant equagesic. His autopsy showed trace amounts of cannabis in his stomach, and he had been known to use cannabis. However, a doctor at the coroner's hearing was quoted as saying that the cannabis in Lee's stomach was "no more significant than if Bruce had drunk a cup of tea that day."
Lee's physician, Donald Langford, and Peter Wu, a doctor who had treated Lee for another edema ten weeks earlier, believed that the fatal edema could have been caused by a rare allergic reaction to an alkaloid in cannabis, as a large quantity of hashish was removed from his stomach during the earlier edema, and he had been warned not to use it again. Wu told the coroner he believed the death was due to hypersensitivity to either cannabis or equagesic. However, Ronald D. Teare, a professor of forensic medicine at the University of London who was flown in to be the chief expert in the coroner's report, said that it was both "irresponsible and irrational" to attribute either edema to cannabis, and concluded the fatal edema was due to a rare reaction to equagesic. Teare, who had supervised nearly 100,000 autopsies and provided evidence for nearly 20,000 inquests in his 35 years of experience, was echoed by R. R. Lycette, the clinical pathologist at Queen Elizabeth Hospital. Lycette told the hearing that his death could not have been caused by cannabis, and that Lee had died from an edema caused by a reaction to one or both of the ingredients in equagesic.
At the time in Hong Kong, cannabis was seen in an extremely negative light—worse than opium—and was "considered a 'foreign' drug with sinister and evil undertones." Bruce Thomas, author of Bruce Lee: Fighting Spirit stated that "this view had a massive impact on the official findings," and that Wu's inclusion of cannabis as a suspected cause of death "reflected this cultural and even political pressure." Wu later said in a 1992 interview with Thomas:
Professor Teare was a forensic scientist recommended by Scotland Yard; he was brought in as the expert, so we can't contradict his testimony. The dosage of cannabis is neither precise nor predictable, but I've never known anyone to die simply from taking it.
Although it could not be completely ruled out that cannabis caused the edema, Teare's view was accepted by the coroner, and the official verdict was "death by misadventure" caused by a reaction to equigesic. Cannabis was not included as a possible cause of Lee's death.
=== Reefer madness ===
Originating in the 1930s, this myth was the basis for films like Reefer Madness, and used by Harry Anslinger of the Federal Bureau of Narcotics as justification for outlawing cannabis. The allegation was that even the calmest, most normal person could be transformed into a psychopathic killer or rapist solely from smoking a joint. No relationship has ever been proven linking such crimes to the acute intoxication of cannabis alone, and cannabis' psychological effects tend to be more associated with pacifism and inactivity than with aggression. For example, studies of the Jamaican working class showed no difference in the crime rates between users and non-user of cannabis.
=== Rick Simpson Oil ===
Rick Simpson Oil is a preparation made from cannabis oil, the oils of Cannabis flower. It is named after its Canadian creator, circa 2003, which he used to treat his tinnitus, and is also known as phoenix tears. It has been claimed to have healing benefits for cancer. As of 2022, no such properties are known.
=== Smoking or "chasing" cannabis with tobacco increases the high ===
In many places, cannabis is routinely mixed with tobacco when rolled into joints. In North America cannabis in any form is also often "chased" with a tobacco cigarette, and hollowed-out cigars filled with cannabis (blunts) are also popular in some subcultures. Some users say that smoking tobacco increases the cannabis high, and this is often attributed to either the nicotine or additives such as menthol. Until recently this was based solely on anecdotal evidence. There may be at least some truth to this legend, as a 2005 study found that a transdermal nicotine patch modestly enhanced the subjective "high" of cannabis relative to a placebo patch—but only in males. Females actually saw a slight reduction in subjective effects. Reasons for the enhancement are not well understood, and this study appears to be the only one as of 2010 that found such effects. However, another study found a significant downside to the practice. It appears that tobacco, which is known to be highly addictive, also enhances the likelihood of developing cannabis dependence symptoms when the two substances are used concurrently.
=== Some Lucky Strike cigarettes contained cannabis ===
It has been claimed the cigarette brand Lucky Strike is so named because every so often, a consumer of the product would have a "lucky strike", finding a cannabis spliff in a pack of cigarettes. The rumor varies in how often the cannabis cigarette would be included, anywhere from one in every thousand cartons to one in every pack. It is unclear when this myth originated; Snopes.com claims it has been floating around for "many years". Lucky Strike's slogan "It's Toasted" fueled belief in the myth further ('toasted' being one slang term for being high on cannabis). Despite the popularity of the myth, there are no reliable reports of any Lucky Strike cigarette containing cannabis. The name "Lucky Strike", in reality, is only a marketing ploy, implying to customers that obtaining their brand is a "Lucky Strike". The "It's Toasted" slogan refers to the product's tobacco being toasted instead of sun-dried, making a supposedly better-tasting product.
Other urban legends offshoot from this one. One of the explanations for the origin of flipping a "lucky" cigarette upside down claims the practice originated from the Lucky Strike myth; it is presumed the superstition arose from flipping the marijuana-containing cigarette upside-down in order to save it for last.
=== Popularity in the United States in the 1960s ===
Although the 1960s are commonly perceived as a time of rampant marijuana use compared with the present day, in a 1969 Gallup poll only 4% of American adults had tried marijuana and 34% did not know its effects. In contrast, later Gallup polls show that the percentage of adults who had tried marijuana had risen to 33% by 1985 and 34% by 1999.
== MDMA (ecstasy) ==
The third most common illicit drug that is the source of urban legends is 3,4-methylenedioxymethamphetamine (MDMA), better known as "ecstasy". In the United States, this substance was banned in 1985, and other countries followed suit. Among American youth, MDMA was most popular in the 1990s and early 2000s, peaking in 2001 and declining thereafter. It was during this time of rather faddish use that numerous urban legends and misconceptions began to surface and be spread through the media, and not all of them necessarily originated from anti-drug organizations.
=== MDMA drains spinal fluid ===
This myth appears to be derived from research in 1994 (This myth was circulating in the UK as early as 1991) in which serotonin breakdown products were measured in the spinal fluid of ecstasy users. However, it was the researchers, not the drug, who drained the fluid (for the purpose of testing). Nonetheless, this legend (and related ones about it damaging one's spinal cord and/or spinal column, which is also false) was popularized in 2000 by Eminem's songs "Drug Ballad" and "The Kids".
=== "Stacks"—Single, double, triple etc. ===
Many ecstasy users describe the potency of various ecstasy pills in terms of their stack such as double stack or triple stack pills. These claims are dubious as there is no way to verify potency objectively without proper testing. The term "stack" is not intended to measure potency of ecstasy pills, but it is used as a measurement of mass. Single stacks weigh in at 0.20 grams, doubles at 0.40 grams, and triples at 0.60 grams. Furthermore, a high percentage of what is sold as "ecstasy" may contain a combination of MDMA and one or more other substances or may in fact contain no MDMA at all. For these reasons, the "stack" system of strength description is not necessarily trustworthy—as is commonly the case in the underground drug market.
== Methamphetamine ==
Though initially there were not very many urban legends about methamphetamine ("crank", "crystal meth", "ice"), the "meth epidemic" of the late 1990s and early 2000s (especially in the USA) led to quite a few new legends.
=== Lung damage from recrystallization ===
One meth legend refers to the method of administration in which the user will heat/melt crystal methamphetamine and inhale the resulting methamphetamine vapor. The legend states that the drug, once inhaled, will re-crystallize in large amounts inside the lungs, damaging them in the process. This is a false claim as crystallized methamphetamine is always in the form of a salt (usually methamphetamine hydrochloride), which is highly soluble in water, as well as hydrophilic, and is instantly absorbed into the user's bloodstream via the alveoli.
However, intravenous methylphenidate (Ritalin) use results in a type of lung damage commonly known as Ritalin lung. Methylphenidate tablets are crushed and dissolved into solution for intravenous injection. The tablets contain talc and other particulates which can deposit in the lung (talcosis) and result in severe emphysema affecting all the lobes of the lung. The "Ritalin lung" effect could be a possible source of how rumors about methamphetamine damaging the lungs could have surfaced.
=== Strawberry Quik ===
Another meth legend is that dealers are selling colored and flavored meth resembling candy (often with names like Strawberry Quick, originating from an idea that dealers would mix the drug with strawberry-flavored Nesquik) to entice children to buy it. It was first reported in 2007 in the western United States, and children were allegedly ingesting it thinking it was candy, and ending up in the ER. According to Snopes.com there is no hard evidence, as of October 2008, that flavored meth is being handed out in schoolyards, nor that children are mistaking meth for candy.
== Heroin ==
=== Cotton fever ===
Cotton fever is a high fever supposedly caused by injecting cotton fibers into the bloodstream when shooting up heroin. Cotton is sometimes used as a crude filter for particulate matter prior to intravenous injection. Other commonly blamed substances include fiberglass if a cigarette filter was used (cigarette filters do not contain fiberglass), or dirt if Mexican heroin was injected. In general, cotton fever refers to a fever that users believe is caused by inanimate particulate matter injected into the bloodstream. In reality, the particulate matter causing cotton fever is bacteria from lack of sterile technique. Most cases of cotton fever resolve as the body clears the infection. Users will often seek medical attention when cotton fever persists. Persistent cotton fever is often infective endocarditis. Although endotoxin shed by the bacteria Enterobacter agglomerans, which colonizes cotton plants, has been implicated as the cause of cotton fever, most clinical cases demonstrate blood cultures positive for skin and fecal bacteria.
=== "Cheese" ===
"Cheese" or "Tylenol with Smack" is a heroin-based recreational drug that came to the attention of the media inside and outside the United States after a string of deaths among adolescents in the Dallas-Fort Worth Metroplex, between 2005 and 2007. It is generally reported to be a mixture of heroin and Tylenol PM (an OTC acetaminophen and diphenhydramine combination) or its generic equivalent, in varying ratios.
It seems likely that the concept was originally created as a joke, and after seizures of low purity heroin cut with paracetamol (acetaminophen) "validated" the claims, the DEA issued a warning. Although the source of the original hoax is gone, newspapers and media outlets continue to make reference to each other with no mention of any primary sources, perpetuating the myth of cheese as "starter heroin" for children. However, there may have been some ostension of this legend in 2007 involving a few individuals in Texas.
In the South Park episode "Major Boobage", which aired for the first time on 28 March 2008, 'cheesing' referred to a moral panic about children using cat urine to get high.
== Phencyclidine (PCP) ==
=== Embalming fluid ===
A commonly held misconception is that phencyclidine (PCP, angel dust) is the same as (or is synthesized from) embalming fluid. Some people, believing this myth, have actually attempted to smoke cigarettes or cannabis dipped in real embalming fluid (i.e. formaldehyde), which is highly toxic. Conversely, some users of PCP-laced cannabis believe (and are often told) that it contains embalming fluid proper and not PCP, or that the slang term "dust" really means embalming fluid proper. Sometimes, the two substances are even mixed together, in a further ostension of this legend. The combination might be called "fry", "wet", "illy", "sherm", "worm", "water-water", "amp", "dust(ed)", or other names.
=== Rodney King was on PCP at the time of his 1991 beating and arrest ===
The Rodney King police beating case in Los Angeles was a source of much controversy and outrage, as well as urban legends. Because King resisted arrest, with several officers needed to subdue him, he was assumed to be on PCP at the time due to its reputation for inciting violent and unpredictable behavior coupled with an inability to feel pain (often misinterpreted as "superhuman" strength). However, toxicology results showed that the only drugs found in his system were alcohol and traces of marijuana.
=== Man slices off his face and feeds it to dogs ===
One legend holds that a man who, while under the influence of the drug, thoroughly sliced off pieces of his own face, including his eyes, to feed to his pet dogs. Some versions of this tale say he suffered permanent brain damage as well. This legend is remarkably similar to what the character Mason Verger did in Thomas Harris' 1999 novel Hannibal. The legend, however, dates back earlier than 1999, and can be traced to former New York homicide detective Vernon J. Geberth, who writes about it in his book Practical Homicide Investigation. According to Geberth, this actually did occur to a man named Michael, and Geberth was one of the detectives called to the scene. A 1989 book by Dr. Joseph Sacco also mentions this story, albeit with a few differences in the details.
=== Superhuman strength ===
Some reports cite a widely held belief that PCP can give its users "superhuman" strength for the duration of its effects, and there are several anecdotes alleging this phenomenon. However, the drug does not typically make the user significantly stronger in reality than they otherwise would be.
== Psilocybin mushrooms ==
=== Super Mario connection to psilocybin mushrooms ===
One legend that is popular among both the drug and video gaming subcultures is that the mushroom powerup in Super Mario games is actually based on psilocybin mushrooms. Somewhat lending credit to the legend, Shigeru Miyamoto, the creator of the Super Mario series, has stated that he chose mushrooms for their relationship to "magical realms", and has drawn connections to other works featuring mushrooms with mysterious powers, such as Lewis Carroll's Alice's Adventures in Wonderland, a story in which eating specific mushrooms cause one to change size. The mushrooms depicted in the game (white circles on red caps) also have a similar appearance to Amanita muscaria which, while being quite distinct from psilocybin mushrooms ("magic mushrooms"), still have hallucinogenic properties, and have been used by humans for their intoxicating effects for hundreds of years.
== Designer drugs ==
The advent of novel illegal or quasi-legal designer drugs intended as substitutes or alternatives to illegal drugs has given rise to several new legends as well.
=== Cannibalism from "bath salts" ===
In 2012, novel substituted cathinones, nicknamed "bath salts" as a result of mephedrone originally being sold as bath salts in the US to evade consumer protection laws, were implicated in several violent attacks, including some highly publicized cases of cannibalism. However, the most well-known cannibal attacker from Miami, Rudy Eugene, tested negative for all drugs known to be nicknamed "bath salts" and every other known psychoactive substance except traces of cannabis.
== General ==
In addition to legends about specific drugs, there are also some more generic ones that are often applied to several types of drugs. Typically, these legends involve rather morbid themes and/or targeted children, but some are told with more levity for the purpose of humor.
=== Drugs smuggled in baby's corpse ===
This legend, dating back to the early 1970s and first appearing on the Internet in 1996, claims that drug traffickers are smuggling illegal drugs (typically cocaine) in hollowed-out dead babies to avoid detection. Allegedly, tourists' babies are kidnapped, killed, cut open, filled with drugs, and sewn shut so the contraband can be more readily sneaked over the border. However, according to U.S. Customs and other law enforcement agencies, there are no verifiable reports of this ever happening, and thus this myth is unfounded.
=== Drug-laced candy or lollipops given to schoolchildren ===
Plenty of lollipops in "hippy" stores sold in countries like the UK and Canada have been alleged to contain CBD, a non-intoxicating phytocannabinoid; age limits on these are unclear and they are sold passively.
This legend, which surfaced on the Internet just in time for Halloween in October 2004, claimed that drug dealers were giving lollipops laced with drugs, typically a combination of THC and PCP, to unsuspecting children and causing them great harm. Such suckers are allegedly referred to as "dro pops" or something to that effect, and various towns around the country have had their own versions of the legend. According to the U.S. DEA, suckers containing THC and/or PCP were found and confiscated in Chicago in the spring of 2004. They also report that in 2003 and 2004 some psilocybin mushroom chocolate candies were seized near Amarillo, Texas, and that hollowed-out lollipops filled with heroin have been seized in New York City. The goal of doing so was likely to evade detection by law enforcement by disguising the drugs as candy. There is no evidence that these were ever given to children, much less that any such children were harmed, or even that such lollipops have been found outside of these specific locations or anywhere since early 2004. Thus, this legend can be considered to be in a similar vein as the infamous blue star tattoo legend.
=== Drug-related Halloween legends ===
Related to the above legend, various drugs have also found their way into the more general and perennial Halloween poisoning legends. Allegedly, unsuspecting trick-or-treaters are given candy (or sometimes fruits) laced with poisons, needles, razor blades, and drugs by strangers. However, virtually all reports of this happening are now known to be either hoaxes, events unrelated to Halloween candy, or non-random poisonings by relatives made to look random. The latest manifestation of drug-related Halloween legends was a prediction by Sheriff Lee Baca of Los Angeles that cannabis edibles (from medical marijuana dispensaries) would possibly end up in the hands of trick-or-treaters on Halloween in 2010. Baca even went so far as to confiscate cannabis edibles from circulation in an attempt to prevent this from happening, and displayed them on television two days before Halloween. Again, there is no evidence that cannabis-laced treats were ever given out to trick-or-treaters in 2010 or in any other year.
=== "Gnome" legend ===
Another legend involves a group of teenagers who, while drunk and/or tripping on some sort of hallucinogen, find what they perceive to be a gnome (sometimes a dwarf, hobgoblin or smurf), capture it, and bring it home. They sleep off the drug's effects, and the next morning they find out that the "gnome" was really a lost (and very frightened) child. Though the story may be told by some tellers in a negative light, it may also have a positive spin in that the teens become unwitting heroes in finding a missing child whose parents (as well as the police) had been unable to find. According to Snopes.com, the legend had first surfaced in 2004, and as of 2020 the legend's truth status remains undetermined and unverifiable. In some versions of a legend the "gnome" is not a child but a person with dwarfism or Down Syndrome; some have even gone as far to say it was a dead baby.
=== "Homeopathic" drug water ===
In 2004–2005, an Internet rumor was being spread that claimed that LSD (and other drugs) were being diluted with water to extremely low concentrations, which allegedly made the drugs even more powerful, yet cheaper and undetectable. This is related to the pseudoscientific "Law of Infinitesimals", one of the principles behind homeopathy. However, there is no evidence that this actually has effects different from a placebo, or that a significant number of users or dealers were ever actually doing this.
== Drug testing ==
The increasingly common practice of drug testing, especially urinalysis, has led to an increase in the number of drug users looking for ways to beat the tests, and has spawned a number of urban legends as a result. One should note that time is the only scientifically proven method for certainly passing a test, apart from not consuming any substances at all that are likely to be tested for. However, this does not stop users from getting creative in their attempts to somehow shorten the detection times and/or mask the contents of their fluid specimens, with varying degrees of success or lack thereof.
=== Secondhand exposure will cause a positive test ===
This legend is technically true but highly misleading. According to a U.S. Army study, the amount of secondhand cannabis smoke needed to cause a false positive result (failure) is quite large indeed, and would require being sealed in an unventilated car or small room filled with marijuana being actively smoked (often referred to as a "hotbox") for several hours. Hair testing, however, is a different matter, particularly with passive exposure to crack/cocaine, which can deposit onto hair and be readily incorporated into it. With regards to cannabis, however, typically only metabolites (produced by the body and thus not found in smoke) are tested rather than THC, so failure is unlikely to result from non-extreme passive exposure.
=== High doses of niacin will help you pass ===
Niacin, also known as Vitamin B3, is speciously claimed by some to "burn it out" of one's system when taken at high doses (250–500 mg per day). While some Internet (and other) sources claim that this works wonders, there is no supporting scientific evidence. Very high doses can also cause adverse side effects.
This legend may have been (inadvertently) inspired by Narconon, a Scientology-based drug rehabilitation program that uses exercise, saunas, and dangerously high doses of niacin (and other vitamins) to detox. It is also part of L. Ron Hubbard's general Purification Rundown, which can supposedly remove pollutants as well as drug residues. Although some drug users claim that this has worked, there are currently no peer-reviewed scientific studies to back these methods up.
== Drug checking ==
=== Moonshine ===
A common folk test for the quality of moonshine was to pour a small quantity of it into a spoon and set it on fire. The theory was that a safe distillate burns with a blue flame, but a tainted distillate burns with a yellow flame. Practitioners of this simple test also held that if a radiator coil had been used as a condenser, then there would be lead in the distillate, which would give a reddish flame. This led to the mnemonic, "Lead burns red and makes you dead," or simply, "Red means dead." In actual fact, the flame color of lead is not red but blue-white.
== See also ==
Moral panic
== References == | Wikipedia/Urban_legends_about_drugs |
A drug class is a group of medications and other compounds that share similar chemical structures, act through the same mechanism of action (i.e., binding to the same biological target), have similar modes of action, and/or are used to treat similar diseases. The FDA has long worked to classify and license new medications. Its Drug Evaluation and Research Center categorizes these medications based on both their chemical and therapeutic classes.
In several major drug classification systems, these four types of classifications are organized into a hierarchy. For example, fibrates are a chemical class of drugs (amphipathic carboxylic acids) that share the same mechanism of action (PPAR agonist), the same mode of action (reducing blood triglyceride levels), and are used to prevent and treat the same disease (atherosclerosis). However, not all PPAR agonists are fibrates, not all triglyceride-lowering agents are PPAR agonists, and not all drugs used to treat atherosclerosis lower triglycerides.
A drug class is typically defined by a prototype drug, the most important, and typically the first developed drug within the class, used as a reference for comparison.
== Comprehensive systems ==
Anatomical Therapeutic Chemical Classification System (ATC) – Combines classification by organ system and therapeutic, pharmacological, and chemical properties into five levels.
Systematized Nomenclature of Medicine (SNOMED) – includes a section devoted to drug classification
== Chemical class ==
This type of categorisation of drugs is from a chemical perspective and categorises them by their chemical structure. Examples of drug classes that are based on chemical structures include:
== Mechanism of action ==
This type of categorisation is from a pharmacological perspective and categorises them by their biological target. Drug classes that share a common molecular mechanism of action modulate the activity of a specific biological target. The definition of a mechanism of action also includes the type of activity at that biological target. For receptors, these activities include agonist, antagonist, inverse agonist, or modulator. Enzyme target mechanisms include activator or inhibitor. Ion channel modulators include opener or blocker. The following are specific examples of drug classes whose definition is based on a specific mechanism of action:
== Mode of alternative ==
This type of categorisation of drugs is from a biological perspective and categorises them by the anatomical or functional change they induce. Drug classes that are defined by common modes of action (i.e. the functional or anatomical change they induce) include:
== Therapeutic class ==
This type of categorisation of drugs is from a medical perspective and categorises them by the pathology they are used to treat. Drug classes that are defined by their therapeutic use (the pathology they are intended to treat) include:
== Amalgamated classes ==
Some drug classes have been amalgamated from these three principles to meet practical needs. The class of nonsteroidal anti-inflammatory drugs (NSAIDs) is one such example. Strictly speaking, and also historically, the wider class of anti-inflammatory drugs also comprises steroidal anti-inflammatory drugs. These drugs were in fact the predominant anti-inflammatories during the decade leading up to the introduction of the term "nonsteroidal anti-inflammatory drugs." Because of the disastrous reputation that the corticosteroids had got in the 1950s, the new term, which offered to signal that an anti-inflammatory drug was not a steroid, rapidly gained currency. The drug class of "nonsteroidal anti-inflammatory drugs" (NSAIDs) is thus composed by one element ("anti-inflammatory") that designates the mechanism of action, and one element ("nonsteroidal") that separates it from other drugs with that same mechanism of action. Similarly, one might argue that the class of disease-modifying anti-rheumatic drugs (DMARD) is composed by one element ("disease-modifying") that albeit vaguely designates a mechanism of action, and one element ("anti-rheumatic drug") that indicates its therapeutic use.
Disease-modifying antirheumatic drug (DMARD)
Nonsteroidal anti-inflammatory drug (NSAID)
== Other systems of classification ==
Other systems of drug classification exist, for example the Biopharmaceutics Classification System which determines a drugs' attributes by solubility and intestinal permeability.
== Legal classification ==
For the Canadian legal classification, see Controlled Drugs and Substances Act
For the UK legal classification, see Drugs controlled by the UK Misuse of Drugs Act
For the US legal classification, see Controlled Substances Act § Schedules of controlled substances
Pregnancy category is defined using a variety of systems by different jurisdictions
== References ==
== External links ==
"Drug Classes". Drugs.com.
"Drug names and classes". PubMed Health. United States National Library of Medicine. Retrieved 2015-11-07.
"Information by Drug Class". Drug Safety and Availability. United States Food and Drug Administration. Archived from the original on January 20, 2017. Retrieved 2015-11-07. | Wikipedia/Drug_class |
Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of use, but largely include an increased risk of gastrointestinal ulcers and bleeds, heart attack, and kidney disease.
The term non-steroidal, common from around 1960, distinguishes these drugs from corticosteroids, another class of anti-inflammatory drugs, which during the 1950s had acquired a bad reputation due to overuse and side-effect problems after their introduction in 1948.
NSAIDs work by inhibiting the activity of cyclooxygenase enzymes (the COX-1 and COX-2 isoenzymes). In cells, these enzymes are involved in the synthesis of key biological mediators, namely prostaglandins, which are involved in inflammation, and thromboxanes, which are involved in blood clotting.
There are two general types of NSAIDs available: non-selective and COX-2 selective. Most NSAIDs are non-selective, and inhibit the activity of both COX-1 and COX-2. These NSAIDs, while reducing inflammation, also inhibit platelet aggregation and increase the risk of gastrointestinal ulcers and bleeds. COX-2 selective inhibitors have fewer gastrointestinal side effects, but promote thrombosis, and some of these agents substantially increase the risk of heart attack. As a result, certain COX-2 selective inhibitors—such as rofecoxib—are no longer used due to the high risk of undiagnosed vascular disease. These differential effects are due to the different roles and tissue localisations of each COX isoenzyme. By inhibiting physiological COX activity, NSAIDs may cause deleterious effects on kidney function, and, perhaps as a result of water and sodium retention and decreases in renal blood flow, may lead to heart problems. In addition, NSAIDs can blunt the production of erythropoietin, resulting in anaemia, since haemoglobin needs this hormone to be produced.
The most prominent NSAIDs are aspirin, ibuprofen, diclofenac and naproxen; all available over the counter (OTC) in most countries. Paracetamol (acetaminophen) is generally not considered an NSAID because it has only minor anti-inflammatory activity. Paracetamol treats pain mainly by blocking COX-2 and inhibiting endocannabinoid reuptake almost exclusively within the brain, and only minimally in the rest of the body.
== Medical uses ==
NSAIDs are often suggested for the treatment of acute or chronic conditions where pain and inflammation are present. NSAIDs are generally used for the symptomatic relief of the following conditions:
=== Chronic pain and cancer-related pain ===
The effectiveness of NSAIDs for treating non-cancer chronic pain and cancer-related pain in children and adolescents is not clear. There have not been sufficient numbers of high-quality randomised controlled trials conducted.
=== Inflammation ===
Differences in anti-inflammatory activity between the various individual NSAIDs are small, but there is considerable variation among individual patients in therapeutic response and tolerance to these drugs. About 60% of patients will respond to any NSAID; of the others, those who do not respond to one may well respond to another. Pain relief starts soon after taking the first dose, and a full analgesic effect should normally be obtained within a week, whereas an anti-inflammatory effect may not be achieved (or may not be clinically assessable) for up to three weeks. If appropriate responses are not obtained within these times, another NSAID should be tried.
=== Surgical pain ===
Pain following surgery can be significant, and many people require strong pain medications such as opioids. There is some low-certainty evidence that starting NSAID painkiller medications in adults early, before surgery, may help reduce post-operative pain, and also reduce the dose or quantity of opioid medications required after surgery. Any increase risk of surgical bleeding, bleeding in the gastrointestinal system, myocardial infarctions, or injury to the kidneys has not been well studied. When used in combination with paracetamol, the analgesic effect on post-operative pain may be improved.
=== Aspirin ===
Aspirin, the only NSAID able to irreversibly inhibit COX-1, is also indicated for antithrombosis through inhibition of platelet aggregation. This is useful for the management of arterial thrombosis, and prevention of adverse cardiovascular events like heart attacks. Aspirin inhibits platelet aggregation by inhibiting the action of thromboxane A2.
=== Dentistry ===
NSAIDs are useful in the management of post-operative dental pain following invasive dental procedures such as dental extraction. When not contra-indicated, they are favoured over the use of paracetamol alone due to the anti-inflammatory effect they provide. There is weak evidence suggesting that taking pre-operative analgesia can reduce the length of post operative pain associated with placing orthodontic spacers under local anaesthetic.
=== Alzheimer's disease ===
Based on observational studies and randomized controlled trials, NSAID use is not effective for the treatment or prevention of Alzheimer's disease.
== Contraindications ==
NSAIDs may be used with caution by people with the following conditions:
Persons who are over age 50, and who have a family history of gastrointestinal (GI) problems
Persons who have had previous gastrointestinal problems from NSAID use
NSAIDs should usually be avoided by people with the following conditions:
== Adverse effects ==
The widespread use of NSAIDs has meant that the adverse effects of these drugs have become increasingly common. Use of NSAIDs increases risk of a range of gastrointestinal (GI) problems, kidney disease and adverse cardiovascular events. As commonly used for post-operative pain, there is evidence of increased risk of kidney complications. Their use following gastrointestinal surgery remains controversial, given mixed evidence of increased risk of leakage from any bowel anastomosis created.
An estimated 10–20% of people taking NSAIDs experience indigestion. In the 1990s, high doses of prescription NSAIDs were associated with serious upper gastrointestinal adverse events, including bleeding.
NSAIDs, like all medications, may interact with other medications. For example, concurrent use of NSAIDs and quinolone antibiotics may increase the risk of quinolones' adverse central nervous system effects, including seizure.
There is an argument over the benefits and risks of NSAIDs for treating chronic musculoskeletal pain. Each drug has a benefit-risk profile and balancing the risk of no treatment with the competing potential risks of various therapies should be considered. For people over the age of 65 years old, the balance between the benefits of pain-relief medications such as NSAIDS and the potential for adverse effects has not been well determined.
There is some evidence suggesting that, for some people, use of NSAIDs (or other anti-inflammatories) may contribute to the initiation of chronic pain.
Side effects are dose-dependent, and in many cases severe enough to pose the risk of ulcer perforation, upper gastrointestinal bleeding, and death, limiting the use of NSAID therapy. An estimated 10–20% of NSAID patients experience dyspepsia, and NSAID-associated upper gastrointestinal adverse events are estimated to result in 103,000 hospitalizations and 16,500 deaths per year in the United States, and represent 43% of drug-related emergency visits. Many of these events are avoidable; a review of physician visits and prescriptions estimated that unnecessary prescriptions for NSAIDs were written in 42% of visits.
Aspirin should not be taken by people who have salicylate intolerance or a more generalized drug intolerance to NSAIDs, and caution should be exercised in those with asthma or NSAID-precipitated bronchospasm. Owing to its effect on the stomach lining, manufacturers recommend people with peptic ulcers, mild diabetes, or gastritis seek medical advice before using aspirin. Use of aspirin during dengue fever is not recommended owing to increased bleeding tendency. People with kidney disease, hyperuricemia, or gout should not take aspirin because it inhibits the kidneys' ability to excrete uric acid, and thus may exacerbate these conditions.
=== Combinational risk ===
If a COX-2 inhibitor is taken, a traditional NSAID (prescription or over-the-counter) should not be taken at the same time.
Rofecoxib (Vioxx) was shown to produce significantly fewer gastrointestinal adverse drug reactions (ADRs) compared with naproxen. The study, the VIGOR trial, raised the issue of the cardiovascular safety of the coxibs (COX-2 inhibitors). A statistically significant increase in the incidence of myocardial infarctions was observed in patients on rofecoxib. Further data, from the APPROVe trial, showed a statistically significant relative risk of cardiovascular events of 1.97 versus placebo—which caused a worldwide withdrawal of rofecoxib in October 2004.
Use of methotrexate together with NSAIDs in rheumatoid arthritis is safe, if adequate monitoring is done.
=== Cardiovascular ===
NSAIDs, aside from aspirin, increase the risk of myocardial infarction and stroke. This occurs at least within a week of use. They are not recommended in those who have had a previous heart attack as they increase the risk of death or recurrent MI. Evidence indicates that naproxen may be the least harmful out of these.
NSAIDs aside from (low-dose) aspirin are associated with a doubled risk of heart failure in people without a history of cardiac disease. In people with such a history, use of NSAIDs (aside from low-dose aspirin) was associated with a more than 10-fold increase in heart failure. If this link is proven causal, researchers estimate that NSAIDs would be responsible for up to 20 percent of hospital admissions for congestive heart failure. In people with heart failure, NSAIDs increase mortality risk (hazard ratio) by approximately 1.2–1.3 for naproxen and ibuprofen, 1.7 for rofecoxib and celecoxib, and 2.1 for diclofenac.
On 9 July 2015, the Food and Drug Administration (FDA) toughened warnings of increased heart attack and stroke risk associated with nonsteroidal anti-inflammatory drugs (NSAIDs) other than aspirin.
=== Possible erectile dysfunction risk ===
A 2005 Finnish survey study found an association between long term (over three months) use of NSAIDs and erectile dysfunction.
A 2011 publication in The Journal of Urology received widespread publicity. According to the study, men who used NSAIDs regularly were at significantly increased risk of erectile dysfunction. A link between NSAID use and erectile dysfunction still existed after controlling for several conditions. However, the study was observational and not controlled, with low original participation rate, potential participation bias, and other uncontrolled factors. The authors warned against drawing any conclusion regarding cause.
=== Gastrointestinal ===
The main adverse drug reactions (ADRs) associated with NSAID use relate to direct and indirect irritation of the gastrointestinal (GI) tract. NSAIDs cause a dual assault on the GI tract: the acidic molecules directly irritate the gastric mucosa, and inhibition of COX-1 and COX-2 reduces the levels of protective prostaglandins. Inhibition of prostaglandin synthesis in the GI tract causes increased gastric acid secretion, diminished bicarbonate secretion, diminished mucus secretion and diminished trophic effects on the epithelial mucosa.
Common gastrointestinal side effects include:
Nausea or vomiting
Indigestion
Gastric ulceration or bleeding
Diarrhea
Clinical NSAID ulcers are related to the systemic effects of NSAID administration. Such damage occurs irrespective of the route of administration of the NSAID (e.g., oral, rectal, or parenteral) and can occur even in people who have achlorhydria.
Ulceration risk increases with therapy duration, and with higher doses. To minimize GI side effects, it is prudent to use the lowest effective dose for the shortest period of time—a practice that studies show is often not followed. Over 50% of patients who take NSAIDs have sustained some mucosal damage to their small intestine.
The risk and rate of gastric adverse effects is different depending on the type of NSAID medication a person is taking. Indomethacin, ketoprofen, and piroxicam use appear to lead to the highest rate of gastric adverse effects, while ibuprofen (lower doses) and diclofenac appear to have lower rates.
Certain NSAIDs, such as aspirin, have been marketed in enteric-coated formulations that manufacturers claim reduce the incidence of gastrointestinal ADRs. Similarly, some believe that rectal formulations may reduce gastrointestinal ADRs. However, consistent with the systemic mechanism of such ADRs, and in clinical practice, these formulations have not demonstrated a reduced risk of GI ulceration.
Numerous "gastro-protective" drugs have been developed with the goal of preventing gastrointestinal toxicity in people who need to take NSAIDs on a regular basis. Gastric adverse effects may be reduced by taking medications that suppress acid production such as proton pump inhibitors (e.g.: omeprazole and esomeprazole), or by treatment with a drug that mimics prostaglandin in order to restore the lining of the GI tract (e.g.: a prostaglandin analog misoprostol). Diarrhea is a common side effect of misoprostol; however, higher doses of misoprostol have been shown to reduce the risk of a person having a complication related to a gastric ulcer while taking NSAIDs. While these techniques may be effective, they are expensive for maintenance therapy.
Hydrogen sulfide NSAID hybrids prevent the gastric ulceration/bleeding associated with taking the NSAIDs alone. Hydrogen sulfide is known to have a protective effect on the cardiovascular and gastrointestinal system.
=== Inflammatory bowel disease ===
NSAIDs should be used with caution in individuals with inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis) due to their tendency to cause gastric bleeding and form ulceration in the gastric lining.
=== Renal ===
NSAIDs are also associated with a fairly high incidence of adverse drug reactions (ADRs) on the kidney and over time can lead to chronic kidney disease. The mechanism of these kidney ADRs is due to changes in kidney blood flow. Prostaglandins normally dilate the afferent arterioles of the glomeruli. This helps maintain normal glomerular perfusion and glomerular filtration rate (GFR), an indicator of kidney function. This is particularly important in kidney failure where the kidney is trying to maintain renal perfusion pressure by elevated angiotensin II levels. At these elevated levels, angiotensin II also constricts the afferent arteriole into the glomerulus in addition to the efferent arteriole it normally constricts. Since NSAIDs block this prostaglandin-mediated effect of afferent arteriole dilation, particularly in kidney failure, NSAIDs cause unopposed constriction of the afferent arteriole and decreased RPF (renal perfusion flow) and GFR.
Common ADRs associated with altered kidney function include:
Sodium and fluid retention
Hypertension (high blood pressure)
These agents may also cause kidney impairment, especially in combination with other nephrotoxic agents. Kidney failure is especially a risk if the patient is also concomitantly taking an ACE inhibitor (which removes angiotensin II's vasoconstriction of the efferent arteriole) and a diuretic (which drops plasma volume, and thereby RPF)—the so-called "triple whammy" effect.
In rarer instances NSAIDs may also cause more severe kidney conditions:
Interstitial nephritis
Nephrotic syndrome
Acute kidney injury
Acute tubular necrosis
Renal papillary necrosis
NSAIDs in combination with excessive use of phenacetin or paracetamol (acetaminophen) may lead to analgesic nephropathy.
=== Photosensitivity ===
Photosensitivity is a commonly overlooked adverse effect of many of the NSAIDs. The 2-arylpropionic acids are the most likely to produce photosensitivity reactions, but other NSAIDs have also been implicated including piroxicam, diclofenac, and benzydamine.
Benoxaprofen, since withdrawn due to its liver toxicity, was the most photoactive NSAID observed. The mechanism of photosensitivity, responsible for the high photoactivity of the 2-arylpropionic acids, is the ready decarboxylation of the carboxylic acid moiety. The specific absorbance characteristics of the different chromophoric 2-aryl substituents, affects the decarboxylation mechanism.
=== During pregnancy ===
While NSAIDs as a class are not direct teratogens, use of NSAIDs in late pregnancy can cause premature closure of the fetal ductus arteriosus and kidney ADRs in the fetus. Thus, NSAIDs are not recommended during the third trimester of pregnancy because of the increased risk of premature constriction of the ductus arteriosus. Additionally, they are linked with premature birth and miscarriage. Aspirin, however, is used together with heparin in pregnant women with antiphospholipid syndrome. Additionally, indomethacin can be used in pregnancy to treat polyhydramnios by reducing fetal urine production via inhibiting fetal renal blood flow.
In contrast, paracetamol (acetaminophen) is regarded as being safe and well tolerated during pregnancy, but Leffers et al. released a study in 2010, indicating that there may be associated male infertility in the unborn. Doses should be taken as prescribed, due to risk of liver toxicity with overdoses.
In France, the country's health agency contraindicates the use of NSAIDs, including aspirin, after the sixth month of pregnancy.
In October 2020, the U.S. Food and Drug Administration (FDA) required the drug label to be updated for all nonsteroidal anti-inflammatory medications, to describe the risk of kidney problems in unborn babies which can then lead to low amniotic fluid levels, as a result of the use of NSAIDs. They are recommending avoiding the use of NSAIDs by pregnant women at 20 weeks or later in pregnancy.
=== Allergy and allergy-like hypersensitivity reactions ===
A variety of allergic or allergic-like NSAID hypersensitivity reactions follow the ingestion of NSAIDs. These hypersensitivity reactions differ from the other adverse reactions listed here which are toxicity reactions, i.e. unwanted reactions that result from the pharmacological action of a drug, are dose-related, and can occur in any treated individual; hypersensitivity reactions are idiosyncratic reactions to a drug. Some NSAID hypersensitivity reactions are truly allergic in origin: 1) repetitive IgE-mediated urticarial skin eruptions, angioedema, and anaphylaxis following immediately to hours after ingesting one structural type of NSAID but not after ingesting structurally unrelated NSAIDs; and 2) Comparatively mild to moderately severe T cell-mediated delayed onset (usually more than 24 hour), skin reactions such as maculopapular rash, fixed drug eruptions, photosensitivity reactions, delayed urticaria, and contact dermatitis; or 3) far more severe and potentially life-threatening t-cell-mediated delayed systemic reactions such as the DRESS syndrome, acute generalized exanthematous pustulosis, the Stevens–Johnson syndrome, and toxic epidermal necrolysis. Other NSAID hypersensitivity reactions are allergy-like symptoms but do not involve true allergic mechanisms; rather, they appear due to the ability of NSAIDs to alter the metabolism of arachidonic acid in favor of forming metabolites that promote allergic symptoms. Affected individuals may be abnormally sensitive to these provocative metabolites or overproduce them and typically are susceptible to a wide range of structurally dissimilar NSAIDs, particularly those that inhibit COX1. Symptoms, which develop immediately to hours after ingesting any of various NSAIDs that inhibit COX-1, are: 1) exacerbations of asthmatic and rhinitis (see aspirin-exacerbated respiratory disease) symptoms in individuals with a history of asthma or rhinitis and 2) exacerbation or first-time development of wheals or angioedema in individuals with or without a history of chronic urticarial lesions or angioedema.
=== Possible effects on bone and soft tissue healing ===
It has been hypothesized that NSAIDs may delay healing from bone and soft-tissue injuries by inhibiting inflammation. On the other hand, it has also been hypothesized that NSAIDs might speed recovery from soft tissue injuries by preventing inflammatory processes from damaging adjacent, non-injured muscles.
There is moderate evidence that they delay bone healing. Their overall effect on soft-tissue healing is unclear.
=== Ototoxicity ===
Long-term use of NSAID analgesics and paracetamol is associated with an increased risk of hearing loss.
=== Other ===
The use of NSAIDs for analgesia following gastrointestinal surgery remains controversial, given mixed evidence of an increased risk of leakage from any bowel anastomosis created. This risk may vary according to the class of NSAID prescribed.
Common adverse drug reactions (ADR), other than listed above, include: raised liver enzymes, headache, dizziness. Uncommon ADRs include an abnormally high level of potassium in the blood, confusion, spasm of the airways, and rash. Ibuprofen may also rarely cause irritable bowel syndrome symptoms. NSAIDs are also implicated in some cases of Stevens–Johnson syndrome.
Most NSAIDs penetrate poorly into the central nervous system (CNS). However, the COX enzymes are expressed constitutively in some areas of the CNS, meaning that even limited penetration may cause adverse effects such as somnolence and dizziness.
NSAIDs may increase the risk of bleeding in patients with Dengue fever For this reason, NSAIDs are only available with a prescription in India.
In very rare cases, ibuprofen can cause aseptic meningitis.
As with other drugs, allergies to NSAIDs might exist. While many allergies are specific to one NSAID, up to 1 in 5 people may have unpredictable cross-reactive allergic responses to other NSAIDs as well.
=== Immune response ===
Although small doses generally have little to no effect on the immune system, large doses of NSAIDs significantly suppress the production of immune cells. As NSAIDs affect prostaglandins, they affect the production of most fast growing cells. This includes immune cells. Unlike corticosteroids, they do not directly suppress the immune system and so their effect on the immune system is not immediately obvious. They suppress the production of new immune cells, but leave existing immune cells functional. Large doses slowly reduce the immune response as the immune cells are renewed at a much lower rate. Causing a gradual reduction of the immune system, much slower and less noticeable than the immediate effect of Corticosteroids. The effect significantly increases with dosage, in a nearly exponential rate. Doubling of dose reduced cells by nearly four times. Increasing dose by five times reduced cell counts to only a few percent of normal levels. This is likely why the effect was not immediately obvious in low dose trials, as the effect is not apparent until much higher dosages are tested.
== Interactions ==
NSAIDs reduce kidney blood flow and thereby decrease the efficacy of diuretics, and inhibit the elimination of lithium and methotrexate.
NSAIDs cause decreased ability to form blood clots, which can increase the risk of bleeding when combined with other drugs that also decrease blood clotting, such as warfarin.
NSAIDs may aggravate hypertension (high blood pressure) and thereby antagonize the effect of antihypertensives, such as ACE inhibitors.
NSAIDs may interfere and reduce effectiveness of SSRI antidepressants through inhibiting TNFα and IFNγ, both of which are cytokine derivatives. NSAIDs, when used in combination with SSRIs, increase the risk of adverse gastrointestinal effects. NSAIDs, when used in combination with SSRIs, increase the risk of internal bleeding and brain hemorrhages.
Various widely used NSAIDs enhance endocannabinoid signaling by blocking the anandamide-degrading membrane enzyme fatty acid amide hydrolase (FAAH).
NSAIDs may reduce the effectiveness of antibiotics. An in-vitro study on cultured bacteria found that adding NSAIDs to antibiotics reduced their effectiveness by around 20%.
The concomitant use of NSAIDs with alcohol and/or tobacco products significantly increases the already elevated risk of peptic ulcers during NSAID therapy.
== Mechanism of action ==
Most NSAIDs act as nonselective inhibitors of the cyclooxygenase (COX) enzymes, inhibiting both the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) isoenzymes. This inhibition is competitively reversible (albeit at varying degrees of reversibility), as opposed to the mechanism of aspirin, which is irreversible inhibition. COX catalyzes the formation of prostaglandins and thromboxane from arachidonic acid (itself derived from the cellular phospholipid bilayer by phospholipase A2). Prostaglandins act (among other things) as messenger molecules in the process of inflammation. This mechanism of action was elucidated in 1970 by John Vane (1927–2004), who received a Nobel Prize for his work (see Mechanism of action of aspirin).
COX-1 is a constitutively expressed enzyme with a "house-keeping" role in regulating many normal physiological processes. One of these is in the stomach lining, where prostaglandins serve a protective role, preventing the stomach mucosa from being eroded by its own acid. COX-2 is an enzyme facultatively expressed in inflammation, and it is inhibition of COX-2 that produces the desirable effects of NSAIDs.
When nonselective COX-1/COX-2 inhibitors (such as aspirin, ibuprofen, and naproxen) lower stomach prostaglandin levels, ulcers of the stomach or duodenum and internal bleeding can result. The discovery of COX-2 led to research to the development of selective COX-2 inhibiting drugs that do not cause gastric problems characteristic of older NSAIDs.
NSAIDs have been studied in various assays to understand how they affect each of these enzymes. While the assays reveal differences, unfortunately, different assays provide differing ratios.
Paracetamol (acetaminophen) is not considered an NSAID because it has little anti-inflammatory activity. It treats pain mainly by blocking COX-2 mostly in the central nervous system, but not much in the rest of the body.
However, many aspects of the mechanism of action of NSAIDs remain unexplained, and for this reason, further COX pathways are hypothesized. The COX-3 pathway was believed to fill some of this gap but recent findings make it appear unlikely that it plays any significant role in humans and alternative explanation models are proposed.
NSAIDs interact with the endocannabinoid system and its endocannabinoids, as COX2 have been shown to utilize endocannabinoids as substrates, and may have a key role in both the therapeutic effects and adverse effects of NSAIDs, as well as in NSAID-induced placebo responses.
NSAIDs are also used in the acute pain caused by gout because they inhibit urate crystal phagocytosis besides inhibition of prostaglandin synthase.
=== Antipyretic activity ===
NSAIDs have antipyretic activity and can be used to treat fever. Fever is caused by elevated levels of prostaglandin E2 (PGE2), which alters the firing rate of neurons within the hypothalamus that control thermoregulation. Antipyretics work by inhibiting the enzyme COX, which causes the general inhibition of prostanoid biosynthesis (PGE2) within the hypothalamus. PGE2 signals to the hypothalamus to increase the body's thermal setpoint. Ibuprofen has been shown more effective as an antipyretic than paracetamol (acetaminophen).
Arachidonic acid is the precursor substrate for cyclooxygenase leading to the production of prostaglandins F, D, and E.
== Classification ==
NSAIDs can be classified based on their chemical structure or mechanism of action. Older NSAIDs were known long before their mechanism of action was elucidated and were for this reason classified by chemical structure or origin. Newer substances are more often classified by mechanism of action.
=== Salicylates ===
=== Propionic acid derivatives ===
=== Acetic acid derivatives ===
=== Enolic acid (oxicam) derivatives ===
=== Anthranilic acid derivatives (Fenamates) ===
The following NSAIDs are derived from fenamic acid, which is a derivative of anthranilic acid,: 235 which in turn is a nitrogen isostere of salicylic acid, which is the active metabolite of aspirin.: 235 : 17
=== Selective COX-2 inhibitors (Coxibs) ===
=== Sulfonanilides ===
Nimesulide (systemic preparations are banned by several countries for the potential risk of hepatotoxicity)
=== Others ===
Benzydamine (commonly branded as Tantum Verde or Difflam) is an indazole derivative with local anaesthetic and analgesic properties
Clonixin
Licofelone acts by inhibiting LOX (lipooxygenase) and COX and hence known as 5-LOX/COX inhibitor
H-harpagide in figwort or devil's claw
Some NSAIDs are also given intravenously, such as Ketorolac and Diclofenac sodium.
=== Chirality ===
Most NSAIDs are chiral molecules; diclofenac and the oxicams are exceptions. However, the majority are prepared as racemic mixtures. Typically, only a single enantiomer is pharmacologically active. For some drugs (typically profens), an isomerase enzyme in vivo converts the inactive enantiomer into the active form, although its activity varies widely in individuals. This phenomenon is likely responsible for the poor correlation between NSAID efficacy and plasma concentration observed in older studies when specific analysis of the active enantiomer was not performed.
Ibuprofen and ketoprofen are now available in single-enantiomer preparations (dexibuprofen and dexketoprofen), which purport to offer quicker onset and an improved side-effect profile. Naproxen has always been marketed as the single active enantiomer.
=== Main practical differences ===
NSAIDs within a group tend to have similar characteristics and tolerability. There is little difference in clinical efficacy among the NSAIDs when used at equivalent doses. Rather, differences among compounds usually relate to dosing regimens (related to the compound's elimination half-life), route of administration, and tolerability profile.
Regarding adverse effects, selective COX-2 inhibitors have lower risk of gastrointestinal bleeding. With the exception of naproxen, nonselective NSAIDs increase the risk of having a heart attack. Some data also supports that the partially selective nabumetone is less likely to cause gastrointestinal events.
A consumer report noted that ibuprofen, naproxen, and salsalate are less expensive than other NSAIDs, and essentially as effective and safe when used appropriately to treat osteoarthritis and pain.
== Pharmacokinetics ==
Most nonsteroidal anti-inflammatory drugs are weak acids, with a pKa of 3–5. They are absorbed well from the stomach and intestinal mucosa. They are highly protein-bound in plasma (typically >95%), usually to albumin, so that their volume of distribution typically approximates to plasma volume. Most NSAIDs are metabolized in the liver by oxidation and conjugation to inactive metabolites that typically are excreted in the urine, though some drugs are partially excreted in bile. Metabolism may be abnormal in certain disease states, and accumulation may occur even with normal dosage.
NSAIDs can also be divided into short-acting (plasma half-life less than 6 h) such as aspirin, diclofenac and ibuprofen and long-acting (half-life approximately greater than 10 h) such as naproxen, celecoxib.
== History ==
It is widely believed that naturally occurring salicin in willow trees and other plants was used by the ancients as a form of analgesic or anti-inflammatory drug, but this story, although compelling, is not entirely true. Hippocrates does not mention willow at all. Dioscorides's De materia medica was arguably the most influential herbal from Roman to Medieval times but, if he mentions willow at all (there is doubt about the identity of 'Itea'), then he used the ashes, steeped in vinegar, as a treatment for corns, which corresponds well with modern uses of salicylic acid.
Willow bark (from trees of the Salix genus) was widely known to be used as a medicine by multiple First Nations communities. The bark would be chewed or steeped in water for its pain relieving and antipyretic effects. The effects are a result of the bark's salicin content. Meadowsweet, another plant to contain salicin, has strong roots in British folk medicine for the same maladies. Willow bark was first reported in Western science by Edward Stone in 1763 as a treatment for ague (fever) according to the pseudoscientific doctrine of signatures.
In the body, salicin is turned into salicylic acid, which produces the antipyretic and analgesic effects that the plants are known for.
Salicin was first isolated by Johann Andreas Buchner in 1827. By 1829, French chemist Henri Leroux had improved the extraction process to obtain about 30g of purified salicin from 1.5 kg of willow bark. By hydrolysis, salicin releases glucose and salicyl alcohol which can be converted into salicylic acid, both in vivo and through chemical methods. In 1869, Hermann Kolbe synthesised salicylic acid, although it was too acidic for the gastric mucosa. The reaction used to synthesise aromatic acid from a phenol in the presence of CO2 is known as the Kolbe-Schmitt reaction.
By 1897, the German chemist Felix Hoffmann and the Bayer company prompted a new age of pharmacology by converting salicylic acid into acetylsalicylic acid—named aspirin by Heinrich Dreser. Other NSAIDs like ibuprofen were developed from the 1950s forward.
In 2001, NSAIDs accounted for 70,000,000 prescriptions and 30 billion over-the-counter doses sold annually in the United States.
== Veterinary use ==
Research supports the use of NSAIDs for the control of pain associated with veterinary procedures such as dehorning and castration of calves. The best effect is obtained by combining a short-term local anesthetic such as lidocaine with an NSAID acting as a longer term analgesic. However, as different species have varying reactions to different medications in the NSAID family, little of the existing research data can be extrapolated to animal species other than those specifically studied, and the relevant government agency in one area sometimes prohibits uses approved in other jurisdictions.
In the United States, meloxicam is approved for use only in canines, whereas (due to concerns about liver damage) it carries warnings against its use in cats except for one-time use during surgery. In spite of these warnings, meloxicam is frequently prescribed "off-label" for non-canine animals including cats and livestock species. In other countries, for example The European Union (EU), there is a label claim for use in cats.
== See also ==
Discovery and development of cyclooxygenase 2 inhibitors
== References ==
== External links ==
"Nonsteroidal Anti-inflammatory Drugs (NSAIDs)". U.S. Food and Drug Administration (FDA). 30 December 2020. Archived from the original on 12 June 2019. | Wikipedia/Nonsteroidal_anti-inflammatory_drug |
Polysubstance use or poly drug use refers to the use of combined psychoactive substances. Polysubstance use may be used for entheogenic, recreational, or off-label indications, with both legal and illegal substances. In many cases one drug is used as a base or primary drug, with additional drugs to leaven or compensate for the side effects, or tolerance, of the primary drug and make the experience more enjoyable with drug synergy effects, or to supplement for primary drug when supply is low.
== Combination drugs ==
Some common combinations that are used recreationally include
Dimenhydrinate (8-chlorotheophylline/diphenhydramine) – used to treat motion sickness and nausea
Adderall (dextroamphetamine sulfate/amphetamine sulfate/dextroamphetamine saccharate/amphetamine aspartate monohydrate) – treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy.
== Drug synergy ==
=== Ayahuasca ===
Some substances, such as the powerful psychedelic drug DMT, are not psychoactive when ingested alone. Ayahuasca, or pharmahuasca, notably consists of DMT combined with MAOIs that interfere with the action of the MAO enzyme and stop the breakdown in the stomach of chemical compounds, which make the DMT psychoactive. The MAOIs are also psychoactive and thus produce a polysubstance effect with the DMT. However, the MAOIs may cause combined drug intoxication with the majority of all psychoactive substances and are therefore usually only combined with DMT.
=== TOMSO ===
TOMSO is a lesser-known psychedelic drug and a substituted amphetamine. TOMSO is inactive on its own; it is activated with the consumption of alcohol.
== Proprietary blends ==
=== Pre-workout ===
Some ingredients such as caffeine, creatine and β-alanine are found in nearly all pre-workout blends, but each branded product is a "proprietary blend" with an average of 18 different ingredients, the exact composition and proportions of which can vary widely between different products. Additionally legal psychoactive substances occasionally used in these proprietary blends that are typically legal include 5-HTP, tyrosine, and yohimbine. Although these products are not banned, the Food and Drug Administration (FDA) warns consumers to be cautious when consuming pre-workout.
== Combined drug intoxication ==
Combined drug intoxication use often carries with it more risk than use of a single drug, due to an increase in side effects, and drug synergy. The potentiating effect of one drug on another is sometimes considerable and here the licit drugs and medicines – such as alcohol, nicotine and antidepressants – have to be considered in conjunction with the controlled psychoactive substances. The risk level will depend on the dosage level of both substances. If the drugs taken are illegal, they have a chance of being mixed (also known as "cutting") with other substances which dealers are reported to do to increase the perceived quantity when selling to others to increase their returns. This is particularly common with powdered drugs such as cocaine or MDMA which can be mixed with relative ease by adding another white powdery substance to the drug. This cumulative effect can lead to further unintended harm to health dependent on what is being covertly added.
=== Common combinations of drug classes ===
Alcohol combined with cannabis – known as cross-fading; may easily cause spins in people who are drunk and use potent cannabis.
Caffeinated alcoholic drinks
Nicotini: Alcohol combined with nicotine.
=== Dangerous combinations of drug classes ===
Concerns exist about a number of pharmacological pairings, especially:
Antidepressants
MAOIs combined with most drug classes, especially stimulants.
SSRIs combined with MAOIs, or opioids.
Depressants combined with depressant. For example:
Benzodiazepines can cause death when mixed with other CNS depressants such as opioids, alcohol, or barbiturates.
GHB combined with alcohol can lead to a long-lasting coma-like state (‘G-sleep’) or even accidental death, particularly in light of GHB's narrow threshold for overdose.
Depressants combined with stimulants. For example:
Alcohol and cocaine (for example coca wine) increase cardiovascular toxicity; alcohol or depressant drugs, when taken with opioids, lead to an increased risk of overdose
Opioids or cocaine taken with ecstasy or amphetamines also result in additional acute toxicity.
== Scheduling ==
Within the general concept of multiple drug use, several specific meanings of the term must be considered. At one extreme is planned use, where the effects of more than one drug are taken for a desired effect. Another type is when other drugs are used to counteract the negative side effects of a different drug (e.g. depressants are used to counteract anxiety and restlessness from taking stimulants). On the other hand, the use of several substances in an intensive and chaotic way, simultaneously or consecutively, in many cases each drug substituting for another according to availability.
== Research ==
The phenomenon is the subject of established academic literature.
A study among treatment admissions found that it is more common for younger people to report polysubstance use.
== See also ==
== References ==
== Bibliography ==
Martin, Christopher S.; Chung, Tammy; Langenbucher, James W. (2017). "Part 1: Defining and Characterizing the Nature and Extent of Substance Use Disorders – Historical and Cultural Perspectives on Substance Use and Substance Use Disorders". In Sher, Kenneth J. (ed.). The Oxford Handbook of Substance Use and Substance Use Disorders: Volume 1. Oxford Library of Psychology. Oxford and New York: Oxford University Press. pp. 27–59. doi:10.1093/oxfordhb/9780199381678.013.001. ISBN 9780199381678. LCCN 2016020729.
Anthony, James; Barondess, David A.; Radovanovic, Mirjana; Lopez-Quintero, Catalina (2017). "Part 1: Psychiatric Comorbidity – Polydrug Use: Research Topics and Issues". In Sher, Kenneth J. (ed.). The Oxford Handbook of Substance Use and Substance Use Disorders: Volume 2. Oxford Library of Psychology. Oxford and New York: Oxford University Press. pp. 27–59. doi:10.1093/oxfordhb/9780199381708.013.006. ISBN 9780199381708. LCCN 2016020729.
Hernández-Serrano, Olga; Gras, Maria E.; Font-Mayolas, Sílvia; Sullman, Mark J. M. (2016). "Part VI: Dual and Polydrug Abuse – Chapter 83: Types of Polydrug Usage". In Preedy, Victor R. (ed.). Neuropathology of Drug Addictions and Substance Misuse, Volume 3: General Processes and Mechanisms, Prescription Medications, Caffeine and Areca, Polydrug Misuse, Emerging Addictions and Non-Drug Addictions. Cambridge, Massachusetts: Academic Press, imprint of Elsevier. pp. 839–849. doi:10.1016/B978-0-12-800634-4.00083-4. ISBN 978-0-12-800634-4.
== External links ==
"The Science of Drug Use: A Resource for the Justice Sector". www.drugabuse.gov. North Bethesda, Maryland: National Institute on Drug Abuse. 26 May 2020. Retrieved 23 December 2021.
School-Based Drug Abuse Prevention: Promising and Successful Programs (PDF). Ottawa, Ontario: Public Safety Canada. 31 January 2018. ISBN 978-1-100-12181-9. Archived (PDF) from the original on 19 May 2021. Retrieved 23 December 2021. {{cite book}}: |website= ignored (help)
Sacco LN, Finklea K (3 May 2016). "Synthetic Drugs: Overview and Issues for Congress" (PDF). Washington, D.C.: Congressional Research Service. Archived (PDF) from the original on 8 December 2021. Retrieved 23 December 2021. | Wikipedia/Poly_drug_use |
The Philippine drug war, also referred to as the Philippine war on drugs, is the intensified anti-drug campaign initiated during the administration of Rodrigo Duterte, who served as President of the Philippines from June 30, 2016, to June 30, 2022. The campaign reduced the proliferation of illegal drugs in the country, but has been marred by extrajudicial killings (EJK) allegedly perpetrated by the police and unknown assailants. By 2022, the number of drug suspects killed since 2016 was officially tallied by the government as totaling 6,252; human rights organizations and academics, however, estimate that 12,000 to 30,000 civilians have been killed in the "anti-drug operations" carried out by the Philippine National Police and vigilantes.
Prior to his presidency, Duterte cautioned that the Philippines was at risk of becoming a narco-state and vowed that his government's fight against illegal drugs would be relentless. He urged the public to kill drug addicts. The anti-narcotics campaign has been condemned by media organizations and human rights groups, which reported staged crime scenes where police allegedly executed unarmed drug suspects, planting guns and drugs as evidence. Philippine authorities have denied misconduct by police.
Duterte has since admitted to underestimating the illegal drug problem when he promised to rid the country of illegal drugs within six months of his presidency, citing border control difficulties against the entry of illegal drugs due to the country's long coastline, and lamenting government officials' and law enforcers' involvement in the drug trade.
In 2022, Duterte urged his successor, Bongbong Marcos, who won the 2022 Philippine presidential election, to continue the war on drugs in "his own way" to protect the youth. Marcos declared his intention to continue the anti-narcotics campaign, but focusing more on prevention and rehabilitation. In 2024, Marcos emphasized that his administration has been following the "8 Es" for an effective strategy against illegal drugs, and that "Extermination was never one of them". Duterte later stated that Marcos' "bloodless" drug war was due to Marcos' privileged background.
Amidst congressional inquiries in 2024 into the drug war, critics began to allege that the campaign was largely used as a front ("grand budol") to benefit a drug syndicate in Davao City connected to Duterte aimed at eliminating its competition. On March 11, 2025, Duterte was arrested by police authorities based on a warrant issued by the International Criminal Court (ICC) accusing him of crimes against humanity for his central role in the drug war; he was extradited to The Hague on the same day. In the same month, Justice Secretary Jesus Crispin Remulla admitted that the justice system in the Philippines failed the EJK victims of the drug war during Duterte's presidency.
== Background ==
Owing to its geographical location, international drug syndicates use the Philippines as a transit hub for the illegal drug trade. Some local drug syndicates and gangs are also involved in narcotics, utilizing drug mules to transport small amounts of illegal drugs to other countries. In the '90s, the Philippines became a temporary theatre of the U.S.-led War on Drugs; at one point the Drug Enforcement Administration conducted their own operations in the country. The new millennium saw a boom in the illegal drug industry. In 2010 alone, a U.S. International Narcotics Control Strategy report estimated the illegal drug trade in the Philippines at $6.4 to $8.4 billion annually.
The perceived growth of illegal drugs in the Philippines led to the nomination of Rodrigo Duterte in the 2016 presidential election, owing to his time as mayor in Davao City, which was allegedly the 9th "safest city in the world" according to the non-peer-reviewed crowd-sourced rating site Numbeo. Numbeo has been criticized for inaccuracy, disinformation and being prone to manipulation, as in reality the highest number of violent incidents in the Philippines occurred in the Davao Region, with Davao City alone making up 45% of the cases in the region.
Duterte won the 2016 Philippine presidential election while promising to kill tens of thousands of criminals, with a platform that urged people to kill drug addicts. Duterte benefited from reports in the national media that he made Davao into one of the world's safest cities, which he in turn cited as justification for his drug policy, even while national police data showed that the city has had the highest murder rate and the second highest rape rate in the Philippines.
As Mayor of Davao City, Duterte was criticized by groups such as Human Rights Watch for the extrajudicial killing of hundreds of street children, petty criminals and drug users carried out by the Davao Death Squad, a vigilante group with which he was allegedly involved. Duterte has alternately confirmed and denied his involvement in the alleged Davao Death Squad killings. Cases of extrajudicial killings have long since been a problem in the Philippines even before the Duterte administration. In a research report for The Asia Foundation conducted by lawyer Al A. Parreno on the grim tradition of police executions, there had been a total of 305 incidents of extrajudicial killings with 390 victims in the country from 2001 to 2010, with only a total of 161 cases or 56% of the incidents filed for prosecution. Parreno also concluded that the number of cases could be higher.
Philippine anti-narcotic officials have admitted that Duterte used flawed and exaggerated data to support his claim that the Philippines is becoming a "narco-state". The Philippines has a low prevalence rate of drug users compared to the global average, according to the United Nations Office on Drugs and Crime. In his inaugural State of the Nation Address, Duterte claimed that data from the Philippine Drug Enforcement Agency (PDEA) showed that there were 3 million drug addicts two to three years previous, which he said may have already increased to 3.7 million. However, according to the Philippine Dangerous Drugs Board, the government drug policy-making body, 1.8 million Filipinos used illegal drugs (mostly cannabis) in 2015—the publication year of the latest official survey—a third of whom had used illegal drugs only once in the past 13 months.
== Death toll and disappearances ==
Estimates of the death toll vary. Officially, as of March 2022, 6,229 drug personalities have been killed. News organizations and human rights groups, however, claim the death toll to be over 12,000. The victims included 54 children in the first year. Opposition senators claimed that in 2018 alone over 20,000 had been killed. In February 2018, the International Criminal Court in The Hague announced a "preliminary examination" into killings linked to the Philippine drug war since at least July 1, 2016.
Based on data from the Philippine National Police (PNP) and PDEA from June 2016 to July 2019, 134,583 anti-drug operations were conducted, 193,086 people were arrested, and 5,526 suspects died during police operations. ₱34.75 billion worth of drugs were seized. 421,275 people surrendered under the PNP's Recovery and Wellness Program (219,979 PNP-initiated, 201,296 community center-supported), and 499 Reformation Centers established. On the law enforcement side, 86 personnel were killed during the drug war with 226 wounded since 2018. According to General Oscar Albayalde and the PNP, since 2019, 50 of these casualties and 144 others who were injured were police.
=== Enforced disappearances ===
According to Families of Victims of Involuntary Disappearances (FIND), of the 50 cases of disappearances under the Duterte administration, 24 cases are allegedly linked to Duterte’s war on drugs.
=== Killings beginning 2022 ===
Supporters of the drug war, such as Department of Interior and Local Government (DILG) Secretary Benhur Abalos Jr. and House Speaker Martin Romualdez, said that the campaign under Marcos had been "bloodless". However, the Dahas Project of the Third World Studies Center reported that the drug war killed 342 people in the first year of the Marcos presidency. The following year, from July 2023 to June 2024, the drug war killed 359 people. State forces were responsible for the majority of the killings during both years, according to the Dahas report. In 2022-2023, Davao Del Sur recorded the highest number of deaths related to the drug war, with 53 fatalities. In 2023-2024, Cebu recorded the highest number of similar deaths, totaling 65.
== Major events ==
=== 2016 ===
==== Prelude ====
According to policewoman Royina Garma, in May 2016 President-elect Rodrigo Duterte requested her to find a person who would help him implement the so-called "Davao model", a system used by Duterte to get rid of drug suspects in Davao City during his time as mayor, in a nationwide scale. She was allegedly requested to look for a Philippine National Police officer or an Iglesia ni Cristo member. This led to her endorsing Edilberto Leonardo for the task. This development of the war on drugs would only be publicized in the House of Representatives inquiries of late 2024.
==== Early months ====
In speeches made after his inauguration on June 30 of 2016, Duterte urged citizens to kill suspected criminals and drug addicts. He said he would order police to adopt a shoot-to-kill policy and would offer them a bounty for dead suspects. In a speech to the military leadership on July 1, Duterte addressed Communist rebels to "use your kangaroo courts to kill them to speed up the solution to our problem". On July 2, the Communist Party of the Philippines stated that it "reiterates its standing order for the NPA to carry out operations to disarm and arrest the chieftains of the biggest drug syndicates, as well as other criminal syndicates involved in human rights violations and destruction of the environment" after its political wing Bagong Alyansang Makabayan accepted Cabinet posts in the new government. On July 3, the Philippine National Police announced that they had killed 30 alleged drug dealers since Duterte was sworn in as president on June 30. They later stated they had killed 103 suspects between May 10 and July 7. On July 9, a spokesperson of the president told critics to show proof that there had been human rights violations in the drug war. Later that day, the Moro Islamic Liberation Front announced it was open to collaborate with police in the drug war. On August 3, Duterte said that the Sinaloa cartel and the Chinese triad are involved in the drug trade in the Philippines. On August 7, Duterte named more than 150 drug suspects, including local politicians, police, judges, and military personnel. On August 8, the United States expressed concern over the extrajudicial killings.
A presidential spokesperson said that Duterte welcomed a proposed congressional investigation into the extrajudicial killings to be chaired by Senator Leila de Lima, his chief critic in the government. On August 17, however, Duterte announced that de Lima had been having an affair with a married man, her driver, Ronnie Palisoc Dayan. Duterte claimed that Dayan was her collector for drug money and had also himself been using drugs.
In a news conference on August 21, Duterte announced that he had in his possession wiretaps and ATM records that confirmed his allegations. He stated: "What is really crucial here is that because of her [romantic] relationship with her driver which I termed 'immoral' because the driver has a family and wife, that connection gave rise to the corruption of what was happening inside the national penitentiary." Dismissing fears for Dayan's safety, he added, "As the President, I got this information … as a privilege. But I am not required to prove it in court. That is somebody else's business. My job is to protect public interest. She's lying through her teeth." He explained that he had acquired the new evidence from an unnamed foreign country.
On August 18, United Nations human rights experts called on the Philippines to halt extrajudicial killings. Agnes Callamard, the UN Special Rapporteur on summary executions, stated that Duterte had given a "license to kill" to his citizens by encouraging them to kill. In response, Duterte threatened to withdraw from the UN and form a separate group with African nations and China. Presidential spokesperson Ernesto Abella later clarified that the Philippines was not leaving the UN. As the official death toll reached 1,800, a congressional investigation of the killings chaired by de Lima was opened.
Then Presidential spokesperson Harry Roque stated that the government would be open to subjecting the Philippines to a probe through regular domestic channels, as long as they were competent and an unbiased rapporteur on the anti-drug campaign.
On August 23, Chito Gascon, head of the Philippine Commission on Human Rights, told the Senate committee that the International Criminal Court may have jurisdiction over the mass killings. On August 25, Duterte released a "drug matrix" that supposedly linked government officials, including de Lima, to the New Bilibid Prison drug trafficking scandal. De Lima stated that the "drug matrix" was like something drawn by a 12-year-old child. She added, "I will not dignify any further this so-called 'drug matrix', which any ordinary lawyer knows too well properly belongs in the garbage can." On August 29, Duterte called on de Lima to resign and "hang herself".
On August 25, urban poor organization Kadamay held a rally to protest the drug-war killings, particularly the killing of 5-year-old Danica May Garcia.
==== State of emergency ====
On September 3, 2016, following the September 2 bombing in Davao City that killed 14 people in the city's central business district, Duterte declared a "state of lawlessness", and on the following day signed a declaration of a "state of national emergency on account of lawless violence in Mindanao". The Armed Forces of the Philippines and the Philippine National Police were ordered to "suppress all forms of lawless violence in Mindanao" and to "prevent lawless violence from spreading and escalating elsewhere". Executive Secretary Salvador Medialdea said that the declaration "does not specify the imposition of curfews", and would remain in force indefinitely. He explained: "The recent incidents, the escape of terrorists from prisons, the beheadings, then eventually what happened in Davao. That was the basis." According to Huffington Post, the state of emergency was seen by government critics as an attempt by Duterte to "enhance his already strong hold on power and give him carte blanche to impose further measures" in the drug war.
At the 2016 ASEAN Summit, US President Barack Obama cancelled scheduled meetings with Duterte to discuss extrajudicial killings after Duterte referred to Obama as a "son of a whore."
==== Senate committee ====
On September 19, 2016, in a motion brought by senator and boxer Manny Pacquiao, the Senate voted 16–4 to remove de Lima from her position as head of the Senate committee investigating the extrajudicial killings. Duterte's allies in the Senate argued that de Lima had damaged the country's reputation by allowing the testimony of Edgar Matobato. She was replaced by Senator Richard Gordon, then a supporter of Duterte. Matobato had testified that while working for the Davao Death Squad he had killed more than 50 people. He said that he witnessed Duterte killing a government agent and had heard Duterte giving orders to carry out executions and ordering the bombing of mosques in retaliation for an attack on a cathedral.
Duterte told reporters that he wanted "a little extension of maybe another six months" for the drug war, as there were so many drug offenders and criminals that he "cannot kill them all". On the following day, a convicted bank robber and two former prison officials testified that they had paid bribes to de Lima, allegations which the senator denied. In a speech on September 20, Duterte promised to protect police in the drug war and urged them to kill drug suspects regardless of whether these latter would draw guns or not during the conduct of the police operations.
At the beginning of October, a senior police officer told The Guardian that 10 "special ops" official police death squads had been operating, each consisting of 15 police officers. The officer said that he had personally been involved in killing 87 suspects, and described how the corpses had their heads wrapped in masking tape with a cardboard placard labelling them as drug offenders so that the killing would not be investigated, and how they were dumped on roadsides (in Philippine English, as "salvage" victims). The chairman of the Philippines' Commission on Human Rights, Chito Gascon, was quoted in the report as saying: "I am not surprised, I have heard of this." The PNP declined to comment. The report stated: "although the Guardian can verify the policeman's rank and his service history, there is no independent, official confirmation for the allegations of state complicity and police coordination in mass murder."
On October 28, Datu Saudi Ampatuan mayor Samsudin Dimaukom and nine others, including his five bodyguards, were killed during an anti-illegal drug operation in Makilala, North Cotabato. According to police, the group were heavily armed and opened fire on police, who found sachets of methamphetamine at the scene. No police were injured. Dimaukom was among those named by Duterte on his "drug list" on August 7; the mayor had immediately surrendered after his implication and then returned to Datu Saudi Ampatuan after being let go.
On November 1, it was reported that the US State Department had halted the sale of 26,000 assault rifles to the PNP after opposition from the Senate Foreign Relations Committee due to concerns about human rights violations. A PNP spokesman said they had not been informed. PNP Chief Ronald dela Rosa suggested China as a possible alternative supplier. On November 7, Duterte reacted to the US decision to halt the sale by announcing that he was "ordering its cancellation".
In the early morning of November 5, Mayor of Albuera, Rolando Espinosa Sr., who had been detained at the Baybay City Sub-Provincial Jail for violation of the Comprehensive Dangerous Drugs Act of 2002, was killed in what was described as a shootout inside his jail cell with personnel from the Criminal Investigation and Detection Group (CIDG). According to the CIDG, Espinosa opened fire on police agents who were executing a search warrant for "illegal firearms." A hard drive of CCTV footage that may have contained recorded data of the shooting of Espinosa went missing, a provincial official said. Espinosa had turned himself in to the PNP after being named by Duterte as one of the personalities in his drug list in August. He was briefly released but then re-arrested for alleged drug possession. The president of the National Union of People's Lawyers, Edre Olalia, told local broadcaster TV5 that the police's version of events was "too contrived". He pointed out that a search warrant is not required to search a jail cell. "Such acts make a mockery of the law, taunt impunity and insult ordinary common sense," he said. Espinosa was the second public official to be killed in the drug war.
On the same day, following the incident, Senator Panfilo Lacson sought to resume the investigation of extrajudicial killings after it was suspended on October 3 by the Senate Committee on Justice and Human Rights.
On November 28, Duterte appeared to threaten that human rights workers would be targeted: "The human rights [defenders] say I kill. If I say: 'Okay, I'll stop'. They [drug users] will multiply. When harvest time comes, there will be more of them who will die. Then I will include you among them because you let them multiply." Amnesty International Philippines stated that Duterte was "inciting hate towards anyone who expresses dissent on his war against drugs." The National Alliance against Killings Philippines criticized Duterte's stated belief that human rights are a part of the illegal drug problem, saying his threats constitute "a declaration of an open season on human rights defenders".
On December 5, Reuters reported that of the drug suspects shot by police, 97% of them died, far more than in other countries with drug-related violence. The news agency also stated that PNP reports on these killings are "remarkably similar", almost always involving a "buy-bust" operation in which the suspect panics and shoots at the officers, who return fire, killing the suspect, and then report finding a packet of white powder and a .38 caliber revolver, often with the serial number removed. "The figures pose a powerful challenge to the official narrative that the Philippines police are only killing drug suspects in self-defense. These statistics and other evidence amassed by Reuters point in the other direction: that police are pro-actively gunning down suspects."
On December 8, the Senate Committee on Justice and Human Rights issued a report stating there was no sufficient evidence to prove the existence of a Davao Death Squad, and no proof of an imposed state-sponsored policy to commit killings "to eradicate illegal drugs in the country". Eleven senators signed the report, while senators Leila de Lima, JV Ejercito, Antonio Trillanes and Senate Minority Leader Ralph Recto did not sign the report or did not subscribe to its findings.
==== 2016 New Bilibid Prison riot ====
On early morning of September 28, 2016, a riot erupted inside Building 14 of the New Bilibid Prison. Initial reports from acting Bureau of Corrections director Rolando Asuncion stated that one inmate witnessed three other convicts, namely Peter Co, Tony Co and Vicente Sy, using methamphetamine moments before the riot started. The inmate alerted former police officer Clarence Dongail, who then entered the cell and told the three to stop. Upon returning to the common area to watch TV, Tony Co attacked Dongail, triggering the riot. Department of Justice Secretary Vitaliano Aguirre II, in his media interview, said that high-profile convict Tony Co was killed after being stabbed. Convict and alleged drug lord Jaybee Sebastian, who was also involved in the riot, Peter Co and Sy were seriously wounded and taken to a hospital; Sebastian was soon in stable condition while Peter Co was announced to be in critical condition. Dongail suffered minimal injuries.
Senator Leila de Lima claimed that the Malacañang Palace was behind the Bilibid riot incident with the aim of persuading the prison's inmates to testify against her for involvement in the alleged drug operations inside the prison. Later, in a press conference, de Lima angrily condemned the incident and challenged Duterte to arrest her.
==== Temporary cessation of police drug operations ====
Following criticism of the police over the kidnapping and killing of Jee Ick-Joo, a South Korean businessman, Duterte ordered the police to suspend drug-related operations while ordering the military and the Philippine Drug Enforcement Agency to take over. Human Rights Watch criticized the South Korean government in May 2018 for continuing to supply materials to the Philippine authorities after the death of Jee Ick-Joo.
=== 2017 ===
On January 4, 2017, a Sputnik gang member by the name of Randy Lizardo shot and killed Police Officer 1 Enrico Domingo in Tondo. Domingo, together with other PNP officers, were conducting a buy-bust operation inside Lizardo's home. As the lawmen burst inside, the gang surprised them from out of the curtains with handguns. Domingo was hit in the head and died instantly, while another, Police Officer 2 Harley Gacera, was wounded in the shoulder. Lizardo and the gang managed to get away, but Lizardo was captured nine days later while attempting to flee the city. The death of Domingo became one of the most covered cases of a police casualty in the drug war.
In March 2017, Duterte issued an executive order creating the Inter-agency Committee on Anti-illegal Drugs (ICAD), composed of 21 government entities headed by the Philippine Drug Enforcement Agency (PDEA), to lead the fight against the illegal drug trade.
==== Amnesty International investigation ====
On January 31, 2017, Amnesty International (AI) published a report of their investigation of 59 drug-related killings in 20 cities and towns, titled "'If you are poor you are killed': Extrajudicial Executions in the Philippines' 'War on Drugs'", which "details how the police have systematically targeted mostly poor and defenceless people across the country while planting 'evidence', recruiting paid killers, stealing from the people they kill and fabricating official incident reports." They stated: "Amnesty International is deeply concerned that the deliberate, widespread and systematic killings of alleged drug offenders, which appear to be planned and organized by the authorities, may constitute crimes against humanity under international law."
The Palace said that the report was wrong, and that there were no such illegal killings, stating: "As for the spate of killings, there is no such thing as state-sponsored since the police has been following the strict protocols in arresting these drug-related criminals." Presidential spokesperson Salvador Panelo said the killings were occurring because the “members of the drug syndicates are killing each other to prevent their competitors from informing the authorities which may lead to their arrest. As for those who were killed by the police, the same were made on the basis of self-defense when they employed unlawful means to resist arrest posing threat to the lives of the police officers."
President Duterte also criticized the double-standard narrative on the killings in the anti-illegal drug campaign. Months after he sat in office, Duterte said, "When you bomb a village, you intend to kill the militants, but you kill in the process the children there. Why do you say it is collateral damage to the West and to us it is murder?"
A police officer with the rank of Senior Police Officer 1, a ten-year veteran of a Metro Manila anti-illegal drugs unit, told AI that police are paid 8,000 pesos (US$161) to 15,000 pesos (US$302) per "encounter" (the term used for extrajudicial executions disguised as legitimate operations); there is no payment for making arrests. He said that some police also receive a payment from the funeral home they send the corpses to. According to two hitmen interviewed by AI, hitmen hired by police are paid 5,000 pesos (US$100) for each drug user killed and 10,000 to 15,000 pesos (US$200–300) for each "drug pusher" killed.
Family members and witnesses repeatedly contested the police description of how people were killed. Police descriptions bore striking similarities from incident to incident; official police reports in several cases documented by Amnesty International claim the suspect's gun “malfunctioned” when he tried to fire at police, after which they shot and killed him. In many instances, the police try to cover up unlawful killings or ensure convictions for those arrested during drug-related operations by planting “evidence” at crime scenes and falsifying incident reports—both practices the police officer said were common.
AI spoke to many witnesses who complained of the dehumanizing treatment of their family members. Crisis Response Director Tirana Hassan stated: "The way dead bodies are treated shows how cheaply human life is regarded by the Philippines police. Covered in blood, they are casually dragged in front of horrified relatives, their heads grazing the ground before being dumped out in the open. The people killed are overwhelmingly drawn from the poorest sections of society and include children, one of them as young as eight years old."
The report makes a series of recommendations addressed to the then-administration of Duterte and his government officials and departments. It also recommends that the International Criminal Court "initiate a preliminary examination into unlawful killings in the Philippines's violent anti-drug campaign and related crimes under the Rome Statute, including the involvement of government officials, irrespective of rank and status" if certain key steps are not going to be swiftly taken by the Duterte government.
The Guardian and Reuters stated that the report added to the evidence they had published previously about police extrajudicial executions. Presidential spokesman Ernesto Abella responded to the report by saying that Philippine Senate committee investigations had proven that there had been no state-sponsored extrajudicial killings. In an interview on February 4, Duterte told a reporter that Amnesty International was "so naive and so stupid", and "a creation of [George] Soros". He asked, "Is that the only thing you [de Lima] can produce? The report of Amnesty?"
De Lima was jailed on February 24, and awaited trial on charges related to allegations made by Duterte in August 2016. A court date was not set.
==== Arturo Lascañas ====
On February 20, Arturo Lascañas, a retired police officer, told reporters at a press conference outside the Philippine Senate building that as a leader of the Davao Death Squad he had carried out extrajudicial killings on the orders of Duterte. He said death squad members were paid 20,000 to 100,000 pesos ($400 to $2,000) per hit, depending on the importance of the target. He gave details of various killings he had carried out on Duterte's orders, including the previously unsolved murder of a radio show host critical of Duterte, and confessed to his involvement with Matobato in the bombing of a mosque on Duterte's orders. On the following day the senate voted in a private session to reopen the investigation, reportedly by a margin of ten votes to eight, with five abstentions.
On March 6, Lascañas gave evidence at the Senate committee hearing, testifying that he had killed approximately 200 criminal suspects, media figures and political opponents on Duterte's orders.
==== Allegations about police using hospitals to hide killings ====
In June 2017 Reuters reported that "Police were sending corpses to hospitals to destroy evidence at crime scenes and hide the fact that they were executing drug suspects." Doctors stated that corpses loaded onto trucks were being dumped at hospitals, sometimes after rigor mortis had already set in, with clearly fatal wounds, the victims having been shot in the chest and head at close range. Reuters examined data from two Manila police districts and found that the proportion of suspects sent to hospitals, where they were pronounced dead on arrival (DOA), increased from 13% in July 2016 to 85% in January 2017. "The totals grew along with international and domestic condemnation of Duterte's campaign," the report added.
PNP Chief dela Rosa dismissed the Reuters report, saying police tried to save the victims’ lives even after encountering violent resistance. He added that police should not be disparaged for trying to save victims and that the removal of bodies from a crime scene did not mean that a proper investigation cannot be carried out.
==== Ozamiz raid, and death of Reynaldo Parojinog ====
On July 30, Reynaldo Parojinog, the mayor of Ozamiz, was killed along with 14 others, including his wife Susan, in a raid at around 2:30 am on his home in barangay Baybay San Roque. According to police, they were serving a search warrant when Parojinog's bodyguards opened fire on them and the police officers responded by shooting back. According to police provincial chief Jaysen De Guzman, the authorities recovered grenades, ammunition and illegal drugs in the raid.
==== "One-time, big-time" operations ====
On August 16, over 32 people were killed in multiple "one-time, big-time" antidrug operations in Bulacan. In Manila, 25 people, including 11 suspected robbers, were also killed in consecutive anti-criminality operations. The multiple deaths within that one day in the large-scale antidrug operations received condemnation from human rights groups and the majority of the Senate.
==== Reshuffling of the Caloocan City Police ====
As a result of their involvement in the deaths of teenagers Kian delos Santos, Carl Angelo Arnaiz and Reynaldo de Guzman, and in robbing a drug suspect during an antidrug raid, then National Capital Region Police Office (NCRPO) chief Oscar Albayalde ordered the firing and retraining of all the members of the Caloocan City Police, with the exception of its newly appointed chief and deputy.
==== Transfer of anti-drug operations to PDEA ====
On October 12, 2017, Duterte announced the transfer of anti-drug operations to the PDEA, ending the involvement of the PNP. The announcement followed the publication of an opinion poll on October 8, which showed a drop in the president's approval rating from 66% to 48%. In a televised speech, Duterte scoffed and mocked the "bleeding hearts" who sympathized with those killed in the drug war, pointedly at the European Union, whom he accused of interfering with Philippine sovereignty.
==== Rodrigo Duterte's refutation to ASEAN representatives ====
In a speech before ASEAN representatives, Duterte refuted all extrajudicial killings related to the Philippine War on Drugs by stating that these stories only served a political agenda to demonize him. He stated that he only used his mouth to tell drug users they will be killed. He stated that "shabu" (crystal meth) users have shrunken brains, which is why they become violent and aggressive, "leading to their deaths." Duterte added that all drug pushers and their henchmen always carry their guns with them and that killing them is justifiable as to not endanger the lives of policemen. He appointed a human rights lawyer, Harry Roque, a Kabayan party-list representative, as his spokesperson. Roque stated that he will change public perception by reducing the impact of the President's statements advocating for extrajudicial killings in his war on drugs.
=== 2018 ===
In a speech on March 26, 2018, Duterte stated that human rights groups "have become unwitting tools of drug lords." Human Rights Watch rejected the claim, calling it "shockingly dangerous and shameful."
