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Psychoactive drug

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Apsychoactive drug,mind-altering drug,orconsciousness-altering drugis achemical substancethat changesbrainfunction and results in alterations inperception,mood,consciousness,cognition,orbehavior.[1]The termpsychotropic drugis often used interchangeably, while some sources presentnarrower definitions.These substances may be used medically;recreationally;to purposefully improve performance or alterconsciousness;asentheogensfor ritual, spiritual, orshamanicpurposes;[2]or for research, includingpsychedelic therapy.Physiciansand otherhealthcare practitionersprescribepsychoactive drugs from several categories for therapeutic purposes.[3]These includeanesthetics,analgesics,anticonvulsantandantiparkinsoniandrugs as well as medications used to treatneuropsychiatric disorders,such asantidepressants,anxiolytics,antipsychotics,andstimulants.Some psychoactive substances may be used indetoxificationandrehabilitationprograms for persons dependent on or addicted to other psychoactive drugs.[4][5]

An assortment of psychoactive drugs, including both street drugs andmedications:
  1. Cocaine
  2. Crack cocaine
  3. Methylphenidate(Ritalin)
  4. Ephedrine
  5. MDMA(ecstasy)
  6. Peyote(mescaline)
  7. LSDblotter
  8. Psilocybinmushroom (Psilocybe cubensis)
  9. Salvia divinorum(salvinorin A)
  10. Diphenhydramine(Benadryl) (Unscheduled drug)
  11. Amanita muscariamushroom (muscimol) (Unscheduled drug)
  12. Tylenol 3(acetaminophen/codeine)
  13. Codeinewith muscle relaxant
  14. Pipe tobacco(nicotine) (Unscheduled drug)
  15. Bupropion(Unscheduled drug)
  16. Cannabis(THC)
  17. Hashish(THC)
The 2010ISCDstudy "Drug Harms in the UK: amulti-criteria decision analysis"found thatalcoholscored highest overall and in "Economic cost", "Injury", "Family adversities", "Environmental damage", and "Community harm".

Psychoactive substances often bring about subjective changes in consciousness and mood (although these may be objectively observed) that the user may find rewarding and pleasant (e.g.,euphoriaor a sense of relaxation) or advantageous in an objectively observable or measurable way (e.g. increased alertness), thus the effects are reinforcing to varying degrees.[6]Substances which arerewardingand thuspositively reinforcinghave the potential to induce a state ofaddiction– compulsive drug use despite negative consequences.[7]In addition, sustained use of some substances may producephysicalorpsychological dependenceor both, associated with physical or psychological withdrawal symptoms respectively.[7]Drug rehabilitationattempts to reduce addiction through a combination ofpsychotherapy,support groups, and other psychoactive substances. Conversely, certain psychoactive drugs may be so unpleasant that the person will never use the substance again. This is especially true of certaindeliriants(e.g.Jimson weed), powerfuldissociatives(e.g.Salvia divinorum), and classic psychedelics (e.g.LSD,psilocybin), in the form of a "bad trip".

Psychoactive drug misuse, dependence, and addiction have resulted in legal measures and moral debate.[8]Governmental controls on manufacture, supply, and prescription attempt to reduce problematic medical drug use; worldwide efforts to combat trafficking in psychoactive drugs are commonly termed the "war on drugs".Ethical concernshave also been raised about the overuse of these drugs clinically and about their marketing by manufacturers.[9]Popular campaigns to decriminalize[10]or legalize the recreational use of certain drugs (e.g.,cannabis) are also ongoing.

History

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Main articles:History of alcoholic drinksandProhibition of drugs

Psychoactive drug use can be traced toprehistory.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.[11]There is evidence of the chewing ofcocaleaves, for example, inPeruviansociety 8,000 years ago.[12][13]

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.[14]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.[15]

InThe Hasheesh Eater(1857), American authorFitz Hugh Ludlowwas 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 casesalcohol,which has enlightening effects only upon very particular characters.[16]

During the 20th century, the majority of countries initially responded to the use of recreational drugs byprohibiting production, distribution, or usethrough criminalization.[citation needed]A notable example occurred withProhibition 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.[citation needed]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."[17][failed verification]

In some countries, there has been a move towardharm 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 withPortugal's drug policyofdecriminalization,with a primary goal of reducing the adverse health effects of drug use.[18]

Terminology

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Psychoactiveandpsychotropicare 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 substancesrefers to the substances specified in theConvention on Psychotropic Substances,which does not include narcotics.[19]

The term "drug" has become askunked 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.[20]

Novel psychoactive substances (NPS)[note 1],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.[21]

Types

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Psychoactive drugs are divided according to their pharmacological effects. Common subtypes include:

  • Anxiolyticsare medicinally used to reduce the symptoms of anxiety, and sometimes insomnia.
Example:benzodiazepinessuch asXanaxandValium;barbiturates
  • Empathogen–entactogensalter emotional state, often resulting in an increased sense of empathy, closeness, and emotional communication.
Example:MDMA(ecstasy),MDA,6-APB,AMT
  • Stimulantsincrease 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 withADHDandnarcolepsy.
Examples:amphetamines,caffeine,cocaine,nicotine
  • Depressantsreduce, or depress, activity and stimulation in the central nervous system. This category encompasses a spectrum of substances with sedative, soporific, and anesthetic properties, and includesedatives,hypnotics,andopioids.
Examples:ethanol(alcohol), opioids such asmorphine,fentanyl,andcodeine,cannabis,barbiturates,andbenzodiazepines
Examples, psychedelics:Psilocybin,LSD,DMT (N,N-Dimethyltryptamine),mescaline
Examples, dissociatives:Dextromethorphan,Salvia divinorum
Examples, deliriants:Datura,scopolamine

Uses

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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,nootropicsupplements, and sleep aids.Caffeineis 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.[23]

Mental disorders

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Main article:Psychiatric medications
Zoloft (sertraline) is anSSRIantidepressant.