In October 2018, Duterte signed an executive order institutionalizing the Philippine Anti-Illegal Drugs Strategy, which prescribes a more balanced government approach in the fight against illegal drugs by directing all government departments and agencies, government-owned and controlled corporations, and state universities and colleges to craft their own plans relative to the strategy.
==== Consecutive assassinations of local government officials ====
The controversial Tanauan, Batangas mayor Antonio Halili was assassinated by an unknown sniper during a flag-raising ceremony on July 2, 2018, becoming the 11th local government official to be killed in the drug war. On the following day, Ferdinand Bote, mayor of General Tinio, was shot dead in his vehicle in Cabanatuan.
==== Supreme Court issuance of writs of amparo ====
After holding deliberations on petitions by the Free Legal Assistance Group and the Center for International Law, the Philippine Supreme Court in December 2017 ordered the solicitor-general to release documents related to the drug war. In January 2018, the Supreme Court granted the petitioners a writ of amparo and issued restraining orders against police officers. The spokesperson for the President said the administration would comply with the order.
The Supreme Court issued a second writ of amparo in February 2018, prohibiting the then Interior Secretary, Ismael Sueno, and police chief dela Rosa from going within one kilometer from the widow of a drug war victim killed in Antipolo, Rizal.
=== 2019 ===
A survey conducted by SWS from December 16–19, 2018, showed that 66% of Filipinos believe that drug addicts in the country have diminished substantially.
However, on March 1, 2019, results were released of an SWS survey also conducted from December 16 to 19, 2018, also on 1,440 adults nationwide, which concluded that 78% (or almost 4 out of 5 Filipinos) were worried "that they, or someone they know, will be a victim of extrajudicial killings (EJK)." Police General Oscar Albayalde, the new Philippine National Police chief, criticized the survey results, pointing out that the survey wrongly presented a question that "cannot be validated by respondents without keen awareness or understanding of EJK as we know it from Administrative Order No. 35 Series of 2012 by President [Benigno Simeon] Aquino [III]." He reiterated that "I take the latest survey results on public perception to alleged extrajudicial killing with a full cup of salt. It shouldn't be surprising that 78 percent are afraid of getting killed. Who isn't afraid to die, anyway?"
On March 14, Duterte released another list of politicians allegedly involved in the illegal drug trade. The list consisted of 45 incumbent officials: 33 mayors, eight vice mayors, three Congress representatives, one provincial board member, and one former mayor. Of all the politicians named, eight belonged to Duterte's own PDP–Laban political party. Opposition figures, such as senatorial candidates from Otso Diretso, said Duterte was using the list "to ensure their allies would win" in the May 2019 election.
On March 17, the country formally withdrew from the ICC after the country's withdrawal notification was received by the Secretary-General of the United Nations the previous year. The Republic of the Philippines announced its withdrawal from the Court on March 17, 2019. On July 18, 2023, the Appeals Chamber of the ICC confirmed the Office of the Prosecutor's recommencement of its investigation of the extrajudicial killings in the Philippine "war on drugs". There is some controversy about this judgment in respect to the effect of the Philippines' withdrawal from the Court. Commenting on the withdrawal, the Philippine Supreme Court stated in a 2021 ruling that the country still has an obligation to cooperate in the ICC proceedings.
In September 2019, Philippine authorities accused Guia Gomez-Castro, former chair of Barangay 484 in Sampaloc, Manila, as a mastermind in the "recycling" of illegal drugs law enforcers have seized. Dubbed by the authorities as a "drug queen", the PDEA added that the corrupt police officers involved had been selling Gomez-Castro's "recycled" shabu, worth ₱16.6 million, as Gomez-Castro's cohorts and that Gomez-Castro had the protection of the police officers and other politicians. On September 25, the Bureau of Immigration (BI) announced that Gomez-Castro had left the country on September 21. On the same day, Manila Mayor Isko Moreno, through Facebook live streaming, urged Gomez-Castro to surrender.
Prior to this, in November 2013, the NBI raided the house of Gomez-Castro in Barangay 484, Sampaloc, Manila, where they seized a ₱240,000-worth shabu haul. In November 2018, seven people were arrested by Tondo police during a drug operation; some of them were the chairwoman's relatives. In a text message, Castro denied the accusations against her.
On October 25, 2019, Clarin, Misamis Occidental mayor David Navarro, one of the mayors Duterte named as being involved in the illegal drug trade, was shot dead by four masked men while being transported to the prosecutor's office in Cebu City following his alleged beating of a massage therapist. Prior to his death, Cebu City police said that, according to Navarro's family, the mayor had been receiving death threats in Misamis Occidental.
The Philippines was deemed the 4th most dangerous country in the world in terms of civilian-targeted violence by a mid-2019 report by the Armed Conflict Location & Event Data Project (Acled). The report declared that 75% of the reported deaths in the country were from the war on drugs pursued by the Philippines' authorities.
==== Ninja cops controversy ====
In October 2019, PNP Chief Albayalde became the center of a controversy when he was accused of protecting so-called "ninja cops" or corrupt police officials. The "ninja cops" moniker refers to police officers who had been accused of "recycling" the illegal drugs they seized during their raids and sting operations.
On November 29, 2013, twelve police officers, led by Major Rodney Baloyo, conducted a raid in Mexico, Pampanga, and seized a 36.68 kg (80.9 lb) methamphetamine (shabu) load. Albayalde was the acting police chief of Pampanga at the time of the raid. The operation supposedly had the objective of seizing Chinese drug lord Johnson Lee, who nevertheless evaded arrest after allegedly bribing the police. The next day, on November 30, the authorities submitted the illegal drugs that they recovered as evidence. In 2019, Albayalde was accused of covering up the issue around the bribing allegation; he was also alleged to have benefited from the selling of the seized contraband. Albayalde denied the accusations.
The Makabayan bloc demanded the immediate resignation of Albayalde from his post and other officials from theirs. On October 14, Albayalde eventually resigned as the PNP chief, and Duterte expressed his disappointment over the issue.
On October 21, 2019, the PNP-CIDG filed a complaint before the Department of Justice against Albayalde and 13 of his personnel, citing a reinvestigation of the alleged recycling of around 162 kilograms of shabu that they seized, while the Senate suggested life imprisonment for the police officers. The PNP said in a statement that all the accused should "remain innocent until proven guilty."
==== Robredo's appointment as ICAD co-chairperson ====
On October 23, 2019, Vice President Leni Robredo made a statement, saying Duterte should allow the United Nations to investigate the war on drugs, adding that the campaign had been "a failure and a dent on the country's international image." Presidential spokesman Salvador Panelo slammed Robredo's remark, saying her claim "lacked factual basis." However, on October 27, Robredo clarified that she was only suggesting "tweaks" to the campaign and denied she was calling for a stop to the war on drugs.
The Dangerous Drugs Board (DDB) said that the vice president was “misled in understanding the anti-drug campaign,” adding that law enforcement is only a part of a multi-faceted dimension in addressing domestic drug issues that uses a holistic, balanced, and comprehensive approach. “While enforcement issues are more evident, we cannot discount the successes we have gained in the demand reduction part of the campaign," the DDB said. Presidential spokesperson Panelo, meanwhile, tagged Robredo's comments as “black propaganda”, as they lacked factual basis and advised the Vice President to detach herself from detractors. Panelo said that while the government is not intolerant of criticisms, Robrado's comments “become a disinformation campaign and an abuse of the freedom of speech and expression, and unproductive to the mature evolution of a democratic society, a hindrance to its progress. On November 12, 2019, former Deputy Director of Human Rights Watch's Asia division Phelim Kline made a statement addressed to Robredo, stating his recommendation of arresting Duterte "and his henchmen for inciting and instigating mass murder."
On November 4, 2019, Panelo announced that Duterte had assigned Robredo to be a co-chairperson of the Inter-Agency Committee on Anti-Illegal Drugs (ICAD), effective until the end of his term in 2022. However, on November 24, after Robredo made a number of suggestions, Duterte fired the Vice President from the post. According to Panelo, her removal was "in response to the taunt and dare" of the Vice President for Duterte "to just tell her that he wants her out."
=== 2020 ===
In January 2020, vice president Leni Robredo reported her findings and recommendations on the drug war. Using data from the Philippine National Police and the Philippine Drug Enforcement Agency, Robredo said, "In spite of all the Filipinos who were killed and all the money spent by the government, we only seized less than 1 percent in supply of shabu and money involved in illegal drugs." In December 2020, Rappler reported that "International Criminal Court (ICC) Prosecutor Fatou Bensouda said there is 'reasonable basis' to believe that crimes against humanity were committed in the killings related to President Rodrigo Duterte's war on drugs."
In June of the same year, a shooting in Parañaque left one policeman and one criminal dead, and one policeman wounded. Police Lt. Armand Melad and his group were sent to Unida and Dimasalang streets, Barangay Baclaran, to answer a complaint about loud noises from a karaoke machine. They then came across two males on a motorcycle without helmets. As they questioned the two men, an argument erupted, which led to the policemen to try to arrest the two. One of them, by the name of Moamar Sarif, stepped down from the motorcycle, drew a .40 Jericho Pistol, and opened fire. The police then grabbed their own guns, while the person on the motorcycle drove away. During the shootout, both Melad and Sarif were critically wounded, later dying in the same hospital. Police Corporal Allan Baltazar was also wounded.
August 2020 was the sight of a bloody series of killings in the province of Leyte, in which many drug dealers and users were killed. Jason Golong, a former drug pusher and user, was killed outside of the Remedios Trinidad Romualdez Hospital on Calanipawan Road, shot upon while driving his car. He was the son of former Tacloban City prosecutor Ruperto Golong and was once captured in a buy-bust operation conducted by the PDEA in 2018. Meanwhile, retired police officer and drug user Pio Molabola Peñaflor was killed in a drive-by shooting together with his son Alphy Chan Peñaflor in Palo, Leyte. In the next month, four more people were killed—namely Constantino Torre, Dennis Monteza, Ian Pat Cabredo and Maritess Pami—two of whom were former police officers. Cabredo was a former guard at the Leyte Provincial Jail and was in the police's drug suspect list before his death.
On November 24, Police Captain Ariel Ilagan of the Southern Police District was driving a Toyota Fortuner in Imus, with his family inside the car, when armed assailants on foot ambushed them, firing at the SUV with M16 rifles. The attackers then fled on board a red Toyota Innova that had no registration plate. The shooting was captured on CCTV. Ilagan was killed, while his wife and daughter sustained injuries. Ilagan previously headed the Taguig City Police's Drug Enforcement Unit and had recently been transferred to the Discipline Law and Order Section (DLOS), which handles “administrative and less grave cases” of policemen.
=== 2021 ===
January 23, 2021 saw a major gun battle between the PNP and a Mindanao drug syndicate in Maguindanao. The shootout started when a joint task force of police and Marines personnel attempted to serve a search warrant to Pendatun Adsis Talusan, a former village chief who was convicted of robbery with homicide, double frustrated murder, and illegal possession of firearms. Members of Talusan's group then holed themselves up inside an apartment where the police besieged them. During the end of the firefight, 12 syndicate members including Talusan were killed, as well as one policeman. The shootout happened only a few days after the assassination of Christopher Cuan, mayor of Libungan and a politician included in Duterte's "drug list".
On February 24, Menardo Guevarra, Duterte's second Department of Justice Secretary who had been in the post since 2018, told the press that his department had started investigating alleged police misconduct during the drug war. The DOJ believed the PNP had constantly failed to observe police protocols and ethics, due to the same similar patterns that led to deaths and lack of any ballistics tests or paraffin tests. Findings from the investigation would be forwarded to Human Rights Watch, and HRW in turn urged the DOJ to keep its promise "regarding the alleged failures of the police force in its anti-drug operations." In the same month, Leila de Lima, one of Duterte's long-time critics, was acquitted of one of the three drug charges filed against her.
In the evening of the same day, a fatal friendly fire incident happened between PNP personnel and PDEA agents near a mall in Quezon City. Both organizations were conducting separate drug operations that intertwined in the area near the Ever Gotesco Mall. A botched buy-bust operation then led to a shootout between the two groups that caused the deaths of two policemen, two PDEA agents, and one PDEA informant. Although the shootout happened near a crowded area, mall management managed to secure the civilians in the mall. During the preliminary investigation, the PNP claimed that the PDEA agents fired first. The PNP and the PDEA decided to have a joint investigation on the matter, while Police General Debold Sinas appointed the CIDG as the lead investigating body. The Department of Justice also ordered the National Bureau of Investigation to create a parallel investigation on the matter.
In June, the International Criminal Court Office of the Prosecutor applied for authorization to open an investigation into the alleged crimes against humanity committed in President Rodrigo Duterte's violent campaign against illegal drugs. It also sought to probe killings committed in Davao City from 2011 to 2016. Prosecutor Fatou Bensouda, whose term was to end a week after the investigation announcement, said a preliminary probe that began in February 2018 determined "that there is a reasonable basis to believe that the crimes against humanity of murder [have been] committed" in the Philippines since Rodrigo Duterte's presidential election win in 2016. Malacañang, through presidential spokesperson Harry Roque, responded to the claims by calling it "legally erroneous." The Philippines cut its ties with the International Criminal Court in 2018 when the Philippine Supreme Court junked petitions that challenged the country's plan to withdraw from the international tribunal. The decision to withdraw was a reaction to the ICC's 2018 preliminary inquiry into accusations that Duterte and other Philippine officials had committed mass murder and crimes against humanity in the course of the drug crackdown.
=== 2022 ===
On January 4, 2022, in his first national address of the year, President Duterte said that he would not apologize for the deaths caused by the war on drugs by his administration.
The 2022 Philippine general election took place on May 9. Duterte was limited to only a single six-year term as president and thus was ineligible to participate. Bongbong Marcos was elected as Duterte's successor, with the latter stepping down from his position on June 30. Duterte said he would still pursue his war on drugs even as a civilian after the end of his presidency.
The war on drugs was a major legacy of Duterte's presidency, being a major crackdown on illegal drugs as part of his presidential campaign back in the 2016 elections. By March 31, 2022, 1,130 drug dens and clandestine laboratories had been dismantled, 24,766 of the 42,045 barangays had been cleared of illegal drug influence, 14,888 "high-value targets" were arrested (including 527 government employees), ₱76.17 billion worth of methamnetamine were seized, and 4,307 minors (aged 4–17) had been "rescued" from the illegal drug trade. 6,241 people were killed in the 233,356 anti-illegal drug operations conducted from July 1, 2016, to March 31, 2022.
Duterte expressed willingness to be tried for his role in the war on drugs, but only in domestic courts. He refused to accept being tried by the International Criminal Court.
=== War on drugs under Marcos ===
In mid-2022, then-outgoing President Duterte advised then President-elect Bongbong Marcos to continue the former's campaign against illegal drugs, even if its continuation under Marcos would mean modifications. Marcos considered giving Duterte the role of anti-drug czar under his administration, but the latter expressed disinterest.
Among the first decisions of Marcos relating to his predecessor's campaign was establishing a stance that the Philippines would not be rejoining the International Criminal Court. Under former President Duterte, the country's membership was withdrawn from the international court in 2019 after Duterte was accused of committing crimes against humanity in relation to his campaign against illegal drugs.
Marcos announced a policy shift on the Philippines' campaign against illegal drugs. He said "drug abuse prevention and education and the improvement of rehabilitation centers will be the focus" of his own campaign. Department of the Interior and Local Government (DILG) Secretary Benjamin Abalos Jr. said that the approach of the government under his watch would be to build "airtight cases" against "big-time" drug traffickers to minimize dismissed cases.
Following the arrest of two suspected drug traffickers in separate operations in Talisay and Cebu City on July 30, which led to the seizing of ₱P8.5 million worth of methamphetamine, PNP Police Regional Office 7 chief Roque Eduardo Vega declared that "the drug war continues".
Marcos appointed his first PNP chief on August 1, 2022. The appointee, Rodolfo Azurin Jr., also believed that the war on drugs should be "relentlessly" continued but must be refined to include rehabilitation. He insisted that "killing is not the solution in drug war" and that drug lords should be arrested while communities affected by the illegal drug trade should be developed instead.
In late 2022, Human Rights Watch disputed the claim that a policy shift occurred under Marcos, citing that the PNP was undercounting war on drugs-related deaths instead of relying on data from the Dahas program of the University of the Philippines' Third World Studies Center which tallied 127 deaths from drug war incidents from July 1 to November 7. HRW disagreed with the assessment of the PNP that there were minimal deaths, even if they were to accept the police's death tally of only 46 people. Justice secretary Crispin Remulla was critical of HRW's statements, viewing it as not objective and saying it was influenced by non-government organizations sympathetic to the Communist Party of the Philippines. He insisted that extrajudicial killing is not state policy and that classifying a death arising from an anti-illegal drug operation as extrajudicial killing is wrong and misleading.
Also in November, former police chief and senator Bato dela Rosa filed a bill in the Senate proposing the decriminalization of usage of illegal drugs in a bid to decongest prisons and fill in the underutilized rehabilitation centers. This proposal was met with opposition from law enforcement agencies who believed such a move would send a "wrong signal" to people that drug abuse is alright.
On November 28, the DILG launched its Buhay Ay Ingatan, Droga'y Ayawan (BIDA; lit. 'Protect Life, Refuse Drugs') program separate from the campaign of law enforcement agencies. In coordination with local governments, the Department of Social Welfare and Development (DSWD) and the Department of Health, the DILG's program is focused on illegal drugs demand reduction and rehabilitation.
In December, Dela Rosa called for action believing there was a resurgence of drug syndicates that had come "back with a vengeance", citing two separate buy-bust operations that led to the arrest of police and PDEA agents. Dela Rosa concluded that syndicates had been emboldened to operate anew due to the departure of Duterte. In response, Interior Secretary Benhur Abalos pointed out that ₱10 billion worth of illegal drugs had been seized since the start of the Marcos administration.
In November 2024, the Department of Justice created a task force to conduct a criminal investigation into the EJKs committed in the drug war of President Duterte. It operated under the OSJPS, led by a senior assistant state prosecutor, regional prosecutor and nine National Prosecution Service members. On March 11, 2025, former president Duterte was arrested and sent to The Hague on charges related to crimes against humanity during his "war on drugs", which allegedly resulted in thousands of deaths.
==== Conviction of Caloocan policemen ====
On June 18, 2024, Caloocan Regional Trial Court, Branch 121 Presiding Judge Maria Rowena Violago Alejandria sentenced Police Master Sergeant Virgilio Cervantes and police corporals Arnel de Guzman, Johnston Alacre, and Artemio Saguros for the homicide of father and son Luis and Gabriel Bonifacio during a 2016 anti-drug operation. This marked the fourth conviction of police personnel related to Duterte's drug war, the first being the conviction around the 2018 murders of Kian delos Santos, Carl Arnaiz and Reynaldo de Guzman.
==== Quad Committee of the House of Representatives hearings ====
In August 2024, the Philippine House of Representatives set up a panel to investigate possible links between Philippine Offshore Gaming Operators (POGOs), extrajudicial killings, illegal drugs, and Chinese syndicates. The panel comprised the House's dangerous drugs committee, human rights committee, public accounts committee, and public order and safety committee. The Quad Committee held its first meeting on August 12, and held its first hearing on August 16.
==== Espenido's accusations against Senators Dela Rosa and Go ====
Also in August 2024, Jovie Espenido, a controversial police officer involved in Duterte's war on drugs, testified before the House Committee on Public Order and Safety and accused Senator Ronald dela Rosa of causing the dismissal of cases against drug lords Kerwin Espinosa and Mayor Reynaldo Parojinog. Espenido also accused senator Bong Go of sourcing intelligence funds from POGOs to fund the alleged "reward system" of Duterte's drug war. Both Dela Rosa and Go vehemently denied Espenido's claims.
== Operations ==
The Philippine National Police manages Oplan Double Barrel as part of its involvement in President Rodrigo Duterte's campaign against illegal drugs in the Philippines. It consists of two main components: Oplan Tokhang and Oplan HVT. Tokhang is characterized as the lower barrel approach while HVT, which stands for high value targets, is described as the police's high barrel approach. The operation was launched in 2016.
The Philippine police temporarily suspended its operations in October 2017 after a directive by President Duterte amidst reports of abuse by the police, with the Philippine Drug Enforcement Agency taking over as the leading agency against illegal drug activities in the country. The police resumed its operations in January 2018, but with the force officially playing a supporting role to PDEA in the campaign.
The latest iteration of Oplan Double Barrel was its Finale edition, which was launched on March 14, 2022. It is also known as the Anti-Illegal Drugs Operations Thru Reinforcement and Education (ADORE) program.
ADORE is still being implemented despite the end of Duterte's presidential term in June 2022, although his successor, President Bongbong Marcos, has indicated a policy shift towards a focus on the rehabilitation of small-time drug users. Deaths still persisted despite this. The PNP policy was placed under review in August 2024.
=== Oplan Tokhang ===
One component of the war on drugs by the administration of President Rodrigo Duterte is Oplan Tokhang, derived from the Cebuano words tuktok (knock) and hangyo (plead). As the name suggests, Oplan Tokhang involves the police visiting the houses of individuals suspected of being involved in the illegal drug trade as dealers or users, to persuade them to stop their activities and submit themselves to authority for potential rehabilitation. A more comprehensive guideline by the Philippine National Police then under the leadership of Police Chief Ronald dela Rosa was released prior to the resumption of police operations on the war on drugs in January 2019 after it was temporarily postponed. Tokhang is characterized as a Police Community Relations operation.
Under its guidelines, in a single operation, four police officers selected by the locality's police chief are designated as tokhangers to visit the suspects' houses in full uniform. They are to be accompanied by one member of the barangay, municipality, or city anti-drug abuse council, one representative from the PNP human-rights affairs office or any human rights advocate and at least one from the religious sector, and members of the media or other prominent personalities in the area. They are only allowed to enter the suspect's house upon the consent of the suspect or the house owner. The police coordinates with the Philippine Drug Enforcement Agency and the local anti-drug abuse councils for the conduct of the operations. The guidelines include the option for drug suspects to surrender themselves to the police or the barangay hall and to avail of rehabilitation. They are not required to sign any document. If the suspect refuses to surrender or engage with the visiting Oplan Tokhang team, their case is to be submitted to the Drug Enforcement Units of the PNP, which will then conduct a relevant police operation against the suspects including case build-up and negation.
The policy was first used in a more local scale in Davao, when Dela Rosa was still the police chief of the locality, leading police visits to drug suspects' houses. The word tokhang has become associated with killings related to the campaign against illegal drugs prior to the release of the guideline, prompting the PDEA chief, General Aaron Aquino, to urge the agency to discontinue the use of the word "tokhang" in reference to the government's operations.
=== Oplan HVT ===
Oplan High Value Targets (HVT) is a component of the Philippine National Police operations under Operation Double Barrel which aims to arrest and neutralize individuals whom the police allege to be involved in the country's illegal drug trade. They include drug lords and pushers who operate in groups. In its November 2016 report, the PNP Directorate for Intelligence said that of the 956 validated high-value targets identified by the national police since the start of the campaign, 23 were killed in police operations, 109 were arrested, and 361 surrendered. This accounts for over 54.6% of the total identified HVTs while another 29 targets were listed as "deaths under investigation". The PNP also reported that at least ₱1.445 billion worth of illegal drugs had been seized in the first four months of their campaign against HVTs.
The high-value targets identified by the national police include Albuera mayor Rolando Espinosa who earlier surrendered to the PNP before being killed in prison, and alleged number 2 Visayas drug lord Franz Sabalones, the brother of San Fernando, Cebu mayor Fralz Sabalones, who surrendered to the PNP after being named by President Duterte in his narco-list speech.
=== PDEA's three-pronged strategy ===
The Philippine Drug Enforcement Agency announced in 2019 that it had adopted a three-pronged strategy to enhance the Philippine government's war on drugs. These three prongs were composed of supply reduction, demand reduction, and harm reduction programs.
During the Duterte Legacy campaign launch in January 2020, PDEA claimed victory of its three-pronged approach, citing its successful activities.
Under supply reduction, PDEA and other law enforcement agencies conducted high-impact operations and arrested high-value targets. Authorities dismantled drug dens and shabu laboratories, seized billions of pesos worth of illegal drugs, and arrested over 200 thousand persons involved in illegal drugs.
Under demand reduction, advocacy campaign activities including lectures, seminars, conferences and film showings were conducted.
Under harm reduction, activities were conducted, including "Balay Silangan", a community-based reform program for surrendering drug offenders; Project "Sagip Batang Solvent", which rescued street children who were hooked on solvent-sniffing; drug-testing of public transportation drivers nationwide; and the establishment of a "Drug-Free Workplace Program" for business establishments.
Although the three-pronged approach by PDEA was only adopted in April 2019, statistics of the above activities cited under victories of the PDEA's three-pronged approach under the Duterte Legacy campaign dated back to June 2016.
== Support of non-state actors ==
Rodrigo Duterte's campaign against illegal drugs was aided by non-government organizations as well as rebel groups and vigilantes. The Communist Party of the Philippines (CPP), and its armed wing, the New People's Army (NPA), initially cooperated with the government but withdrew their support for the government's campaign in August 2016, vowing to continue their own operations against drug suspects.
The Moro Islamic Liberation Front, a rebel group in a truce with the government, forged a protocol with the Republic of the Philippines in July 2017, in which it pledged to arrest and turn over drug suspects taking refuge in the rebel group's camps and that it would allow the government to conduct its anti-drug operations in areas controlled by the group.
Killings by armed vigilantes, motorcycle-riding gunmen, and hired killers had led to accusations that the PNP had been working with these non-state actors during the campaign.
== Youth casualties ==
Children's rights non-governmental organizations reported that there were 101 child fatalities in the drug war from July 2016 through December 2018. Some children had to leave their homes and their family, fearing for their safety. Government authorities called the killings "collateral damage".
On August 23, 2016, a 5-year-old student named Danica May Garcia was killed by a stray bullet coming from unidentified gunmen in Dagupan during an "anti-drug operation". Another minor, 4-year-old Skyler Abatayo of Cebu was killed by a stray bullet from another anti-drug operation. On the same week, a 15-year-old by the name of Angelika Bonita (sometimes spelled "Angelica") was killed while riding inside the Toyota Hilux of 48-year-old narco-lawyer Rogelio Bato Jr., the attorney of Rolando Espinosa. The two were cruising in a subdivision near a mall in Marasbaras, Tacloban when they were fired upon by M16s and .45 caliber guns. Both were killed instantly. Bato and Bonita were not related, and questions surrounded their relationship. Rumors speculated that Bonita was Bato's girlfriend and that she was caught in the crossfire. In the first year of the drug war, 54 children were recorded as casualties.
On August 16, 2017, Kian Loyd delos Santos, a 17-year-old Grade 11 student, was shot dead in an antidrug operation in Caloocan. CCTV footage appeared to show Kian being dragged by two policemen. Police said they killed delos Santos in self-defense and claimed they retrieved a gun and two packets of methamphetamine. Delos Santos was the son of an overseas Filipino worker, a key demographic that supported Duterte. The teenager's death caused condemnation by senators. His funeral on August 25, attended by more than a thousand people, was to that date one of the largest protests against the drug war.
Carl Angelo Arnaiz, a 19-year-old, last found in Cainta, Rizal, was tortured and shot dead on August 17 (one day after delos Santos was killed) by police after allegedly robbing a taxi in Caloocan. His 14-year-old friend, Reynaldo de Guzman, also known by the nickname "Kulot", was stabbed to death thirty times and thrown into a creek in Gapan, Nueva Ecija. The deaths of Arnaiz and de Guzman, along with the death of delos Santos, triggered public outrage and condemnation.
Human Rights Watch repeated their call for a UN investigation. HRW Asia director Phelim Kine commented: "The apparent willingness of Philippine police to deliberately target children for execution marks an appalling new level of depravity in this so-called drug war." Duterte called the deaths of Arnaiz and de Guzman (the former being a relative of the President on his mother's side) "sabotage", claiming some groups were using the Philippine National Police to destroy his public image. Presidential spokesman Abella said, "It should not come as a surprise that these malignant elements would conspire to sabotage the president's campaign to rid the Philippines of illegal drugs and criminality," which "may include creating scenarios stoking public anger against the government."
Newly seated senator Ronald dela Rosa made a statement about the death of a 3-year-old child named Myka Ulpina who was killed in a crossfire during police operations in Rodriguez, Rizal on June 29, 2019, reacting to the incident by saying, "shit happens". It was alleged that Renato Dolofrina took his 3-year-old daughter hostage and that both were killed by the police after the father used the child as a "human shield." However, the family denied the allegations of hostage taking, insisting that the child was killed by a stray bullet. According to a police report, a police officer went undercover to buy crystal meth from Dolofrina, and that Dolofrina's companion discovered the ruse, prompting Dolofrina to grab his gun. A few days later, several militant groups and netizens, as well as opposition senators, condemned dela Rosa's remarks. The Commission on Human Rights also condemned the child's death. On July 8, 2019, dela Rosa apologized for his remarks and retracted his earlier statement, saying that the incident was "unfortunate."
On August 2, 2023, Jerhode Jemboy Baltazar, mistaken for a murderer, was shot by Navotas policemen in Barangay NBBS Kaunlaran (North Bay Boulevard South). In a 44-page decision promulgated on February 27, 2024, the Navotas Regional Trial Court, Branch 286 convicted Police Staff Sergeant Gerry Maliban of homicide and sentenced him to 4 years, 2 months, and 10 days up to six years, four months, and 20 days in prison and ordered him to pay Baltazar's heirs the sum of ₱50,000 in civil liability and ₱50,000 in moral damages. The court also convicted former Police Executive Master Sergeant Roberto Balais Jr., Police Staff Sergeant Nikko Esquilon, Police Corporal Edmark Jake Blanco, and Patrolman Benedict Mangada for the illegal discharge of firearms, with a sentence of up to 4 months and 1 day of imprisonment; former Police Staff Sergeant Antonio Bugayong was acquitted, noting that there were conflicting accounts about Bugayong firing his gun.
== Reactions ==
== Accusations of genocide ==
Many observers have compared the mass killings of alleged drug users and dealers to a genocide, and the ICC has opened a case of crimes against humanity. Writing for the Washington Post, Maia Szalavitz argued that the campaign had not had much blowback because drug users are seen by many as worthless members of society and therefore easy targets. In his book Dopeworld, former drug dealer turned author Niko Vorobyov compared the drug war to the stages of annihilation leading to the Holocaust outlined by Raul Hilberg:
Identification – singling out a group of people as subhuman (Duterte has said meth addicts have shrunken brains).
Confiscation and concentration – finding a way of taking those people's property before taking themselves away, either to prisons, concentration camps, or to a deportation destination.
Annihilation – the final solution, where the unwanted people(s) are simply exterminated.
At a press conference on September 30, 2016, Duterte appeared to make a comparison between the drug war and the Holocaust, saying "Hitler massacred three million Jews. Now there are three million drug addicts. I'd be happy to slaughter them." His remarks generated an international outcry; United States Secretary of Defense Ash Carter said the statement was "deeply troubling", and the German government told the Philippine ambassador that Duterte's remarks were "unacceptable". On October 2, Duterte announced, "I apologize profoundly and deeply to the Jewish"; but he explained, "It's not really that I said something wrong but rather they don't really want you to tinker with the memory".
St. John's University visiting professor Daniel Franklin Pilario said he needed to tell the stories of the widows and orphans, and asked theologians what theology they should do after extrajudicial killings, which was the same question the German theologians of the time asked after the Holocaust.
== Investigations and reports ==
Investigations on the drug war have been conducted by lawmakers, human rights groups, academic institutions, and the media. Philippine law-enforcement agencies launched #RealNumbersPH on May 2, 2017, to publish data and publicity related to the drug war.
In the Philippine Senate, on August 22, 2016, the Senate committee on justice and human rights opened a Senate inquiry on extrajudicial killings and police operations under the Philippine Drug War. After three public hearings, however, on September 19, the Senate ousted Senator Leila de Lima, Duterte's staunchest critic, as chair of the committee leading the investigation and replaced her with Senator Richard Gordon as the new chair.
The International Criminal Court (ICC) announced in February 2018 that it was launching a preliminary inquiry on alleged crimes done during the Philippine drug war.
Philippine Commission on Human Rights conducted investigations into the Philippine drug war. However, its investigations were "hampered by the predilection and uncooperativeness" of Philippine National Police, which denied access to evidence. The PNP cited directives by President Duterte as basis for its refusal to cooperate. In 2022, the Commission on Human Rights stated that the Duterte government "failed in its obligation to respect and protect human rights of every citizen, in particular, victims of drug-related killings."
In August 2024, four committees of House of Representatives (i.e., Dangerous Drugs, Public Order and Safety, Human Rights, and Public Accounts) began hearings on extrajudicial killings allegedly committed as part of the Philippine drug war. By mid-December 2024, the "quad committee" issued a preliminary report claiming that the anti-drug campaign was likely a front that largely benefitted a drug syndicate in Davao City connected to Duterte by eliminating its competition, stating that with the hearings, they have "started to uncover a grand criminal enterprise, and it would seem that at the center of it is former President Duterte."
After Duterte's arrest on March 11, 2025, the House stated that it may turn over drug war evidence to the ICC. On March 17, 2025, Zambales 1st district congressman and quad committee member Jay Khonghun expressed support for the ICC's upcoming trial, hoping that it will bring more evidence regarding their allegation that Duterte's drug war was "a billion-peso business" to benefit a drug syndicate in Davao City and other powerful individuals, which he dubbed a "grand budol" (lit. 'grand swindling').
The Third World Studies Center of University of the Philippines examined different sources to tally drug-related killings under President Duterte through the Dahas Project. The Dahas Project continues to track the killings under President Bongbong Marcos.
== In popular media ==
=== Television and film ===
In 2018, director Brillante Mendoza filmed Alpha: The Right to Kill, which follows themes of poverty, drugs, and corruption in the police force. In the same year, Netflix aired its first series from the Philippines entitled Amo, also made by Mendoza.
The long-running action-drama series Ang Probinsyano has also tackled the issue in its storyline. The show's portrayal of the PNP and its handling of the drug war, however, was criticized by then PNP Chief Oscar Albayalde for its alleged negative portrayal of the force. The PNP at one point also withdrew its support of the show and threatened legal action if the show's storyline was not changed. Netizens, politicians, artists and others, on the other hand, defended the show's depiction of the police force and of the drug war.
On August 1, 2018, the action film BuyBust was released; it similarly tackles the subject of the drug war. The film was released internationally and was an entry to the 2018 New York Asian Film Festival.
Also in 2018, Alyx Ayn Arumpac filmed the documentary Aswang, which frames events related to the drug war, trailing journalists and interviewing people left behind by victims. It premiered at the 2019 International Documentary Film Festival Amsterdam (IDFA) in the Netherlands.
A multi-award-winning joint production by PBS and the BBC, titled On the President's Orders; was first aired in mid-2019; it highlights to audiences in the West the war on drugs in the Philippines. The film was produced and directed by two-time Emmy Award-winning and five-time BAFTA Awards-nominated director James Jones and filmed and co-directed by Emmy Award-winner for cinematography Olivier Sarbil.
=== Music ===
In December 2016, American singer James Taylor posted on social media that he canceled his concert in Manila, which was set for February 2017, citing the increasing number of deaths related to the drug war.
"Hustisya" is a rap song about the drug war, created by a Pasay rap group called One Pro Exclusive. The song was inspired by the death of the group's friend, Micheal Siaron, whose dead body with his grieving partner was immortalized in a photograph often compared to Michelangelo's Pieta.
The 2017 song "Manila Ice" by musician Eyedress, along with its music video, depicts violence and corruption and were created as a response to the Philippine drug war.
In May 2019, the PDEA called for a ban on rapper Shanti Dope's song "Amatz" for allegedly promoting marijuana use, which is illegal in the Philippines. The Concerned Artists of the Philippines criticized the PDEA for the attempt to suppress freedom of expression. In June 2019, the National Telecommunications Commission ordered the Kapisanan ng mga Brodkaster ng Pilipinas (Association of Broadcasters of the Philippines) to stop the airing of the song.
The 2019 rap album Kolateral tells the story of the Philippine drug war through the eyes of the drug war's victims. The album features 12 songs by artists BLKD (pronounced Balakid), Calix, and others.
On December 10, 2019, Irish musician Bono of U2 sent a message to Duterte during his visit to Manila on a concert tour, saying that he "can't compromise on human rights." In a press conference, Bono said that he had been a member of Amnesty International and is "critical" when it comes to human rights. During U2's concert, the band paid tribute to important women in history during the performance of the song "Ultraviolet (Light My Way)" and included women from the Philippines, showing on a large screen pictures of former President Corazon Aquino, Rappler CEO and journalist Maria Ressa, and human rights and social justice activist Lidy Nacpil, among others.
=== Photography ===
La Pieta, or the "Philippines' Pieta", named after the sculpture by Michelangelo, refers to a photograph of Jennilyn Olayres holding the corpse of Michael Siaron, who was shot dead by unidentified assailants in Pasay, Metro Manila, on July 23, 2016. A piece of cardboard with the words "Wag tularan si Siaron dahil pusher umano" (Do not be like Siaron because they say he's a pusher) was placed on his body. The image was widely used in the national press. Malacañang alleged that the killing was committed by drug syndicates themselves. One year and three months after Siaron was killed, the police identified the suspected assailant as Nesty Santiago through a ballistic exam on the recovered firearm. Santiago was allegedly a member of a syndicate involved in robberies, car thefts, hired killings and illegal drugs. The Pasay city police declared Siaron's death as "case closed" since Santiago was himself killed in a drive-by shooting by "riding-in-tandem" assailants on December 29, 2016. No further investigation was made.
On April 11, 2017, The New York Times won a Pulitzer Prize for breaking news photography on their Philippine drug war report. The story was published on December 7, 2016, and was titled "They Are Slaughtering Us Like Animals".
A photo by Noel Celis of a body of an alleged drug dealer killed during a police anti-drug operation in Manila was selected as one of Time magazine's top 100 photos of 2017.
=== Video games ===
The war on drugs became the subject of various video games on mobile platforms where players—as caricatures of Duterte and other government officials—take on criminals through violent means. Many of these games have been removed by Apple Inc. from their App Store for having been in violation of Apple's content guidelines following an appeal by regional organization Asian Network of People Who Use Drugs. Ben Joseph Banta, a managing partner of Ranida Games, denied that their game Tsip Bato glorified violence and maintained that it discourages recreational drug use through the use of anti-drug messages incorporated in the game.
=== Contemporary art ===
In 2016, a group of artists exhibited Everyday Impunity: Ang Mga Walang Pangalan (Everyday Impunity: The Nameless Ones) during the year's Art Fair Philippines. It was curated by Erwin Romulo, with photography by Carlo Gabuco, music by Juan Miguel Sobrepeña, sound system design by Mark Laccay, and lighting design by Lyle Sacris. The exhibit revealed a wall of photographs by Gabuco, taken from his coverage of the Philippine drug war. Central to the exhibit space was a blue sofa, which was revealed to be from a crime scene where a drug suspect was shot. The spectator was invited to sit and hear the suspect's daughter, who talked about her father and their life in Payatas.
A work by muralist Archie Oclos also references the Philippine drug war. His work, entitled Ang Mamatay nang Dahil sa Iyo and displayed at the Cultural Center of the Philippines, shows a dead body wrapped in a blanket. The work consists of 20,000 black ink strokes, roughly the estimated number of drug war casualties.
=== Literature ===
An anthology of poems, titled Bloodlust: Philippine Protest Poetry (From Marcos to Duterte), was published in 2017. Edited by Alfred Yuson and Gemino Abad, the book contains works by 65 Filipino poets writing about dictatorship, mass killings, and related subjects. Reuters also covered the war on drugs with their 2018 Pulitzer Prize-winning special report, Duterte's War, written by Clare Baldwin, Andrew Marshall, and Manuel Mogato. In 2023, journalist Patricia Evangelista published her memoir about the drug war entitled Some People Need Killing.
== See also ==
=== Other drug wars ===
Bangladesh drug war
Colombian drug war
Mexican drug war
Thailand drug war
War on drugs in Ecuador
War on drugs (United States-led global campaign)
=== Related topics ===
Extrajudicial killing
2017 Bureau of Customs drug smuggling scandal
Comprehensive Dangerous Drugs Act of 2002
Illegal drug trade in the Philippines
Illegal firearm trade in the Philippines
Mega Drug Treatment and Rehabilitation Center
== Notes ==
== References ==
== External links ==
The Nightcrawlers – National Geographic documentary on the photojournalists covering the Philippine drug war (geo-locked, may require VPN)
On the President's Orders – Award-winning documentary. "A searing, on-the-ground look at President Rodrigo Duterte's deadly campaign against suspected drug dealers and users in the Philippines"
Ang Pangako – Interactive Philippine drug war victim map Archived February 18, 2019, at the Wayback Machine (click on Victims panel toggle button at upper left)
Paalam – Remembering The Victims of the Drug War
Duterte's War – Inside the bloody drug crackdown in the Philippines. Reuters series, winner of the 2018 Pulitzer Prize for International Reporting.
The Drug Archive – a data-driven examination of the Philippine anti-drug campaign
The Killing State: The Unrelenting War Against Human Rights
Summary and Extrajudicial Killings in the Philippines.pdf Archived August 19, 2019, at the Wayback Machine, A Submission to the United Nations Human Rights Council for the Universal Periodic Review of the Philippines (3rd Cycle, 27th Session, 2017), (Ateneo Human Rights Center)
The Kill List – published by the Philippine Daily Inquirer in an attempt to document the casualties of the Philippine Drug War
The Duterte list: Judges, mayors, police officials linked to drugs – A list of officials who are allegedly involved in the drug trade named by President Rodrigo Duterte on early morning of August 7, 2016. | Wikipedia/Philippine_drug_war |
The term drug paraphernalia refers to any equipment that is used to produce, conceal, and consume illicit drugs. It includes but is not limited to items such as bongs, roach clips, miniature spoons, and various types of pipes.
== Product types ==
In the United States, Under federal law the term drug paraphernalia means "any equipment, product or material of any kind which is primarily intended or designed for use in manufacturing, compounding, converting, concealing, producing, processing, preparing, injecting, ingesting, inhaling, or otherwise introducing into the human body a controlled substance."
=== Aluminum foil ===
"Chasing the dragon" (CTD) (traditional Chinese: 追龍; simplified Chinese: 追龙; pinyin: zhuī lóng; Jyutping: zeoi1 lung4), or "foily" in Australian English, refers to inhaling the vapor of a powdered psychoactive drug off a heated sheet of aluminium foil. The moving vapor is chased after with a tube (often rolled foil) through which the user inhales.
=== Banknotes (risky "drug paraphernalia") ===
Sharing snorting equipment (straws, banknotes, bullets, etc) has been linked to the transmission of hepatitis C. (Bonkovsky and Mehta) In one study, the University of Tennessee Medical Center researches warned that other blood-borne diseases such as HIV, the AIDS-causing virus, could be transmitted as well.
=== Scales ===
=== Gravity bong ===
A gravity bong, also known as a GB, bucket bong, grav, geeb, gibby, yoin, or ghetto bong, is a method of consuming smokable substances such as cannabis. The term describes both a bucket bong and a waterfall bong, since both use air pressure and water to draw smoke. A lung uses similar equipment but instead of water draws the smoke by removing a compacted plastic bag or similar from the chamber.
The bucket bong is made out of two containers, with the larger, open top container filled with water. The smaller has an attached bowl and open bottom, and the smaller is placed into the larger. Once the bowl is lit, the operator must move the small container up, causing a pressure difference. Smoke slowly fills the small jar until the user removes the bowl and inhales the contents. A waterfall bong is made up of only one container. The container must have a bowl and a small hole near the base so the water can drain easily. As the water flows out of the container, air is forced through the bowl and causes the substance to burn and accumulate smoke in the bong.
=== Love rose ===
A "love rose" is a glass tube with a paper or plastic rose inside of it, and a bit of cork or foil on the ends to keep the rose from falling out. While ostensibly intended as romantic gifts, their primary known use is as a pipe to smoke drugs such as crack cocaine or methamphetamine. They are commonly sold at convenience stores in the United States, particularly in inner-city locations.
=== Magnifying lens ===
Solar puffing (also called solar toking or taking solar hits) is the act of using the sun's rays with a magnifying lens or burning glass to heat cannabis for consumption.
=== Drug designed equipment ===
==== Bong ====
A bong (also known as a water pipe) is a filtration device generally used for smoking cannabis, tobacco, or other herbal substances.
Bongs have been in use by the Hmong in Laos and Thailand, as well all over Africa, for centuries.
==== Bulb syringe ====
==== Cocaine spoon ====
A snuff spoon is a tiny spoon used for nasal insufflation of powdered substances. In the ancient time the spoons were used to ingest psychotropic substances, in the 18th century − tobacco, in the 20th century − cocaine (the spoon is thus also known as a cocaine spoon or coke spoon). Some local statutes in the US treat this spoon as drug paraphernalia, defining it as a spoon that is too small and thus "unsuited for the typical, lawful uses of a spoon".
==== Glass blades ====
Spots (also known as spotting, knifers, knife hits, knife tokes, dots, hot knives, kitchen tracking blades, or bladers) refers to a method of smoking cannabis. Small pieces of cannabis are rolled (or simply torn from a larger bud) to form the spot.
The practice originated in the 1970s when drops or dabs of hashish oil were smoked (three dabs of hash oil were considered to be a good standard dose). Generally, the tips of two knife blades are heated, the spot or drop of hash oil, is compressed between the two blades, and the subsequent smoke is inhaled through the nose or mouth.
Another means that is gaining popularity is specially made glass presses heated with a propane or butane torch. In order to facilitate this process, a spottle (also referred to as a bowser, hooter or toker) or hitter is often, but not always, used to funnel the smoke and maximize the amount inhaled. A spottle is generally made from a funnel or cone-shaped container, such as the top (or neck) of a plastic or glass bottle or a gallon of milk/water.
==== One-hitter ====
A one-hitter has been considered drug paraphernalia in certain regions.
==== Pizzo ====
A pizzo – also known as an pilo, oil burner, bubble, tweak pipe, meth pipe, gack pipe, crank pipe, crack pipe, pookie pipe, chicken bone, or ice pipe – AKA “Billy” – is a glass pipe which consists of a tube connected to a spherical bulb with a small opening on top designed for smoking methamphetamine or freebasing crack cocaine as well as other drugs. There are some legitimate uses for these pipes including applying the hole "on the top of an eucalyptus bottle" for inhaling aromas or moisture.
==== Snuff bullets ====
==== Free base equipment ====
== Contamination ==
Sharing snorting equipment (straws, banknotes, bullets, etc) has been linked to the transmission of hepatitis C. (Bonkovsky and Mehta) In one study, the University of Tennessee Medical Center researches warned that other blood-borne diseases such as HIV, the AIDS-causing virus, could be transmitted as well.
Bongs that are cleaned regularly eliminates yeast, fungi, bacteria and pathogens that can cause several symptoms that vary from allergy to lung infection.
Re-used uncleaned vapes, and vape sharing, may cause bacterial pneumonia, fungal pneumonia, and viral pneumonia.
== Legality ==
=== United States ===
In the US, enterprising individuals would sell items openly in the street, until anti-paraphernalia laws in the 1980s eventually ended the practice. With the growth of the Internet, drug paraphernalia sellers have greatly expanded their sales to a worldwide market.
According to the Federal Drug Paraphernalia Statute, 21 USC 863, which is part of the Controlled Substances Act, in the US it is illegal to sell, transport through the mail, transport across state lines, import, or export drug paraphernalia as defined. Possession is usually illegal under State law. The law gives specific guidance on determining what constitutes drug paraphernalia. Many states have also enacted their own laws prohibiting drug paraphernalia. In the 1982 case Hoffman Estates v. The Flipside, Hoffman Estates, Inc., the US Supreme Court found a municipal ordinance requiring licensing for paraphernalia sales to have sufficiently distinguished marketing for illegal use to be constitutional. Government crackdowns have resulted in the arrest of sellers of recreational drug paraphernalia, such as actor Tommy Chong, who spent time in prison in 2003 for having his name used on bongs for sale via the internet.
Head shops are very much alive and well in the US, however. Generally, though, they have signs near presumable paraphernalia saying "For tobacco use only" or "Not for use with illicit drugs." Many also ban customers for referencing the use of illegal drugs when buying items. Similar policies are used in online head shops, where customers are often made to verify detailed disclaimers of their non-use of illegal substances before buying items.
==== Reagent testing ====
Home pill testing equipment is illegal in the US state of Illinois where the (720 ILCS 600/) Drug Paraphernalia Control Act specifically outlaws "testing equipment intended to be used unlawfully in a private home for identifying or in analyzing the strength, effectiveness or purity of cannabis or controlled substances;"
=== United Kingdom ===
In the UK, while cannabis is illegal, owning drug paraphernalia is not illegal, but under the Misuse of Drugs Act 1971, the individual may be committing a criminal offense if the items contain traces of drugs.
Under Section 9A of the Misuse of Drugs Act 1971, It is a criminal offense "to supply or offer to supply an object for providing or preparing a controlled drug if a person believes that the article will be used in circumstances where the administration is unlawful. If convicted in a magistrates' court, the penalty is a maximum of six months in prison and/or a £5,000 fine.
{{CIA World Factbook}}
=== Sweden ===
==== Injection equipment ====
In Sweden, pharmacies can only sell syringes and hypodermic needles to people with a doctor's prescription for medical use.
== See also ==
Drug checking
Harm reduction
One hitter (smoking)
Philadelphia blunt ban
Paraphernalia
Recreational drug use
== References ==
As of this edit, this article uses content from "Routes of Administration", authored by https://psychonautwiki.org/w/index.php?title=Routes_of_administration&action=history, which is licensed in a way that permits reuse under the Creative Commons Attribution-ShareAlike 4.0 International License, but not under the GFDL. All relevant terms must be followed.
== Sources ==
Childress, David Hatcher (2012). Ancient Technology in Peru & Bolivia. Adventures Unlimited Press. ISBN 978-1-935487-81-4. OCLC 788245749.
Hopkins, Tighe (1897). "The Spoon". The Leisure Hour. Vol. 47. W. Stevens, printer. pp. 51–56. OCLC 145390810. | Wikipedia/Drug_paraphernalia |
Recreational drug use is the use of one or more psychoactive drugs to induce an altered state of consciousness, either for pleasure or for some other casual purpose or pastime. When a psychoactive drug enters the user's body, it induces an intoxicating effect. Recreational drugs are commonly divided into three categories: depressants (drugs that induce a feeling of relaxation and calmness), stimulants (drugs that induce a sense of energy and alertness), and hallucinogens (drugs that induce perceptual distortions such as hallucination).
In popular practice, recreational drug use is generally tolerated as a social behaviour, rather than perceived as the medical condition of self-medication. However, drug use and drug addiction are severely stigmatized everywhere in the world. Many people also use prescribed and controlled depressants such as opioids, opiates, and benzodiazepines. What controlled substances are considered generally unlawful to possess varies by country, but usually includes cannabis, cocaine, opioids, MDMA, amphetamine, methamphetamine, psychedelics, benzodiazepines, and barbiturates. As of 2015, it is estimated that about 5% of people worldwide aged 15 to 65 (158 million to 351 million) had used controlled drugs at least once.
Common recreational drugs include caffeine, commonly found in coffee, tea, soft drinks, and chocolate; alcohol, commonly found in beer, wine, cocktails, and distilled spirits; nicotine, commonly found in tobacco, tobacco-based products, and electronic cigarettes; cannabis and hashish (with legality of possession varying inter/intra-nationally); and the controlled substances listed as controlled drugs in the Single Convention on Narcotic Drugs (1961) and the Convention on Psychotropic Substances (1971) of the United Nations (UN). Since the early 2000s, the European Union (EU) has developed several comprehensive and multidisciplinary strategies as part of its drug policy in order to prevent the diffusion of recreational drug use and abuse among the European population and raise public awareness on the adverse effects of drugs among all member states of the European Union, as well as conjoined efforts with European law enforcement agencies, such as Europol and EMCDDA, in order to counter organized crime and illegal drug trade in Europe.
== Reasons for use ==
Many researchers have explored the etiology of recreational drug use. Some of the most common theories are: genetics, personality type, psychological problems, self-medication, sex, age, depression, curiosity, boredom, rebelliousness, a sense of belonging to a group, family and attachment issues, history of trauma, failure at school or work, socioeconomic stressors, peer pressure, juvenile delinquency, availability, historical factors, or socio-cultural influences. There has been no consensus on a single cause. Instead, experts tend to apply the biopsychosocial model. Any number of factors may influence an individual's drug use, as they are not mutually exclusive. Regardless of genetics, mental health, or traumatic experiences, social factors play a large role in the exposure to and availability of certain types of drugs and patterns of use.
According to addiction researcher Martin A. Plant, some people go through a period of self-redefinition before initiating recreational drug use. They tend to view using drugs as part of a general lifestyle that involves belonging to a subculture that they associate with heightened status and the challenging of social norms. Plant states: "From the user's point of view there are many positive reasons to become part of the milieu of drug taking. The reasons for drug use appear to have as much to do with needs for friendship, pleasure and status as they do with unhappiness or poverty. Becoming a drug taker, to many people, is a positive affirmation rather than a negative experience".
=== Evolution ===
Anthropological research has suggested that humans "may have evolved to counter-exploit plant neurotoxins". The ability to use botanical chemicals to serve the function of endogenous neurotransmitters may have improved survival rates, conferring an evolutionary advantage. A typically restrictive prehistoric diet may have emphasized the apparent benefit of consuming psychoactive drugs, which had themselves evolved to imitate neurotransmitters. Chemical–ecological adaptations and the genetics of hepatic enzymes, particularly cytochrome P450, have led researchers to propose that "humans have shared a co-evolutionary relationship with psychotropic plant substances that is millions of years old."
== Health risks ==
The severity of impact and type of risks that come with recreational drug use vary widely with the drug in question and the amount being used. There are many factors in the environment and within the user that interact with each drug differently. Alcohol is sometimes considered one of the most dangerous recreational drugs. Alcoholic drinks, tobacco products and other nicotine-based products (e.g., electronic cigarettes), and cannabis are regarded by various medical professionals as the most common and widespread gateway drugs. In the United States, Australia, and New Zealand, the general onset of drinking alcohol, tobacco smoking, cannabis smoking, and consumption of multiple drugs most frequently occurs during adolescence and in middle school and secondary school settings.
Some scientific studies in the early 21st century found that a low to moderate level of alcohol consumption, particularly of red wine, might have substantial health benefits such as decreased risk of cardiovascular diseases, stroke, and cognitive decline. This claim has been disputed, specifically by British researcher David Nutt, professor of neuropsychopharmacology at the Imperial College London, who stated that studies showing benefits for "moderate" alcohol consumption in "some middle-aged men" lacked controls for the variable of what the subjects were drinking beforehand. Experts in the United Kingdom have suggested that some psychoactive drugs that may be causing less harm to fewer users (although they are also used less frequently in the first place) are cannabis, psilocybin mushrooms, LSD, and MDMA; however, these drugs have risks and side effects of their own.
=== Drug harmfulness ===
Drug harmfulness is defined as the degree to which a psychoactive drug has the potential to cause harm to the user and is measured in several ways, such as by addictiveness and the potential for physical harm. More objectively harmful drugs may be colloquially referred to as "hard drugs", and less harmful drugs as "soft drugs". The term "soft drug" is considered controversial by critics as it may imply the false belief that soft drugs cause lesser or insignificant harm.
=== Responsible use ===
Responsible drug use advocates that users should not take drugs at the same time as activities such as driving, swimming, operating machinery, or other activities that are unsafe without a sober state. Responsible drug use is emphasized as a primary prevention technique in harm-reduction drug policies. Harm-reduction policies were popularized in the late 1980s, although they began in the 1970s counter-culture, through cartoons explaining responsible drug use and the consequences of irresponsible drug use to users. Another issue is that the illegality of drugs causes social and economic consequences for users—the drugs may be "cut" with adulterants and the purity varies wildly, making overdoses more likely—and legalization of drug production and distribution could reduce these and other dangers of illegal drug use.
== Prevention ==
In efforts to curtail recreational drug use, governments worldwide introduced several laws prohibiting the possession of almost all varieties of recreational drugs during the 20th century. The "War on Drugs" promoted by the United States, however, is now facing increasing criticism. Evidence is insufficient to tell if behavioral interventions help prevent recreational drug use in children.
One in four adolescents has used an illegal drug, and one in ten of those adolescents who need addiction treatment get some type of care. School-based programs are the most commonly used method for drug use education; however, the success rates of these intervention programs are highly dependent on the commitment of participants and are limited in general.
== Demographics ==
=== Australia ===
Alcohol is the most widely used recreational drug in Australia. 86.2% of Australians aged 12 years and over have consumed alcohol at least once in their lifetime, compared to 34.8% of Australians aged 12 years and over who have used cannabis at least once in their lifetime.
=== United States ===
From the mid-19th century to the 1930s, American physicians prescribed Cannabis sativa as a prescription drug for various medical conditions. In the 1960s, the counterculture movement introduced the use of psychoactive drugs, including cannabis. Young adults and college students reported the recreational prevalence of cannabis, among other drugs, at 20-25% while the cultural mindset of using was open and curious. In 1969, the FBI reported that between the years 1966 and 1968, the number of arrests for marijuana possession, which had been outlawed throughout the United States under Marijuana Tax Act of 1937, had increased by 98%. Despite acknowledgement that drug use was greatly growing among America's youth during the late 1960s, surveys have suggested that only as much as 4% of the American population had ever smoked marijuana by 1969. By 1972, however, that number would increase to 12%. That number would then double by 1977.
The Controlled Substances Act of 1970 classified marijuana along with heroin and LSD as a Schedule I drug, i.e., having the relatively highest abuse potential and no accepted medical use. Most marijuana at that time came from Mexico, but in 1975 the Mexican government agreed to eradicate the crop by spraying it with the herbicide paraquat, raising fears of toxic side effects. Colombia then became the main supplier. The "zero tolerance" climate of the Reagan and Bush administrations (1981–1993) resulted in passage of strict laws and mandatory sentences for possession of marijuana. The "War on Drugs" thus brought with it a shift from reliance on imported supplies to domestic cultivation, particularly in Hawaii and California. Beginning in 1982, the Drug Enforcement Administration turned increased attention to marijuana farms in the United States, and there was a shift to the indoor growing of plants specially developed for small size and high yield. After over a decade of decreasing use, marijuana smoking began an upward trend once more in the early 1990s, especially among teenagers, but by the end of the decade this upswing had leveled off well below former peaks of use.
== Society and culture ==
Many movements and organizations are advocating for or against the liberalization of the use of recreational drugs, most notably regarding the legalization of marijuana and cannabinoids for medical and/or recreational use. Subcultures have emerged among users of recreational drugs, as well as alternative lifestyles and social movements among those who abstain from them, such as teetotalism and "straight edge".
Since the early 2000s, medical professionals have acknowledged and addressed the problem of the increasing consumption of alcoholic drinks and club drugs (such as MDMA, cocaine, rohypnol, GHB, ketamine, PCP, LSD, and methamphetamine) associated with rave culture among adolescents and young adults in the Western world. Studies have shown that adolescents are more likely than young adults to use multiple drugs, and the consumption of club drugs is highly associated with the presence of criminal behaviors and recent alcohol abuse or dependence.
The prevalence of recreational drugs in human societies is widely reflected in fiction, entertainment, and the arts, subject to prevailing laws and social conventions. For instance, in the music industry, the musical genres hip hop, hardcore rap, and trap, alongside their derivative subgenres and subcultures, are most notorious for having continuously celebrated and promoted drug trafficking, gangster lifestyle, and consumption of alcohol and other drugs since their inception in the United States during the late 1980s–early 1990s. In video games, for example, drugs are portrayed in a variety of ways: including power-ups (cocaine gum replenishes stamina in Red Dead Redemption 2), obstacles to be avoided (such as the Fuzzies in Super Mario World 2: Yoshi's Island that distort the player's view when accidentally consumed), items to be bought and sold for in-game currency (coke dealing is a big part of Scarface: The World Is Yours). In the Fallout video game franchise, drugs ("chems" in the game) can fill the role of any above mentioned. Drug trafficking, gang rivalries, and their related criminal underworld also play a big part in the Grand Theft Auto video game franchise.
== Common recreational drugs ==
The following substances are commonly used recreationally:
Alcohol: Most drinking alcohol is ethanol, CH3CH2OH. Drinking alcohol creates intoxication, relaxation and lowered inhibitions. It is produced by the fermentation of sugars by yeasts to create wine, beer, and distilled liquor (e.g., vodka, rum, gin, etc.). In most areas of the world, it is legal for those over a certain age (18 in most countries). It is an IARC Group 1 carcinogen and a teratogen. Alcohol withdrawal can be life-threatening.
Amphetamines: Used recreationally to provide alertness and a sense of energy. Prescribed for ADHD, narcolepsy, depression, and weight loss. A potent central nervous system stimulant, in the 1940s and 50s methamphetamine was used by Axis and Allied troops in World War II, and, later on, other armies, and by Japanese factory workers. It increases muscle strength and fatigue resistance and improves reaction time. Methamphetamine use can be neurotoxic, which means it damages dopamine neurons. As a result of this brain damage, chronic use can lead to post acute withdrawal syndrome.
Caffeine: Often found in coffee, black tea, energy drinks, some soft drinks (e.g., Coca-Cola, Pepsi, and Mountain Dew, among others), and chocolate. It is the world's most widely consumed psychoactive drug, but has only mild dependence liability for long-term users.
Cannabis: Its common forms include marijuana and hashish, which are smoked, vaporized or eaten. It contains at least 85 cannabinoids. The primary psychoactive component is THC, which mimics the neurotransmitter anandamide, named after the Hindu ananda, "joy, bliss, delight". When cannabis is eaten, THC metabolized into 11-OH-THC, this molecule is the primary psychoactive compound of edible forms of cannabis. THC and 11-OH-THC are partial agonist at CB1 and CB2 receptors of the endocannabinoid system.
Cocaine: It is available as a white powder, which is insufflated ("sniffed" into the nostrils) or converted into a solution with water and injected. A popular derivative, crack cocaine is typically smoked. When transformed into its freebase form, crack, the cocaine vapour may be inhaled directly. This is thought to increase bioavailability, but has also been found to be toxic, due to the production of methylecgonidine during pyrolysis.
MDMA: Commonly known as ecstasy, it is a common club drug in the rave scene.
Ketamine: An anesthetic used legally by paramedics and doctors in emergency situations for its dissociative and analgesic qualities and illegally in the club drug scene.
Lean: A liquid drug mixture made when mixing cough syrup, sweets, soft drinks and codeine. It originated in the 1990s in Houston. Ever since then, this drug usage has grown and is often used at parties and in the trap music scene. Many people would get a drowsy feeling when consuming this drug.
LSD: A popular ergoline derivative, that was first synthesized in 1938 by Albert Hofmann. However, he failed to notice its psychedelic effects until 1943. It's a serotonergic psychedelic (partial agonist at serotonin receptors, particularly the 5-HT2A subtypes) like psilocin, mescaline and DMT. But LSD is unique because it is also a partial agonist of dopamine and norepinephrine receptors, particularly the D2R subtypes. LSD (d-Lysergic Acid Diethylamide) is a molecule of the lysergamide family, a subclass of the tryptamine family. In the 1950s, it was used in psychological therapy, and, covertly, by the CIA in Project MKULTRA, in which the drug was administered to unwitting US and Canadian citizens. It played a central role in 1960s 'counter-culture', and was banned in October 1968 by US President Lyndon B Johnson.
Nitrous oxide: legally used by dentists as an anxiolytic and anaesthetic, it is also used recreationally by users who obtain it from whipped cream canisters (whippets or whip-its) (see inhalant), as it causes perceptual effects, a "high" and at higher doses, hallucinations.
Opiates and opioids: Available by prescription for pain relief. Commonly used opioids include oxycodone, hydrocodone, codeine, fentanyl, heroin, methadone, and morphine. Opioids have a high potential for addiction and have the ability to induce severe physical withdrawal symptoms upon cessation of frequent use. Heroin can be smoked, insufflated, or turned into a solution with water and injected. Percocet is a prescription opioid containing oxycodone and acetaminophen.
Psilocybin mushrooms: This hallucinogenic drug was an important drug in the psychedelic scene. Until 1963, when it was chemically analysed by Albert Hofmann, it was completely unknown to modern science that Psilocybe semilanceata ("Liberty Cap", common throughout Europe) contains psilocybin, a hallucinogen previously identified only in species native to Mexico, Asia, and North America.
Tobacco: Nicotiana tabacum. Nicotine is the key drug contained in tobacco leaves, which are either smoked, chewed or snuffed. It contains nicotine, which crosses the blood–brain barrier in 10–20 seconds. It mimics the action of the neurotransmitter acetylcholine at nicotinic acetylcholine receptors in the brain and the neuromuscular junction. The neuronal forms of the receptor are present both post-synaptically (involved in classical neurotransmission) and pre-synaptically, where they can influence the release of multiple neurotransmitters.
Tranquilizers: barbiturates, benzodiazepines (e.g. alprazolam, diazepam, etc.)(commonly prescribed for anxiety disorders; known to cause dementia and post acute withdrawal syndrome)
"Bath salts": slang term that generally refers to substituted cathinones such as Mephedrone and Methylenedioxypyrovalerone (MDPV), but not always
DMT – primary ingredient in ayahuasca, can also be smoked (inhalation causes a brief effect lasting usually 5 to 15 minutes).
Peyote: This hallucinogen contains mescaline, native to southwestern Texas and Mexico. Echinopsis pachanoi is a faster growing cactus containing mescaline. It is one of the few narcotics legally available in the United States for religious purposes by the Native American Church.
Salvia divinorum: This hallucinogenic Mexican herb in the mint family; not considered recreational, most likely due to the nature of the hallucinations (legal in some jurisdictions)
Synthetic cannabis: "Spice", "K2", JWH-018, AM-2201
Quaaludes: A popular club drug in the 1970s. No longer prescribed or manufactured in many countries but remains popular in South Africa.
== Routes of administration ==
Drugs are often associated with a particular route of administration. Many drugs can be consumed in more than one way. For example, marijuana can be swallowed like food or smoked, and cocaine can be "sniffed" in the nostrils, injected, or, with various modifications, smoked.
inhalation: all intoxicative inhalants (see below) that are gases or solvent vapours that are inhaled through the trachea, as the name suggests
insufflation: also known as "snorting", or "sniffing", this method involves the user placing a powder in the nostrils and breathing in through the nose, so that the drug is absorbed by the mucous membranes. Drugs that are "snorted", or "sniffed", include powdered amphetamines, cocaine, heroin, ketamine, MDMA, and snuff tobacco.
Subcutaneous injection (see also the article Skin popping): injection of drug into the third lowest layer of skin.
Intramuscular injection: injection of drug into a muscle.
intravenous injection (see also the article Drug injection): the user injects a solution of water and the drug into a vein, or less commonly, into the tissue. Drugs that are injected include morphine and heroin, less commonly other opioids. Stimulants like cocaine or methamphetamine may also be injected. In rare cases, users inject other drugs.
oral intake: caffeine, ethanol, cannabis edibles, psilocybin mushrooms, coca tea, poppy tea, laudanum, GHB, ecstasy pills with MDMA or various other substances (mainly stimulants and psychedelics), prescription and over-the-counter drugs (ADHD and narcolepsy medications, benzodiazepines, anxiolytics, sedatives, cough suppressants, morphine, codeine, opioids and others)
sublingual: substances diffuse into the blood through tissues under the tongue. Many psychoactive drugs can be or have been specifically designed for sublingual administration, including barbiturates, benzodiazepines, opioid analgesics with poor gastrointestinal bioavailability, LSD blotters, coca leaves, some hallucinogens. This route of administration is activated when chewing some forms of smokeless tobacco (e.g. dipping tobacco, snus).
intrarectal ("plugging"): administering into the rectum, most water-soluble drugs can be used this way.
smoking (see also the section below): tobacco, cannabis, opium, crystal meth, phencyclidine, crack cocaine, and heroin (diamorphine as freebase) known as chasing the dragon.
transdermal patches with prescription drugs: e.g. methylphenidate (Daytrana) and fentanyl.
Many drugs are taken through various routes. Intravenous route is the most efficient, but also one of the most dangerous. Nasal, rectal, inhalation and smoking are safer. The oral route is one of the safest and most comfortable, but of little bioavailability.
== Types ==
=== Depressants ===
Depressants are psychoactive drugs that temporarily diminish the function or activity of a specific part of the body or mind. Colloquially, depressants are known as "downers", and users generally take them to feel more relaxed and less tense. Examples of these kinds of effects may include anxiolysis, sedation, and hypotension. Depressants are widely used throughout the world as prescription medicines and as illicit substances. When these are used, effects may include anxiolysis (reduction of anxiety), analgesia (pain relief), sedation, somnolence, cognitive/memory impairment, dissociation, muscle relaxation, lowered blood pressure/heart rate, respiratory depression, anesthesia, and anticonvulsant effects. Depressants exert their effects through a number of different pharmacological mechanisms, the most prominent of which include potentiation of GABA or opioid activity, and inhibition of adrenergic, histamine or acetylcholine activity. Some are also capable of inducing feelings of euphoria. The most widely used depressant by far is alcohol (i.e. ethanol).
Stimulants or "uppers", such as amphetamines or cocaine, which increase mental or physical function, have an opposite effect to depressants.
Depressants, in particular alcohol, can precipitate psychosis. A 2019 systematic review and meta-analysis by Murrie et al. found that the rate of transition from opioid, alcohol and sedative induced psychosis to schizophrenia was 12%, 10% and 9% respectively.
==== Antihistamines ====
Antihistamines (or "histamine antagonists") inhibit the release or action of histamine. "Antihistamine" can be used to describe any histamine antagonist, but the term is usually reserved for the classical antihistamines that act upon the H1 histamine receptor. Antihistamines are used as treatment for allergies. Allergies are caused by an excessive response of the body to allergens, such as the pollen released by grasses and trees. An allergic reaction causes release of histamine by the body. Other uses of antihistamines are to help with normal symptoms of insect stings even if there is no allergic reaction. Their recreational appeal exists mainly due to their anticholinergic properties, that induce anxiolysis and, in some cases such as diphenhydramine, chlorpheniramine, and orphenadrine, a characteristic euphoria at moderate doses. High dosages taken to induce recreational drug effects may lead to overdoses. Antihistamines are also consumed in combination with alcohol, particularly by youth who find it hard to obtain alcohol. The combination of the two drugs can cause intoxication with lower alcohol doses.
Hallucinations and possibly delirium resembling the effects of Datura stramonium can result if the drug is taken in much higher than therapeutic doses. Antihistamines are widely available over the counter at drug stores (without a prescription), in the form of allergy medication and some cough medicines. They are sometimes used in combination with other substances such as alcohol.
The most common unsupervised use of antihistamines in terms of volume and percentage of the total is perhaps in parallel to the medicinal use of some antihistamines to extend and intensify the effects of opioids and depressants. The most commonly used are hydroxyzine, mainly to extend a supply of other drugs, as in medical use, and the above-mentioned ethanolamine and alkylamine-class first-generation antihistamines, which are – once again as in the 1950s – the subject of medical research into their anti-depressant properties.
For all of the above reasons, the use of medicinal scopolamine for recreational uses is also observed.
==== Analgesics ====
Analgesics (also known as "painkillers") are used to relieve pain (achieve analgesia). The word analgesic derives from Greek "αν-" (an-, "without") and "άλγος" (álgos, "pain"). Analgesic drugs act in various ways on the peripheral and central nervous systems; they include paracetamol (also known in the US as acetaminophen), the nonsteroidal anti-inflammatory drugs (NSAIDs) such as the salicylates (e.g. aspirin), and opioid drugs such as hydrocodone, codeine, heroin and oxycodone. Some further examples of the brand name prescription opiates and opioid analgesics that may be used recreationally include Vicodin, Lortab, Norco (hydrocodone), Avinza, Kapanol (morphine), Opana, Paramorphan (oxymorphone), Dilaudid, Palladone (hydromorphone), and OxyContin (oxycodone).
==== Tranquilizers ====
The following are examples of tranquilizers (GABAergics):
Barbiturates
Benzodiazepines
Ethanol (drinking alcohol; ethyl alcohol)
Nonbenzodiazepines
Others
carisoprodol (Soma)
chloral hydrate
diethyl ether
ethchlorvynol (Placidyl; "jelly-bellies")
gamma-butyrolactone (GBL, a prodrug to GHB)
gamma-hydroxybutyrate (GHB; G; Xyrem; "Liquid Ecstasy", "Fantasy")
glutethimide (Doriden)
kava (from Piper methysticum; contains kavalactones)
ketamine, a phencyclidine (PCP) analog
meprobamate (Miltown)
methaqualone (Sopor, Mandrax; "Quaaludes")
phenibut
propofol (Diprivan), a general anesthetic
theanine (found in Camellia sinensis, the tea plant)
valerian (from Valeriana officinalis)
=== Stimulants ===
Stimulants, also known as "psychostimulants", induce euphoria with improvements in mental and physical function, such as enhanced alertness, wakefulness, and locomotion. Stimulants are also occasionally called "uppers". Depressants or "downers", which decrease mental or physical function, are in stark contrast to stimulants and are considered to be their functional opposites.
Stimulants enhance the activity of the central and peripheral nervous systems. Common effects may include increased alertness, awareness, wakefulness, endurance, productivity, and motivation, arousal, locomotion, heart rate, and blood pressure, and a diminished desire for food and sleep.
Use of stimulants may cause the body to significantly reduce its production of endogenous compounds that fulfill similar functions. Once the effect of the ingested stimulant has worn off the user may feel depressed, lethargic, confused, and dysphoric. This is colloquially termed a "crash" and may promote reuse of the stimulant.
Amphetamines are a significant cause of drug-induced psychosis. Importantly, a 2019 meta-analysis found that 22% of people with amphetamine-induced psychosis transition to a later diagnosis of schizophrenia.
Examples of stimulants include:
Sympathomimetics (catecholaminergics)—e.g. amphetamine, methamphetamine, cocaine, methylphenidate, ephedrine, pseudoephedrine
Entactogens (serotonergics, primarily phenethylamines)—e.g. MDMA (which is also an amphetamine)
Eugeroics, e.g. modafinil
Others
arecoline (found in Areca catechu)
caffeine (found in Coffea spp.)
nicotine (found in Nicotiana spp.)
rauwolscine (found in Rauvolfia serpentina)
yohimbine (Procomil; a tryptamine alkaloid found in Pausinystalia johimbe)
=== Euphoriants ===
Alcohol: "Euphoria, the feeling of well-being, has been reported during the early (10–15 min) phase of alcohol consumption" (e.g., beer, wine or spirits)
Cannabis: Tetrahydrocannabinol, the main psychoactive ingredient in this plant, can have sedative and euphoric properties.
Catnip: Catnip contains a sedative known as nepetalactone that activates opioid receptors. In cats it elicits sniffing, licking, chewing, head shaking, rolling, and rubbing which are indicators of pleasure. In humans, however, catnip does not act as a euphoriant.
Stimulants: "Psychomotor stimulants produce locomotor activity (the subject becomes hyperactive), euphoria, (often expressed by excessive talking and garrulous behaviour), and anorexia. The amphetamines are the best known drugs in this category..."
MDMA: The "euphoriant drugs such as MDMA ('ecstasy') and MDEA ('eve')" are popular among young adults. MDMA "users experience short-term feelings of euphoria, rushes of energy and increased tactility" as well as interpersonal connectedness.
Opium: This "drug derived from the unripe seed-pods of the opium poppy…produces drowsiness and euphoria and reduces pain. Morphine and codeine are opium derivatives." Opioids have led to many deaths in the United States, particularly by causing respiratory depression.
=== Hallucinogens ===
Hallucinogens can be divided into three broad categories: psychedelics, dissociatives, and deliriants. They can cause subjective changes in perception, thought, emotion and consciousness. Unlike other psychoactive drugs such as stimulants and opioids, hallucinogens do not merely amplify familiar states of mind but also induce experiences that differ from those of ordinary consciousness, often compared to non-ordinary forms of consciousness such as trance, meditation, conversion experiences, and dreams.
Psychedelics, dissociatives, and deliriants have a long worldwide history of use within medicinal and religious traditions. They are used in shamanic forms of ritual healing and divination, in initiation rites, and in the religious rituals of syncretistic movements such as União do Vegetal, Santo Daime, Temple of the True Inner Light, and the Native American Church. When used in religious practice, psychedelic drugs, as well as other substances like tobacco, are referred to as entheogens.
Hallucinogen-induced psychosis occurs when psychosis persists despite no longer being intoxicated with the drug. It is estimated that 26% of people with hallucinogen-induced psychosis will transition to a diagnosis of schizophrenia. This percentage is less than the psychosis transition rate for cannabis (34%) but higher than that of amphetamines (22%).
Starting in the mid-20th century, psychedelic drugs have been the object of extensive attention in the Western world. They have been and are being explored as potential therapeutic agents in treating depression, post-traumatic stress disorder, obsessive–compulsive disorder, alcoholism, and opioid addiction. Yet the most popular, and at the same time most stigmatized, use of psychedelics in Western culture has been associated with the search for direct religious experience, enhanced creativity, personal development, and "mind expansion". The use of psychedelic drugs was a major element of the 1960s counterculture, where it became associated with various social movements and a general atmosphere of rebellion and strife between generations.
Deliriants
atropine (alkaloid found in plants of the family Solanaceae, including datura, deadly nightshade, henbane and mandrake)
dimenhydrinate (Dramamine, an antihistamine)
diphenhydramine (Benadryl, Unisom, Nytol)
hyoscyamine (alkaloid also found in the Solanaceae)
hyoscine hydrobromide (another Solanaceae alkaloid)
myristicin (found in Myristica fragrans ("Nutmeg"))
ibotenic acid (found in Amanita muscaria ("Fly Agaric"); prodrug to muscimol)
muscimol (also found in Amanita muscaria, a GABAergic)
Dissociatives
dextromethorphan (DXM; Robitussin, Delsym, etc.; "Dex", "Robo", "Cough Syrup", "DXM")
"Triple C's, Coricidin, Skittles" refer to a potentially fatal formulation containing both dextromethorphan and chlorpheniramine.
ketamine (K; Ketalar, Ketaset, Ketanest; "Ket", "Kit Kat", "Special-K", "Vitamin K", "Jet Fuel", "Horse Tranquilizer")
methoxetamine (Mex, Mket, Mexi)
phencyclidine (PCP; Sernyl; "Angel Dust", "Rocket Fuel", "Sherm", "Killer Weed", "Super Grass")
nitrous oxide (N2O; "NOS", "Laughing Gas", "Whippets", "Balloons")
Psychedelics
Phenethylamines
2C-B ("Nexus", "Venus", "Eros", "Bees")
2C-E ("Eternity", "Hummingbird")
2C-I ("Infinity")
2C-T-2 ("Rosy")
2C-T-7 ("Blue Mystic", "Lucky 7")
DOB
DOC
DOI
DOM ("Serenity, Tranquility, and Peace" ("STP"))
MDMA ("Ecstasy", "E", "Molly", "Mandy", "MD", "Crystal Love")
mescaline (found in peyote and Trichocereus macrogonus (Peruvian torch, San Pedro cactus))
Tryptamines (including ergolines and lysergamides)
5-MeO-DiPT ("Foxy", "Foxy Methoxy")
5-MeO-DMT (found in various plants like chacruna, jurema, vilca, and yopo)
alpha-methyltryptamine (αMT; Indopan; "Spirals")
bufotenin (secreted by Bufo alvarius, also found in various Amanita mushrooms)
N,N-dimethyltryptamine (N,N-DMT; DMT; "Dimitri", "Disneyland", "Spice"; found in large amounts in Psychotria and in D. cabrerana)
lysergic acid amide (LSA; ergine; found in morning glory and Hawaiian baby woodrose seeds)
lysergic acid diethylamide (LSD; L; Delysid; "Acid", "Sid". "Cid", "Lucy", "Sidney", "Blotters", "Droppers", "Sugar Cubes")
O-Acetylpsilocin (believed to be a prodrug of psilocin)
psilocin (found in psilocybin mushrooms)
psilocybin (also found in psilocybin mushrooms; prodrug to psilocin)
ibogaine (found in Tabernanthe iboga ("Iboga"))
Atypicals
salvinorin A (found in Salvia divinorum, a trans-neoclerodane diterpenoid ("Diviner's Sage", "Lady Salvia", "Salvinorin"))
tetrahydrocannabinol (found in cannabis)
=== Inhalants ===
Inhalants are gases, aerosols, or solvents that are breathed in and absorbed through the lungs. While some "inhalant" drugs are used for medical purposes, as in the case of nitrous oxide, a dental anesthetic, inhalants are used as recreational drugs for their intoxicating effect. Most inhalant drugs that are used non-medically are ingredients in household or industrial chemical products that are not intended to be concentrated and inhaled, including organic solvents (found in cleaning products, fast-drying glues, and nail polish removers), fuels (gasoline (petrol) and kerosene), and propellant gases such as Freon and compressed hydrofluorocarbons that are used in aerosol cans such as hairspray, whipped cream, and non-stick cooking spray. A small number of recreational inhalant drugs are pharmaceutical products that are used illicitly, such as anesthetics (ether and nitrous oxide) and volatile anti-angina drugs (alkyl nitrites, more commonly known as "poppers").
The most serious inhalant abuse occurs among children and teens who "[...] live on the streets completely without family ties". Inhalant users inhale vapor or aerosol propellant gases using plastic bags held over the mouth or by breathing from a solvent-soaked rag or an open container. The effects of inhalants range from an alcohol-like intoxication and intense euphoria to vivid hallucinations, depending on the substance and the dosage. Some inhalant users are injured due to the harmful effects of the solvents or gases, or due to other chemicals used in the products inhaled. As with any recreational drug, users can be injured due to dangerous behavior while they are intoxicated, such as driving under the influence. Computer cleaning dusters are dangerous to inhale, because the gases expand and cool rapidly upon being sprayed. In many cases, users have died from hypoxia (lack of oxygen), pneumonia, cardiac failure or arrest, or aspiration of vomit.
Examples include:
Chloroform
Ethyl chloride
Diethyl ether
Ethane and ethylene
Laughing gas (nitrous oxide)
Poppers (alkyl nitrites)
Solvents and propellants (including propane, butane, freon, gasoline, kerosene, toluene) along with the fumes of glues containing them
== List of drugs which can be smoked ==
Plants:
black tar heroin
cannabis
datura and other Solanaceae (formerly smoked to treat asthma)
opium
salvia divinorum
tobacco
possibly other plants (see the section below)
Substances (also not necessarily psychoactive plants smoked within them):
5-MeO-DMT
Bufotenine
crack cocaine
dimethyltryptamine (DMT)
DiPT
methamphetamine
Methaqualone
phencyclidine (PCP)
synthetic cannabinoids (see also: synthetic cannabis)
many others, including some prescription drugs
== List of psychoactive plants, fungi, and animals ==
Minimally psychoactive plants which contain mainly caffeine and theobromine:
cocoa
coffee
guarana (caffeine in guarana is sometimes called guaranine)
kola
tea (caffeine in tea is sometimes called theine) – also contains theanine
yerba mate (caffeine in yerba mate is sometimes called mateine)
Most known psychoactive plants:
cannabis: cannabinoids
coca: cocaine
kava: kavalactones
khat: cathine and cathinone
nutmeg: myristicin and elemicin
opium poppy: morphine, codeine, and other opiates
salvia divinorum: salvinorin A
tobacco: nicotine and beta-carboline alkaloids
Solanaceae plants—contain atropine, hyoscyamine, and scopolamine:
datura
deadly nightshade Atropa belladonna
henbane
mandrake (mandragora)
other Solanaceae
Cacti with mescaline:
Peyote
Trichocereus macrogonus, the Peruvian torch cactus, and in particular its variety T. macrogonus var. pachanoi, the San Pedro cactus
Other plants:
Areca catechu (see: betel and paan)—arecoline
Ayahuasca (for DMT)
Calea zacatechichi
damiana
ephedra: ephedrine
kratom: mitragynine, mitraphylline, 7-hydroxymitragynine, raubasine, and corynanthine
Morning glory and Hawaiian Baby Woodrose – lysergic acid amide (LSA, ergine)
Rauvolfia serpentina: rauwolscine
Silene capensis
Tabernanthe iboga ("Iboga")—ibogaine
valerian: valerian (the chemical with the same name)
various plants like chacruna, jurema, vilca, and yopo – 5-MeO-DMT
yohimbe (Pausinystalia johimbe): yohimbine and corynanthine
many others
Fungi:
various Amanita mushrooms: muscimol
Amanita muscaria: ibotenic acid and muscimol
Claviceps purpurea and other Clavicipitaceae: ergotamine (not psychoactive itself but used in synthesis of LSD)
psilocybin mushrooms: psilocybin and psilocin
Psychoactive animals:
hallucinogenic fish
psychoactive toads: Bufo alvarius (Colorado River toad or Sonoran Desert toad) contains bufotenin (5-MeO-DMT)
== See also ==
== References ==
== Further reading ==
Martin, Christopher S.; Chung, Tammy; Langenbucher, James W. (2017). "Part 1: Defining and Characterizing the Nature and Extent of Substance Use Disorders – Historical and Cultural Perspectives on Substance Use and Substance Use Disorders". In Sher, Kenneth J. (ed.). The Oxford Handbook of Substance Use and Substance Use Disorders: Volume 1. Oxford Library of Psychology. Oxford and New York: Oxford University Press. pp. 27–59. doi:10.1093/oxfordhb/9780199381678.013.001. ISBN 9780199381678. LCCN 2016020729.
Anthony, James; Barondess, David A.; Radovanovic, Mirjana; Lopez-Quintero, Catalina (2017). "Part 1: Psychiatric Comorbidity – Polydrug Use: Research Topics and Issues". In Sher, Kenneth J. (ed.). The Oxford Handbook of Substance Use and Substance Use Disorders: Volume 2. Oxford Library of Psychology. Oxford and New York: Oxford University Press. pp. 27–59. doi:10.1093/oxfordhb/9780199381708.013.006. ISBN 9780199381708. LCCN 2016020729.
Hernández-Serrano, Olga; Gras, Maria E.; Font-Mayolas, Sílvia; Sullman, Mark J. M. (2016). "Part VI: Dual and Polydrug Abuse – Chapter 83: Types of Polydrug Usage". In Preedy, Victor R. (ed.). Neuropathology of Drug Addictions and Substance Misuse, Volume 3: General Processes and Mechanisms, Prescription Medications, Caffeine and Areca, Polydrug Misuse, Emerging Addictions and Non-Drug Addictions. Cambridge, Massachusetts: Academic Press, imprint of Elsevier. pp. 839–849. doi:10.1016/B978-0-12-800634-4.00083-4. ISBN 978-0-12-800634-4.
== External links ==
"The Science of Drug Use: A Resource for the Justice Sector". www.drugabuse.gov. North Bethesda, Maryland: National Institute on Drug Abuse. 26 May 2020. Archived from the original on 6 September 2023. Retrieved 21 March 2024.
School-Based Drug Abuse Prevention: Promising and Successful Programs (PDF). Ottawa, Ontario: Public Safety Canada. 31 January 2018. ISBN 978-1-100-12181-9. Archived (PDF) from the original on 19 May 2021. Retrieved 21 March 2024.
Sacco, L. N.; Finklea, K. (3 May 2016). "Synthetic Drugs: Overview and Issues for Congress" (PDF). Washington, D.C.: Congressional Research Service. Archived (PDF) from the original on 8 December 2021. Retrieved 21 March 2024. | Wikipedia/Recreational_drug |
Lean or purple drank (known by numerous local and street names) is a polysubstance drink used as a recreational drug. It is prepared by mixing prescription-grade cough or cold syrup containing an opioid drug and an anti-histamine drug with a soft drink and sometimes hard candy. The beverage originated in Houston as early as the 1960s and is popular in hip hop culture, especially within the Southern United States. Codeine/promethazine syrup is usually used to make lean, but other syrups are also used.
Users of lean are at risk of addiction, and serious complications include respiratory depression, respiratory arrest, and cardiac arrest. Lean is especially dangerous when consumed with alcohol.
== Names ==
The term lean refers to the tendency for users to have difficulty standing up straight while under the influence of the drug. "Purple drank" references its typically purple hue, as the cough syrups employed are often purple in color, and an African-American Vernacular English term for an alcoholic beverage or intoxicating drink. Other names include "syrup/sizzurp", "jelly", "Tussin/Tuss'", "barre", "Wock'", "Act'", "Texas tea", "mud", "dirty Sprite", and "tsikuni". In areas where lean had not yet been introduced, codeine-based cough syrup mixed with pills was called "juice and beans". Lean is also sometimes referred to by its color in slang, usually purple (or "purp'"), but can also be red, green, or yellow based on the ingredients used.
== Preparation ==
Typically, the base for lean is a strong prescription cold medicine, specifically cough syrup that contains both promethazine and codeine. Other preparations use codeine/guaifenasin, hydrocodone/chlorphenamine, hydrocodone/APAP, and hydrocodone/homatropine. Over-the-counter cold medicines that contain dextromethorphan (often paired with guaifenasin or acetaminophen) as the active ingredient have also been used, as they do not require acquiring a prescription.
To create a drinkable mixture, the cough syrup is combined with soft drinks, especially fruit-flavored drinks such as Sprite, Mountain Dew, or Fanta, and is typically served in two foam cups. A hard candy, usually a Jolly Rancher, may be added to give the mixture a sweeter flavor. Masking the undesired taste may impair judgment of the potency, which is a factor in overdosing.
== Effects ==
The physiological effects of lean on the user are to produce mild "euphoric side effects", which are accompanied by "motor-skill impairment, lethargy, drowsiness, and a dissociative feeling from all other parts of the body." It has been suggested that the super-sweet combination of soda, cough syrup, and Jolly Ranchers provides a pleasing flavor and mouthfeel that lingers on the user's tongue for an extended duration. This phenomenon is often appealing to first-time users. Lean is often used in combination with alcohol and/or other drugs.
=== Hazards ===
When taken in prescribed quantities, codeine-promethazine is quite safe, but dangers arise in higher doses since promethazine is a depressant of the central nervous system (CNS), and codeine is a respiratory depressant. When codeine is taken in very large amounts, it can cause one to stop breathing. Using alcohol and other drugs alongside lean increases the chance of respiratory depression. It seems that the concoction does not cause seizures itself, but increases their likelihood in those susceptible to them. The drink includes a massive amount of the opiate codeine, and it has been suggested that promethazine may heighten the euphoric effects of codeine.
The addictive nature of the drink means that trying to discontinue regular usage can bring about symptoms of withdrawal. In a 2008 interview with MTV News, Lil Wayne described the withdrawal as feeling "like death in your stomach when you stop. Everybody wants me to stop all this and all that. It ain't that easy."
Respiratory depression is a potentially serious or fatal adverse drug reaction associated with the use of codeine, but mainly the danger lies in the much more potent and CNS-depressing phenothiazine-related antihistamine promethazine. This depression is dose-related and is the mechanism for the potentially fatal consequences of overdose: respiratory or cardiac arrest. As with most CNS depressants, mixing with alcohol greatly increases the risk of respiratory failure and other complications.
== History ==
Lean is thought to have developed in Houston around the 1960s, when blues musicians would take Robitussin and cut it with beer. Later, when wine coolers came onto the market, they substituted for beer. These blues musicians lived in Houston's Fifth Ward, Third Ward, and South Park neighborhoods and the practice was taken up by the generation of rappers growing up in the same parts of the city. In the 1980s and 1990s the formula changed to using codeine promethazine cough syrup, somewhat like the glutethimide and codeine combination that was popular from the 1970s up to the early 1990s. Codeine-based cough syrups were also turned to as an alternative to pentazocine/tripelennamine ("T's and blues") after the pharmaceutical industry added naloxone to its constitutent drugs, effectively blocking their potential for abuse.
Lean remained a local phenomenon in Houston until the 1990s, when the American rapper DJ Screw released several tunes mentioning the drink in his mixtapes, which were extremely popular in the Houston area. DJ Screw's music was particularly appropriate for Houston's climate. Due to the heat and expanse of the Houston area residents spent long drives in their cars, "the music that most appropriately complements that has always been the music of DJ Screw, it's slowed down—and when I say slowed down I mean he would record sessions in his apartment with rappers freestyling over beats and he would make these big mixtapes and then he would actually slow them down even further on his cassette recorder." DJ Screw's invoking lean in his lyrics and his use of slow tempos had caused his style to be characterized "[a]s if the song itself has taken too much codeine promethazine". Rappers far beyond Houston would come to adopt aspects of DJ Screw's unique style, but not before he died of a codeine overdose in 2000.
=== Popularization ===
Houston producer DJ Screw popularized the concoction, which is widely attributed as a source of inspiration for the chopped-and-screwed style of hip hop music. The promethazine and codeine concoction first gained popularity in the underground hip hop scene in Houston, where musician Big Hawk said it was consumed as early as the 1960s and 1970s, becoming more widely used in the early 1990s. Because of usage by rap artists in Houston, it became more popular in the 1990s. Its use later spread to other States in the South. In June 2000, Three 6 Mafia's single "Sippin' on Some Syrup", featuring UGK, brought the term purple drank to a nationwide audience.
In 2004, the University of Texas at Austin found that 8.3% of secondary school students in Texas had taken codeine syrup to get high. The Drug Enforcement Administration reports busts involving syrup across the Southern United States, particularly in Texas and Florida. As of 2011, the price of lean in Houston was twice the price it is in Los Angeles.
In a 2019 interview, American rapper Future spoke about quitting lean and stated that he was afraid that his fans would believe his music has changed if he had publicly admitted to quitting earlier. Future expressed disappointment after American rapper Juice Wrld told him that he was influenced by his music to try lean when he was young. Future stated "It's like, 'Oh shit.' How many other sixth-graders did I influence to drink lean?" The two artists had released a collaborative mixtape titled Wrld on Drugs in October 2018. Lil Nas X's hit song "Old Town Road" includes the line "Lean all in my bladder", though Lil Nas X has stated he does not endorse the drug.
=== Notable incidents of use ===
DJ Screw, who popularized the codeine-based drink, died of a codeine–promethazine, Valium, and PCP overdose on November 16, 2000, several months after the video of Three 6 Mafia's single debuted.
Big Moe, a DJ Screw protégé whose albums City of Syrup and Purple World were based on the drink and who has been described as having "rapped obsessively about the drug", died at age 33 on October 14, 2007, after suffering a heart attack one week earlier that left him in a coma. There was speculation that lean may have contributed to his death.
Pimp C, a widely influential rapper from Port Arthur, Texas and member of the rap duo UGK, was found dead on December 4, 2007, at the Mondrian Hotel in West Hollywood, California. The Los Angeles County Coroner's Office reported that the rapper's death was "due to promethazine-codeine effects and other unestablished factors." Ed Winter, assistant chief of the Coroner's Office, said the levels of the medication were elevated, but not enough to deem the death an overdose. However, Pimp C had a history of sleep apnea, a condition that causes one to stop breathing for short periods during sleep. A spokesman for the coroner's office said that the combination of sleep apnea and cough medication probably suppressed Pimp C's breathing long enough to bring on his death.
Fredo Santana, an American rapper who frequently made references to the drink in his music, died of a seizure on January 19, 2018. According to TMZ, he had been suffering from liver and kidney problems, which were believed to be the result of his addiction.
In September 2006, Terrence Kiel, a San Diego Chargers player, was arrested during practice for the possession with intent to sell prescription cough syrup for use in making the drink. Kiel was caught trying to ship a case of syrup to a friend via FedEx. Kiel was charged with two felony counts of transporting a controlled substance and three counts of possession for sale of a controlled substance.
On July 8, 2008, Johnny Jolly, a Green Bay Packers player, was pulled over in his car by the police for playing excessively loud music in a nightclub parking lot. The officers found a Dr Pepper bottle in a holder next to two Styrofoam cups containing soda and ice. The case was dismissed, but charges were refiled in December 2009 after the Houston Police Department acquired new equipment that allowed the police to test the evidence again. Jolly faced a possible maximum sentence of up to 20 years in jail, but as a first time offender he would be eligible for probation.
On July 5, 2010, former Oakland Raiders quarterback JaMarcus Russell was arrested at his home in Mobile, Alabama, for possession of codeine syrup without a prescription. He was arrested as part of an undercover narcotics investigation. Russell was booked into city jail and released soon afterwards after making his bail.
On June 11, 2013, just days after being robbed at gunpoint in San Francisco, rapper 2 Chainz was arrested at Los Angeles International Airport on charges of possessing promethazine and codeine (the primary ingredients of lean) along with marijuana.
Mac Miller, who died of a drug overdose not involving lean, spoke openly of his addiction to lean.
On April 7, 2015, Swedish rapper Yung Lean, while living in Miami Beach, Florida, and recording his second studio album Warlord, was hospitalized at Mount Sinai Medical Center due to an overdose stemming from an addiction to Xanax, cocaine, and lean.
== Commercial products ==
Several legal commercial products loosely based on the concept of "purple drank" are marketed in the United States. In June 2008, Innovative Beverage Group, a Houston, Texas-based company, released a beverage called "Drank". The commercial product contains no codeine or promethazine, but claims to "Slow Your Roll" with a combination of herbal ingredients such as valerian root and rose hips as well as the hormone melatonin.
Similar "anti-energy" or relaxation drinks on the commercial market use the names "Purple Stuff", "Sippin Syrup", and "Lean".
These commercial products have been criticized for their potential to serve as gateways to the dangerous illegal concoction. The marketing push has been described as akin to the making of candy cigarettes.
== See also ==
Ayahuasca
Benadryl challenge
Coca wine
Recreational use of dextromethorphan
== References == | Wikipedia/Lean_(drug) |
A designer drug is a structural or functional analog of a controlled substance that has been designed to mimic the pharmacological effects of the original drug, while avoiding classification as illegal and/or detection in standard drug tests. Designer drugs include psychoactive substances that have been designated by the European Union, Australia, and New Zealand, as new psychoactive substances (NPS) as well as analogs of performance-enhancing drugs such as designer steroids.
Some of these designer drugs were originally synthesized by academic or industrial researchers in an effort to discover more potent derivatives with fewer side effects and shorter duration (and possibly also because it is easier to apply for patents for new molecules) and were later co-opted for recreational use. Other designer drugs were prepared for the first time in clandestine laboratories. Because the efficacy and safety of these substances have not been thoroughly evaluated in animal and human trials, the use of some of these drugs may result in unexpected side effects.
The development of designer drugs may be considered a subfield of drug design. The exploration of modifications to known active drugs—such as their structural analogues, stereoisomers, and derivatives—yields drugs that may differ significantly in effects from their "parent" drug (e.g., showing increased potency, or decreased side effects). In some instances, designer drugs have similar effects to other known drugs, but have completely dissimilar chemical structures (e.g. JWH-018 vs THC). Despite being a very broad term, applicable to almost every synthetic drug, it is often used to connote synthetic recreational drugs, sometimes even those that have not been designed at all (e.g., LSD, the psychedelic side effects of which were discovered unintentionally).
In some jurisdictions, drugs that are highly similar in structure to a prohibited drug are illegal to trade regardless of that drug's legal status (or indeed whether or not the structurally similar analogue has similar pharmacological effects). In other jurisdictions, their trade is a legal grey area, making them grey market goods. Some jurisdictions may have analogue laws that ban drugs similar in chemical structure to other prohibited drugs, while some designer drugs may be prohibited irrespective of the legal status of structurally similar drugs; in both cases, their trade may take place on the black market.
== History ==
=== United States ===
==== 1920s–1930s ====
Following the passage of the second International Opium Convention in 1925, which specifically banned morphine and the diacetyl ester of morphine, heroin, a number of alternative esters of morphine quickly started to be manufactured and sold. The most notable of these were dibenzoylmorphine and acetylpropionylmorphine, which have virtually identical effects to heroin but were not covered by the Opium Convention. This then led the Health Committee of the League of Nations to pass several resolutions attempting to bring these new drugs under control, ultimately leading in 1930 to the first broad analogues provisions extending legal control to all esters of morphine, oxycodone and hydromorphone. Another early example of what could loosely be termed designer drug use, was during the Prohibition era in the 1930s, when diethyl ether was sold and used as an alternative to illegal alcoholic beverages in a number of countries.
==== 1960s–1970s ====
During the 1960s and 1970s, a number of new synthetic hallucinogens were introduced, with a notable example being the sale of highly potent tablets of DOM in San Francisco in 1967. There was little scope to prosecute people over drug analogues at this time, with new compounds instead being added to the controlled drug schedules one by one as they became a problem. One significant court case from this period was in 1973, when Tim Scully and Nicholas Sand were prosecuted for making the acetyl amide of LSD, known as ALD-52. At this time ALD-52 was not a controlled drug, but they were convicted on the grounds that in order to make ALD-52, they would have had to be in possession of LSD, which was illegal. The late 1960s also saw the introduction of various analogues of phencyclidine (PCP) to the illicit market, with Eticyclidine (PCE) first being detected in 1969.
==== 1980s–early 1990s ====
The modern use of the term designer drug was coined in the 1980s to refer to various synthetic opioid drugs, based mostly on the fentanyl molecule (such as α-methylfentanyl). The term gained widespread popularity when MDMA (ecstasy) experienced a popularity boom in the mid-1980s. When the term was coined in the 1980s, a wide range of narcotics were being sold as heroin on the black market. Many were based on fentanyl or meperidine. One, MPPP, was found in some cases to contain an impurity called MPTP, which caused brain damage that could result in a syndrome identical to late stage Parkinson's disease, from only a single dose. Other problems were highly potent fentanyl analogues that caused many accidental overdoses.
Because the government was powerless to prosecute people for these drugs until after they had been marketed successfully, laws were passed to give the DEA power to emergency schedule chemicals for a year, with an optional 6-month extension, while gathering evidence to justify permanent scheduling, as well as the analogue laws mentioned previously. Emergency-scheduling power was used for the first time for MDMA. In this case, the DEA scheduled MDMA as a Schedule I drug and retained this classification after review, even though their own judge ruled that MDMA should be classified Schedule III on the basis of its demonstrated uses in medicine. The emergency scheduling power has subsequently been used for a variety of other drugs including 2C-B, AMT, and BZP. In 2004, a piperazine drug, TFMPP, became the first drug that had been emergency-scheduled to be denied permanent scheduling and revert to legal status.
The late 1980s and early 1990s also saw the re-emergence of methamphetamine in the United States as a widespread public health issue, leading to increasing controls on precursor chemicals in an attempt to cut down on domestic manufacture of the drug. This led to several alternative stimulant drugs emerging, the most notable ones being methcathinone and 4-methylaminorex, but, despite attracting enough attention from authorities to provoke legal scheduling of these compounds, their distribution was relatively limited in extent and methamphetamine continued to dominate the illicit synthetic stimulant market overall.
==== Late 1990s–2004 ====
In the late 1990s and early 2000s, there was a huge explosion in designer drugs being sold over the internet. The term and concept of "research chemicals" was coined by some marketers of designer drugs (in particular, of psychedelic drugs in the tryptamine and phenethylamine family). The idea was that, by selling the chemicals as for "scientific research" rather than human consumption, the intent clause of the U.S. analogue drug laws would be avoided. Nonetheless, the DEA raided multiple suppliers, first JLF Primary Materials, and then multiple vendors (such as RAC Research) several years later in Operation Web Tryp. This process was accelerated greatly when vendors began advertising via search engines like Google by linking their sites to searches on key words such as chemical names and terms like psychedelic or hallucinogen. Widespread discussion of consumptive use and the sources for the chemicals in public forums also drew the attention of the media and authorities.
In 2004, the US Drug Enforcement Administration raided and shut down several Internet-based research chemical vendors in an operation called Web Tryp. With help from the authorities in India and China, two chemical manufacturers were also closed. Many other internet-based vendors promptly stopped doing business, even though their products were still legal throughout much of the world.
Most substances that were sold as "research chemicals" in this period of time are hallucinogens and bear a chemical resemblance to drugs such as psilocybin and mescaline. As with other hallucinogens, these substances are often taken for the purposes of facilitating spiritual processes, mental reflection or recreation. Some research chemicals on the market were not psychoactive, but can be used as precursors in the synthesis of other potentially psychoactive substances, for example, 2C-H, which could be used to make 2C-B and 2C-I among others. Extensive surveys of structural variations have been conducted by pharmaceutical corporations, universities and independent researchers over the last century, from which some of the presently available research chemicals derive. One particularly notable researcher is Alexander Shulgin, who presented syntheses and pharmacological explorations of hundreds of substances in the books TiHKAL and PiHKAL (co-authored with Ann Shulgin), and served as an expert witness for the defense in several court cases against manufacturers of psychoactive drugs.
The majority of chemical suppliers sold research chemicals in bulk form as powder, not as pills, as selling in pill form would invalidate the claims that they were being sold for non-consumptive research. Active dosages vary widely from substance to substance, ranging from micrograms to hundreds of milligrams, but while it is critical for the end user to weigh doses with a precision scale, instead of guessing ("eyeballing"), many users did not do this and this led to many emergency room visits and several deaths, which were a prominent factor leading to the emergency scheduling of several substances and eventually Operation Web Tryp. Some compounds such as 2C-B and 5-Meo-DiPT did eventually increase in popularity to the point that they were sold in pill form to reach a wider market, and acquired popular street names ("Nexus" and "Foxy," respectively). Once a chemical reaches this kind of popularity, it is usually just a matter of time before it is added to the list of scheduled (i.e., illegal) drugs.
The late 1990s and early 2000s also saw the first widespread use of novel anabolic steroids by athletes in competition. Steroids had been banned by the International Olympic Committee since 1976, but due to the large number of different anabolic agents available for human and veterinary use, the ability of laboratories to test for all available drugs had always lagged behind the ability of athletes to find new compounds to use. The introduction of increasingly formalised testing procedures, especially with the creation of the World Anti-Doping Agency in 1999, made it much more difficult for athletes to get away with using these drugs without detection, which then led to the synthesis of novel and potent anabolic steroid drugs such as tetrahydrogestrinone (THG), which were not detectable by the standard tests.
==== 2005–2021 ====
While through recent history most designer drugs had been either opioids, hallucinogens, or anabolic steroids, the range of possible compounds is limited only by the scientific and patent literature, and recent years have been characterised by a broadening of the range of compounds sold as designer drugs. These have included a wide variety of designer stimulants such as geranamine, mephedrone, MDPV and desoxypipradrol, several designer sedatives such as methylmethaqualone and premazepam, and designer analogues of sildenafil (Viagra), which have been reported as active compounds in "herbal" aphrodisiac products. Designer cannabinoids are another recent development, with two compounds JWH-018 and (C8)-CP 47,497 initially found in December 2008 as active components of "herbal smoking blends" sold as legal alternatives to marijuana. Subsequently, a growing range of synthetic cannabinoid agonists have continued to appear, including by 2010, novel compounds such as RCS-4, RCS-8, and AB-001, which had never been reported in the literature, and appear to have been invented by designer drug manufacturers themselves. Another novel development is the use of research ligands for cosmetic rather than strictly recreational purposes, such as grey-market internet sales of the non-approved alpha-melanocyte-stimulating hormone tanning drugs known as melanotan peptides.
"...what is new is the wide range of substances now being explored, the aggressive marketing of products that have been intentionally mislabelled, the growing use of the internet, and the speed at which the market reacts to control measures."
Mephedrone and the cathinones marked somewhat of a turning point for designer drugs, turning them from little known, ineffective substances sold in head shops to powerful substances able to compete with classical drugs on the black market. Mephedrone especially experienced a somewhat meteoric rise in popularity in 2009 and the resulting media panic resulted in its prohibition in multiple countries. Following this there was a considerable emergence of other cathinones which attempted to mimic the effects of mephedrone, and with a newly attracted customer base, plenty of money to drive innovation.
Subsequently, the market rapidly expanded, with more and more substances being detected every year. In 2009, the EMCDDA's early warning system discovered 24 new drugs. In 2010, it found another 41; in 2011, another 49; and in 2012, there were 73 more. In 2013, a further 81 were identified: a total of 268 new drugs in just four years. These have not been limited to cathinones, with 35% being cannabinoids and the rest being composed of stimulants, benzodiazepines, psychedelics, dissociatives and to a lesser extent, every other class of drugs, even ibogoids and nootropics. The largest group of drugs being monitored by the EMCDDA is synthetic cannabinoids, with 209 different synthetic cannabinoids reported between 2008 and 2021 - including 11 new cannabinoids identified for the first time in 2020.
Since 2019, highly potent nitazenes (benzimidazole opioids) have proliferated as ″new synthetic opioids″ in the North American and European narcotics markets and as such have become a formative component of the opioid epidemic in the United States. Overdoses of nitazene opioids have led to several hundred documented fatalities.
==== 2022–present ====
In the early 2020s, safety and legal difficulty of regulating peptides spurred the growth of grey-market synthetic peptide hormone vendors. These peptides are marketed as non-recreational and sold for their purported anti-aging, performance enhancing and cosmetic benefits, such vendors may employ medical professionals using legal ambiguity for their operations.
== Terminology ==
Many terms exist other than "designer drug" often depending on the context and geographical region. For example, the term new psychoactive substance (NPS) is more commonly used in academic settings, and in regions such as Australia, New Zealand, and European Union, including United Kingdom (UK).
=== Common names ===
In the UK to avoid being controlled by the Medicines Act, designer drugs such as mephedrone have been described as "plant food", despite the compounds having no history of being used for these purposes.
In the US, similar descriptions ("bath salts" is the most common) have been used to describe mephedrone as well as methylone and methylenedioxypyrovalerone (MDPV). Combined with labeling that they are "not for human consumption," these descriptions are an attempt to skirt the Federal Analog Act which forbids drugs that are "substantially similar" to already classified drugs from being sold for human use.
Synthetic cannabinoids are known under a variety of names including K2, Spice, Black Mamba, Bombay Blue, Genie, Zohai, Banana Cream Nuke, Krypton, and Lava Red. They are often called "synthetic marijuana," "herbal incense," or "herbal smoking blends" and often labeled "not for human consumption."
== Safety ==
The safety of research chemicals is untested and little if any research has been done on the toxicology or pharmacology of most of these drugs. Few, if any, human or animal studies have been done. Many research compounds have produced unexpected side-effects and adverse incidents due to the lack of screening for off-target effects prior to marketing; both bromo-dragonfly and mephedrone seem to be capable of producing pronounced vasoconstriction under some circumstances, which has resulted in several deaths, although the mechanism remains unclear. Substituted phenethylamines such as the 2C family and substituted amphetamines such as the DOx family have also caused a limited number of deaths.
== Law ==
Due to the recent development of many designer drugs, laws banning or regulating their use have not been developed yet, and in recent cases novel drugs have appeared directly in response to legislative action, to replace a similar compound that had recently been banned. Many of the chemicals fall under the various drug analogue legislations in certain countries, but most countries have no general analogue act or equivalent legislation and so novel compounds may fall outside of the law after only minor structural modifications.
In the United States, the Controlled Substances Act was amended by the Controlled Substance Analogue Enforcement of 1986, which attempted to ban designer drugs pre-emptively by making it illegal to manufacture, sell, or possess chemicals that were substantially similar in chemistry and pharmacology to Schedule I or Schedule II drugs.
Other countries have dealt with the issue differently. In some, the new drugs are banned as they become a concern, as in Germany, Canada, the United Kingdom, and Sweden. In Sweden, the police and customs may also seize drugs that are not on the list of drugs covered by the anti-drug laws if the police suspect that the purpose of the holding is related to drug abuse. Following a decision by a prosecutor, the police may destroy the seized drugs.
In Ireland, the Criminal Justice (Psychoactive Substances) Act 2010 bans substances based on their psychoactive effect, and was introduced as a catch-all to address the time lag between new substances appearing and their being banned individually. In the United Kingdom, the Psychoactive Substances Act 2016 adopts a similar approach.
Some countries, such as Australia, have enacted generic bans but based on chemical structure rather than psychoactive effect: if a chemical fits a set of rules regarding substitutions and alterations of an already-banned drug, then it too is banned. Brazil adopted the same model as Australia, in a recent ruling from ANVISA, which is responsible to define what constitute drugs.
=== Temporary class drug ===
A temporary class drug is a relatively new status for controlled drugs, which has been adopted in some jurisdictions, notably New Zealand and the United Kingdom, to attempt to bring newly synthesized designer drugs under legal control. The controlled drug legislation in these jurisdictions requires drug scheduling decisions to follow an evidence-based process, where the harms of the drug are assessed and reviewed so that an appropriate legal status can be assigned. Since many designer drugs sold in recent years have had little or no published research that could help inform such a decision, they have been widely sold as "legal highs", often for months, before sufficient evidence accumulates to justify placing them on the controlled drug schedules.
== List ==
== See also ==
Controlled Substances Act
Controlled Substance Analogue Enforcement of 1986
Controlled Drugs and Substances Act
New chemical entity
Operation Web Tryp
Federal Analogue Act
Pharmaceutical company
Psychoactive Substances Act 2013 – New Zealand
Psychoactive Substances Act 2016 – UK ban on all drugs based on psychoactive effect
Research chemical
== Notes ==
== References ==
== External links ==
Substances and classifications table (31/10/2008) – European Legal Database on Drugs Archived 2021-02-25 at the Wayback Machine Report on all substances controlled in at least one EU country in XLS format
Designer Drug Compound List Archived 2017-11-07 at the Wayback Machine at Chemograph Plus, DigiLab Software GmbH
"Fentanyl landscape | PiHKAL · info". isomerdesign.com. | Wikipedia/Designer_drug |
Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid prescription. In many countries, OTC drugs are selected by a regulatory agency to ensure that they contain ingredients that are safe and effective when used without a physician's care. OTC drugs are usually regulated according to their active pharmaceutical ingredient (API) and strengths of final products.
The term over-the-counter (OTC) refers to a medication that can be purchased without a medical prescription. In contrast, prescription drugs require a prescription from a doctor or other health care professional and should only be used by the prescribed individual. Some drugs may be legally classified as over-the-counter (i.e. no prescription is required), but may only be dispensed by a pharmacist after an assessment of the patient's needs or the provision of patient education. Regulations detailing the establishments where drugs may be sold, who is authorized to dispense them, and whether a prescription is required vary considerably from country to country.
== Usage ==
As of 2011, around a third of older adults in the US reportedly used OTC drugs, and this number is increasing. By 2018, the prevalence of use by adults in the U.S. as first-line treatment for minor illnesses had reached 81%: however, there is some debate as to whether this figure relates to an actual improvement of health.
== Regulation by country ==
=== Canada ===
In Canada, there are four drug schedules:
Schedule 1: Requires a prescription for sale and is provided to the public by a licensed pharmacist.
Schedule 2: Does not require a prescription but requires an assessment by a pharmacist prior to sale. These drugs are kept in an area of the pharmacy where there is no public access and may also be referred to as "behind-the-counter" drugs.
Schedule 3: Does not require a prescription but must be kept in an area under the supervision of a pharmacist. These drugs are kept in an area of the retail outlet where self-selection is possible, but a pharmacist must be available to assist in the self-selection of medication if required.
Unscheduled: Does not require a prescription and may be sold in any retail outlet.
All medications other than Schedule 1 may be considered an OTC drug, as they do not require prescriptions for sale. While the National Association of Pharmacy Regulatory Authorities provides recommendations on the scheduling of drugs for sale in Canada, each province may determine its own scheduling. The drugs found in each schedule may vary from province to province.
=== India ===
In November 2016, India's Drug Consultative Committee announced it was embarking on establishing a definition of drugs which could be dispensed without a prescription. Prior to this, the general assumption was that any drug which did not fall into a prescription schedule could be purchased without a prescription. However, the needed definition had not been enacted by early 2018. The lack of a legal definition for OTC drugs has led to this US$4 billion market segment being effectively unregulated.
=== Netherlands ===
In the Netherlands, there are four categories:
UR (Uitsluitend Recept): prescription only
UA (Uitsluitend Apotheek): pharmacist only
UAD (Uitsluitend Apotheek of Drogist): pharmacist or drugstore only
AV (Algemene Verkoop): may be sold in general stores
A drug that is UA may be sold OTC but only by pharmacists. The drug can be on the shelves like any other product. Examples are domperidone, 400 mg ibuprofen up to 50 tablets and dextromethorphan. A drug that is UAD can also be sold at drugstores which are stores where no prescription can be filled. The drugs are usually on the shelves, and the store also sells items like toys, gadgets, perfumes and homeopathic products. The drugs in this category have limited risk and addiction potential. Examples are naproxen and diclofenac in small amounts, cinnarizine, 400 mg ibuprofen up to 20 tablets and also 500 mg paracetamol up to 50 tablets. Drugs in the AV category can be sold at supermarkets, gas stations, etc. and include only drugs with minimal risk to the public, like paracetamol up to 20 tablets, 200 mg ibuprofen up to 10 tablets, cetirizine and loperamide.
=== United States ===
In the United States, the manufacture and sale of OTC substances are regulated by the Food and Drug Administration. The FDA requires that all "new drugs" obtain a New Drug Application (NDA) before entering interstate commerce, but the act exempts any drugs generally recognized as safe and effective (GRAS/E). To deal with the vast number of OTC drugs that were already on the market before the requirement that all drugs obtain an NDA, the FDA created the OTC monograph system to review classes of drugs and to categorize them as GRAS/E after review by expert panels. Certain classes of OTC drugs would not be required to obtain an NDA and could remain on the market if they conformed to the monograph guidelines for doses, labeling, and warnings finalized in the Code of Federal Regulations
Thus, an OTC drug product is allowed to be marketed either (1) pursuant to an FDA monograph or (2) pursuant to an NDA for products that do not fit within a specific monograph. There is also the possibility that certain OTC drug products are marketed under the grandfathering provisions of the Federal Food, Drug, and Cosmetic Act, but the FDA has never formally acknowledged that any legitimate grandfathered OTC drug exists.
Examples of OTC substances approved in the United States are sunscreens, anti-microbial and anti-fungal products, external and internal analgesics such as lidocaine and aspirin, psoriasis and eczema topical treatments, anti-dandruff shampoos containing coal tar, and other topical products with a therapeutic effect.
The Federal Trade Commission regulates advertising of OTC products, in contrast to prescription drug advertising, which is regulated by the FDA.
The FDA requires OTC products to be labeled with an approved "Drug Facts" label to educate consumers about their medications. The labels comply to a standard format and are intended to be easy for typical consumers to understand. Drug Facts labels include information on the product's active ingredient(s), indications and purpose, safety warnings, directions for use, and inactive ingredients.
The 2020 Coronavirus Aid, Relief, and Economic Security Act (CARES Act) includes reforms that modernize the way certain OTC drugs are regulated in the United States. Many OTC monographs need to be updated but updating or changing an OTC monograph requires the slow and burdensome notice-and-comment rulemaking process. The CARES Act includes OTC monograph reform provisions that replace the rulemaking process with an administrative order process.
=== United Kingdom ===
In the United Kingdom, medication is governed by the Human Medicines Regulations, 2012. Medication falls into one of three categories:
Prescription Only Medication (POM), which is legally available only with a valid prescription from a prescriber. A pharmacist has to be on the premises for POM medicines to be dispensed, required by law. The medicine has been specifically prescribed for the patient holding the prescription, so it is considered safe for only the recipient to take. Just a small example of these include most antibiotics and all antidepressants or antidiabetic medications. Certain POM medicines are additionally marked Controlled Drug (CD) due to risk of abuse and the possibility of diversion for sale as street drugs. Examples of CDs include all benzodiazepines and strong opioids such as heroin and fentanyl.
General Sales List (GSL), available off the shelf with no pharmacy training required to sell (so they can be sold anywhere, such as supermarkets). In general, they are considered safe for most people when taken correctly. Examples of these include 16-packs (or less) of painkillers such as paracetamol, ibuprofen, and aspirin as well as a host of other medications such as small pack sizes of some antihistamines, some laxative medication, and skin creams. This also includes the recreational substances alcohol and caffeine (where they are included in medicinal products), and some nicotine preparations.
Pharmacy Medicines (P) are medicines that are legally neither a POM or GSL medication. These can be sold from a registered pharmacy but should not be available for self-selection (although directions to discuss a 'P' product may be allocated shelf space with associated GSL items). 'P' medications are reserved from the GSL list as they are either associated with a need for advice on use, or used in conditions which may require referral to a medical prescriber. Suitably trained counter assistants may sell a 'P' medication under the supervision of a pharmacist and will ask questions to determine if the customer needs to be referred for a discussion with a pharmacist. Some 'POM' medicines are available for use in certain situations and doses as 'P' medicines.
If it is not appropriate to sell a 'P' medication – i.e. the condition is not suitable for self-management and requires referral to a medical prescriber – then a sale should not occur and the pharmacist has a legal and professional obligation to refer this on to an appropriate service.
Examples of these include some sleep aid tablets such as diphenhydramine, human deworming tablets such as mebendazole, painkillers with small amounts of codeine (up to 12.8 mg per tablet), and pseudoephedrine. Medication available only with a prescription is marked somewhere on the box/container with [POM]. Pharmacy-only products are marked with [P]. A prescription is not required for [P] medicines, and pharmacy sales assistants are required by Royal Pharmaceutical Society codes to ask certain questions, which varies for what the customer says. If they ask for a specific product, the pharmacy assistant must ask "Who is it for?", "How long have you had the symptoms?", "Are you allergic to any medication?", "Are you taking any medication?" ('WHAM' questions). If a customer asks for a remedy, e.g., hay fever, then the '2WHAM questions' must be asked "Who is it for?", "What are the symptoms?", "How long have you had the symptoms?", "Have you taken any action towards your symptoms?", and "Are you taking any other medication?". It is with this information that the pharmacist can halt the sale, if need be. No [POM], [P] or [GSL] products that are stocked in a pharmacy can be sold, dispensed, or pre-made until a responsible pharmacist is signed in and on the premises. Some medication available in supermarkets and petrol stations is sold only in smaller packet sizes. Often, larger packs will be marked as [P] and available only from a pharmacy. Frequently, customers buying larger-than-usual doses of [P] medicines (such as DXM, promethazine, codeine or Gee's Linctus) will be queried, due to the possibility of abuse.
== Transitions between prescription and OTC ==
As a general rule, over-the-counter drugs have to be used primarily to treat a condition that does not require the direct supervision of a doctor and must be proven to be reasonably safe and well tolerated. OTC drugs are usually also required to have little or no abuse potential, although in some areas drugs such as codeine are available OTC (usually in strictly limited formulations or requiring paperwork or identification to be submitted during purchase).
Over time, often 3–6 years, drugs that prove themselves safe and appropriate as prescription medicines may be switched from prescription to OTC. An example of this is diphenhydramine (Benadryl), an anti-histamine which once required a prescription but now is available OTC nearly everywhere. More recent examples are cimetidine and loratadine in the United States, and ibuprofen in Australia.
It is somewhat unusual for an OTC drug to be withdrawn from the market as a result of safety concerns, rather than market forces, though it does happen occasionally. For example, phenylpropanolamine was removed from sale in the United States over concern regarding strokes in young women. A study has been done examining consumer's perceptions about the risk of and access to nonprescription medication. The study concluded that a small percentage of consumers prefer having access to medication over potential risks of taking non-prescribed medication. Ranitidine was suspended in multiple markets due to concerns over the presence of the carcinogen N-nitrosodimethylamine (NDMA).
In the United Kingdom, it was announced in February 2007 that Boots the Chemist would try over-the-counter sales of Viagra in stores in Manchester, England (previous available as prescription only). Men aged between 30 and 65 could buy four tablets after a consultation with a pharmacist.
== See also ==
== References ==
== External links ==
Complete list of OTC drugs
"Over-the-Counter Medicines Guide" Archived 9 March 2021 at the Wayback Machine, Tool Box at ConsumerMedSafety.org
Over-the-counter (OTC) medicines at FamilyDoctor.org, maintained by the American Academy of Family Physicians. Contains extensive information on over-the-counter drugs and their responsible use, including specific guidance on several drug classes in question-and-answer format and information on common drug interactions.
UK Medicines and Healthcare Products Regulatory Agency list of substances on general sales list Archived 7 March 2014 at the Wayback Machine
National Institute on Drug Abuse: "NIDA for Teens: Cough and Cold Medicine (DXM and Codeine Syrup)" | Wikipedia/Over-the-counter_drug |
A drug test (also often toxicology screen or tox screen) is a technical analysis of a biological specimen, for example urine, hair, blood, breath, sweat, or oral fluid/saliva—to determine the presence or absence of specified parent drugs or their metabolites. Major applications of drug testing include detection of the presence of performance enhancing steroids in sport, employers and parole/probation officers screening for drugs prohibited by law (such as cocaine, methamphetamine, and heroin) and police officers testing for the presence and concentration of alcohol (ethanol) in the blood commonly referred to as BAC (blood alcohol content). BAC tests are typically administered via a breathalyzer while urinalysis is used for the vast majority of drug testing in sports and the workplace. Numerous other methods with varying degrees of accuracy, sensitivity (detection threshold/cutoff), and detection periods exist.
A drug test may also refer to a test that provides quantitative chemical analysis of an illegal drug, typically intended to help with responsible drug use.
== Detection periods ==
The detection windows depend upon multiple factors: drug class, amount and frequency of use, metabolic rate, body mass, age, overall health, and urine pH. For ease of use, the detection times of metabolites have been incorporated into each parent drug. For example, heroin and cocaine can only be detected for a few hours after use, but their metabolites can be detected for several days in urine. The chart depicts the longer detection times of the metabolites. In the case of hair testing, the metabolytes are permanently embedded into hair, and the detection time is determined by the length of the hair sample used in the analysis. The standard length of head hair used in the test is 1.5", which corresponds to about 3 months. Body/pubic hair grows slower, and the same 1.5" would result in a longer detection time.
Oral fluid or saliva testing results for the most part mimic that of blood. The only exceptions are THC (tetrahydrocannabinol) and benzodiazepines. Oral fluid will likely detect THC from ingestion up to a maximum period of 6–12 hours. This continues to cause difficulty in oral fluid detection of THC and benzodiazepines.
Breath air for the most part mimics blood tests as well. Due to the very low levels of substances in the breath air, liquid chromatography—mass spectrometry has to be used to analyze the sample according to a recent publication wherein 12 analytes were investigated.
Rapid oral fluid products are not approved for use in workplace drug testing programs and are not FDA cleared. Using rapid oral fluid drug tests in the workplace is prohibited in only:
California
Kansas
Maine
Minnesota
New York
Vermont
The following chart gives approximate detection periods for each substance by test type.
== Types ==
=== Urine drug screen ===
Urine analysis is primarily used because of its low cost. Urine drug testing is one of the most common testing methods used. The enzyme-multiplied immune test is the most frequently used urinalysis. Complaints have been made about the relatively high rates of false positives using this test.
Urine drug tests screen the urine for the presence of a parent drug or its metabolites. The level of drug or its metabolites is not predictive of when the drug was taken or how much the patient used.
Urine drug testing is an immunoassay based on the principle of competitive binding. Drugs which may be present in the urine specimen compete against their respective drug conjugate for binding sites on their specific antibody. During testing, a urine specimen migrates upward by capillary action. A drug, if present in the urine specimen below its cut-off concentration, will not saturate the binding sites of its specific antibody. The antibody will then react with the drug-protein conjugate and a visible colored line will show up in the test line region of the specific drug strip.
A common misconception is that a drug test that is testing for a class of drugs, for example, opioids, will detect all drugs of that class. However, most opioid tests will not reliably detect oxycodone, oxymorphone, meperidine, or fentanyl. Likewise, most benzodiazepine drug tests will not reliably detect lorazepam. However, urine drug screens that test for a specific drug, rather than an entire class, are often available.
When an employer requests a drug test from an employee, or a physician requests a drug test from a patient, the employee or patient is typically instructed to go to a collection site or their home. The urine sample goes through a specified 'chain of custody' to ensure that it is not tampered with or invalidated through lab or employee error. The patient or employee's urine is collected at a remote location in a specially designed secure cup, sealed with tamper-resistant tape, and sent to a testing laboratory to be screened for drugs (typically the Substance Abuse and Mental Health Services Administration 5 panel). The first step at the testing site is to split the urine into two aliquots. One aliquot is first screened for drugs using an analyzer that performs immunoassay as the initial screen. To ensure the specimen integrity and to detect possible adulterants, additional parameters are tested for. Some test the properties of normal urine, such as, urine creatinine, pH, and specific gravity. Others are intended to catch substances added to the urine to alter the test result, such as, oxidants (including bleach), nitrites, and gluteraldehyde. If the urine screen is positive then another aliquot of the sample is used to confirm the findings by gas chromatography—mass spectrometry (GC-MS) or liquid chromatography - mass spectrometry methodology. If requested by the physician or employer, certain drugs are screened for individually; these are generally drugs part of a chemical class that are, for one of many reasons, considered more habit-forming or of concern. For instance, oxycodone and diamorphine may be tested, both sedative analgesics. If such a test is not requested specifically, the more general test (in the preceding case, the test for opioids) will detect most of the drugs of a class, but the employer or physician will not have the benefit of the identity of the drug.
Employment-related test results are relayed to a medical review office (MRO) where a medical physician reviews the results. If the result of the screen is negative, the MRO informs the employer that the employee has no detectable drug in the urine, typically within 24 hours. However, if the test result of the immunoassay and GC-MS are non-negative and show a concentration level of parent drug or metabolite above the established limit, the MRO contacts the employee to determine if there is any legitimate reason—such as a medical treatment or prescription.
On-site instant drug testing is a more cost-efficient method of effectively detecting substance use amongst employees, as well as in rehabilitation programs to monitor patient progress. These instant tests can be used for both urine and saliva testing. Although the accuracy of such tests varies with the manufacturer, some kits have rates of accuracy correlating closely with laboratory test results.
=== Breath test ===
Breath test is a widespread method for quickly determining alcohol intoxication. A breath test measures the alcohol concentration in the body by a deep-lung breath. There are different instruments used for measuring the alcohol content of an individual though their breath. Breathalyzer is a widely known instrument which was developed in 1954 and contained chemicals unlike other breath-testing instruments. More modernly used instruments are the infrared light-absorption devices and fuel cell detectors, these two testers are microprocessor controlled meaning the operator only has to press the start button.
To get accurate readings on a breath-testing device the individual must blow for approximately 6 seconds and need to contain roughly 1.1 to 1.5 liters of breath. For a breath-test to result accurately and truly an operator must take steps such as avoiding measuring "mouth alcohol" which is a result from regurgitation, belching, or recent intake of an alcoholic beverage. To avoid measuring "mouth alcohol" the operator must not allow the individual that's taking the test to consume any materials for at least fifteen minutes before the breath test. When pulled over for a driving violation if an individual in the United States refuses to take a breath test that individual's driver's license can be suspended for a 6 to 12 months time period.
=== Hair testing ===
Hair analysis to detect addictive substances has been used by court systems in the United States, United Kingdom, Canada, and other countries worldwide. In the United States, hair testing has been accepted in court cases as forensic evidence following the Frye Rule, the Federal Rules of Evidence, and the Daubert Rule. As such, hair testing results are legally and scientifically recognized as admissible evidence. Hair testing is commonly used in the USA as pre-employment drug test. The detection time for this test is roughly 3 months, which is the time, that takes head hair to grow ca. 1.5 inches, that are collected as a specimen. Longer detection times are possible with longer hair samples.
A 2014 collaborative US study of 359 adults with moderate-risk drug use found, that a large number of participants, who reported drug use in the last 3 months, had negative hair tests. The tests were done using an immunoassay followed by a confirmatory GC-MS.
For marijuana, only about half of self-disclosed users had a positive hair test. Under-identification of drug use by hair testing (or over-reporting) was also widespread for cocaine, amphetamines, and opioids. Because such under-identification was more common among participants, who self-reported an infrequent use, the authors suggested, that the immunoassay did not have the sensitivity required for such infrequent uses. It is worth noting, that most earlier studies reported, that hair tests found ca. 50-fold higher prevalence of illicit drug use, than self reports.
In late 2022 the US Federal Motor Carrier Safety Administration denied a petition to recognize hair samples as an alternative (to the currently used urine samples) drug-testing method for truckers. The agency did not comment on the test validity, but rather stated, that it lacks the statutory authority to adopt new analytical methods.
Although some lower courts may have accepted hair test evidence, there is no controlling judicial ruling in either the federal or any state system declaring any type of hair test as reliable.
Hair testing is now recognized in both the UK and US judicial systems. There are guidelines for hair testing that have been published by the Society of Hair Testing (a private company in France) that specify the markers to be tested for and the cutoff concentrations that need to be tested. Addictive substances that can be detected include Cannabis, Cocaine, Amphetamines and drugs new to the UK such as Mephedrone.
==== Alcohol ====
In contrast to other drugs consumed, alcohol is deposited directly in the hair. For this reason the investigation procedure looks for direct products of ethanol metabolism. The main part of alcohol is oxidized in the human body. This means it is released as water and carbon dioxide. One part of the alcohol reacts with fatty acids to produce esters. The sum of the concentrations of four of these fatty acid ethyl esters (FAEEs: ethyl myristate, ethyl palmitate, ethyl oleate and ethyl stearate) are used as indicators of the alcohol consumption. The amounts found in hair are measured in nanograms (one nanogram equals only one billionth of a gram), however with the benefit of modern technology, it is possible to detect such small amounts. In the detection of ethyl glucuronide, or EtG, testing can detect amounts in picograms (one picogram equals 0.001 nanograms).
However, there is one major difference between most drugs and alcohol metabolites in the way in which they enter into the hair: on the one hand like other drugs FAEEs enter into the hair via the keratinocytes, the cells responsible for hair growth. These cells form the hair in the root and then grow through the skin surface taking any substances with them. On the other hand, the sebaceous glands produce FAEEs in the scalp and these migrate together with the sebum along the hair shaft (Auwärter et al., 2001, Pragst et al., 2004). So these glands lubricate not only the part of the hair that is just growing at 0.3 mm per day on the skin surface, but also the more mature hair growth, providing it with a protective layer of fat.
FAEEs (nanogram = one billionth of a gram) appear in hair in almost one order of magnitude lower than (the relevant order of magnitude of) EtG (picogram = one trillionth of a gram). It has been technically possible to measure FAEEs since 1993, and the first study reporting the detection of EtG in hair was done by Sachs in 1993.
In practice, most hair which is sent for analysis has been cosmetically treated in some way (bleached, permed etc.). It has been proven that FAEEs are not significantly affected by such treatments (Hartwig et al., 2003a). FAEE concentrations in hair from other body sites can be interpreted in a similar fashion as scalp hair (Hartwig et al., 2003b).
=== Presumptive substance testing ===
Presumptive substance tests attempt to identify a suspicious substance, material or surface where traces of drugs are thought to be, instead of testing individuals through biological methods such as urine or hair testing. The test involves mixing the suspicious material with a chemical in order to trigger a color change to indicate if a drug is present. Most are now available over-the-counter for consumer use, and do not require a lab to read results.
Benefits to this method include that the person who is suspected of drug use does not need to be confronted or aware of testing. Only a very small amount of material is needed to obtain results, and can be used to test powder, pills, capsules, crystals, or organic material. There is also the ability to detect illicit material when mixed with other non-illicit materials. The tests are used for general screening purposes, offering a generic result for the presence of a wide range of drugs, including Heroin, Cocaine, Methamphetamine, Amphetamine, Ecstasy/MDMA, Methadone, Ketamine, PCP, PMA, DMT, MDPV, and may detect rapidly evolving synthetic designer drugs. Separate tests for Marijuana/Hashish are also available.
There are five primary color-tests reagents used for general screening purposes. The Marquis reagent turns into a variety of colors when in the presence of different substances. Dille-Koppanyi reagent uses two chemical solutions which turns a violet-blue color in the presence of barbiturates. Duquenois-Levine reagent is a series of chemical solutions that turn to the color of purple when the vegetation of marijuana is added. Van Urk reagent turns blue-purple when in the presence of LSD. Scott test's chemical solution shows up as a faint blue for cocaine base.
In recent years, the use of presumptive test kits in the criminal justice system has come under great scrutiny due to the lack to forensic studies, questioned reliability, rendering of false positives with legal substances, and wrongful arrests.
=== Saliva drug screen / Oral fluid-based drug screen ===
Saliva / oral fluid-based drug tests can generally detect use during the previous few days. It is better at detecting very recent use of a substance. THC may only be detectable for 2–24 hours in most cases. On site drug tests are allowed per the Department of Labor.
Detection in saliva tests begins almost immediately upon use of the following substances, and lasts for approximately the following times:
Alcohol: 6-12 h
Marijuana: 1-24h
A disadvantage of saliva based drug testing is that it is not approved by FDA or SAMHSA for use with DOT / Federal Mandated Drug Testing. Oral fluid is not considered a bio-hazard unless there is visible blood; however, it should be treated with care.
=== Sweat drug screen ===
Sweat patches are attached to the skin to collect sweat over a long period of time (up to 14 days). These are used by child protective services, parole departments, and other government institutions concerned with drug use over long periods, when urine testing is not practical.
There are also surface drug tests that test for the metabolite of parent drug groups in the residue of drugs left in sweat. An example of a rapid, non-invasive, sweat-based drug test is fingerprint drug screening. This 10 minute fingerprint test is in use by a variety of organisations in the UK and beyond, including within workplaces, drug treatment and family safeguarding services at airport border control (to detect drug mules) and in mortuaries to assist in investigations into cause of death.
=== Blood ===
Drug-testing a blood sample measures whether or not a drug or a metabolite is in the body at a particular time. These types of tests are considered to be the most accurate way of telling if a person is intoxicated. Blood drug tests are not used very often because they need specialized equipment and medically trained administrators.
Depending on how much marijuana was consumed, it can usually be detected in blood tests within six hours of consumption. After six hours has passed, the concentration of marijuana in the blood decreases significantly. It generally disappears completely within 30 days.
=== Random drug testing ===
Can occur at any time, usually when the investigator has reason to believe that a substance is possibly being used by the subject by behavior or immediately after an employee-related incident occurs during work hours. Testing protocol typically conforms to the national medical standard, candidates are given up to 120 minutes to reasonably produce a urine sample from the time of commencement (in some instances this time frame may be extended at the examiner's discretion).
=== Diagnostic screening ===
In the case of life-threatening symptoms, unconsciousness, or bizarre behavior in an emergency situation, screening for common drugs and toxins may help find the cause, called a toxicology test or tox screen to denote the broader area of possible substances beyond just self-administered drugs. These tests can also be done post-mortem during an autopsy in cases where a death was not expected. The test is usually done within 96 hours (4 days) after the desire for the test is realized. Both a urine sample and a blood sample may be tested. A blood sample is routinely used to detect ethanol/methanol and ASA/paracetamol intoxication. Various panels are used for screening urine samples for common substances, e.g. triage 8 that detects amphetamines, benzodiazepines, cocaine, methadone, opiates, cannabis, barbiturates and tricyclic antidepressants. Results are given in 10–15 min.
Similar screenings may be used to evaluate the possible use of date rape drugs. This is usually done on a urine sample.
=== Optional harm reduction scheme ===
Drug checks/tests (also known as pill testing) are provided at some events such as concerts and music festivals. Attendees can voluntarily hand over a sample of any drug or drugs in their possession to be tested to check what the drug is and its purity. The scheme is used as a harm reduction technique so people are more aware of what they are taking and the potential risks.
=== Occupational harm reduction strategies ===
Drug and alcohol impairment while at work increases the risk of work-place accidents and decreases productivity. Employers such as the commercial driving and airline industry may conduct random drug tests on employees with the goal of deterring use to improve safety. There is some evidence that increasing the use of random drug testing in the airline industry reduces the percentage of people who test positive, however, it is unclear if this decrease is associated with a corresponding decrease in fatal or non-fatal injuries, other accidents, number of days absent from work. It is also not clear if there are other unwanted side effects that may result from random drug and alcohol testing in the workplace.
== Commonly tested substances ==
=== Anabolic steroids ===
Anabolic steroids are used to enhance performance in sports and as they are prohibited in most high-level competitions drug testing is used extensively in order to enforce this prohibition. This is particularly so in individual (rather than team) sports such as athletics and cycling.
== Methodologies ==
Before testing samples, the tamper-evident seal is checked for integrity. If it appears to have been tampered with or damaged, the laboratory rejects the sample and does not test it.
Next, the sample must be made testable. Urine and oral fluid can be used "as is" for some tests, but other tests require the drugs to be extracted from urine. Strands of hair, patches, and blood must be prepared before testing. Hair is washed in order to eliminate second-hand sources of drugs on the surface of the hair, then the keratin is broken down using enzymes. Blood plasma may need to be separated by centrifuge from blood cells prior to testing. Sweat patches are opened and the sweat collection component is removed and soaked in a solvent to dissolve any drugs present.
Laboratory-based drug testing is done in two steps. The first step is the screening test, which is an immunoassay based test applied to all samples. The second step, known as the confirmation test, is usually undertaken by a laboratory using highly specific chromatographic techniques and only applied to samples that test positive during the screening test. Screening tests are usually done by immunoassay (EMIT, ELISA, and RIA are the most common). A "dipstick" drug testing method which could provide screening test capabilities to field investigators has been developed at the University of Illinois.
After a suspected positive sample is detected during screening, the sample is tested using a confirmation test. Samples that are negative on the screening test are discarded and reported as negative. The confirmation test in most laboratories (and all SAMHSA certified labs) is performed using mass spectrometry, and is precise but expensive. False positive samples from the screening test will almost always be negative on the confirmation test. Samples testing positive during both screening and confirmation tests are reported as positive to the entity that ordered the test. Most laboratories save positive samples for some period of months or years in the event of a disputed result or lawsuit. For workplace drug testing, a positive result is generally not confirmed without a review by a Medical Review Officer who will normally interview the subject of the drug test.
=== Urine drug testing ===
Urine drug test kits are available as on-site tests, or laboratory analysis. Urinalysis is the most common test type and used by federally mandated drug testing programs and is considered the Gold Standard of drug testing. Urine based tests have been upheld in most courts for more than 30 years. However, urinalysis conducted by the Department of Defense has been challenged for reliability of testing the metabolite of cocaine. There are two associated metabolites of cocaine, benzoylecgonine (BZ) and ecgonine methyl ester (EME), the first (BZ) is created by the presence of cocaine in an aqueous solution with a pH greater than 7.0, while the second (EME) results from the actual human metabolic process. The presence of EME confirms actual ingestion of cocaine by a human being, while the presence of BZ is indicative only. BZ without EME is evidence of sample contamination, however, the US Department of Defense has chosen not to test for EME in its urinalysis program.
A number of different analyses (defined as the unknown substance being tested for) are available on Urine Drug Screens.
=== Spray drug testing ===
Spray (sweat) drug test kits are non-invasive. It is a simple process to collect the required specimen, no bathroom is needed, no laboratory is required for analysis, and the tests themselves are difficult to manipulate and relatively tamper-resistant. The detection window is long and can detect recent drug use within several hours.
There are also some disadvantages to spray or sweat testing. There is not much variety in these drug tests, only a limited number of drugs can be detected, prices tend to be higher, and inconclusive results can be produced by variations in sweat production rates in donors. They also have a relatively long specimen collection period and are more vulnerable to contamination than other common forms of testing.
=== Hair drug testing ===
Hair drug testing is a method that can detect drug use over a much longer period of time than saliva, sweat or urine tests. Hair testing is also more robust with respect to tampering. Thus, hair sampling is preferred by the US military and by many large corporations, which are subject to Drug-Free Workplace Act of 1988.
Head hair normally growth at the rate of 0.5 inches per month. Thus, the most common hair sample length of 1.5" from the scalp would detect drug use within the last 90-100 days. 80-120 strands of hair are sufficient for the test. In the absence of hair on the head, body hair can be used as an acceptable substitute. This includes facial hair, the underarms, arms, and legs or even pubic hair. Because body hair usually grows slower than head hair, drugs can often be detected in body hair for longer periods, e.g. up to 12 months.
Most drugs are analysed in hair samples not as the original psychoactive molecules, but rather as their metabolytes. For example, ethanol is determined as ethyl glucuronide, while cocaine use is confirmed using ecgonine. Testing for metabolytes reduces the likelihood of false positive results due to contamination. One disadvantage of hair testing is, that it cannot detect recent drug use, because it takes at least a week after a drug intake for the metabolytes to show up in a growing hair above the skin. Urine tests are better suited for detecting recent (within a week) drug use.
In a practical test, hair sample is usually washed with a low polarity solvent (such as dichloromethane) to remove surface contaminations. Then, the sample is pulverized and extracted with a more polar solvent, such as methanol.
Although thousand different substances can be determined in a single gas chromatography–mass spectrometry or liquid chromatography–mass spectrometry experiment, due to the low concentration of analytes, practical measurements (see selective ion monitoring) are limited to a smaller number (10-20) of analytes. Designer drugs are usually missed in such measurements, because the analyst must know in advance what chemicals to look for.
Most hair testing laboratories use the aforementioned chromato-mass-spectrometry methods for confirmation or for rarely tested drugs only. Mass screening (preliminary or final) is usually done with immunoassays, because of their lower cost.
== Legality, ethics and politics ==
The results of federally mandating drug testing were similar to the effects of simply extending to the trucking industry the right to perform drug tests, and it has been argued that the latter approach would have been as effective at lower cost.
Psychologist Tony Buon has criticized the use of workplace drug testing on a number of grounds, including:
Flawed technology: The real world performance of testing is much lower than that claimed by its promoters. Buon suggest that tests are probably adequate for rehabilitation and treatment situations, possibly adequate for pre-employment situations, but not for dismissing employees.
Ethical Issues: Because of the fairly simple ways that an employee can invalidate the test, drug testing must be strictly monitored. This means that the specimen must be observed leaving the body. Many legal objections currently being raised in the courts about drug testing are pointing to legal requirements of prior notice, consent, due process, and cause.
Wrong focus: As has been shown with Employee Assistance Programs, the focus of management concern should be on work performance decline. Buon suggests effective management practices are an infinitely better approach to managing workplace alcohol and other drug issues.
Tony Buon has also reported by the CIPD as stating that "drug testing captures the stupid—experienced drug users know how to beat the tests".
From a penological standpoint, one purpose of drug testing is to help classify the
people taking the drug test within risk groups so that those who pose more of a danger to the public can be incapacitated through incarceration or other restrictions on liberty. Thus, the drug testing serves a crime control purpose even if there is no expectation of rehabilitating the drug user through treatment, deterring drug use through sanctions, or sending a message that drug use is a deviant behavior that will not be tolerated.
=== United Kingdom ===
A study in 2004 by the Independent Inquiry into Drug Testing at Work found that attempts by employers to force employees to take drug tests could potentially be challenged as a violation of privacy under the Human Rights Act 1998 and Article 8 of the European Convention of Human Rights. However, this does not apply to industries where drug testing is a matter of personal and public safety or security rather than productivity.
=== United States ===
In consultation with Dr. Carlton Turner, President Ronald Reagan issued Executive Order 12564. In doing so, he instituted mandatory drug-testing for all safety-sensitive executive-level and civil-service Federal employees. This was challenged in the courts by the National Treasury Employees Union. In 1988, this challenge was considered by the US Supreme Court. A similar challenge resulted in the Court extending the drug-free workplace concept to the private sector. These decisions were then incorporated into the White House Drug Control Strategy directive issued by President George H.W. Bush in 1989. All defendants serving on federal probation or federal supervised release are required to submit to at least three drug tests. Failing a drug test can be construed as possession of a controlled substance, resulting in mandatory revocation and imprisonment.
There have been inconsistent evaluation results as to whether continued pretrial drug testing has beneficial effects.
Testing positive can lead to bail not being granted, or if bail has already been granted, to bail revocation or other sanctions. Arizona also adopted a law in 1987 authorizing mandatory drug testing of felony arrestees for the purpose of informing the pretrial release decision, and the District of Columbia has had a similar law since the 1970s. It has been argued that one of the problems with such testing is that there is often not enough time between the arrest and the bail decision to confirm positive results using GC/MS technology. It has also been argued that such testing potentially implicates the Fifth Amendment privilege against self-incrimination, the right to due process (including the prohibition against gathering evidence in a manner that shocks the conscience or constitutes outrageous government conduct), and the prohibition against unreasonable searches and seizures contained in the Fourth Amendment.
According to Henriksson, the anti-drug appeals of the Reagan administration "created an environment in which many employers felt compelled to implement drug testing programs because failure to do so might be perceived as condoning drug use. This fear was easily exploited by aggressive marketing and sales forces, who often overstated the value of testing and painted a bleak picture of the consequences of failing to use the drug testing product or service being offered." On March 10, 1986, the Commission on Organized Crime asked all U.S. companies to test employees for drug use. By 1987, nearly 25% of the Fortune 500 companies used drug tests.
According to an uncontrolled self-report study done by DATIA and Society for Human Resource Management in 2012 (sample of 6,000 randomly selected human resource professionals), human resource professionals reported the following results after implementing a drug testing program: 19% of companies reported a subjective increase in employee productivity, 16% reported a decrease in employee turnover (8% reported an increase), and unspecified percentages reported decreases in absenteeism and improvement of workers' compensation incidence rates.
According to US Chamber of Commerce 70% of all illicit drug users are employed. Some industries have high rates of employee drug use such as construction (12.8%), repair (11.1%), and hospitality (7.9-16.3%).
=== Australia ===
A person conducting a business or undertaking (PCBU—the new term that includes employers) has duties under the work health and safety (WHS) legislation to ensure a worker affected by alcohol or other drugs does not place themselves or other persons at risk of injury while at work. Workplace policies and prevention programs can help change the norms and culture around substance use.
All organisations—large and small—can benefit from an agreed policy on alcohol and drug misuse that applies to all workers. Such a policy should form part of an organisations overall health and safety management system. PCBUs are encouraged to establish a policy and procedure, in consultation with workers, to constructively manage alcohol and other drug related hazards in their workplace. A comprehensive workplace alcohol and other drug policy should apply to everyone in the workplace and include prevention, education, counselling and rehabilitation arrangements. In addition, the roles and responsibilities of managers and supervisors should be clearly outlined.
All Australian workplace drug testing must comply with Australian standard AS/NZS4308:2008.
In Victoria, roadside saliva tests detect drugs that contain:
THC (Delta-9 tetrahydrocannabinol), the active component in cannabis.
methamphetamine, also known as "ice", "crystal" and "crank".
MDMA (Methylenedioxymethamphetamine), which is known as ecstasy.
In February 2016 a New South Wales magistrate "acquitted a man who tested positive for cannabis". He had been arrested and charged after testing positive during a roadside drug test, despite not having smoked for nine days. He was relying on advice previously given to him by police.
== Refusal ==
In the United States federal criminal system, refusing to take a drug test triggers an automatic revocation of probation or supervised release.
In Victoria, Australia the driver of the car has the option to refuse the drug test. Refusing to undergo a drug test or refusing to undergo a secondary drug test after the first one, triggers an automatic suspension and disqualification for a period of two years and a fine of AUD$1000. The second refusal triggers an automatic suspension and disqualification for a period of four years and an even larger fine.
=== Historical cases ===
In 2000, an Australian Mining Company South Blackwater Coal Ltd with 400 employees, imposed drug-testing procedures, and the trade unions advised their members to refuse to take the tests, partly because a positive result does not necessarily indicate present impairment; the workers were stood-down by the company without pay for a week.
In 2003, sixteen members of the Chicago White Sox considered refusing to take a drug test, in hopes of making steroid testing mandatory.
In 2006, Levy County, Florida, volunteer librarians resigned en masse rather than take drug tests.
In 2010, Iranian super heavyweight class weightlifters refused to submit to a drug test authorized by the Iran Weightlifting League.
== See also ==
== References ==
== External links ==
National Institute on Drug Abuse Archived May 29, 2020, at the Wayback Machine | Wikipedia/Drug_test |
The Illegal drug trade in Puerto Rico is a problem from a criminal, social, and medical perspective. Located in the Caribbean, Puerto Rico has become a major transshipment point for drugs into the United States. Violent and property crimes have increased due in part to dealers trying to keep their drug business afloat, using guns and violence to protect themselves, their turfs, and drug habits.
Crimes related to drugs are not the only crimes plaguing the island. Along with gang violence the island has also been victim to Police and political corruption.
== Chronology ==
=== 1970–2008 ===
The Government of Puerto Rico has struggled to combat illegal drug use and the resulting crime since the mid-1970s. Their efforts have been referred to as a "War on Drugs". Though drug use was uncommon in Puerto Rico in the 1950s, it markedly increased in the late 1960s. In the 1970s the increase in drug use, particularly among those under the age of 25, became a major concern in Puerto Rico. During this era, a person named Rafy Dones surfaced as one of the first, alleged major drug traffickers operating in Puerto Rico; he was sentenced to a jail term on 30 September 1977. A number of drug cartels have used Puerto Rico as a transfer point for trafficking cocaine to the mainland United States.
Many Puerto Ricans have attributed the increase in crime to the drug trade. This led to a major focus on crime and drugs in Puerto Rican politics. In response, federal and local law enforcement agencies have attempted to integrate their efforts to fight drug crime.
Strategies used by the government of Puerto Rico include long sentences for criminals, increased funding for law enforcement equipment, and the construction of new prisons. At times, however, the DEA and the Puerto Rican police have struggled to work together and some commentators have questioned the effectiveness of government drug policy.
In the early 1990s, law enforcement began targeting white collar drug users.
=== 2009–present ===
The start of the "Drug Wars" in Puerto Rico was in 2009 in a conflict between Police and drug dealers which police wounded and killed two men. This occurred in Naranjito, Puerto Rico, the place where the drug dealers distributed their drugs to many places in Puerto Rico. In the house they found AK-47, M9 pistols and the drugs. Also they found that they were working with corrupt politicians to approve marijuana legalization and the export of exotic animals. In 2010 police captured 16 drug dealer "clans" that had the same information and they worked together to defeat opposing dealers. They also started to "clean house" in 2010, when they killed about 44 men attached to some drug dealers or those that were compromising the dealer. In 2011 the death toll was 1,266 at one point, due to many big drug arrests different gangs went into war with each other for the control of drugs in the island. In 2011 it was discovered that many of the killings were to cover up some corrupt politicians. In 2012, around 1,000 murders were reported. Also in Bayamon, a major city of Puerto Rico, many drug cartels started to defend their dealers by getting snipers and attackers on rooftops. "Sikarios" would be put on the rooftops to defend their drug turf in different housing projects due to wars against rival gangs that would try to take over the drug turf. Police captured a sniper in late 2011, the sniper had a Dragunov Caliber Sniper Rifle and was arrested with 5 other drug dealers. In early 2012, two assassinations occurred in Humacao involving the Carteli.
The FBI, with its field office in San Juan, along with the Department of Homeland Security, and the DEA have multiple task forces working on the illegal drug trade in Puerto Rico.
== Drug trafficking ==
As early as 1978, Puerto Rico had already become a transshipment point for illegal drugs that are smuggled from source countries like Colombia, Venezuela, and Peru into the U.S. mainland. Most of it is transported to and through the island from drug trafficking organizations in the Dominican Republic and Colombia, and criminal organizations in Puerto Rico.
=== Cocaine ===
U.S. Customs and Border Protection (CBP) seized 1,176.74 pounds of cocaine in 2001 from commercial maritime vessels and 14, 932.53 pounds of cocaine from private maritime vessels in Puerto Rico. Go-fast boats are the most favorable, as they are fast and stealthy, and have been used to intercept drug shipments that have been dropped off into the open water from other larger ships or airdropped from aircraft.
In June 2012, 36 people were arrested in Puerto Rico and the U.S. mainland for smuggling 61,000 pounds of cocaine into the U.S through Puerto Rico's Luis Muñoz Marín International Airport aboard flights operated by American Airlines. The smuggling had been taking place since 1999.
In 1996, a group of researchers from Puerto Rico's Mental Health and Anti Addiction Services Administration, published the results of a study involving 849 out-of-treatment drug users in the San Juan area. Their study found that 36.5% of the drug users in the study were crack cocaine users only, 42.4% were drug injectors only and 21.1% were both drug injectors and crack users.
In April 2021, a shipment of cocaine with an estimated value of $50 million was intercepted in Yabucoa.
=== Heroin ===
In 2001, U.S. Customs and Border Protection in Puerto Rico seized 56 kilograms of heroin from commercial aircraft at airports and 28 kilograms of heroin from commercial maritime vessels in Puerto Rico. That same year, government officials arrested seven individuals in Puerto Rico, for swallowing between 36 and 98 condoms full of heroin, when they arrived from Aruba on a cruise ship. In June 2002, drug detecting dogs detected and CBP seized 24 kilograms of heroin in a cargo storage area on a pier in San Juan. That same year federal law enforcement officials in San Juan seized 1.4 kilograms of heroin from a passenger arriving from Aruba on a cruise ship.
Addicts "shooting up" with dirty needles has created a public health emergency in Puerto Rico with an HIV positive rate that is 4 times higher than the U.S. national average. Hogares CREA is one of the few organizations offering addicts rehabilitation services.
=== Marijuana ===
In 2001, CBP confiscated 205 kilos of marijuana at airports throughout Puerto Rico. In 2002, a resident of San Juan was arrested at the airport, when government officials found 12.7 kilograms of marijuana hidden in his luggage.
== Police corruption ==
In 2008, four police officers in Puerto Rico were arrested by the Federal Bureau of Investigation (FBI), including a Lieutenant with 33 years on the force, for extortion and distribution of cocaine and heroin. In 2007, 9 police officers and their lieutenant were arrested for planting drug evidence, including cocaine, heroin, and crack, on people living in the city's low-income housing projects, prompting Puerto Rico's attorney general's office to review previous cases, making sure no innocent people were put in prison. Between 2003 and 2007, 100 officers had been under investigation and 75 others convicted under federal court for police corruption.
In 2001, one of the biggest police corruption busts in U.S. history took place in Puerto Rico, when 28 state police officers in Puerto Rico were arrested for drug-running charges. The yearlong undercover operation was initiated by the FBI, after authorities got a tip about the police possibly being involved in drug dealing, and protecting cocaine dealers and shipments and movement throughout the island. Between 1993 and 2000, 1,000 police officers in Puerto Rico lost their jobs from the department due to criminal charges. Police corruption in Puerto Rico stems from the fact that police officers make small wages and are so close to the cocaine trafficking.
Operation Guard Shack was a two-year FBI investigation into law enforcement corruption in Puerto Rico. The operation came to a conclusion on 6 October 2010 with a series of pre-dawn raids that led to over 130 arrests of members of the Puerto Rico Police Department, various municipal departments, and the Puerto Rico Corrections Department. The operation began at 3 a.m., when 65 tactical teams, including FBI SWAT and the Hostage Rescue Team (HRT), fanned out across the island in a series of sneak attack arrests. On hand were a range of Bureau personnel—crisis negotiators, evidence response team members, canines and their handlers, and 80 medical personnel from first responders and nurses to a trauma surgeon and a veterinarian. The central thread of the corruption was law enforcement officers providing protection and other services to drug traffickers. Over 1,000 agents of the FBI conducted the raids. Many of them were flown in secretly. The agency characterized the action as, "likely the largest police corruption case in the FBI's history."
== Gangs ==
It is cheap and easy to buy and deal to the public in housing projects in Puerto Rico, leading to the second highest homicide rates in the United States or its territories. New gangs like La ONU and Rompe ONU are also prominent in Puerto Rico. They are in the illegal drug trade.
== Crime reduction ==
The Puerto Rican government has implemented a series of law enforcement operations in relation to the federal "war on drugs" in order to minimize drug-related crimes and trafficking on the island. In 1985, the government started Operation Greenback, an investigation by the FBI, Internal Revenue Service (IRS), the Department of Justice (DOJ), and the Drug Enforcement Administration (DEA), into the inconsistencies between the drastic increase of cash flow into the Puerto Rican economy and the double digit unemployment rate and bad economy in the 70s and early 1980s. The operation uncovered money laundering schemes from within financial institutions and from the sale of illegal lottery tickets. Federal agents raided 10 banks and arrested 17 people on money laundering charges.
In 1990, Operation Lucky Strike was put in motion by the FBI and local law enforcement officials, when residents of Vega Baja unearthed $20 million on a nearby farm. They tried to stop the circulation of the illegal money and mobilized to arrest the individuals connected to the money.
== See also ==
Puerto Rican people
Organizacion de Narcotraficantes Unidos-"La ONU"
Edsel Torres Gomez
Cayey Massacre
Wes Solano
Alexis Candelario Santana
2009 Sabana Seca massacre
Alex Trujillo
Papo Cachete
Regional:
Mexican War on Drugs, an armed conflict between the Mexican government and drug trafficking cartels
Colombian War on Drugs, an ongoing armed conflict involving the Colombian government, Colombian Drug gangs, narco-paramilitary groups and guerrillas (the guerrillas are known to use drug trafficking to finance their operations).
== References ==
== External links ==
Puerto Rico Herald Crime and Punishment
Puerto Rico Herald Crime and Corruption | Wikipedia/Illegal_drug_trade_in_Puerto_Rico |
The illegal drug trade in Aruba involves trans-shipment of cocaine and other drugs through Aruba to the United States.
== Background ==
Corruption in Aruba is so widespread that Claire Sterling, widely acclaimed for her works on drugs and crime, said of it: "The world's first independent mafia state emerged in 1993." The Italian daily Corriere della Sera described Aruba as "the first state to be bought by the bosses Cosa Nostra." Between 1988 and 1992 the Cuntrera-Caruana Mafia clan was said to have acquired 60% of Aruba through investments in hotels, casinos and the election-campaign of a Prime Minister. As a result of the public outcry, Aruba's independence from the Netherlands, planned for 1996, was cancelled.
== Tugboat Off Aruba Coast ==
The route taken by a strange tugboat that was intercepted off the coast of Aruba and found to have two tons of cocaine on board provides information regarding smuggling techniques and the present position of the Caribbean island in the drug trade. According to El Pitazo, the tugboat was halted on October 13 in the territorial seas of Aruba, one of the Dutch Antilles' islands. The five-person crew, all Venezuelans, were detained and the boat was confiscated after 2.2 tons of cocaine were discovered during an Aruban government check of the vessel. Members of the Colombian navy have scoured the boat, which left from Cartagena, with drug-sniffing dogs. Authorities claimed that the cocaine was likely brought aboard the boat in open waters and that the boat eventually vanished from radar. A cocaine smuggling boat has been discovered in Aruba's territorial seas before this year. Off the island's northern shore, officials detained a suspicious watercraft in August. About 500 kilograms of cocaine were inside.
https://insightcrime.org/news/brief/tugboat-off-aruba-coast-hides-more-than-just-cocaine/
== Decline ==
While drug trafficking through Aruba used to be a major issue, it is much less so today. Aruba was removed from the US State Department's list of major drug producing and transit countries in 1999. The reason for this decline is unclear. Case Study
== See also ==
Designer drug
Drug liberalization
Drug policy of the Netherlands
Legality of cannabis by country
Minors and the legality of cannabis
== References == | Wikipedia/Illegal_drug_trade_in_Aruba |
A psychoactive drug, psychopharmaceutical, mind-altering drug, consciousness-altering drug, psychoactive substance, or psychotropic substance is a chemical substance that alters psychological functioning by modulating central nervous system activity. Psychoactive and psychotropic drugs both affect the brain, with psychotropics sometimes referring to psychiatric drugs or high-abuse substances, while “drug” can have negative connotations. Novel psychoactive substances are designer drugs made to mimic illegal ones and bypass laws.
Psychoactive drug use dates back to prehistory for medicinal and consciousness-altering purposes, with evidence of widespread cultural use. Many animals intentionally consume psychoactive substances, and some traditional legends suggest animals first introduced humans to their use. Psychoactive substances are used across cultures for purposes ranging from medicinal and therapeutic treatment of mental disorders and pain, to performance enhancement. Their effects are influenced by the drug itself, the environment, and individual factors. Psychoactive drugs are categorized by their pharmacological effects into types such as anxiolytics (reduce anxiety), empathogen–entactogens (enhance empathy), stimulants (increase CNS activity), depressants (decrease CNS activity), and hallucinogens (alter perception and emotions). Psychoactive drugs are administered through various routes—including oral ingestion, injection, rectal use, and inhalation—with the method and efficiency differing by drug.
Psychoactive drugs alter brain function by interacting with neurotransmitter systems—either enhancing or inhibiting activity—which can affect mood, perception, cognition, behavior, and potentially lead to dependence or long-term neural adaptations such as sensitization or tolerance. Addiction and dependence involve psychological and physical reliance on psychoactive substances, with treatments ranging from psychotherapy and medication to emerging psychedelic therapies; global prevalence is highest for alcohol, cannabis, and opioid use disorders.
The legality of psychoactive drugs has long been controversial, shaped by international treaties like the 1961 Single Convention on Narcotic Drugs and national laws such as the United States Controlled Substances Act. Distinctions are made between recreational and medical use. Enforcement varies across countries. While the 20th century saw global criminalization, recent shifts favor harm reduction and regulation over prohibition. Widely used psychoactive drugs include legal substances like caffeine, alcohol, and nicotine; prescribed medications such as SSRIs, opioids, and benzodiazepines; and illegal recreational drugs like cocaine, LSD, and MDMA.
== History ==
Psychoactive drug use can be traced to prehistory. Archaeological evidence of the use of psychoactive substances, mostly plants, dates back at least 10,000 years; historical evidence indicates cultural use 5,000 years ago. There is evidence of the chewing of coca leaves, for example, in Peruvian society 8,000 years ago.
Psychoactive substances have been used medicinally and to alter consciousness. Consciousness altering may be a primary drive, akin to the need to satiate thirst, hunger, or sexual desire. This may be manifest in the long history of drug use, and even in children's desire for spinning, swinging, or sliding, suggesting that the drive to alter one's state of mind is universal.
In The Hasheesh Eater (1857), American author Fitz Hugh Ludlow was one of the first to describe in modern terms the desire to change one's consciousness through drug use:[D]rugs are able to bring humans into the neighborhood of divine experience and can thus carry us up from our personal fate and the everyday circumstances of our life into a higher form of reality. It is, however, necessary to understand precisely what is meant by the use of drugs. We do not mean the purely physical craving ... That of which we speak is something much higher, namely the knowledge of the possibility of the soul to enter into a lighter being, and to catch a glimpse of deeper insights and more magnificent visions of the beauty, truth, and the divine than we are normally able to spy through the cracks in our prison cell. But there are not many drugs which have the power of stilling such craving. The entire catalog, at least to the extent that research has thus far written it, may include only opium, hashish, and in rarer cases alcohol, which has enlightening effects only upon very particular characters.
During the 20th century, the majority of countries initially responded to the use of recreational drugs by prohibiting production, distribution, or use through criminalization. A notable example occurred with Prohibition in the United States, where early in the century alcohol was made illegal for 13 years. In recent decades, an emerging perspective among governments and law enforcement holds that illicit drug use cannot be stopped through prohibition. One organization holding that view, Law Enforcement Against Prohibition (LEAP), concluded that "[in] fighting a war on drugs the government has increased the problems of society and made them far worse. A system of regulation rather than prohibition is a less harmful, more ethical and a more effective public policy."
In some countries, there has been a move toward harm reduction, where the use of illicit drugs is neither condoned nor promoted, but services and support are provided to ensure users have adequate factual information readily available, and that the negative effects of their use be minimized. Such is the case with Portugal's drug policy of decriminalization, with a primary goal of reducing the adverse health effects of drug use.
== Terminology ==
Psychoactive and psychotropic are often used interchangeably in general and academic sources, to describe substances that act on the brain to alter cognition and perception; some sources make a distinction between the terms. One narrower definition of psychotropic refers to drugs used to treat mental disorders, such as anxiolytic sedatives, antidepressants, antimanic agents, and neuroleptics. Another usage of psychotropic refers to substances determined to pose "high abuse liability", including stimulants, hallucinogens, opioids, and sedatives/hypnotics including alcohol. In international drug control, psychotropic substances refers to the substances specified in the Convention on Psychotropic Substances, which does not include narcotics.
The term "drug" has become a skunked term. "Drugs" can have a negative connotation, often associated with illegal substances like cocaine or heroin, despite the fact that the terms "drug" and "medicine" are sometimes used interchangeably.
Novel psychoactive substances (NPS), also known as "designer drugs" are a category of psychoactive drugs (substances) that are designed to mimic the effects of often illegal drugs, usually in efforts to circumvent existing drug laws.
== Types ==
Psychoactive drugs are divided according to their pharmacological effects. Common subtypes include:
Anxiolytics are medicinally used to reduce the symptoms of anxiety, and sometimes insomnia.
Example: benzodiazepines such as Xanax and Valium; barbiturates
Empathogen–entactogens alter emotional state, often resulting in an increased sense of empathy, closeness, and emotional communication.
Example: MDMA (ecstasy), MDA, 6-APB, AMT
Stimulants increase activity, or arousal, of the central nervous system. They can enhance alertness, attention, cognition, mood and physical performance. Some stimulants are used medicinally to treat individuals with ADHD and narcolepsy.
Examples: amphetamines, caffeine, cocaine, nicotine
Depressants reduce, or depress, activity and stimulation in the central nervous system. This category encompasses a spectrum of substances with sedative, soporific, and anesthetic properties, and include sedatives, hypnotics, and opioids.
Examples: ethanol (alcohol), opioids such as morphine, fentanyl, and codeine, barbiturates, and benzodiazepines
Hallucinogens, including psychedelics, dissociatives and deliriants, encompass substances that produce distinct alterations in perception, sensation of space and time, and emotional state.
Examples, psychedelics: Psilocybin, LSD, DMT (N,N-Dimethyltryptamine), mescaline, cannabis
Examples, dissociatives: Dextromethorphan, Salvia divinorum
Examples, deliriants: Datura, scopolamine
== Uses ==
The ways in which psychoactive substances are used vary widely between cultures. Some substances may have controlled or illegal uses, others may have shamanic purposes, and others are used medicinally. Examples would be social drinking, nootropic supplements, and sleep aids. Caffeine is the world's most widely consumed psychoactive substance, and is legal and unregulated in nearly all jurisdictions; in North America, 90% of adults consume caffeine daily.
=== Mental disorders ===
Psychiatric medications are psychoactive drugs prescribed for the management of mental and emotional disorders, or to aid in overcoming challenging behavior. There are six major classes of psychiatric medications:
Antidepressants treat disorders such as clinical depression, dysthymia, anxiety, eating disorders, and borderline personality disorder.
Stimulants, used to treat disorders such as attention deficit hyperactivity disorder and narcolepsy, and for weight reduction.
Antipsychotics, used to treat psychotic symptoms, such as those associated with schizophrenia or severe mania, or as adjuncts to relieve clinical depression.
Mood stabilizers, used to treat bipolar disorder and schizoaffective disorder.
Anxiolytics, used to treat anxiety disorders.
Depressants, used as hypnotics, sedatives, and anesthetics, depending upon dosage.
In addition, several psychoactive substances are currently employed to treat various addictions. These include acamprosate or naltrexone in the treatment of alcoholism, or methadone or buprenorphine maintenance therapy in the case of opioid addiction.
Exposure to psychoactive drugs can cause changes to the brain that counteract or augment some of their effects; these changes may be beneficial or harmful. However, there is a significant amount of evidence that the relapse rate of mental disorders negatively corresponds with the length of properly followed treatment regimens (that is, relapse rate substantially declines over time), and to a much greater degree than placebo.
=== Military ===
==== Drugs used by militaries ====
Militaries worldwide have used or are using various psychoactive drugs to treat pain and to improve performance of soldiers by suppressing hunger, increasing the ability to sustain effort without food, increasing and lengthening wakefulness and concentration, suppressing fear, reducing empathy, and improving reflexes and memory-recall among other things.
Both military and civilian American intelligence officials are known to have used psychoactive drugs while interrogating captives apprehended in its "war on terror". In July 2012 Jason Leopold and Jeffrey Kaye, psychologists and human rights workers, had a Freedom of Information Act request fulfilled that confirmed that the use of psychoactive drugs during interrogation was a long-standing
practice. Captives and former captives had been reporting medical staff collaborating with interrogators to drug captives with powerful psychoactive drugs prior to interrogation since the very first captives release.
In May 2003 recently released Pakistani captive Sha Mohammed Alikhel described the routine use of psychoactive drugs. He said that Jihan Wali, a captive kept in a nearby cell, was rendered catatonic through the use of these drugs.
Alcohol has a long association of military use, and has been called "liquid courage" for its role in preparing troops for battle, anaesthetize injured soldiers, and celebrate military victories. It has also served as a coping mechanism for combat stress reactions and a means of decompression from combat to everyday life. However, this reliance on alcohol can have negative consequences for physical and mental health.
The first documented case of a soldier overdosing on methamphetamine during combat, was the Finnish corporal Aimo Koivunen, a soldier who fought in the Winter War and the Continuation War.
==== Psychochemical warfare ====
Psychoactive drugs have been used in military applications as non-lethal weapons.
=== Pain management ===
Psychoactive drugs are often prescribed to manage pain. The subjective experience of pain is primarily regulated by endogenous opioid peptides. Thus, pain can often be managed using psychoactives that operate on this neurotransmitter system, also known as opioid receptor agonists. This class of drugs can be highly addictive, and includes opiate narcotics, like morphine and codeine. NSAIDs, such as aspirin and ibuprofen, are also analgesics. These agents also reduce eicosanoid-mediated inflammation by inhibiting the enzyme cyclooxygenase.
==== Anesthesia ====
General anesthetics are a class of psychoactive drug used on people to block physical pain and other sensations. Most anesthetics induce unconsciousness, allowing the person to undergo medical procedures like surgery, without the feelings of physical pain or emotional trauma. To induce unconsciousness, anesthetics affect the GABA and NMDA systems. For example, Propofol is a GABA agonist, and ketamine is an NMDA receptor antagonist.
=== Performance-enhancement ===
Performance-enhancing substances, also known as performance-enhancing drugs (PEDs), are substances that are used to improve any form of activity performance in humans. A well-known example of cheating in sports involves doping in sport, where banned physical performance-enhancing drugs are used by athletes and bodybuilders. Athletic performance-enhancing substances are sometimes referred as ergogenic aids. Cognitive performance-enhancing drugs, commonly called nootropics, are sometimes used by students to improve academic performance. Performance-enhancing substances are also used by military personnel to enhance combat performance.
=== Recreation ===
Many psychoactive substances are used for their mood and perception altering effects, including those with accepted uses in medicine and psychiatry. Examples of psychoactive substances include caffeine, alcohol, cocaine, LSD, nicotine, cannabis, and dextromethorphan. Classes of drugs frequently used recreationally include:
Stimulants, which activate the central nervous system. These are used recreationally for their euphoric effects.
Hallucinogens (psychedelics, dissociatives and deliriants), which induce perceptual and cognitive alterations.
Hypnotics, which depress the central nervous system.
Opioid analgesics, which also depress the central nervous system. These are used recreationally because of their euphoric effects.
Inhalants, in the forms of gas aerosols, or solvents, which are inhaled as a vapor because of their stupefying effects. Many inhalants also fall into the above categories (such as nitrous oxide which is also an analgesic).
In some modern and ancient cultures, drug usage is seen as a status symbol. Recreational drugs are seen as status symbols in settings such as at nightclubs and parties. For example, in ancient Egypt, gods were commonly pictured holding hallucinogenic plants.
Because there is controversy about regulation of recreational drugs, there is an ongoing debate about drug prohibition. Critics of prohibition believe that regulation of recreational drug use is a violation of personal autonomy and freedom. In the United States, critics have noted that prohibition or regulation of recreational and spiritual drug use might be unconstitutional, and causing more harm than is prevented.
Some people who take psychoactive drugs experience drug or substance induced psychosis. A 2019 systematic review and meta-analysis by Murrie et al. found that the pooled proportion of transition from substance-induced psychosis to schizophrenia was 25% (95% CI 18%–35%), compared with 36% (95% CI 30%–43%) for brief, atypical and not otherwise specified psychoses. Type of substance was the primary predictor of transition from drug-induced psychosis to schizophrenia, with highest rates associated with cannabis (6 studies, 34%, CI 25%–46%), hallucinogens (3 studies, 26%, CI 14%–43%) and amphetamines (5 studies, 22%, CI 14%–34%). Lower rates were reported for opioid (12%), alcohol (10%) and sedative (9%) induced psychoses. Transition rates were slightly lower in older cohorts but were not affected by sex, country of the study, hospital or community location, urban or rural setting, diagnostic methods, or duration of follow-up.
=== Ritual and spiritual ===
==== Offerings ====
Alcohol and tobacco (nicotine) have been and are used as offerings in various religions and spiritual practices. Coca leaves have been used as offerings in rituals.
===== Alcohol =====
According to the Catholic Church, the sacramental wine used in the Eucharist must contain alcohol. Canon 924 of the present Code of Canon Law (1983) states:
§3 The wine must be natural, made from grapes of the vine, and not corrupt.
==== Psychoactive use ====
===== Entheogen =====
Certain psychoactives, particularly hallucinogens, have been used for religious purposes since prehistoric times. Native Americans have used peyote cacti containing mescaline for religious ceremonies for as long as 5700 years. The muscimol-containing Amanita muscaria mushroom was used for ritual purposes throughout prehistoric Europe.
The use of entheogens for religious purposes resurfaced in the West during the counterculture movements of the 1960s and 70s. Under the leadership of Timothy Leary, new spiritual and intention-based movements began to use LSD and other hallucinogens as tools to access deeper inner exploration. In the United States, the use of peyote for ritual purposes is protected only for members of the Native American Church, which is allowed to cultivate and distribute peyote. However, the genuine religious use of peyote, regardless of one's personal ancestry, is protected in Colorado, Arizona, New Mexico, Nevada, and Oregon.
===== Psychedelic therapy =====
Psychedelic therapy (or psychedelic-assisted therapy) refers to the proposed use of psychedelic drugs, such as psilocybin, MDMA, LSD, and ayahuasca, to treat mental disorders. As of 2021, psychedelic drugs are controlled substances in most countries and psychedelic therapy is not legally available outside clinical trials, with some exceptions.
===== Psychonautics =====
The aims and methods of psychonautics, when state-altering substances are involved, is commonly distinguished from recreational drug use by research sources. Psychonautics as a means of exploration need not involve drugs, and may take place in a religious context with an established history. Cohen considers psychonautics closer in association to wisdom traditions and other transpersonal and integral movements.
=== Self-medication ===
Self-medication, sometime called do-it-yourself (DIY) medicine, is a human behavior in which an individual uses a substance or any exogenous influence to self-administer treatment for physical or psychological conditions, for example headaches or fatigue.
The substances most widely used in self-medication are over-the-counter drugs and dietary supplements, which are used to treat common health issues at home. These do not require a doctor's prescription to obtain and, in some countries, are available in supermarkets and convenience stores.
=== Sex ===
Sex and drugs date back to ancient humans and have been interlocked throughout human history. Both legal and illegal, the consumption of drugs and their effects on the human body encompasses all aspects of sex, including desire, performance, pleasure, conception, gestation, and disease.
There are many different types of drugs that are commonly associated with their effects on sex, including alcohol, cannabis, cocaine, MDMA, GHB, amphetamines, opioids, antidepressants, and many others.
=== Social movements ===
==== Cannabis ====
In the US, NORML (National Organization for the Reform of Marijuana Laws) has led since the 1970s a movement to legalize cannabis nationally. The so-called "420 movement" is the global association of the number 420 with cannabis consumption: April 20th – fourth month, twentieth day – has become an international counterculture holiday based on the celebration and consumption of cannabis; 4:20 pm on any day is a time to consume cannabis.
===== Operation Overgrow =====
Operation Overgrow is the name, given by cannabis activists, of an "operation" to spread marijuana seeds wildly "so it grows like weed". The thought behind the operation is to draw attention to the debate about legalization/decriminalization of marijuana.
=== Suicide ===
A drug overdose involves taking a dose of a drug that exceeds safe levels. In the UK (England and Wales) until 2013, a drug overdose was the most common suicide method in females. In 2019 in males the percentage is 16%. Self-poisoning accounts for the highest number of non-fatal suicide attempts. In the United States about 60% of suicide attempts and 14% of suicide deaths involve drug overdoses. The risk of death in suicide attempts involving overdose is about 2%.
Most people are under the influence of sedative-hypnotic drugs (such as alcohol or benzodiazepines) when they die by suicide, with alcoholism present in between 15% and 61% of cases. Countries that have higher rates of alcohol use and a greater density of bars generally also have higher rates of suicide. About 2.2–3.4% of those who have been treated for alcoholism at some point in their life die by suicide. Alcoholics who attempt suicide are usually male, older, and have tried to take their own lives in the past. In adolescents who misuse alcohol, neurological and psychological dysfunctions may contribute to the increased risk of suicide.
Overdose attempts using painkillers are among the most common, due to their easy availability over-the-counter.
== Route of administration ==
Psychoactive drugs are administered via oral ingestion as a tablet, capsule, powder, liquid, and beverage; via injection by subcutaneous, intramuscular, and intravenous route; via rectum by suppository and enema; and via inhalation by smoking, vaporizing, and snorting. The efficiency of each method of administration varies from drug to drug.
The psychiatric drugs fluoxetine, quetiapine, and lorazepam are ingested orally in tablet or capsule form. Alcohol and caffeine are ingested in beverage form; nicotine and cannabis are smoked or vaporized; peyote and psilocybin mushrooms are ingested in botanical form or dried; and crystalline drugs such as cocaine and methamphetamine are usually inhaled or snorted.
== Determinants of effects ==
The theory of dosage, set, and setting is a useful model in dealing with the effects of psychoactive substances, especially in a controlled therapeutic setting as well as in recreational use. Dr. Timothy Leary, based on his own experiences and systematic observations on psychedelics, developed this theory along with his colleagues Ralph Metzner, and Richard Alpert (Ram Dass) in the 1960s.
Dosage
The first factor, dosage, has been a truism since ancient times, or at least since Paracelsus who said, "Dose makes the poison." Some compounds are beneficial or pleasurable when consumed in small amounts, but harmful, deadly, or evoke discomfort in higher doses.
Set
The set is the internal attitudes and constitution of the person, including their expectations, wishes, fears, and sensitivity to the drug. This factor is especially important for the hallucinogens, which have the ability to make conscious experiences out of the unconscious. In traditional cultures, set is shaped primarily by the worldview, health and genetic characteristics that all the members of the culture share.
Setting
The third aspect is setting, which pertains to the surroundings, the place, and the time in which the experiences transpire.
This theory clearly states that the effects are equally the result of chemical, pharmacological, psychological, and physical influences. The model that Timothy Leary proposed applied to the psychedelics, although it also applies to other psychoactives.
== Effects ==
Psychoactive drugs operate by temporarily affecting a person's neurochemistry, which in turn causes changes in a person's mood, cognition, perception and behavior. There are many ways in which psychoactive drugs can affect the brain. Each drug has a specific action on one or more neurotransmitter or neuroreceptor in the brain.
Drugs that increase activity in particular neurotransmitter systems are called agonists. They act by increasing the synthesis of one or more neurotransmitters, by reducing its reuptake from the synapses, or by mimicking the action by binding directly to the postsynaptic receptor. Drugs that reduce neurotransmitter activity are called antagonists, and operate by interfering with synthesis or blocking postsynaptic receptors so that neurotransmitters cannot bind to them.
Exposure to a psychoactive substance can cause changes in the structure and functioning of neurons, as the nervous system tries to re-establish the homeostasis disrupted by the presence of the drug (see also, neuroplasticity). Exposure to antagonists for a particular neurotransmitter can increase the number of receptors for that neurotransmitter or the receptors themselves may become more responsive to neurotransmitters; this is called sensitization. Conversely, overstimulation of receptors for a particular neurotransmitter may cause a decrease in both number and sensitivity of these receptors, a process called desensitization or tolerance. Sensitization and desensitization are more likely to occur with long-term exposure, although they may occur after only a single exposure. These processes are thought to play a role in drug dependence and addiction. Physical dependence on antidepressants or anxiolytics may result in worse depression or anxiety, respectively, as withdrawal symptoms. Unfortunately, because clinical depression (also called major depressive disorder) is often referred to simply as depression, antidepressants are often requested by and prescribed for patients who are depressed, but not clinically depressed.
=== Affected neurotransmitter systems ===
The following is a brief table of notable drugs and their primary neurotransmitter, receptor or method of action. Many drugs act on more than one transmitter or receptor in the brain.
== Addiction and dependence ==
Psychoactive drugs are often associated with addiction or drug dependence. Dependence can be divided into two types: psychological dependence, by which a user experiences negative psychological or emotional withdrawal symptoms (e.g., depression) and physical dependence, by which a user must use a drug to avoid physically uncomfortable or even medically harmful physical withdrawal symptoms. Drugs that are both rewarding and reinforcing are addictive; these properties of a drug are mediated through activation of the mesolimbic dopamine pathway, particularly the nucleus accumbens. Not all addictive drugs are associated with physical dependence, e.g., amphetamine, and not all drugs that produce physical dependence are addictive drugs, e.g., oxymetazoline.
Globally, as of 2016, alcohol use disorders were the most prevalent of all substance use disorders (SUD) worldwide; cannabis dependence and opioid dependence were the next most prevalent SUDs.
Many professionals, self-help groups, and businesses specialize in drug rehabilitation, with varying degrees of success, and many parents attempt to influence the actions and choices of their children regarding psychoactives.
Common forms of rehabilitation include psychotherapy, support groups and pharmacotherapy, which uses psychoactive substances to reduce cravings and physiological withdrawal symptoms while a user is going through detox. Methadone, itself an opioid and a psychoactive substance, is a common treatment for heroin addiction, as is another opioid, buprenorphine. Recent research on addiction has shown some promise in using psychedelics such as ibogaine to treat and even cure drug addictions, although this has yet to become a widely accepted practice.
== Legality ==
The legality of psychoactive drugs has been controversial through most of recent history; the Second Opium War and Prohibition are two historical examples of legal controversy surrounding psychoactive drugs. However, in recent years, the most influential document regarding the legality of psychoactive drugs is the Single Convention on Narcotic Drugs, an international treaty signed in 1961 as an Act of the United Nations. Signed by 73 nations including the United States, the USSR, Pakistan, India, and the United Kingdom, the Single Convention on Narcotic Drugs established Schedules for the legality of each drug and laid out an international agreement to fight addiction to recreational drugs by combatting the sale, trafficking, and use of scheduled drugs. All countries that signed the treaty passed laws to implement these rules within their borders. However, some countries that signed the Single Convention on Narcotic Drugs, such as the Netherlands, are more lenient with their enforcement of these laws.
In the United States, the Food and Drug Administration (FDA) has authority over all drugs, including psychoactive drugs. The FDA regulates which psychoactive drugs are over the counter and which are only available with a prescription. However, certain psychoactive drugs, like alcohol, tobacco, and drugs listed in the Single Convention on Narcotic Drugs are subject to criminal laws. The Controlled Substances Act of 1970 regulates the recreational drugs outlined in the Single Convention on Narcotic Drugs. Alcohol is regulated by state governments, but the federal National Minimum Drinking Age Act penalizes states for not following a national drinking age. Tobacco is also regulated by all fifty state governments. Most people accept such restrictions and prohibitions of certain drugs, especially the "hard" drugs, which are illegal in most countries.
In the medical context, psychoactive drugs as a treatment for illness is widespread and generally accepted. Little controversy exists concerning over the counter psychoactive medications in antiemetics and antitussives. Psychoactive drugs are commonly prescribed to patients with psychiatric disorders. However, certain critics believe that certain prescription psychoactives, such as antidepressants and stimulants, are overprescribed and threaten patients' judgement and autonomy.
== Effect on animals ==
A number of animals consume different psychoactive plants, animals, berries and even fermented fruit, becoming intoxicated. An example of this is cats after consuming catnip. Traditional legends of sacred plants often contain references to animals that introduced humankind to their use. Animals and psychoactive plants appear to have co-evolved, possibly explaining why these chemicals and their receptors exist within the nervous system.
== Widely used psychoactive drugs ==
This is a list of commonly used drugs that contain psychoactive ingredients. Please note that the following lists contains legal and illegal drugs (based on the country's laws).
=== Common legal drugs ===
The most widely consumed psychotropic drugs worldwide are:
Caffeine
Alcohol
Nicotine
=== Common prescribed drugs ===
Benzodiazepines
Cannabis
Opioids
Amphetamines
SSRIs
=== Common street drugs ===
== See also ==
== Notes ==
== References ==
== External links ==
Neuroscience of Psychoactive Substance Use and Dependence by the WHO | Wikipedia/Psychoactive_drug |
A membrane transport protein is a membrane protein involved in the movement of ions, small molecules, and macromolecules, such as another protein, across a biological membrane. Transport proteins are integral transmembrane proteins; that is they exist permanently within and span the membrane across which they transport substances. The proteins may assist in the movement of substances by facilitated diffusion, active transport, osmosis, or reverse diffusion. The two main types of proteins involved in such transport are broadly categorized as either channels or carriers (a.k.a. transporters, or permeases). Examples of channel/carrier proteins include the GLUT 1 uniporter, sodium channels, and potassium channels. The solute carriers and atypical SLCs are secondary active or facilitative transporters in humans. Collectively membrane transporters and channels are known as the transportome. Transportomes govern cellular influx and efflux of not only ions and nutrients but drugs as well.
== Difference between channels and carriers ==
A carrier is not open simultaneously to both the extracellular and intracellular environments. Either its inner gate is open, or outer gate is open. In contrast, a channel can be open to both environments at the same time, allowing the molecules to diffuse without interruption. Carriers have binding sites, but pores and channels do not. When a channel is opened, millions of ions can pass through the membrane per second, but only 100 to 1000 molecules typically pass through a carrier molecule in the same time. Each carrier protein is designed to recognize only one substance or one group of very similar substances. Research has correlated defects in specific carrier proteins with specific diseases.
== Active transport ==
Active transport is the movement of a substance across a membrane against its concentration gradient. This is usually to accumulate high concentrations of molecules that a cell needs, such as glucose or amino acids. If the process uses chemical energy, such as adenosine triphosphate (ATP), it is called primary active transport. Membrane transport proteins that are driven directly by the hydrolysis of ATP are referred to as ATPase pumps. These types of pumps direct the exergonic hydrolysis of ATP to the unfavorable movement of molecules against their concentration gradient. Examples of ATPase pumps include P-type ATPase's, V-type ATPases, F-type ATPases, and ABC binding cassettes.
Secondary active transport involves the use of an electrochemical gradient, and does not use energy produced in the cell. Secondary active transport commonly uses types of carrier proteins, typically symporters and antiporters. Symporter proteins couple the transport of one molecule down its concentration gradient to the transport of another molecule against its concentration gradient, and both molecules diffuse in the same direction. Antiporter proteins transport one molecule down its concentration gradient to transport another molecule against its concentration gradient, but the molecules diffuse in opposite directions. As symporters and antiporters are involved in coupling the transport of two molecules, they are commonly referred to as cotransporters. Unlike channel proteins which only transport substances through membranes passively, carrier proteins can transport ions and molecules either passively through facilitated diffusion, or via secondary active transport. A carrier protein is required to move particles from areas of low concentration to areas of high concentration. These carrier proteins have receptors that bind to a specific molecule (substrate) needing transport. The molecule or ion to be transported (the substrate) must first bind at a binding site at the carrier molecule, with a certain binding affinity. Following binding, and while the binding site is facing the same way, the carrier will capture or occlude (take in and retain) the substrate within its molecular structure and cause an internal translocation so that the opening in the protein now faces the other side of the plasma membrane. The carrier protein substrate is released at that site, according to its binding affinity there.
== Facilitated diffusion ==
Facilitated diffusion is the passage of molecules or ions across a biological membrane through specific transport proteins and requires no energy input. Facilitated diffusion is used especially in the case of large polar molecules and charged ions; once such ions are dissolved in water they cannot diffuse freely across cell membranes due to the hydrophobic nature of the fatty acid tails of the phospholipids that make up the bilayers.
The type of carrier proteins used in facilitated diffusion is slightly different from those used in active transport. They are still transmembrane carrier proteins, but these are gated transmembrane channels, meaning they do not internally translocate, nor require ATP to function. The substrate is taken in one side of the gated carrier, and without using ATP the substrate is released into the cell. Facilitated diffusion does not require the use of ATP as facilitated diffusion, like simple diffusion, transports molecules or ions along their concentration gradient.
== Osmosis ==
Osmosis is the passive diffusion of water across a cell membrane from an area of high concentration to an area of low concentration. Since Osmosis is a passive process, like facilitated diffusion and simple diffusion, it does not require the use of ATP. Osmosis is important in regulating the balance of water and salt within cells, thus it plays a critical role in maintaining homeostasis. Aquaporins are integral membrane proteins that allow for the rapid passage of water and glycerol through membranes. The aquaporin monomers consist of six transmembrane alpha-helix domains and these monomers can assemble to form the aquaporin proteins. As four of these monomers come together to form the aquaporin protein, it is known as a homotetramer, meaning it is made up of four identical subunits. All aquaporins are tetrameric membrane integral proteins, and the water passes through each individual monomer channel rather than between all of the four channels. Since aquaporins are transmembrane channels for the diffusion of water, the channels that make up the aquaporin are typically lined with hydrophilic side chains to allow water to pass through.
== Reverse diffusion ==
Reverse transport, or transporter reversal, is a phenomenon in which the substrates of a membrane transport protein are moved in the opposite direction to that of their typical movement by the transporter. Transporter reversal typically occurs when a membrane transport protein is phosphorylated by a particular protein kinase, which is an enzyme that adds a phosphate group to proteins.
== Types ==
(Grouped by Transporter Classification database categories)
=== 1: Channels/pores ===
α-helical protein channels such as voltage-gated ion channel (VIC), ligand-gated ion channels(LGICs)
β-barrel porins such as aquaporin
channel-forming toxins, including colicins, diphtheria toxin, and others
Nonribosomally synthesized channels such as gramicidin
Holins; which function in export of enzymes that digest bacterial cell walls in an early step of cell lysis.
Facilitated diffusion occurs in and out of the cell membrane via channels/pores and carriers/porters.
Note:
Channels:
Channels are either in open state or closed state. When a channel is opened with a slight conformational switch, it is open to both environment simultaneously (extracellular and intracellular)
Pores:
Pores are continuously open to these both environment, because they do not undergo conformational changes. They are always open and active.
=== 2: Electrochemical potential-driven transporters ===
Also named carrier proteins or secondary carriers.
2.A: Porters (uniporters, symporters, antiporters), SLCs.
Excitatory amino acid transporters (EAATs)
EAAT1
EAAT2
EAAT3
EAAT4
EAAT5
Glucose transporter
Monoamine transporters, including:
Dopamine transporter (DAT)
Norepinephrine transporter (NET)
Serotonin transporter (SERT)
Vesicular monoamine transporters (VMAT)
Adenine nucleotide translocator (ANT)
2.B: Nonribosomally synthesized porters, such as:
The Nigericin family
The Ionomycin family
2.C: Ion-gradient-driven energizers
=== 3: Primary Active Transporters ===
3.A: P-P-bond-hydrolysis-driven transporters (a.k.a. ATP-driven pumps, or transport ATPases):
ATP-binding cassette transporter (ABC transporter), such as MDR, CFTR
V-type ATPase ; ( "V" related to vacuolar ).
P-type ATPase ; ( "P" related to phosphorylation), such as:
Na+/K+-ATPase
Plasma membrane Ca2+ ATPase
Proton pump
F-type ATPase; ("F" related to factor), including: mitochondrial ATP synthase, chloroplast ATP synthase1
3.B: Decarboxylation-driven transporters
3.C: Methyltransfer-driven transporters
3.D: Oxidoreduction-driven transporters
3.E: Light absorption-driven transporters, such as rhodopsin
=== 4: Group translocators ===
The group translocators provide a special mechanism for the phosphorylation of sugars as they are transported into bacteria (PEP group translocation)
=== 5: Electron carriers ===
The transmembrane electron transfer carriers in the membrane include two-electron carriers, such as the disulfide bond oxidoreductases (DsbB and DsbD in E. coli) as well as one-electron carriers such as NADPH oxidase. Often these redox proteins are not considered transport proteins.
== Relevant Examples ==
=== GLUT 1 ===
Every carrier protein, especially within the same cell membrane, is specific to one type or family of molecules. GLUT1 is a named carrier protein found in almost all animal cell membranes that transports glucose across the bilayer. This protein is a uniporter, meaning it transports glucose along its concentration in a singular direction. It is an integral membrane protein carrier with a hydrophilic interior, which allows it to bind to glucose. As GLUT 1 is a type of carrier protein, it will undergo a conformational change to allow glucose to enter the other side of the plasma membrane. GLUT 1 is commonly found in the red blood cell membranes of mammals.
=== Sodium/Potassium Channels ===
While there are many examples of channels within the human body, two notable ones are sodium and potassium channels. Potassium channels are typically involved in the transport of potassium ions across the cell membrane to the outside of the cell, which helps maintain the negative membrane potential of cells. As there are more potassium channels than sodium channels, more potassium flows out of the cell than sodium into a cell, thus why the membrane potential is negative. Sodium channels are typically involved in the transport of sodium ions across the cell membrane into the cell. These channels are commonly associated with excitable neurons, as an influx of sodium can trigger depolarization, which in turn propagates an action potential. As these proteins are types of channel proteins, they do not undergo a change of conformation after binding their respective substrates.
=== Other Examples ===
Other specific carrier proteins also help the body function in important ways. Cytochromes operate in the electron transport chain as carrier proteins for electrons.
== Pathology ==
A number of inherited diseases involve defects in carrier proteins in a particular substance or group of cells. Cysteinuria (cysteine in the urine and the bladder) is such a disease involving defective cysteine carrier proteins in the kidney cell membranes. This transport system normally removes cysteine from the fluid destined to become urine and returns this essential amino acid to the blood. When this carrier malfunctions, large quantities of cysteine remain in the urine, where it is relatively insoluble and tends to precipitate. This is one cause of urinary stones. Some vitamin carrier proteins have been shown to be overexpressed in patients with malignant disease. For example, levels of riboflavin carrier protein (RCP) have been shown to be significantly elevated in people with breast cancer.
== See also ==
Cotransport
Cotransporter
C14orf102, a 3810bp protein-encoding gene
Ion channel
Permease
P-loop
Solute carrier family (classification)
TC number (classification)
Translocase
Flippases
Vesicular transport protein
Endocytosis
== References ==
== Sources ==
Sadava, David E; Hillis, David M; Heller, H Craig; Berenbaum, May (2011). Life: The Science of Biology. Macmillan. ISBN 978-1-4292-4644-6.
Han, Seong S.; Ashley, Ruth; Hann, Gary (1974). Cell Biology. University of Michigan. OCLC 1532651.
== External links ==
"Transport protein" at Dorland's Medical Dictionary | Wikipedia/Membrane_transport_protein |
Cannabis (), commonly known as marijuana (), weed, pot, and ganja, among other names, is a non-chemically uniform psychoactive drug from the Cannabis plant. Native to Central or South Asia, cannabis has been used as a drug for both recreational and entheogenic purposes and in various traditional medicines for centuries. Tetrahydrocannabinol (THC) is the main psychoactive component of cannabis, which is one of the 483 known compounds in the plant, including at least 65 other cannabinoids, such as cannabidiol (CBD). Cannabis can be used by smoking, vaporizing, within food, or as an extract.
Cannabis has various mental and physical effects, which include euphoria, altered states of mind and sense of time, difficulty concentrating, impaired short-term memory, impaired body movement (balance and fine psychomotor control), relaxation, and an increase in appetite. Onset of effects is felt within minutes when smoked, but may take up to 90 minutes when eaten (as orally consumed drugs must be digested and absorbed). The effects last for two to six hours, depending on the amount used. At high doses, mental effects can include anxiety, delusions (including ideas of reference), hallucinations, panic, paranoia, and psychosis. There is a strong relation between cannabis use and the risk of psychosis, though the direction of causality is debated. Physical effects include increased heart rate, difficulty breathing, nausea, and behavioral problems in children whose mothers used cannabis during pregnancy; short-term side effects may also include dry mouth and red eyes. Long-term adverse effects may include addiction, decreased mental ability in those who started regular use as adolescents, chronic coughing, susceptibility to respiratory infections, and cannabinoid hyperemesis syndrome.
Cannabis is mostly used recreationally or as a medicinal drug, although it may also be used for spiritual purposes. In 2013, between 128 and 232 million people used cannabis (2.7% to 4.9% of the global population between the ages of 15 and 65). It is the most commonly used largely-illegal drug in the world, with the highest use among adults in Zambia, the United States, Canada, and Nigeria. Since the 1970s, the potency of illicit cannabis has increased, with THC levels rising and CBD levels dropping.
Cannabis plants have been grown since at least the 3rd millennium BCE and there is evidence of it being smoked for its psychoactive effects around 500 BCE in the Pamir Mountains, Central Asia. Since the 14th century, cannabis has been subject to legal restrictions. The possession, use, and cultivation of cannabis has been illegal in most countries since the 20th century. In 2013, Uruguay became the first country to legalize recreational use of cannabis. Other countries to do so are Canada, Georgia, Germany, Luxembourg, Malta, South Africa, and Thailand. In the U.S., the recreational use of cannabis is legalized in 24 states, 3 territories, and the District of Columbia, though the drug remains federally illegal. In Australia, it is legalized only in the Australian Capital Territory.
== Etymology ==
Cannabis is a Scythian word. The ancient Greeks learned of the use of cannabis by observing Scythian funerals, during which cannabis was consumed. In Akkadian, cannabis was known as qunubu (𐎯𐎫𐎠𐎭𐏂). The word was adopted in to the Hebrew as qaneh bosem (קָנֶה בֹּשׂם).
== Uses ==
=== Medical ===
Medical cannabis, or medical marijuana, refers to the use of cannabis to treat disease or improve symptoms; however, there is no single agreed-upon definition (e.g., cannabinoids derived from cannabis and synthetic cannabinoids are also used). The rigorous scientific study of cannabis as a medicine has been hampered by production restrictions and by the fact that it is classified as an illegal drug by many governments. There is some evidence suggesting cannabis can be used to reduce nausea and vomiting during chemotherapy, to improve appetite in people with HIV/AIDS, or to treat chronic pain and muscle spasms. Evidence for its use for other medical applications is insufficient for drawing conclusions about safety or efficacy. There is evidence supporting the use of cannabis or its derivatives in the treatment of chemotherapy-induced nausea and vomiting, neuropathic pain, and multiple sclerosis. Lower levels of evidence support its use for AIDS wasting syndrome, epilepsy, rheumatoid arthritis, and glaucoma.
The medical use of cannabis is legal only in a limited number of territories, including Canada, Belgium, Australia, the Netherlands, New Zealand, Spain, and many U.S. states. This usage generally requires a prescription, and distribution is usually done within a framework defined by local laws.
=== Recreational ===
Being under the effects of cannabis is usually referred to as being "high". Cannabis consumption has both psychoactive and physiological effects. The "high" experience can vary widely, based (among other things) on the user's prior experience with cannabis, and the type of cannabis consumed.: p647 When smoking cannabis, a euphoriant effect can occur within minutes of smoking.: p104 Aside from a subjective change in perception and mood, the most common short-term physical and neurological effects include increased heart rate, increased appetite, impairment of short-term and working memory, and impairment of psychomotor coordination.
Additional desired effects from consuming cannabis include relaxation, a general alteration of conscious perception, increased awareness of sensation, increased libido and distortions in the perception of time and space. In some cases, cannabis can lead to dissociative states such as depersonalization and derealization.
=== Spiritual ===
Cannabis has held sacred status in several religions and has served as an entheogen – a chemical substance used in religious, shamanic, or spiritual contexts – in the Indian subcontinent since the Vedic period. The earliest known reports regarding the sacred status of cannabis in the Indian subcontinent come from the Atharva Veda, estimated to have been composed sometime around 1400 BCE.
The Hindu god Shiva is described as a cannabis user, known as the "Lord of bhang".: p19
In modern culture, the spiritual use of cannabis has been spread by the disciples of the Rastafari movement who use cannabis as a sacrament and as an aid to meditation.
== Consumption ==
=== Modes of consumption ===
Many different ways to consume cannabis involve heat to decarboxylate THCA into THC; common modes include:
Smoking, involves burning and inhaling cannabinoids ("smoke") from small pipes, bongs (portable versions of hookahs with a water chamber), paper-wrapped joints, tobacco-leaf-wrapped blunts, or the like.
Vaporizing, heating various forms of cannabis to 165–190 °C (329–374 °F), causing the active ingredients to form vapor without combustion of the plant material (the boiling point of THC is 157 °C (315 °F) at atmospheric pressure).
Edibles, adding cannabis as an ingredient to a wide variety of foods, including butter and baked goods. In India it is commonly consumed as the beverage bhang.
Cannabis tea, prepared with attention to the lipophilic quality of THC, which is only slightly water-soluble (2.8 mg per liter), often involving cannabis in a saturated fat.
Tincture of cannabis, sometimes known as green dragon, is an alcoholic cannabis concentrate.
Capsules, typically containing cannabis oil, and other dietary supplement products, for which some 220 were approved in Canada in 2018.
=== Consumption by country ===
In 2013, between 128 and 232 million people used cannabis (2.7% to 4.9% of the global population between the ages of 15 and 65). Cannabis is by far the most widely used illicit substance, with the highest use among adults (as of 2018) in Zambia, the United States, Canada, and Nigeria.
==== United States ====
Between 1973 and 1978, eleven states decriminalized marijuana. In 2001, Nevada reduced marijuana possession to a misdemeanor and since 2012, several other states have decriminalized and even legalized marijuana.
In 2018, surveys indicated that almost half of the people in the United States had tried marijuana, 16% had used it in the past year, and 11% had used it in the past month. In 2014, surveys said daily marijuana use amongst US college students had reached its highest level since records began in 1980, rising from 3.5% in 2007 to 5.9% in 2014 and had surpassed daily cigarette use.
In the US, men are over twice as likely to use marijuana as women, and 18–29-year-olds are six times more likely to use as over-65-year-olds. In 2015, a record 44% of the US population has tried marijuana in their lifetime, an increase from 38% in 2013 and 33% in 1985.
Marijuana use in the United States is three times above the global average, but in line with other Western democracies. Forty-four percent of American 12th graders have tried the drug at least once, and the typical age of first-use is 16, similar to the typical age of first-use for alcohol but lower than the first-use age for other illicit drugs.
A 2022 Gallup poll concluded Americans are smoking more marijuana than cigarettes for the first time.
== Adverse effects ==
=== Short-term ===
Acute negative effects may include anxiety and panic, impaired attention and memory, an increased risk of psychotic symptoms, the inability to think clearly, and an increased risk of accidents. Cannabis impairs a person's driving ability, and THC was the illicit drug most frequently found in the blood of drivers who have been involved in vehicle crashes. Those with THC in their system are from three to seven times more likely to be the cause of the accident than those who had not used either cannabis or alcohol, although its role is not necessarily causal because THC stays in the bloodstream for days to weeks after intoxication.
Some immediate undesired side effects include a decrease in short-term memory, dry mouth, impaired motor skills, reddening of the eyes, dizziness, feeling tired and vomiting. Some users may experience an episode of acute psychosis, which usually abates after six hours, but in rare instances, heavy users may find the symptoms continuing for many days.
Legalization has increased the rates at which children are exposed to cannabis, particularly from edibles. While the toxicity and lethality of THC in children is not known, they are at risk for encephalopathy, hypotension, respiratory depression severe enough to require ventilation, somnolence and coma.
=== Fatality ===
There is no clear evidence for a link between cannabis use and deaths from cardiovascular disease, but a 2019 review noted that it may be an under-reported, contributory factor or direct cause in cases of sudden death, due to the strain it can place on the cardiovascular system. Some deaths have also been attributed to cannabinoid hyperemesis syndrome. There is an association between cannabis use and suicide, particularly in younger users.
A 16-month survey of Oregon and Alaska emergency departments found a report of the death of an adult who had been admitted for acute cannabis toxicity.
A recent study in 2025 suggests that individuals diagnosed with cannabis use disorder—characterized by an inability to stop using cannabis despite its negative effects—face a nearly threefold increase in mortality rates compared to those without the condition over a five-year period. The research indicates that people with this disorder are ten times more likely to die by suicide than the general population. Additionally, they have a higher risk of death from trauma, drug poisoning, and lung cancer. In a separate study researchers found an increase in schizophrenia and psychosis cases in Canada linked to cannabis use disorder following the drug’s legalization.
=== Long-term ===
==== Psychological effects ====
A 2015 meta-analysis found that, although a longer period of abstinence was associated with smaller magnitudes of impairment, both retrospective and prospective memory were impaired in cannabis users. The authors concluded that some, but not all, of the deficits associated with cannabis use were reversible. A 2012 meta-analysis found that deficits in most domains of cognition persisted beyond the acute period of intoxication, but was not evident in studies where subjects were abstinent for more than 25 days. Few high quality studies have been performed on the long-term effects of cannabis on cognition, and the results were generally inconsistent. Furthermore, effect sizes of significant findings were generally small. One review concluded that, although most cognitive faculties were unimpaired by cannabis use, residual deficits occurred in executive functions. Impairments in executive functioning are most consistently found in older populations, which may reflect heavier cannabis exposure, or developmental effects associated with adolescent cannabis use. One review found three prospective cohort studies that examined the relationship between self-reported cannabis use and intelligence quotient (IQ). The study following the largest number of heavy cannabis users reported that IQ declined between ages 7–13 and age 38. Poorer school performance and increased incidence of leaving school early were both associated with cannabis use, although a causal relationship was not established. Cannabis users demonstrated increased activity in task-related brain regions, consistent with reduced processing efficiency.
A reduced quality of life is associated with heavy cannabis use, although the relationship is inconsistent and weaker than for tobacco and other substances. The direction of cause and effect, however, is unclear.
The long-term effects of cannabis are not clear. There are concerns surrounding memory and cognition problems, risk of addiction, and the risk of schizophrenia in young people.
==== Neuroimaging ====
Although global abnormalities in white matter and grey matter are not consistently associated with cannabis use, reduced hippocampal volume is consistently found. Amygdala abnormalities are sometimes reported, although findings are inconsistent.
Cannabis use is associated with increased recruitment of task-related areas, such as the dorsolateral prefrontal cortex, which is thought to reflect compensatory activity due to reduced processing efficiency. Cannabis use is also associated with downregulation of CB1 receptors. The magnitude of down regulation is associated with cumulative cannabis exposure, and is reversed after one month of abstinence. There is limited evidence that chronic cannabis use can reduce levels of glutamate metabolites in the human brain.
=== Cannabis dependence ===
About 9% of those who experiment with marijuana eventually become dependent according to DSM-IV (1994) criteria. A 2013 review estimates daily use is associated with a 10–20% rate of dependence. The highest risk of cannabis dependence is found in those with a history of poor academic achievement, deviant behavior in childhood and adolescence, rebelliousness, poor parental relationships, or a parental history of drug and alcohol problems. Of daily users, about 50% experience withdrawal upon cessation of use (i.e. are dependent), characterized by sleep problems, irritability, dysphoria, and craving. Cannabis withdrawal is less severe than withdrawal from alcohol.
According to DSM-5 criteria, 9% of those who are exposed to cannabis develop cannabis use disorder, compared to 20% for cocaine, 23% for alcohol and 68% for nicotine. Cannabis use disorder in the DSM-5 involves a combination of DSM-IV criteria for cannabis abuse and dependence, plus the addition of craving, without the criterion related to legal troubles.
==== Psychiatric ====
From a clinical perspective, two significant school of thought exists for psychiatric conditions associated with cannabis (or cannabinoids) use: transient, non-persistent psychotic reactions, and longer-lasting, persistent disorders that resemble schizophrenia. The former is formally known as acute cannabis-associated psychotic symptoms (CAPS).
At an epidemiological level, a dose–response relationship exists between cannabis use and increased risk of psychosis and earlier onset of psychosis. Although the epidemiological association is robust, evidence to prove a causal relationship is lacking.
Cannabis may also increase the risk of depression, but insufficient research has been performed to draw a conclusion. Cannabis use is associated with increased risk of anxiety disorders, although causality has not been established.
A review in 2019 found that research was insufficient to determine the safety and efficacy of using cannabis to treat schizophrenia, psychosis, or other mental disorders. Another found that cannabis during adolescence was associated with an increased risk of developing depression and suicidal behavior later in life, while finding no effect on anxiety.
==== Physical ====
Heavy, long-term exposure to marijuana may have physical, mental, behavioral and social health consequences. It may be "associated with diseases of the liver (particularly with co-existing hepatitis C), lungs, heart, and vasculature". A 2014 review found that while cannabis use may be less harmful than alcohol use, the recommendation to substitute it for problematic drinking was premature without further study. Various surveys conducted between 2015 and 2019 found that many users of cannabis substitute it for prescription drugs (including opioids), alcohol, and tobacco; most of those who used it in place of alcohol or tobacco either reduced or stopped their intake of the latter substances.
Cannabinoid hyperemesis syndrome (CHS) is a severe condition seen in some chronic cannabis users where they have repeated bouts of uncontrollable vomiting for 24–48 hours.
Four cases of death have been reported as a result of CHS.
A limited number of studies have examined the effects of cannabis smoking on the respiratory system. Chronic heavy marijuana smoking is associated with respiratory infections, coughing, production of sputum, wheezing, and other symptoms of chronic bronchitis. The available evidence does not support a causal relationship between cannabis use and chronic obstructive pulmonary disease. Short-term use of cannabis is associated with bronchodilation. Other side effects of cannabis use include cannabinoid hyperemesis syndrome (CHS), a condition which involves recurrent nausea, cramping abdominal pain, and vomiting.
Cannabis smoke contains thousands of organic and inorganic chemical compounds. This tar is chemically similar to that found in tobacco smoke, and over fifty known carcinogens have been identified in cannabis smoke, including; nitrosamines, reactive aldehydes, and polycyclic aromatic hydrocarbons, including benz[a]pyrene. Cannabis smoke is also inhaled more deeply than tobacco smoke. As of 2015, there is no consensus regarding whether cannabis smoking is associated with an increased risk of cancer. Light and moderate use of cannabis is not believed to increase risk of lung or upper airway cancer. Evidence for causing these cancers is mixed concerning heavy, long-term use. In general there are far lower risks of pulmonary complications for regular cannabis smokers when compared with those of tobacco. A 2015 review found an association between cannabis use and the development of testicular germ cell tumors (TGCTs), particularly non-seminoma TGCTs. Another 2015 meta-analysis found no association between lifetime cannabis use and risk of head or neck cancer. Combustion products are not present when using a vaporizer, consuming THC in pill form, or consuming cannabis foods.
There is concern that cannabis may contribute to cardiovascular disease, but as of 2018, evidence of this relationship was unclear. Research in these events is complicated because cannabis is often used in conjunction with tobacco, and drugs such as alcohol and cocaine that are known to have cardiovascular risk factors. Smoking cannabis has also been shown to increase the risk of myocardial infarction by 4.8 times for the 60 minutes after consumption.
There is preliminary evidence that cannabis interferes with the anticoagulant properties of prescription drugs used for treating blood clots. As of 2019, the mechanisms for the anti-inflammatory and possible pain relieving effects of cannabis were not defined, and there were no governmental regulatory approvals or clinical practices for use of cannabis as a drug.
===== Emergency department visits =====
Emergency room (ER) admissions associated with cannabis use rose significantly from 2012 to 2016; adolescents from age 12–17 had the highest risk. At one Colorado medical center following legalization, approximately two percent of ER admissions were classified as cannabis users. The symptoms of one quarter of these users were partially attributed to cannabis (a total of 2567 out of 449,031 patients); other drugs were sometimes involved. Of these cannabis admissions, one quarter were for acute psychiatric effects, primarily suicidal ideation, depression, and anxiety. An additional third of the cases were for gastrointestinal issues including cannabinoid hyperemesis syndrome.
According to the United States Department of Health and Human Services, there were 455,000 emergency room visits associated with cannabis use in 2011. These statistics include visits in which the patient was treated for a condition induced by or related to recent cannabis use. The drug use must be "implicated" in the emergency department visit, but does not need to be the direct cause of the visit. Most of the illicit drug emergency room visits involved multiple drugs. In 129,000 cases, cannabis was the only implicated drug.
==== Reproductive health ====
=== Secondhand cannabis smoke ===
A 2022 study found that smoking cannabis using a bong can greatly increase background levels of fine particulate matter, a carcinogen, in an enclosed space such as a living room. After 15 minutes, mean levels of particulate matter were more than twice the Environmental Protection Agency hazardous air quality threshold, and after 140 minutes, the concentrations were four times greater than those generated by smoking tobacco using a cigarette or hookah. This suggests secondhand cannabis smoke from bongs may present a health risk to non-smokers.
== Pharmacology ==
=== Mechanism of action ===
THC is a weak partial agonist at CB1 receptors, while CBD is a CB1 receptor antagonist.
The CB1 receptor is found primarily in the brain as well as in some peripheral tissues, and the CB2 receptor is found primarily in peripheral tissues, but is also expressed in neuroglial cells. THC appears to alter mood and cognition through its agonist actions on the CB1 receptors, which inhibit a secondary messenger system (adenylate cyclase) in a dose-dependent manner.
Via CB1 receptor activation, THC indirectly increases dopamine release and produces psychotropic effects. CBD also acts as an allosteric modulator of the μ- and δ-opioid receptors. THC also potentiates the effects of the glycine receptors. It is unknown if or how these actions contribute to the effects of cannabis.
=== Pharmacokinetics ===
The high lipid-solubility of cannabinoids results in their persisting in the body for long periods of time. Even after a single administration of THC, detectable levels of THC can be found in the body for weeks or longer (depending on the amount administered and the sensitivity of the assessment method). Investigators have suggested that this is an important factor in marijuana's effects, perhaps because cannabinoids may accumulate in the body, particularly in the lipid membranes of neurons.
== Chemistry ==
=== Chemical composition ===
The main psychoactive component of cannabis is tetrahydrocannabinol (THC), which is formed via decarboxylation of tetrahydrocannabinolic acid (THCA) from the application of heat. Raw leaf is not psychoactive because the cannabinoids are in the form of carboxylic acids. THC is one of the 483 known compounds in the plant, including at least 65 other cannabinoids, such as cannabidiol (CBD).
=== Detection in body fluids ===
THC and its major (inactive) metabolite, THC-COOH, can be measured in blood, urine, hair, oral fluid or sweat using chromatographic techniques as part of a drug use testing program or a forensic investigation of a traffic or other criminal offense. The concentrations obtained from such analyses can often be helpful in distinguishing active use from passive exposure, elapsed time since use, and extent or duration of use. These tests cannot, however, distinguish authorized cannabis smoking for medical purposes from unauthorized recreational smoking. Commercial cannabinoid immunoassays, often employed as the initial screening method when testing physiological specimens for marijuana presence, have different degrees of cross-reactivity with THC and its metabolites. Urine contains predominantly THC-COOH, while hair, oral fluid and sweat contain primarily THC. Blood may contain both substances, with the relative amounts dependent on the recency and extent of usage.
The Duquenois–Levine test is commonly used as a screening test in the field, but it cannot definitively confirm the presence of cannabis, as a large range of substances have been shown to give false positives. Researchers at John Jay College of Criminal Justice reported that dietary zinc supplements can mask the presence of THC and other drugs in urine. However, a 2013 study conducted by researchers at the University of Utah School of Medicine refute the possibility of self-administered zinc producing false-negative urine drug tests.
== Varieties and strains ==
CBD is a 5-HT1A receptor agonist, which is under laboratory research to determine if it has an anxiolytic effect. It is often claimed that sativa strains provide a more stimulating psychoactive high while indica strains are more sedating with a body high. However, this is disputed by researchers.
A 2015 review found that the use of high CBD-to-THC strains of cannabis showed significantly fewer positive symptoms, such as delusions and hallucinations, better cognitive function and both lower risk for developing psychosis, as well as a later age of onset of the illness, compared to cannabis with low CBD-to-THC ratios.
=== Psychoactive ingredients ===
According to the United Nations Office on Drugs and Crime (UNODC), "the amount of THC present in a cannabis sample is generally used as a measure of cannabis potency." The three main forms of cannabis products are the flower/fruit, resin (hashish), and oil (hash oil). The UNODC states that cannabis often contains 5% THC content, resin "can contain up to 20% THC content", and that "Cannabis oil may contain more than 60% THC content."
Studies have found that the potency of illicit cannabis has greatly increased since the 1970s, with THC levels rising and CBD levels dropping. It is unclear, however, whether the increase in THC content has caused people to consume more THC or if users adjust based on the potency of the cannabis. It is likely that the higher THC content allows people to ingest less tar. At the same time, CBD levels in seized samples have lowered, in part because of the desire to produce higher THC levels and because more illegal growers cultivate indoors using artificial lights. This helps avoid detection but reduces the CBD production of the plant.
Australia's National Cannabis Prevention and Information Centre (NCPIC) states that the buds (infructescences) of the female Cannabis plant contain the highest concentration of THC, followed by the leaves. The stalks and seeds have "much lower THC levels". The UN states that the leaves can contain ten times less THC than the buds, and the stalks 100 times less THC.
After revisions to cannabis scheduling in the UK, the government moved cannabis back from a class C to a class B drug. A purported reason was the appearance of high potency cannabis. They believe skunk accounts for between 70% and 80% of samples seized by police (despite the fact that skunk can sometimes be incorrectly mistaken for all types of herbal cannabis). Extracts such as hashish and hash oil typically contain more THC than high potency cannabis infructescences.
==== Laced cannabis and synthetic cannabinoids ====
Hemp buds (or low-potency cannabis buds) laced with synthetic cannabinoids started to be sold as cannabis street drug in 2020.
The short-term effects of cannabis can be altered if it has been laced with opioid drugs such as heroin or fentanyl. The added drugs are meant to enhance the psychoactive properties, add to its weight, and increase profitability, despite the increased danger of overdose.
== Preparations ==
=== Marijuana ===
Marijuana or marihuana (herbal cannabis) consists of the dried flowers and fruits and subtending leaves and stems of the female cannabis plant. This is the most widely consumed form, containing 3% to 20% THC, with reports of up to 33% THC. This is the stock material from which all other preparations are derived. Although herbal cannabis and industrial hemp derive from the same species and contain the psychoactive component (THC), they are distinct strains with unique biochemical compositions and uses. Hemp has lower concentrations of THC and higher concentrations of CBD, which gives lesser psychoactive effects.
=== Kief ===
Kief is a powder, rich in trichomes, which can be sifted from the leaves, flowers and fruits of cannabis plants and either consumed in powder form or compressed to produce cakes of hashish. The word "kif" derives from colloquial Arabic كيف kēf/kīf, meaning pleasure.
=== Hashish ===
Hashish (also spelled hasheesh, hashisha, or simply hash) is a concentrated resin cake or ball produced from pressed kief, the detached trichomes and fine material that falls off cannabis fruits, flowers and leaves, or from scraping the resin from the surface of the plants and rolling it into balls. It varies in color from black to golden brown depending upon purity and variety of cultivar it was obtained from. It can be consumed orally or smoked, and is also vaporized, or 'vaped'. The term "rosin hash" refers to a high quality solventless product obtained through heat and pressure.
=== Tincture ===
Cannabinoids can be extracted from cannabis plant matter using high-proof spirits (often grain alcohol) to create a tincture, often referred to as "green dragon".: p17 Nabiximols is a branded product name from a tincture manufacturing pharmaceutical company.
=== Hash oil ===
Hash oil is a resinous matrix of cannabinoids obtained from the cannabis plant by solvent extraction, formed into a hardened or viscous mass. Hash oil can be the most potent of the main cannabis products because of its high level of psychoactive compound per its volume, which can vary depending on the plant's mix of essential oils and psychoactive compounds. Butane and supercritical carbon dioxide hash oil have become popular in recent years.
=== Infusions ===
There are many varieties of cannabis infusions owing to the variety of non-volatile solvents used. The plant material is mixed with the solvent and then pressed and filtered to express the oils of the plant into the solvent. Examples of solvents used in this process are cocoa butter, dairy butter, cooking oil, glycerine, and skin moisturizers. Depending on the solvent, these may be used in cannabis foods or applied topically.
=== Marihuana prensada ===
Marihuana prensada ('pressed marijuana') is a cannabis-derived product widespread among the lower classes of South America, especially from the 90s. Locally it is known as "paraguayo" or "paragua", since its main producer is Paraguay. Marijuana is dried and mixed with binding agents that make it toxic and highly harmful to health. It is cut into the shape of bricks (ladrillos) and sold for a low price in Argentina, Brazil, Chile, Peru, Venezuela, and even the United States.
== History ==
=== Ancient history ===
Cannabis is indigenous to Central or South Asia and its uses for fabric and rope dates back to the Neolithic age in China and Japan. It is unclear when cannabis first became known for its psychoactive properties. The oldest archeological evidence for the burning of cannabis was found in Romanian kurgans dated 3,500 BC, and scholars suggest that the drug was first used in ritual ceremonies by Proto-Indo-European tribes living in the Pontic-Caspian steppe during the Chalcolithic period, a custom they eventually spread throughout Western Eurasia during the Indo-European migrations. Some research suggests that the ancient Indo-Iranian drug soma, mentioned in the Vedas, sometimes contained cannabis. This is based on the discovery of a basin containing cannabis in a shrine of the second millennium BC in Turkmenistan.
Cannabis was known to the ancient Assyrians, who discovered its psychoactive properties through the Iranians. Using it in some religious ceremonies, they called it qunubu (meaning "way to produce smoke"), a probable origin of the modern word cannabis. The Iranians also introduced cannabis to the Scythians, Thracians and Dacians, whose shamans (the kapnobatai – "those who walk on smoke/clouds") burned cannabis infructescences to induce trance. The plant was used in China before 2800 BC, and found therapeutic use in India by 1000 BC, where it was used in food and drink, including bhang.
Cannabis has an ancient history of ritual use and has been used by religions around the world. It has been used as a drug for both recreational and entheogenic purposes and in various traditional medicines for centuries. The earliest evidence of cannabis smoking has been found in the 2,500-year-old tombs of Jirzankal Cemetery in the Pamir Mountains in Western China, where cannabis residue were found in burners with charred pebbles possibly used during funeral rituals. Hemp seeds discovered by archaeologists at Pazyryk suggest early ceremonial practices like eating by the Scythians occurred during the 5th to 2nd century BC, confirming previous historical reports by Herodotus. It was used by Muslims in various Sufi orders as early as the Mamluk period, for example by the Qalandars. Smoking pipes uncovered in Ethiopia and carbon-dated to around c. AD 1320 were found to have traces of cannabis.
=== Modern history ===
Cannabis was introduced to the New World by the Spaniards in 1530–1545. Following an 1836–1840 travel in North Africa and the Middle East, French physician Jacques-Joseph Moreau wrote on the psychological effects of cannabis use; he founded the Paris' Club des Hashischins in 1844. In 1842, Irish physician William Brooke O'Shaughnessy, who had studied the drug while working as a medical officer in Bengal with the East India Company, brought a quantity of cannabis with him on his return to Britain, provoking renewed interest in the West. Examples of classic literature of the period featuring cannabis include Les paradis artificiels (1860) by Charles Baudelaire and The Hasheesh Eater (1857) by Fitz Hugh Ludlow.
Cannabis was criminalized in some countries beginning in the 14th century and was illegal in most countries by the middle of the 20th century. The colonial government of Mauritius banned cannabis in 1840 over concerns on its effect on Indian indentured workers; the same occurred in Singapore in 1870. In the United States, the first restrictions on sale of cannabis came in 1906 (in the District of Columbia). Canada criminalized cannabis in The Opium and Narcotic Drug Act, 1923, before any reports of the use of the drug in Canada, but eventually legalized its consumption for recreational and medicinal purposes in 2018.
In 1925, a compromise was made at an international conference in The Hague about the International Opium Convention that banned exportation of "Indian hemp" to countries that had prohibited its use, and requiring importing countries to issue certificates approving the importation and stating that the shipment was required "exclusively for medical or scientific purposes". It also required parties to "exercise an effective control of such a nature as to prevent the illicit international traffic in Indian hemp and especially in the resin". In the United States in 1937, the Marihuana Tax Act was passed, and prohibited the production of hemp in addition to cannabis.
In 1972, the Dutch government divided drugs into more- and less-dangerous categories, with cannabis being in the lesser category. Accordingly, possession of 30 grams (1.1 oz) or less was made a misdemeanor. Cannabis has been available for recreational use in coffee shops since 1976. Cannabis products are only sold openly in certain local "coffeeshops" and possession of up to 5 grams (0.18 oz) for personal use is decriminalized, however: the police may still confiscate it, which often happens in car checks near the border. Other types of sales and transportation are not permitted, although the general approach toward cannabis was lenient even before official decriminalization.
In Uruguay, President Jose Mujica signed legislation to legalize recreational cannabis in December 2013, making Uruguay the first country in the modern era to legalize cannabis. In August 2014, Uruguay legalized growing up to six plants at home, as well as the formation of growing clubs (Cannabis social club), and a state-controlled marijuana dispensary regime.
As of 17 October 2018, when recreational use of cannabis was legalized in Canada, dietary supplements for human use and veterinary health products containing not more than 10 parts per million of THC extract were approved for marketing; Nabiximols (as Sativex) is used as a prescription drug in Canada.
The United Nations' World Drug Report stated that cannabis "was the world's most widely produced, trafficked, and consumed drug in the world in 2010", and estimated between 128 million and 238 million users globally in 2015.
== Culture, legality and economics ==
=== Culture ===
Cannabis has been one of the most used psychoactive drugs in the world since the late 20th century, following only tobacco and alcohol in popularity. According to Vera Rubin, the use of cannabis has been encompassed by two major cultural complexes over time: a continuous, traditional folk stream, and a more circumscribed, contemporary configuration. The former involves both sacred and secular use, and is usually based on small-scale cultivation: the use of the plant for cordage, clothing, medicine, food, and a "general use as an euphoriant and symbol of fellowship." The second stream of expansion of cannabis use encompasses "the use of hemp for commercial manufacturers utilizing large-scale cultivation primarily as a fiber for mercantile purposes"; but it is also linked to the search for psychedelic experiences (which can be traced back to the formation of the Parisian Club des Hashischins).
=== Legality ===
Since the beginning of the 20th century, most countries have enacted laws against the cultivation, possession or transfer of cannabis. These laws have had an adverse effect on cannabis cultivation for non-recreational purposes, but there are many regions where handling of cannabis is legal or licensed. Many jurisdictions have lessened the penalties for possession of small quantities of cannabis so that it is punished by confiscation and sometimes a fine, rather than imprisonment, focusing more on those who traffic the drug on the black market.
In some areas where cannabis use had been historically tolerated, new restrictions were instituted, such as the closing of cannabis coffee shops near the borders of the Netherlands, and closing of coffee shops near secondary schools in the Netherlands. In Copenhagen, Denmark in 2014, mayor Frank Jensen discussed possibilities for the city to legalize cannabis production and commerce.
Some jurisdictions use free voluntary or mandatory treatment programs for frequent known users. Simple possession can carry long prison terms in some countries, particularly in East Asia, where the sale of cannabis may lead to a sentence of life in prison or even execution. Political parties, non-profit organizations, and causes based on the legalization of medical cannabis or legalizing the plant entirely (with some restrictions) have emerged in such countries as China and Thailand.
In December 2012, the U.S. state of Washington became the first state to officially legalize cannabis in a state law (Washington Initiative 502) (but still illegal by federal law), with the state of Colorado following close behind (Colorado Amendment 64). On 1 January 2013, the first cannabis "club" for private marijuana smoking (no buying or selling, however) was allowed for the first time in Colorado. The California Supreme Court decided in May 2013 that local governments can ban medical cannabis dispensaries despite a state law in California that permits the use of cannabis for medical purposes. At least 180 cities across California have enacted bans in recent years.
On 30 April 2024, the United States Department of Justice announced it would move to reclassify cannabis from a Schedule I to a Schedule III controlled substance.
In December 2013, Uruguay became the first country to legalize growing, sale and use of cannabis. After a long delay in implementing the retail component of the law, in 2017 sixteen pharmacies were authorized to sell cannabis commercially. On 19 June 2018, the Canadian Senate passed a bill and the Prime Minister announced the effective legalization date as 17 October 2018. Canada is the second country to legalize the drug.
In November 2015, Uttarakhand became the first state of India to legalize the cultivation of hemp for industrial purposes. Usage within the Hindu and Buddhist cultures of the Indian subcontinent is common, with many street vendors in India openly selling products infused with cannabis, and traditional medical practitioners in Sri Lanka selling products infused with cannabis for recreational purposes and well as for religious celebrations. Indian laws criminalizing cannabis date back to the colonial period. India and Sri Lanka have allowed cannabis to be taken in the context of traditional culture for recreational/celebratory purposes and also for medicinal purposes.
On 17 October 2015, Australian health minister Sussan Ley presented a new law that will allow the cultivation of cannabis for scientific research and medical trials on patients.
On 17 October 2018, Canada legalized cannabis for recreational adult use making it the second country in the world to do so after Uruguay and the first G7 nation. This legalization comes with regulation similar to that of alcohol in Canada, age restrictions, limiting home production, distribution, consumption areas and sale times. Laws around use vary from province to province including age limits, retail structure, and growing at home. The Canadian Licensed Producer system aims to become the Gold Standard in the world for safe and secure cannabis production, including provisions for a robust craft cannabis industry where many expect opportunities for experimenting with different strains.
As the drug has increasingly been seen as a health issue instead of criminal behavior, cannabis has also been legalized or decriminalized in: Czech Republic, Colombia, Ecuador, Portugal, South Africa and Canada. Medical marijuana was legalized in Mexico in mid-2017 and legalized for recreational use in June 2021.
Germany legalized cannabis for recreational use in April 2024.
==== Legal status by country ====
As of 2022, Uruguay and Canada are the only countries that have fully legalized the cultivation, consumption and bartering of recreational cannabis nationwide. In the United States, 24 states, 3 territories, and the District of Columbia have legalized the recreational use of cannabis – though the drug remains illegal at the federal level. Laws vary from state to state when it comes to the commercial sale. Court rulings in Georgia and South Africa have led to the legalization of cannabis consumption, but not legal sales. A policy of limited enforcement has also been adopted in many countries, in particular Spain and the Netherlands where the sale of cannabis is tolerated at licensed establishments. Contrary to popular belief, cannabis is not legal in the Netherlands, but it has been decriminalized since the 1970s. In 2021, Malta was the first European Union member to legalize the use of cannabis for recreational purposes. In Estonia, it is only legal to sell cannabis products with a THC content of less than 0.2%, although products may contain more cannabidiol. Lebanon has recently become the first Arab country to legalize the plantation of cannabis for medical use.
Penalties for illegal recreational use ranges from confiscation or small fines to jail time and even death. In some countries citizens can be punished if they have used the drug in another country, including Singapore and South Korea.
=== Economics ===
==== Production ====
Sinsemilla (Spanish for "without seed") is the dried, seedless (i.e. parthenocarpic) infructescences of female cannabis plants. Because THC production drops off once pollination occurs, the male plants (which produce little THC themselves) are eliminated before they shed pollen to prevent pollination, thus inducing the development of parthenocarpic fruits gathered in dense infructescences. Advanced cultivation techniques such as hydroponics, cloning, high-intensity artificial lighting, and the sea of green method are frequently employed as a response (in part) to prohibition enforcement efforts that make outdoor cultivation more risky.
"Skunk" refers to several named strains of potent cannabis, grown through selective breeding and sometimes hydroponics. It is a cross-breed of Cannabis sativa and C. indica (although other strains of this mix exist in abundance). Skunk cannabis potency ranges usually from 6% to 15% and rarely as high as 20%. The average THC level in coffee shops in the Netherlands is about 18–19%.
The average levels of THC in cannabis sold in the United States rose dramatically between the 1970s and 2000. This is disputed for various reasons, and there is little consensus as to whether this is a fact or an artifact of poor testing methodologies. According to Daniel Forbes writing for slate.com, the relative strength of modern strains are likely skewed because undue weight is given to much more expensive and potent, but less prevalent, samples. Some suggest that results are skewed by older testing methods that included low-THC-content plant material such as leaves in the samples, which are excluded in contemporary tests. Others believe that modern strains actually are significantly more potent than older ones.
The main producing countries of cannabis are Afghanistan, Canada, China, Colombia, India, Jamaica, Lebanon, Mexico, Morocco, the Netherlands, Pakistan, Paraguay, Spain, Thailand, Turkey, the United Kingdom, and the United States.
==== Price ====
The price or street value of cannabis varies widely depending on geographic area and potency. Prices and overall markets have also varied considerably over time.
In 1997, cannabis was estimated to be overall the number four value crop in the US, and number one or two in many states, including California, New York, and Florida. This estimate is based on a value to growers of ~60% of retail value, or $3,000 per pound ($6,600/kg).
In 2006, cannabis was estimated to have been a $36 billion market. This estimate has been challenged as exaggerated. The UN World Drug Report (2008) estimated that 2006 street prices in the US and Canada ranged from about US$8.8 to $25 per gram (approximately $250 to $700 per ounce), depending on quality. Typical U.S. retail prices were $10–15 per gram (approximately $280–420 per ounce).
In 2017, the U.S. was estimated to constitute 90% of the worldwide $9.5 billion legal trade in cannabis.
After some U.S. states legalized cannabis, street prices began to drop. In Colorado, the price of smokable buds (infructescences) dropped 40 percent between 2014 and 2019, from $200 per ounce to $120 per ounce ($7 per gram to $4.19 per gram).
The European Monitoring Centre for Drugs and Drug Addiction reports that typical retail prices in Europe for cannabis varied from €2 to €20 per gram in 2008, with a majority of European countries reporting prices in the range €4–10.
== Cannabis as a gateway drug ==
The gateway hypothesis states that cannabis use increases the probability of trying "harder" drugs. The hypothesis has been hotly debated as it is regarded by some as the primary rationale for the United States prohibition on cannabis use. A Pew Research Center poll found that political opposition to marijuana use was significantly associated with concerns about the health effects and whether legalization would increase cannabis use by children.
Some studies state that while there is no proof for the gateway hypothesis, young cannabis users should still be considered as a risk group for intervention programs. Other findings indicate that hard drug users are likely to be poly-drug users, and that interventions must address the use of multiple drugs instead of a single hard drug. Almost two-thirds of the poly drug users in the 2009–2010 Scottish Crime and Justice Survey used cannabis.
The gateway effect may appear due to social factors involved in using any illegal drug. Because of the illegal status of cannabis, its consumers are likely to find themselves in situations allowing them to acquaint with individuals using or selling other illegal drugs. Studies have shown that alcohol and tobacco may additionally be regarded as gateway drugs; however, a more parsimonious explanation could be that cannabis is simply more readily available (and at an earlier age) than illegal hard drugs. In turn, alcohol and tobacco are typically easier to obtain at an earlier age than is cannabis (though the reverse may be true in some areas), thus leading to the "gateway sequence" in those individuals, since they are most likely to experiment with any drug offered.
A related alternative to the gateway hypothesis is the common liability to addiction (CLA) theory. It states that some individuals are, for various reasons, willing to try multiple recreational substances. The "gateway" drugs are merely those that are (usually) available at an earlier age than the harder drugs. Researchers have noted in an extensive review that it is dangerous to present the sequence of events described in gateway "theory" in causative terms as this hinders both research and intervention.
In 2020, the National Institute on Drug Abuse released a study backing allegations that marijuana is a gateway to harder drugs, though not for the majority of marijuana users. The National Institute on Drug Abuse determined that marijuana use is "likely to precede use of other licit and illicit substances" and that "adults who reported marijuana use during the first wave of the survey were more likely than adults who did not use marijuana to develop an alcohol use disorder within 3 years; people who used marijuana and already had an alcohol use disorder at the outset were at greater risk of their alcohol use disorder worsening. Marijuana use is also linked to other substance use disorders including nicotine addiction." It also reported that "These findings are consistent with the idea of marijuana as a "gateway drug". However, the majority of people who use marijuana do not go on to use other, "harder" substances. Also, cross-sensitization is not unique to marijuana. Alcohol and nicotine also prime the brain for a heightened response to other drugs and are, like marijuana, also typically used before a person progresses to other, more harmful substances."
== Research ==
Research on cannabis is challenging since the plant is illegal in most countries. Research-grade samples of the drug are difficult to obtain for research purposes, unless granted under authority of national regulatory agencies, such as the US Food and Drug Administration.
There are also other difficulties in researching the effects of cannabis. Many people who smoke cannabis also smoke tobacco. This causes confounding factors, where questions arise as to whether the tobacco, the cannabis, or both that have caused a cancer. Another difficulty researchers have is in recruiting people who smoke cannabis into studies. Because cannabis is an illegal drug in many countries, people may be reluctant to take part in research, and if they do agree to take part, they may not say how much cannabis they actually smoke.
== See also ==
Cannabis rights
Glossary of cannabis terms
List of books about cannabis
List of celebrities who own cannabis businesses
== References ==
Footnotes
Citations
== Further reading ==
Booth, Martin (2004). Cannabis: A History. Picador. ISBN 978-0-312-42494-7.
Drake, Bill (2002). The Marijuana Food Handbook: A Guide for the Sensuous Connoisseur. Ronin Publishing. ISBN 978-0-914171-99-7.
Grinspoon, Lester (1994). Marihuana Reconsidered. Quick American Archives. ISBN 978-0-932551-13-9.
== External links ==
Media related to Cannabis at Wikimedia Commons
The dictionary definition of marijuana at Wiktionary
"Cannabis". European Union Drugs Agency (EUDA). | Wikipedia/Cannabis_(drug) |
Psychedelic therapy (or psychedelic-assisted therapy) refers to the proposed use of psychedelic drugs, such as psilocybin, ayahuasca, LSD, psilocin, mescaline (peyote), DMT, 5-MeO-DMT, Ibogaine, MDMA, to treat mental disorders. As of 2021, psychedelic drugs are controlled substances in most countries and psychedelic therapy is not legally available outside clinical trials, with some exceptions.
The procedure for psychedelic therapy differs from that of therapies using conventional psychiatric medications. While conventional medications are usually taken without supervision at least once daily, in contemporary psychedelic therapy the drug is administered in a single session (or sometimes up to three sessions) in a therapeutic context. The therapeutic team prepares the patient for the experience beforehand and helps them integrate insights from the drug experience afterwards. After ingesting the drug, the patient normally wears eyeshades and listens to music to facilitate focus on the psychedelic experience, with the therapeutic team interrupting only to provide reassurance if adverse effects such as anxiety or disorientation arise.
As of 2022, the body of high-quality evidence on psychedelic therapy remains relatively small and more, larger studies are needed to reliably show the effectiveness and safety of psychedelic therapy's various forms and applications. On the basis of favorable early results, ongoing research is examining proposed psychedelic therapies for conditions including major depressive disorder, anxiety and depression linked to terminal illness, and post-traumatic stress disorder. The United States Food and Drug Administration has granted "breakthrough therapy" status, which expedites the potential approval of promising drug therapies, to psychedelic therapies using psilocybin (for treatment-resistant depression and major depressive disorder) and MDMA (for post-traumatic stress disorder).
== History ==
=== Prehistoric use of psychedelic substances ===
Humans have long consumed psychedelic substances derived from cacti, seeds, bark, and roots of various plants and fungi. Since ancient times, shamans and medicine men have used psychedelics as a way to gain access to the spirit world. Though western culture usually views the practice of shamans and medicine men as predominantly spiritual in nature, elements of psychotherapeutic practice can be read into the entheogenic or shamanic rituals of many cultures.
=== Research in the mid-20th century ===
Shortly after Albert Hofmann discovered the psychoactive properties of LSD in 1943, Sandoz Laboratories began widespread distribution of LSD to researchers in 1949. Throughout the 1950s and 1960s, scientists in several countries (e.g., U.S.A.: Langley Porter Psychiatric Institute, MKUltra) conducted extensive research into experimental chemotherapeutic and psychotherapeutic uses of psychedelic drugs. In addition to spawning six international conferences and the release of dozens of books, over 1,000 peer-reviewed clinical papers detailing the use of psychedelic compounds (administered to approximately 40,000 patients) were published by the mid-1960s. Proponents believed that psychedelic drugs facilitated psychoanalytic processes, making them particularly useful for patients with conditions such as alcoholism that are otherwise difficult to treat. However, many of these trials did not meet the methodological standards that are required today.
Researchers like Timothy Leary felt psychedelics could alter the fundamental personality structure or subjective value-system of an individual to great potential benefit. Beginning in 1961, he conducted experiments with prison inmates in an attempt to reduce recidivism with short, intense psychotherapy sessions. Participants were administered psilocybin during these sessions weeks apart with regular group therapy sessions in between. Psychedelic therapy was also applied in a number of other specific patient populations including individuals with alcoholism, children with autism, and persons with terminal illness.
=== Regulation and prohibition in the late 20th century ===
Throughout the 1960s, concerns raised about the proliferation of unauthorized use of psychedelic drugs by the general public (and, most notably, the counterculture) resulted in the imposition of increasingly severe restrictions on medical and psychiatric research conducted with psychedelic substances. Many countries either banned LSD outright or made it extremely scarce, and, bowing to governmental concerns, Sandoz halted production of LSD in 1965. During a congressional hearing in 1966, Senator Robert F. Kennedy questioned the shift of opinion, stating, "Perhaps to some extent we have lost sight of the fact that (LSD) can be very, very helpful in our society if used properly." In 1968, Dahlberg and colleagues published an article in the American Journal of Psychiatry detailing various forces that had successfully discredited legitimate LSD research. The essay argues that individuals in government and the pharmaceutical industry sabotaged the psychedelic research community by canceling ongoing studies and analysis while labeling genuine scientists as charlatans.
Studies on medicinal applications of psychedelics ceased entirely in the United States when the Controlled Substances Act was passed in 1970. LSD and many other psychedelics were placed into the most restrictive "Schedule I" category by the United States Drug Enforcement Administration. Schedule I compounds are claimed to possess "a high potential for abuse and the potential to create severe psychological and/or physical dependence" and have "no currently accepted medical use", effectively rendering them illegal to use in the United States for all purposes. Despite objections from the scientific community, authorized research into therapeutic applications of psychedelic drugs had been discontinued worldwide by the 1980s.
Despite broad prohibition, unofficial psychedelic research and therapeutic sessions continued nevertheless in the following decades. Some therapists exploited windows of opportunity preceding scheduling of particular psychedelic drugs. Informal psychedelic therapy was conducted clandestinely in underground networks consisting of sessions carried out both by licensed therapists and autodidacts within the community. Due to the largely illegal nature of psychedelic therapy in this period, little information is available concerning the methods that were used. Individuals having published information between 1980 and 2000 regarding psychedelic psychotherapy include George Greer, Ann and Alexander Shulgin (PiHKAL and TiHKAL), Myron Stolaroff (The Secret Chief, regarding the underground therapy done by Leo Zeff), and Athanasios Kafkalides.
=== Resurgence in the early 21st century ===
In the early 2000s, a renewal of interest in the psychiatric use of psychedelics contributed to an increase in clinical research centering on the psychopharmacological effects of these drugs and their subsequent applications. Advances in science and technology allowed researchers to collect and interpret extensive data from animal studies, and the advent of new technologies such as PET and MRI scanning made it possible to examine the sites of action of hallucinogens in the brain. Furthermore, retrospective studies involving users of illicit drugs as voluntary subjects were conducted, allowing data to be collected on how psychedelics affect the human brain while simultaneously sidestepping bureaucratic difficulties associated with providing illegal substances to subjects. The new century also ushered in a broader change in political attitude towards psychedelic medicine—specifically within the Food and Drug Administration. Curtis Wright, then deputy director of the FDA Division of Anesthetic, Critical Care and Addiction Drugs explained a motivation for this change: "the agency was challenged legally in a number of cases and also underwent a process of introspection, asking 'Is it proper to treat this class of drugs differently?'"
As of 2014, global treaties listing LSD and psilocybin as "Schedule I" controlled substances continues to inhibit a better understanding of these drugs. Much of the renewed clinical research has been conducted with psilocybin and MDMA in the United States with special permission and breakthrough therapy designations by the FDA, while other studies have investigated the mechanisms and effects of ayahuasca and LSD. MDMA-assisted psychotherapy is being actively researched by MAPS.
As of 2023, many new centers for psychedelics research have been launched, including the Centre for Psychedelic Research at Imperial College London, the UC Berkeley Center for the Science of Psychedelics, the Center for Psychedelic and Consciousness Research at Johns Hopkins University, the Center for Psychedelic Research and Therapy at Dell Medical School at the University of Texas at Austin, the Center for Psychedelic Psychotherapy and Trauma Research at the Icahn School of Medicine at Mount Sinai, the Psychae Institute in Melbourne, and the Naut sa mawt Center for Psychedelic Research at Vancouver Island University. Harvard will create a Study of Psychedelics in Society and Culture.
A survey published in 2023 found strong support for psychedelic therapy among psychiatrists in the United States, revealing a significant positive shift in attitudes toward this treatment modality in comparison to a previous survey published in 2018. More than half of psychiatrists in the 2023 study expressed intentions to incorporate psychedelic therapy into their practice if regulatory approval is granted. In Australia, authorised psychiatrists can prescribe psilocybin for treatment-resistant depression, and MDMA for post-traumatic stress disorder.
In 2024, an FDA advisory panel voted against approving MDMA-assisted therapy for PTSD, "raising questions about the credibility of the research being conducted and the safety of those involved in the trials". The FDA advisors voted 9-2 that the available data didn’t show MDMA was effective in treating PTSD, and 10-1 that the benefits of MDMA-assisted therapy did not outweigh the risks. However, the U.S. Department of Veterans Affairs has since committed $1.5 million to its first study on psychedelic-assisted therapy for PTSD and alcohol use disorder in veterans, signaling growing institutional interest despite FDA skepticism.
In addition, veteran-led nonprofits like the Heroic Hearts Project are working with researchers to expand access to psychedelic therapies for military personnel and veterans.
In 2025, PsychedeliCare launched a European Citizens’ Initiative aiming to enable the implementation of psychedelic-assisted therapies in the EU to ensure safe and affordable psychedelic-assisted therapies.
== Applications ==
Psychedelic substances which may have therapeutic uses include psilocybin (the main active compound found in "magic" mushrooms), mescaline (the main active compound in the peyote cactus), and LSD. Although the history behind these substances has hindered research into their potential medicinal value, scientists are now able to conduct studies and renew research that was halted in the 1970s. Some research has shown that these substances have helped people with such mental disorders as obsessive-compulsive disorder, post-traumatic stress disorder, alcoholism, depression, and cluster headaches. Some of the well known particular psychedelic substances that have been used to this day are: LSD, DMT, psilocybin, mescaline, 2C-B, 2C-I, 5-MeO-DMT, AMT, ibogaine, and DOM. In general, the mechanism of action of how these drugs have therapeutic effects is poorly understood. Their effects are strongly dependent on the environment in which they are given and on the recipient's state of mind (set and setting).
=== In substance use disorders ===
Studies by Humphry Osmond, Betty Eisner, and others examined the possibility that psychedelic therapy could treat alcoholism (or, less commonly, other addictions). Bill Wilson, the founder of Alcoholics Anonymous, used LSD during supervised experiments with Betty Eisner, Gerald Heard, and Aldous Huxley. He ingested LSD for the first time on August 29, 1956. With Wilson's invitation, his wife Lois, his spiritual adviser Father Ed Dowling, and Nell Wing also participated in experimentation of this drug. Later Wilson wrote to Carl Jung, praising the results and recommending it as validation of Jung's spiritual experience. According to Wilson, the session allowed him to re-experience a spontaneous spiritual experience he had had years before, which had enabled him to overcome his own alcoholism.
A 1998 review of the effectiveness of psychedelic therapy for treating alcoholism concluded that due to methodological difficulties in the research prior to that time, it was not possible to state whether it was effective. A 2012 meta-analysis found that "In a pooled analysis of six randomized controlled clinical trials, a single dose of LSD had a significant beneficial effect on alcohol misuse at the first reported follow-up assessment, which ranged from 1 to 12 months after discharge from each treatment program. This treatment effect from LSD on alcohol misuse was also seen at 2 to 3 months and at 6 months, but was not statistically significant at 12 months post-treatment. Among the three trials that reported total abstinence from alcohol use, there was also a significant beneficial effect of LSD at the first reported follow-up, which ranged from 1 to 3 months after discharge from each treatment program."
In 2022 a systematic review was published on the efficacy of ibogaine/noribogaine, an indole alkaloid with “anti-addictive” properties, to treat substance use disorders looking at studies up to December 2020. Oral ingestion of ibogaine leads to an intense psychedelic experience with effects lasting up to 72 hours that lead participants to insights that may change the way they view life and their ways of thinking; however, the mechanism of how this drug works to reduce substance use is not yet understood. Evidence suggests that ibogaine does have some reduction on opioid and cocaine misuse, but more well designed, larger randomly controlled trials are required to fully understand the therapeutic benefits. Significant adverse reactions were experienced by participants including cardiotoxicity, QT prolongation, ataxia, psychosis, and several fatalities were reported due to toxic adverse events. Analysis of the fatalities concluded that patients with cardiac comorbidities and that those that are taking concurrent medications are at higher risk of a medical emergency.
A systematic review completed in 2023, containing studies from the past decade, looked at the ability of psychedelic therapy in combination with psychotherapy to help reduce substance use, cravings, and abstinence of addictions including alcohol, cocaine, opioids, and nicotine. Studies commonly reported reductions in substance misuse, however, the quality of evidence is too low to draw solid conclusions on the efficacy of psychedelic treatments for substance use disorders.
However, a systematic review of human and animal studies showed that a single dose of LSD for treatment of AUD led to greater odds of improvement in alcohol consumption than control participants.
=== In terminal illness ===
During the early 1950s and 1960s the National Institute of Mental Health sponsored the study of psychedelic drugs such as psilocybin and LSD to alleviate the debilitating anxiety and depression patients with terminal diagnoses may feel. While these early studies are hard to find, the resurgence of interest in psychedelic drugs to treat humans end of life mindset has led to some small studies in the 21st century. The more recently published research strengthens the findings from the 1950s and 1960s showing the drug is extremely effective in reducing anxiety and depression in this patient population once carefully screened and has few adverse effects when administered in a psychotherapy setting and under medical supervision. The psychologists leading psychedelic drug therapy trials found that end of life patients often experience the emotional turmoil of dying more than the physical aspects. This mindset makes it difficult for patients to find meaning and enjoyment in life during their last few months or years. While all patients have completely different experiences on these mind altering drugs the research subjects interviewed all expressed they had, "heightened clarity and confidence about their personal values and priorities, and a renewed or enhanced recognition of intrinsic meaning and value of life." More recently, researchers have argued that psychedelic therapy is beneficial for these patients because it may specifically reduce their fear of dying.
As of 2016, Johns Hopkins University and New York University have conducted large randomized, placebo-controlled studies. These two studies are some of the first large controlled studies measuring the effects of psychedelic therapy on depression and anxiety in cancer patients. Across clinician-ratings and self-ratings, the psychedelic treatment produced statistically significant lowered anxiety and depression, with sustenance for at least 6 months. The studies monitored for adverse effects from the drugs but no serious adverse effects were observed. Both studies also attributed the efficacy in part to patients experiencing a "mystical experience". A mystical experience is a very personal introspective experience where some sort of unity or transcendence of time and space is described. More research is necessary to expand generalizability of the conclusions. Also, more research is necessary to understand the biological properties of a mystical experience.
Evidence is growing for the use of atypical psychedelics such as ketamine for treating depression in terminally ill patients, with repeated IV administration having the most therapeutic effect. These studies did not have any patients experience any serious adverse effects; however, ketamine-induced ulcerative cystitis is a concern for repeated long-term administration. Qualitative studies are required to better understand the mechanism and thought process changes that lead to therapeutic outcomes.
=== In post-traumatic stress disorder (PTSD) ===
The Multidisciplinary Association for Psychedelic Studies (MAPS) is conducting studies in the psychedelic treatment of post-traumatic stress disorder. The Phase 2 trials of these studies, conducted in the U.S., Canada, and Israel, consisted of 107 participants who had chronic, treatment-resistant PTSD, and had had PTSD for an average of 17.8 years. Out of the 107 participants, 61% no longer qualified for PTSD after three sessions of MDMA-assisted psychotherapy two months after the treatment. At the 12-month follow-up session, 68% no longer had PTSD. Phase 2 trials conducted between 2004 and 2010 reported an overall remission rate of 66.2% and low rates of adverse effects for subjects with chronic PTSD. In 2017, MAPS and the FDA reached an agreement on the special protocol for phase 3 trials.
Evidence shows that MDMA-assisted psychotherapy versus control shows clinically significant improvement in Clinician-Administered PTSD Scale (CAPS) scores from baseline, with most of the patients no longer meeting the CAPS score for PTSD. Effects of MDMA-assisted psychotherapy can be observed up to 12 months after receiving 2-3 active sessions of moderate to high dose MDMA (75–125 mg).
It is important to note that given the difficulties with appropriate blinding in trials of MDMA- and psychedelic-assisted psychotherapy the results are likely overestimated. Furthermore, there are no superiority or non-inferiority clinical trials comparing MDMA-assisted psychotherapy to already existent evidence-based treatments for PTSD, but given the effects reported in clinical trials of MDMA-assisted psychotherapy for PTSD there is no reason to believe that this treatment modality is more effective than existent trauma-focused psychological treatments.
In 2024, an FDA advisory panel voted against approving MDMA-assisted therapy for PTSD, "raising questions about the credibility of the research being conducted and the safety of those involved in the trials". The FDA advisors voted 9-2 that the available data didn’t show MDMA was effective in treating PTSD, and 10-1 that the benefits of MDMA-assisted therapy did not outweigh the risks. However, the U.S. Department of Veterans Affairs has since committed $1.5 million to its first study on psychedelic-assisted therapy for PTSD and alcohol use disorder in veterans, signaling growing institutional interest despite FDA skepticism.
In addition, veteran-led nonprofits like the Heroic Hearts Project are working with researchers to expand access to psychedelic therapies for military personnel and veterans.
=== In depressive and anxiety disorders ===
In 2019, the FDA approved the use of esketamine for intranasal use for major depressive disorder (MDD) and treatment-resistant depression (TRD), in conjunction with an oral antidepressant.
Also in 2019, the FDA granted "breakthrough therapy" status to psilocybin for treatment-resistant depression and major depressive disorder in order to hasten the process for potential regulatory approval. The designation of "breakthrough therapy" fast-tracks the study of drugs where preliminary clinical evidence shows that they could be substantially more effective than therapies that are already available.
Studies on the clinical effects of ayahuasca have found significant antidepressant and anxiety-reducing effects, leading to calls for further research to overcome methodological limitations in the existing studies.
There is some evidence that psilocybin in combination with MDMA could be helpful for treating psychiatric disorders, but only when administered in a controlled clinical setting.
There is limited evidence that reductions in suicidality scores can be observed immediately after administration of ayahuasca or psilocybin, observable up to 6 months after administration.
=== In Obsessive Compulsive Disorder (OCD) ===
Since 1964, multiple case studies with psychedelic drugs have been performed in patients with either diagnosed OCD or patients exhibiting obsessive and/or compulsive symptoms. In 1964 and 1977, two case studies were published that showed a reduction in symptoms of patients who had previously exhibited obsessive and/or compulsive behaviors after taking Psilocybe mushrooms. In addition, three studies from 1987 to 1997 reported reductions in obsessive and/or compulsive symptoms in patients with diagnosed OCD after taking LSD and psilocybin. In 2014 and 2021, two case studies published by researchers from Arizona and Mexico, respectively, explained how patients taking 2 grams of psilocybin every 2-3 weeks not only saw qualitative improvements in their OCD symptoms, but also sustained this symptom improvement for several weeks after each dose.
In 2024, a systematic review was published analyzing the possible therapeutic benefits of psychedelics on OCD and related disorders. Findings include that LSD may be less tolerable than psilocybin due to more potential exacerbations of anxiety and OCD symptoms. Case reports found that psilocybin must be given in repeated doses in order to maintain reduction in OCD symptoms, which differentiates from its effect on depression. In patients diagnosed with body dysmorphic disorder and OCD, a single dose of psilocybin given for OCD symptoms was found to increase insight into the patient's disease, resulting in these patients seeking mental health treatment and recognizing that more effort was needed to tolerate their obsessions and resist their compulsions. This is important because among individuals with OCD, poor insight into their condition is associated with a worse prognosis.
Because of existing research showing the efficacy of Exposure and Response Prevention (ERP) in psychiatric disorders, future studies may seek to combine psychedelic therapy, specifically with psilocybin, with ERP as an adjunct for symptom remission, although no such studies have yet been conducted.
=== In reducing criminal behavior ===
In 2017, researchers mainly from the University of Birmingham published research suggesting that psilocybin use is correlated with reduced criminal behavior. The researchers analyzed data from 480,000 U.S. adults collected by the National Survey on Drug Use and Health on their past use of psychedelics, including ayahuasca, dimethyltryptamine, LSD, mescaline, peyote, San Pedro, and psilocybin mushrooms. While other illicit drugs have been associated with increased criminal behavior, the researchers found that psychedelic substances were instead associated with reduced criminal behavior. Usage of these substances was associated with a 12% reduction in likelihood of assault, 18% reduction in likelihood of other violent crimes, 27% reduction in likelihood of committing larceny and theft, and 22% reduction in likelihood of committing other property crimes. These findings potentially support the use of psychedelic therapy in forensic and clinical settings.
In a prior 2014 study, researchers explored the relationship between recidivism and naturalistic hallucinogens in criminal justice populations with a history of substance use. The results concluded that hallucinogens promoted prosocial behaviors in a population which is typically associated with high recidivism rates. The usage of hallucinogens has been found to reduce supervision failure in ex-convicts. This inherently encourages drug abstinence, including the use of alcohol, resulting in lower rates of recidivism.
A 2018 study found that men who had used psychedelic drugs in the past were less likely to commit violence against their current partners compared to those who had not used these substances. The study suggests that the use of psychedelic drugs in men might be associated with a reduced likelihood of committing violence against intimate partners, potentially due to improved emotion regulation.
A 2022 U.S. study found that use of classic psychedelics was associated with lowered odds of criminal arrest. The research suggests that 7 of the 11 arrest variables were reduced with lifetime psilocybin use. Peyote use was found to reduce the odds of driving under the influence and vehicle theft. Lastly, mescaline use was found to reduce drug possession/sale. No other substances shared a positive relationship with reducing criminal behavior.
== Contraindications ==
Psychedelic therapy is contraindicated for people who:
are pregnant,
have a history of epilepsy/other seizure disorder,
have severe cardiovascular disease including uncontrolled blood pressure, heart failure, coronary artery disease, or previous heart attack or stroke,
use medications like SSRI or MAO-I antidepressants,
have a personal or family history of primary psychotic or affective disorders like schizophrenia, schizoaffective disorder, Bipolar I disorder, or psychotic symptoms in the setting of depression.
== Criticisms and controversies ==
Although psychedelic therapy has shown promise in treating a range of mental health conditions—including depression, PTSD, and substance use disorders—it has also generated significant debate across ethical, cultural, and scientific domains. Critics have raised concerns about the overenthusiastic framing of psychedelics as a universal or revolutionary solution, cautioning that such narratives may overshadow limitations in clinical evidence, long-term safety data, and equity in access. Others argue that the rapid commercialization and medicalization of psychedelics risks reproducing existing structural inequalities in mental health care. In response, scholars have called for a more cautious, interdisciplinary approach that considers social context, informed consent, community frameworks, and culturally responsive practices.
=== Ethical and safety concerns ===
Critics have raised significant concerns regarding the ethical implications of psychedelic-assisted therapies, particularly focusing on the challenges surrounding informed consent and patient safety. The inherently unpredictable and often ineffable nature of psychedelic experiences can make it difficult for patients to fully comprehend and anticipate potential psychological risks. These challenges complicate the process of obtaining fully informed consent, especially in therapeutic contexts where long-term monitoring or integration support may be limited.
In August 2024, the U.S. Food and Drug Administration (FDA) declined to approve the first MDMA-based treatment for post-traumatic stress disorder (PTSD), citing insufficient data and concerns about trial methodology. The agency highlighted issues such as a "striking lack" of documentation regarding participants' prior substance use, problems with trial design, and the necessity for more robust evidence. The FDA requested an additional late-stage trial to further assess the drug's safety and efficacy.
Further ethical concerns have emerged from reports of misconduct within clinical trials. For instance, in August 2024, three papers on MDMA-assisted psychotherapy for PTSD were retracted from the journal *Psychopharmacology* due to ethical violations. These included inappropriate physical contact between a trial participant and an unlicensed therapist, leading to an unethical sexual relationship and alleged sexual assault. The data from this site were not removed from the analyses, raising questions about the integrity of the research.
The potential for therapist misconduct is a significant safety concern in psychedelic-assisted therapy. The altered states of consciousness induced by psychedelics can increase patients' suggestibility and vulnerability, necessitating rigorous ethical standards and oversight. Ensuring patient safety requires comprehensive training for therapists, strict adherence to ethical guidelines, and robust mechanisms for reporting and addressing any instances of misconduct.
Addressing these ethical and safety concerns is crucial for the responsible development and implementation of psychedelic-assisted therapies. This includes establishing clear protocols for informed consent, ensuring transparency in clinical trial methodologies, implementing stringent ethical standards for therapists, and conducting thorough long-term follow-up studies to monitor patient outcomes.
=== Methodological and structural limitations ===
Psychedelic clinical trials have faced recurring criticism for methodological shortcomings, particularly small sample sizes, short follow-up durations, and the exclusion of participants with comorbid or severe psychiatric conditions. These constraints reduce the external validity of findings, limiting their applicability to broader, real-world populations. For instance, many studies prioritize controlled environments and relatively healthy participants, thereby excluding those who may be most in need of innovative mental health treatments, such as individuals with trauma histories, substance use disorders, or severe depression.
In addition to these design limitations, demographic homogeneity remains a persistent issue in psychedelic research. A review of 18 psychedelic clinical trials found that 82.3% of participants were non-Hispanic White, with minimal inclusion of Black, Latino, Indigenous, and Asian individuals. More recent analyses suggest that despite growing interest in equitable access, racial and ethnic minorities remain significantly underrepresented in both research studies and clinical practice settings.
This underrepresentation has sparked broader concerns about systemic exclusion and the equitable distribution of therapeutic benefits. Historical medical abuses—such as the Tuskegee Syphilis Study and CIA-led MK-Ultra experiments—have contributed to deep mistrust in research institutions among marginalized communities.
To address these disparities, scholars and clinicians have called for more inclusive and culturally responsive research practices. Proposed strategies include partnering with community organizations, diversifying research staff, and creating protocols that respect cultural traditions and concerns. Such efforts aim not only to expand access but also to rebuild trust and ensure that psychedelic-assisted therapies are effective and ethical across diverse populations.
=== Sociological critiques and inequality in access and outcomes ===
Although psychedelic therapy is often presented as a universally beneficial mental health intervention, emerging sociological and epidemiological research has identified disparities in outcomes across demographic groups. Studies suggest that benefits associated with psychedelic use may be unequally distributed due to structural and social inequalities.
Several peer-reviewed studies have documented that racial and ethnic minorities often experience diminished psychological benefits from psychedelics compared to White participants, even when controlling for socioeconomic status, education, and baseline health. Additional research focusing on American Indian Areas has linked geographic and historical disadvantage to more limited mental health improvements following psychedelic use.
Gender differences have also been observed. Findings indicate that women may experience more variable or attenuated outcomes than men, particularly in relation to stigma reduction and distress. Other research suggests that education moderates these gender differences, with highly educated men reporting the strongest positive effects.
Disparities based on marital and employment status have also been explored. Individuals who are married or employed report greater psychological benefit, potentially due to social support systems and improved access to post-experience integration resources.
Variation has been noted in outcomes by religious affiliation and participation. Some studies suggest that individuals with strong religious integration may experience more meaningful or sustained benefits due to the availability of social and interpretive frameworks, while others with rigid or punitive religious backgrounds may experience conflict or distress.
LGBTQ+ individuals have also been found to experience unique patterns of benefit and risk in relation to psychedelic use. While some research documents substantial mental health improvements, others point to amplified vulnerability due to minority stress or inadequate therapeutic frameworks.
In addition, findings suggest that those from historically marginalized populations are more likely to avoid formal healthcare following psychedelic use due to prior stigma or systemic exclusion, potentially increasing risk or reducing access to integration services.
Collectively, this growing body of research challenges assumptions of universal benefit and has contributed to calls for equity-centered approaches in psychedelic science. These include greater attention to structural context, culturally responsive practices, and the inclusion of diverse communities in both research and therapeutic design.
=== Overmedicalization and commercialization ===
==== Marginalization of traditional and community-based healing ====
Scholars and activists have raised concerns that the medicalization of psychedelics risks marginalizing longstanding traditional, spiritual, and community-based approaches to healing. Tightly regulated clinical models—especially those requiring physician oversight and FDA approval—often exclude practices rooted in Indigenous knowledge, harm-reduction communities, or informal peer support structures. Critics argue that this narrowing of acceptable use may replicate colonial dynamics by privileging biomedical authority while disregarding alternative cultural and historical frameworks for psychedelic use.
Some researchers note that medical gatekeeping can deter vulnerable populations—especially those with prior trauma or medical mistrust—from seeking care. Others argue that community-first models, such as peer-led integration circles or underground networks, have demonstrated safety and efficacy outside of formal institutions but remain unrecognized in dominant medical discourse. These concerns have fueled calls for pluralistic frameworks that allow coexistence between clinical models and culturally grounded or community-led approaches to psychedelic healing.
==== Organizational influence and conflicts of interest ====
The influence of prominent organizations and individuals in the psychedelic field has raised concerns about transparency, accountability, and potential conflicts of interest. The Multidisciplinary Association for Psychedelic Studies (MAPS), a leading organization in psychedelic research and advocacy, has faced scrutiny regarding its internal governance and handling of ethical violations. In 2019, MAPS publicly disclosed that former clinical sub-investigators in a sponsored trial had violated ethical standards during therapy sessions. While MAPS stated that it responded promptly and transparently, critics questioned the adequacy of the organization's oversight mechanisms.
Further concerns emerged from the 2023 Psychedelic Science conference in Denver, Colorado, hosted by MAPS and the Multidisciplinary Association for Psychedelic Studies Public Benefit Corporation (MAPS PBC). The conference featured over 300 speakers, including academic researchers, therapists, entrepreneurs, and policy advocates. Many speakers disclosed financial interests in psychedelic companies, intellectual property claims, or affiliations with private clinics. Notable figures with such disclosures included:
- **Robin Carhart-Harris**, a leading neuroscientist in psychedelic research
- **Bia Labate**, an anthropologist and executive director of the Chacruna Institute
- **Rick Doblin**, founder and president of MAPS
- **Tim Ferriss**, author and investor
- **Charles Raison**, psychiatrist and director of the Center for Compassion Studies at the University of Arizona
- **Matthew Johnson**, professor of psychiatry and behavioral sciences at Johns Hopkins University
These conflict of interest disclosures were initially made available through the conference’s mobile app by the Postgraduate Institute for Medicine (PIM) but were later removed. Psymposia, a nonprofit media organization, archived the full list to preserve public access and transparency.
Rick Doblin has faced criticism for his dual role as both an advocate and the head of an organization poised to benefit financially from the potential FDA approval of MDMA-assisted therapy. Observers argue that this overlap between activism, research, and commercial interest may compromise objectivity in public discourse and trial reporting.
Broader concerns have been raised about how financial entanglements could influence research agendas and regulatory frameworks. In 2024, the Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics at Harvard Law School hosted a panel titled “Disclosed: Conflicts of Interest in the Psychedelics Ecosystem,” which examined how investment structures, private equity, and market speculation are shaping the future of psychedelic medicine.
These developments have led to calls for independent oversight, greater funding transparency, and more inclusive governance models to protect the integrity of psychedelic science and practice.
==== Patents, venture capital, and market consolidation ====
As the psychedelic field attracts increasing financial interest, critics have raised alarms about the ethical and structural implications of venture capital investment, aggressive patent strategies, and the potential monopolization of psychedelic therapies. A number of biotechnology companies and investors have moved quickly to patent not only psychedelic compounds—such as psilocybin analogs and synthetic DMT—but also delivery methods, treatment protocols, and even aspects of the therapeutic experience itself. This surge of intellectual property claims has sparked debates over the ethics of commodifying substances that have deep cultural, communal, and spiritual significance.
Some researchers and Indigenous advocates argue that patenting naturally occurring substances or ceremonial knowledge represents a form of "biopiracy," in which Western institutions extract and profit from traditional practices without community consent or benefit-sharing mechanisms. The controversy has intensified as corporations such as COMPASS Pathways and MindMed have secured patents on specific synthetic formulations or therapy session structures, prompting concerns about limited access, market exclusivity, and the suppression of innovation.
In parallel, the influx of venture capital has raised questions about whether financial incentives may undermine patient well-being. Observers note that the pressure to deliver returns to shareholders could lead to expedited clinical trials, underreporting of adverse effects, or the commercialization of unproven therapies. These dynamics are increasingly seen as misaligned with the values of many early psychedelic researchers, who viewed the field as an opportunity to promote personal transformation, healing, and societal reflection rather than profit maximization.
To mitigate these risks, scholars and advocacy groups have called for stronger open-access protections, ethical licensing models, and international standards to prevent monopolistic control. Some propose that non-profit and community-based models be protected or prioritized in future regulatory frameworks to ensure the equitable and culturally sensitive development of psychedelic therapies.
== Methods ==
=== Standard psychedelic therapy ===
The main approach used in the contemporary resurgence of research, often simply called psychedelic therapy, involves the use of moderate-to-high doses of psychedelic drugs. The psychedelic therapy method was initiated by Humphry Osmond and Abram Hoffer (with some influence from Al Hubbard) and replicated by Keith Ditman, and is more closely aligned to transpersonal psychology than to traditional psychoanalysis. Most recent research on psychedelic therapy has used psilocybin or ayahuasca.
Patients spend most of the acute period of the drug's activity lying down with eyeshades listening to music selected beforehand and exploring their inner experience. Dialogue with the therapists the drug session(s) but essential during the preparation session before and the integration session afterwards. The therapeutic team normally consists of a man and a woman, who are both present throughout the psychedelic experience. One aspect that occurs in most participants undergoing psychedelic therapy with moderate-to-high doses is transcendental, mystical, or peak experiences. Research has suggested that the strength of these experiences, together with discussion of them soon after in a therapeutic session, could be a major determinant of how great the longer-term effects on symptoms will be.
Some studies of psychedelic therapy have incorporated cognitive behavioral therapy (CBT) or motivational enhancement therapy (MET). Within a structured CBT intervention and a dose of psilocybin, patients are given the opportunity to experience cognitive and emotional states that are altered. With these psychedelic effects, cognitive reframing of detrimental schemas and self-identity can be modified positively.
In a MET environment, patients are able to reflect on their own behaviors to make changes in problematic manners, such as alcohol use disorder. Additionally, it could potentially enhance motivation to change and decrease possible ambivalence about behavioral changes. Within psychedelic drug sessions, through a reevaluation of the concept of self and reconnecting with core beliefs and values, this can be achieved.
Psychedelic-assisted group psychotherapy can be more cost-efficient, because therapists can split the costs among all participants of the group.
=== Psycholytic therapy ===
Psycholytic therapy involves the use of low-to-medium doses of psychedelic drugs, repeatedly at intervals of 1–2 weeks. The therapist is present during the peak of the experience to assist the patient in processing material that arises and to offer support. This general form of therapy was mostly used to treat patients with neurotic and psychosomatic disorders. The name psycholytic therapy was coined by Ronald A. Sandison, literally meaning "soul-dissolving", refers to the belief that the therapy can dissolve conflicts in the mind. Psycholytic therapy was historically an important approach to psychedelic psychotherapy in Europe, and was also practiced in the United States by some psychotherapists, including Betty Eisner. In the time since the 1970s, psycholytic therapy has not been a focus of research.
Psychedelic drugs are useful for exploring the subconscious because a conscious sliver of the adult ego usually remains active during the experience.: 196 Patients remain intellectually alert throughout the process and remember their experiences vividly afterward.: 196 In this highly introspective state, patients are actively aware of ego defenses such as projection, denial, and displacement as they react to themselves and their choices.: 196
The ultimate goal of the therapy is to provide a safe, mutually compassionate context through which the profound and intense reliving of memories can be filtered through the principles of genuine psychotherapy. Aided by the deeply introspective state attained by the patient, the therapist assists him/her in developing a new life framework or personal philosophy that recognizes individual responsibility for change.: 196
In Germany, Hanscarl Leuner designed a form of psycholytic therapy, which was developed officially but was also used by some socio-politically motivated underground therapists in the 1970s.
In Switzerland, Friedericke Meckel Fisher (trained by Stanislav Grof in Breathwork and Samuel Widmer in group psychedelic sessions) practiced group psycholytic therapy mainly from the early 2000s and until 2015. Meckel Fischer developed her own system of psycholytic therapy which she conducted underground, in group weekend sessions of 15 to 19 people, using medium dosages of psychedelic substances. She added and combined into this psycholytic group work, techniques of her own modified family constellation work, cathartic body work, evocative music, and periods of sharing and feedback within the group.
=== Other variations ===
==== Claudio Naranjo ====
The Chilean therapist Claudio Naranjo developed a branch of psychedelic therapy that utilized drugs like MDA, MDMA, harmaline, and ibogaine.
==== Anaclitic therapy ====
The term anaclitic (from the Ancient Greek "ἀνάκλιτος", anaklitos – "for reclining") refers to primitive, infantile needs and tendencies directed toward a pre-genital love object. Developed by two London psychoanalysts, Joyce Martin and Pauline McCririck, this form of treatment is similar to psycholytic approaches as it is based largely on a psychoanalytic interpretation of abreactions produced by the treatment, but it tends to focus on those experiences in which the patient re-encounters carnal feelings of emotional deprivation and frustration stemming from the infantile needs of their early childhood. As a result, the treatment was developed with the aim to directly fulfill or satisfy those repressed, agonizing cravings for love, physical contact, and other instinctual needs re-lived by the patient. Therefore, the therapist is completely engaged with the subject, as opposed to the traditional detached attitude of the psychoanalyst. With the intense emotional episodes that came with the psychedelic experience, Martin and McCririck aimed to sit in as the "mother" role who would enter into close physical contact with the patients by rocking them, giving them milk from a bottle, etc.
==== Hypnodelic therapy ====
Hypnodelic therapy, as the name suggests, was developed with the goal to maximize the power of hypnotic suggestion by combining it with the psychedelic experience. After training the patient to respond to hypnosis, LSD would be administered, and during the onset phase of the drug the patient would be placed into a state of trance. Levine and Ludwig found the combination of these techniques to be more effective than the use of either of these two components separately.
== Public interest ==
A resurgence of public interest in psychedelic drug therapy in the 21st century has been driven in part by articles in The New Yorker, The New York Times, and The Wall Street Journal.
=== Psychedelic tourism ===
The first article to bring attention to the uses of psychedelic drugs for mental health was titled, "Seeking the Magic Mushroom", written by Robert Gordon Wasson and published in 1957 by TIME magazine. It detailed his experience traveling to Oaxaca, Mexico, and taking "magic mushrooms" (psilocybin) within the cultural practices that started the "trip" experience. Since that time, there has been growing interest within the United States to travel for these unique psychedelic experiences. The market for psychedelic tourism is currently growing rapidly. While typically the vacation destinations for psychedelics are based in Central and South America, there is a rise in western culture taking over their traditional practices. In the Netherlands, there are psychedelic society retreats ranging in cost from $500–1200 that center on a ceremony in which tourists take magic mushrooms and trip together for around six hours. There are also underground psychedelic "guides" popping up around the United States that include leaders who claim to assist people through their trip similar to shamans in other cultures. An article in The Guardian entitled "Welcome to the trip of your life: the rise of underground LSD guides" details various styles of guides that can be found within the United States.
=== Psilocybin therapy ===
Psilocybin therapy is the use of psilocybin (the psychoactive ingredient in psilocybin mushrooms) in treating a range of mental health conditions, such as depression, anxiety, addictions, obsessive compulsive disorder, and psychosis.
As of January 1, 2023, psilocybin services facilitator training is available for individuals aged 21 and above who are Oregon residents. To become a psilocybin facilitator, an individual must complete a 120-hour regulated facilitator course, after which they may guide a client through a psilocybin experience. The facilitator may not engage the client in therapy; the therapeutic sessions held before and after the psilocybin experience itself are held by a psychotherapist. As of March 2023, there are currently graduates who can practice as licensed facilitators; however, no licensed service centers are yet operating.
== See also ==
== Notes ==
== References ==
== External links ==
History of LSD Therapy (Ch. 1 of Grof's, LSD Psychotherapy)
Reimbursement Pathways for Psychedelic Therapies in Europe Magnetar Access & Blossom
The Second International Conference on the Use of LSD in Psychotherapy and Alcoholism Archived 2016-03-05 at the Wayback Machine (1967) (entire book) | Wikipedia/Psychedelic_therapy |
Performance-enhancing substances (PESs), also known as performance-enhancing drugs (PEDs), are substances that are used to improve any form of activity performance in humans.
Many substances, such as anabolic steroids, can be used to improve athletic performance and build muscle, which in most cases is considered cheating by organized athletic organizations. This usage is often referred to as doping. Athletic performance-enhancing substances are sometimes referred to as ergogenic aids. Cognitive performance-enhancing drugs, commonly called nootropics, are sometimes used by students to improve academic performance. Performance-enhancing substances are also used by military personnel to enhance combat performance.
== Definition ==
The classifications of substances as performance-enhancing substances are not entirely clear-cut and objective. As in other types of categorization, certain prototype performance enhancers are universally classified as such (like anabolic steroids), whereas other substances (like vitamins and protein supplements) are virtually never classified as performance enhancers despite their effects on performance. As is usual with categorization, there are borderline cases; caffeine, for example, is considered a performance enhancer by some but not others.
== Types ==
The phrase has been used to refer to several distinct classes of drugs:
=== Anabolic steroids ===
Anabolic steroids are synthetically derived from testosterone and modified to have greater anabolic effects. They work by increasing the concentration of nitrogen in the muscle which inhibits catabolic glucocorticoid binding to muscle. This ultimately prohibits the breakdown of muscle and preserves muscle mass. Examples of anabolic steroids include: oxandrolone, stanozolol and nandrolone. Anabolic steroids can be taken through a transdermal method, orally, or through injection. Injectable forms of the steroid are the most potent and long-lasting. In general, potential side effects include: muscle hypertrophy, acne, hypertension, elevated cholesterol, thrombosis, decreased high-density lipoproteins, altered libido, hepatic carcinoma, cholestasis, peliosis hepatitis, septic arthritis, Wilm's tumor, psychosis, aggression, addiction, and depression. Potential side effects specifically in males include: male pattern baldness, oligospermia, prostate hypertrophy, testicular atrophy, and prostate cancer. Potential side specifically in females include: hirsutism, uterine atrophy, amenorrhea, breast atrophy, and thickening of vocal cords (voice deepening). Urine samples are tested to determine the ratio of testosterone glucuronide to epitestosterone glucuronide, which should be 3:1. Any ratio of 4:1 or greater is considered a positive test. The 1988 Anti-Drug Abuse Act and 1990 Anabolic Steroid Act both deemed anabolic steroids as an illegal substance when not used for disease treatment.
=== Stimulants ===
Stimulants improve focus and alertness. Low (therapeutic) doses of dopaminergic stimulants (e.g., reuptake inhibitors and releasing agents) also promote mental and athletic performance, as cognitive enhancers and ergogenic aids respectively, by improving muscle strength and endurance while decreasing reaction time and fatigue. Stimulants are commonly used in lengthy exercises that require short bursts (e.g., tennis, team sports, etc.). Stimulants work by increasing catecholamine levels and agonistic activity at the adrenergic receptors. Examples of stimulants include caffeine, ephedrine, methylphenidate and amphetamine. Potential side effects include hypertension, insomnia, headaches, weight loss, arrhythmia, tremors, anxiety, addiction, and strokes. Some stimulants are allowed in competitive sports and are widely accessible, though may also be monitored by the World Anti-Doping Agency (WADA), such as caffeine. Others are banned as per the WADA (e.g., cocaine, amphetamines, ephedrine, etc.).
=== Ergogenic aids ===
Ergogenic aids, or athletic performance-enhancing substances, include a number of drugs with various effects on physical performance. Drugs such as amphetamine and methylphenidate increase power output at constant levels of perceived exertion and delay the onset of fatigue, among other athletic-performance-enhancing effects; bupropion also increases power output at constant levels of perceived exertion, but only during short-term use.
==== Examples ====
Creatine: one of the most popular nutritional supplements, it contributes to 400 million dollars in sales globally every year. It is a nonessential amino acid that helps to improve an athlete's performance during short-term, high intensity exercises such as weightlifting. Supplementation of creatine increases skeletal muscle creatine levels, this boosts performance by increasing the rate at which adenosine triphosphate can be replenished from adenosine diphosphate, thereby increasing maximal power output. Potential side effects include gastrointestinal cramps, weight gain, fatigue, and diarrhea. Creatine is currently not recognized as a prohibited substance and can be purchased as a legal dietary supplement.
β-hydroxy β-methylbutyrate, a metabolite of leucine also used as a supplement, has positive effects on lean muscle mass, possibly through a decrease in muscle catabolism.
Human Growth Hormone (hGH): endogenous hormone that can help decrease fat mass while increasing lean body mass. hGH is one of the most commonly used substances among professional athletes because it has a small window for detection. It works by promoting the release of IGF-1, insulin-like growth factor, the release of which has anabolic effects on the body. Potential side effects include: cardiomyopathy, diabetes, renal failure, and hepatitis. If not prescribed by a professional, it is a banned substance in competition per WADA. Despite its small window for detection, two primary methods of testing have been developed for hGH, one being an isoform test which detects changes in growth hormone structure in the blood, and the markers test, which detects changes in serum protein ratios.
=== Adaptogens ===
Adaptogens are plants that support health through nonspecific effects, neutralize various environmental and physical stressors while being relatively safe and free of side effects. As of 2008, the position of the European Medicines Agency was that "The principle of an adaptogenic action needs further clarification and studies in the pre-clinical and clinical area. As such, the term is not accepted in pharmacological and clinical terminology that is commonly used in the EU."
=== Actoprotectors ===
Actoprotectors or synthetic adaptogens are compounds that enhance an organism's resilience to physical stress without increasing heat output. Actoprotectors are distinct from other doping compounds in that they increase physical and psychological resilience via non-exhaustive action. Actoprotectors such as bemethyl and bromantane have been used to prepare athletes and enhance performance in Olympic competition. However, only bromantane has been placed on the World Anti-Doping Agency's banned list.
=== Nootropics ===
Nootropics, or "cognition enhancers", are substances that are claimed to benefit overall cognition by improving memory (e.g., increasing working memory capacity or updating) or other aspects of cognitive control (e.g., inhibitory control, attentional control, attention span, etc.).
=== CNS agents ===
==== Painkillers ====
Allows performance beyond the usual pain threshold. Some painkillers raise blood pressure, increasing oxygen supply to muscle cells. Painkillers used by athletes range from common over-the-counter medicines such as NSAIDs (such as ibuprofen) to powerful prescription narcotics.
==== Sedatives and anxiolytics ====
Sedatives and anxiolytics are used in sports like archery which require steady hands and accurate aim, and also to overcome excessive nervousness or discomfort for more dangerous sports. Diazepam, nicotine, and propranolol are common examples. Ethanol, the most commonly used substance by athletes, can be used for cardiovascular improvements though has significant detrimental effects. Ethanol was formerly banned by WADA during performance for athletes performing in aeronautics, archery, automobile, karate, motorcycling and powerboating, but was taken off the ban list in 2017. It is detected by breath or blood testing. Cannabis is banned at all times for an athlete by WADA, though performance-enhancing effects have yet to be studied. Cannabis and nicotine are detected through urine analysis.
=== Blood boosters ===
Blood doping agents increase the oxygen-carrying capacity of blood beyond the individual's natural capacity. They are used in endurance sports like long-distance running, cycling, and Nordic skiing. Recombinant human erythropoietin (rhEPO) is one of the most widely known drugs in this class. The Athlete Biological Passport is the only indirect testing method for detection of blood doping.
==== Erythropoietin ====
Erythropoietin, or EPO, is a hormone that helps increase the production of red blood cells which increases the delivery of oxygen to muscles. It is commonly used among endurance athletes such as cyclists. It functions by protecting red blood cells against destruction whilst simultaneously stimulating bone marrow cells to produce more red blood cells. Potential side effects include: dehydration and an increase in blood viscosity which could result in a pulmonary embolism or stroke. Per the WADA, it is a banned substance. Urine samples can be tested via electrophoresis, and blood samples via indirect markers.
=== Gene doping ===
Gene doping agents are a relatively recently described class of athletic performance-enhancing substances. These drug therapies, which involve viral vector-mediated gene transfer, are not known to currently be in use as of 2020.
=== Prohormones ===
Also known as anabolic steroid precursors, they promote lean body mass. Once in the body, these precursors are converted to testosterone and increase endogenous testosterone. The desired effects of steroid precursors however, are often not seen as they do not bind well to androgen receptors. Examples of prohormones include norandrostendione, androstenediol, and dehydroepiandrosterone (DHEA). These steroids have little desired effect compared to anabolic steroids, but have the same side effects. Androstenedione in 2005 became classified as a controlled substance by WADA, however DHEA can still be obtained legally as an over-the-counter nutritional supplement.
== History ==
While the use of PEDs has expanded in recent times, the practice of using substances to improve performance has been around since the Ancient Olympic Games. In the Olympic Games of 668 BC, Charmis had consumed a diet consisting of dried figs which was thought, at the time, to be a significant factor in winning the 200-yard stade race. Ancient Greek athletes at the time also incorporated substances such as wine and brandy into their training routines. Stimulants derived from plants (e.g., Cola nitida, Bufotein, etc.) were used by the Roman gladiators to overcome injuries and fatigue.
In the late 19th century as modern medicine and pharmacology were developing, PEDs saw an increase in use. Supplements were now exclusively being used to enhance muscular work capacity. The main substances being used included alcoholic drinks, caffeine, and mixtures created by the athletic trainers (e.g., strychnine tablets made of cocaine and brandy).
In the 20th century, testosterone was isolated and characterized by scientists. In 1941, the first record of synthesized testosterone use occurred when a horse was given testosterone which successfully improved its race performance. Sports trainers soon after began advocating for testosterone use. Images of bodybuilders with massive muscles began circulating which further perpetuated a desire among athletes to use testosterone. In 1967, the first prohibited substance list and anti-doping measures were implemented at the 1968 Olympics.
In the 1980s, the main PEDs were cortisone and anabolic steroids. In 1988, the United States Congress established the Anti-Drug Abuse Act to criminalize the distribution and possession of non-medical anabolic steroids. In 1999, WADA was formed to address the escalating use of substances in sports, particularly after the 1998 doping scandal in cycling.
== Risk factors ==
Adolescents are the most vulnerable group when it comes to taking performance-enhancing substances. This is in part due to the significance placed on physical appearance by this age group as well as feelings of invincibility combined with a lack of knowledge surrounding long-term consequences. Studies have shown that the most common gendered risk factors include being an adolescent female dissatisfied with their body weight or an adolescent male who perceives larger body sizes as the ideal. Having a negative body image or a history of depression can also be a significant risk factor. These are further exacerbated by parental pressures surrounding appearance, media influence, and peer pressure.
Studies show that adolescent males who engage with fitness magazines are twice as likely to use performance-enhancing substances. Adolescents who partake in competitive sports are at a particularly high risk, with those involved in gridiron football, basketball, wrestling, baseball, and gymnastics at the top.
== Usage in sport ==
In sports, the term performance-enhancing drugs is popularly used in reference to anabolic steroids or their precursors (hence the colloquial term steroids); anti-doping organizations apply the term broadly. Agencies such as the WADA and United States Anti-Doping Agency try to prevent athletes from using these drugs by performing drug tests. When medical exemptions are granted they are called therapeutic use exemptions.
== See also ==
Cosmetic pharmacology
Ergogenic use of anabolic steroids
List of doping cases in sport
List of drugs used by militaries
Natural bodybuilding
Neuroenhancement
Steroid use in American football
== References ==
== External links ==
Media related to Ergogenic aids at Wikimedia Commons | Wikipedia/Performance-enhancing_drugs |
Being involved in the illegal drug trade in certain countries, which may include illegally importing, exporting, selling or possession of significant amounts of drugs, constitutes a capital offence and may result in capital punishment for drug trafficking, or possession assumed to be for drug trafficking. There are also extrajudicial executions of suspected drug users and traffickers in at least 2 countries without drug death penalties by law: Mexico and Philippines.
As of December 2022 Harm Reduction International (HRI) reports 3700+ people are on death row for drug offences worldwide. For 2022 HRI reports at least 285 executions by law for drug offences globally in 6 countries. 252+ in Iran. 22 in Saudi Arabia. 11 in Singapore. Exact numbers are not possible due to "extreme opacity" in some countries: China, North Korea, and Vietnam.
A Harm Reduction International global overview of 2022 reported: "HRI has identified 35 countries and territories that retain the death penalty for drug offences in law. Only a small number of these countries carry out executions for drug offences regularly. In fact, six of these states are classified by Amnesty International as abolitionist in practice. This means that they have not carried out executions for any crime in the past ten years (although in some cases death sentences are still pronounced), and 'are believed to have a policy or established practice of not carrying out executions.' Other countries have neither sentenced to death nor executed anyone for a drug offence, despite having dedicated laws in place."
A March 2018 report by Harm Reduction International says: "Between January 2015 and December 2017, at least 1,320 people are known to have been executed for drug-related offences – 718 in 2015; 325 in 2016; and 280 in 2017. These estimates do not include China, as reliable figures continue to be unavailable for the country." 1,176 of the 1,320 total were in Iran.
According to a 2011 article by the Lawyers Collective, an NGO in India, "32 countries impose capital punishment for offences involving narcotic drugs and psychotropic substances." A 2015 article by The Economist says that the laws of 32 countries provide for capital punishment for drug smuggling.
== Overview ==
Sentences for drug-related crimes, especially for trafficking, are the strictest in Asian countries. In January 2014, then-President Thein Sein of Myanmar commuted all the country's death sentences to life imprisonment. In South Korea, the law continues to provide for the death penalty for drug offences, although it currently has a moratorium on capital punishment: there have been no executions since 1997, but there are still people on death row, and new death sentences continue to be handed down. While capital punishment has been abolished in the Philippines, the Philippine Drug War has led to thousands of extrajudicial executions against drug traffickers, which are endorsed by president Rodrigo Duterte and his government.
== Use by country ==
Harm Reduction International breaks down nations by high application, low application, symbolic application, and insufficient data.
Note: Asterisk (*) after country name indicates Crime in LOCATION links.
== Gallery ==
== See also ==
Capital punishment
Use of capital punishment by country
Capital punishment for cannabis trafficking
Maritime drug trafficking in Latin America
Mexican drug war
Philippine drug war
United Nations Office on Drugs and Crime
United Nations Commission on Narcotic Drugs
== References ==
== External links ==
Methods of execution:
Methods of Execution Archived 22 December 2015 at the Wayback Machine. Death Penalty Worldwide project.
Methods of Execution by Country - NutzWorld.com Archived 14 July 2011 at the Wayback Machine
Resources for references:
Death Penalty | StoptheDrugWar.org. Ongoing compilation of articles about countries sentencing people to death for drug offenses. | Wikipedia/Capital_punishment_for_drug_trafficking |
Lexicography is the study of lexicons and the art of compiling dictionaries. It is divided into two separate academic disciplines:
Practical lexicography is the art or craft of compiling, writing and editing dictionaries.
Theoretical lexicography is the scholarly study of semantic, orthographic, syntagmatic and paradigmatic features of lexemes of the lexicon (vocabulary) of a language, developing theories of dictionary components and structures linking the data in dictionaries, the needs for information by users in specific types of situations, and how users may best access the data incorporated in printed and electronic dictionaries. This is sometimes referred to as "metalexicography".
There is some disagreement on the definition of lexicology, as distinct from lexicography. Some use "lexicology" as a synonym for theoretical lexicography; others use it to mean a branch of linguistics pertaining to the inventory of words in a particular language.
A person devoted to lexicography is called a lexicographer and is, according to a jest of Samuel Johnson, a "harmless drudge".
== Focus ==
Generally, lexicography focuses on the design, compilation, use and evaluation of general dictionaries, i.e. dictionaries that provide a description of the language in general use. Such a dictionary is usually called a general dictionary or LGP dictionary (Language for General Purpose). Specialized lexicography focuses on the design, compilation, use and evaluation of specialized dictionaries, i.e. dictionaries that are devoted to a (relatively restricted) set of linguistic and factual elements of one or more specialist subject fields, e.g. legal lexicography. Such a dictionary is usually called a specialized dictionary or Language for specific purposes dictionary and following Nielsen 1994, specialized dictionaries are either multi-field, single-field or sub-field dictionaries.
It is now widely accepted that lexicography is a scholarly discipline in its own right and not a sub-branch of applied linguistics, as the chief object of study in lexicography is the dictionary (see e.g. Bergenholtz/Nielsen/Tarp 2009).
Lexicography is the practice of creating books, computer programs, or databases that reflect lexicographical work and are intended for public use. These include dictionaries and thesauri which are widely accessible resources that present various aspects of lexicology, such as spelling, pronunciation, and meaning.
Lexicographers are tasked with defining simple words as well as figuring out how compound or complex words or words with many meanings can be clearly explained. They also make decisions regarding which words should be kept, added, or removed from a dictionary. They are responsible for arranging lexical material (usually alphabetically) to facilitate understanding and navigation.
== Etymology ==
Coined in English 1680, the word "lexicography" derives from the Greek λεξικογράφος (lexikographos), "lexicographer", from λεξικόν (lexicon), neut. of λεξικός lexikos, "of or for words", from λέξις (lexis), "speech", "word" (in turn from λέγω (lego), "to say", "to speak") and γράφω (grapho), "to scratch, to inscribe, to write".
== Aspects ==
Practical lexicographic work involves several activities, and the compilation of well-crafted dictionaries requires careful consideration of all or some of the following aspects:
profiling the intended users (i.e. linguistic and non-linguistic competences) and identifying their needs
defining the communicative and cognitive functions of the dictionary
selecting and organizing the components of the dictionary
choosing the appropriate structures for presenting the data in the dictionary (i.e. frame structure, distribution structure, macro-structure, micro-structure and cross-reference structure)
selecting words and affixes for systematization as entries
selecting collocations, phrases and examples
choosing lemma forms for each word or part of word to be lemmatized
defining words
organizing definitions
specifying pronunciations of words
labeling definitions and pronunciations for register and dialect, where appropriate
selecting equivalents in bi- and multi-lingual dictionaries
translating collocations, phrases and examples in bi- and multilingual dictionaries
designing the best way in which users can access the data in printed and electronic dictionaries
One important goal of lexicography is to keep the lexicographic information costs incurred by dictionary users as low as possible. Nielsen (2008) suggests relevant aspects for lexicographers to consider when making dictionaries as they all affect the users' impression and actual use of specific dictionaries.
Theoretical lexicography concerns the same aspects as lexicography, but aims to develop principles that can improve the quality of future dictionaries, for instance in terms of access to data and lexicographic information costs. Several perspectives or branches of such academic dictionary research have been distinguished: 'dictionary criticism' (or evaluating the quality of one or more dictionaries, e.g. by means of reviews (see Nielsen 1999), 'dictionary history' (or tracing the traditions of a type of dictionary or of lexicography in a particular country or language), 'dictionary typology' (or classifying the various genres of reference works, such as dictionary versus encyclopedia, monolingual versus bilingual dictionary, general versus technical or pedagogical dictionary), 'dictionary structure' (or formatting the various ways in which the information is presented in a dictionary), 'dictionary use' (or observing the reference acts and skills of dictionary users), and 'dictionary IT' (or applying computer aids to the process of dictionary compilation).
One important consideration is the status of 'bilingual lexicography', or the compilation and use of the bilingual dictionary in all its aspects (see e.g. Nielsen 1994). In spite of a relatively long history of this type of dictionary, it is often said to be less developed in a number of respects than its unilingual counterpart, especially in cases where one of the languages involved is not a major language. Not all genres of reference works are available in interlingual versions, e.g. LSP, learners' and encyclopedic types, although sometimes these challenges produce new subtypes, e.g. 'semi-bilingual' or 'bilingualised' dictionaries such as Hornby's (Oxford) Advanced Learner's Dictionary English-Chinese, which have been developed by translating existing monolingual dictionaries (see Marello 1998).
== History ==
Traces of lexicography can be identified as early late 4th millennium BCE, with the first known examples being Sumerian cuneiform texts uncovered in the city of Uruk. Ancient lexicography usually consisted of word lists documenting a language's lexicon. Other early word lists have been discovered in Egyptian, Akkadian, Sanskrit, and Eblaite, and take the shape of mono- and bilingual word lists. They were organized in different ways including by subject and part of speech. The first extensive glosses, or word lists with accompanying definitions, began to appear around 300 BCE, and the discipline begins to develop more steadily. Lengthier glosses started to emerge in the literary cultures of antiquity, including Greece, Rome, China, India, Sasanian Persia, and the Middle East. In 636, Isidore of Seville published the first formal etymological compendium. The word dictionarium was first applied to this type of text by the late 14th century.
With the invention and spread of Gutenberg's printing press in the 15th century, lexicography flourished. Dictionaries became increasingly widespread, and their purpose shifted from a way to store lexical knowledge to a mode of disseminating lexical information. Modern lexicographical practices began taking shape during the 18th and 19th centuries, led by notable lexicographers such as Samuel Johnson, Vladimir Dal, the Brothers Grimm, Noah Webster, James Murray, Peter Mark Roget, Joseph Emerson Worcester, and others.
During the 20th century, the invention of computers changed lexicography again. With access to large databases, finding lexical evidence became significantly faster and easier. Corpus research also enables lexicographers to discriminate different senses of a word based on said evidence. Additionally, lexicographers were now able to work nonlinearly, rather than being bound to a traditional lexicographical ordering like alphabetical ordering.
In the early 21st century, the increasing ubiquity of artificial intelligence began to impact the field, which had traditionally been a time-consuming, detail-oriented task. The advent of AI has been hailed by some as the "end of lexicography". Others are skeptical that human lexicographers will be outmoded in a field studying the particularly human substance of language.
== See also ==
== References ==
== Further reading ==
Atkins, B.T.S. & Rundell, Michael (2008) The Oxford Guide to Practical Lexicography, Oxford U.P. ISBN 978-0-19-927771-1
Béjoint, Henri (2000) Modern Lexicography: An Introduction, Oxford U.P. ISBN 978-0-19-829951-6
Considine, John, ed. (2019) The Cambridge World History of Lexicography. Cambridge University Press. ISBN 9781107178861
Bergenholtz, H., Nielsen, S., Tarp, S. (eds.): Lexicography at a Crossroads: Dictionaries and Encyclopedias Today, Lexicographical Tools Tomorrow. Peter Lang 2009. ISBN 978-3-03911-799-4
Bergenholtz, Henning & Tarp, Sven (eds.) (1995) Manual of Specialised Lexicography: The Preparation of Specialised Dictionaries, J. Benjamins. ISBN 978-90-272-1612-0
Green, Jonathon (1996) Chasing the Sun: Dictionary-Makers and the Dictionaries They Made, J. Cape. ISBN 0-7126-6216-2
Hartmann, R.R.K. (2001) Teaching and Researching Lexicography, Pearson Education. ISBN 978-0-582-36977-1
Hartmann, R.R.K. (ed.) (2003) Lexicography: Critical Concepts, Routledge/Taylor & Francis, 3 volumes. ISBN 978-0-415-25365-9
Hartmann, R.R.K. & James, Gregory (comps.) (1998/2001) Dictionary of Lexicography, Routledge. ISBN 978-0-415-14144-4
Inglis, Douglas (2004) Cognitive Grammar and lexicography. Payap University Graduate School Linguistics Department.
Kirkness, Alan (2004) "Lexicography", in The Handbook of Applied Linguistics ed. by A. Davies & C. Elder, Oxford: Blackwell, pp. 54–81. ISBN 978-1-4051-3809-3
Landau, Sidney (2001) Dictionaries: The Art and Craft of Lexicography, Cambridge U.P. 2nd ed. ISBN 0-521-78512-X
Marello, Carla (1998) "Hornby's bilingualized dictionaries", in International Journal of Lexicography 11,4, pp. 292–314.
Nielsen, Sandro (1994) The Bilingual LSP Dictionary, G. Narr. ISBN 978-3-8233-4533-6
Nielsen, Sandro (2008) "The effect of lexicographical information costs on dictionary making and use", in Lexikos (AFRILEX-reeks/series 18), pp. 170–189.
Nielsen, Sandro (2009): "Reviewing printed and electronic dictionaries: A theoretical and practical framework". In S. Nielsen/S. Tarp (eds): Lexicography in the 21st Century. In honour of Henning Bergenholtz. Amsterdam/Philadelphia: John Benjamins, 23–41. ISBN 978-90-272-2336-4.
Ooi, Vincent (1998) Computer Corpus Lexicography, Edinburgh U.P. [1] ISBN 0-7486-0815-X
Zgusta, Ladislav (1971) Manual of lexicography (Janua Linguarum. Series maior 39). Prague: Academia / The Hague, Paris: Mouton. ISBN 978-90-279-1921-2
== External links ==
International Journal of Lexicography
Lexicographica. International Annual for Lexicography - Revue Internationale de Lexicographie - Internationales Jahrbuch für Lexikographie
=== Societies ===
Centre for Lexicography EN version
Dictionary Society of North America
Euralex – European Association for Lexicography
Afrilex – African Association for Lexicography
Australex – Australasian Association for Lexicography
Nordic Federation for Lexicography
Asialex – Asian Association for Lexicography | Wikipedia/Lexicographer |
A temporary class drug is a relatively new status for controlled drugs, which has been adopted in some jurisdictions, notably New Zealand and the United Kingdom, to attempt to bring newly synthesised designer drugs under legal control. The controlled drug legislation in these jurisdictions requires drug scheduling decisions to follow an evidence-based process, where the harms of the drug are assessed and reviewed so that an appropriate legal status can be assigned. Since many designer drugs sold in recent years have had little or no published research that could help inform such a decision, they have been widely sold as "legal highs", often for months, before sufficient evidence accumulates to justify placing them on the controlled drug schedules.
This situation has been deemed to be undesirable, as every time a designer drug has been banned, novel compounds with similar effects have been quickly developed and brought to market, often with worse health consequences reported than the original compound. The temporary class drug status has been developed to circumvent the evidential requirements and allow drugs to be banned temporarily as soon as they are deemed by authorities to be causing harm to individuals or society. The temporary ban lasts for a period of 1 year, after which the drug would in theory be made legal again, if sufficient evidence to ban it permanently had not been forthcoming. During the period of the temporary ban, the temporary class drugs are treated equivalently to established illegal drugs, though with reduced or absent penalties for personal use amounts, and the main focus of enforcement being on importation and sale of the drugs.
== United Kingdom ==
The Secretary of State has the authority to make temporary class drug orders under the Misuse of Drugs Act section 2A(1).
Initially, only the dissociative arylcyclohexylamine derivative methoxetamine was banned as a temporary class drug in the UK, effective from 5 April 2012. On 26 February 2013 methoxetamine was banned as a Class B drug under the Misuse of Drugs Act along with a large number of other arylcyclohexylamine derivatives under a 'catch-all' chemical structure clause. "In an attempt to prevent legal high manufacturers looking for a new ketamine analogue to sell, the government has placed countless other ketamine analogues into Class B and Schedule 1."
On 10 June 2013, a total of 10 benzofuran and indole analogues and four NBOMe hallucinogens were classified as Temporary Class Drugs in the UK following an ACMD recommendation. Specifically these include 5-APB, 6-APB, 5-APDB, 6-APDB and their N-methyl derivatives 5-MAPB, 6-MAPB, 5-MAPDB and 6-MAPDB, as well as 5-IT and its isomer 6-IT, plus NBOMe-2C-C, NBOMe-2C-B, NBOMe-2C-I and NBOMe-2C-D. This means that sale and import of the named substances are criminal offences and are treated as for Class B drugs.
On 31 March 2015, five derivatives of methylphenidate were recommended to be banned in the UK as Temporary Class Drugs following their sale as uncontrolled stimulant drugs. The compounds listed for control were ethylphenidate, propylphenidate, isopropylphenidate, methylnaphthidate and 3,4-Dichloromethylphenidate.
On 25 June 2015, two more derivatives of methylphenidate, 4-Methylmethylphenidate and ethylnaphthidate, were recommended to be banned in the UK as Temporary Class Drugs following their sale as uncontrolled stimulant drugs.
Following the ban on ethylphenidate authorities noticed that methiopropamine had replaced it as the stimulant of choice for injecting users. A TCDO was announced a week later and it was banned 48 hours after this.
== New Zealand ==
In New Zealand, 35 drugs have been banned as temporary class drugs since August 2011, 24 of which have subsequently had the temporary ban renewed for a further year after reaching the end of the initial one-year ban period. These include; JWH-018, JWH-022, JWH-073, JWH-081, JWH-122, JWH-201, JWH-203, JWH-210, JWH-250, JWH-302, AM-694, AM-2201, RCS-4, RCS-4 butyl homologue, 2-methoxy isomer of RCS-4, and 2-methoxy isomer of RCS-4 butyl homologue, which were banned on 16 August 2011, JWH-019, JWH-200 and AM-1220, which were banned on 14 October 2011, AM-2233, banned on 29 December 2011, AM-1248, AM-2232 and UR-144, banned on 6 April 2012, and the stimulant methylhexanamine, banned on 9 April 2012. Another four cannabinoid compounds, namely CB-13, MAM-2201, AKB48 and XLR-11, were banned on 13 July 2012. A further cannabinoid compound NNE1 was banned from 8 November 2012. Two more cannabinoids APICA (also known as 2NE1) and its 5-fluoropentyl derivative STS-135 were banned from 22 November 2012. Another cannabinoid EAM-2201 was banned from 6 December 2012. Another stimulant, the phenyltropane derivative RTI-126, was banned from 27 December 2012. Two more cannabinoids QUCHIC (also known as BB-22) and 5F-AKB48 were banned from 9 May 2013.
On 18 July 2013, the Psychoactive Substances Act 2013 came into effect in New Zealand. This superseded the Temporary Class Drug scheme, as all novel psychoactive substances are restricted by default, except where specifically licensed. This Act promises to introduce strict toxicity testing and quality control standards for recreational psychoactive substances, with products that are proved to meet the safety criteria being allowed to be sold legally. Products that were on sale immediately prior to the introduction of the Act were allowed to continue to be on sale while the safety testing regime is implemented, but can be removed from sale if significant adverse events are reported. A number of interim licenses have been refused or revoked under this process, and by January 2014 a total of twelve more synthetic cannabis products had been removed from sale, containing ingredients such as ADB-CHMICA (SGT-7), 5F-PB-22, SGT-55 (CUMYL-BICA), SGT-56 (CUMYL-PICA), 4-F-AM-2201, 4-Cl-AM-2201 and PB-22.
On 27 April 2014 it was announced that all 41 remaining untested "legal high" products, which had been allowed to continue to be on sale during an interim period, were to be banned on 9 May 2014. These were mainly synthetic cannabis products containing ingredients such as AB-FUBINACA, PB-22 (QUPIC), 5F-PB-22, SGT-24 (CUMYL-PINACA), CP 55,244, 4-F-AM-2201, 4-Cl-AM-2201, 5F-ADBICA and AB-005. There was also one cannabinoid pill containing SGT-42 (CUMYL-THPINACA), and several "party pill" products containing mixtures of ingredients such as caffeine, hordenine, synephrine and kava. No "legal high" products will be allowed back on sale in New Zealand under the Psychoactive Substances Act until they have been tested in a manner yet to be determined, and found to present a "low risk of harm". This process is expected to take at least 18 months or more. Six of the synthetic cannabis products were ordered to be immediately removed from sale by emergency recall on 1 May 2014, to ensure that users would not be able to stockpile supplies of these products before the general ban took effect on 9 May.
== See also ==
Designer drug
== References == | Wikipedia/Temporary_class_drug |
Recreational drug use is the use of one or more psychoactive drugs to induce an altered state of consciousness, either for pleasure or for some other casual purpose or pastime. When a psychoactive drug enters the user's body, it induces an intoxicating effect. Recreational drugs are commonly divided into three categories: depressants (drugs that induce a feeling of relaxation and calmness), stimulants (drugs that induce a sense of energy and alertness), and hallucinogens (drugs that induce perceptual distortions such as hallucination).
In popular practice, recreational drug use is generally tolerated as a social behaviour, rather than perceived as the medical condition of self-medication. However, drug use and drug addiction are severely stigmatized everywhere in the world. Many people also use prescribed and controlled depressants such as opioids, opiates, and benzodiazepines. What controlled substances are considered generally unlawful to possess varies by country, but usually includes cannabis, cocaine, opioids, MDMA, amphetamine, methamphetamine, psychedelics, benzodiazepines, and barbiturates. As of 2015, it is estimated that about 5% of people worldwide aged 15 to 65 (158 million to 351 million) had used controlled drugs at least once.
Common recreational drugs include caffeine, commonly found in coffee, tea, soft drinks, and chocolate; alcohol, commonly found in beer, wine, cocktails, and distilled spirits; nicotine, commonly found in tobacco, tobacco-based products, and electronic cigarettes; cannabis and hashish (with legality of possession varying inter/intra-nationally); and the controlled substances listed as controlled drugs in the Single Convention on Narcotic Drugs (1961) and the Convention on Psychotropic Substances (1971) of the United Nations (UN). Since the early 2000s, the European Union (EU) has developed several comprehensive and multidisciplinary strategies as part of its drug policy in order to prevent the diffusion of recreational drug use and abuse among the European population and raise public awareness on the adverse effects of drugs among all member states of the European Union, as well as conjoined efforts with European law enforcement agencies, such as Europol and EMCDDA, in order to counter organized crime and illegal drug trade in Europe.
== Reasons for use ==
Many researchers have explored the etiology of recreational drug use. Some of the most common theories are: genetics, personality type, psychological problems, self-medication, sex, age, depression, curiosity, boredom, rebelliousness, a sense of belonging to a group, family and attachment issues, history of trauma, failure at school or work, socioeconomic stressors, peer pressure, juvenile delinquency, availability, historical factors, or socio-cultural influences. There has been no consensus on a single cause. Instead, experts tend to apply the biopsychosocial model. Any number of factors may influence an individual's drug use, as they are not mutually exclusive. Regardless of genetics, mental health, or traumatic experiences, social factors play a large role in the exposure to and availability of certain types of drugs and patterns of use.
According to addiction researcher Martin A. Plant, some people go through a period of self-redefinition before initiating recreational drug use. They tend to view using drugs as part of a general lifestyle that involves belonging to a subculture that they associate with heightened status and the challenging of social norms. Plant states: "From the user's point of view there are many positive reasons to become part of the milieu of drug taking. The reasons for drug use appear to have as much to do with needs for friendship, pleasure and status as they do with unhappiness or poverty. Becoming a drug taker, to many people, is a positive affirmation rather than a negative experience".
=== Evolution ===
Anthropological research has suggested that humans "may have evolved to counter-exploit plant neurotoxins". The ability to use botanical chemicals to serve the function of endogenous neurotransmitters may have improved survival rates, conferring an evolutionary advantage. A typically restrictive prehistoric diet may have emphasized the apparent benefit of consuming psychoactive drugs, which had themselves evolved to imitate neurotransmitters. Chemical–ecological adaptations and the genetics of hepatic enzymes, particularly cytochrome P450, have led researchers to propose that "humans have shared a co-evolutionary relationship with psychotropic plant substances that is millions of years old."
== Health risks ==
The severity of impact and type of risks that come with recreational drug use vary widely with the drug in question and the amount being used. There are many factors in the environment and within the user that interact with each drug differently. Alcohol is sometimes considered one of the most dangerous recreational drugs. Alcoholic drinks, tobacco products and other nicotine-based products (e.g., electronic cigarettes), and cannabis are regarded by various medical professionals as the most common and widespread gateway drugs. In the United States, Australia, and New Zealand, the general onset of drinking alcohol, tobacco smoking, cannabis smoking, and consumption of multiple drugs most frequently occurs during adolescence and in middle school and secondary school settings.
Some scientific studies in the early 21st century found that a low to moderate level of alcohol consumption, particularly of red wine, might have substantial health benefits such as decreased risk of cardiovascular diseases, stroke, and cognitive decline. This claim has been disputed, specifically by British researcher David Nutt, professor of neuropsychopharmacology at the Imperial College London, who stated that studies showing benefits for "moderate" alcohol consumption in "some middle-aged men" lacked controls for the variable of what the subjects were drinking beforehand. Experts in the United Kingdom have suggested that some psychoactive drugs that may be causing less harm to fewer users (although they are also used less frequently in the first place) are cannabis, psilocybin mushrooms, LSD, and MDMA; however, these drugs have risks and side effects of their own.
=== Drug harmfulness ===
Drug harmfulness is defined as the degree to which a psychoactive drug has the potential to cause harm to the user and is measured in several ways, such as by addictiveness and the potential for physical harm. More objectively harmful drugs may be colloquially referred to as "hard drugs", and less harmful drugs as "soft drugs". The term "soft drug" is considered controversial by critics as it may imply the false belief that soft drugs cause lesser or insignificant harm.
=== Responsible use ===
Responsible drug use advocates that users should not take drugs at the same time as activities such as driving, swimming, operating machinery, or other activities that are unsafe without a sober state. Responsible drug use is emphasized as a primary prevention technique in harm-reduction drug policies. Harm-reduction policies were popularized in the late 1980s, although they began in the 1970s counter-culture, through cartoons explaining responsible drug use and the consequences of irresponsible drug use to users. Another issue is that the illegality of drugs causes social and economic consequences for users—the drugs may be "cut" with adulterants and the purity varies wildly, making overdoses more likely—and legalization of drug production and distribution could reduce these and other dangers of illegal drug use.
== Prevention ==
In efforts to curtail recreational drug use, governments worldwide introduced several laws prohibiting the possession of almost all varieties of recreational drugs during the 20th century. The "War on Drugs" promoted by the United States, however, is now facing increasing criticism. Evidence is insufficient to tell if behavioral interventions help prevent recreational drug use in children.
One in four adolescents has used an illegal drug, and one in ten of those adolescents who need addiction treatment get some type of care. School-based programs are the most commonly used method for drug use education; however, the success rates of these intervention programs are highly dependent on the commitment of participants and are limited in general.
== Demographics ==
=== Australia ===
Alcohol is the most widely used recreational drug in Australia. 86.2% of Australians aged 12 years and over have consumed alcohol at least once in their lifetime, compared to 34.8% of Australians aged 12 years and over who have used cannabis at least once in their lifetime.
=== United States ===
From the mid-19th century to the 1930s, American physicians prescribed Cannabis sativa as a prescription drug for various medical conditions. In the 1960s, the counterculture movement introduced the use of psychoactive drugs, including cannabis. Young adults and college students reported the recreational prevalence of cannabis, among other drugs, at 20-25% while the cultural mindset of using was open and curious. In 1969, the FBI reported that between the years 1966 and 1968, the number of arrests for marijuana possession, which had been outlawed throughout the United States under Marijuana Tax Act of 1937, had increased by 98%. Despite acknowledgement that drug use was greatly growing among America's youth during the late 1960s, surveys have suggested that only as much as 4% of the American population had ever smoked marijuana by 1969. By 1972, however, that number would increase to 12%. That number would then double by 1977.
The Controlled Substances Act of 1970 classified marijuana along with heroin and LSD as a Schedule I drug, i.e., having the relatively highest abuse potential and no accepted medical use. Most marijuana at that time came from Mexico, but in 1975 the Mexican government agreed to eradicate the crop by spraying it with the herbicide paraquat, raising fears of toxic side effects. Colombia then became the main supplier. The "zero tolerance" climate of the Reagan and Bush administrations (1981–1993) resulted in passage of strict laws and mandatory sentences for possession of marijuana. The "War on Drugs" thus brought with it a shift from reliance on imported supplies to domestic cultivation, particularly in Hawaii and California. Beginning in 1982, the Drug Enforcement Administration turned increased attention to marijuana farms in the United States, and there was a shift to the indoor growing of plants specially developed for small size and high yield. After over a decade of decreasing use, marijuana smoking began an upward trend once more in the early 1990s, especially among teenagers, but by the end of the decade this upswing had leveled off well below former peaks of use.
== Society and culture ==
Many movements and organizations are advocating for or against the liberalization of the use of recreational drugs, most notably regarding the legalization of marijuana and cannabinoids for medical and/or recreational use. Subcultures have emerged among users of recreational drugs, as well as alternative lifestyles and social movements among those who abstain from them, such as teetotalism and "straight edge".
Since the early 2000s, medical professionals have acknowledged and addressed the problem of the increasing consumption of alcoholic drinks and club drugs (such as MDMA, cocaine, rohypnol, GHB, ketamine, PCP, LSD, and methamphetamine) associated with rave culture among adolescents and young adults in the Western world. Studies have shown that adolescents are more likely than young adults to use multiple drugs, and the consumption of club drugs is highly associated with the presence of criminal behaviors and recent alcohol abuse or dependence.
The prevalence of recreational drugs in human societies is widely reflected in fiction, entertainment, and the arts, subject to prevailing laws and social conventions. For instance, in the music industry, the musical genres hip hop, hardcore rap, and trap, alongside their derivative subgenres and subcultures, are most notorious for having continuously celebrated and promoted drug trafficking, gangster lifestyle, and consumption of alcohol and other drugs since their inception in the United States during the late 1980s–early 1990s. In video games, for example, drugs are portrayed in a variety of ways: including power-ups (cocaine gum replenishes stamina in Red Dead Redemption 2), obstacles to be avoided (such as the Fuzzies in Super Mario World 2: Yoshi's Island that distort the player's view when accidentally consumed), items to be bought and sold for in-game currency (coke dealing is a big part of Scarface: The World Is Yours). In the Fallout video game franchise, drugs ("chems" in the game) can fill the role of any above mentioned. Drug trafficking, gang rivalries, and their related criminal underworld also play a big part in the Grand Theft Auto video game franchise.
== Common recreational drugs ==
The following substances are commonly used recreationally:
Alcohol: Most drinking alcohol is ethanol, CH3CH2OH. Drinking alcohol creates intoxication, relaxation and lowered inhibitions. It is produced by the fermentation of sugars by yeasts to create wine, beer, and distilled liquor (e.g., vodka, rum, gin, etc.). In most areas of the world, it is legal for those over a certain age (18 in most countries). It is an IARC Group 1 carcinogen and a teratogen. Alcohol withdrawal can be life-threatening.
Amphetamines: Used recreationally to provide alertness and a sense of energy. Prescribed for ADHD, narcolepsy, depression, and weight loss. A potent central nervous system stimulant, in the 1940s and 50s methamphetamine was used by Axis and Allied troops in World War II, and, later on, other armies, and by Japanese factory workers. It increases muscle strength and fatigue resistance and improves reaction time. Methamphetamine use can be neurotoxic, which means it damages dopamine neurons. As a result of this brain damage, chronic use can lead to post acute withdrawal syndrome.
Caffeine: Often found in coffee, black tea, energy drinks, some soft drinks (e.g., Coca-Cola, Pepsi, and Mountain Dew, among others), and chocolate. It is the world's most widely consumed psychoactive drug, but has only mild dependence liability for long-term users.
Cannabis: Its common forms include marijuana and hashish, which are smoked, vaporized or eaten. It contains at least 85 cannabinoids. The primary psychoactive component is THC, which mimics the neurotransmitter anandamide, named after the Hindu ananda, "joy, bliss, delight". When cannabis is eaten, THC metabolized into 11-OH-THC, this molecule is the primary psychoactive compound of edible forms of cannabis. THC and 11-OH-THC are partial agonist at CB1 and CB2 receptors of the endocannabinoid system.
Cocaine: It is available as a white powder, which is insufflated ("sniffed" into the nostrils) or converted into a solution with water and injected. A popular derivative, crack cocaine is typically smoked. When transformed into its freebase form, crack, the cocaine vapour may be inhaled directly. This is thought to increase bioavailability, but has also been found to be toxic, due to the production of methylecgonidine during pyrolysis.
MDMA: Commonly known as ecstasy, it is a common club drug in the rave scene.
Ketamine: An anesthetic used legally by paramedics and doctors in emergency situations for its dissociative and analgesic qualities and illegally in the club drug scene.
Lean: A liquid drug mixture made when mixing cough syrup, sweets, soft drinks and codeine. It originated in the 1990s in Houston. Ever since then, this drug usage has grown and is often used at parties and in the trap music scene. Many people would get a drowsy feeling when consuming this drug.
LSD: A popular ergoline derivative, that was first synthesized in 1938 by Albert Hofmann. However, he failed to notice its psychedelic effects until 1943. It's a serotonergic psychedelic (partial agonist at serotonin receptors, particularly the 5-HT2A subtypes) like psilocin, mescaline and DMT. But LSD is unique because it is also a partial agonist of dopamine and norepinephrine receptors, particularly the D2R subtypes. LSD (d-Lysergic Acid Diethylamide) is a molecule of the lysergamide family, a subclass of the tryptamine family. In the 1950s, it was used in psychological therapy, and, covertly, by the CIA in Project MKULTRA, in which the drug was administered to unwitting US and Canadian citizens. It played a central role in 1960s 'counter-culture', and was banned in October 1968 by US President Lyndon B Johnson.
Nitrous oxide: legally used by dentists as an anxiolytic and anaesthetic, it is also used recreationally by users who obtain it from whipped cream canisters (whippets or whip-its) (see inhalant), as it causes perceptual effects, a "high" and at higher doses, hallucinations.
Opiates and opioids: Available by prescription for pain relief. Commonly used opioids include oxycodone, hydrocodone, codeine, fentanyl, heroin, methadone, and morphine. Opioids have a high potential for addiction and have the ability to induce severe physical withdrawal symptoms upon cessation of frequent use. Heroin can be smoked, insufflated, or turned into a solution with water and injected. Percocet is a prescription opioid containing oxycodone and acetaminophen.
Psilocybin mushrooms: This hallucinogenic drug was an important drug in the psychedelic scene. Until 1963, when it was chemically analysed by Albert Hofmann, it was completely unknown to modern science that Psilocybe semilanceata ("Liberty Cap", common throughout Europe) contains psilocybin, a hallucinogen previously identified only in species native to Mexico, Asia, and North America.
Tobacco: Nicotiana tabacum. Nicotine is the key drug contained in tobacco leaves, which are either smoked, chewed or snuffed. It contains nicotine, which crosses the blood–brain barrier in 10–20 seconds. It mimics the action of the neurotransmitter acetylcholine at nicotinic acetylcholine receptors in the brain and the neuromuscular junction. The neuronal forms of the receptor are present both post-synaptically (involved in classical neurotransmission) and pre-synaptically, where they can influence the release of multiple neurotransmitters.
Tranquilizers: barbiturates, benzodiazepines (e.g. alprazolam, diazepam, etc.)(commonly prescribed for anxiety disorders; known to cause dementia and post acute withdrawal syndrome)
"Bath salts": slang term that generally refers to substituted cathinones such as Mephedrone and Methylenedioxypyrovalerone (MDPV), but not always
DMT – primary ingredient in ayahuasca, can also be smoked (inhalation causes a brief effect lasting usually 5 to 15 minutes).
Peyote: This hallucinogen contains mescaline, native to southwestern Texas and Mexico. Echinopsis pachanoi is a faster growing cactus containing mescaline. It is one of the few narcotics legally available in the United States for religious purposes by the Native American Church.
Salvia divinorum: This hallucinogenic Mexican herb in the mint family; not considered recreational, most likely due to the nature of the hallucinations (legal in some jurisdictions)
Synthetic cannabis: "Spice", "K2", JWH-018, AM-2201
Quaaludes: A popular club drug in the 1970s. No longer prescribed or manufactured in many countries but remains popular in South Africa.
== Routes of administration ==
Drugs are often associated with a particular route of administration. Many drugs can be consumed in more than one way. For example, marijuana can be swallowed like food or smoked, and cocaine can be "sniffed" in the nostrils, injected, or, with various modifications, smoked.
inhalation: all intoxicative inhalants (see below) that are gases or solvent vapours that are inhaled through the trachea, as the name suggests
insufflation: also known as "snorting", or "sniffing", this method involves the user placing a powder in the nostrils and breathing in through the nose, so that the drug is absorbed by the mucous membranes. Drugs that are "snorted", or "sniffed", include powdered amphetamines, cocaine, heroin, ketamine, MDMA, and snuff tobacco.
Subcutaneous injection (see also the article Skin popping): injection of drug into the third lowest layer of skin.
Intramuscular injection: injection of drug into a muscle.
intravenous injection (see also the article Drug injection): the user injects a solution of water and the drug into a vein, or less commonly, into the tissue. Drugs that are injected include morphine and heroin, less commonly other opioids. Stimulants like cocaine or methamphetamine may also be injected. In rare cases, users inject other drugs.
oral intake: caffeine, ethanol, cannabis edibles, psilocybin mushrooms, coca tea, poppy tea, laudanum, GHB, ecstasy pills with MDMA or various other substances (mainly stimulants and psychedelics), prescription and over-the-counter drugs (ADHD and narcolepsy medications, benzodiazepines, anxiolytics, sedatives, cough suppressants, morphine, codeine, opioids and others)
sublingual: substances diffuse into the blood through tissues under the tongue. Many psychoactive drugs can be or have been specifically designed for sublingual administration, including barbiturates, benzodiazepines, opioid analgesics with poor gastrointestinal bioavailability, LSD blotters, coca leaves, some hallucinogens. This route of administration is activated when chewing some forms of smokeless tobacco (e.g. dipping tobacco, snus).
intrarectal ("plugging"): administering into the rectum, most water-soluble drugs can be used this way.
smoking (see also the section below): tobacco, cannabis, opium, crystal meth, phencyclidine, crack cocaine, and heroin (diamorphine as freebase) known as chasing the dragon.
transdermal patches with prescription drugs: e.g. methylphenidate (Daytrana) and fentanyl.
Many drugs are taken through various routes. Intravenous route is the most efficient, but also one of the most dangerous. Nasal, rectal, inhalation and smoking are safer. The oral route is one of the safest and most comfortable, but of little bioavailability.
== Types ==
=== Depressants ===
Depressants are psychoactive drugs that temporarily diminish the function or activity of a specific part of the body or mind. Colloquially, depressants are known as "downers", and users generally take them to feel more relaxed and less tense. Examples of these kinds of effects may include anxiolysis, sedation, and hypotension. Depressants are widely used throughout the world as prescription medicines and as illicit substances. When these are used, effects may include anxiolysis (reduction of anxiety), analgesia (pain relief), sedation, somnolence, cognitive/memory impairment, dissociation, muscle relaxation, lowered blood pressure/heart rate, respiratory depression, anesthesia, and anticonvulsant effects. Depressants exert their effects through a number of different pharmacological mechanisms, the most prominent of which include potentiation of GABA or opioid activity, and inhibition of adrenergic, histamine or acetylcholine activity. Some are also capable of inducing feelings of euphoria. The most widely used depressant by far is alcohol (i.e. ethanol).
Stimulants or "uppers", such as amphetamines or cocaine, which increase mental or physical function, have an opposite effect to depressants.
Depressants, in particular alcohol, can precipitate psychosis. A 2019 systematic review and meta-analysis by Murrie et al. found that the rate of transition from opioid, alcohol and sedative induced psychosis to schizophrenia was 12%, 10% and 9% respectively.
==== Antihistamines ====
Antihistamines (or "histamine antagonists") inhibit the release or action of histamine. "Antihistamine" can be used to describe any histamine antagonist, but the term is usually reserved for the classical antihistamines that act upon the H1 histamine receptor. Antihistamines are used as treatment for allergies. Allergies are caused by an excessive response of the body to allergens, such as the pollen released by grasses and trees. An allergic reaction causes release of histamine by the body. Other uses of antihistamines are to help with normal symptoms of insect stings even if there is no allergic reaction. Their recreational appeal exists mainly due to their anticholinergic properties, that induce anxiolysis and, in some cases such as diphenhydramine, chlorpheniramine, and orphenadrine, a characteristic euphoria at moderate doses. High dosages taken to induce recreational drug effects may lead to overdoses. Antihistamines are also consumed in combination with alcohol, particularly by youth who find it hard to obtain alcohol. The combination of the two drugs can cause intoxication with lower alcohol doses.
Hallucinations and possibly delirium resembling the effects of Datura stramonium can result if the drug is taken in much higher than therapeutic doses. Antihistamines are widely available over the counter at drug stores (without a prescription), in the form of allergy medication and some cough medicines. They are sometimes used in combination with other substances such as alcohol.
The most common unsupervised use of antihistamines in terms of volume and percentage of the total is perhaps in parallel to the medicinal use of some antihistamines to extend and intensify the effects of opioids and depressants. The most commonly used are hydroxyzine, mainly to extend a supply of other drugs, as in medical use, and the above-mentioned ethanolamine and alkylamine-class first-generation antihistamines, which are – once again as in the 1950s – the subject of medical research into their anti-depressant properties.
For all of the above reasons, the use of medicinal scopolamine for recreational uses is also observed.
==== Analgesics ====
Analgesics (also known as "painkillers") are used to relieve pain (achieve analgesia). The word analgesic derives from Greek "αν-" (an-, "without") and "άλγος" (álgos, "pain"). Analgesic drugs act in various ways on the peripheral and central nervous systems; they include paracetamol (also known in the US as acetaminophen), the nonsteroidal anti-inflammatory drugs (NSAIDs) such as the salicylates (e.g. aspirin), and opioid drugs such as hydrocodone, codeine, heroin and oxycodone. Some further examples of the brand name prescription opiates and opioid analgesics that may be used recreationally include Vicodin, Lortab, Norco (hydrocodone), Avinza, Kapanol (morphine), Opana, Paramorphan (oxymorphone), Dilaudid, Palladone (hydromorphone), and OxyContin (oxycodone).
==== Tranquilizers ====
The following are examples of tranquilizers (GABAergics):
Barbiturates
Benzodiazepines
Ethanol (drinking alcohol; ethyl alcohol)
Nonbenzodiazepines
Others
carisoprodol (Soma)
chloral hydrate
diethyl ether
ethchlorvynol (Placidyl; "jelly-bellies")
gamma-butyrolactone (GBL, a prodrug to GHB)
gamma-hydroxybutyrate (GHB; G; Xyrem; "Liquid Ecstasy", "Fantasy")
glutethimide (Doriden)
kava (from Piper methysticum; contains kavalactones)
ketamine, a phencyclidine (PCP) analog
meprobamate (Miltown)
methaqualone (Sopor, Mandrax; "Quaaludes")
phenibut
propofol (Diprivan), a general anesthetic
theanine (found in Camellia sinensis, the tea plant)
valerian (from Valeriana officinalis)
=== Stimulants ===
Stimulants, also known as "psychostimulants", induce euphoria with improvements in mental and physical function, such as enhanced alertness, wakefulness, and locomotion. Stimulants are also occasionally called "uppers". Depressants or "downers", which decrease mental or physical function, are in stark contrast to stimulants and are considered to be their functional opposites.
Stimulants enhance the activity of the central and peripheral nervous systems. Common effects may include increased alertness, awareness, wakefulness, endurance, productivity, and motivation, arousal, locomotion, heart rate, and blood pressure, and a diminished desire for food and sleep.
Use of stimulants may cause the body to significantly reduce its production of endogenous compounds that fulfill similar functions. Once the effect of the ingested stimulant has worn off the user may feel depressed, lethargic, confused, and dysphoric. This is colloquially termed a "crash" and may promote reuse of the stimulant.
Amphetamines are a significant cause of drug-induced psychosis. Importantly, a 2019 meta-analysis found that 22% of people with amphetamine-induced psychosis transition to a later diagnosis of schizophrenia.
Examples of stimulants include:
Sympathomimetics (catecholaminergics)—e.g. amphetamine, methamphetamine, cocaine, methylphenidate, ephedrine, pseudoephedrine
Entactogens (serotonergics, primarily phenethylamines)—e.g. MDMA (which is also an amphetamine)
Eugeroics, e.g. modafinil
Others
arecoline (found in Areca catechu)
caffeine (found in Coffea spp.)
nicotine (found in Nicotiana spp.)
rauwolscine (found in Rauvolfia serpentina)
yohimbine (Procomil; a tryptamine alkaloid found in Pausinystalia johimbe)
=== Euphoriants ===
Alcohol: "Euphoria, the feeling of well-being, has been reported during the early (10–15 min) phase of alcohol consumption" (e.g., beer, wine or spirits)
Cannabis: Tetrahydrocannabinol, the main psychoactive ingredient in this plant, can have sedative and euphoric properties.
Catnip: Catnip contains a sedative known as nepetalactone that activates opioid receptors. In cats it elicits sniffing, licking, chewing, head shaking, rolling, and rubbing which are indicators of pleasure. In humans, however, catnip does not act as a euphoriant.
Stimulants: "Psychomotor stimulants produce locomotor activity (the subject becomes hyperactive), euphoria, (often expressed by excessive talking and garrulous behaviour), and anorexia. The amphetamines are the best known drugs in this category..."
MDMA: The "euphoriant drugs such as MDMA ('ecstasy') and MDEA ('eve')" are popular among young adults. MDMA "users experience short-term feelings of euphoria, rushes of energy and increased tactility" as well as interpersonal connectedness.
Opium: This "drug derived from the unripe seed-pods of the opium poppy…produces drowsiness and euphoria and reduces pain. Morphine and codeine are opium derivatives." Opioids have led to many deaths in the United States, particularly by causing respiratory depression.
=== Hallucinogens ===
Hallucinogens can be divided into three broad categories: psychedelics, dissociatives, and deliriants. They can cause subjective changes in perception, thought, emotion and consciousness. Unlike other psychoactive drugs such as stimulants and opioids, hallucinogens do not merely amplify familiar states of mind but also induce experiences that differ from those of ordinary consciousness, often compared to non-ordinary forms of consciousness such as trance, meditation, conversion experiences, and dreams.
Psychedelics, dissociatives, and deliriants have a long worldwide history of use within medicinal and religious traditions. They are used in shamanic forms of ritual healing and divination, in initiation rites, and in the religious rituals of syncretistic movements such as União do Vegetal, Santo Daime, Temple of the True Inner Light, and the Native American Church. When used in religious practice, psychedelic drugs, as well as other substances like tobacco, are referred to as entheogens.
Hallucinogen-induced psychosis occurs when psychosis persists despite no longer being intoxicated with the drug. It is estimated that 26% of people with hallucinogen-induced psychosis will transition to a diagnosis of schizophrenia. This percentage is less than the psychosis transition rate for cannabis (34%) but higher than that of amphetamines (22%).
Starting in the mid-20th century, psychedelic drugs have been the object of extensive attention in the Western world. They have been and are being explored as potential therapeutic agents in treating depression, post-traumatic stress disorder, obsessive–compulsive disorder, alcoholism, and opioid addiction. Yet the most popular, and at the same time most stigmatized, use of psychedelics in Western culture has been associated with the search for direct religious experience, enhanced creativity, personal development, and "mind expansion". The use of psychedelic drugs was a major element of the 1960s counterculture, where it became associated with various social movements and a general atmosphere of rebellion and strife between generations.
Deliriants
atropine (alkaloid found in plants of the family Solanaceae, including datura, deadly nightshade, henbane and mandrake)
dimenhydrinate (Dramamine, an antihistamine)
diphenhydramine (Benadryl, Unisom, Nytol)
hyoscyamine (alkaloid also found in the Solanaceae)
hyoscine hydrobromide (another Solanaceae alkaloid)
myristicin (found in Myristica fragrans ("Nutmeg"))
ibotenic acid (found in Amanita muscaria ("Fly Agaric"); prodrug to muscimol)
muscimol (also found in Amanita muscaria, a GABAergic)
Dissociatives
dextromethorphan (DXM; Robitussin, Delsym, etc.; "Dex", "Robo", "Cough Syrup", "DXM")
"Triple C's, Coricidin, Skittles" refer to a potentially fatal formulation containing both dextromethorphan and chlorpheniramine.
ketamine (K; Ketalar, Ketaset, Ketanest; "Ket", "Kit Kat", "Special-K", "Vitamin K", "Jet Fuel", "Horse Tranquilizer")
methoxetamine (Mex, Mket, Mexi)
phencyclidine (PCP; Sernyl; "Angel Dust", "Rocket Fuel", "Sherm", "Killer Weed", "Super Grass")
nitrous oxide (N2O; "NOS", "Laughing Gas", "Whippets", "Balloons")
Psychedelics
Phenethylamines
2C-B ("Nexus", "Venus", "Eros", "Bees")
2C-E ("Eternity", "Hummingbird")
2C-I ("Infinity")
2C-T-2 ("Rosy")
2C-T-7 ("Blue Mystic", "Lucky 7")
DOB
DOC
DOI
DOM ("Serenity, Tranquility, and Peace" ("STP"))
MDMA ("Ecstasy", "E", "Molly", "Mandy", "MD", "Crystal Love")
mescaline (found in peyote and Trichocereus macrogonus (Peruvian torch, San Pedro cactus))
Tryptamines (including ergolines and lysergamides)
5-MeO-DiPT ("Foxy", "Foxy Methoxy")
5-MeO-DMT (found in various plants like chacruna, jurema, vilca, and yopo)
alpha-methyltryptamine (αMT; Indopan; "Spirals")
bufotenin (secreted by Bufo alvarius, also found in various Amanita mushrooms)
N,N-dimethyltryptamine (N,N-DMT; DMT; "Dimitri", "Disneyland", "Spice"; found in large amounts in Psychotria and in D. cabrerana)
lysergic acid amide (LSA; ergine; found in morning glory and Hawaiian baby woodrose seeds)
lysergic acid diethylamide (LSD; L; Delysid; "Acid", "Sid". "Cid", "Lucy", "Sidney", "Blotters", "Droppers", "Sugar Cubes")
O-Acetylpsilocin (believed to be a prodrug of psilocin)
psilocin (found in psilocybin mushrooms)
psilocybin (also found in psilocybin mushrooms; prodrug to psilocin)
ibogaine (found in Tabernanthe iboga ("Iboga"))
Atypicals
salvinorin A (found in Salvia divinorum, a trans-neoclerodane diterpenoid ("Diviner's Sage", "Lady Salvia", "Salvinorin"))
tetrahydrocannabinol (found in cannabis)
=== Inhalants ===
Inhalants are gases, aerosols, or solvents that are breathed in and absorbed through the lungs. While some "inhalant" drugs are used for medical purposes, as in the case of nitrous oxide, a dental anesthetic, inhalants are used as recreational drugs for their intoxicating effect. Most inhalant drugs that are used non-medically are ingredients in household or industrial chemical products that are not intended to be concentrated and inhaled, including organic solvents (found in cleaning products, fast-drying glues, and nail polish removers), fuels (gasoline (petrol) and kerosene), and propellant gases such as Freon and compressed hydrofluorocarbons that are used in aerosol cans such as hairspray, whipped cream, and non-stick cooking spray. A small number of recreational inhalant drugs are pharmaceutical products that are used illicitly, such as anesthetics (ether and nitrous oxide) and volatile anti-angina drugs (alkyl nitrites, more commonly known as "poppers").
The most serious inhalant abuse occurs among children and teens who "[...] live on the streets completely without family ties". Inhalant users inhale vapor or aerosol propellant gases using plastic bags held over the mouth or by breathing from a solvent-soaked rag or an open container. The effects of inhalants range from an alcohol-like intoxication and intense euphoria to vivid hallucinations, depending on the substance and the dosage. Some inhalant users are injured due to the harmful effects of the solvents or gases, or due to other chemicals used in the products inhaled. As with any recreational drug, users can be injured due to dangerous behavior while they are intoxicated, such as driving under the influence. Computer cleaning dusters are dangerous to inhale, because the gases expand and cool rapidly upon being sprayed. In many cases, users have died from hypoxia (lack of oxygen), pneumonia, cardiac failure or arrest, or aspiration of vomit.
Examples include:
Chloroform
Ethyl chloride
Diethyl ether
Ethane and ethylene
Laughing gas (nitrous oxide)
Poppers (alkyl nitrites)
Solvents and propellants (including propane, butane, freon, gasoline, kerosene, toluene) along with the fumes of glues containing them
== List of drugs which can be smoked ==
Plants:
black tar heroin
cannabis
datura and other Solanaceae (formerly smoked to treat asthma)
opium
salvia divinorum
tobacco
possibly other plants (see the section below)
Substances (also not necessarily psychoactive plants smoked within them):
5-MeO-DMT
Bufotenine
crack cocaine
dimethyltryptamine (DMT)
DiPT
methamphetamine
Methaqualone
phencyclidine (PCP)
synthetic cannabinoids (see also: synthetic cannabis)
many others, including some prescription drugs
== List of psychoactive plants, fungi, and animals ==
Minimally psychoactive plants which contain mainly caffeine and theobromine:
cocoa
coffee
guarana (caffeine in guarana is sometimes called guaranine)
kola
tea (caffeine in tea is sometimes called theine) – also contains theanine
yerba mate (caffeine in yerba mate is sometimes called mateine)
Most known psychoactive plants:
cannabis: cannabinoids
coca: cocaine
kava: kavalactones
khat: cathine and cathinone
nutmeg: myristicin and elemicin
opium poppy: morphine, codeine, and other opiates
salvia divinorum: salvinorin A
tobacco: nicotine and beta-carboline alkaloids
Solanaceae plants—contain atropine, hyoscyamine, and scopolamine:
datura
deadly nightshade Atropa belladonna
henbane
mandrake (mandragora)
other Solanaceae
Cacti with mescaline:
Peyote
Trichocereus macrogonus, the Peruvian torch cactus, and in particular its variety T. macrogonus var. pachanoi, the San Pedro cactus
Other plants:
Areca catechu (see: betel and paan)—arecoline
Ayahuasca (for DMT)
Calea zacatechichi
damiana
ephedra: ephedrine
kratom: mitragynine, mitraphylline, 7-hydroxymitragynine, raubasine, and corynanthine
Morning glory and Hawaiian Baby Woodrose – lysergic acid amide (LSA, ergine)
Rauvolfia serpentina: rauwolscine
Silene capensis
Tabernanthe iboga ("Iboga")—ibogaine
valerian: valerian (the chemical with the same name)
various plants like chacruna, jurema, vilca, and yopo – 5-MeO-DMT
yohimbe (Pausinystalia johimbe): yohimbine and corynanthine
many others
Fungi:
various Amanita mushrooms: muscimol
Amanita muscaria: ibotenic acid and muscimol
Claviceps purpurea and other Clavicipitaceae: ergotamine (not psychoactive itself but used in synthesis of LSD)
psilocybin mushrooms: psilocybin and psilocin
Psychoactive animals:
hallucinogenic fish
psychoactive toads: Bufo alvarius (Colorado River toad or Sonoran Desert toad) contains bufotenin (5-MeO-DMT)
== See also ==
== References ==
== Further reading ==
Martin, Christopher S.; Chung, Tammy; Langenbucher, James W. (2017). "Part 1: Defining and Characterizing the Nature and Extent of Substance Use Disorders – Historical and Cultural Perspectives on Substance Use and Substance Use Disorders". In Sher, Kenneth J. (ed.). The Oxford Handbook of Substance Use and Substance Use Disorders: Volume 1. Oxford Library of Psychology. Oxford and New York: Oxford University Press. pp. 27–59. doi:10.1093/oxfordhb/9780199381678.013.001. ISBN 9780199381678. LCCN 2016020729.
Anthony, James; Barondess, David A.; Radovanovic, Mirjana; Lopez-Quintero, Catalina (2017). "Part 1: Psychiatric Comorbidity – Polydrug Use: Research Topics and Issues". In Sher, Kenneth J. (ed.). The Oxford Handbook of Substance Use and Substance Use Disorders: Volume 2. Oxford Library of Psychology. Oxford and New York: Oxford University Press. pp. 27–59. doi:10.1093/oxfordhb/9780199381708.013.006. ISBN 9780199381708. LCCN 2016020729.
Hernández-Serrano, Olga; Gras, Maria E.; Font-Mayolas, Sílvia; Sullman, Mark J. M. (2016). "Part VI: Dual and Polydrug Abuse – Chapter 83: Types of Polydrug Usage". In Preedy, Victor R. (ed.). Neuropathology of Drug Addictions and Substance Misuse, Volume 3: General Processes and Mechanisms, Prescription Medications, Caffeine and Areca, Polydrug Misuse, Emerging Addictions and Non-Drug Addictions. Cambridge, Massachusetts: Academic Press, imprint of Elsevier. pp. 839–849. doi:10.1016/B978-0-12-800634-4.00083-4. ISBN 978-0-12-800634-4.
== External links ==
"The Science of Drug Use: A Resource for the Justice Sector". www.drugabuse.gov. North Bethesda, Maryland: National Institute on Drug Abuse. 26 May 2020. Archived from the original on 6 September 2023. Retrieved 21 March 2024.
School-Based Drug Abuse Prevention: Promising and Successful Programs (PDF). Ottawa, Ontario: Public Safety Canada. 31 January 2018. ISBN 978-1-100-12181-9. Archived (PDF) from the original on 19 May 2021. Retrieved 21 March 2024.
Sacco, L. N.; Finklea, K. (3 May 2016). "Synthetic Drugs: Overview and Issues for Congress" (PDF). Washington, D.C.: Congressional Research Service. Archived (PDF) from the original on 8 December 2021. Retrieved 21 March 2024. | Wikipedia/Drug_harmfulness |
Drug courts are problem-solving courts that take a public health approach to criminal offending using a specialized model in which the judiciary, prosecution, defense bar, probation, law enforcement, mental health, social service, and treatment communities work together to help addicted offenders into long-term recovery. Instead of punishment, their purpose is to address one of the underlying drivers of crime and, in the process, reduce the use of imprisonment, potentially leading to substantial cost-savings. Drug courts aim to do this by incentivizing or mandating offenders into addiction treatment combined with frequent drug testing and regular monitoring by the judge.
== Key components ==
In 1997, the National Association of Drug Court Professionals in the United States published Defining Drug Courts: The Key Components. They named these as key components:
Drug courts integrate alcohol and other drug treatment services with justice system case processing
Using a non-adversarial approach, prosecution and defense counsel promote public safety. Participants must waive their due process rights to a speedy trial and sign a pre-emptive confession before being allowed to participate.
Eligible participants are identified early and promptly placed in the drug court program
Drug courts provide access to a continuum of alcohol, drug, and other related treatment and rehabilitation services
Abstinence is monitored by frequent drug testing (including alcohol)
A coordinated strategy governs drug court responses to participants' compliance
Ongoing judicial interaction with each drug court participant is essential
Monitoring and evaluation measure the achievement of program goals and gauge effectiveness
Continuing interdisciplinary education promotes effective drug court planning, implementation, and operations
Forging partnerships among drug courts, public agencies, and community-based organizations generates local support and enhances their effectiveness
== Effectiveness ==
How effective drug courts are largely depends on how well they adhere to the ten key components described above. The United States has more drug courts than any other country in the world, so most studies of their effectiveness are based on results in the USA. Out of thousands of drug courts operating in the US, 40% of states which have them do not have a management information system, required by the key components, which would enable their performance to be monitored properly.
=== Length of follow-up period ===
Another factor which affects how successful a drug court appears to be is the length of the follow-up period after participants have finished treatment. The longer the follow-up (sometimes as much as four years), the more likely participants are to relapse and reoffend. Results almost always look better if the follow-up period is only 12 months, while participants are often still engaged in the treatment program ordered by the court.
As a result of these methodological issues, meta-studies which have been conducted over the years describe quite variable results. Few studies have found drug courts which reduce reoffending by more than 20%. Studies which have found more positive results may not have taken confounding issues into account which undermine the reliability of their conclusions. For instance, the Government Accountability Office (GAO) study from 2005, which assessed 27 different drug courts, found that 24 of them reduced recidivism by between 1% and 13%. But one court in this study reported a reduction of 35%, which appeared to make it one of the best performing drug courts in the United States. However, this result was based on a follow-up period of only 12 months.
Another study which suggested a better result than 20% was the GAO analysis from 2011. This described reductions in recidivism from 32 different US drug courts, one of which achieved a reduction in the re-arrest rate of 26%. This was the Kings County Drug Treatment Alternative to Prison Program (DTAP) in New York which is “recognized as one of the nation’s most successful diversion programmes”. However, the reason this result appears better than all the others is because it refers solely to reduced offending by graduates – those who completed the programme. The other drug courts in this analysis appear less successful because their results include defendants who dropped out of treatment and reoffended.
A meta-study in the Journal of Criminal Justice looked at 154 independent drug court evaluations. It claimed that participation in one of these courts led to "a drop in recidivism" between 38% and 50%. However, these studies used a variety of different measures for recidivism (such as re-arrest, reconviction, or re-imprisonment) which tends to confound the results. And the claimed reductions in recidivism were all based on a 12-month follow-up period which mostly overlapped with the period that participants were still in treatment in the court. Recidivism rates generally increase significantly after completing treatment when the level of supervision falls away.
=== Compliance with key components ===
Evaluations of individual drug courts where compliance with the ten key components is monitored, tend to show better results. One such study of a mature drug court which has been operating for over ten years found that over the entire period, the re-arrest rate declined by nearly 30%. This was the Multnomah County Drug Court in Portland, Oregon, which is the second oldest drug court in the country. One finding was that the longer drug court judges worked with addicts, and the more experience they had in the court (key component #7), the better the success rates were for participants. The authors of the study concluded that "this model provides clear support that drug court does reduce criminal recidivism".
=== Retention rate ===
Another important factor in determining a drug court's effectiveness is the retention and graduation rate. For instance, the King's County DTAP programme attributes its 35% reduction in re-arrests to its excellent retention rate of 71% in the first 12 months of the programme. But over the following four years, its graduation rate falls to 41%.
A review conducted in 2001 for the National Drug Court Institute Program found that graduation rates nationally were around 47% (in the first 12 months). The authors noted that "the research on long-term outcomes was less definitive".
== Comparison with other interventions ==
Another way of measuring the effectiveness of drug courts is to compare them with 'business as usual' or a variety of counterfactuals. One counterfactual is that drug addicted offenders would likely be sent to prison if a drug court was not available. Recidivism rates vary from one country to another depending on a variety of factors. In the U.S. nearly 44% of prisoners return to prison within 12 months of release. The rate varies from state to state. In any given state, the re-incarceration rate would need to compared with the re-incarceration rate of drug court participants in that state - which is different from the re-arrest rate usually reported in drug court evaluations.
The availability of rehabilitation programs also varies from state to state. So another counterfactual is to compare reoffending rates of drug court participants in a given state with prisoners who attended addiction treatment while in prison in that state.
== By country ==
=== Australia ===
In Australia, drug courts operate in various jurisdictions, although their formation, process and procedures differ. The main aim of the Australian courts is to divert illicit drug users from incarceration into treatment programs for their addiction. Drug courts have been established in New South Wales, Queensland, South Australia, Victoria, and Western Australia. People appearing in Australian drug courts often fall outside the parameters for other pre-court services
=== Canada ===
Drug treatment courts (DTCs) are a recent phenomenon in the Canadian criminal justice system. The first Canadian DTC commenced in Toronto in 1998. The Federal Government currently supports Edmonton (December 2005), Winnipeg (January 2006), Ottawa (March 2006), Regina (October 2006), Toronto (1998), and Vancouver (2001). Hamilton, Calgary and Durham have also recently initiated DTCs.
=== New Zealand ===
A five-year pilot Alcohol and Other Drug Treatment Court was opened in Auckland, New Zealand, in 2012, the first of its type for the country. Since the pilot was established, 46% of participants have graduated. According to the New Zealand Drug Foundation, this rate is six times higher than that achieved by most ‘voluntary’ rehabilitation programmes. Graduates were 62% less likely to reoffend and 71% less likely to return to prison in the first 12 months after treatment. When non-graduates were included in the analysis, 54% (of participants overall) were less likely to reoffend and 58% less likely to go back to prison in the following 12 months.
=== United Kingdom ===
In the UK, drug courts are currently being tested in various places. In December 2005, the United Kingdom began a pilot scheme of dedicated drug courts. Family Drug and Alcohol Court are in operation in various locations throughout the country, including London, Gloucestershire and Milton Keynes where the service is run by the Tavistock and Portman NHS Foundation Trust. In February 2015 it was announced that more would open in East Sussex, Kent and Medway, Plymouth, Torbay and Exeter, and West Yorkshire.
=== United States ===
The first drug court in the US took shape in Miami-Dade County, Florida in 1989 as a response to the growing crack cocaine problem plaguing the city. Chief Judge Gerald Wetherington, Judge Herbert Klein, then State Attorney Janet Reno, and Public Defender Bennett Brummer designed the court for nonviolent offenders to receive treatment. In the United States, according to the National Association of Drug Court Professionals, as of December 31, 2014, there are 3,057 drug courts representing all 50 states, the District of Columbia, Guam, Puerto Rico, Northern Mariana Islands, and various tribal regions.
=== Women and drug courts in United States ===
There are many variations to drug courts and more recently some have opened up to deal specifically with women drug users. Some even treat women who engage in prostitution because of their drug addiction.
A research study has shown how addiction can be the results of mental illness derived from interpersonal violence. This shows that crime that results from drug addiction can be tied to trauma that is a result of interpersonal violence. This indicates a societal problem that must be dealt with treatment instead of incarceration.
=== Juvenile drug courts in the United States ===
Drug courts also exist to treat juveniles with substance abuse issues. They work similarly to adult drug courts but are tailored to meet the needs of children. One research study on juvenile drug courts stated that many previous research studies have inconsistent results due to different methodological problems making the results hard to generalize to the population. This research study done over ten randomized different jurisdictions shows promising results. The results show that juvenile drug courts reduced marijuana use rates, increased accessibility to resources, and overall reduced rearrest rates also known as recidivism. However, the positive effects observed were small to moderate. The effects in this study were discovered to be more beneficial for high-risk youth.
== Drug courts in the news ==
Drug courts have had many successful graduates. They have bi-partisan support in the political arena.
== See also ==
DWI court
Veterans treatment court
== References ==
== Further reading ==
Gerra, Gilberto; Clark, Nicolas (2010). From coercion to cohesion: Treating drug dependence through health care, not punishment (PDF). New York: United Nations: Office on Drugs and Crime. p. 13.{{cite book}}: CS1 maint: publisher location (link) This discussion paper is based on the deliberations of a group of international experts present at a scientific workshop held at Vienna in October 2009, called Voluntary-based or compulsory drug dependence treatment? From mandated treatment to therapeutic alliance.
National Association of Drug Court Professionals (2013–2015). Adult Drug Court Best Practice Standards, Volumes I and II. | Wikipedia/Drug_court |
The economy of Myanmar is the seventh largest in Southeast Asia. After the return of civilian rule in 2011, the new government launched large-scale reforms, focused initially on the political system to restore peace and achieve national unity and moving quickly to an economic and social reform program. Current economic statistics were a huge decline from the economic statistics of Myanmar in the fiscal year of 2020, in which Myanmar’s nominal GDP was $81.26 billion and its purchasing power adjusted GDP was $279.14 billion. Myanmar has faced an economic crisis since the 2021 coup d'état. According to International Monetary Fund (IMF) Myanmar GDP per capita in 2024 is estimated to reach $1.179
== History ==
=== Classical era ===
Burma has been the main trade route between China and India since 100 BC. The Mon Kingdom of lower Burma served as important trading centre in the Bay of Bengal. The majority of the population was involved in rice production and other forms of agriculture. Burma used silver as a medium of exchange. All land was technically owned by the Burmese monarch. Exports, along with oil wells, gem mining and teak production were controlled by the monarch. Burma was vitally involved in the Indian Ocean trade. Logged teak was a prized export that was used in European shipbuilding because of its durability, and became the focal point of Burmese exports from the 1700s to the 1800s.
Under the monarchy, the economy of Myanmar had been one of redistribution, a concept embedded in local society, religion, and politics (Dāna). The state set the prices of the most important commodities. Agrarian self-sufficiency was vital, while trade was only of secondary importance.
=== British Burma (1885–1948) ===
Under the British administration, the people of Burma were at the bottom of social hierarchy, with Europeans at the top, Indians, Chinese, and Christianized minorities in the middle, and Buddhist Burmese at the bottom. Integrated into the world economy by force, economic growth in Burma was driven by the extractive industries and cash crop agriculture, and the country had the second-highest GDP per capita in Southeast Asia. However, much of the wealth was concentrated in the hands of Europeans. The country became the world's largest exporter of rice, mainly to European markets, while other colonies like India suffered mass starvation. The British followed the ideologies of Social Darwinism and the free market, and opened up the country to a large-scale immigration with Rangoon exceeding New York City as the greatest immigration port in the world in the 1920s. Historian Thant Myint-U states, "This was out of a total population of only 13 million; it was equivalent to the United Kingdom today taking 2 million people a year." By then, in most of the largest cities in Burma, Rangoon, Akyab, Bassein and Moulmein, the Indian immigrants formed a majority of the population. The Burmese under British rule felt helpless, and reacted with a "racism that combined feelings of superiority and fear".
Crude oil production, an indigenous industry of Yenangyaung, was taken over by the British and put under Burmah Oil monopoly. British Burma began exporting crude oil in 1853. It produced 75% of the world's teak. The wealth was however, mainly concentrated in the hands of Europeans. In the 1930s, agricultural production fell dramatically as international rice prices declined and did not recover for several decades.
During the Japanese invasion of Burma in World War II, the British followed a scorched earth policy. They destroyed the major government buildings, oil wells and mines for tungsten, tin, lead and silver to keep them from the Japanese. Myanmar was bombed extensively by the Allies. After independence, the country was in ruins with its major infrastructure completely destroyed. With the loss of India, Burma lost relevance and obtained independence from the British. After a parliamentary government was formed in 1948, Prime Minister U Nu embarked upon a policy of nationalisation and the state was declared the owner of all land. The government tried to implement an eight-year plan partly financed by injecting money into the economy which caused some inflation.
=== Post-independence and under U Nu and Ne Win (1948–1988) ===
After a parliamentary government was formed in 1948, Prime Minister U Nu embarked upon a policy of nationalisation. He attempted to make Burma a welfare state by adopting central planning measures. By the 1950s, rice exports had decreased by two-thirds and mineral exports by over 96%. Plans were implemented in setting up light consumer industries by private sector. The 1962 Burmese coup d'état was followed by an economic scheme called the Burmese Way to Socialism, a plan to nationalise all industries, with the exception of agriculture. The catastrophic program turned Burma into one of the world's most impoverished countries. Burma was classified as a least developed country by the United Nations in 1987.
=== Rule of the generals (1988–2011) ===
After 1988, the regime retreated from a command economy. It permitted modest expansion of the private sector, allowed some foreign investment, and received much needed foreign exchange. Than Shwe advocated for some deregulation economic policies, despite his relaxation of some restrictions on Burma's economy, his economic policies have been often criticized as ill-planned. Shwe relaxed some state control over the economy, and was a supporter of Burma's participation in the Association of South East Asian Nations (ASEAN). He also oversaw a large crackdown on corruption, which saw the sackings of a number of cabinet ministers and regional commanders in 1997. Shwe advocated for Crony capitalism. The economy was rated in 2009 as the least free in Asia (tied with North Korea). All basic market institutions are suppressed. Private enterprises were often co-owned or indirectly owned by state. The corruption watchdog organisation Transparency International in its 2007 Corruption Perceptions Index released on 26 September 2007 ranked Burma the most corrupt country in the world, tied with Somalia.
The national currency is the kyat. Burma currently has a dual exchange rate system similar to Cuba. The market rate was around two hundred times below the government-set rate in 2006. In 2011, the Burmese government enlisted the aid of the International Monetary Fund to evaluate options to reform the current exchange rate system, to stabilise the domestic foreign exchange trading market and reduce economic distortions. The dual exchange rate system allows for the government and state-owned enterprises to divert funds and revenues, while also giving the government more control over the local economy and making it possible to temporarily subdue inflation.
Inflation averaged 30.1% between 2005 and 2007. In April 2007, the National League for Democracy organised a two-day workshop on the economy. The workshop concluded that skyrocketing inflation was impeding economic growth. "Basic commodity prices have increased from 30% to 60% since the military regime promoted a pay rise for government workers in April 2006," said Soe Win, the moderator of the workshop. "Inflation is also correlated with corruption." Myint Thein, an NLD spokesperson, added: "Inflation is the critical source of the current economic crisis."
In recent years, China and India attempted to strengthen ties with Myanmar for mutual benefit. The European Union and some nations including the United States and Canada imposed investment and trade sanctions on Burma. The United States banned all imports from Burma, though this restriction was since lifted. Foreign investment comes primarily from China, Singapore, South Korea, India, and Thailand.
=== Economic liberalisation (2011–2019) ===
In 2011, when new President Thein Sein's government came to power, Burma embarked on a major policy of reforms including anti-corruption, currency exchange rate regulation, foreign investment laws and taxation. Foreign investments increased from US$300 million in 2009–10 to a US$20 billion in 2010–11 by about 6567%. Large inflow of capital results in stronger Burmese currency, kyat by about 25%. In response, the government relaxed import restrictions and abolished export taxes. Despite current currency problems, Burmese economy is expected to grow by about 8.8% in 2011. After the completion of 58-billion dollar Dawei deep seaport, Burma is expected be at the hub of trade connecting Southeast Asia and the South China Sea, via the Andaman Sea, to the Indian Ocean receiving goods from countries in the Middle East, Europe and Africa, and spurring growth in the ASEAN region.
In 2012, the Asian Development Bank formally began re-engaging with the country, to finance infrastructure and development projects in the country. The $512 million loan is the first issued by the ADB to Myanmar in 30 years and will target banking services, ultimately leading to other major investments in road, energy, irrigation and education projects.
In March 2012, a draft foreign investment law emerged, the first in more than 2 decades. This law oversees the unprecedented liberalisation of the economy. It for example stipulates that foreigners no longer require a local partner to start a business in the country and can legally lease land. The draft law also stipulates that Burmese citizens must constitute at least 25% of the firm's skilled workforce, and with subsequent training, up to 50–75%.
On 28 January 2013, the government of Myanmar announced deals with international lenders to cancel or refinance nearly $6 billion of its debt, almost 60 per cent of what it owes to foreign lenders. Japan wrote off US$3 Billion, nations in the group of Paris Club wrote off US$2.2 Billion and Norway wrote off US$534 Million.
Myanmar's inward foreign direct investment has steadily increased since its reform. The country approved US$4.4 billion worth of investment projects between January and November 2014.
According to one report released on 30 May 2013, by the McKinsey Global Institute, Burma's future looks bright, with its economy expected to quadruple by 2030 if it invests in more high-tech industries. This however does assume that other factors (such as drug trade, the continuing war of the government with specific ethnic groups, etc.) do not interfere.
As of October 2017, less than 10% of Myanmar's population has a bank account. As of 2016–17 approximately 98 percent of the population has smartphones and mobile money schemes are being implemented without the use of banks similar to African countries.
=== Economic crisis (2020–present) ===
Myanmar's economy has been in economic crisis since the coup d’état in February 2021. On April 30, 2021, the United Nations Development Programme noted that the COVID-19 pandemic and the 2021 Myanmar coup d'état could reverse economic gains made over the last sixteen years. Overall, Myanmar’s economy under SAC rule is defined by stagnation, inflation, capital flight, and fractured governance. With no political resolution in sight, prospects for recovery and inclusive growth remain bleak. The SAC’s economic strategy prioritizes regime survival through resource extraction and coercive controls, such as forced currency conversions and price fixing. This erratic and reactionary governance has undermined investor confidence and distorted markets.
Under the military-led State Administration Council (SAC), Myanmar’s economy has sharply declined, becoming the weakest in Southeast Asia. In fiscal year 2024-25, real GDP is projected to contract by 1%, continuing a prolonged downturn following an 18% collapse post-coup. Agriculture shrank by 4%, while industry and services showed no growth. As the formal economy contracts, informal and illicit sectors have expanded. Myanmar is now the world’s largest opium producer and a major hub for synthetic drugs and online scam centers. Foreign investment has plummeted, with FDI approvals dropping from over $5 billion in fiscal year 2019-20 to $662 million in fiscal year 2023-24. International sanctions, financial blacklisting, and growing regulatory opacity have further discouraged engagement.
Poverty has surged nationwide, with 77% of households now poor or near-poor, up from 58% in 2017. High inflation—driven by extensive money printing—peaked at 35% in 2022 and remains elevated, particularly for food and transport. Real wages have fallen across sectors, deepening household vulnerability. Labour shortages have worsened due to mass outmigration, particularly after the 2024 conscription law. An estimated one-fifth of the population has left their communities due to conflict or hardship, draining the workforce and reducing productivity. Trade declined in 2023 after a brief rebound, with exports down $4 billion and land border trade sharply reduced in 2024. The financial sector remains weak, with liquidity shortages, low public trust, and a shrinking microfinance industry.
When the kyat fell by a third of its pre-coup value, the central bank then sold $600 million worth of foreign reserves (10% of the entire country's total) to prop up the kyat. By April 2022, reserves dwindled, foreign investment fell and remittances plummeted. This led the junta to impose capital controls and import restrictions which led to shortages of diabetes and cancer medicines.
The overall loss of skilled workers has contributed to a 9–11% GDP contraction since 2020. With the SAC prioritizing military aims over economic and human development, Myanmar faces a prolonged human resource crisis that could impact its economic recovery for decades.
== Still unresolved internal problems ==
In a first ever countrywide study in 2013, the Myanmar government found that 37 per cent of the population were unemployed and 26 per cent lived in poverty.
The current state of the Burmese economy has also had a significant impact on the people of Burma, as economic hardship results in extreme delays of marriage and family building. The average age of marriage in Burma is 27.5 for men, 26.4 for women, almost unparalleled in the region, with the exception of developed countries like Singapore.
Burma also has a low fertility rate of 2.07 children per woman (2010), especially as compared to other Southeast Asian countries of similar economic standing, like Cambodia (3.18) and Laos (4.41), representing a significant decline from 4.7 in 1983, despite the absence of a national population policy. This is at least partly attributed to the economic strain that additional children place on family income, and has resulted in the prevalence of illegal abortions in the country, as well as use of other forms of birth control.
The 2012 foreign investment law draft, included a proposal to transform the Myanmar Investment Commission from a government-appointed body into an independent board. This could bring greater transparency to the process of issuing investment licenses, according to the proposed reforms drafted by experts and senior officials. However, even with this draft, it will still remain a question on whether corruption in the government can be addressed (links have been shown between certain key individuals inside the government and the drug trade, as well as many industries that use forced labour -for example the mining industry-).
Many regions (such as the Golden Triangle) remain off-limits for foreigners, and in some of these regions, the government is at war with the country's ethnic minorities and the opposition.
== Industries ==
The major agricultural product is rice which covers about 60% of the country's total cultivated land area. Rice accounts for 97% of total food grain production by weight. Through collaboration with the International Rice Research Institute (IRRI), 52 modern rice varieties were released in the country between 1966 and 1997, helping increase national rice production to 14 million tons in 1987 and to 19 million tons in 1996. By 1988, modern varieties were planted on half of the country's rice fields, including 98% of the irrigated areas. In 2011, Myanmar's total milled rice production accounted for 10.60 million tons, an increase from the 1.8 per cent back in 2010.
In northern Burma, opium bans have ended a century old tradition of growing poppy. Between 20,000 and 30,000 ex-poppy farmers left the Kokang region as a result of the ban in 2002.
Rubber plantations are being promoted in areas of high elevation like Mong Mao. Sugar is grown in the lowlands such as Mong Pawk District.
The lack of an educated workforce skilled in modern technology contributes to the country's economic problems.
Lately, the Myanmar lacks adequate infrastructure. Goods travel primarily across Thai and China borders and through the main port in Yangon.
Railroads are old and dilapidated, with few repairs since their construction under British rule in the late nineteenth century. Presently China and Japan are providing aid to upgrade rail transport. Highways are normally paved, except in remote border regions. Energy shortages are common throughout the country including in Yangon. About 30 percent of the country's population does not have access to electricity, with 70 per cent of people living in rural areas. The civilian government has indicated that electricity will be imported from Laos to fulfil demand.
Other industries include agricultural goods, textiles, wood products, construction materials, gems, metals, oil and natural gas.
The private sector dominates agriculture, light industry, and transport activities, while the government controls energy, heavy industry, and military industries.
=== Garment production ===
The garment industry is a major job creator in the Yangon area, with around 200,000 workers employed in total in mid-2015. The Myanmar Government has introduced minimum wage of MMK 4,800 (US$3.18) per day for the garment workers from March 2018.
The Myanmar garments sector has seen significant influx of foreign direct investment, if measured by the number of entries
rather than their value. In March 2012, six of Thailand's largest garment manufacturers announced that they would move production to Myanmar, principally to the Yangon area, citing lower labour costs. In mid-2015, about 55% of officially registered garment firms in Myanmar were known to be fully or partly foreign-owned, with about 25% of the foreign firms from China and 17% from Hong Kong. Foreign-linked firms supply almost all garment exports, and these have risen rapidly in recent years, especially since EU sanctions were lifted in 2012. Myanmar exported $1.6 billion worth of garments and textiles in 2016.
=== Illegal drug trade ===
Burma (Myanmar) is the largest producer of methamphetamines in the world, with the majority of ya ba found in Thailand produced in Burma, particularly in the Golden Triangle and Northeastern Shan State, which borders Thailand, Laos and China. Burmese-produced ya ba is typically trafficked to Thailand via Laos, before being transported through the northeastern Thai region of Isan.
In 2010, Burma trafficked 1 billion tablets to neighbouring Thailand. In 2009, the Chinese authorities seized over 40 million tablets that had been illegally trafficked from Burma. Ethnic militias and rebel groups (in particular the United Wa State Army) are responsible for much of this production; however, the Burmese military units are believed to be heavily involved in the trafficking of the drugs.
Burma is also the second largest supplier of opium (following Afghanistan) in the world, with 95% of opium grown in Shan State. Illegal narcotics have generated $1 to US$2 billion in exports annually, with estimates of 40% of the country's foreign exchange coming from drugs. Efforts to eradicate opium cultivation have pushed many ethnic rebel groups, including the United Wa State Army and the Kokang to diversify into methamphetamine production.
Prior to the 1980s, heroin was typically transported from Burma to Thailand, before being trafficked by sea to Hong Kong, which was and still remains the major transit point at which heroin enters the international market. Now, drug trafficking has shifted to southern China (from Yunnan, Guizhou, Guangxi, Guangdong) because of a growing market for drugs in China, before reaching Hong Kong.
The prominence of major drug traffickers have allowed them to penetrate other sectors of the Burmese economy, including the banking, airline, hotel and infrastructure industries. Their investment in infrastructure have allowed them to make more profits, facilitate drug trafficking and money laundering. The share of informal economy in Myanmar is one of the largest in the world that feeds into trade in illegal drugs.
=== Oil and gas ===
Myanma Oil and Gas Enterprise (MOGE) is the national oil and gas company of Burma. The company is a sole operator of oil and gas exploration and production, as well as domestic gas transmission through a 1,900-kilometre (1,200 mi) onshore pipeline grid.
The Yadana Project is a project to exploit the Yadana gas field in the Andaman Sea and to carry natural gas to Thailand through Myanmar.
Sino-Burma pipelines refers to planned oil and natural gas pipelines linking Burma's deep-water port of Kyaukphyu (Sittwe) in the Bay of Bengal with Kunming in Yunnan province, China.
The Norwegian company Seadrill owned by John Fredriksen is involved in offshore oildrilling, expected to give the Burmese government oil and oil export revenues.
Myanmar exported $3.5 billion worth of gas, mostly to Thailand in the fiscal year up to March 2012.
Initiation to bid on oil exploration licenses for 18 of Myanmar's onshore oil blocks has been released on 18 January 2013.
=== Renewable energy ===
Myanmar has rich solar power and hydropower potential. The country's technical solar power potential is the greatest among the countries of the Greater Mekong Subregion. Wind energy, biogas and biomass have limited potential and are weakly developed.
Financing geothermal projects in Myanmar use an estimated break even power cost of 5.3–8.6 U.S cents/kWh or in Myanmar Kyat 53–86K per kWh. This pegs a non-fluctuating $1=1000K, which is a main concern for power project funding. The main drawback with depreciation pressures, in the current FX market.
Between June 2012 and October 2015, the Myanmar Kyat depreciated by approximately 35%, from 850 down to 1300 against the US Dollar. Local businesses with foreign denominated loans from abroad suddenly found themselves rushing for a strategy to mitigate currency risks. Myanmar's current lack of available currency hedging solutions presents a real challenge for geothermal project financing.
=== Gemstones ===
Myanmar's economy depends heavily on sales of precious stones such as sapphires, pearls and jade. Rubies are the biggest earner; 90% of the world's rubies come from the country, whose red stones are prized for their purity and hue. Thailand buys the majority of the country's gems. Burma's "Valley of Rubies", the mountainous Mogok area, 200 km (120 mi) north of Mandalay, is noted for its rare pigeon's blood rubies and blue sapphires. Burma's gemstone industry is a cornerstone of the Burmese economy with exports topping $1 billion.
In 2007, following the crackdown on pro-democracy protests in Myanmar, human rights organisations, gem dealers, and US First Lady Laura Bush called for a boycott of a Myanmar gem auction held twice yearly, arguing that the sale of the stones profited the dictatorial regime in that country. Debbie Stothard of the Alternative ASEAN Network on Burma stated that mining operators used drugs on employees to improve productivity, with needles shared, raising the risk of HIV infection. Richard W. Hughes, a Bangkok-based gemologist makes the point that for every ruby sold through the junta, another gem that supports subsistence mining is smuggled over the Thai border.
The Chinese have also been the chief driving force behind Burma's gem mining industry and jade exports. The industry is completely under Chinese hands at every level, from the financiers, concession operators, all the way to the retail merchants that own scores of newly opened gem markets. One Chinese-owned jeweller reportedly controls 100 gem mines and produces over 2,000 kilograms of raw rubies annually. Since the privatization of the gem industry during the 1990s, Burmese jewelers and entrepreneurs of Chinese ancestry have transformed Burma's gem industry into new retail jewelry shops, selling coveted pieces of expensive jewelry to customers mainly hailing from Hong Kong and Taiwan.
The permits for new gem mines in Mogoke, Mineshu and Nanyar state will be issued by the ministry according to a statement issued by the ministry on 11 February. While many sanctions placed on the former regime were eased or lifted in 2012, the US has left restrictions on importing rubies and jade from Myanmar intact. According to recent amendments to the new Myanmar foreign investment law, there is no longer a minimum capital requirement for investments, except in mining ventures, which require substantial proof of capital and must be documented through a domestic bank. Another important clarification in the investment law is the dropping of foreign ownership restrictions in joint ventures, except in restricted sectors, such as mining, where FDI will be capped at 80 per cent.
Myanmar is famed for its production of Golden South Sea Pearls. In recent years, the countries has auctioned its production in Hong Kong, first organized by Belpearl company in 2013 to critical acclaim and premium prices due to strong Chinese demand. Notable pearls include the New Dawn of Myanmar, a 19mm round golden pearl which sold to an anonymous buyer for undisclosed price.
=== Tourism ===
Since 1992, the government has encouraged tourism. Until 2008, fewer than 750,000 tourists entered the country annually, but there has been substantial growth over the past years. In 2012, 1.06 million tourists visited the country, and 1.8 million are expected to visit by the end of 2013.
Tourism is a growing sector of the economy of Burma. Burma has diverse and varied tourist attractions and is served internationally by numerous airlines via direct flights. Domestic and foreign airlines also operate flights within the country. Cruise ships also dock at Yangon. Overland entry with a border pass is permitted at several border checkpoints. The government requires a valid passport with an entry visa for all tourists and business people. As of May 2010, foreign business visitors from any country can apply for a visa on arrival when passing through Yangon and Mandalay international airports without having to make any prior arrangements with travel agencies. Both the tourist visa and business visa are valid for 28 days, renewable for an additional 14 days for tourism and three months for business. Seeing Burma through a personal tour guide is popular. Travellers can hire guides through travel agencies.
Aung San Suu Kyi has requested that international tourists not visit Burma. Moreoever, the junta's forced labour programmes were focused on tourist destinations; these designations have been heavily criticised for their human rights records. Even disregarding the obviously governmental fees, Burma's Minister of Hotels and Tourism Major-General Saw Lwin admitted that the government receives a significant percentage of the income of private sector tourism services. In addition, only a very small minority of impoverished people in Burma receive any money with any relation to tourism.
Before 2012, much of the country was completely off-limits to tourists, and the military tightly controlled interactions between foreigners and the people of Burma. Locals were not allowed to discuss politics with foreigners, under penalty of imprisonment, and in 2001, the Myanmar Tourism Promotion Board issued an order for local officials to protect tourists and limit "unnecessary contact" between foreigners and ordinary Burmese people. Since 2012, Burma has opened up to more tourism and foreign capital, synonymous with the country's transition to democracy.
=== Infrastructure ===
The Myanmar Infrastructure Summit 2018 noted that Myanmar has an urgent need to "close its infrastructure gap", with an anticipated expenditure of US$120 billion funding its infrastructural projects between now and 2030. More specifically, infrastructural development in Myanmar should address three major challenges over the upcoming years: 1) Road modernization and integration with neighboring roads and transportation networks; 2) Development of regional airports and expansion of existing airport capacity, and 3) Maintenance and consolidation of urban transport infrastructure, through instalments of innovative transportation tools including but not limited to water-taxis and air-conditioned buses. Myanmar needs to scale up its enabling infrastructure like transport, power supply and public utilities.
China's Belt and Road Initiative (BRI) infrastructure projects may affect 24 million people in Myanmar living in the BRI corridors, thus transforming the allocation of economic benefits and losses among economic actors in the country.
== External trade ==
== Macro-economic trends ==
This is a chart of trend of gross domestic product of Burma at market prices estimated by the International Monetary Fund and EconStats with figures in millions of Myanmar kyats.
The following table shows the main economic indicators in 1999–2024.
According to the CIA World Factbook,
Burma, a resource-rich country, suffers from pervasive government controls, inefficient economic policies, and rural poverty. The junta took steps in the early 1990s to liberalize the economy after decades of failure under the "Burmese Way to Socialism," but those efforts stalled, and some of the liberalization measures were rescinded. Burma does not have monetary or fiscal stability, so the economy suffers from serious macroeconomic imbalances – including inflation, multiple official exchange rates that overvalue the Burmese kyat, and a distorted interest rate regime. Most overseas development assistance ceased after the junta began to suppress the democracy movement in 1988 and subsequently refused to honor the results of the 1990 legislative elections. In response to the government of Burma's attack in May 2003 on Aung San Suu Kyi and her convoy, the US imposed new economic sanctions against Burma – including a ban on imports of Burmese products and a ban on provision of financial services by US persons. A poor investment climate further slowed the inflow of foreign exchange. The most productive sectors will continue to be in extractive industries, especially oil and gas, mining, and timber. Other areas, such as manufacturing and services, are struggling with inadequate infrastructure, unpredictable import/export policies, deteriorating health and education systems, and corruption. A major banking crisis in 2003 shuttered the country's 20 private banks and disrupted the economy. As of December 2005, the largest private banks operate under tight restrictions limiting the private sector's access to formal credit. Official statistics are inaccurate. Published statistics on foreign trade are greatly understated because of the size of the black market and unofficial border trade – often estimated to be as large as the official economy. Burma's trade with Thailand, China, and India is rising. Though the Burmese government has good economic relations with its neighbors, better investment and business climates and an improved political situation are needed to promote foreign investment, exports, and tourism. The economy saw continuous real GDP growth of at least 5% from 2009 onwards.
== Foreign investment ==
Though foreign investment has been encouraged, it has so far met with only moderate success. The United States has placed trade sanctions on Burma. The European Union has placed embargoes on arms, non-humanitarian aid, visa bans on military regime leaders, and limited investment bans. Both the European Union and the US have placed sanctions on grounds of human rights violations in the country. Many nations in Asia, particularly India, Thailand and China have actively traded with Burma. However, on April 22, 2013, the EU suspended economic and political sanctions against Burma.
The public sector enterprises remain highly inefficient and also privatisation efforts have stalled. The estimates of Burmese foreign trade are highly ambiguous because of the great volume of black market trading. A major ongoing problem is the failure to achieve monetary and fiscal stability. One government initiative was to utilise Burma's large natural gas deposits. Currently, Burma has attracted investment from Thai, Malaysian, Filipino, Russian, Australian, Indian, and Singaporean companies. Trade with the US amounted to $243.56 million as of February 2013, accounting for 15 projects and just 0.58 per cent of the total, according to government statistics.
=== Asian investment ===
The Economist's special report on Burma points to increased economic activity resulting from Burma's political transformation and influx of foreign direct investment from Asian neighbours. Near the Mingaladon Industrial Park, for example, Japanese-owned factories have risen from the "debris" caused by "decades of sanctions and economic mismanagement." Japanese Prime Minister Shinzō Abe has identified Burma as an economically attractive market that will help stimulate the Japanese economy. Among its various enterprises, Japan is helping build the Thilawa Port, which is part of the Thilawa Special Economic Zone, and helping fix the electricity supply in Yangon.
Japan is not the largest investor in Myanmar. "Thailand, for instance, the second biggest investor in Myanmar after China, is forging ahead with a bigger version of Thilawa at Dawei, on Myanmar's Tenasserim Coast ... Thai rulers have for centuries been toying with the idea of building a canal across the Kra Isthmus, linking the Gulf of Thailand directly to the Andaman Sea and the Indian Ocean to avoid the journey round peninsular Malaysia through the Strait of Malacca." Dawei would give Thailand that connection.
=== Chinese investment ===
China, by far the biggest investor in Burma, has focused on constructing oil and gas pipelines that "crisscross the country, starting from a new terminus at Kyaukphyu, just below Sittwe, up to Mandalay and on to the Chinese border town of Ruili and then Kunming, the capital of Yunnan province". This would prevent China from "having to funnel oil from Africa and the Middle East through the bottleneck around Singapore".
Since the Myanmar's military junta took power as the State Peace and Development Council junta in 1988, the ties between China's People's Liberation Army and Myanmar's military forces developed and formalised key ties between the two states. China became Myanmar's key source of aid, loans and other financial assistance. China remained Myanmar's biggest foreign investor in 2013 even after the economy opened up to other providers like Japan and India. Chinese monetary assistance allowed China to gain structural power of Myanmar and a dominant position within the natural resource sector. During this period, an underdeveloped Burmese industrial sector was driven in part by Chinese investment and consumption of a few key extractive sectors such as mining, driving domestic production away from consumer goods sectors like textiles and electronics.
Legal two-way trade between Burma and mainland China reached US$1.5 billion annually by 1988 and additional Chinese trade, investment, economic, and military aid was sought to invigorate and jumpstart the re-emerging Burmese economy. An influx of foreign capital investment from mainland China, Germany, and France has led to the development of new potential construction projects across Burma. Many of these infrastructure projects are in the hands of Chinese construction contractors and civil engineers with various projects such as irrigation dams, highways, bridges, ground satellite stations, and an international airport for Mandalay. Burmese entrepreneurs of Chinese ancestry have also established numerous joint ventures and corporate partnerships with mainland Chinese State-owned enterprises to facilitate the construction of oil pipelines that potentially could create thousands of jobs throughout the country. Private Chinese companies rely on the established overseas Chinese bamboo network as a conduit between mainland China and Burmese Chinese businesses to navigate the local economic landscape and facilitate trade between the two countries. Mainland China is now Burma's most important source of foreign goods and services as well as one of the most important sources of capital for foreign direct investment (FDI) in the country. In the fiscal year 2013, Chin accounted for 61 percent of all foreign direct investment. Between 2007 and 2015, Chinese FDI increased from US$775 million to US$21.867 billion accounting for 40 percent of all FDI in the country. Much of this investment went into Burma's energy and mining industries. Chinese private firms account for 87% percent of total legal cross-border trade at Ruili and have a considerable amount of structural power over the illicit economy of Myanmar. Chinese structural power over Burma's structure of finance also allows China to maintain a dominant position within the country's natural resource sector, primarily Burma's latent oil, gas, and uranium sectors. China's position as the country's primary investor also allows it to be its largest consumer of its extractive industries. Many Chinese state-owned enterprises have set their sights on Burma's high-value natural resource industries such as raw jade stones, teak and timber, rice, and marine fisheries.
=== Foreign aid ===
The level of international aid to Burma ranks amongst the lowest in the world (and the lowest in the Southeast Asian region)—Burma receives $4 per capita in development assistance, as compared to the average of $42.30 per capita.
In April 2007, the US Government Accountability Office (GAO) identified the financial and other restrictions that the military government places on international humanitarian assistance in the Southeast Asian country. The GAO report, entitled "Assistance Programs Constrained in Burma," outlines the specific efforts of the Burmese government to hinder the humanitarian work of international organisations, including by restricting the free movement of international staff within the country. The report notes that the regime has tightened its control over assistance work since former Prime Minister Khin Nyunt was purged in October 2004.
Furthermore, the reports states that the military government passed guidelines in February 2006, which formalised Burma's restrictive policies. According to the report, the guidelines require that programs run by humanitarian groups "enhance and safeguard the national interest" and that international organisations co-ordinate with state agents and select their Burmese staff from government-prepared lists of individuals. United Nations officials have declared these restrictions unacceptable.
The shameful behavior of Burma's military regime in tying the hand of humanitarian organizations is laid out in these pages for all to see, and it must come to an end," said U.S. Representative Tom Lantos (D-CA). "In eastern Burma, where the military regime has burned or otherwise destroyed over 3,000 villages, humanitarian relief has been decimated. At least one million people have fled their homes and many are simply being left to die in the jungle."
US Representative Ileana Ros-Lehtinen (R-FL) said that the report "underscores the need for democratic change in Burma, whose military regime arbitrarily arrests, tortures, rapes and executes its own people, ruthlessly persecutes ethnic minorities, and bizarrely builds itself a new capital city while failing to address the increasingly urgent challenges of refugee flows, illicit narcotics and human trafficking, and the spread of HIV/AIDS and other communicable diseases."
== Other statistics ==
Electricity – production:
17,866.99 GWh (2016 est.)
Electricity – consumption:
7,572.60 GWh Residential, 4,650.90 GWh Industrial, 3,023.27 GWh Commercial, 2,384.89 GWh Loss (2016 est.)
Electricity – exports:
2,381.34 kWh (2016)
Electricity – imports:
0 kWh (2006)
Agriculture – products:
rice, pulses, beans, sesame, groundnuts, watermelon, avocado sugarcane; hardwood; fish and fish products
Currency:
1 kyat (K) = 100 pyas
Exchange rates:
kyats per US dollar – 1,205 (2008 est.), 1,296 (2007), 1,280 (2006), 5.82 (2005), 5.7459 (2004), 6.0764 (2003)
note: unofficial exchange rates ranged in 2004 from 815 kyat/US dollar to nearly 970 kyat/US dollar, and by year end 2005, the unofficial exchange rate was 1,075 kyat/US dollar; data shown for 2003–05 are official exchange rates
Foreign Direct Investment
In the first eight months, Myanmar has received investment of US$5.7 billion. Singapore has remained as the top source of foreign direct investments into Myanmar in the financial year of 2019-2020 with 20 Singapore-listed enterprises bringing in US$1.85 billion into Myanmar in the financial year 2019-2020. Hong Kong stood as the second-largest investors with an estimated capital of US$1.42 billion from 46 enterprises, followed by Japan investing $760 million in Myanmar.
Foreign Trade
Total foreign trade reached over US$24.5 billion in the first eight months of the fiscal year (FY) 2019-2020 .
Internet Usage
In January 2024, there were 24.11 million internet users
in Myanmar. This means 44.0% of the total population used the internet.
== See also ==
Economics portal
Myanmar portal
== References ==
== Further reading ==
Myanmar Business Today; Print Edition, 5 November 2015. Geothermal Energy in Myanmar, Securing Electricity for Eastern Border Development Archived 20 November 2015 at the Wayback Machine, by David DuByne & Hishamuddin Koh
Myanmar Business Today; Print Edition, 19 June 2014. Myanmar's Institutional Infrastructure Constraints and How to Fill the Gaps Archived 13 September 2014 at the Wayback Machine, by David DuByne & Hishamuddin Koh
Myanmar Business Today; Print Edition, 27 February 2014. A Roadmap to Building Myanmar into the Food Basket of Asia, by David DuByne & Hishamuddin Koh
Taipei American Chamber of Commerce; Topics Magazine, Analysis, November 2012. Myanmar: Southeast Asia's Last Frontier for Investment Archived 25 February 2014 at the Wayback Machine, by David DuByne
Taiwan ASEAN Studies Center; ASEAN Outlook Magazine, May 2013. Myanmar's Overlooked Industry Opportunities and Investment Climate Archived 28 August 2013 at the Wayback Machine, by David DuByne
Myanmar Economic Monitor Report June 2023 (English); The World Bank, 28 June 2023. June 2023 Myanmar Economic Monitor : A Fragile Recovery - Special Focus on Employment, Incomes and Coping Mechanisms (English) Archived 4 November 2023 at the Wayback Machine, by Edwards,Kim Alan, Mansaray,Kemoh Myint,Thi Da Hayati,Fayavar Maw,Aka Kyaw Min
== External links ==
Google Earth Map of oil and gas infrastructure in Myanmar Archived 12 January 2014 at the Wayback Machine
Myanmar Ministry of Commerce (MMC) News, information, journals, magazines related to Burmese business and commerce
Myanmar-US Chamber of Commerce
Union of Myanmar Federation of Chambers of Commerce and Industry (UMFCCI) [1] Archived 23 November 2012 at the Wayback Machine
World Bank Summary Trade Statistics Myanmar Archived 12 May 2014 at the Wayback Machine | Wikipedia/Illegal_drug_trade_in_Burma |
Protein metabolism denotes the various biochemical processes responsible for the synthesis of proteins and amino acids (anabolism), and the breakdown of proteins by catabolism.
The steps of protein synthesis include transcription, translation, and post translational modifications. During transcription, RNA polymerase transcribes a coding region of the DNA in a cell producing a sequence of RNA, specifically messenger RNA (mRNA). This mRNA sequence contains codons: 3 nucleotide long segments that code for a specific amino acid. Ribosomes translate the codons to their respective amino acids. In humans, non-essential amino acids are synthesized from intermediates in major metabolic pathways such as the Citric Acid Cycle. Essential amino acids must be consumed and are made in other organisms. The amino acids are joined by peptide bonds making a polypeptide chain. This polypeptide chain then goes through post translational modifications and is sometimes joined with other polypeptide chains to form a fully functional protein.
Dietary proteins are first broken down to individual amino acids by various enzymes and hydrochloric acid present in the gastrointestinal tract. These amino acids are absorbed into the bloodstream to be transported to the liver and onward to the rest of the body. Absorbed amino acids are typically used to create functional proteins, but may also be used to create energy. They can also be converted into glucose. This glucose can then be converted to triglycerides and stored in fat cells.
Proteins can be broken down by enzymes known as peptidases or can break down as a result of denaturation. Proteins can denature in environmental conditions the protein is not made for.
== Protein synthesis ==
Protein anabolism is the process by which proteins are formed from amino acids. It relies on five processes: amino acid synthesis, transcription, translation, post translational modifications, and protein folding. Proteins are made from amino acids. In humans, some amino acids can be synthesized using already existing intermediates. These amino acids are known as non-essential amino acids. Essential amino acids require intermediates not present in the human body. These intermediates must be ingested, mostly from eating other organisms.
=== Amino Acid Synthesis ===
=== Polypeptide synthesis ===
==== Transcription ====
In transcription, RNA polymerase reads a DNA strand and produces an mRNA strand that can be further translated. In order to initiate transcription, the DNA segment that is to be transcribed must be accessible (i.e. it cannot be tightly packed). Once the DNA segment is accessible, the RNA polymerase can begin to transcribe the coding DNA strand by pairing RNA nucleotides to the template DNA strand. During the initial transcription phase, the RNA polymerase searches for a promoter region on the DNA template strand. Once the RNA polymerase binds to this region, it begins to “read” the template DNA strand in the 3’ to 5’ direction. RNA polymerase attaches RNA bases complementary to the template DNA strand (Uracil will be used instead of Thymine). The new nucleotide bases are bonded to each other covalently. The new bases eventually dissociate from the DNA bases but stay linked to each other, forming a new mRNA strand. This mRNA strand is synthesized in the 5’ to 3’ direction. Once the RNA reaches a terminator sequence, it dissociates from the DNA template strand and terminates the mRNA sequence as well.
Transcription is regulated in the cell via transcription factors. Transcription factors are proteins that bind to regulatory sequences in the DNA strand such as promoter regions or operator regions. Proteins bound to these regions can either directly halt or allow RNA polymerase to read the DNA strand or can signal other proteins to halt or allow RNA polymerase reading.
==== Translation ====
During translation, ribosomes convert a sequence of mRNA (messenger RNA) to an amino acid sequence. Each 3-base-pair-long segment of mRNA is a codon which corresponds to one amino acid or stop signal. Amino acids can have multiple codons that correspond to them. Ribosomes do not directly attach amino acids to mRNA codons. They must utilize tRNAs (transfer RNAs) as well. Transfer RNAs can bind to amino acids and contain an anticodon which can hydrogen bind to an mRNA codon. The process of bind an amino acid to a tRNA is known as tRNA charging. Here, the enzyme aminoacyl-tRNA-synthetase catalyzes two reactions. In the first one, it attaches an AMP molecule (cleaved from ATP) to the amino acid. The second reaction cleaves the aminoacyl-AMP producing the energy to join the amino acid to the tRNA molecule.
Ribosomes have two subunits, one large and one small. These subunits surround the mRNA strand. The larger subunit contains three binding sites: A (aminoacyl), P (peptidyl), and E (exit). After translational initiation (which is different in prokaryotes and eukaryotes), the ribosome enters the elongation period which follows a repetitive cycle. First a tRNA with the correct amino acid enters the A site. The ribosome transfers the peptide from the tRNA in the P site to the new amino acid on the tRNA in the A site. The tRNA from the P site will be shifted into the E site where it will be ejected. This continually occurs until the ribosome reaches a stop codon or receives a signal to stop. A peptide bond forms between the amino acid attached to the tRNA in the P site and the amino acid attached to a tRNA in the A site. The formation of a peptide bond requires an input of energy. The two reacting molecules are the alpha amino group of one amino acid and the alpha carboxyl group of the other amino acids. A by-product of this bond formation is the release of water (the amino group donates a proton while the carboxyl group donates a hydroxyl).
Translation can be downregulated by miRNAs (microRNAs). These RNA strands can cleave mRNA strands they are complementary to and will thus stop translation. Translation can also be regulated via helper proteins. For example, a protein called eukaryotic initiation factor-2 (eIF-2) can bind to the smaller subunit of the ribosome, starting translation. When elF-2 is phosphorylated, it cannot bind to the ribosome and translation is halted.
==== Post-translational Modifications ====
Once the peptide chain is synthesized, it still must be modified. Post-translational modifications can occur before protein folding or after. Common biological methods of modifying peptide chains after translation include methylation, phosphorylation, and disulfide bond formation. Methylation often occurs to arginine or lysine and involves adding a methyl group to a nitrogen (replacing a hydrogen). The R groups on these amino acids can be methylated multiple times as long as the bonds to nitrogen does not exceed 4. Methylation reduces the ability of these amino acids to form hydrogen bonds so arginine and lysine that are methylated have different properties than their standard counterparts. Phosphorylation often occurs to serine, threonine, and tyrosine and involves replacing a hydrogen on the alcohol group at the terminus of the R group with a phosphate group. This adds a negative charge on the R groups and will thus change how the amino acids behave in comparison to their standard counterparts. Disulfide bond formation is the creation of disulfide bridges (covalent bonds) between two cysteine amino acids in a chain which adds stability to the folded structure.
==== Protein folding ====
A polypeptide chain in the cell does not have to stay linear; it can become branched or fold in on itself. Polypeptide chains fold in a particular manner depending on the solution they are in. The fact that all amino acids contain R groups with different properties is the main reason proteins fold.
In a hydrophilic environment such as cytosol, the hydrophobic amino acids will concentrate at the core of the protein, while the hydrophilic amino acids will be on the exterior. This is entropically favorable since water molecules can move much more freely around hydrophilic amino acids than hydrophobic amino acids.
In a hydrophobic environment, the hydrophilic amino acids will concentrate at the core of the protein, while the hydrophobic amino acids will be on the exterior. Since the new interactions between the hydrophilic amino acids are stronger than hydrophobic-hydrophilic interactions, this is enthalpically favorable.
Once a polypeptide chain is fully folded, it is called a protein. Often many subunits will combine to make a fully functional protein although physiological proteins do exist that contain only one polypeptide chain. Proteins may also incorporate other molecules such as the heme group in hemoglobin, a protein responsible for carrying oxygen in the blood.
== Protein breakdown ==
Protein catabolism is the process by which proteins are broken down to their amino acids. This is also called proteolysis and can be followed by further amino acid degradation.
=== Protein catabolism via enzymes ===
==== Proteases ====
Originally thought to only disrupt enzymatic reactions, proteases (also known as peptidases) actually help with catabolizing proteins through cleavage and creating new proteins that were not present before. Proteases also help to regulate metabolic pathways. One way they do this is to cleave enzymes in pathways that do not need to be running (i.e. gluconeogenesis when blood glucose concentrations are high). This helps to conserve as much energy as possible and to avoid futile cycles. Futile cycles occur when the catabolic and anabolic pathways are both in effect at the same time and rate for the same reaction. Since the intermediates being created are consumed, the body makes no net gain. Energy is lost through futile cycles. Proteases prevent this cycle from occurring by altering the rate of one of the pathways, or by cleaving a key enzyme, they can stop one of the pathways. Proteases are also nonspecific when binding to substrate, allowing for great amounts of diversity inside the cells and other proteins, as they can be cleaved much easier in an energy efficient manner.
Because many proteases are nonspecific, they are highly regulated in the cell. Without regulation, proteases will destroy many proteins which are essential to physiological processes. One way the body regulates proteases is through protease inhibitors. Protease inhibitors can be other proteins, small peptides, or molecules. There are two types of protease inhibitors: reversible and irreversible. Reversible protease inhibitors form non-covalent interactions with the protease limiting its functionality. They can be competitive inhibitors, uncompetitive inhibitors, and noncompetitive inhibitors. Competitive inhibitors compete with the peptide to bind to the protease active site. Uncompetitive inhibitors bind to the protease while the peptide is bound but do not let the protease cleave the peptide bond. Noncompetitive inhibitors can do both. Irreversible protease inhibitors covalently modify the active site of the protease so it cannot cleave peptides.
===== Exopeptidases =====
Exopeptidases are enzymes that can cleave the end of an amino acid side chain mostly through the addition of water. Exopeptidase enzymes exist in the small intestine. These enzymes have two classes: aminopeptidases are a brush border enzyme and carboxypeptidases which is from the pancreas. Aminopeptidases are enzymes that remove amino acids from the amino terminus of protein. They are present in all lifeforms and are crucial for survival since they do many cellular tasks in order to maintain stability. This form of peptidase is a zinc metalloenzyme and it is inhibited by the transition state analog. This analog is similar to the actual transition state, so it can make the enzyme bind to it instead of the actual transition state, thus preventing substrate binding and decreasing reaction rates. Carboxypeptidases cleave at the carboxyl end of the protein. While they can catabolize proteins, they are more often used in post-transcriptional modifications.
===== Endopeptidases =====
Endopeptidases are enzymes that add water to an internal peptide bond in a peptide chain and break that bond. Three common endopeptidases that come from the pancreas are pepsin, trypsin, and chymotrypsin. Chymotrypsin performs a hydrolysis reaction that cleaves after aromatic residues. The main amino acids involved are serine, histidine, and aspartic acid. They all play a role in cleaving the peptide bond. These three amino acids are known as the catalytic triad which means that these three must all be present in order to properly function. Trypsin cleaves after long positively charged residues and has a negatively charged binding pocket at the active site. Both are produced as zymogens, meaning they are initially found in their inactive state and after cleavage though a hydrolysis reaction, they becomes activated. Non-covalent interactions such as hydrogen bonding between the peptide backbone and the catalytic triad help increase reaction rates, allowing these peptidases to cleave many peptides efficiently.
=== Protein catabolism via environmental changes ===
==== pH ====
Cellular proteins are held in a relatively constant pH in order to prevent changes in the protonation state of amino acids. If the pH drops, some amino acids in the polypeptide chain can become protonated if the pka of their R groups is higher than the new pH. Protonation can change the charge these R groups have. If the pH raises, some amino acids in the chain can become deprotonated (if the pka of the R group is lower than the new pH). This also changes the R group charge. Since many amino acids interact with other amino acids based on electrostatic attraction, changing the charge can break these interactions. The loss of these interactions alters the proteins structure, but most importantly it alters the proteins function, which can be beneficial or detrimental. A significant change in pH may even disrupt many interactions the amino acids make and denature (unfold) the protein.
==== Temperature ====
As the temperature in the environment increases, molecules move faster. Hydrogen bonds and hydrophobic interactions are important stabilizing forces in proteins. If the temperature rises and molecules containing these interactions are moving too fast, the interactions become compromised or even break. At high temperatures, these interactions cannot form, and a functional protein is denatured. However, it relies on two factors; the type of protein used and the amount of heat applied. The amount of heat applied determines whether this change in protein is permanent or if it can be transformed back to its original form.
== References == | Wikipedia/Protein_metabolism |
Diabetes mellitus is a metabolic disease that is characterized by chronic elevated blood glucose levels (hyperglycemia). Therefore, the main goal of diabetes management is to keep blood glucose levels within normal limits or a target range as much as possible. If diabetes is not well controlled, further challenges to health may occur. People with diabetes can measure blood sugar by various methods, such as with a glucose meter or a continuous glucose monitor, which monitors over several days. Glucose can also be measured by analysis of a routine blood sample. In addition to lifestyle modification, some individuals may need medications to adequately control their blood sugar levels. Other goals of diabetes management are prevention or treatment of complications that can result from the disease itself and from its treatment.
== Description ==
Diabetes is a well known chronic disease that affects many individuals of all ages worldwide. There are many subtypes including Type 1, Type 2, gestational diabetes, maturity-onset diabetes of the young (MODY), neonatal diabetes, etc., with Type 1 and Type 2 being the most common. It is important to have control of this condition as uncontrolled diabetes can cause many complications. Diabetes can cause acute problems such blood sugar that is too low (hypoglycemia) or too high (hyperglycemia) which can cause acute symptoms. Diabetes also affects the blood vessels in the body, which are the routes blood take to deliver nutrients and oxygen to the organs in the body. By affecting the blood flow, diabetes increases the risk of other conditions such as strokes and heart disease (heart attacks). Diabetes is also associated with microvascular affects (small blood vessels) in organs such as the eyes and the kidneys and can cause diabetic retinopathy and diabetic nephropathy, respectively.
In addition to maintaining adequate blood sugar levels in the body, control of other risk factors that contribute to complications such as smoking, alcohol use, excessive weight, high blood pressure, and high cholesterol are also very important. Often, the recommended treatment for diabetes mellitus is a combination of lifestyle changes such as increasing exercise and healthy eating, along with medications to help control the blood glucose levels in the long term. In addition to management of the diabetes, it is recommended to have routine follow up with a primary care physician or endocrinologist as well a variety of specialists to assist in managing possible common complications such as foot ulcers, vision changes, and hearing loss.
=== Glucose Measurement ===
There are several methods in which blood sugar is measured including with a glucose meter, continuous glucose monitor (CGM), and routine bloodwork.
The glucose meter, also known as a glucometer, is a common and simple method using a portable electronic device to measure glucose levels either at home or in a clinical setting. The glucose meter works by taking a small sample of blood using a lancet (a sterile pointed needle) to prick a fingertip, usually the index or middle finger (Image 1). The blood droplet is usually collected at the bottom of a test strip, while the other end is inserted in the glucose meter. The drop of blood is drawn into the meter and can directly measure the glucose in the sample. The units of blood sugar level from a glucose meter, will result in either mg/dL (milligrams per deciliter in the US) or mmol/L (millimoles per liter in Canada and Eastern Europe) of blood. Proper user technique and environmental conditions are important in obtaining reliable readings and accurate glucose measurements. Control of diabetes may be improved using home glucose meters to regularly measure glucose levels as this method provides rapid results allowing individuals to make timely decisions regarding diet, exercise, and medication.
Continuous glucose monitors (CGMs) are another method to measure blood glucose levels and is widely used among individuals with diabetes. A continuous glucose monitor is a device that sits on the surface of the skin (usually on the arm or abdomen) and measures the amount of glucose between the cells with a probe. The device does not directly measure the blood sugar but rather tracks the interstitial glucose levels which are similar to blood glucose levels. The other part of the CGM, known as the transmitter, then sends the information to a receiver, an insulin pump, or a compatible smart device. Unlike the traditional glucose meter, CGMs will report the glucose level continuously and has an alarm that will alert the person if the glucose level is too high or low, helping to prevent emergencies. The device is able to graph the glucose readings over the time the sensor was in use and track trends. This allows for timely adjustment of diet, activity levels, medications, and/or illness In addition, the information from the CGM can be downloaded and sent to a second person (such as a parent, caregiver, or partner) or physician for their review. CGMs have also been shown to improve glycemic control, reduce Hb A1c levels, and/or reduce the risk of hypoglycemic events. They also can reduce the need for multiple fingersticks throughout the day, which may be preferred by some individuals. Popular CGM devices include Dexcom, Freestyle Libre, and Medtronic.
In addition to the above tests, glucose can be measured on routine labs. One common test ordered by healthcare providers is a Basic Metabolic Panel which is a blood test that looks at several different substances in the body, including blood glucose. Usually, individuals are told to fast for 8 hours before drawing the labs so that the provider can see the fasting glucose level. The normal range for fasting blood sugar in people without diabetes is 70 to 99 mg/dL (3.9 to 5.5 mmol/L). The range for individuals considered to have prediabetes is 100 to 125 mg/dL (5.6 to 6.9 mmol/L). If the fasting blood sugar is greater than 126 mg/dL (7.0 mmol/L) on blood tests taken on separate occasions, individuals are considered to have diabetes.
Another useful test that is usually done via a blood test is the measurement of blood HbA1c (hemoglobin A1c) levels. In the blood, there is a molecule called hemoglobin which carries oxygen to the cells. Glucose can attach itself to this molecule and if the blood glucose is consistently high, the value of the A1c will increase. This test, unlike the other tests, is measured as a percentage because the test measures the proportion of all the hemoglobin that has glucose attached. This test measures the average amount of blood sugar control over a period of about 3 months (90 days). In people without diabetes, the HbA1c level ranges from 4.0 to 5.7%. The range for people with prediabetes is 5.7 to 6.4%, and anything above 6.4% is considered diabetic range. Due to the HbA1c serving as a accurate indicator of overall glycemic control, regular 6 month laboratory testing of HbA1c (glycated hemoglobin) is recommended to gauge long-term control and allows for more information to then adjust a person's lifestyle as well as routine medication dosages in such cases.
Optimal management of diabetes involves individuals measuring and recording their own blood glucose levels. By keeping a diary of blood glucose measurements and noting the effect of food and activity levels, individuals can modify their lifestyle to better control their diabetes. Studies suggest that the self-monitoring of blood glucose can improve HbA1c levels both in the short and long-term in patients with type 2 diabetes that are not on insulin. For individuals on insulin, glucose monitoring is also crucial in achieving effective dosing and timing.
=== Glycemic Control ===
Glycemic control is a medical term referring to the typical levels of blood glucose in a person with diabetes mellitus. Much evidence suggests that many of the long-term complications of diabetes, result from many years of hyperglycemia (elevated levels of glucose in the blood).
"Perfect glycemic control" would mean that glucose levels were always normal (70–130 mg/dL or 3.9–7.2 mmol/L) and indistinguishable from a person without diabetes. Good glycemic control, in the sense of a "target" for treatment, has become an important goal of diabetes care. Poor glycemic control refers to persistent (over several months) elevated blood glucose in the 200 to 500 mg/dL (11–28 mmol/L) range. This is also measured by Hb A1c levels, which may range 6.5% or higher.
=== Goals ===
They are suggested in clinical practice guidelines released by various national and international diabetes organizations.
The glycemic targets are:
HbA1c of less than 7.0% if they are achievable without significant hypoglycemia
Preprandial (before eating) blood glucose: 70 to 130 mg/dL (3.9 to 7.2 mmol/L)
2-hour postprandial (after eating) blood glucose: Less than 180 mg/dL (<10 mmol/L)
Goals should be individualized based on:
Duration of diabetes
Age/life expectancy
Comorbidity
Known cardiovascular disease or advanced microvascular disease
Hypoglycemia awareness
In older people, clinical practice guidelines by the American Geriatrics Society recommend, in frail people who have a life expectancy of less than 5 years, a target a Hb A1c of 8% is appropriate as the risk of very low blood sugar outweighs the long term benefits of a lower A1c.
When comparing the effects of tight versus conventional (more relaxed) glycemic control in type 2 diabetics, studies failed to demonstrate a difference in all-cause cardiovascular death, non-fatal stroke, or limb amputation, but decreased the risk of nonfatal myocardial infarction (heart attack) by 15%. Additionally, tight glucose control decreased the risk of progression of kidney, nerve, and eye complications, but increased the risk of severe hypoglycemia.
== Lifestyle Modification ==
=== Diet ===
Dietary changes have been shown to significantly help patients manage diabetes. There are many diets that are effective at managing diabetes however, it is important that patients understand that there is no one diet that all patients should use. Some diets that have strong evidence and have commonly been used successfully in diabetes management and assist with weight loss include Mediterranean diet, Dietary Approaches to Stop Hypertension (DASH), Alternative Healthy Eating Index (AHEI), vegetarian, low carb, or carb-controlled. In addition, it is recommended that individuals choose a diet that can be adhered to long-term. Even in the most ideal diet becomes impractical if the patient has difficulty following it.
A regular diet that has reduced variability in carbohydrates is an important factor in producing normal blood sugars. Patients with diabetes should eat preferably a balanced and healthy diet. Meals should consist of half a plate of non-starchy vegetables, 1/4 plate of lean protein, and 1/4 plate of starch/grain. Patients should avoid excess simple carbs or added fat (such as butter, salad dressing) and instead eat complex carbohydrates such as whole grains. In addition, patients should also avoid consumption of processed meat and foods and sugar-sweetened beverages. In the long term, it is helpful to eat a consistent diet and amount of carbohydrate to make blood sugar management easier. It is important for patients to eat 3 meals a day in order to reduce the chances of hypoglycemia, especially with patients that take insulin.
There is a lack of evidence of the usefulness of low-carbohydrate dieting for people with type 1 diabetes (T1D). Although for certain individuals it may be feasible to follow a low-carbohydrate regime combined with carefully managed insulin dosing, this is hard to maintain and there are concerns about potential adverse health effects caused by the diet. In general people with T1D are advised to follow an individualized eating plan rather than a pre-decided one.
=== Physical Activity/Exercise ===
Along with diet, physical activity is also important for the management of diabetes. Not only does exercising regularly help manage blood sugar levels and weight, it helps reduce the risk of heart attack and stroke, reduces cholesterol and blood pressure levels, reduces risk of diabetes related complications, increases the effect of insulin, provides a boost in energy levels, helps reduce stress, and contributes to positive self-esteem. By exercising, the body becomes more sensitive to insulin, allowing for better absorption of glucose by the muscle cells, for up to 24 hours after exercise. In addition, studies have shown that physical activity, even below recommended amounts, has the ability to reduce risk fo diabetic-related complications.
In people with type 2 diabetes, the combination of aerobic ("cardio") exercise and strength training is effective. Aerobic exercise has been shown to largely improve HbA1c, and contributes to weight loss and the enhanced regulation of cholesterol and lipoproteins. This may be any form of continuous exercise that elevates breathing and heart rate, such as walking, swimming, or dancing. During the last 20 years, resistance training has gained recognition as an effective form of exercise for people with type 2 diabetes.
In youths with type 1 diabetes, there is an association between exercise and lower HBA1c. Furthermore, studies have shown that the longer the length of the exercise program, the better the reduction in HBA1c and insulin requirements.
=== Weight Loss ===
In addition to diet and exercise, weight loss is an important tool to help with diabetes management. T2D is often associated with obesity and increased abdominal circumference. Often patients who are at risk of diabetes may be able to reverse their progression to T2D with weight loss as well. Weight loss can help improve metabolic control, reduce the risk of further complications, other health related problems, and helps improve the effects of insulin on the body. Weight loss helps reduce the destruction of the beta cells, which produce insulin in the body, as well.
It is recommended for patients who have been diagnosed with T2D who are overweight or obese to lose at least 5% of their weight and maintain the weight loss. There have been studies that have demonstrated that by losing about 5 to 10% of their weight at diagnosis, there is a reduction in heart disease risk factors, lowered Hb A1c, less diabetes medications, lower cholesterol and improved fitness.
Common strategies to help reduce weight many include lifestyle measures such as diet and exercise, behavioral therapy, pharmacologic interventions, and surgery. The goal of weight loss and method for achievement should be individualized based on the patient's desires and motivation. It is important for providers to help maintain patient motivation and provide education to assist individuals in their weight journey. Additionally, some medications that reduce blood sugars such as insulin may initially cause weight gain due to the increased conversion of blood sugar to stored forms such as fat. Therefore, in patients with diabetes, providers may try other medications that lower blood sugar but not cause as much weight gain.
== Medications ==
There are several medications classes that are commonly used to control blood sugar levels in patients with diabetes. Most of the medications used are either oral or injected. In patients with T1D, insulin is required because the body no longer produces insulin. In patients with T2D, management is largely more variable as lifestyle changes can have a significant impact. However, medications may be added to further help control blood glucose levels if the lifestyle changes are not effectively controlling the condition. Unlike patients with type 1 diabetes, patients with T2D can still produce insulin, so usually oral medications are recommended as first line treatment before requiring insulin for diabetic control. Patient education and adherance with treatment is very important in managing the disease. Improper use of medications and insulin can be very dangerous causing hypo- or hyper-glycemic episodes.
=== Insulin ===
Insulin is the hormone that is made by the body that controls the cell intake of glucose. Normally, the pancreas produces insulin in response to high glucose levels in the body to bring the blood glucose levels down. For those with type 1 diabetes, there will always be a need for insulin injections throughout their life, as the pancreatic beta cells are not capable of producing sufficient insulin. Insulin can not be taken orally because insulin is a hormone and is destroyed by the digestive track. Insulin can be injected by several methods, including a hypodermic needle, jet injector, or insulin pump. There is also inhaled insulin that can be used in adults with diabetes.
There are several types of insulin that are commonly used in medical practice, with varying times of onset and duration of action. These include:
Rapid acting (i.e. insulin lispro) with onset in 15 minutes and duration of about 4 hrs
Short acting (i.e. regular insulin) with onset in 30 minutes and duration of about 6 hrs
Intermediate acting (i.e NPH insulin) with onset in 2 hours and duration of about 14 hrs
Long acting (i.e. detemir) with onset in 1 hour and duration of about 24 hrs
Premixed which are usually combinations of short and long acting insulin
Insulin is usually taken several times per day in patients who require it to control their diabetes. Patients usually take long acting insulin once per day and then take insulin before meals. The time of onset of the insulin determines how far in advance patients should take the insulin before they eat.
Insulin therapy requires close monitoring and a great deal of patient education, as improper administration is quite dangerous. Insulin can easily cause hypoglycemia if the patient does not eat after administering insulin or accidentally took too much insulin. A previously satisfactory dosing may be too much if less food is consumed causing hypoglycemia. Exercise decreases insulin requirements as exercise increases glucose uptake by body cells whose glucose is controlled by the insulin.
Insulin therapy creates risk because of the inability to continuously know a person's blood glucose level and adjust insulin infusion appropriately. However, new advances in technology have significantly alleviated many of these risks, although they can still occur. Small, portable insulin infusion pumps are available from several manufacturers. They allow a continuous infusion of small amounts of insulin to be delivered through the skin around the clock. They also have the ability to give bolus doses when a person eats or has elevated blood glucose levels. They are also capable to being used in conjunction with continuous glucose monitors for optimal glucose management. This is very similar to how the pancreas works, but these pumps lack a continuous "feed-back" mechanism. Thus, the user is still at risk of giving too much or too little insulin unless blood glucose measurements are made.
=== Oral Medications ===
==== Metformin ====
One of the most common drugs used in T2D, metformin is the drug of choice to help patients lower their blood sugar levels. Metformin is an example of a class of medicine called biguanides. The medication works by reducing the new creation of glucose from the liver and by reducing absorption of sugar from food. In addition, the medication also works to help increase the effects of insulin on muscle cells, which take in glucose. The medicine is not used for T1D as these patients do not produce any insulin and metformin relies on some insulin production in order to be effective. There are several preparations of the medication such as tablets, extend release tablets, and liquid suspensions. Metformin is usually started as 500 to 1000 mg tablets twice a day by mouth (PO), usually with meals. If taking the extended release tablets, they should be always swallowed whole as cutting the tablet will cause faster release of the medication. The medication most commonly may cause side effects such as stomach upset and diarrhea, but in general is well tolerated and has a relatively low chance of causing hypoglycemia. One rare (about 1% chance) but serious side effect of metformin is that it can cause lactic acidosis, usually in patients with poor kidney function. To assist in tolerance of the metformin, practitioners may recommend gradual increase of the dose of the medication.
==== Sulfonylureas ====
Another commonly used class of medications to treat T2D are sulfonylureas. This class of medicine increases the release of insulin from the beta cells in the pancreas. The medication can not be used in patients with T1D, as they do not have functioning beta cells and can not produce insulin. Some common examples of a sulfonylurea is glipizide, glyburide, glimepiride and gliclazide. Depending on the medication, there are different size tablets but in general, the sizes range from about 1 mg to 10 mg. Usually, the tablet is taken about 30 minutes before a meal and can be either once or twice a day. The most common adverse effects of the medication are lightheadedness and stomach irritation. Sulfonylureas have a greater risk of hypoglycemia but the risk is still only around 3% of patients who use them. In patients who have a greater risk of low sugar, such as in the elderly and patients with kidney disease, the starting dose can be as low as 0.5 mg.
=== GLP-1 agonists ===
Another popular medication that is used in T2D management are glucagon like peptide 1 (GLP-1) agonists. This class of medication works by mimicking a hormone called glucagon-like peptide which has many effects in the body. One effect of the hormone is that it helps time the release of insulin when patients eat and the blood glucose rises. In addition, it can significantly increase the amount of insulin release. Lastly, the medication also slows down the movement of food through the digestive tract and can increase feeling of fullness while eating, decreasing appetite and weight. These drugs are very effective at controlling T2D and reducing risk of heart attacks, strokes, and other complications due to diabetes. In addition, patients usually lose weight and have improved blood pressure and cholesterol. Common names of these medications include semaglutide (Ozempic and Wegovy), liraglutide (Victoza, Saxenda), and dulaglutide (Trulicity). These medications must be injected and are usually injected in the upper arm, thighs or stomach areas. They are usually given once a week but some of the medication can be as frequent as twice daily. The dose is usually started low and tapered gradually. Some of the common side effects of the medication is nausea, vomiting, and diarrhea. Patients with a family history of medullary thyroid cancer or Multiple Endocrine Neoplasia type 2 should not be prescribed the drug as it may increase the risk of developing cancer.
== Surgery ==
While weight loss is beneficial in improving glycemic control in patients with T2D, maintaining significant weight loss can be challenging. People with diabetes who have a body mass index (BMI) of 35 or higher, and who have been unable to lose weight otherwise, bariatric surgery offers a viable option to help achieve that goal. In 2018, a Patient-Centered Outcomes Research Institute funded study was published which analyzed the effects of three common types of bariatric surgery on sustained weight loss and long-lasting glycemic control in patients with T2D. The results of this study demonstrated that five years after bariatric surgery, there was significant weight loss in a large majority of patients. In addition, and more importantly, this study showed that, in patients with type 2 diabetes with a BMI of 35 or higher, bariatric surgery has the potential to lead to complete remission of diabetes in as many as 40% of those people who have the procedure. Like any operation, bariatric surgery is not without risks and complications, and those risks need to weighed against the potential benefits in anyone considering the procedure.
== Additional Monitoring ==
=== Foot Care ===
Foot monitoring can help in predicting the likelihood of developing diabetic foot ulcers, a common complication in persistent uncontrolled diabetes. A common method for this is using a special thermometer to look for spots on the foot that have higher temperature which indicate the possibility of an ulcer developing. At the same time there is no strong scientific evidence supporting the effectiveness of at-home foot temperature monitoring. The current guideline in the United Kingdom recommends collecting 8-10 pieces of information for predicting the development of foot ulcers. A simpler method proposed by researchers provides a more detailed risk score based on three pieces of information (insensitivity, foot pulse, previous history of ulcers or amputation). This method is not meant to replace individuals regularly checking their own feet but complement it.
=== Dental Care ===
High blood glucose levels in individuals with diabetes is a risk factor for developing gum and tooth problems. For patients with diabetes, there are increased risk of developing oral health problems such as tooth decay, saliva production dysfunction, fungal infections, and periodontal disease Diabetes lowers the ability to resist infection and also slows healing and therefore individuals may experience more severe periodontitis. In turn, the chronic infection from periodontal disease can cause difficulties in controlling diabetes, leading to worsening of diabetic complications. The oral problems in persons with diabetes can be prevented with a good control of the blood sugar levels, regular check-ups with their dental provider, and good oral hygiene. Looking for early signs of gum disease (redness, swelling, bleeding gums) and informing the dentist about them is also helpful in preventing further complications. Quitting smoking is recommended to avoid serious diabetes complications and oral diseases. By maintaining a good oral status, diabetic persons prevent losing their teeth as a result of various periodontal conditions.
=== Eye Care ===
Any individual with diabetes is at risk for diabetes-related eye conditions and it is recommended to have an initial diabetic eye exam screening and subsequent annual comprehensive dilated eye exam with either an optometrist or ophthalmologist. Diabetic retinopathy is the most common complication of diabetes and one of the leading causes of blindness worldwide. Individuals with diabetes are at greater risk for developing eye conditions such as glaucoma and cataracts earlier or more frequently. Blood sugar control continues to be the most effective way to decrease the risk or slow the progression of diabetic retinopathy.
=== Digital Tools ===
==== Electronic Health Records ====
Sharing their electronic health records with people who have T2D helps them to reduce their blood sugar levels. It is a way of helping people understand their own health condition and involving them actively in its management.
==== m-health Monitoring Applications ====
The widespread use of smartphones has turned mobile applications (apps) into a popular means of the usage of all forms of software. The number of health-related apps accessible in the App Store and Google Play is approximately 100,000, and among these apps, the ones related to diabetes are the highest in number. Conducting regular self-management tasks such as medication and insulin intake, blood sugar checkup, diet observance, and physical exercise are really demanding. This is why the use of diabetes-related apps for the purposes of recording diet and medication intake or blood glucose level is promising to improve the health condition for diabetic people.
== Complexities ==
The main complexities stem from the nature of the feedback loop of glucose in the blood stream.
The glucose cycle is a system which is affected by two factors: entry of glucose into the bloodstream and also blood levels of insulin to control its transport out of the bloodstream
As a system, it is sensitive to diet and exercise
It is affected by the need for patient anticipation due to the complicating effects of time delays between any activity and the respective impact on the glucose
Management is highly intrusive, and compliance is an issue, since it relies upon user lifestyle change and often upon regular sampling and measuring of blood glucose levels, multiple times a day in many cases
It changes as people grow and develop
It is highly individual
As diabetes is a prime risk factor for cardiovascular disease, controlling other risk factors which may give rise to secondary conditions, as well as the diabetes itself, is one of the facets of diabetes management. Checking cholesterol, LDL, HDL and triglyceride levels may indicate hyperlipoproteinemia, which may warrant treatment with hypolipidemic drugs. Checking the blood pressure and keeping it within strict limits (using diet and antihypertensive treatment) protects against the retinal, renal and cardiovascular complications of diabetes. Regular follow-up by a podiatrist or other foot health specialists is encouraged to prevent the development of diabetic foot. Annual eye exams are suggested to monitor for progression of diabetic retinopathy.
=== Hypoglycemia ===
A level of <70 mg/dL (<3.8 mmol/L) is described as a hypoglycemic attack (low blood sugar). Most diabetics know when they are hypoglycemic and seek food or a sweet drink to raise their glucose levels. Intensive efforts to achieve blood sugar levels close to normal have been shown to triple the risk of the most severe form of hypoglycemia, in which the person requires assistance from by-standers in order to treat the episode. Among intensively controlled type 1 diabetics, 55% of episodes of severe hypoglycemia occur during sleep, and 6% of all deaths in diabetics under the age of 40 are from hypoglycemia at night.
Hypoglycemia can be problematic if it occurs while driving as it can affect a person's thinking process, coordination, and state of consciousness. Some people are more prone to hypoglycemia as they have reported fewer warning symptoms, and their body released less epinephrine (a hormone that helps raise blood glucose). Additionally, individuals with a history of hypoglycemia-related driving mishaps appear to use sugar at a faster rate.
Drivers with diabetes susceptible to driving mishaps should monitor their blood sugar to be not less than 70 mg/dL (3.9 mmol/L). Instead, these drivers are advised to treat hypoglycemia and delay driving until their blood glucose is above 90 mg/dL (5 mmol/L).
=== Hyperglycemia ===
A patient is considered to have hyperglycemia (high glucose) if the patient has a sugar level of greater than 230–270 mg/dL (13–15 mmol/L). Sometimes patient may be temporarily hypoglycemic under certain conditions (e.g. not eating regularly, or after strenuous exercise). Patients should closely monitor their sugar levels to ensure that they reduce rather than continue to remain high. High blood sugar levels are not as easy to detect as hypoglycemia and usually happens over a period of days rather than hours or minutes. If left untreated, this can result in diabetic coma and death.
Prolonged and elevated levels of glucose in the blood, which is left unchecked and untreated, will, over time, result in serious diabetic complications in those susceptible and sometimes even death. There is currently no way of testing for susceptibility to complications. Diabetics are therefore recommended to check their blood sugar levels either daily or every few days. There is also diabetes management software available from blood testing manufacturers which can display results and trends over time.
=== Medication nonadherence ===
Because many patients with diabetes have two or more comorbidities, they often require multiple medications. The prevalence of medication nonadherence is high among patients with chronic conditions, such as diabetes, and nonadherence is associated with public health issues and higher health care costs. One reason for nonadherence is the cost of medications. Being able to detect cost-related nonadherence is important for health care professionals, because this can lead to strategies to assist patients with problems paying for their medications. Some of these strategies are use of generic drugs or therapeutic alternatives, substituting a prescription drug with an over-the-counter medication, and pill-splitting. Interventions to improve adherence can achieve reductions in diabetes morbidity and mortality, as well as significant cost savings to the health care system. Smartphone apps have been found to improve self-management and health outcomes in people with diabetes through functions such as specific reminder alarms, while working with mental health professionals has also been found to help people with diabetes develop the skills to manage their medications and challenges of self-management effectively.
=== Psychological mechanisms and adherence ===
As self-management of diabetes typically involves lifestyle modifications, adherence may pose a significant self-management burden on many individuals. For example, individuals with diabetes may find themselves faced with the need to self-monitor their blood glucose levels, adhere to healthier diets and maintain exercise regimens regularly in order to maintain metabolic control and reduce the risk of developing cardiovascular problems. Barriers to adherence have been associated with key psychological mechanisms: knowledge of self-management, beliefs about the efficacy of treatment and self-efficacy/perceived control. Such mechanisms are inter-related, as one's thoughts (e.g. one's perception of diabetes, or one's appraisal of how helpful self-management is) is likely to relate to one's emotions (e.g. motivation to change), which in turn, affects one's self-efficacy (one's confidence in their ability to engage in a behaviour to achieve a desired outcome).
As diabetes management is affected by an individual's emotional and cognitive state, there has been evidence suggesting the self-management of diabetes is negatively affected by diabetes-related distress and depression. There is growing evidence that there is higher levels of clinical depression in patients with diabetes compared to the non-diabetic population. Depression in individuals with diabetes has been found to be associated with poorer self-management of symptoms. This suggests that it may be important to target mood in treatment. In the case of children and young people, especially if they are socially disadvantaged, research suggests that it is important that healthcare providers listen to and discuss their feelings and life situation to help them engage with diabetes services and self-management.
To this end, treatment programs such as the Cognitive Behavioural Therapy - Adherence and Depression program (CBT-AD) have been developed to target the psychological mechanisms underpinning adherence.
== See also ==
Ambulatory care sensitive conditions
Diabetes and exercise
Diabetic coma
Diabetic hypoglycemia
Diabetic Hypoglycemia (journal)
Glycemic efficacy
Latent autoimmune diabetes of adults
== References ==
== External links ==
American College of Physicians Diabetes Portal – Resources for patients and clinicians
American Diabetes Association
Prevent Diabetes Problems: Keep Your Diabetes Under Control Archived 2011-06-06 at the Wayback Machine – Self-care tips at the United States "National Diabetes Information Clearinghouse" | Wikipedia/Glycemic_control |
In molecular biology, protein catabolism is the breakdown of proteins into smaller peptides and ultimately into amino acids. Protein catabolism is a key function of digestion process. Protein catabolism often begins with pepsin, which converts proteins into polypeptides. These polypeptides are then further degraded. In humans, the pancreatic proteases include trypsin, chymotrypsin, and other enzymes. In the intestine, the small peptides are broken down into amino acids that can be absorbed into the bloodstream. These absorbed amino acids can then undergo amino acid catabolism, where they are utilized as an energy source or as precursors to new proteins.
The amino acids produced by catabolism may be directly recycled to form new proteins, converted into different amino acids, or can undergo amino acid catabolism to be converted to other compounds via the Krebs cycle.
== Interface with other metabolic and salvage pathways ==
Protein catabolism produces amino acids that are used to form other proteins or oxidized to meet the energy needs of the cell. The amino acids that are produced by protein catabolism can then be further catabolized in amino acid catabolism. Among the several degradative processes for amino acids are Deamination (removal of an amino group), transamination (transfer of amino group), decarboxylation (removal of carboxyl group), and dehydrogenation (removal of hydrogen). Degradation of amino acids can function as part of a salvage pathway, whereby parts of degraded amino acids are used to create new amino acids, or as part of a metabolic pathway whereby the amino acid is broken down to release or recapture chemical energy. For example, the chemical energy that is released by oxidization in a dehydrogenation reaction can be used to reduce NAD+ to NADH, which can then be fed directly into the Krebs/Citric Acid (TCA) Cycle.
== Protein degradation ==
Protein degradation differs from protein catabolism. Proteins are produced and destroyed routinely as part of the normal operations of the cell. Transcription factors, proteins that help regulate protein synthesis, are targets of such degradations. Their degradation is not a significant contributor to the energy needs of the cell. The addition of ubiquitin (ubiquitylation) marks a protein for degradation via the proteasome.
== Amino acid degradation ==
Oxidative deamination is the first step to breaking down the amino acids so that they can be converted to sugars. The process begins by removing the amino group of the amino acids. The amino group becomes ammonium as it is lost and later undergoes the urea cycle to become urea, in the liver. It is then released into the blood stream, where it is transferred to the kidneys, which will secrete the urea as urine. The remaining portion of the amino acid becomes oxidized, resulting in an α-keto acid. The alpha-keto acid will then proceed into the TCA cycle, in order to produce energy. The acid can also enter glycolysis, where it will be eventually converted into pyruvate. The pyruvate is then converted into acetyl-CoA so that it can enter the TCA cycle and convert the original pyruvate molecules into ATP, or usable energy for the organism.
Transamination leads to the same result as deamination: the remaining acid will undergo either glycolysis or the TCA cycle to produce energy that the organism's body will use for various purposes. This process transfers the amino group instead of losing the amino group to be converted into ammonium. The amino group is transferred to α-ketoglutarate, so that it can be converted to glutamate. Then glutamate transfers the amino group to oxaloacetate. This transfer is so that the oxaloacetate can be converted to aspartate or other amino acids. Eventually, this product will also proceed into oxidative deamination to once again produce alpha-ketoglutarate, an alpha-keto acid that will undergo the TCA cycle, and ammonium, which will eventually undergo the urea cycle.
Transaminases are enzymes that help catalyze the reactions that take place in transamination. They help catalyze the reaction at the point when the amino group is transferred from the original amino acid, like glutamate to α-ketoglutarate, and hold onto it to transfer it to another α-ketoacid.
== Factors determining protein half-life ==
Some key factors that determine overall rate include protein half-life, pH, and temperature.
Protein half-life helps determine the overall rate as this designates the first step in protein catabolism. Depending on whether this step is short or long will influence the rest of the metabolic process. One key component in determining the protein half-life is based on the N-end rule. This states that the amino acid present at the N-terminus of a protein helps determine the protein's half-life.
== Further reading ==
Bojkowska, Karolina; Santoni de Sio, Francesca; Barde, Isabelle; Offner, Sandra; Verp, Sonia; Heinis, Christian; Johnsson, Kai; Trono, Didier (2011-06-24). "Measuring In Vivo Protein Half-Life". Chemistry & Biology. 18 (6): 805–815. doi:10.1016/j.chembiol.2011.03.014. PMID 21700215.
== See also ==
Amino acid synthesis
Anabolism
Metabolism
Proteolysis
== References == | Wikipedia/Protein_catabolism |
The Consortium for Functional Glycomics (CFG) is a large research initiative funded in 2001 by a glue grant from the National Institute of General Medical Sciences (NIGMS) to “define paradigms by which protein-carbohydrate interactions mediate cell communication”. To achieve this goal, the CFG studies the functions of:
the three major classes of mammalian glycan-binding proteins (GBPs): C-type lectin, galectin, and SIGLEC
immune receptors that bind carbohydrates: CD1, T cell receptor, and anti-carbohydrate antibodies
GBPs of microorganisms that bind to host cell glycans as receptors.
The CFG comprises eight core facilities and 500+ participating investigators that work together to develop resources and services and make them available to the scientific community free of charge. The data generated by these resources are captured in databases accessible through the Functional Glycomics Gateway, a web resource maintained through a partnership between the CFG and Nature Publishing Group.
== Organization ==
The CFG is composed of three main components: the participating investigators, the cores, and the steering committee.
=== Participating investigators ===
Progress towards the CFG's overall goal is driven by the research of more than 500 participating investigators] (PIs) around the world, whose laboratories utilize resources, services, and data produced by the CFG scientific cores.
The PIs are the largest component of the program, continuing to grow with new members each year. Each PI also has a program of research within the scope of the CFG, supported by non-CFG funds. Investigators apply for membership and must have a funded grant within the scope of the CFG, but they are not required to join the CFG to access resources. Several PIs also have CFG-funded bridging grants that are primarily tied to and enable the goals of the scientific cores, for the benefit of all PIs.
The PIs are organized into 10 subgroups led by subgroup leaders:
Microorganism recognition of host glycans
Immune recognition of glycans
Glycans in immune cell communication
Glycans in development and physiology
Glycans in cancer biology
Glycans in protein conformation and function
Analytical glycomics
Chemical synthesis and glycan microarrays
3-D Structural glycobiology
Bioinformatics
The subgroups hold at least three workshops per year, where they have formed several working groups to leverage CFG funding in their efforts to define GBP biology. PI contributions toward elucidating paradigms that define GBP function are captured in the CFG's databases, as well as research publications and review articles.
=== Cores ===
The majority of CFG funds are invested in the scientific cores, which are responsible for generating novel resources, new technologies, and a platform of information that investigators use in their research. The eight CFG cores are described below:
Administrative Core (A), located at The Scripps Research Institute, supports the CFG steering committee, cores, and participating investigators, plans meetings and workshops, publishes a quarterly newsletter, facilitates resource requests, tracks CFG-related publications, and writes progress reports to NIGMS. Core A also works closely with Core B to update and develop new content for the Functional Glycomics Gateway site.
Bioinformatics Core (B), located at the Massachusetts Institute of Technology, is responsible for acquiring, storing, and disseminating all CFG-related data and information. For this purpose, Core B works with Nature Publishing Group to develop the CFG's Functional Glycomics Gateway site. Here, Core B has constructed complex relational databases to integrate diverse data sets generated by the CFG scientific cores and participating investigators, as well as data sets from other public databases. To increase the usability of these databases, Core B collaborates with the scientific cores to develop bioinformatics tools for data mining and prediction
Analytical Glycotechnology Core (C), located at Imperial College London, offers mass spectrometry profiling of protein N- and O-linked glycans from mammalian cells, with highest priority given to pure populations of human or murine immune cells.
Glycan Array Synthesis Core (D), located at The Scripps Research Institute, produces and collects carbohydrate compounds (monosaccharides, disaccharides, etc.), glycan-binding proteins, and anti-glycan antibodies for distribution to investigators. Many of these reagents were generously contributed by participating investigators. Core D also synthesizes glycans for and prints the CFG glycan array (see Core H below)
Gene Microarray Core (E), located at The Scripps Research Institute, screens RNA samples provided by investigators on a custom-designed glycogene chip array developed using Affymetrix technology. The chip contains probe sets designed to monitor the expression of approximately 2000 human and mouse genes, including glycosyltransferases, glycan-binding proteins, glycan degradation proteins, intercellular protein transport proteins, sugar transporters, adhesion molecules, interleukins, mucins, growth factors, cytokines, chemokines, and more.
Mouse Transgenics Core (F), formerly located at The Scripps Research Institute, is now closed. From 2001 to 2009, Core F generated 26 total and conditional knockout mouse lines deficient in glycan-binding proteins or glycosyltransferases. All Core F strains are now archived at the Mutant Mouse Regional Resource Center (MMRRC) at the University of California, Davis or The Jackson Laboratory (Jax). As a service to the community, the CFG still maintains a site in the Functional Glycomics Gateway to help investigators locate potential sources of glycogene knockout mouse lines.
Mouse Phenotype Core (G), located at the Sanford-Burnham Medical Research Institute, works with participating investigator “mentors” to assess the histology, hematology, metabolism, immunological function, and behavior of Core F-generated mouse lines in order to describe the phenotypic results of deleting one or more glycogenes. At the discretion of the Mouse Subcommittee, Core G also occasionally evaluates mouse lines provided by investigators.
Protein-Glycan Interaction Core (H), located at Emory University, analyzes investigator-generated lectins, antibodies, antisera, microorganisms, or suspected glycan-binding proteins of human, animal, and microbial origins on a mammalian glycan array to determine carbohydrate specificity and identify specific ligands. The current version of the array (v4.1), developed and printed by Core D, contains 465 different glycans.
=== Steering Committee ===
The CFG is managed by a steering committee chaired by James C. Paulson, Ph.D., professor at The Scripps Research Institute and Principal Investigator of the CFG glue grant. Eleven additional glycomics experts and one NIGMS scientific officer make up the rest of the committee.
Five subcommittees oversee the cores and make recommendations to the steering committee regarding resource priorities and technology development: Bioinformatics Subcommittee, Glycan Array/Carbohydrate Library Subcommittee, Glycan Analysis Subcommittee, Mouse Subcommittee, and Nomenclature Subcommittee.
== Resources ==
The CFG resources and services described above are free for the use of investigators studying the complex biology that governs the interactions of glycan-binding proteins and their ligands in mediating cell communication.
Resources can be requested by submitting a form at the Functional Glycomics Gateway website. Once a request is received, the appropriate core director reviews it and contacts the investigator if more information is needed. Once the core director finalizes a request and determines whether or not the core is capable of fulfilling it, the CFG Steering Committee reviews the request for final approval.
Membership in the CFG is not a requirement for receiving resources, but an investigator's institution must endorse the CFG's data sharing agreement to complete the resource request process.
== Databases ==
Data obtained by CFG scientific cores with samples submitted by PIs, and data obtained by investigators in their own labs using CFG resources, are uploaded into the CFG databases for dissemination to investigators and to the scientific community. Specialty databases for GBPs, glycan structures, and glycosyltransferases are designed to help integrate data and assess progress against the overall goal.
The easiest way to search through all CFG-related information is to enter a keyword (e.g. “galectin-1”, “sialic acid”, etc.) or IUPAC carbohydrate nomenclature in the search box at the top of the Functional Glycomics Gateway.
== Funding ==
In 2001, the CFG was awarded a five-year, $34 million glue grant] from NIGMS. In 2006, the CFG glue grant was renewed for another five years with an additional $40.7 million. Glue grant funding ended August 31, 2011. The CFG is seeking alternate funding to continue many aspects of the CFG beyond the glue grant funding period.
== References == | Wikipedia/Consortium_for_Functional_Glycomics |
Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. Secreted extracellular proteins are often glycosylated.
In proteins that have segments extending extracellularly, the extracellular segments are also often glycosylated. Glycoproteins are also often important integral membrane proteins, where they play a role in cell–cell interactions. It is important to distinguish endoplasmic reticulum-based glycosylation of the secretory system from reversible cytosolic-nuclear glycosylation. Glycoproteins of the cytosol and nucleus can be modified through the reversible addition of a single GlcNAc residue that is considered reciprocal to phosphorylation and the functions of these are likely to be an additional regulatory mechanism that controls phosphorylation-based signalling. In contrast, classical secretory glycosylation can be structurally essential. For example, inhibition of asparagine-linked, i.e. N-linked, glycosylation can prevent proper glycoprotein folding and full inhibition can be toxic to an individual cell. In contrast, perturbation of glycan processing (enzymatic removal/addition of carbohydrate residues to the glycan), which occurs in both the endoplasmic reticulum and Golgi apparatus, is dispensable for isolated cells (as evidenced by survival with glycosides inhibitors) but can lead to human disease (congenital disorders of glycosylation) and can be lethal in animal models. It is therefore likely that the fine processing of glycans is important for endogenous functionality, such as cell trafficking, but that this is likely to have been secondary to its role in host-pathogen interactions. A famous example of this latter effect is the ABO blood group system.
Though there are different types of glycoproteins, the most common are N-linked and O-linked glycoproteins. These two types of glycoproteins are distinguished by structural differences that give them their names. Glycoproteins vary greatly in composition, making many different compounds such as antibodies or hormones. Due to the wide array of functions within the body, interest in glycoprotein synthesis for medical use has increased. There are now several methods to synthesize glycoproteins, including recombination and glycosylation of proteins.
Glycosylation is also known to occur on nucleo cytoplasmic proteins in the form of O-GlcNAc.
== Types of glycosylation ==
There are several types of glycosylation, although the first two are the most common.
In N-glycosylation, sugars are attached to nitrogen, typically on the amide side-chain of asparagine.
In O-glycosylation, sugars are attached to oxygen, typically on serine or threonine, but also on tyrosine or non-canonical amino acids such as hydroxylysine and hydroxyproline.
In P-glycosylation, sugars are attached to phosphorus on a phosphoserine.
In C-glycosylation, sugars are attached directly to carbon, such as in the addition of mannose to tryptophan.
In S-glycosylation, a beta-GlcNAc is attached to the sulfur atom of a cysteine residue.
In glypiation, a GPI glycolipid is attached to the C-terminus of a polypeptide, serving as a membrane anchor.
In glycation, also known as non-enzymatic glycosylation, sugars are covalently bonded to a protein or lipid molecule, without the controlling action of an enzyme, but through a Maillard reaction.
== Monosaccharides ==
Monosaccharides commonly found in eukaryotic glycoproteins include:: 526
The sugar group(s) can assist in protein folding, improve proteins' stability and are involved in cell signalling.
== Structure ==
The critical structural element of all glycoproteins is having oligosaccharides bonded covalently to a protein. There are 10 common monosaccharides in mammalian glycans including: glucose (Glc), fucose (Fuc), xylose (Xyl), mannose (Man), galactose (Gal), N-acetylglucosamine (GlcNAc), glucuronic acid (GlcA), iduronic acid (IdoA), N-acetylgalactosamine (GalNAc), sialic acid, and 5-N-acetylneuraminic acid (Neu5Ac). These glycans link themselves to specific areas of the protein amino acid chain.
The two most common linkages in glycoproteins are N-linked and O-linked glycoproteins. An N-linked glycoprotein has glycan bonds to the nitrogen containing an asparagine amino acid within the protein sequence. An O-linked glycoprotein has the sugar is bonded to an oxygen atom of a serine or threonine amino acid in the protein.
Glycoprotein size and composition can vary largely, with carbohydrate composition ranges from 1% to 70% of the total mass of the glycoprotein. Within the cell, they appear in the blood, the extracellular matrix, or on the outer surface of the plasma membrane, and make up a large portion of the proteins secreted by eukaryotic cells. They are very broad in their applications and can function as a variety of chemicals from antibodies to hormones.
=== Glycomics ===
Glycomics is the study of the carbohydrate components of cells. Though not exclusive to glycoproteins, it can reveal more information about different glycoproteins and their structure. One of the purposes of this field of study is to determine which proteins are glycosylated and where in the amino acid sequence the glycosylation occurs. Historically, mass spectrometry has been used to identify the structure of glycoproteins and characterize the carbohydrate chains attached.
== Examples ==
The unique interaction between the oligosaccharide chains have different applications. First, it aids in quality control by identifying misfolded proteins. The oligosaccharide chains also change the solubility and polarity of the proteins that they are bonded to. For example, if the oligosaccharide chains are negatively charged, with enough density around the protein, they can repulse proteolytic enzymes away from the bonded protein. The diversity in interactions lends itself to different types of glycoproteins with different structures and functions.
One example of glycoproteins found in the body is mucins, which are secreted in the mucus of the respiratory and digestive tracts. The sugars when attached to mucins give them considerable water-holding capacity and also make them resistant to proteolysis by digestive enzymes.
Glycoproteins are important for white blood cell recognition. Examples of glycoproteins in the immune system are:
molecules such as antibodies (immunoglobulins), which interact directly with antigens.
molecules of the major histocompatibility complex (or MHC), which are expressed on the surface of cells and interact with T cells as part of the adaptive immune response.
sialyl Lewis X antigen on the surface of leukocytes.
H antigen of the ABO blood compatibility antigens.
Other examples of glycoproteins include:
gonadotropins (luteinizing hormone and follicle-stimulating hormone)
glycoprotein IIb/IIIa, an integrin found on platelets that is required for normal platelet aggregation and adherence to the endothelium.
components of the zona pellucida, which surrounds the oocyte, and is important for sperm-egg interaction.
structural glycoproteins, which occur in connective tissue. These help bind together the fibers, cells, and ground substance of connective tissue. They may also help components of the tissue bind to inorganic substances, such as calcium in bone.
Glycoprotein-41 (gp41) and glycoprotein-120 (gp120) are HIV viral coat proteins.
Soluble glycoproteins often show a high viscosity, for example, in egg white and blood plasma.
Miraculin, is a glycoprotein extracted from Synsepalum dulcificum a berry which alters human tongue receptors to recognize sour foods as sweet.
Variable surface glycoproteins allow the sleeping sickness Trypanosoma parasite to escape the immune response of the host.
The viral spike of the human immunodeficiency virus is heavily glycosylated. Approximately half the mass of the spike is glycosylation and the glycans act to limit antibody recognition as the glycans are assembled by the host cell and so are largely 'self'. Over time, some patients can evolve antibodies to recognise the HIV glycans and almost all so-called 'broadly neutralising antibodies (bnAbs) recognise some glycans. This is possible mainly because the unusually high density of glycans hinders normal glycan maturation and they are therefore trapped in the premature, high-mannose, state. This provides a window for immune recognition. In addition, as these glycans are much less variable than the underlying protein, they have emerged as promising targets for vaccine design.
P-glycoproteins are critical for antitumor research due to its ability block the effects of antitumor drugs. P-glycoprotein, or multidrug transporter (MDR1), is a type of ABC transporter that transports compounds out of cells. This transportation of compounds out of cells includes drugs made to be delivered to the cell, causing a decrease in drug effectiveness. Therefore, being able to inhibit this behavior would decrease P-glycoprotein interference in drug delivery, making this an important topic in drug discovery. For example, P-Glycoprotein causes a decrease in anti-cancer drug accumulation within tumor cells, limiting the effectiveness of chemotherapies used to treat cancer.
== Hormones ==
Hormones that are glycoproteins include:
Follicle-stimulating hormone
Luteinizing hormone
Thyroid-stimulating hormone
Human chorionic gonadotropin
Alpha-fetoprotein
Erythropoietin (EPO)
== Distinction between glycoproteins and proteoglycans ==
== Functions ==
== Analysis ==
A variety of methods used in detection, purification, and structural analysis of glycoproteins are: 525
== Synthesis ==
The glycosylation of proteins has an array of different applications from influencing cell to cell communication to changing the thermal stability and the folding of proteins. Due to the unique abilities of glycoproteins, they can be used in many therapies. By understanding glycoproteins and their synthesis, they can be made to treat cancer, Crohn's Disease, high cholesterol, and more.
The process of glycosylation (binding a carbohydrate to a protein) is a post-translational modification, meaning it happens after the production of the protein. Glycosylation is a process that roughly half of all human proteins undergo and heavily influences the properties and functions of the protein. Within the cell, glycosylation occurs in the endoplasmic reticulum.
=== Recombination ===
There are several techniques for the assembly of glycoproteins. One technique utilizes recombination. The first consideration for this method is the choice of host, as there are many different factors that can influence the success of glycoprotein recombination such as cost, the host environment, the efficacy of the process, and other considerations. Some examples of host cells include E. coli, yeast, plant cells, insect cells, and mammalian cells. Of these options, mammalian cells are the most common because their use does not face the same challenges that other host cells do such as different glycan structures, shorter half life, and potential unwanted immune responses in humans. Of mammalian cells, the most common cell line used for recombinant glycoprotein production is the Chinese hamster ovary line. However, as technologies develop, the most promising cell lines for recombinant glycoprotein production are human cell lines.
=== Glycosylation ===
The formation of the link between the glycan and the protein is key element of the synthesis of glycoproteins. The most common method of glycosylation of N-linked glycoproteins is through the reaction between a protected glycan and a protected Asparagine. Similarly, an O-linked glycoprotein can be formed through the addition of a glycosyl donor with a protected Serine or Threonine. These two methods are examples of natural linkage. However, there are also methods of unnatural linkages. Some methods include ligation and a reaction between a serine-derived sulfamidate and thiohexoses in water. Once this linkage is complete, the amino acid sequence can be expanded upon using solid-phase peptide synthesis.
== See also ==
== Notes and references ==
== Further reading ==
== External links ==
Glycoproteins at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
"Biological Importance of the glycosylation of a protein". BiochemPages. 15 August 2015. Archived from the original on 30 November 2020. Retrieved 18 August 2015.
"Carbohydrate Chemistry and Glycobiology: A Web Tour". Science. 291 (5512): 2263–2502. 23 March 2001. Archived from the original on 9 January 2008. Special Web Supplement
"Glycan Recognizing Proteins". bioWORLD.
"Structure of Glycoprotein and Carbohydrate Chain". Home Page for Learning Environmental Chemistry. | Wikipedia/Glycoprotein |
In carbohydrate chemistry, the Lobry de Bruyn–Van Ekenstein transformation also known as the Lobry de Bruyn–Alberda van Ekenstein transformation is the base or acid catalyzed transformation of an aldose into the ketose isomer or vice versa, with a tautomeric enediol as reaction intermediate. Ketoses may be transformed into 3-ketoses, etcetera. The enediol is also an intermediate for the epimerization of an aldose or ketose.
The reactions are usually base catalyzed, but can also take place under acid or neutral conditions. A typical rearrangement reaction is that between the aldose glyceraldehyde and the ketose dihydroxyacetone in a chemical equilibrium.
The Lobry de Bruyn–Van Ekenstein transformation is relevant for the industrial production of certain ketoses and was discovered in 1885 by Cornelis Adriaan Lobry van Troostenburg de Bruyn and Willem Alberda van Ekenstein.
== Aldose-ketose transformation ==
The following scheme describes the interconversion between an aldose and a ketose, where R is any organic residue.
The equilibrium or the reactant to product ratio depends on concentration, solvent, pH and temperature. At equilibrium the aldose and ketose form a mixture which in the case of the glyceraldehyde and dihydroxyacetone is also called glycerose.
A related reaction is the alpha-ketol rearrangement.
== Epimerization ==
The carbon atom at which the initial deprotonation takes place is a stereocenter. If, for example, D-glucose (an Aldose) rearranges to D-fructose, the ketose, the stereochemical configuration is lost in the enol form. In the chemical reaction the enol can be protonated from two faces, resulting in the backformation of glucose or the formation of the epimer D-mannose. The final product is a mix of D-glucose, D-fructose and D-mannose.
== References == | Wikipedia/Lobry_de_Bruyn–Van_Ekenstein_transformation |
A biomolecule or biological molecule is loosely defined as a molecule produced by a living organism and essential to one or more typically biological processes. Biomolecules include large macromolecules such as proteins, carbohydrates, lipids, and nucleic acids, as well as small molecules such as vitamins and hormones. A general name for this class of material is biological materials. Biomolecules are an important element of living organisms. They are often endogenous, i.e. produced within the organism, but organisms usually also need exogenous biomolecules, for example certain nutrients, to survive.
Biomolecules and their reactions are studied in biology and its subfields of biochemistry and molecular biology. Most biomolecules are organic compounds, and just four elements—oxygen, carbon, hydrogen, and nitrogen—make up 96% of the human body's mass. But many other elements, such as the various biometals, are also present in small amounts.
The uniformity of both specific types of molecules (the biomolecules) and of certain metabolic pathways are invariant features among the wide diversity of life forms; thus these biomolecules and metabolic pathways are referred to as "biochemical universals" or "theory of material unity of the living beings", a unifying concept in biology, along with cell theory and evolution theory.
== Types of biomolecules ==
A diverse range of biomolecules exist, including:
Small molecules:
Lipids, fatty acids, glycolipids, sterols, monosaccharides
Vitamins
Hormones, neurotransmitters
Metabolites
Monomers, oligomers and polymers:
== Nucleosides and nucleotides ==
Nucleosides are molecules formed by attaching a nucleobase to a ribose or deoxyribose ring. Examples of these include cytidine (C), uridine (U), adenosine (A), guanosine (G), and thymidine (T).
Nucleosides can be phosphorylated by specific kinases in the cell, producing nucleotides.
Both DNA and RNA are polymers, consisting of long, linear molecules assembled by polymerase enzymes from repeating structural units, or monomers, of mononucleotides. DNA uses the deoxynucleotides C, G, A, and T, while RNA uses the ribonucleotides (which have an extra hydroxyl(OH) group on the pentose ring) C, G, A, and U. Modified bases are fairly common (such as with methyl groups on the base ring), as found in ribosomal RNA or transfer RNAs or for discriminating the new from old strands of DNA after replication.
Each nucleotide is made of an acyclic nitrogenous base, a pentose and one to three phosphate groups. They contain carbon, nitrogen, oxygen, hydrogen and phosphorus. They serve as sources of chemical energy (adenosine triphosphate and guanosine triphosphate), participate in cellular signaling (cyclic guanosine monophosphate and cyclic adenosine monophosphate), and are incorporated into important cofactors of enzymatic reactions (coenzyme A, flavin adenine dinucleotide, flavin mononucleotide, and nicotinamide adenine dinucleotide phosphate).
=== DNA and RNA structure ===
DNA structure is dominated by the well-known double helix formed by Watson-Crick base-pairing of C with G and A with T. This is known as B-form DNA, and is overwhelmingly the most favorable and common state of DNA; its highly specific and stable base-pairing is the basis of reliable genetic information storage. DNA can sometimes occur as single strands (often needing to be stabilized by single-strand binding proteins) or as A-form or Z-form helices, and occasionally in more complex 3D structures such as the crossover at Holliday junctions during DNA replication.
RNA, in contrast, forms large and complex 3D tertiary structures reminiscent of proteins, as well as the loose single strands with locally folded regions that constitute messenger RNA molecules. Those RNA structures contain many stretches of A-form double helix, connected into definite 3D arrangements by single-stranded loops, bulges, and junctions. Examples are tRNA, ribosomes, ribozymes, and riboswitches. These complex structures are facilitated by the fact that RNA backbone has less local flexibility than DNA but a large set of distinct conformations, apparently because of both positive and negative interactions of the extra OH on the ribose. Structured RNA molecules can do highly specific binding of other molecules and can themselves be recognized specifically; in addition, they can perform enzymatic catalysis (when they are known as "ribozymes", as initially discovered by Tom Cech and colleagues).
== Saccharides ==
Monosaccharides are the simplest form of carbohydrates with only one simple sugar. They essentially contain an aldehyde or ketone group in their structure. The presence of an aldehyde group in a monosaccharide is indicated by the prefix aldo-. Similarly, a ketone group is denoted by the prefix keto-. Examples of monosaccharides are the hexoses, glucose, fructose, Trioses, Tetroses, Heptoses, galactose, pentoses, ribose, and deoxyribose. Consumed fructose and glucose have different rates of gastric emptying, are differentially absorbed and have different metabolic fates, providing multiple opportunities for two different saccharides to differentially affect food intake. Most saccharides eventually provide fuel for cellular respiration.
Disaccharides are formed when two monosaccharides, or two single simple sugars, form a bond with removal of water. They can be hydrolyzed to yield their saccharin building blocks by boiling with dilute acid or reacting them with appropriate enzymes. Examples of disaccharides include sucrose, maltose, and lactose.
Polysaccharides are polymerized monosaccharides, or complex carbohydrates. They have multiple simple sugars. Examples are starch, cellulose, and glycogen. They are generally large and often have a complex branched connectivity. Because of their size, polysaccharides are not water-soluble, but their many hydroxy groups become hydrated individually when exposed to water, and some polysaccharides form thick colloidal dispersions when heated in water. Shorter polysaccharides, with 3 to 10 monomers, are called oligosaccharides.
A fluorescent indicator-displacement molecular imprinting sensor was developed for discriminating saccharides. It successfully discriminated three brands of orange juice beverage. The change in fluorescence intensity of the sensing films resulting is directly related to the saccharide concentration.
== Lignin ==
Lignin is a complex polyphenolic macromolecule composed mainly of beta-O4-aryl linkages. After cellulose, lignin is the second most abundant biopolymer and is one of the primary structural components of most plants. It contains subunits derived from p-coumaryl alcohol, coniferyl alcohol, and sinapyl alcohol, and is unusual among biomolecules in that it is racemic. The lack of optical activity is due to the polymerization of lignin which occurs via free radical coupling reactions in which there is no preference for either configuration at a chiral center.
== Lipid ==
Lipids (oleaginous) are chiefly fatty acid esters, and are the basic building blocks of biological membranes. Another biological role is energy storage (e.g., triglycerides). Most lipids consist of a polar or hydrophilic head (typically glycerol) and one to three non polar or hydrophobic fatty acid tails, and therefore they are amphiphilic. Fatty acids consist of unbranched chains of carbon atoms that are connected by single bonds alone (saturated fatty acids) or by both single and double bonds (unsaturated fatty acids). The chains are usually 14–24 carbon groups long, but it is always an even number.
For lipids present in biological membranes, the hydrophilic head is from one of three classes:
Glycolipids, whose heads contain an oligosaccharide with 1-15 saccharide residues.
Phospholipids, whose heads contain a positively charged group that is linked to the tail by a negatively charged phosphate group.
Sterols, whose heads contain a planar steroid ring, for example, cholesterol.
Other lipids include prostaglandins and leukotrienes which are both 20-carbon fatty acyl units synthesized from arachidonic acid.
They are also known as fatty acids
== Amino acids ==
Amino acids contain both amino and carboxylic acid functional groups. (In biochemistry, the term amino acid is used when referring to those amino acids in which the amino and carboxylate functionalities are attached to the same carbon, plus proline which is not actually an amino acid).
Modified amino acids are sometimes observed in proteins; this is usually the result of enzymatic modification after translation (protein synthesis). For example, phosphorylation of serine by kinases and dephosphorylation by phosphatases is an important control mechanism in the cell cycle. Only two amino acids other than the standard twenty are known to be incorporated into proteins during translation, in certain organisms:
Selenocysteine is incorporated into some proteins at a UGA codon, which is normally a stop codon.
Pyrrolysine is incorporated into some proteins at a UAG codon. For instance, in some methanogens in enzymes that are used to produce methane.
Besides those used in protein synthesis, other biologically important amino acids include carnitine (used in lipid transport within a cell), ornithine, GABA and taurine.
=== Protein structure ===
The particular series of amino acids that form a protein is known as that protein's primary structure. This sequence is determined by the genetic makeup of the individual. It specifies the order of side-chain groups along the linear polypeptide "backbone".
Proteins have two types of well-classified, frequently occurring elements of local structure defined by a particular pattern of hydrogen bonds along the backbone: alpha helix and beta sheet. Their number and arrangement is called the secondary structure of the protein. Alpha helices are regular spirals stabilized by hydrogen bonds between the backbone CO group (carbonyl) of one amino acid residue and the backbone NH group (amide) of the i+4 residue. The spiral has about 3.6 amino acids per turn, and the amino acid side chains stick out from the cylinder of the helix. Beta pleated sheets are formed by backbone hydrogen bonds between individual beta strands each of which is in an "extended", or fully stretched-out, conformation. The strands may lie parallel or antiparallel to each other, and the side-chain direction alternates above and below the sheet. Hemoglobin contains only helices, natural silk is formed of beta pleated sheets, and many enzymes have a pattern of alternating helices and beta-strands. The secondary-structure elements are connected by "loop" or "coil" regions of non-repetitive conformation, which are sometimes quite mobile or disordered but usually adopt a well-defined, stable arrangement.
The overall, compact, 3D structure of a protein is termed its tertiary structure or its "fold". It is formed as result of various attractive forces like hydrogen bonding, disulfide bridges, hydrophobic interactions, hydrophilic interactions, van der Waals force etc.
When two or more polypeptide chains (either of identical or of different sequence) cluster to form a protein, quaternary structure of protein is formed. Quaternary structure is an attribute of polymeric (same-sequence chains) or heteromeric (different-sequence chains) proteins like hemoglobin, which consists of two "alpha" and two "beta" polypeptide chains.
==== Apoenzymes ====
An apoenzyme (or, generally, an apoprotein) is the protein without any small-molecule cofactors, substrates, or inhibitors bound. It is often important as an inactive storage, transport, or secretory form of a protein. This is required, for instance, to protect the secretory cell from the activity of that protein.
Apoenzymes become active enzymes on addition of a cofactor. Cofactors can be either inorganic (e.g., metal ions and iron-sulfur clusters) or organic compounds, (e.g., [Flavin group|flavin] and heme). Organic cofactors can be either prosthetic groups, which are tightly bound to an enzyme, or coenzymes, which are released from the enzyme's active site during the reaction.
==== Isoenzymes ====
Isoenzymes, or isozymes, are multiple forms of an enzyme, with slightly different protein sequence and closely similar but usually not identical functions. They are either products of different genes, or else different products of alternative splicing. They may either be produced in different organs or cell types to perform the same function, or several isoenzymes may be produced in the same cell type under differential regulation to suit the needs of changing development or environment. LDH (lactate dehydrogenase) has multiple isozymes, while fetal hemoglobin is an example of a developmentally regulated isoform of a non-enzymatic protein. The relative levels of isoenzymes in blood can be used to diagnose problems in the organ of secretion .
== See also ==
Biomolecular engineering
List of biomolecules
Metabolism
Multi-state modeling of biomolecules
== References ==
== External links ==
Society for Biomolecular Sciences provider of a forum for education and information exchange among professionals within drug discovery and related disciplines. | Wikipedia/Biomolecules |
Low-carbohydrate diets restrict carbohydrate consumption relative to the average diet. Foods high in carbohydrates (e.g., sugar, bread, pasta) are limited, and replaced with foods containing a higher percentage of fat and protein (e.g., meat, poultry, fish, shellfish, eggs, cheese, nuts, and seeds), as well as low carbohydrate foods (e.g. spinach, kale, chard, collards, and other fibrous vegetables).
There is a lack of standardization of how much carbohydrate low-carbohydrate diets must have, and this has complicated research. One definition, from the American Academy of Family Physicians, specifies low-carbohydrate diets as having less than 20% of calories from carbohydrates.
There is no good evidence that low-carbohydrate dieting confers any particular health benefits apart from weight loss, where low-carbohydrate diets achieve outcomes similar to other diets, as weight loss is mainly determined by calorie restriction and adherence.
One form of low-carbohydrate diet called the ketogenic diet was first established as a medical diet for treating epilepsy. It became a popular diet for weight loss through celebrity endorsement, but there is no evidence of any distinctive benefit for this purpose and the diet carries a risk of adverse effects, with the British Dietetic Association naming it one of the "top five worst celeb diets to avoid" in 2018.
== Definition and classification ==
=== Macronutrient ratios ===
The macronutrient ratios of low-carbohydrate diets are not standardized. As of 2018, the conflicting definitions of "low-carbohydrate" diets have complicated research into the subject.
The National Lipid Association Nutrition and Lifestyle Task Force define low-carbohydrate diets and those containing less than 25% of calories from carbohydrates, and very low carbohydrate diets being those containing less than 10% carbohydrates. A 2016 review of low-carbohydrate diets classified diets with 50 g of carbohydrate per day (less than 10% of total calories) as "very low" and diets with 40% of calories from carbohydrates as "mild" low-carbohydrate diets. The UK National Health Service recommend that "carbohydrates should be the body's main source of energy in a healthy, balanced diet."
=== Foodstuffs ===
There is evidence that the quality, rather than the quantity, of carbohydrate in a diet is important for health, and that high-fiber slow-digesting carbohydrate-rich foods are healthful while highly refined and sugary foods are less so. A diet chosen to address health concerns should be tailored to the individual's specific needs.
Most vegetables are low- or moderate-carbohydrate foods (in some low-carbohydrate diets, fiber is excluded because it is not a nutritive carbohydrate). Some vegetables, such as potatoes, carrots, maize (corn) and rice are high in starch. Most low-carbohydrate diet plans accommodate vegetables such as broccoli, spinach, kale, lettuce, cucumbers, cauliflower, Brussels sprouts, peppers and most green-leafy vegetables.
== Authority opinions ==
The National Academy of Medicine recommends a daily average of 130 g of carbohydrates per day. The FAO and WHO similarly recommend that the majority of dietary energy come from carbohydrates. Low-carbohydrate diets are not an option recommended in the 2015–2020 edition of Dietary Guidelines for Americans, which instead recommends a low-fat diet.
Carbohydrate has been wrongly accused of being a uniquely "fattening" macronutrient, misleading many dieters into compromising the nutritiousness of their diet by eliminating carbohydrate-rich food. Low-carbohydrate diet proponents emphasize research saying that low-carbohydrate diets can initially cause slightly greater weight loss than a balanced diet, but any such advantage does not persist. In the long-term successful weight maintenance is determined by calorie intake, and not by macronutrient ratios.
The public has become confused by the way in which some diets, such as the Zone diet and the South Beach diet are promoted as "low-carbohydrate" when in fact they would more properly be termed "medium-carbohydrate" diets.
=== Carbohydrate-insulin hypothesis ===
Low-carbohydrate diet advocates including Gary Taubes and David Ludwig have proposed a "carbohydrate-insulin hypothesis" in which carbohydrates are said to be uniquely fattening because they raise insulin levels and cause fat to accumulate unduly. The hypothesis appears to run counter to known human biology whereby there is no good evidence of any such association between the actions of insulin, fat accumulation, and obesity. The hypothesis predicted that low-carbohydrate dieting would offer a "metabolic advantage" of increased energy expenditure equivalent to 400–600 kcal(kilocalorie)/day, in accord with the promise of the Atkin's diet: a "high calorie way to stay thin forever".
With funding from the Laura and John Arnold Foundation, in 2012, Taubes co-founded the Nutrition Science Initiative (NuSI), with the aim of raising over $200 million to undertake a "Manhattan Project For Nutrition" and validate the hypothesis. Intermediate results, published in the American Journal of Clinical Nutrition did not provide convincing evidence of any advantage to a low-carbohydrate diet as compared to diets of other composition. This study revealed a marginal (~100 kcal/d) but statistically significant effect of the ketogenic diet to increase 24-hour energy expenditure measured in a respiratory chamber, but the effect waned over time. Ultimately a very low-calorie, ketogenic diet (of 5% carbohydrate) "was not associated with significant loss of fat mass" compared to a non-specialized diet with the same calories; there was no useful "metabolic advantage". In 2017, Kevin Hall, a National Institutes of Health researcher hired to assist with the project, wrote that the carbohydrate-insulin hypothesis had been falsified by experiment. Hall wrote "the rise in obesity prevalence may be primarily due to increased consumption of refined carbohydrates, but the mechanisms are likely to be quite different from those proposed by the carbohydrate–insulin model."
== Health aspects ==
=== Adherence ===
It has been repeatedly found that in the long-term, all diets with the same calorific value perform the same for weight loss, except for the one differentiating factor of how well people can faithfully follow the dietary programme. A study comparing groups taking low-fat, low-carbohydrate and Mediterranean diets found at six months the low-carbohydrate diet still had most people adhering to it, but thereafter the situation reversed: at two years the low-carbohydrate group had the highest incidence of lapses and dropouts. This may be due to the comparatively limited food choice of low-carbohydrate diets.
=== Body weight ===
In the short and medium term, people taking a low-carbohydrate diet can experience more weight loss than people taking a low-fat diet. The Endocrine Society stated that "when calorie intake is held constant ... body-fat accumulation does not appear to be affected by even very pronounced changes in the amount of fat vs. carbohydrate in the diet". People on such a diet have very slightly more weight loss initially, equivalent to approximately 100kcal/day, but that advantage diminishes over time and is ultimately insignificant. A Cochrane review from 2022 looked into longer periods of two years and found no benefit for adhering to a low-carbohydrate diet in comparison to balanced diets.
Much of the research comparing low-fat vs. low-carbohydrate dieting has been of poor quality and studies which reported large effects have garnered disproportionate attention in comparison to those which are methodologically sound. A 2018 review said "higher-quality meta-analyses reported little or no difference in weight loss between the two diets." Low-quality meta-analyses have tended to report favourably on the effect of low-carbohydrate diets: a systematic review reported that 8 out of 10 meta-analyses assessed whether weight loss outcomes could have been affected by publication bias, and 7 of them concluded positively. A 2017 review concluded that a variety of diets, including low-carbohydrate diets, achieve similar weight loss outcomes, which are mainly determined by calorie restriction and adherence rather than the type of diet.
=== Cardiovascular health ===
Eating a low-carbohydrate diet for less than two years was found to not worsen markers for cardiovascular health. However, following a low-carb diet for many years is associated with dying from heart disease. Low-carbohydrate diets in the long-term have detrimental effects on lipid parameters such as increase in total and LDL cholesterol. This is because most people on low-carbohydrate diets eat more animal source foods and less fruits and vegetables rich in fiber and micronutrients.
The American College of Cardiology recommends a clinician-patient discussion for people who want to go on a very low-carbohydrate diet. People on the diet should be informed that it may worsen LDL-C levels and cardiovascular health in the long-term. Those with atherosclerosis should be counseled to avoid low-carbohydrate diets.
=== Diabetes ===
There is limited evidence for the effectiveness of low-carbohydrate diets for people with type 1 diabetes. For certain individuals, it may be feasible to follow a low-carbohydrate regime combined with carefully managed insulin dosing. This can be hard to maintain and there are concerns about potential adverse health effects caused by the diet. In general, people with type 1 diabetes are advised to follow an individualized eating plan.
The proportion of carbohydrate in a diet is not linked to the risk of type 2 diabetes, although there is some evidence that diets containing certain high-carbohydrate items – such as sugar-sweetened drinks or white rice – are associated with an increased risk. Some evidence indicates that consuming fewer carbohydrate foods may reduce biomarkers of type 2 diabetes.
A 2019 consensus report on nutrition therapy for adults with diabetes and prediabetes the American Diabetes Association (ADA) states "Reducing overall carbohydrate intake for individuals with diabetes has demonstrated the most evidence for improving glycemia (blood sugar) and may be applied in a variety of eating patterns that meet individual needs and preferences." However, another source states that there is no good evidence that low-carbohydrate diets are better than a conventional healthy diet in which carbohydrates typically account for more than 40% of calories consumed. Low-carbohydrate dieting has no effect on the kidney function of people who have type 2 diabetes.
Limiting carbohydrate consumption generally results in improved glucose control, although without long-term weight loss. Low-carbohydrate diets can be useful to help people with type 2 diabetes lose weight, but "no single approach has been proven to be consistently superior." According to the ADA, people with diabetes should be "developing healthy eating patterns rather than focusing on individual macronutrients, micronutrients, or single foods." They recommended that the carbohydrates in a diet should come from "vegetables, legumes, fruits, dairy (milk and yogurt), and whole grains", while highly refined foods and sugary drinks should be avoided. For individuals with type 2 diabetes who can't meet the glycemic targets or where reducing anti-glycemic medications is a priority, the ADA says that low or very-low carbohydrate diets are a viable approach.
A 2021 umbrella review found that low-carbohydrate diets are no better for weight loss than higher-carbohydrate or low-fat diets in diabetic patients.
=== Exercise and fatigue ===
A low-carbohydrate diet has been found to reduce endurance capacity for intense exercise efforts, and depleted muscle glycogen following such efforts is only slowly replenished if a low-carbohydrate diet is taken. Inadequate carbohydrate intake during athletic training causes metabolic acidosis, which may be responsible for the impaired performance which has been observed.
=== Safety ===
A low-carbohydrate diet causes extensive metabolism of fatty acids, which are used by the liver to make ketone bodies, which provide energy to important organs, including the brain, heart, and kidneys, in a condition called ketosis. Ketosis can have other causes such as alcoholism and diabetes. Excessive accumulation of ketone bodies occurs when its production is greater than consumption, leading to ketoacidosis, a potentially life-threatening condition. Rarely, a low-carbohydrate ketogenic diet can also give rise to ketoacidosis, especially in patients with comorbid conditions. There are infrequent case reports of ketoacidosis occurring in people who follow low-carbohydrate diets such as the Atkins and South Beach diets. This has led to the suggestion that ketoacidosis should be considered a potential hazard of low-carbohydrate dieting.
High- and low-carbohydrate diets that are rich in animal-derived proteins and fats may be associated with increased mortality. Conversely, with plant-derived proteins and fats, there may be a decrease of mortality. A 2021 study from Japan looked at the long-term aspects of low-carb eating. The study included 90,171 participants with a median 17 years of follow-up. The study found that a high adherence to low-carb eating was associated with increased overall cancer risk. Looking at the diet composition the authors found that eating more animals foods was associated with an increased cancer risk while plant fat consumption was not.
As of 2018, research has paid insufficient attention to the potential adverse effects of carbohydrate restricted dieting, particularly for micronutrient sufficiency, bone health and cancer risk. One low-quality meta-analysis reported that adverse effects could include "constipation, headache, halitosis, muscle cramps and general weakness".
In a comprehensive systematic review of 2018, Churuangsuk and colleagues reported that other case reports give rise to concerns of other potential risks of low-carbohydrate dieting including hyperosmolar coma, Wernicke's encephalopathy, optic neuropathy from thiamine deficiency, acute coronary syndrome and anxiety disorder.
Significantly restricting the proportion of carbohydrate in diet risks causing malnutrition, and can make it difficult to get enough dietary fiber to stay healthy.
As of 2014, it appeared that with respect to the risk of death for people with cardiovascular disease, the kind of carbohydrates consumed are important; diets relatively higher in fiber and whole grains lead to reduced risk of death from cardiovascular disease compared to diets high in refined grains.
== History ==
=== First descriptions ===
In 1797, John Rollo reported on the results of treating two diabetic Army officers with a low-carbohydrate diet and medications. A very low-carbohydrate diet was the standard treatment for diabetes throughout the nineteenth century.
In 1825, Jean Brillat-Savarin promoted a low-carb diet in his book, The Physiology of Taste.
In 1863, William Banting, a formerly obese English undertaker and coffin maker, published "Letter on Corpulence Addressed to the Public", in which he described a diet for weight control giving up bread, butter, milk, sugar, beer, and potatoes. His booklet was widely read, so much so that some people used the term "Banting" for the activity now called "dieting".
Physicians who advocated a low-carbohydrate diet consisting of large amounts of animal fat and protein to treat diabetes in the late 1800s include James Lomax Bardsley, Apollinaire Bouchardat and Frederick William Pavy. Arnaldo Cantani isolated his diabetic patients in locked rooms and prescribed them an exclusive animal-based diet.
In the early 1900s Frederick Madison Allen developed a highly restrictive short term regime which was described by Walter R. Steiner at the 1916 annual convention of the Connecticut State Medical Society as The Starvation Treatment of Diabetes Mellitus.: 176–177 This diet was often administered in a hospital in order to better ensure compliance and safety.: 179
=== Modern low-carbohydrate diets ===
Other low-carbohydrate diets in the 1960s included the Air Force diet, "Martinis & Whipped Cream" in 1966, and the Drinking Man's Diet. In 1972, Robert Atkins published Dr. Atkins' Diet Revolution, which advocated the low-carbohydrate diet he had successfully used in treating people in the 1960s. The book was a publishing success, but was widely criticized by the mainstream medical community as being dangerous and misleading, thereby limiting its appeal at the time.
The concept of the glycemic index was developed in 1981 by David Jenkins to account for variances in speed of digestion of different types of carbohydrates. This concept classifies foods according to the rapidity of their effect on blood sugar levels – with fast-digesting simple carbohydrates causing a sharper increase and slower-digesting complex carbohydrates, such as whole grains, a slower one. Jenkins's research laid the scientific groundwork for subsequent low-carbohydrate diets.
In 1992, Atkins published an update from his 1972 book, Dr. Atkins' New Diet Revolution, and other doctors began to publish books based on the same principles. During the late 1990s and early 2000s, low-carbohydrate diets became some of the most popular diets in the US. By some accounts, up to 18% of the population was using one type of low-carbohydrate diet or another at the peak of their popularity. Food manufacturers and restaurant chains noted the trend, as it affected their businesses. Parts of the mainstream medical community have denounced low-carbohydrate diets as being dangerous to health, such as the AHA in 2001 and the American Kidney Fund in 2002.
==== Ketogenic diet ====
The original ketogenic diet is a high-fat, low-carbohydrate diet developed in the 1920s and used to treat drug-resistant childhood epilepsy. Most epilepsy specialists order these children to eat 80% of the diet from fat by weight (90% of calories), plus carbohydrate-free vitamins and minerals to prevent vitamin deficiency. Although this extreme diet plan can be life-saving compared to the alternative, it is not a harmless diet. Children on this diet are at risk of broken bones, stunted growth, kidney stones, high cholesterol, and micronutrient deficiency.
The fad diet that adopted the same name is also a high-fat, low-carb diet, but with a lower fat content. A typical version of this keto diet for adults has about 50% of food by weight coming from fat (70% of calories). Proponents claim that it induces weight loss. The premise of the weight-loss ketogenic diet is that if the body is deprived of glucose obtained from carbohydrate foods, it will produce energy from stored fat. There are some different approaches to a keto diet, including:
ketogenic diet (KD) – usually less than 50 grams of carbohydrates per day (assuming total intake of 2,000 calories).
very low-calorie ketogenic diet (VLCKD) – same as KD, but limits total calories to a maximum of 800 calories per day.
ketogenic low-carbohydrate high-fat diet (K-LCHF) – same as KD, with the additional restriction of 60 to 80% of calories coming from fat.
modified Atkins diet (MAD) – fewer carbohydrates than K-LCHF (less than 10 grams per day), and encourages high-fat foods without specifying a specific required amount.
A very low calorie ketogenic diet that is high in fat but low in protein is an effective means for weight loss in those who are overweight or obese, yielding an average weight loss of 10 kg over four weeks, with maintenance of the weight loss for up to two years. However, concerns about serum sodium levels led researchers to propose the diet only be used in "selected" people, and under strict medical supervision.
In 2021 the American Heart Association issued a scientific statement on dietary guidance to improve cardiovascular health which noted that "there is insufficient evidence to support any existing popular or fad diets such as the ketogenic diet and intermittent fasting to promote heart health".
== See also ==
== References ==
== Further reading == | Wikipedia/Low-carbohydrate_diet |
Digestion is the breakdown of carbohydrates to yield an energy-rich compound called ATP. The production of ATP is achieved through the oxidation of glucose molecules. In oxidation, the electrons are stripped from a glucose molecule to reduce NAD+ and FAD. NAD+ and FAD possess a high energy potential to drive the production of ATP in the electron transport chain. ATP production occurs in the mitochondria of the cell. There are two methods of producing ATP: aerobic and anaerobic.
In aerobic respiration, oxygen is required. Using oxygen increases ATP production from 4 ATP molecules to about 30 ATP molecules.
In anaerobic respiration, oxygen is not required. When oxygen is absent, the generation of ATP continues through fermentation. There are two types of fermentation: alcohol fermentation and lactic acid fermentation.
There are several different types of carbohydrates: polysaccharides (e.g., starch, amylopectin, glycogen, cellulose), monosaccharides (e.g., glucose, galactose, fructose, ribose) and the disaccharides (e.g., sucrose, maltose, lactose).
Monosaccharides, also known as simple sugars, are the most basic, fundamental unit of a carbohydrate. These are simple sugars with the general chemical structure of C6H12O6.
Disaccharides are a type of carbohydrate. Disaccharides consist of compound sugars containing two monosaccharides with the elimination of a water molecule with the general chemical structure C12H22O11.
Oligosaccharides are carbohydrates that consist of a polymer that contains three to ten monosaccharides linked together by glycosidic bonds.
Glucose reacts with oxygen in the following reaction, C6H12O6 + 6O2 → 6CO2 + 6H2O. Carbon dioxide and water are waste products, and the overall reaction is exothermic.
The reaction of glucose with oxygen releasing energy in the form of molecules of ATP is therefore one of the most important biochemical pathways found in living organisms.
== Glycolysis ==
Glycolysis, which means “sugar splitting,” is the initial process in the cellular respiration pathway. Glycolysis can be either an aerobic or anaerobic process. When oxygen is present, glycolysis continues along the aerobic respiration pathway. If oxygen is not present, then ATP production is restricted to anaerobic respiration. The location where glycolysis, aerobic or anaerobic, occurs is in the cytosol of the cell. In glycolysis, a six-carbon glucose molecule is split into two three-carbon molecules called pyruvate. These carbon molecules are oxidized into NADH and ATP. For the glucose molecule to oxidize into pyruvate, an input of ATP molecules is required. This is known as the investment phase, in which a total of two ATP molecules are consumed. At the end of glycolysis, the total yield of ATP is four molecules, but the net gain is two ATP molecules. Even though ATP is synthesized, the two ATP molecules produced are few compared to the second and third pathways, Krebs cycle and oxidative phosphorylation.
== Fermentation ==
Even if there is no oxygen present, glycolysis can continue to generate ATP. However, for glycolysis to continue to produce ATP, there must be NAD+ present, which is responsible for oxidizing glucose. This is achieved by recycling NADH back to NAD+. When NAD+ is reduced to NADH, the electrons from NADH are eventually transferred to a separate organic molecule, transforming NADH back to NAD+. This process of renewing the supply of NAD+ is called fermentation, which falls into two categories.
=== Alcohol Fermentation ===
In alcohol fermentation, when a glucose molecule is oxidized, ethanol (ethyl alcohol) and carbon dioxide are byproducts. The organic molecule that is responsible for renewing the NAD+ supply in this type of fermentation is the pyruvate from glycolysis. Each pyruvate releases a carbon dioxide molecule, turning into acetaldehyde. The acetaldehyde is then reduced by the NADH produced from glycolysis, forming the alcohol waste product, ethanol, and forming NAD+, thereby replenishing its supply for glycolysis to continue producing ATP.
=== Lactic Acid Fermentation ===
In lactic acid fermentation, each pyruvate molecule is directly reduced by NADH. The only byproduct from this type of fermentation is lactate. Lactic acid fermentation is used by human muscle cells as a means of generating ATP during strenuous exercise where oxygen consumption is higher than the supplied oxygen. As this process progresses, the surplus of lactate is brought to the liver, which converts it back to pyruvate.
== Respiration ==
=== The Citric acid cycle (also known as the Krebs cycle) ===
If oxygen is present, then following glycolysis, the two pyruvate molecules are brought into the mitochondrion itself to go through the Krebs cycle. In this cycle, the pyruvate molecules from glycolysis are further broken down to harness the remaining energy. Each pyruvate goes through a series of reactions that converts it to acetyl coenzyme A. From here, only the acetyl group participates in the Krebs cycle—in which it goes through a series of redox reactions, catalyzed by enzymes, to further harness the energy from the acetyl group. The energy from the acetyl group, in the form of electrons, is used to reduce NAD+ and FAD to NADH and FADH2, respectively. NADH and FADH2 contain the stored energy harnessed from the initial glucose molecule and is used in the electron transport chain where the bulk of the ATP is produced.
=== Oxidative phosphorylation ===
The last process in aerobic respiration is oxidative phosphorylation, also known as the electron transport chain. Here NADH and FADH2 deliver their electrons to oxygen and protons at the inner membranes of the mitochondrion, facilitating the production of ATP. Oxidative phosphorylation contributes the majority of the ATP produced, compared to glycolysis and the Krebs cycle. While the ATP count is glycolysis and the Krebs cycle is two ATP molecules, the electron transport chain contributes, at most, twenty-eight ATP molecules. A contributing factor is due to the energy potentials of NADH and FADH2. A second contributing factor is that cristae, the inner membranes of mitochondria, increase the surface area and therefore the amount of proteins in the membrane that assist in the synthesis of ATP. Along the electron transport chain, there are separate compartments, each with their own concentration gradient of H + ions, which are the power source of ATP synthesis. To convert ADP to ATP, energy must be provided. That energy is provided by the H+ gradient. On one side of the membrane compartment, there is a high concentration of H+ ions compared to the other. The shuttling of H+ to one side of the membrane is driven by the exergonic flow of electrons throughout the membrane. These electrons are supplied by NADH and FADH2 as they transfer their potential energy. Once the H+ concentration gradient is established, a proton-motive force is established, which provides the energy to convert ADP to ATP. The H+ ions that were initially forced to one side of the mitochondrion membrane now naturally flow through a membrane protein called ATP synthase, a protein that converts ADP to ATP with the help of H+ ions.
== See also ==
cellular respiration
== References == | Wikipedia/Carbohydrate_catabolism |
Carbohydrate metabolism is the whole of the biochemical processes responsible for the metabolic formation, breakdown, and interconversion of carbohydrates in living organisms.
Carbohydrates are central to many essential metabolic pathways. Plants synthesize carbohydrates from carbon dioxide and water through photosynthesis, allowing them to store energy absorbed from sunlight internally. When animals and fungi consume plants, they use cellular respiration to break down these stored carbohydrates to make energy available to cells. Both animals and plants temporarily store the released energy in the form of high-energy molecules, such as adenosine triphosphate (ATP), for use in various cellular processes.
While carbohydrates are essential to human biological processes, consuming them is not essential for humans. There are healthy human populations that do not consume carbohydrates.
In humans, carbohydrates are available directly from consumption, from carbohydrate storage, or by conversion from fat components including fatty acids that are either stored or consumed directly.
== Metabolic pathways ==
=== Glycolysis ===
Glycolysis is the process of breaking down a glucose molecule into two pyruvate molecules, while storing energy released during this process as adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NADH). Nearly all organisms that break down glucose utilize glycolysis. Glucose regulation and product use are the primary categories in which these pathways differ between organisms. In some tissues and organisms, glycolysis is the sole method of energy production. This pathway is common to both anaerobic and aerobic respiration.
Glycolysis consists of ten steps, split into two phases. During the first phase, it requires the breakdown of two ATP molecules. During the second phase, chemical energy from the intermediates is transferred into ATP and NADH. The breakdown of one molecule of glucose results in two molecules of pyruvate, which can be further oxidized to access more energy in later processes.
Glycolysis can be regulated at different steps of the process through feedback regulation. The step that is regulated the most is the third step. This regulation is to ensure that the body is not over-producing pyruvate molecules. The regulation also allows for the storage of glucose molecules into fatty acids. There are various enzymes that are used throughout glycolysis. The enzymes upregulate, downregulate, and feedback regulate the process.
=== Gluconeogenesis ===
Gluconeogenesis (GNG) is a metabolic pathway that results in the generation of glucose from certain non-carbohydrate carbon substrates. It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In vertebrates, gluconeogenesis occurs mainly in the liver and, to a lesser extent, in the cortex of the kidneys. It is one of two primary mechanisms – the other being degradation of glycogen (glycogenolysis) – used by humans and many other animals to maintain blood sugar levels, avoiding low levels (hypoglycemia). In ruminants, because dietary carbohydrates tend to be metabolized by rumen organisms, gluconeogenesis occurs regardless of fasting, low-carbohydrate diets, exercise, etc. In many other animals, the process occurs during periods of fasting, starvation, low-carbohydrate diets, or intense exercise.
In humans, substrates for gluconeogenesis may come from any non-carbohydrate sources that can be converted to pyruvate or intermediates of glycolysis (see figure). For the breakdown of proteins, these substrates include glucogenic amino acids (although not ketogenic amino acids); from breakdown of lipids (such as triglycerides), they include glycerol, odd-chain fatty acids (although not even-chain fatty acids, see below); and from other parts of metabolism they include lactate from the Cori cycle. Under conditions of prolonged fasting, acetone derived from ketone bodies can also serve as a substrate, providing a pathway from fatty acids to glucose. Although most gluconeogenesis occurs in the liver, the relative contribution of gluconeogenesis by the kidney is increased in diabetes and prolonged fasting.
The gluconeogenesis pathway is highly endergonic until it is coupled to the hydrolysis of ATP or guanosine triphosphate (GTP), effectively making the process exergonic. For example, the pathway leading from pyruvate to glucose-6-phosphate requires 4 molecules of ATP and 2 molecules of GTP to proceed spontaneously. These ATPs are supplied from fatty acid catabolism via beta oxidation.
=== Glycogenolysis ===
Glycogenolysis refers to the breakdown of glycogen. In the liver, muscles, and the kidney, this process occurs to provide glucose when necessary. A single glucose molecule is cleaved from a branch of glycogen, and is transformed into glucose-1-phosphate during this process. This molecule can then be converted to glucose-6-phosphate, an intermediate in the glycolysis pathway.
Glucose-6-phosphate can then progress through glycolysis. Glycolysis only requires the input of one molecule of ATP when the glucose originates in glycogen. Alternatively, glucose-6-phosphate can be converted back into glucose in the liver and the kidneys, allowing it to raise blood glucose levels if necessary.
Glucagon in the liver stimulates glycogenolysis when the blood glucose is lowered, known as hypoglycemia. The glycogen in the liver can function as a backup source of glucose between meals. Liver glycogen mainly serves the central nervous system. Adrenaline stimulates the breakdown of glycogen in the skeletal muscle during exercise. In the muscles, glycogen ensures a rapidly accessible energy source for movement.
=== Glycogenesis ===
Glycogenesis refers to the process of synthesizing glycogen. In humans, glucose can be converted to glycogen via this process. Glycogen is a highly branched structure, consisting of the core protein Glycogenin, surrounded by branches of glucose units, linked together. The branching of glycogen increases its solubility, and allows for a higher number of glucose molecules to be accessible for breakdown at the same time. Glycogenesis occurs primarily in the liver, skeletal muscles, and kidney. The Glycogenesis pathway consumes energy, like most synthetic pathways, because an ATP and a UTP are consumed for each molecule of glucose introduced.
=== Pentose phosphate pathway ===
The pentose phosphate pathway is an alternative method of oxidizing glucose. It occurs in the liver, adipose tissue, adrenal cortex, testis, mammary glands, phagocytes, and red blood cells. It produces products that are used in other cell processes, while reducing NADP to NADPH. This pathway is regulated through changes in the activity of glucose-6-phosphate dehydrogenase.
=== Fructose metabolism ===
Fructose must undergo certain extra steps in order to enter the glycolysis pathway. Enzymes located in certain tissues can add a phosphate group to fructose. This phosphorylation creates fructose-6-phosphate, an intermediate in the glycolysis pathway that can be broken down directly in those tissues. This pathway occurs in the muscles, adipose tissue, and kidney. In the liver, enzymes produce fructose-1-phosphate, which enters the glycolysis pathway and is later cleaved into glyceraldehyde and dihydroxyacetone phosphate.
=== Galactose metabolism ===
Lactose, or milk sugar, consists of one molecule of glucose and one molecule of galactose. After separation from glucose, galactose travels to the liver for conversion to glucose. Galactokinase uses one molecule of ATP to phosphorylate galactose. The phosphorylated galactose is then converted to glucose-1-phosphate, and then eventually glucose-6-phosphate, which can be broken down in glycolysis.
== Energy production ==
Many steps of carbohydrate metabolism allow the cells to access energy and store it more transiently in ATP. The cofactors NAD+ and FAD are sometimes reduced during this process to form NADH and FADH2, which drive the creation of ATP in other processes. A molecule of NADH can produce 1.5–2.5 molecules of ATP, whereas a molecule of FADH2 yields 1.5 molecules of ATP.
Typically, the complete breakdown of one molecule of glucose by aerobic respiration (i.e. involving glycolysis, the citric-acid cycle and oxidative phosphorylation, the last providing the most energy) is usually about 30–32 molecules of ATP. Oxidation of one gram of carbohydrate yields approximately 4 kcal of energy.
== Carbohydrate Consumption ==
Humans can consume a variety of carbohydrates, digestion breaks down complex carbohydrates into simple monomers (monosaccharides): glucose, fructose, mannose and galactose. After resorption in the gut, the monosaccharides are transported, through the portal vein, to the liver, where all non-glucose monosacharids (fructose, galactose) are transformed into glucose as well. Glucose (blood sugar) is distributed to cells in the tissues, where it is broken down via cellular respiration, or stored as glycogen. In cellular (aerobic) respiration, glucose and oxygen are metabolized to release energy, with carbon dioxide and water as endproducts.
== Hormonal regulation ==
Glucoregulation is the maintenance of steady levels of glucose in the body.
Hormones released from the pancreas regulate the overall metabolism of glucose. Insulin and glucagon are the primary hormones involved in maintaining a steady level of glucose in the blood, and the release of each is controlled by the amount of nutrients currently available. The amount of insulin released in the blood and sensitivity of the cells to the insulin both determine the amount of glucose that cells break down. Increased levels of glucagon activates the enzymes that catalyze glycogenolysis, and inhibits the enzymes that catalyze glycogenesis. Conversely, glycogenesis is enhanced and glycogenolysis inhibited when there are high levels of insulin in the blood.
The level of circulatory glucose (known informally as "blood sugar"), as well as the detection of nutrients in the Duodenum is the most important factor determining the amount of glucagon or insulin produced. The release of glucagon is precipitated by low levels of blood glucose, whereas high levels of blood glucose stimulates cells to produce insulin. Because the level of circulatory glucose is largely determined by the intake of dietary carbohydrates, diet controls major aspects of metabolism via insulin. In humans, insulin is made by beta cells in the pancreas, fat is stored in adipose tissue cells, and glycogen is both stored and released as needed by liver cells. Regardless of insulin levels, no glucose is released to the blood from internal glycogen stores from muscle cells.
== Carbohydrates as storage ==
Carbohydrates are typically stored as long polymers of glucose molecules with glycosidic bonds for structural support (e.g. chitin, cellulose) or for energy storage (e.g. glycogen, starch). However, the strong affinity of most carbohydrates for water makes storage of large quantities of carbohydrates inefficient due to the large molecular weight of the solvated water-carbohydrate complex. In most organisms, excess carbohydrates are regularly catabolised to form acetyl-CoA, which is a feed stock for the fatty acid synthesis pathway; fatty acids, triglycerides, and other lipids are commonly used for long-term energy storage. The hydrophobic character of lipids makes them a much more compact form of energy storage than hydrophilic carbohydrates. Gluconeogenesis permits glucose to be synthesized from various sources, including lipids.
In some animals (such as termites) and some microorganisms (such as protists and bacteria), cellulose can be disassembled during digestion and absorbed as glucose.
== Human diseases ==
Diabetes mellitus
Lactose intolerance
Fructose malabsorption
Galactosemia
Glycogen storage disease
== See also ==
Inborn errors of carbohydrate metabolism
Hitting the wall (glycogen depletion)
Second wind (increased ATP from fatty acids after glycogen depletion)
== References ==
== External links ==
Carbohydrate+metabolism at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
BBC - GCSE Bitesize - Biology | Humans | Glucoregulation
Sugar4Kids | Wikipedia/Carbohydrate_metabolism |
Substrate-level phosphorylation is a metabolism reaction that results in the production of ATP or GTP supported by the energy released from another high-energy bond that leads to phosphorylation of ADP or GDP to ATP or GTP (note that the reaction catalyzed by creatine kinase is not considered as "substrate-level phosphorylation"). This process uses some of the released chemical energy, the Gibbs free energy, to transfer a phosphoryl (PO3) group to ADP or GDP. Occurs in glycolysis and in the citric acid cycle.
Unlike oxidative phosphorylation, oxidation and phosphorylation are not coupled in the process of substrate-level phosphorylation, and reactive intermediates are most often gained in the course of oxidation processes in catabolism. Most ATP is generated by oxidative phosphorylation in aerobic or anaerobic respiration while substrate-level phosphorylation provides a quicker, less efficient source of ATP, independent of external electron acceptors. This is the case in human erythrocytes, which have no mitochondria, and in oxygen-depleted muscle.
== Overview ==
Adenosine triphosphate (ATP) is a major "energy currency" of the cell. The high energy bonds between the phosphate groups can be broken to power a variety of reactions used in all aspects of cell function.
Substrate-level phosphorylation occurs in the cytoplasm of cells during glycolysis and in mitochondria either during the Krebs cycle or by MTHFD1L (EC 6.3.4.3), an enzyme interconverting ADP + phosphate + 10-formyltetrahydrofolate to ATP + formate + tetrahydrofolate (reversibly), under both aerobic and anaerobic conditions. In the pay-off phase of glycolysis, a net of 2 ATP are produced by substrate-level phosphorylation.
== Glycolysis ==
The first substrate-level phosphorylation occurs after the conversion of 3-phosphoglyceraldehyde and Pi and NAD+ to 1,3-bisphosphoglycerate via glyceraldehyde 3-phosphate dehydrogenase. 1,3-bisphosphoglycerate is then dephosphorylated via phosphoglycerate kinase, producing 3-phosphoglycerate and ATP through a substrate-level phosphorylation.
The second substrate-level phosphorylation occurs by dephosphorylating phosphoenolpyruvate, catalyzed by pyruvate kinase, producing pyruvate and ATP.
During the preparatory phase, each 6-carbon glucose molecule is broken into two 3-carbon molecules. Thus, in glycolysis dephosphorylation results in the production of 4 ATP. However, the prior preparatory phase consumes 2 ATP, so the net yield in glycolysis is 2 ATP. 2 molecules of NADH are also produced and can be used in oxidative phosphorylation to generate more ATP.
== Mitochondria ==
ATP can be generated by substrate-level phosphorylation in mitochondria in a pathway that is independent from the proton motive force. In the matrix there are three reactions capable of substrate-level phosphorylation, utilizing either phosphoenolpyruvate carboxykinase or succinate-CoA ligase, or monofunctional C1-tetrahydrofolate synthase.
=== Phosphoenolpyruvate carboxykinase ===
Mitochondrial phosphoenolpyruvate carboxykinase is thought to participate in the transfer of the phosphorylation potential from the matrix to the cytosol and vice versa. However, it is strongly favored towards GTP hydrolysis, thus it is not really considered as an important source of intra-mitochondrial substrate-level phosphorylation.
=== Succinate-CoA ligase ===
Succinate-CoA ligase is a heterodimer composed of an invariant α-subunit and a substrate-specific ß-subunit, encoded by either SUCLA2 or SUCLG2. This combination results in either an ADP-forming succinate-CoA ligase (A-SUCL, EC 6.2.1.5) or a GDP-forming succinate-CoA ligase (G-SUCL, EC 6.2.1.4). The ADP-forming succinate-CoA ligase is potentially the only matrix enzyme generating ATP in the absence of a proton motive force, capable of maintaining matrix ATP levels under energy-limited conditions, such as transient hypoxia.
=== Monofunctional C1-tetrahydrofolate synthase ===
This enzyme is encoded by MTHFD1L and reversibly interconverts ADP + phosphate + 10-formyltetrahydrofolate to ATP + formate + tetrahydrofolate.
== Other mechanisms ==
In working skeletal muscles and the brain, Phosphocreatine is stored as a readily available high-energy phosphate supply, and the enzyme creatine phosphokinase transfers a phosphate from phosphocreatine to ADP to produce ATP. Then the ATP releases giving chemical energy. This is sometimes erroneously considered to be substrate-level phosphorylation, although it is a transphosphorylation.
== Importance of substrate-level phosphorylation in anoxia ==
During anoxia, provision of ATP by substrate-level phosphorylation in the matrix is important not only as a mere means of energy, but also to prevent mitochondria from straining glycolytic ATP reserves by maintaining the adenine nucleotide translocator in ‘forward mode’ carrying ATP towards the cytosol.
== Oxidative phosphorylation ==
An alternative method used to create ATP is through oxidative phosphorylation, which takes place during cellular respiration. This process utilizes the oxidation of NADH to NAD+, yielding 3 ATP, and of FADH2 to FAD, yielding 2 ATP. The potential energy stored as an electrochemical gradient of protons (H+) across the inner mitochondrial membrane is required to generate ATP from ADP and Pi (inorganic phosphate molecule), a key difference from substrate-level phosphorylation. This gradient is exploited by ATP synthase acting as a pore, allowing H+ from the mitochondrial intermembrane space to move down its electrochemical gradient into the matrix and coupling the release of free energy to ATP synthesis. Conversely, electron transfer provides the energy required to actively pump H+ out of the matrix.
== References == | Wikipedia/Substrate-level_phosphorylation |
Carbohydrate NMR spectroscopy is the application of nuclear magnetic resonance (NMR) spectroscopy to structural and conformational analysis of carbohydrates. This method allows the scientists to elucidate structure of monosaccharides, oligosaccharides, polysaccharides, glycoconjugates and other carbohydrate derivatives from synthetic and natural sources. Among structural properties that could be determined by NMR are primary structure (including stereochemistry), saccharide conformation, stoichiometry of substituents, and ratio of individual saccharides in a mixture. Modern high field NMR instruments used for carbohydrate samples, typically 500 MHz or higher, are able to run a suite of 1D, 2D, and 3D experiments to determine a structure of carbohydrate compounds.
== Carbohydrate NMR observables ==
=== Chemical shift ===
Common chemical shift ranges for nuclei within carbohydrate residues are:
Typical 1H NMR chemical shifts of carbohydrate ring protons are 3–6 ppm (4.5–5.5 ppm for anomeric protons).
Typical 13C NMR chemical shifts of carbohydrate ring carbons are 60–110 ppm
In the case of simple mono- and oligosaccharide molecules, all proton signals are typically separated from one another (usually at 500 MHz or better NMR instruments) and can be assigned using 1D NMR spectrum only. However, bigger molecules exhibit significant proton signal overlap, especially in the non-anomeric region (3-4 ppm). Carbon-13 NMR overcomes this disadvantage by larger range of chemical shifts and special techniques allowing to block carbon-proton spin coupling, thus making all carbon signals high and narrow singlets distinguishable from each other.
The typical ranges of specific carbohydrate carbon chemical shifts in the unsubstituted monosaccharides are:
Anomeric carbons: 90-100 ppm
Sugar ring carbons bearing a hydroxy function: 68-77
Open-form sugar carbons bearing a hydroxy function: 71-75
Sugar ring carbons bearing an amino function: 50-56
Exocyclic hydroxymethyl groups: 60-64
Exocyclic carboxy groups: 172-176
Desoxygenated sugar ring carbons: 31-40
A carbon at pyranose ring closure: 71-73 (α-anomers), 74-76 (β-anomers)
A carbon at furanose ring closure: 80-83 (α-anomers), 83-86 (β-anomers)
=== Coupling constants ===
Direct carbon-proton coupling constants are used to study the anomeric configuration of a sugar.
Vicinal proton-proton coupling constants are used to study stereo orientation of protons relatively to the other protons within a sugar ring, thus identifying a monosaccharide.
Vicinal heteronuclear H-C-O-C coupling constants are used to study torsional angles along glycosidic bond between sugars or along exocyclic fragments, thus revealing a molecular conformation.
Sugar rings are relatively rigid molecular fragments, thus vicinal proton-proton couplings are characteristic:
Equatorial to axial: 1–4 Hz
Equatorial to equatorial: 0–2 Hz
Axial to axial non-anomeric: 9–11 Hz
Axial to axial anomeric: 7–9 Hz
Axial to exocyclic hydroxymethyl: 5 Hz, 2 Hz
Geminal between hydroxymethyl protons: 12 Hz
=== Nuclear Overhauser effects (NOEs) ===
NOEs are sensitive to interatomic distances, allowing their usage as a conformational probe, or proof of a glycoside bond formation. It's a common practice to compare calculated to experimental proton-proton NOEs in oligosaccharides to confirm a theoretical conformational map. Calculation of NOEs implies an optimization of molecular geometry.
=== Other NMR observables ===
Relaxivities, nuclear relaxation rates, line shape and other parameters were reported useful in structural studies of carbohydrates.
== Elucidation of carbohydrate structure by NMR spectroscopy ==
=== Structural parameters of carbohydrates ===
The following is a list of structural features that can be elucidated by NMR:
Chemical structure of each carbohydrate residue in a molecule, including
carbon skeleton size and sugar type (aldose/ketose)
cycle size (pyranose/furanose/linear)
stereo configuration of all carbons (monosaccharide identification)
stereo configuration of anomeric carbon (α/β)
absolute configuration (D/L)
location of amino-, carboxy-, deoxy- and other functions
Chemical structure of non-carbohydrate residues in molecule (amino acids, fatty acids, alcohols, organic aglycons etc.)
Substitution positions in residues
Sequence of residues
Stoichiometry of terminal residues and side chains
Location of phosphate and sulfate diester bonds
Polymerization degree and frame positioning (for polysaccharides)
=== NMR spectroscopy vs. other methods ===
Widely known methods of structural investigation, such as mass-spectrometry and X-ray analysis are only limitedly applicable to carbohydrates. Such structural studies, such as sequence determination or identification of new monosaccharides, benefit the most from the NMR spectroscopy.
Absolute configuration and polymerization degree are not always determinable using NMR only, so the process of structural elucidation may require additional methods. Although monomeric composition can be solved by NMR, chromatographic and mass-spectroscopic methods provide this information sometimes easier. The other structural features listed above can be determined solely by the NMR spectroscopic methods.
The limitation of the NMR structural studies of carbohydrates is that structure elucidation can hardly be automatized and require a human expert to derive a structure from NMR spectra.
=== Application of various NMR techniques to carbohydrates ===
Complex glycans possess a multitude of overlapping signals, especially in a proton spectrum. Therefore, it is advantageous to utilize 2D experiments for the assignment of signals.
The table and figures below list most widespread NMR techniques used in carbohydrate studies.
=== Research scheme ===
NMR spectroscopic research includes the following steps:
Extraction of carbohydrate material (for natural glycans)
Chemical removal of moieties masking regularity (for polymers)
Separation and purification of carbohydrate material (for 2D NMR experiments, 10 mg or more is recommended)
Sample preparation (usually in D2O)
Acquisition of 1D spectra
Planning, acquisition and processing of other NMR experiments (usually requires from 5 to 20 hours)
Assignment and interpretation of spectra (see exemplary figure)
If a structural problem could not be solved: chemical modification/degradation and NMR analysis of products
Acquisition of spectra of the native (unmasked) compound and their interpretation based on modified structure
Presentation of results
== Carbohydrate NMR databases and tools ==
Multiple chemical shift databases and related services have been created to aid structural elucidation of and expert analysis of their NMR spectra. Of them, several informatics tools are dedicated solely to carbohydrates:
GlycoSCIENCES.de
over 4,000 NMR spectra of mammalian glycans
search of structure by NMR signals and vice versa
CSDB (carbohydrate structure database) contains:
over 20,000 NMR spectra (as of 2024) of bacterial, plant, fungal and protistal glycans,
search of structure by NMR signals and vice versa
empirical spectra simulation routine optimized for carbohydrates,
statistical chemical shift estimation based on HOSE algorithm optimized for carbohydrates,
structure generation and NMR-based ranking tool.
CASPER (computer assisted spectrum evaluation of regular polysaccharides). contains:
chemical shift database,
empirical spectra simulation routine optimized for carbohydrates,
online interface.
structure matching tool. Both proton and carbon C and H chemical shifts can be used to access structural information.
=== Simulation of the NMR observables ===
Several approaches to simulate NMR observables of carbohydrates has been reviewed. They include:
Universal statistical database approaches (ACDLabs, Modgraph, etc.)
Usage of neural networks to refine the predictions
Regression based methods
CHARGE
Carbohydrate-optimized empirical schemes (CSDB/BIOPSEL, CASPER).
Combined molecular mechanics/dynamics geometry calculation and quantum-mechanical simulation/iteration of NMR observables (PERCH NMR Software)
ONIOM approaches (optimization of different parts of molecule with different accuracy)
Ab initio calculations.
Growing computational power allows usage of thorough quantum-mechanical calculations at high theory levels and large basis sets for refining the molecular geometry of carbohydrates and subsequent prediction of NMR observables using GIAO and other methods with or without solvent effect account. Among combinations of theory level and a basis set reported as sufficient for NMR predictions were B3LYP/6-311G++(2d,2p) and PBE/PBE (see review). It was shown for saccharides that carbohydrate-optimized empirical schemes provide significantly better accuracy (0.0-0.5 ppm per 13C resonance) than quantum chemical methods (above 2.0 ppm per resonance) reported as best for NMR simulations, and work thousands times faster. However, these methods can predict only chemical shifts and perform poor for non-carbohydrate parts of molecules.
As a representative example, see figure on the right.
== See also ==
Methods of 1D and 2D NMR spectroscopy in structural studies of natural glycopolymers (lection)
Carbohydrate databases in the recent decade (lection; includes NMR simulation data)
Carbohydrate
Glycan
Nuclear magnetic resonance
Nuclear magnetic resonance spectroscopy of nucleic acids
Nuclear magnetic resonance spectroscopy of proteins
NMR spectroscopy
Nuclear Overhauser effect
== References ==
== Further reading ==
D. Łowicki; A. Czarny; J. Mlynarski (2013). Nuclear Magnetic Resonance: NMR of carbohydrates. Royal Society of Chemistry. p. 383. ISBN 978-1-84973-577-3.
== External links ==
Media related to Nuclear magnetic resonance spectroscopy of carbohydrates at Wikimedia Commons | Wikipedia/Carbohydrate_NMR |
A metabolic network is the complete set of metabolic and physical processes that determine the physiological and biochemical properties of a cell. As such, these networks comprise the chemical reactions of metabolism, the metabolic pathways, as well as the regulatory interactions that guide these reactions.
With the sequencing of complete genomes, it is now possible to reconstruct the network of biochemical reactions in many organisms, from bacteria to human. Several of these networks are available online:
Kyoto Encyclopedia of Genes and Genomes (KEGG), EcoCyc, BioCyc and metaTIGER.
Metabolic networks are powerful tools for studying and modelling metabolism.
== Uses ==
Metabolic networks can be used to detect comorbidity patterns in diseased patients. Certain diseases, such as obesity and diabetes, can be present in the same individual concurrently, sometimes one disease being a significant risk factor for the other disease. The disease phenotypes themselves are normally the consequence of the cell's inability to breakdown or produce an essential substrate. However, an enzyme defect at one reaction may affect the fluxes of other subsequent reactions. These cascading effects couple the metabolic diseases associated with subsequent reactions resulting in comorbidity effects. Thus, metabolic disease networks can be used to determine if two disorders are connected due to their correlated reactions.
== See also ==
Metabolic network modelling
Metabolic pathway
== References == | Wikipedia/Metabolic_network |
In carbohydrate chemistry carbohydrate acetalisation is an organic reaction and a very effective means of providing a protecting group. The example below depicts the acetalisation reaction of D-ribose 1. With acetone or 2,2-dimethoxypropane as the acetalisation reagent the reaction is under thermodynamic reaction control and results in the pentose 2. The latter reagent in itself is an acetal and therefore the reaction is actually a cross-acetalisation.
Kinetic reaction control results from 2-methoxypropene as the reagent. D-ribose in itself is a hemiacetal and in equilibrium with the pyranose 3. In aqueous solution ribose is 75% pyranose and 25% furanose and a different acetal 4 is formed.
Selective acetalization of carbohydrate and formation of acetals possessing atypical properties is achieved by using arylsulfonyl acetals. An example of arylsulfonyl acetals as carbohydrate-protective groups are phenylsulfonylethylidene acetals. These acetals are resistant to the acid hydrolysis and can be deprotected easily by classical reductive conditions.
== References ==
Preparative Carbohydrate Chemistry Calinaud, P.; Gelas, J. in . Hanessian, S. Ed. Marcel Dekker, Inc.: New York, 1997. ISBN 0-8247-9802-3
== External links ==
Media related to Carbohydrate acetalisation at Wikimedia Commons | Wikipedia/Carbohydrate_acetalisation |
A carbohydrate () is a biomolecule composed of carbon (C), hydrogen (H), and oxygen (O) atoms. The typical hydrogen-to-oxygen atomic ratio is 2:1, analogous to that of water, and is represented by the empirical formula Cm(H2O)n (where m and n may differ). This formula does not imply direct covalent bonding between hydrogen and oxygen atoms; for example, in CH2O, hydrogen is covalently bonded to carbon, not oxygen. While the 2:1 hydrogen-to-oxygen ratio is characteristic of many carbohydrates, exceptions exist. For instance, uronic acids and deoxy-sugars like fucose deviate from this precise stoichiometric definition. Conversely, some compounds conforming to this definition, such as formaldehyde and acetic acid, are not classified as carbohydrates.
The term is predominantly used in biochemistry, functioning as a synonym for saccharide (from Ancient Greek σάκχαρον (sákkharon) 'sugar'), a group that includes sugars, starch, and cellulose. The saccharides are divided into four chemical groups: monosaccharides, disaccharides, oligosaccharides, and polysaccharides. Monosaccharides and disaccharides, the smallest (lower molecular weight) carbohydrates, are commonly referred to as sugars. While the scientific nomenclature of carbohydrates is complex, the names of the monosaccharides and disaccharides very often end in the suffix -ose, which was originally taken from the word glucose (from Ancient Greek γλεῦκος (gleûkos) 'wine, must'), and is used for almost all sugars (e.g., fructose (fruit sugar), sucrose (cane or beet sugar), ribose, lactose (milk sugar)).
Carbohydrates perform numerous roles in living organisms. Polysaccharides serve as an energy store (e.g., starch and glycogen) and as structural components (e.g., cellulose in plants and chitin in arthropods and fungi). The 5-carbon monosaccharide ribose is an important component of coenzymes (e.g., ATP, FAD and NAD) and the backbone of the genetic molecule known as RNA. The related deoxyribose is a component of DNA. Saccharides and their derivatives include many other important biomolecules that play key roles in the immune system, fertilization, preventing pathogenesis, blood clotting, and development.
Carbohydrates are central to nutrition and are found in a wide variety of natural and processed foods. Starch is a polysaccharide and is abundant in cereals (wheat, maize, rice), potatoes, and processed food based on cereal flour, such as bread, pizza or pasta. Sugars appear in human diet mainly as table sugar (sucrose, extracted from sugarcane or sugar beets), lactose (abundant in milk), glucose and fructose, both of which occur naturally in honey, many fruits, and some vegetables. Table sugar, milk, or honey is often added to drinks and many prepared foods such as jam, biscuits and cakes.
Cellulose, a polysaccharide found in the cell walls of all plants, is one of the main components of insoluble dietary fiber. Although it is not digestible by humans, cellulose and insoluble dietary fiber generally help maintain a healthy digestive system by facilitating bowel movements. Other polysaccharides contained in dietary fiber include resistant starch and inulin, which feed some bacteria in the microbiota of the large intestine, and are metabolized by these bacteria to yield short-chain fatty acids.
== Terminology ==
In scientific literature, the term "carbohydrate" has many synonyms, like "sugar" (in the broad sense), "saccharide", "ose", "glucide", "hydrate of carbon" or "polyhydroxy compounds with aldehyde or ketone". Some of these terms, especially "carbohydrate" and "sugar", are also used with other meanings.
In food science and in many informal contexts, the term "carbohydrate" often means any food that is particularly rich in the complex carbohydrate starch (such as cereals, bread and pasta) or simple carbohydrates, such as sugar (found in candy, jams, and desserts). This informality is sometimes confusing since it confounds chemical structure and digestibility in humans.
The term "carbohydrate" (or "carbohydrate by difference") refers also to dietary fiber, which is a carbohydrate, but, unlike sugars and starches, fibers are not hydrolyzed by human digestive enzymes. Fiber generally contributes little food energy in humans, but is often included in the calculation of total food energy. The fermentation of soluble fibers by gut microflora can yield short-chain fatty acids, and soluble fiber is estimated to provide about 2 kcal/g.
== History ==
The history of the discovery regarding carbohydrates dates back around 10,000 years ago in Papua New Guinea during the cultivation of sugarcane during the Neolithic agricultural revolution. The term "carbohydrate" was first proposed by German chemist Carl Schmidt (chemist) in 1844. In 1856, glycogen, a form of carbohydrate storage in animal livers, was discovered by French physiologist Claude Bernard.
== Structure ==
Formerly the name "carbohydrate" was used in chemistry for any compound with the formula Cm (H2O)n. Following this definition, some chemists considered formaldehyde (CH2O) to be the simplest carbohydrate, while others claimed that title for glycolaldehyde. Today, the term is generally understood in the biochemistry sense, which excludes compounds with only one or two carbons and includes many biological carbohydrates which deviate from this formula. For example, while the above representative formulas would seem to capture the commonly known carbohydrates, ubiquitous and abundant carbohydrates often deviate from this. For example, carbohydrates often display chemical groups such as: N-acetyl (e.g., chitin), sulfate (e.g., glycosaminoglycans), carboxylic acid and deoxy modifications (e.g., fucose and sialic acid).
Natural saccharides are generally built of simple carbohydrates called monosaccharides with general formula (CH2O)n where n is three or more. A typical monosaccharide has the structure H–(CHOH)x(C=O)–(CHOH)y–H, that is, an aldehyde or ketone with many hydroxyl groups added, usually one on each carbon atom that is not part of the aldehyde or ketone functional group. Examples of monosaccharides are glucose, fructose, and glyceraldehydes. However, some biological substances commonly called "monosaccharides" do not conform to this formula (e.g., uronic acids and deoxy-sugars such as fucose) and there are many chemicals that do conform to this formula but are not considered to be monosaccharides (e.g., formaldehyde CH2O and inositol (CH2O)6).
The open-chain form of a monosaccharide often coexists with a closed ring form where the aldehyde/ketone carbonyl group carbon (C=O) and hydroxyl group (–OH) react forming a hemiacetal with a new C–O–C bridge.
Monosaccharides can be linked together into what are called polysaccharides (or oligosaccharides) in a large variety of ways. Many carbohydrates contain one or more modified monosaccharide units that have had one or more groups replaced or removed. For example, deoxyribose, a component of DNA, is a modified version of ribose; chitin is composed of repeating units of N-acetyl glucosamine, a nitrogen-containing form of glucose.
== Division ==
Carbohydrates are polyhydroxy aldehydes, ketones, alcohols, acids, their simple derivatives and their polymers having linkages of the acetal type. They may be classified according to their degree of polymerization, and may be divided initially into three principal groups, namely sugars, oligosaccharides and polysaccharides.
== Monosaccharides ==
Monosaccharides are the simplest carbohydrates in that they cannot be hydrolyzed to smaller carbohydrates. They are aldehydes or ketones with two or more hydroxyl groups. The general chemical formula of an unmodified monosaccharide is (C•H2O)n, literally a "carbon hydrate". Monosaccharides are important fuel molecules as well as building blocks for nucleic acids. The smallest monosaccharides, for which n=3, are dihydroxyacetone and D- and L-glyceraldehydes.
=== Classification of monosaccharides ===
Monosaccharides are classified according to three different characteristics: the placement of its carbonyl group, the number of carbon atoms it contains, and its chiral handedness. If the carbonyl group is an aldehyde, the monosaccharide is an aldose; if the carbonyl group is a ketone, the monosaccharide is a ketose. Monosaccharides with three carbon atoms are called trioses, those with four are called tetroses, five are called pentoses, six are hexoses, and so on. These two systems of classification are often combined. For example, glucose is an aldohexose (a six-carbon aldehyde), ribose is an aldopentose (a five-carbon aldehyde), and fructose is a ketohexose (a six-carbon ketone).
Each carbon atom bearing a hydroxyl group (-OH), with the exception of the first and last carbons, are asymmetric, making them stereo centers with two possible configurations each (R or S). Because of this asymmetry, a number of isomers may exist for any given monosaccharide formula. Using Le Bel-van't Hoff rule, the aldohexose D-glucose, for example, has the formula (C·H2O)6, of which four of its six carbons atoms are stereogenic, making D-glucose one of 24=16 possible stereoisomers. In the case of glyceraldehydes, an aldotriose, there is one pair of possible stereoisomers, which are enantiomers and epimers. 1, 3-dihydroxyacetone, the ketose corresponding to the aldose glyceraldehydes, is a symmetric molecule with no stereo centers. The assignment of D or L is made according to the orientation of the asymmetric carbon furthest from the carbonyl group: in a standard Fischer projection if the hydroxyl group is on the right the molecule is a D sugar, otherwise it is an L sugar. The "D-" and "L-" prefixes should not be confused with "d-" or "l-", which indicate the direction that the sugar rotates plane polarized light. This usage of "d-" and "l-" is no longer followed in carbohydrate chemistry.
=== Ring-straight chain isomerism ===
The aldehyde or ketone group of a straight-chain monosaccharide will react reversibly with a hydroxyl group on a different carbon atom to form a hemiacetal or hemiketal, forming a heterocyclic ring with an oxygen bridge between two carbon atoms. Rings with five and six atoms are called furanose and pyranose forms, respectively, and exist in equilibrium with the straight-chain form.
During the conversion from straight-chain form to the cyclic form, the carbon atom containing the carbonyl oxygen, called the anomeric carbon, becomes a stereogenic center with two possible configurations: The oxygen atom may take a position either above or below the plane of the ring. The resulting possible pair of stereoisomers is called anomers. In the α anomer, the -OH substituent on the anomeric carbon rests on the opposite side (trans) of the ring from the CH2OH side branch. The alternative form, in which the CH2OH substituent and the anomeric hydroxyl are on the same side (cis) of the plane of the ring, is called the β anomer.
=== Use in living organisms ===
Monosaccharides are the major fuel source for metabolism, and glucose is an energy-rich molecule utilized to generate ATP in almost all living organisms. Glucose is a high-energy substrate produced in plants through photosynthesis by combining energy-poor water and carbon dioxide in an endothermic reaction fueled by solar energy. When monosaccharides are not immediately needed, they are often converted to more space-efficient (i.e., less water-soluble) forms, often polysaccharides. In animals, glucose circulating the blood is a major metabolic substrate and is oxidized in the mitochondria to produce ATP for performing useful cellular work. In humans and other animals, serum glucose levels must be regulated carefully to maintain glucose within acceptable limits and prevent the deleterious effects of hypo- or hyperglycemia. Hormones such as insulin and glucagon serve to keep glucose levels in balance: insulin stimulates glucose uptake into the muscle and fat cells when glucose levels are high, whereas glucagon helps to raise glucose levels if they dip too low by stimulating hepatic glucose synthesis. In many animals, including humans, this storage form is glycogen, especially in liver and muscle cells. In plants, starch is used for the same purpose. The most abundant carbohydrate, cellulose, is a structural component of the cell wall of plants and many forms of algae. Ribose is a component of RNA. Deoxyribose is a component of DNA. Lyxose is a component of lyxoflavin found in the human heart. Ribulose and xylulose occur in the pentose phosphate pathway. Galactose, a component of milk sugar lactose, is found in galactolipids in plant cell membranes and in glycoproteins in many tissues. Mannose occurs in human metabolism, especially in the glycosylation of certain proteins. Fructose, or fruit sugar, is found in many plants and humans, it is metabolized in the liver, absorbed directly into the intestines during digestion, and found in semen. Trehalose, a major sugar of insects, is rapidly hydrolyzed into two glucose molecules to support continuous flight.
== Disaccharides ==
Two joined monosaccharides are called a disaccharide, the simplest kind of polysaccharide. Examples include sucrose and lactose. They are composed of two monosaccharide units bound together by a covalent bond known as a glycosidic linkage formed via a dehydration reaction, resulting in the loss of a hydrogen atom from one monosaccharide and a hydroxyl group from the other. The formula of unmodified disaccharides is C12H22O11. Although there are numerous kinds of disaccharides, a handful of disaccharides are particularly notable.
Sucrose, pictured to the right, is the most abundant disaccharide, and the main form in which carbohydrates are transported in plants. It is composed of one D-glucose molecule and one D-fructose molecule. The systematic name for sucrose, O-α-D-glucopyranosyl-(1→2)-D-fructofuranoside, indicates four things:
Its monosaccharides: glucose and fructose
Their ring types: glucose is a pyranose and fructose is a furanose
How they are linked together: the oxygen on carbon number 1 (C1) of α-D-glucose is linked to the C2 of D-fructose.
The -oside suffix indicates that the anomeric carbon of both monosaccharides participates in the glycosidic bond.
Lactose, a disaccharide composed of one D-galactose molecule and one D-glucose molecule, occurs naturally in mammalian milk. The systematic name for lactose is O-β-D-galactopyranosyl-(1→4)-D-glucopyranose. Other notable disaccharides include maltose (two D-glucoses linked α-1,4) and cellobiose (two D-glucoses linked β-1,4). Disaccharides can be classified into two types: reducing and non-reducing disaccharides. If the functional group is present in bonding with another sugar unit, it is called a reducing disaccharide or biose.
== Oligosaccharides and polysaccharides ==
=== Oligosaccharides ===
Oligosaccharides are saccharide polymers composed of three to ten units of monosaccharides, connected via glycosidic linkages, similar to disaccharides. They are usually linked to lipids or amino acids glycosic linkage with oxygen or nitrogen to form glycolipids and glycoproteins, though some, like the raffinose series and the fructooligosaccharides, do not. They have roles in cell recognition and cell adhesion.
=== Polysaccharides ===
== Nutrition ==
Carbohydrate consumed in food yields 3.87 kilocalories of energy per gram for simple sugars, and 3.57 to 4.12 kilocalories per gram for complex carbohydrate in most other foods. Relatively high levels of carbohydrate are associated with processed foods or refined foods made from plants, including sweets, cookies and candy, table sugar, honey, soft drinks, breads and crackers, jams and fruit products, pastas and breakfast cereals. Refined carbohydrates from processed foods such as white bread or rice, soft drinks, and desserts are readily digestible, and many are known to have a high glycemic index, which reflects a rapid assimilation of glucose. By contrast, the digestion of whole, unprocessed, fiber-rich foods such as beans, peas, and whole grains produces a slower and steadier release of glucose and energy into the body. Animal-based foods generally have the lowest carbohydrate levels, although milk does contain a high proportion of lactose.
Organisms typically cannot metabolize all types of carbohydrate to yield energy. Glucose is a nearly universal and accessible source of energy. Many organisms also have the ability to metabolize other monosaccharides and disaccharides but glucose is often metabolized first. In Escherichia coli, for example, the lac operon will express enzymes for the digestion of lactose when it is present, but if both lactose and glucose are present, the lac operon is repressed, resulting in the glucose being used first (see: Diauxie). Polysaccharides are also common sources of energy. Many organisms can easily break down starches into glucose; most organisms, however, cannot metabolize cellulose or other polysaccharides such as chitin and arabinoxylans. These carbohydrate types can be metabolized by some bacteria and protists. Ruminants and termites, for example, use microorganisms to process cellulose, fermenting it to caloric short-chain fatty acids. Even though humans lack the enzymes to digest fiber, dietary fiber represents an important dietary element for humans. Fibers promote healthy digestion, help regulate postprandial glucose and insulin levels, reduce cholesterol levels, and promote satiety.
The Institute of Medicine recommends that American and Canadian adults get between 45 and 65% of dietary energy from whole-grain carbohydrates. The Food and Agriculture Organization and World Health Organization jointly recommend that national dietary guidelines set a goal of 55–75% of total energy from carbohydrates, but only 10% directly from sugars (their term for simple carbohydrates). A 2017 Cochrane Systematic Review concluded that there was insufficient evidence to support the claim that whole grain diets can affect cardiovascular disease.
=== Classification ===
The term complex carbohydrate was first used in the U.S. Senate Select Committee on Nutrition and Human Needs publication Dietary Goals for the United States (1977) where it was intended to distinguish sugars from other carbohydrates (which were perceived to be nutritionally superior). However, the report put "fruit, vegetables and whole-grains" in the complex carbohydrate column, despite the fact that these may contain sugars as well as polysaccharides. The standard usage, however, is to classify carbohydrates chemically: simple if they are sugars (monosaccharides and disaccharides) and complex if they are polysaccharides (or oligosaccharides). Carbohydrates are sometimes divided into "available carbohydrates", which are absorbed in the small intestine and "unavailable carbohydrates", which pass to the large intestine, where they are subject to fermentation by the gastrointestinal microbiota.
==== Glycemic index ====
The glycemic index (GI) and glycemic load concepts characterize the potential for carbohydrates in food to raise blood glucose compared to a reference food (generally pure glucose). Expressed numerically as GI, carbohydrate-containing foods can be grouped as high-GI (score more than 70), moderate-GI (56–69), or low-GI (less than 55) relative to pure glucose (GI=100). Consumption of carbohydrate-rich, high-GI foods causes an abrupt increase in blood glucose concentration that declines rapidly following the meal, whereas low-GI foods with lower carbohydrate content produces a lower blood glucose concentration that returns gradually after the meal.
Glycemic load is a measure relating the quality of carbohydrates in a food (low- vs. high-carbohydrate content – the GI) by the amount of carbohydrates in a single serving of that food.
=== Health effects of dietary carbohydrate restriction ===
Low-carbohydrate diets may miss the health advantages – such as increased intake of dietary fiber and phytochemicals – afforded by high-quality plant foods such as legumes and pulses, whole grains, fruits, and vegetables. A "meta-analysis, of moderate quality," included as adverse effects of the diet halitosis, headache and constipation.
Carbohydrate-restricted diets can be as effective as low-fat diets in helping achieve weight loss over the short term when overall calorie intake is reduced. An Endocrine Society scientific statement said that "when calorie intake is held constant [...] body-fat accumulation does not appear to be affected by even very pronounced changes in the amount of fat vs carbohydrate in the diet." In the long term, low-carbohydrate diets do not appear to confer a "metabolic advantage," and effective weight loss or maintenance depends on the level of calorie restriction, not the ratio of macronutrients in a diet. The reasoning of diet advocates that carbohydrates cause undue fat accumulation by increasing blood insulin levels, but a more balanced diet that restricts refined carbohydrates can also reduce serum glucose and insulin levels and may also suppress lipogenesis and promote fat oxidation. However, as far as energy expenditure itself is concerned, the claim that low-carbohydrate diets have a "metabolic advantage" is not supported by clinical evidence. Further, it is not clear how low-carbohydrate dieting affects cardiovascular health, although two reviews showed that carbohydrate restriction may improve lipid markers of cardiovascular disease risk.
Carbohydrate-restricted diets are no more effective than a conventional healthy diet in preventing the onset of type 2 diabetes, but for people with type 2 diabetes, they are a viable option for losing weight or helping with glycemic control. There is limited evidence to support routine use of low-carbohydrate dieting in managing type 1 diabetes. The American Diabetes Association recommends that people with diabetes should adopt a generally healthy diet, rather than a diet focused on carbohydrate or other macronutrients.
An extreme form of low-carbohydrate diet – the ketogenic diet – is established as a medical diet for treating epilepsy. Through celebrity endorsement during the early 21st century, it became a fad diet as a means of weight loss, but with risks of undesirable side effects, such as low energy levels and increased hunger, insomnia, nausea, and gastrointestinal discomfort. The British Dietetic Association named it one of the "top 5 worst celeb diets to avoid in 2018".
== Sources ==
Most dietary carbohydrates contain glucose, either as their only building block (as in the polysaccharides starch and glycogen), or together with another monosaccharide (as in the hetero-polysaccharides sucrose and lactose). Unbound glucose is one of the main ingredients of honey. Glucose is extremely abundant and has been isolated from a variety of natural sources across the world, including male cones of the coniferous tree Wollemia nobilis in Rome, the roots of Ilex asprella plants in China, and straws from rice in California.
^A The carbohydrate value is calculated in the USDA database and does not always correspond to the sum of the sugars, the starch, and the "dietary fiber".
== Metabolism ==
Carbohydrate metabolism is the series of biochemical processes responsible for the formation, breakdown and interconversion of carbohydrates in living organisms.
The most important carbohydrate is glucose, a simple sugar (monosaccharide) that is metabolized by nearly all known organisms. Glucose and other carbohydrates are part of a wide variety of metabolic pathways across species: plants synthesize carbohydrates from carbon dioxide and water by photosynthesis storing the absorbed energy internally, often in the form of starch or lipids. Plant components are consumed by animals and fungi, and used as fuel for cellular respiration. Oxidation of one gram of carbohydrate yields approximately 16 kJ (4 kcal) of energy, while the oxidation of one gram of lipids yields about 38 kJ (9 kcal). The human body stores between 300 and 500 g of carbohydrates depending on body weight, with the skeletal muscle contributing to a large portion of the storage. Energy obtained from metabolism (e.g., oxidation of glucose) is usually stored temporarily within cells in the form of ATP. Organisms capable of anaerobic and aerobic respiration metabolize glucose and oxygen (aerobic) to release energy, with carbon dioxide and water as byproducts.
=== Catabolism ===
Catabolism is the metabolic reaction which cells undergo to break down larger molecules, extracting energy. There are two major metabolic pathways of monosaccharide catabolism: glycolysis and the citric acid cycle.
In glycolysis, oligo- and polysaccharides are cleaved first to smaller monosaccharides by enzymes called glycoside hydrolases. The monosaccharide units can then enter into monosaccharide catabolism. A 2 ATP investment is required in the early steps of glycolysis to phosphorylate Glucose to Glucose 6-Phosphate (G6P) and Fructose 6-Phosphate (F6P) to Fructose 1,6-biphosphate (FBP), thereby pushing the reaction forward irreversibly. In some cases, as with humans, not all carbohydrate types are usable as the digestive and metabolic enzymes necessary are not present.
== Carbohydrate chemistry ==
Carbohydrate chemistry is a large and economically important branch of organic chemistry. Some of the main organic reactions that involve carbohydrates are:
Amadori rearrangement
Carbohydrate acetalisation
Carbohydrate digestion
Cyanohydrin reaction
Koenigs–Knorr reaction
Lobry de Bruyn–Van Ekenstein transformation
Nef reaction
Wohl degradation
Tipson-Cohen reaction
Ferrier rearrangement
Ferrier II reaction
== Chemical synthesis ==
Carbohydrate synthesis is a sub-field of organic chemistry concerned specifically with the generation of natural and unnatural carbohydrate structures. This can include the synthesis of monosaccharide residues or structures containing more than one monosaccharide, known as oligosaccharides. Selective formation of glycosidic linkages and selective reactions of hydroxyl groups are very important, and the usage of protecting groups is extensive.
Common reactions for glycosidic bond formation are as follows:
Chemical glycosylation
Fischer glycosidation
Koenigs-Knorr reaction
Crich beta-mannosylation
While some common protection methods are as below:
Carbohydrate acetalisation
Trimethylsilyl
Benzyl ether
p-Methoxybenzyl ether
== See also ==
Bioplastic
Carbohydrate NMR
Gluconeogenesis – A process where glucose can be synthesized by non-carbohydrate sources.
Glycobiology
Glycogen
Glycoinformatics
Glycolipid
Glycome
Glycomics
Glycosyl
Macromolecule
Saccharic acid
== References ==
== Further reading ==
"Compolition of foods raw, processed, prepared" (PDF). United States Department of Agriculture. September 2015. Archived (PDF) from the original on October 31, 2016. Retrieved October 30, 2016.
== External links ==
Carbohydrates, including interactive models and animations (Requires MDL Chime)
IUPAC-IUBMB Joint Commission on Biochemical Nomenclature (JCBN): Carbohydrate Nomenclature
Carbohydrates detailed
Carbohydrates and Glycosylation – The Virtual Library of Biochemistry, Molecular Biology and Cell Biology
Functional Glycomics Gateway, a collaboration between the Consortium for Functional Glycomics and Nature Publishing Group | Wikipedia/Carbohydrate_digestion |
High-energy X-rays or HEX-rays are very hard X-rays, with typical energies of 80–1000 keV (1 MeV), about one order of magnitude higher than conventional X-rays used for X-ray crystallography (and well into gamma-ray energies over 120 keV). They are produced at modern synchrotron radiation sources such as the Cornell High Energy Synchrotron Source, SPring-8, and the beamlines ID15 and BM18 at the European Synchrotron Radiation Facility (ESRF). The main benefit is the deep penetration into matter which makes them a probe for thick samples in physics and materials science and permits an in-air sample environment and operation. Scattering angles are small and diffraction directed forward allows for simple detector setups.
High energy (megavolt) X-rays are also used in cancer therapy, using beams generated by linear accelerators to suppress tumors.
== Advantages ==
High-energy X-rays (HEX-rays) between 100 and 300 keV have several advantages over conventional hard X-rays, which lie in the range of 5–20 keV They can be listed as follows:
High penetration into materials due to a strongly reduced photo-absorption cross-section. The photo-absorption strongly depends on the atomic number of the material and the X-ray energy. Several centimeter thick volumes can be accessed in steel and millimeters in lead containing samples.
No radiation damage to the sample, which can pin incommensurations or destroy the chemical compound to be analyzed.
The Ewald sphere has a curvature ten times smaller than in the low energy case, and allows whole regions to be mapped in a reciprocal lattice, similar to electron diffraction.
Access to diffuse scattering. This is absorption and not extinction limited at low energies, while volume enhancement takes place at high energies. Complete 3D maps over several Brillouin zones can be easily obtained.
High momentum transfers are naturally accessible due to the high momentum of the incident wave. This is of particular importance for studies of liquid, amorphous and nanocrystalline materials as well as for pair distribution function analysis.
Realization of the Materials oscilloscope.
Simple diffraction setups due to operation in air.
Diffraction in forward direction for easy registration with a 2D detector. Forward scattering and penetration make sample environments easy and straightforward.
Negligible polarization effects due to relative small scattering angles.
Special non-resonant magnetic scattering.
LLL (Triple Laue) interferometry
Access to high-energy spectroscopic levels, both electronic and nuclear.
Neutron-like, but complementary studies combined with high precision spatial resolution.
Cross-sections for Compton scattering are similar to coherent scattering or absorption cross-sections.
== Applications ==
With these advantages, HEX-rays can be applied for a wide range of investigations. An overview, which is far from complete:
Structural investigations of real materials, such as metals, ceramics, and liquids. In particular, in-situ studies of phase transitions at elevated temperatures up to the melt of any metal. Phase transitions, recovery, chemical segregation, recrystallization, twinning and domain formation are a few aspects to follow in a single experiment.
Materials in chemical or operation environments, such as electrodes in batteries, fuel cells, high-temperature reactors, electrolytes etc. The penetration and a well-collimated pencil beam allows focusing in the region and material of interest while it undergoes a chemical reaction.
Study of 'thick' layers, such as oxidation of steel in its production and rolling process, which are too thick for classical reflectometry experiments. Interfaces and layers in complicated environments, such as the intermetallic reaction of Zincalume surface coating on industrial steel in the liquid bath.
In situ studies of industrial like strip casting processes for light metals. A casting setup can be set up on a beamline and probed with the HEX-ray beam in real time.
Bulk studies in single crystals differ from studies in surface-near regions limited by the penetration of conventional X-rays. It has been found and confirmed in almost all studies, that critical scattering and correlation lengths are strongly affected by this effect.
Combination of neutron and HEX-ray investigations on the same sample, such as contrast variations due to the different scattering lengths.
Residual stress analysis in the bulk with unique spatial resolution in centimeter thick samples; in-situ under realistic load conditions.
In-situ studies of thermo-mechanical deformation processes such as forging, rolling, and extrusion of metals.
Real time texture measurements in the bulk during a deformation, phase transition or annealing, such as in metal processing.
Structures and textures of geological samples which may contain heavy elements and are thick.
High resolution triple crystal diffraction for the investigation of single crystals with all the advantages of high penetration and studies from the bulk.
Compton spectroscopy for the investigation of momentum distribution of the valence electron shells.
Imaging and tomography with high energies. Dedicated sources can be strong enough to obtain 3D tomograms in a few seconds. Combination of imaging and diffraction is possible due to simple geometries. For example, tomography combined with residual stress measurement or structural analysis.
== See also ==
== Notes ==
== References ==
== Further reading ==
Liss, Klaus-Dieter; Bartels, Arno; Schreyer, Andreas; Clemens, Helmut (2003). "High-Energy X-Rays: A tool for Advanced Bulk Investigations in Materials Science and Physics". Textures and Microstructures. 35 (3–4): 219–252. doi:10.1080/07303300310001634952.
Benmore, C. J. (2012). "A Review of High-Energy X-Ray Diffraction from Glasses and Liquids". ISRN Materials Science. 2012: 1–19. doi:10.5402/2012/852905.
Eberhard Haug; Werner Nakel (2004). The elementary process of Bremsstrahlung. World Scientific Lecture Notes in Physics. Vol. 73. River Edge, NJ: World Scientific. ISBN 978-981-238-578-9.
== External links ==
Liss, Klaus-Dieter; et al. (2006). "Recrystallization and phase transitions in a γ-Ti Al-based alloy as observed by ex situ and in situ high-energy X-ray diffraction". Acta Materialia. 54 (14): 3721–3735. Bibcode:2006AcMat..54.3721L. doi:10.1016/j.actamat.2006.04.004. | Wikipedia/High-energy_X-rays |
Dual-energy X-ray absorptiometry (DXA, or DEXA) is a means of measuring bone mineral density (BMD) with spectral imaging. Two X-ray beams, with different energy levels, are aimed at the patient's bones. When soft tissue absorption is subtracted, the bone mineral density (BMD) can be determined from the absorption of each beam by bone. Dual-energy X-ray absorptiometry is the most widely used and most thoroughly studied bone density measurement technology.
The DXA scan is typically used to diagnose and follow osteoporosis, as contrasted to the nuclear bone scan, which is sensitive to certain metabolic diseases of bones in which bones are trying to heal from infections, fractures, or tumors. It is also sometimes used to assess body composition.
== Physics ==
Soft tissue and bone have different attenuation coefficients to X-rays. A single X-ray beam passing through the body is attenuated by both soft tissue and bone, and it is not possible to determine from a single beam how much attenuation is attributable to the bone. However, attenuation coefficients vary with the energy of the X-rays, and, crucially, the ratio of the attenuation coefficients also varies. DXA uses two energies of X-ray. The difference in total absorption between the two can be used, by suitable weighting, to subtract out the absorption by soft tissue, leaving just the absorption by bone, which is related to bone density.
One type of DXA scanner uses a cerium filter with a tube voltage of 80 kV, resulting in effective photon energies of about 40 and 70 keV. Another type of DXA scanner uses a samarium filter with a tube voltage of 100 kV, which produces effective energies of 47 and 80 keV. Also, the tube voltage can be continuously switched between a low (for example 70 kV) and high (for example 140 kV) value in synchronism with the
frequency of the electrical mains, resulting in effective energies alternating between 45 and 100 keV.
The combination of dual X-ray absorptiometry and laser uses the laser to measure the thickness of the region scanned, allowing for varying proportions of lean soft tissue and adipose tissue within the soft tissue to be controlled for and improving the accuracy.
== Bone density measurement ==
=== Indications ===
The U.S. Preventive Services Task Force recommends that women over the age of 65 should get a DXA scan. The age when men should be tested is uncertain, but some sources recommend age 70. At-risk women should consider getting a scan when their risk is equal to that of a normal 65-year-old woman.
A person's risk can be measured with the University of Sheffield's FRAX calculator—which includes many clinical risk factors, including prior fragility fracture, use of glucocorticoids, heavy smoking, excess alcohol intake, rheumatoid arthritis, history of parental hip fracture, chronic renal and liver disease, chronic respiratory disease, long-term use of phenobarbital or phenytoin, celiac disease, inflammatory bowel disease, and other risks.
=== Scoring ===
The World Health Organization has defined the following categories based on bone density in white women:
Bone densities are often given to patients as a T score or a Z score. A T score tells the patient what their bone mineral density is in comparison to a young adult of the same gender with peak bone mineral density. A normal T score is -1.0 and above, low bone density is between -1.0 and -2.5, and osteoporosis is -2.5 and lower. A Z score is just a comparison of what a patient's bone mineral density is in comparison to the average bone mineral density of a male or female of their age and weight.
The WHO committee did not have enough data to create definitions for men or nonwhite women.
Special considerations are involved in the use of DXA to assess bone mass in children. Specifically, comparing the bone mineral density of children to the reference data of adults (to calculate a T-score) underestimates the BMD of children, because children have less bone mass than fully developed adults. This would lead to an over-diagnosis of osteopenia for children. To avoid an overestimation of bone mineral deficits, BMD scores are commonly compared to reference data for the same gender and age (by calculating a Z-score).
Also, there are other variables in addition to age that are suggested to confound the interpretation of BMD as measured by DXA. One important confounding variable is bone size. DXA has been shown to overestimate the bone mineral density of taller subjects and underestimate the bone mineral density of smaller subjects. This error is due to the way DXA calculates BMD. In DXA, bone mineral content (measured as the attenuation of the X-ray by the bones being scanned) is divided by the area (also measured by the machine) of the site being scanned.
Because DXA calculates BMD using area (aBMD: areal Bone Mineral Density), it is not an accurate measurement of true bone mineral density, which is mass divided by a volume. To distinguish DXA BMD from volumetric bone-mineral density, researchers sometimes refer to DXA BMD as an areal bone mineral density (aBMD). The confounding effect of differences in bone size is due to the missing depth value in the calculation of bone mineral density. Despite DXA technology's problems with estimating volume, it is still a fairly accurate measure of bone mineral content. Methods to correct for this shortcoming include the calculation of a volume that is approximated from the projected area measure by DXA. DXA BMD results adjusted in this manner are referred to as the bone mineral apparent density (BMAD) and are a ratio of the bone mineral content versus a cuboidal estimation of the volume of bone. Like the results for aBMD, BMAD results do not accurately represent true bone mineral density, since they use approximations of the bone's volume. BMAD is used primarily for research purposes and is not yet used in clinical settings.
Other imaging technologies such as quantitative computed tomography (QCT) are capable of measuring the bone's volume, and are, therefore, not susceptible to the confounding effect of bone-size in the way that DXA results are susceptible.
It is important for patients to get repeat BMD measurements done on the same machine each time, or at least a machine from the same manufacturer. Error between machines, or trying to convert measurements from one manufacturer's standard to another can introduce errors large enough to wipe out the sensitivity of the measurements.
DXA results must be adjusted if the patient is taking strontium supplements.
DXA can also used to measure trabecular bone score.
=== Current clinical practice in pediatrics ===
DXA is, by far, the most widely used technique for bone mineral density measurements, since it is relatively inexpensive, accessible, easy to use, and provides an accurate estimation of bone mineral density in adults.
The official position of the International Society for Clinical Densitometry (ISCD) is that a patient be tested for BMD if they have a condition that could precipitate bone loss, are to be prescribed pharmaceuticals known to cause bone loss, or are being treated and need reqiore monitoring. The ISCD states that there is no clearly understood correlation between BMD and the risk of a child's sustaining a fracture; the diagnosis of osteoporosis in children cannot be made on the basis of densitometry criteria. T-scores are prohibited with children and should not even appear on DXA reports. Thus, the WHO classification of osteoporosis and osteopenia in adults cannot be applied to children, but Z-scores can be used to assist diagnosis.
Some clinics may routinely carry out DXA scans on pediatric patients with conditions such as nutritional rickets, lupus, and Turner syndrome. DXA has been demonstrated to measure skeletal maturity and body fat composition and has been used to evaluate the effects of pharmaceutical therapy. It may also aid pediatricians in diagnosing and monitoring treatment of disorders of bone mass acquisition in childhood.
However, it seems that DXA is still in its early days in pediatrics, and there are widely acknowledged limitations and disadvantages with DXA. A view exists that DXA scans for diagnostic purposes should not even be performed outside specialist centers, and, if a scan is done outside one of these centers, it should not be interpreted without consultation with an expert in the field. Furthermore, most of the pharmaceuticals given to adults with low bone mass can be given to children only in strictly monitored clinical trials.
Whole-body calcium measured by DXA has been validated in adults using in-vivo neutron activation of total body calcium but this is not suitable for paediatric subjects and studies have been carried out on paediatric-sized animals.
== Body composition measurement ==
DXA scans can also be used to measure total body composition and fat content with a high degree of accuracy comparable to hydrostatic weighing with a few important caveats. From the DXA scans, a low resolution "fat shadow" image can also be generated, which gives an overall impression of fat distribution throughout the body. It has been suggested that, while very accurately measuring minerals and lean soft tissue (LST), DXA may provide skewed results due to its method of indirectly calculating fat mass by subtracting it from the LST and/or body cell mass (BCM) that DXA actually measures.
DXA scans have been suggested as useful tools to diagnose conditions with an abnormal fat distribution, such as familial partial lipodystrophy. They are also used to assess adiposity in children, especially to conduct clinical research.
== Radiation exposure ==
DXA uses X-rays to measure bone mineral density. The radiation dose of current DEXA systems is small, as low as 0.001 mSv, much less than a standard chest or dental x-ray. However, the dose delivered by older DEXA radiation sources (that used radioisotopes rather than x-ray generators) could be as high as 35 mGy, considered a significant dose by radiological health standards.
== Regulation ==
=== United States ===
The quality of DXA operators varies widely. DXA is not regulated like other radiation-based imaging techniques because of its low dosage. Each US state has a different policy as to what certifications are needed to operate a DXA machine. California, for example, requires coursework and a state-run test, whereas Maryland has no requirements for DXA technicians. Many states require a training course and certificate from the International Society of Clinical Densitometry (ISCD).
=== Australia ===
In Australia, regulation differs according to the applicable state or territory. For example, in Victoria, an individual performing DXA scans is required to completed a recognised course in safe use of bone mineral densitometers. In NSW and QLD a DXA technician only requires prior study in science, nursing or other related undergraduate study. The Environmental Protection Agency (EPA) oversees licensing of technicians, however, this is far from rigorous and regulation is non-existent.
== References ==
== External links ==
Non-invasive testing of bone density explained
Information for patients, from RSNA
Bone Densitometry explained | Wikipedia/Dual-energy_X-ray_absorptiometry |
Nuclear magnetic resonance spectroscopy of proteins (usually abbreviated protein NMR) is a field of structural biology in which NMR spectroscopy is used to obtain information about the structure and dynamics of proteins, and also nucleic acids, and their complexes. The field was pioneered by Richard R. Ernst and Kurt Wüthrich at the ETH, and by Ad Bax, Marius Clore, Angela Gronenborn at the NIH, and Gerhard Wagner at Harvard University, among others. Structure determination by NMR spectroscopy usually consists of several phases, each using a separate set of highly specialized techniques. The sample is prepared, measurements are made, interpretive approaches are applied, and a structure is calculated and validated.
NMR involves the quantum-mechanical properties of the central core ("nucleus") of the atom. These properties depend on the local molecular environment, and their measurement provides a map of how the atoms are linked chemically, how close they are in space, and how rapidly they move with respect to each other. These properties are fundamentally the same as those used in the more familiar magnetic resonance imaging (MRI), but the molecular applications use a somewhat different approach, appropriate to the change of scale from millimeters (of interest to radiologists) to nanometers (bonded atoms are typically a fraction of a nanometer apart), a factor of a million. This change of scale requires much higher sensitivity of detection and stability for long term measurement. In contrast to MRI, structural biology studies do not directly generate an image, but rely on complex computer calculations to generate three-dimensional molecular models.
Currently most samples are examined in a solution in water, but methods are being developed to also work with solid samples. Data collection relies on placing the sample inside a powerful magnet, sending radio frequency signals through the sample, and measuring the absorption of those signals. Depending on the environment of atoms within the protein, the nuclei of individual atoms will absorb different frequencies of radio signals. Furthermore, the absorption signals of different nuclei may be perturbed by adjacent nuclei. This information can be used to determine the distance between nuclei. These distances in turn can be used to determine the overall structure of the protein.
A typical study might involve how two proteins interact with each other, possibly with a view to developing small molecules that can be used to probe the normal biology of the interaction ("chemical biology") or to provide possible leads for pharmaceutical use (drug development). Frequently, the interacting pair of proteins may have been identified by studies of human genetics, indicating the interaction can be disrupted by unfavorable mutations, or they may play a key role in the normal biology of a "model" organism like the fruit fly, yeast, the worm C. elegans, or mice. To prepare a sample, methods of molecular biology are typically used to make quantities by bacterial fermentation. This also permits changing the isotopic composition of the molecule, which is desirable because the isotopes behave differently and provide methods for identifying overlapping NMR signals.
== Sample preparation ==
Protein nuclear magnetic resonance is performed on aqueous samples of highly purified protein. Usually, the sample consists of between 300 and 600 microlitres with a protein concentration in the range 0.1 – 3 millimolar. The source of the protein can be either natural or produced in a production system using recombinant DNA techniques through genetic engineering. Recombinantly expressed proteins are usually easier to produce in sufficient quantity, and this method makes isotopic labeling possible.
The purified protein is usually dissolved in a buffer solution and adjusted to the desired solvent conditions. The NMR sample is prepared in a thin-walled glass tube.
== Data collection ==
Protein NMR utilizes multidimensional nuclear magnetic resonance experiments to obtain information about the protein. Ideally, each distinct nucleus in the molecule experiences a distinct electronic environment and thus has a distinct chemical shift by which it can be recognized. However, in large molecules such as proteins the number of resonances can typically be several thousand and a one-dimensional spectrum inevitably has incidental overlaps. Therefore, multidimensional experiments that correlate the frequencies of distinct nuclei are performed. The additional dimensions decrease the chance of overlap and have a larger information content, since they correlate signals from nuclei within a specific part of the molecule. Magnetization is transferred into the sample using pulses of electromagnetic (radiofrequency) energy and between nuclei using delays; the process is described with so-called pulse sequences. Pulse sequences allow the experimenter to investigate and select specific types of connections between nuclei. The array of nuclear magnetic resonance experiments used on proteins fall in two main categories — one where magnetization is transferred through the chemical bonds, and one where the transfer is through space, irrespective of the bonding structure. The first category is used to assign the different chemical shifts to a specific nucleus, and the second is primarily used to generate the distance restraints used in the structure calculation, and in the assignment with unlabelled protein.
Depending on the concentration of the sample, the magnetic field of the spectrometer, and the type of experiment, a single multidimensional nuclear magnetic resonance experiment on a protein sample may take hours or even several days to obtain suitable signal-to-noise ratio through signal averaging, and to allow for sufficient evolution of magnetization transfer through the various dimensions of the experiment. Other things being equal, higher-dimensional experiments will take longer than lower-dimensional experiments.
Typically, the first experiment to be measured with an isotope-labelled protein is a 2D heteronuclear single quantum correlation (HSQC) spectrum, where "heteronuclear" refers to nuclei other than 1H. In theory, the heteronuclear single quantum correlation has one peak for each H bound to a heteronucleus. Thus, in the 15N-HSQC, with a 15N labelled protein, one signal is expected for each nitrogen atom in the back bone, with the exception of proline, which has no amide-hydrogen due to the cyclic nature of its backbone. Additional 15N-HSQC signals are contributed by each residue with a nitrogen-hydrogen bond in its side chain (W, N, Q, R, H, K). The 15N-HSQC is often referred to as the fingerprint of a protein because each protein has a unique pattern of signal positions. Analysis of the 15N-HSQC allows researchers to evaluate whether the expected number of peaks is present and thus to identify possible problems due to multiple conformations or sample heterogeneity. The relatively quick heteronuclear single quantum correlation experiment helps determine the feasibility of doing subsequent longer, more expensive, and more elaborate experiments. It is not possible to assign peaks to specific atoms from the heteronuclear single quantum correlation alone.
== Resonance assignment ==
In order to analyze the nuclear magnetic resonance data, it is important to get a resonance assignment for the protein, that is to find out which chemical shift corresponds to which atom. This is typically achieved by sequential walking using information derived from several different types of NMR experiment. The exact procedure depends on whether the protein is isotopically labelled or not, since a lot of the assignment experiments depend on carbon-13 and nitrogen-15.
=== Homonuclear nuclear magnetic resonance ===
With unlabelled protein the usual procedure is to record a set of two-dimensional homonuclear nuclear magnetic resonance experiments through correlation spectroscopy (COSY), of which several types include conventional correlation spectroscopy, total correlation spectroscopy (TOCSY) and nuclear Overhauser effect spectroscopy (NOESY). A two-dimensional nuclear magnetic resonance experiment produces a two-dimensional spectrum. The units of both axes are chemical shifts. The COSY and TOCSY transfer magnetization through the chemical bonds between adjacent protons. The conventional correlation spectroscopy experiment is only able to transfer magnetization between protons on adjacent atoms, whereas in the total correlation spectroscopy experiment the protons are able to relay the magnetization, so it is transferred among all the protons that are connected by adjacent atoms. Thus in a conventional correlation spectroscopy, an alpha proton transfers magnetization to the beta protons, the beta protons transfers to the alpha and gamma protons, if any are present, then the gamma proton transfers to the beta and the delta protons, and the process continues. In total correlation spectroscopy, the alpha and all the other protons are able to transfer magnetization to the beta, gamma, delta, epsilon if they are connected by a continuous chain of protons. The continuous chain of protons are the sidechain of the individual amino acids. Thus these two experiments are used to build so called spin systems, that is build a list of resonances of the chemical shift of the peptide proton, the alpha protons and all the protons from each residue’s sidechain. Which chemical shifts corresponds to which nuclei in the spin system is determined by the conventional correlation spectroscopy connectivities and the fact that different types of protons have characteristic chemical shifts. To connect the different spinsystems in a sequential order, the nuclear Overhauser effect spectroscopy experiment has to be used. Because this experiment transfers magnetization through space, it will show crosspeaks for all protons that are close in space regardless of whether they are in the same spin system or not. The neighbouring residues are inherently close in space, so the assignments can be made by the peaks in the NOESY with other spin systems.
One important problem using homonuclear nuclear magnetic resonance is overlap between peaks. This occurs when different protons have the same or very similar chemical shifts. This problem becomes greater as the protein becomes larger, so homonuclear nuclear magnetic resonance is usually restricted to small proteins or peptides.
=== Nitrogen-15 nuclear magnetic resonance ===
The most commonly performed 15N experiment is the 1H-15N HSQC. The experiment is highly sensitive and therefore can be performed relatively quickly. It is often used to check the suitability of a protein for structure determination using NMR, as well as for the optimization of the sample conditions. It is one of the standard suite of experiments used for the determination of the solution structure of protein. The HSQC can be further expanded into three- and four dimensional NMR experiments, such as 15N-TOCSY-HSQC and 15N-NOESY-HSQC.
=== Carbon-13 and nitrogen-15 nuclear magnetic resonance ===
When the protein is labelled with carbon-13 and nitrogen-15 it is possible to record triple resonance experiments that transfer magnetisation over the peptide bond, and thus connect different spin systems through bonds. This is usually done using some of the following experiments, HNCO, HN(CA)CO}, HNCA, HN(CO)CA, HNCACB and CBCA(CO)NH. All six experiments consist of a 1H-15N plane (similar to a HSQC spectrum) expanded with a carbon dimension. In the HN(CA)CO, each HN plane contains the peaks from the carbonyl carbon from its residue as well the preceding one in the sequence. The HNCO contains the carbonyl carbon chemical shift from only the preceding residue, but is much more sensitive than HN(CA)CO. These experiments allow each 1H-15N peak to be linked to the preceding carbonyl carbon, and sequential assignment can then be undertaken by matching the shifts of each spin system's own and previous carbons. The HNCA and HN(CO)CA works similarly, just with the alpha carbons (Cα) rather than the carbonyls, and the HNCACB and the CBCA(CO)NH contains both the alpha carbon and the beta carbon (Cβ). Usually several of these experiments are required to resolve overlap in the carbon dimension. This procedure is usually less ambiguous than the NOESY-based method since it is based on through bond transfer. In the NOESY-based methods, additional peaks corresponding to atoms that are close in space but that do not belong to sequential residues will appear, confusing the assignment process. Following the initial sequential resonance assignment, it is usually possible to extend the assignment from the Cα and Cβ to the rest of the sidechain using experiments such as HCCH-TOCSY, which is basically a TOCSY experiment resolved in an additional carbon dimension.
== Restraint generation ==
In order to make structure calculations, a number of experimentally determined restraints have to be generated. These fall into different categories; the most widely used are distance restraints and angle restraints.
=== Distance restraints ===
A crosspeak in a NOESY experiment signifies spatial proximity between the two nuclei in question. Thus each peak can be converted into a maximum distance between the nuclei, usually between 1.8 and 6 angstroms. The intensity of a NOESY peak is proportional to the distance to the minus 6th power, so the distance is determined according to the intensity of the peak. The intensity-distance relationship is not exact, so usually a distance range is used.
It is of great importance to assign the NOESY peaks to the correct nuclei based on the chemical shifts. If this task is performed manually it is usually very labor-intensive, since proteins usually have thousands of NOESY peaks. Some computer programs such as PASD/XPLOR-NIH, UNIO, CYANA, ARIA/CNS, and AUDANA/PONDEROSA-C/S in the Integrative NMR platform perform this task automatically on manually pre-processed listings of peak positions and peak volumes, coupled to a structure calculation. Direct access to the raw NOESY data without the cumbersome need of iteratively refined peak lists is so far only granted by the PASD algorithm implemented in XPLOR-NIH, the ATNOS/CANDID approach implemented in the UNIO software package, and the PONDEROSA-C/S and thus indeed guarantees objective and efficient NOESY spectral analysis.
To obtain as accurate assignments as possible, it is a great advantage to have access to carbon-13 and nitrogen-15 NOESY experiments, since they help to resolve overlap in the proton dimension. This leads to faster and more reliable assignments, and in turn to better structures.
=== Angle restraints ===
In addition to distance restraints, restraints on the torsion angles of the chemical bonds, typically the psi and phi angles, can be generated. One approach is to use the Karplus equation, to generate angle restraints from coupling constants. Another approach uses the chemical shifts to generate angle restraints. Both methods use the fact that the geometry around the alpha carbon affects the coupling constants and chemical shifts, so given the coupling constants or the chemical shifts, a qualified guess can be made about the torsion angles.
=== Orientation restraints ===
The analyte molecules in a sample can be partially ordered with respect to the external magnetic field of the spectrometer by manipulating the sample conditions. Common techniques include addition of bacteriophages or bicelles to the sample, or preparation of the sample in a stretched polyacrylamide gel. This creates a local environment that favours certain orientations of nonspherical molecules. Normally in solution NMR the dipolar couplings between nuclei are averaged out because of the fast tumbling of the molecule. The slight overpopulation of one orientation means that a residual dipolar coupling remains to be observed. The dipolar coupling is commonly used in solid state NMR and provides information about the relative orientation of the bond vectors relative to a single global reference frame. Typically the orientation of the N-H vector is probed in an HSQC-like experiment. Initially, residual dipolar couplings were used for refinement of previously determined structures, but attempts at de novo structure determination have also been made.
== Hydrogen–deuterium exchange ==
NMR spectroscopy is nucleus specific. Thus, it can distinguish between hydrogen and deuterium. The amide protons in the protein exchange readily with the solvent, and, if the solvent contains a different isotope, typically deuterium, the reaction can be monitored by NMR spectroscopy. How rapidly a given amide exchanges reflects its solvent accessibility. Thus amide exchange rates can give information on which parts of the protein are buried, hydrogen-bonded, etc. A common application is to compare the exchange of a free form versus a complex. The amides that become protected in the complex, are assumed to be in the interaction interface.
== Structure calculation ==
The experimentally determined restraints can be used as input for the structure calculation process. Researchers, using computer programs such as XPLOR-NIH, CYANA, GeNMR, or RosettaNMR attempt to satisfy as many of the restraints as possible, in addition to general properties of proteins such as bond lengths and angles. The algorithms convert the restraints and the general protein properties into energy terms, and then try to minimize this energy. The process results in an ensemble of structures that, if the data were sufficient to dictate a certain fold, will converge.
== Structure validation ==
The ensemble of structures obtained is an "experimental model", i.e., a representation of certain kind of experimental data. To acknowledge this fact is important because it means that the model could be a good or bad representation of that experimental data. In general, the quality of a model will depend on both the quantity and quality of experimental data used to generate it and the correct interpretation of such data.
Every experiment has associated errors. Random errors will affect the reproducibility and precision of the resulting structures. If the errors are systematic, the accuracy of the model will be affected. The precision indicates the degree of reproducibility of the measurement and is often expressed as the variance of the measured data set under the same conditions. The accuracy, however, indicates the degree to which a measurement approaches its "true" value.
Ideally, a model of a protein will be more accurate the more fit the actual molecule that represents and will be more precise as there is less uncertainty about the positions of their atoms. In practice there is no "standard molecule" against which to compare models of proteins, so the accuracy of a model is given by the degree of agreement between the model and a set of experimental data. Historically, the structures determined by NMR have been, in general, of lower quality than those determined by X-ray diffraction. This is due, in part, to the lower amount of information contained in data obtained by NMR. Because of this fact, it has become common practice to establish the quality of NMR ensembles, by comparing it against the unique conformation determined by X-ray diffraction, for the same protein. However, the X-ray diffraction structure may not exist, and, since the proteins in solution are flexible molecules, a protein represented by a single structure may lead to underestimate the intrinsic variation of the atomic positions of a protein. A set of conformations, determined by NMR or X-ray crystallography may be a better representation of the experimental data of a protein than a unique conformation.
The utility of a model will be given, at least in part, by the degree of accuracy and precision of the model. An accurate model with relatively poor precision could be useful to study the evolutionary relationships between the structures of a set of proteins, whereas the rational drug design requires both precise and accurate models. A model that is not accurate, regardless of the degree of precision with which it was obtained will not be very useful.
Since protein structures are experimental models that can contain errors, it is very important to be able to detect these errors. The process aimed at the detection of errors is known as validation.
There are several methods to validate structures, some are statistical like PROCHECK and WHAT IF while others are based on physical principles as CheShift, or a mixture of statistical and physics principles PSVS.
== Dynamics ==
In addition to structures, nuclear magnetic resonance can yield information on the dynamics of various parts of the protein. This usually involves measuring relaxation times such as T1 and T2 to determine order parameters, correlation times, and chemical exchange rates. NMR relaxation is a consequence of local fluctuating magnetic fields within a molecule. Local fluctuating magnetic fields are generated by molecular motions. In this way, measurements of relaxation times can provide information of motions within a molecule on the atomic level. In NMR studies of protein dynamics, the nitrogen-15 isotope is the preferred nucleus to study because its relaxation times are relatively simple to relate to molecular motions. This, however, requires isotope labeling of the protein. The T1 and T2 relaxation times can be measured using various types of HSQC-based experiments. The types of motions that can be detected are motions that occur on a time-scale ranging from about 10 picoseconds to about 10 nanoseconds. In addition, slower motions, which take place on a time-scale ranging from about 10 microseconds to 100 milliseconds, can also be studied. However, since nitrogen atoms are found mainly in the backbone of a protein, the results mainly reflect the motions of the backbone, which is the most rigid part of a protein molecule. Thus, the results obtained from nitrogen-15 relaxation measurements may not be representative of the whole protein. Therefore, techniques utilising relaxation measurements of carbon-13 and deuterium have recently been developed, which enables systematic studies of motions of the amino acid side-chains in proteins.
A challenging and special case of study regarding dynamics and flexibility of peptides and full-length proteins is represented by disordered structures. Nowadays, it is an accepted concept that proteins can exhibit a more flexible behaviour known as disorder or lack of structure; however, it is possible to describe an ensemble of structures instead of a static picture representing a fully functional state of the protein. Many advances are represented in this field in particular in terms of new pulse sequences, technological improvement, and rigorous training of researchers in the field.
== NMR spectroscopy on large proteins ==
Traditionally, nuclear magnetic resonance spectroscopy has been limited to relatively small proteins or protein domains. This is in part caused by problems resolving overlapping peaks in larger proteins, but this has been alleviated by the introduction of isotope labelling and multidimensional experiments. Another more serious problem is the fact that in large proteins the magnetization relaxes faster, which means there is less time to detect the signal. This in turn causes the peaks to become broader and weaker, and eventually disappear. Two techniques have been introduced to attenuate the relaxation: transverse relaxation optimized spectroscopy (TROSY) and deuteration of proteins. By using these techniques it has been possible to study proteins in complex with the 900 kDa chaperone GroES-GroEL.
== Automation of the process ==
Structure determination by NMR has traditionally been a time-consuming process, requiring interactive analysis of the data by a highly trained scientist. There has been considerable interest in automating the process to increase the throughput of structure determination and to make protein NMR accessible to non-experts (See structural genomics). The two most time-consuming processes involved are the sequence-specific resonance assignment (backbone and side-chain assignment) and the NOE assignment tasks. Several different computer programs have been published that target individual parts of the overall NMR structure determination process in an automated fashion. Most progress has been achieved for the task of automated NOE assignment. So far, only the FLYA and the UNIO approach were proposed to perform the entire protein NMR structure determination process in an automated manner without any human intervention. Modules in the NMRFAM-SPARKY such as APES (two-letter-code: ae), I-PINE/PINE-SPARKY (two-letter-code: ep; I-PINE web server) and PONDEROSA (two-letter-code: c3, up; PONDEROSA web server) are integrated so that it offers full automation with visual verification capability in each step. Efforts have also been made to standardize the structure calculation protocol to make it quicker and more amenable to automation. Recently, the POKY suite, the successor of programs mentioned above, has been released to provide modern GUI tools and AI/ML features.
== See also ==
NMR spectroscopy
Nuclear magnetic resonance
Nuclear magnetic resonance spectroscopy of carbohydrates
Nuclear magnetic resonance spectroscopy of nucleic acids
Protein crystallization
Protein dynamics
Relaxation (NMR)
X-ray crystallography
== References ==
== Further reading ==
== External links ==
NOESY-Based Strategy for Assignments of Backbone and Side Chain Resonances of Large Proteins without Deuteration (a protocol)
relax Software for the analysis of NMR dynamics
ProSA-web Archived 2011-05-11 at the Wayback Machine Web service for the recognition of errors in experimentally or theoretically determined protein structures
Protein structure determination from sparse experimental data - an introductory presentation
Protein NMR Protein NMR experiments | Wikipedia/Protein_nuclear_magnetic_resonance_spectroscopy |
Nuclear magnetic resonance spectroscopy of proteins (usually abbreviated protein NMR) is a field of structural biology in which NMR spectroscopy is used to obtain information about the structure and dynamics of proteins, and also nucleic acids, and their complexes. The field was pioneered by Richard R. Ernst and Kurt Wüthrich at the ETH, and by Ad Bax, Marius Clore, Angela Gronenborn at the NIH, and Gerhard Wagner at Harvard University, among others. Structure determination by NMR spectroscopy usually consists of several phases, each using a separate set of highly specialized techniques. The sample is prepared, measurements are made, interpretive approaches are applied, and a structure is calculated and validated.
NMR involves the quantum-mechanical properties of the central core ("nucleus") of the atom. These properties depend on the local molecular environment, and their measurement provides a map of how the atoms are linked chemically, how close they are in space, and how rapidly they move with respect to each other. These properties are fundamentally the same as those used in the more familiar magnetic resonance imaging (MRI), but the molecular applications use a somewhat different approach, appropriate to the change of scale from millimeters (of interest to radiologists) to nanometers (bonded atoms are typically a fraction of a nanometer apart), a factor of a million. This change of scale requires much higher sensitivity of detection and stability for long term measurement. In contrast to MRI, structural biology studies do not directly generate an image, but rely on complex computer calculations to generate three-dimensional molecular models.
Currently most samples are examined in a solution in water, but methods are being developed to also work with solid samples. Data collection relies on placing the sample inside a powerful magnet, sending radio frequency signals through the sample, and measuring the absorption of those signals. Depending on the environment of atoms within the protein, the nuclei of individual atoms will absorb different frequencies of radio signals. Furthermore, the absorption signals of different nuclei may be perturbed by adjacent nuclei. This information can be used to determine the distance between nuclei. These distances in turn can be used to determine the overall structure of the protein.
A typical study might involve how two proteins interact with each other, possibly with a view to developing small molecules that can be used to probe the normal biology of the interaction ("chemical biology") or to provide possible leads for pharmaceutical use (drug development). Frequently, the interacting pair of proteins may have been identified by studies of human genetics, indicating the interaction can be disrupted by unfavorable mutations, or they may play a key role in the normal biology of a "model" organism like the fruit fly, yeast, the worm C. elegans, or mice. To prepare a sample, methods of molecular biology are typically used to make quantities by bacterial fermentation. This also permits changing the isotopic composition of the molecule, which is desirable because the isotopes behave differently and provide methods for identifying overlapping NMR signals.
== Sample preparation ==
Protein nuclear magnetic resonance is performed on aqueous samples of highly purified protein. Usually, the sample consists of between 300 and 600 microlitres with a protein concentration in the range 0.1 – 3 millimolar. The source of the protein can be either natural or produced in a production system using recombinant DNA techniques through genetic engineering. Recombinantly expressed proteins are usually easier to produce in sufficient quantity, and this method makes isotopic labeling possible.
The purified protein is usually dissolved in a buffer solution and adjusted to the desired solvent conditions. The NMR sample is prepared in a thin-walled glass tube.
== Data collection ==
Protein NMR utilizes multidimensional nuclear magnetic resonance experiments to obtain information about the protein. Ideally, each distinct nucleus in the molecule experiences a distinct electronic environment and thus has a distinct chemical shift by which it can be recognized. However, in large molecules such as proteins the number of resonances can typically be several thousand and a one-dimensional spectrum inevitably has incidental overlaps. Therefore, multidimensional experiments that correlate the frequencies of distinct nuclei are performed. The additional dimensions decrease the chance of overlap and have a larger information content, since they correlate signals from nuclei within a specific part of the molecule. Magnetization is transferred into the sample using pulses of electromagnetic (radiofrequency) energy and between nuclei using delays; the process is described with so-called pulse sequences. Pulse sequences allow the experimenter to investigate and select specific types of connections between nuclei. The array of nuclear magnetic resonance experiments used on proteins fall in two main categories — one where magnetization is transferred through the chemical bonds, and one where the transfer is through space, irrespective of the bonding structure. The first category is used to assign the different chemical shifts to a specific nucleus, and the second is primarily used to generate the distance restraints used in the structure calculation, and in the assignment with unlabelled protein.
Depending on the concentration of the sample, the magnetic field of the spectrometer, and the type of experiment, a single multidimensional nuclear magnetic resonance experiment on a protein sample may take hours or even several days to obtain suitable signal-to-noise ratio through signal averaging, and to allow for sufficient evolution of magnetization transfer through the various dimensions of the experiment. Other things being equal, higher-dimensional experiments will take longer than lower-dimensional experiments.
Typically, the first experiment to be measured with an isotope-labelled protein is a 2D heteronuclear single quantum correlation (HSQC) spectrum, where "heteronuclear" refers to nuclei other than 1H. In theory, the heteronuclear single quantum correlation has one peak for each H bound to a heteronucleus. Thus, in the 15N-HSQC, with a 15N labelled protein, one signal is expected for each nitrogen atom in the back bone, with the exception of proline, which has no amide-hydrogen due to the cyclic nature of its backbone. Additional 15N-HSQC signals are contributed by each residue with a nitrogen-hydrogen bond in its side chain (W, N, Q, R, H, K). The 15N-HSQC is often referred to as the fingerprint of a protein because each protein has a unique pattern of signal positions. Analysis of the 15N-HSQC allows researchers to evaluate whether the expected number of peaks is present and thus to identify possible problems due to multiple conformations or sample heterogeneity. The relatively quick heteronuclear single quantum correlation experiment helps determine the feasibility of doing subsequent longer, more expensive, and more elaborate experiments. It is not possible to assign peaks to specific atoms from the heteronuclear single quantum correlation alone.
== Resonance assignment ==
In order to analyze the nuclear magnetic resonance data, it is important to get a resonance assignment for the protein, that is to find out which chemical shift corresponds to which atom. This is typically achieved by sequential walking using information derived from several different types of NMR experiment. The exact procedure depends on whether the protein is isotopically labelled or not, since a lot of the assignment experiments depend on carbon-13 and nitrogen-15.
=== Homonuclear nuclear magnetic resonance ===
With unlabelled protein the usual procedure is to record a set of two-dimensional homonuclear nuclear magnetic resonance experiments through correlation spectroscopy (COSY), of which several types include conventional correlation spectroscopy, total correlation spectroscopy (TOCSY) and nuclear Overhauser effect spectroscopy (NOESY). A two-dimensional nuclear magnetic resonance experiment produces a two-dimensional spectrum. The units of both axes are chemical shifts. The COSY and TOCSY transfer magnetization through the chemical bonds between adjacent protons. The conventional correlation spectroscopy experiment is only able to transfer magnetization between protons on adjacent atoms, whereas in the total correlation spectroscopy experiment the protons are able to relay the magnetization, so it is transferred among all the protons that are connected by adjacent atoms. Thus in a conventional correlation spectroscopy, an alpha proton transfers magnetization to the beta protons, the beta protons transfers to the alpha and gamma protons, if any are present, then the gamma proton transfers to the beta and the delta protons, and the process continues. In total correlation spectroscopy, the alpha and all the other protons are able to transfer magnetization to the beta, gamma, delta, epsilon if they are connected by a continuous chain of protons. The continuous chain of protons are the sidechain of the individual amino acids. Thus these two experiments are used to build so called spin systems, that is build a list of resonances of the chemical shift of the peptide proton, the alpha protons and all the protons from each residue’s sidechain. Which chemical shifts corresponds to which nuclei in the spin system is determined by the conventional correlation spectroscopy connectivities and the fact that different types of protons have characteristic chemical shifts. To connect the different spinsystems in a sequential order, the nuclear Overhauser effect spectroscopy experiment has to be used. Because this experiment transfers magnetization through space, it will show crosspeaks for all protons that are close in space regardless of whether they are in the same spin system or not. The neighbouring residues are inherently close in space, so the assignments can be made by the peaks in the NOESY with other spin systems.
One important problem using homonuclear nuclear magnetic resonance is overlap between peaks. This occurs when different protons have the same or very similar chemical shifts. This problem becomes greater as the protein becomes larger, so homonuclear nuclear magnetic resonance is usually restricted to small proteins or peptides.
=== Nitrogen-15 nuclear magnetic resonance ===
The most commonly performed 15N experiment is the 1H-15N HSQC. The experiment is highly sensitive and therefore can be performed relatively quickly. It is often used to check the suitability of a protein for structure determination using NMR, as well as for the optimization of the sample conditions. It is one of the standard suite of experiments used for the determination of the solution structure of protein. The HSQC can be further expanded into three- and four dimensional NMR experiments, such as 15N-TOCSY-HSQC and 15N-NOESY-HSQC.
=== Carbon-13 and nitrogen-15 nuclear magnetic resonance ===
When the protein is labelled with carbon-13 and nitrogen-15 it is possible to record triple resonance experiments that transfer magnetisation over the peptide bond, and thus connect different spin systems through bonds. This is usually done using some of the following experiments, HNCO, HN(CA)CO}, HNCA, HN(CO)CA, HNCACB and CBCA(CO)NH. All six experiments consist of a 1H-15N plane (similar to a HSQC spectrum) expanded with a carbon dimension. In the HN(CA)CO, each HN plane contains the peaks from the carbonyl carbon from its residue as well the preceding one in the sequence. The HNCO contains the carbonyl carbon chemical shift from only the preceding residue, but is much more sensitive than HN(CA)CO. These experiments allow each 1H-15N peak to be linked to the preceding carbonyl carbon, and sequential assignment can then be undertaken by matching the shifts of each spin system's own and previous carbons. The HNCA and HN(CO)CA works similarly, just with the alpha carbons (Cα) rather than the carbonyls, and the HNCACB and the CBCA(CO)NH contains both the alpha carbon and the beta carbon (Cβ). Usually several of these experiments are required to resolve overlap in the carbon dimension. This procedure is usually less ambiguous than the NOESY-based method since it is based on through bond transfer. In the NOESY-based methods, additional peaks corresponding to atoms that are close in space but that do not belong to sequential residues will appear, confusing the assignment process. Following the initial sequential resonance assignment, it is usually possible to extend the assignment from the Cα and Cβ to the rest of the sidechain using experiments such as HCCH-TOCSY, which is basically a TOCSY experiment resolved in an additional carbon dimension.
== Restraint generation ==
In order to make structure calculations, a number of experimentally determined restraints have to be generated. These fall into different categories; the most widely used are distance restraints and angle restraints.
=== Distance restraints ===
A crosspeak in a NOESY experiment signifies spatial proximity between the two nuclei in question. Thus each peak can be converted into a maximum distance between the nuclei, usually between 1.8 and 6 angstroms. The intensity of a NOESY peak is proportional to the distance to the minus 6th power, so the distance is determined according to the intensity of the peak. The intensity-distance relationship is not exact, so usually a distance range is used.
It is of great importance to assign the NOESY peaks to the correct nuclei based on the chemical shifts. If this task is performed manually it is usually very labor-intensive, since proteins usually have thousands of NOESY peaks. Some computer programs such as PASD/XPLOR-NIH, UNIO, CYANA, ARIA/CNS, and AUDANA/PONDEROSA-C/S in the Integrative NMR platform perform this task automatically on manually pre-processed listings of peak positions and peak volumes, coupled to a structure calculation. Direct access to the raw NOESY data without the cumbersome need of iteratively refined peak lists is so far only granted by the PASD algorithm implemented in XPLOR-NIH, the ATNOS/CANDID approach implemented in the UNIO software package, and the PONDEROSA-C/S and thus indeed guarantees objective and efficient NOESY spectral analysis.
To obtain as accurate assignments as possible, it is a great advantage to have access to carbon-13 and nitrogen-15 NOESY experiments, since they help to resolve overlap in the proton dimension. This leads to faster and more reliable assignments, and in turn to better structures.
=== Angle restraints ===
In addition to distance restraints, restraints on the torsion angles of the chemical bonds, typically the psi and phi angles, can be generated. One approach is to use the Karplus equation, to generate angle restraints from coupling constants. Another approach uses the chemical shifts to generate angle restraints. Both methods use the fact that the geometry around the alpha carbon affects the coupling constants and chemical shifts, so given the coupling constants or the chemical shifts, a qualified guess can be made about the torsion angles.
=== Orientation restraints ===
The analyte molecules in a sample can be partially ordered with respect to the external magnetic field of the spectrometer by manipulating the sample conditions. Common techniques include addition of bacteriophages or bicelles to the sample, or preparation of the sample in a stretched polyacrylamide gel. This creates a local environment that favours certain orientations of nonspherical molecules. Normally in solution NMR the dipolar couplings between nuclei are averaged out because of the fast tumbling of the molecule. The slight overpopulation of one orientation means that a residual dipolar coupling remains to be observed. The dipolar coupling is commonly used in solid state NMR and provides information about the relative orientation of the bond vectors relative to a single global reference frame. Typically the orientation of the N-H vector is probed in an HSQC-like experiment. Initially, residual dipolar couplings were used for refinement of previously determined structures, but attempts at de novo structure determination have also been made.
== Hydrogen–deuterium exchange ==
NMR spectroscopy is nucleus specific. Thus, it can distinguish between hydrogen and deuterium. The amide protons in the protein exchange readily with the solvent, and, if the solvent contains a different isotope, typically deuterium, the reaction can be monitored by NMR spectroscopy. How rapidly a given amide exchanges reflects its solvent accessibility. Thus amide exchange rates can give information on which parts of the protein are buried, hydrogen-bonded, etc. A common application is to compare the exchange of a free form versus a complex. The amides that become protected in the complex, are assumed to be in the interaction interface.
== Structure calculation ==
The experimentally determined restraints can be used as input for the structure calculation process. Researchers, using computer programs such as XPLOR-NIH, CYANA, GeNMR, or RosettaNMR attempt to satisfy as many of the restraints as possible, in addition to general properties of proteins such as bond lengths and angles. The algorithms convert the restraints and the general protein properties into energy terms, and then try to minimize this energy. The process results in an ensemble of structures that, if the data were sufficient to dictate a certain fold, will converge.
== Structure validation ==
The ensemble of structures obtained is an "experimental model", i.e., a representation of certain kind of experimental data. To acknowledge this fact is important because it means that the model could be a good or bad representation of that experimental data. In general, the quality of a model will depend on both the quantity and quality of experimental data used to generate it and the correct interpretation of such data.
Every experiment has associated errors. Random errors will affect the reproducibility and precision of the resulting structures. If the errors are systematic, the accuracy of the model will be affected. The precision indicates the degree of reproducibility of the measurement and is often expressed as the variance of the measured data set under the same conditions. The accuracy, however, indicates the degree to which a measurement approaches its "true" value.
Ideally, a model of a protein will be more accurate the more fit the actual molecule that represents and will be more precise as there is less uncertainty about the positions of their atoms. In practice there is no "standard molecule" against which to compare models of proteins, so the accuracy of a model is given by the degree of agreement between the model and a set of experimental data. Historically, the structures determined by NMR have been, in general, of lower quality than those determined by X-ray diffraction. This is due, in part, to the lower amount of information contained in data obtained by NMR. Because of this fact, it has become common practice to establish the quality of NMR ensembles, by comparing it against the unique conformation determined by X-ray diffraction, for the same protein. However, the X-ray diffraction structure may not exist, and, since the proteins in solution are flexible molecules, a protein represented by a single structure may lead to underestimate the intrinsic variation of the atomic positions of a protein. A set of conformations, determined by NMR or X-ray crystallography may be a better representation of the experimental data of a protein than a unique conformation.
The utility of a model will be given, at least in part, by the degree of accuracy and precision of the model. An accurate model with relatively poor precision could be useful to study the evolutionary relationships between the structures of a set of proteins, whereas the rational drug design requires both precise and accurate models. A model that is not accurate, regardless of the degree of precision with which it was obtained will not be very useful.
Since protein structures are experimental models that can contain errors, it is very important to be able to detect these errors. The process aimed at the detection of errors is known as validation.
There are several methods to validate structures, some are statistical like PROCHECK and WHAT IF while others are based on physical principles as CheShift, or a mixture of statistical and physics principles PSVS.
== Dynamics ==
In addition to structures, nuclear magnetic resonance can yield information on the dynamics of various parts of the protein. This usually involves measuring relaxation times such as T1 and T2 to determine order parameters, correlation times, and chemical exchange rates. NMR relaxation is a consequence of local fluctuating magnetic fields within a molecule. Local fluctuating magnetic fields are generated by molecular motions. In this way, measurements of relaxation times can provide information of motions within a molecule on the atomic level. In NMR studies of protein dynamics, the nitrogen-15 isotope is the preferred nucleus to study because its relaxation times are relatively simple to relate to molecular motions. This, however, requires isotope labeling of the protein. The T1 and T2 relaxation times can be measured using various types of HSQC-based experiments. The types of motions that can be detected are motions that occur on a time-scale ranging from about 10 picoseconds to about 10 nanoseconds. In addition, slower motions, which take place on a time-scale ranging from about 10 microseconds to 100 milliseconds, can also be studied. However, since nitrogen atoms are found mainly in the backbone of a protein, the results mainly reflect the motions of the backbone, which is the most rigid part of a protein molecule. Thus, the results obtained from nitrogen-15 relaxation measurements may not be representative of the whole protein. Therefore, techniques utilising relaxation measurements of carbon-13 and deuterium have recently been developed, which enables systematic studies of motions of the amino acid side-chains in proteins.
A challenging and special case of study regarding dynamics and flexibility of peptides and full-length proteins is represented by disordered structures. Nowadays, it is an accepted concept that proteins can exhibit a more flexible behaviour known as disorder or lack of structure; however, it is possible to describe an ensemble of structures instead of a static picture representing a fully functional state of the protein. Many advances are represented in this field in particular in terms of new pulse sequences, technological improvement, and rigorous training of researchers in the field.
== NMR spectroscopy on large proteins ==
Traditionally, nuclear magnetic resonance spectroscopy has been limited to relatively small proteins or protein domains. This is in part caused by problems resolving overlapping peaks in larger proteins, but this has been alleviated by the introduction of isotope labelling and multidimensional experiments. Another more serious problem is the fact that in large proteins the magnetization relaxes faster, which means there is less time to detect the signal. This in turn causes the peaks to become broader and weaker, and eventually disappear. Two techniques have been introduced to attenuate the relaxation: transverse relaxation optimized spectroscopy (TROSY) and deuteration of proteins. By using these techniques it has been possible to study proteins in complex with the 900 kDa chaperone GroES-GroEL.
== Automation of the process ==
Structure determination by NMR has traditionally been a time-consuming process, requiring interactive analysis of the data by a highly trained scientist. There has been considerable interest in automating the process to increase the throughput of structure determination and to make protein NMR accessible to non-experts (See structural genomics). The two most time-consuming processes involved are the sequence-specific resonance assignment (backbone and side-chain assignment) and the NOE assignment tasks. Several different computer programs have been published that target individual parts of the overall NMR structure determination process in an automated fashion. Most progress has been achieved for the task of automated NOE assignment. So far, only the FLYA and the UNIO approach were proposed to perform the entire protein NMR structure determination process in an automated manner without any human intervention. Modules in the NMRFAM-SPARKY such as APES (two-letter-code: ae), I-PINE/PINE-SPARKY (two-letter-code: ep; I-PINE web server) and PONDEROSA (two-letter-code: c3, up; PONDEROSA web server) are integrated so that it offers full automation with visual verification capability in each step. Efforts have also been made to standardize the structure calculation protocol to make it quicker and more amenable to automation. Recently, the POKY suite, the successor of programs mentioned above, has been released to provide modern GUI tools and AI/ML features.
== See also ==
NMR spectroscopy
Nuclear magnetic resonance
Nuclear magnetic resonance spectroscopy of carbohydrates
Nuclear magnetic resonance spectroscopy of nucleic acids
Protein crystallization
Protein dynamics
Relaxation (NMR)
X-ray crystallography
== References ==
== Further reading ==
== External links ==
NOESY-Based Strategy for Assignments of Backbone and Side Chain Resonances of Large Proteins without Deuteration (a protocol)
relax Software for the analysis of NMR dynamics
ProSA-web Archived 2011-05-11 at the Wayback Machine Web service for the recognition of errors in experimentally or theoretically determined protein structures
Protein structure determination from sparse experimental data - an introductory presentation
Protein NMR Protein NMR experiments | Wikipedia/Nuclear_magnetic_resonance_spectroscopy_of_proteins |
Resolution in the context of structural biology is the ability to distinguish the presence or absence of atoms or groups of atoms in a biomolecular structure. Usually, the structure originates from methods such as X-ray crystallography, electron crystallography, or cryo-electron microscopy. The resolution is measured of the "map" of the structure produced from experiment, where an atomic model would then be fit into. Due to their different natures and interactions with matter, in X-ray methods the map produced is of the electron density of the system (usually a crystal), whereas in electron methods the map is of the electrostatic potential of the system. In both cases, atomic positions are assumed similarly.
== Qualitative measures ==
In structural biology, resolution can be broken down into 4 groups: (1) sub-atomic, when information about the electron density is obtained and quantum effects can be studied, (2) atomic, individual atoms are visible and an accurate three-dimensional model can be constructed, (3) helical, secondary structure, such as alpha helices and beta sheets; RNA helices (in ribosomes), (4) domain, no secondary structure is resolvable.
== X-ray crystallography ==
As the crystal's repeating unit, its unit cell, becomes larger and more complex, the atomic-level picture provided by X-ray crystallography becomes less well-resolved (more "fuzzy") for a given number of observed reflections. Two limiting cases of X-ray crystallography are often discerned, "small-molecule" and "macromolecular" crystallography. Small-molecule crystallography typically involves crystals with fewer than 100 atoms in their asymmetric unit; such crystal structures are usually so well resolved that its atoms can be discerned as isolated "blobs" of electron density. By contrast, macromolecular crystallography often involves tens of thousands of atoms in the unit cell. Such crystal structures are generally less well-resolved (more "smeared out"); the atoms and chemical bonds appear as tubes of electron density, rather than as isolated atoms. In general, small molecules are also easier to crystallize than macromolecules; however, X-ray crystallography has proven possible even for viruses with hundreds of thousands of atoms.
== Cryo-electron microscopy ==
In cryo-electron microscopy (cryoEM), resolution is typically measured by the Fourier shell correlation (FSC), a three-dimensional extension of the Fourier ring correlation (FRC), which is also known as the spatial frequency correlation function. The FSC is a comparison of the Fourier transforms of two different constructed electrostatic potential maps, each map constructed from a random half of the original dataset.
Historically, there was much disagreement on which cutoff in the FSC would provide a good estimation of resolution, but the emerging gold-standard is the FSC cutoff of 0.143. This cutoff is derived from equivalencies to the X-ray crystallography standards of resolution definition.
=== Historical measurements ===
Many other criteria for determining resolution using the FSC curve exist, including the 3-σ criterion, 5-σ criterion, and 0.5 threshold. However, fixed-value thresholds (like 0.5, or 0.143) were argued to be based on incorrect statistical assumptions, though 0.143 has been shown to be strict enough so as to likely not overestimate resolution. The half-bit criterion indicates at which resolution there exists enough information to reliably interpret the volume, and the (modified) 3-σ criterion indicates where the FSC systematically emerges above the expected random correlations of the background noise.
In 2007, a resolution criterion independent of the FSC, Fourier Neighbor Correlation (FNC), was developed using the correlation between neighboring Fourier voxels to distinguish signal from noise. The FNC can be used to predict a less-biased FSC.
== See also ==
Structural biology
X-ray crystallography
Cryogenic electron microscopy
Image resolution
== Notes ==
== References ==
Harauz, G.; M. van Heel (1986). "Exact filters for general geometry three dimensional reconstruction". Optik. 73: 146–156.
van Heel, M.; Keegstra, W.; Schutter, W.; van Bruggen E.F.J. (1982). Arthropod hemocyanin studies by image analysis, in: Structure and Function of Invertebrate Respiratory Proteins, EMBO Workshop 1982, E.J. Wood. Life Sciences Reports. Vol. Suppl. 1. pp. 69–73. ISBN 9783718601554.
Saxton, W.O.; W. Baumeister (1982). "The correlation averaging of a regularly arranged bacterial cell envelope protein". Journal of Microscopy. 127 (2): 127–138. doi:10.1111/j.1365-2818.1982.tb00405.x. PMID 7120365. S2CID 27206060.
Böttcher, B.; Wynne, S.A.; Crowther, R.A. (1997). "Determination of the fold of the core protein of hepatitis B virus by electron microscopy". Nature. 386 (6620): 88–91. Bibcode:1997Natur.386...88B. doi:10.1038/386088a0. PMID 9052786. S2CID 275192.
van Heel, M.; Schatz, M. (2005). "Fourier shell correlation threshold criteria". Journal of Structural Biology. 151 (3): 250–262. doi:10.1016/j.jsb.2005.05.009. PMID 16125414.
Frank, Joachim (2006). Three-Dimnsional Electron Microscopy of Macromolecular Assemblies. New York: Oxford University Press. ISBN 0-19-518218-9.
Sousa, Duncan; Nikolaus Grigorieff (2007). "Ab initio resolution measurement for single particle structures". J Struct Biol. 157 (1): 201–210. doi:10.1016/j.jsb.2006.08.003. PMID 17029845.
== External links ==
PDB 101 Looking at Structures: Resolution
EMstats Trends and distributions of maps in EM Data Bank (EMDB), e.g. resolution trends
Structural resolution and electron density
Learning crystallography | Wikipedia/Resolution_(electron_density) |
Protein crystallization is the process of formation of a regular array of individual protein molecules stabilized by crystal contacts. If the crystal is sufficiently ordered, it will diffract. Some proteins naturally form crystalline arrays, like aquaporin in the lens of the eye.
In the process of protein crystallization, proteins are dissolved in an aqueous environment and sample solution until they reach the supersaturated state. Different methods are used to reach that state such as vapor diffusion, microbatch, microdialysis, and free-interface diffusion. Developing protein crystals is a difficult process influenced by many factors, including pH, temperature, ionic strength in the crystallization solution, and even gravity. Once formed, these crystals can be used in structural biology to study the molecular structure of the protein, particularly for various industrial or medical purposes.
== Development ==
For over 150 years, scientists from all around the world have known about the crystallization of protein molecules.
In 1840, Friedrich Ludwig Hünefeld accidentally discovered the formation of crystalline material in samples of earthworm blood held under two glass slides and occasionally observed small plate-like crystals in desiccated swine or human blood samples. These crystals were named as 'haemoglobin', by Felix Hoppe-Seyler in 1864. The seminal findings of Hünefeld inspired many scientists in the future.
In 1851, Otto Funke described the process of producing human haemoglobin crystals by diluting red blood cells with solvents, such as pure water, alcohol or ether, followed by slow evaporation of the solvent from the protein solution. In 1871, William T. Preyer, Professor at University of Jena, published a book entitled Die Blutkrystalle (The Crystals of Blood), reviewing the features of haemoglobin crystals from around 50 species of mammals, birds, reptiles and fishes.
In 1909, the physiologist Edward T. Reichert, together with the mineralogist Amos P. Brown, published a treatise on the preparation, physiology and geometrical characterization of haemoglobin crystals from several hundreds animals, including extinct species such as the Tasmanian wolf. Increasing protein crystals were found.
In 1934, John Desmond Bernal and his student Dorothy Hodgkin discovered that protein crystals surrounded by their mother liquor gave better diffraction patterns than dried crystals. Using pepsin, they were the first to discern the diffraction pattern of a wet, globular protein. Prior to Bernal and Hodgkin, protein crystallography had only been performed in dry conditions with inconsistent and unreliable results. This is the first X‐ray diffraction pattern of a protein crystal.
In 1958, the structure of myoglobin (a red protein containing heme), determined by X-ray crystallography, was first reported by John Kendrew. Kendrew shared the 1962 Nobel Prize in Chemistry with Max Perutz for this discovery.
Now, based on the protein crystals, the structures of them play a significant role in biochemistry and translational medicine.
== Background ==
=== The theory of protein crystallization ===
Protein crystallization is governed by the same physics that governs the formation of inorganic crystals. For crystallization to occur spontaneously, the crystal state must be favored thermodynamically. This is described by the Gibbs free energy (∆G), defined as ∆G = ∆H- T∆S, which captures how the enthalpy change of a process, ∆H, trades off with the corresponding change in entropy, ∆S. Entropy, roughly, describes the disorder of a system. Highly ordered states, such as protein crystals, are disfavored thermodynamically compared to more disordered states, such as solutions of proteins in solvent, because the transition to a more ordered state would decrease the total entropy of the system (negative ∆S). For crystals to form spontaneously, the ∆G of crystal formation must be negative. In other words, the entropic penalty must be paid by a corresponding decrease in the total energy of the system (∆H). Familiar inorganic crystals such as sodium chloride spontaneously form at ambient conditions because the crystal state decreases the total energy of the system. However, crystallization of some proteins under ambient conditions would both decrease the entropy (negative ∆S) and increase the total energy (positive ∆H) of the system, and thus does not occur spontaneously. To achieve crystallization of such proteins conditions are modified to make crystal formation energetically favorable. This is often accomplished by creation of a supersaturated solution of the sample.
=== A molecular view going from solution to crystal ===
Crystal formation requires two steps: nucleation and growth. Nucleation is the initiation step for crystallization. At the nucleation phase, protein molecules in solution come together as aggregates to form a stable solid nucleus. As the nucleus forms, the crystal grows bigger and bigger by molecules attaching to this stable nucleus. The nucleation step is critical for crystal formation since it is the first-order phase transition of samples moving from having a high degree of freedom to obtaining an ordered state (aqueous to solid). For the nucleation step to succeed, the manipulation of crystallization parameters is essential. The approach behind getting a protein to crystallize is to yield a lower solubility of the targeted protein in solution. Once the solubility limit is exceeded and crystals are present, crystallization is accomplished.
== Methods ==
=== Vapor diffusion ===
Vapor diffusion is the most commonly employed method of protein crystallization. In this method, droplets containing purified protein, buffer, and precipitant are allowed to equilibrate with a larger reservoir containing similar buffers and precipitants in higher concentrations. Initially, the droplet of protein solution contains comparatively low precipitant and protein concentrations, but as the drop and reservoir equilibrate, the precipitant and protein concentrations increase in the drop. If the appropriate crystallization solutions are used for a given protein, crystal growth occurs in the drop. This method is used because it allows for gentle and gradual changes in concentration of protein and precipitant concentration, which aid in the growth of large and well-ordered crystals.
Vapor diffusion can be performed in either hanging-drop or sitting-drop format. Hanging-drop apparatus involve a drop of protein solution placed on an inverted cover slip, which is then suspended above the reservoir. Sitting-drop crystallization apparatus place the drop on a pedestal that is separated from the reservoir. Both of these methods require sealing of the environment so that equilibration between the drop and reservoir can occur.
=== Microbatch ===
A microbatch usually involves immersing a very small volume of protein droplets in oil (as little as 1 μL). The reason that oil is required is because such low volume of protein solution is used and therefore evaporation must be inhibited to carry out the experiment aqueously. Although there are various oils that can be used, the two most common sealing agent are paraffin oils (described by Chayen et al.) and silicon oils (described by D’Arcy). There are also other methods for microbatching that do not use a liquid sealing agent and instead require a scientist to quickly place a film or some tape on a welled plate after placing the drop in the well.
Besides the very limited amounts of sample needed, this method also has as a further advantage that the samples are protected from airborne contamination, as they are never exposed to the air during the experiment.
=== Microdialysis ===
Microdialysis takes advantage of a semi-permeable membrane, across which small molecules and ions can pass, while proteins and large polymers cannot cross. By establishing a gradient of solute concentration across the membrane and allowing the system to progress toward equilibrium, the system can slowly move toward supersaturation, at which point protein crystals may form.
Microdialysis can produce crystals by salting out, employing high concentrations of salt or other small membrane-permeable compounds that decrease the solubility of the protein. Very occasionally, some proteins can be crystallized by dialysis salting in, by dialyzing against pure water, removing solutes, driving self-association and crystallization.
=== Free-interface diffusion ===
This technique brings together protein and precipitation solutions without premixing them, but instead, injecting them through either sides of a channel, allowing equilibrium through diffusion. The two solutions come into contact in a reagent chamber, both at their maximum concentrations, initiating spontaneous nucleation. As the system comes into equilibrium, the level of supersaturation decreases, favouring crystal growth.
== Influencing factors ==
=== pH ===
The basic driving force for protein crystallization is to optimize the number of bonds one can form with another protein through intermolecular interactions. These interactions depend on electron densities of molecules and the protein side chains that change as a function of pH. The tertiary and quaternary structure of proteins are determined by intermolecular interactions between the amino acids’ side groups, in which the hydrophilic groups are usually facing outwards to the solution to form a hydration shell to the solvent (water). As the pH changes, the charge on these polar side group also change with respect to the solution pH and the protein's pKa. Hence, the choice of pH is essential either to promote the formation of crystals where the bonding between molecules to each other is more favorable than with water molecules. pH is one of the most powerful manipulations that one can assign for the optimal crystallization condition.
=== Temperature ===
Temperature is another interesting parameter to discuss since protein solubility is a function of temperature. In protein crystallization, manipulation of temperature to yield successful crystals is one common strategy. Unlike pH, temperature of different components of the crystallography experiments could impact the final results such as temperature of buffer preparation, temperature of the actual crystallization experiment, etc.
=== Chemical additives ===
Chemical additives are small chemical compounds that are added to the crystallization process to increase the yield of crystals. The role of small molecules in protein crystallization had not been well thought of in the early days since they were thought of as contaminants in most case. Smaller molecules crystallize better than macromolecules such as proteins, therefore, the use of chemical additives had been limited prior to the study by McPherson. However, this is a powerful aspect of the experimental parameters for crystallization that is important for biochemists and crystallographers to further investigate and apply.
== Technologies ==
=== High throughput crystallization screening ===
High through-put methods exist to help streamline the large number of experiments required to explore the various conditions that are necessary for successful crystal growth. There are numerous commercial kits available for order which apply preassembled ingredients in systems guaranteed to produce successful crystallization. Using such a kit, a scientist avoids the hassle of purifying a protein and determining the appropriate crystallization conditions.
Liquid-handling robots can be used to set up and automate large number of crystallization experiments simultaneously. What would otherwise be slow and potentially error-prone process carried out by a human can be accomplished efficiently and accurately with an automated system. Robotic crystallization systems use the same components described above, but carry out each step of the procedure quickly and with a large number of replicates. Each experiment utilizes tiny amounts of solution, and the advantage of the smaller size is two-fold: the smaller sample sizes not only cut-down on expenditure of purified protein, but smaller amounts of solution lead to quicker crystallizations. Each experiment is monitored by a camera which detects crystal growth.
=== Protein engineering ===
Proteins can be engineered to improve the chance of successful protein crystallization by using techniques like Surface Entropy Reduction or engineering in crystal contacts. Frequently, problematic cysteine residues can be replaced by alanine to avoid disulfide-mediated aggregation, and residues such as lysine, glutamate, and glutamine can be changed to alanine to reduce intrinsic protein flexibility, which can hinder crystallization..
== Applications ==
Macromolecular structures can be determined from protein crystal using a variety of methods, including X-ray diffraction/X-ray crystallography, cryogenic electron microscopy (CryoEM) (including electron crystallography and microcrystal electron diffraction (MicroED)), small-angle X-ray scattering, and neutron diffraction. See also Structural biology.
Crystallization of proteins can also be useful in the formulation of proteins for pharmaceutical purposes.
== See also ==
== References ==
== Further reading ==
== External links ==
This page was reproduced (with modifications) with expressed consent from Dr. A. Malcolm Campbell. As of 2010, the original page can be found at Campbell AM (2003). "Protein Crystallization". Davidson, NC: Department of Biology, Davidson College. | Wikipedia/Protein_crystallization |
The Crystallography Open Database (COD) is a database of crystal structures. Unlike similar crystallographic databases, the database is entirely open-access, with registered users able to contribute published and unpublished structures of small molecules and small to medium-sized unit cell crystals to the database. As of November 2024, the database has more than 520,000 entries. The database has various contributors, and contains Crystallographic Information Files as defined by the International Union of Crystallography (IUCr). There are currently five sites worldwide that mirror this database. The 3D structures of compounds can be converted to input files for 3D printers.
== See also ==
Crystallography
Crystallographic database
== References ==
== External links ==
https://www.crystallography.net
http://cod.ibt.lt/
https://archive.today/20130714225104/http://cod.ensicaen.fr/
https://qiserver.ugr.es/cod/
http://nanocrystallography.research.pdx.edu/search/codmirror/
https://nanocrystallography.research.pdx.edu
https://crystallography.io/ Archived 2022-05-16 at the Wayback Machine | Wikipedia/Crystallography_open_database |
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