Psychiatric medications are psychoactive drugs prescribed for the management ofmental and emotional disorders,or to aid in overcomingchallenging behavior.[24]There are six major classes of psychiatric medications:

In addition, several psychoactive substances are currently employed to treat various addictions. These includeacamprosateornaltrexonein the treatment of alcoholism, ormethadoneorbuprenorphinemaintenance therapyin the case ofopioid addiction.[26]

Exposure to psychoactive drugs can causechanges to the brainthat 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.[27]

Military

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Drugs used by militaries

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Twohip flasks,located in the left-center, are featured in the military equipment used as emergencysustenanceby theLuftwaffe,which was the air force of Nazi Germany during World War II.
Main article:List of drugs used by militaries

Militaries worldwide have used or are using various psychoactive drugs to treat pain and toimprove performanceof soldiers by suppressing hunger, increasing the ability to sustain effort without food, increasing and lengtheningwakefulnessand concentration, suppressingfear,reducing empathy, and improving reflexes and memory-recall among other things.[28][29]

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 2012Jason LeopoldandJeffrey Kaye,psychologists and human rights workers, had aFreedom of Information Actrequest fulfilled that confirmed that the use of psychoactive drugs during interrogation was a long-standing practice.[30][31]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.[32][33] In May 2003 recently releasedPakistani captiveSha Mohammed Alikheldescribed the routine use of psychoactive drugs. He said thatJihan Wali,a captive kept in a nearby cell, was rendered catatonic through the use of these drugs.[citation needed]

Alcohol has a long association of military use, and has been called "liquid courage"for its role in preparing troops for battle,anaesthetizeinjured soldiers, and celebrate militaryvictories.It has also served as a coping mechanism forcombat stress reactionsand a means of decompression from combat to everyday life. However, this reliance on alcohol can have negative consequences for physical and mental health.[34]

The first documented case of a soldier overdosing onmethamphetamineduring combat, was the Finnish corporalAimo Koivunen,a soldier who fought in theWinter Warand theContinuation War.[35][36]

Psychochemical warfare

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Main article:Psychochemical warfare

Psychoactive drugs have been used in military applications asnon-lethal weapons.

Pain management

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Main article:Analgesics

Psychoactive drugs are often prescribed tomanage pain.The subjective experience of pain is primarily regulated byendogenousopioid peptides.Thus, pain can often be managed using psychoactives that operate on this neurotransmitter system, also known asopioid receptor agonists.This class of drugs can be highly addictive, and includesopiatenarcotics,likemorphineandcodeine.[37]NSAIDs,such asaspirinandibuprofen,are also analgesics. These agents also reduceeicosanoid-mediatedinflammationby inhibiting the enzymecyclooxygenase.

Anesthesia

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Main article:Anesthesia

General anestheticsare a class of psychoactive drug used on people to block physical pain and other sensations. Most anesthetics induceunconsciousness,allowing the person to undergo medical procedures likesurgery,without the feelings ofphysical painoremotional trauma.[38]To induce unconsciousness, anesthetics affect theGABAandNMDAsystems. For example,Propofolis a GABA agonist,[39]andketamineis anNMDA receptor antagonist.[40]

Performance-enhancement

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Main article:Performance-enhancing substance

Performance-enhancing substances,also known as performance-enhancing drugs (PEDs),[41]are substances that are used to improve any form of activity performance in humans. A well-known example ofcheating in sportsinvolvesdoping in sport,where banned physical performance-enhancing drugs are used by athletes andbodybuilders.Athletic performance-enhancing substances are sometimes referred as ergogenic aids.[42][43]Cognitive performance-enhancing drugs, commonly callednootropics,[44]are sometimes used by students to improve academic performance. Performance-enhancing substances are also used by military personnel to enhance combat performance.[45]

Recreation

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Main article:Recreational drug use
See also:Clubbing (subculture)
Global per capita alcohol consumption has shown a downward trajectory since the 20th century, suggesting a shift towards prioritizing health and well-being.

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 includecaffeine,alcohol,cocaine,LSD,nicotine,cannabis,anddextromethorphan.[46]Classes of drugs frequently used recreationally include:

In some modern and ancient cultures, drug usage is seen as astatussymbol. Recreational drugs are seen as status symbols in settings such as atnightclubsand parties.[47]For example, inancient Egypt,gods were commonly pictured holding hallucinogenic plants.[48]

Because there is controversy about regulation of recreational drugs, there is anongoing debate about drug prohibition.Critics of prohibition believe that regulation of recreational drug use is a violation of personal autonomy andfreedom.[49]In the United States, critics have noted that prohibition or regulation of recreational and spiritual drug use might beunconstitutional,and causing more harm than is prevented.[50]

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.[51]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.[51]

Ritual and spiritual

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Offerings

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Alcohol and tobacco (nicotine) have been and are used as offerings in various religions and spiritual practices.[citation needed]Coca leaves have been used as offerings in rituals.[52]

Alcohol
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Main article:Religion and alcohol

According to theCatholic Church,the sacramental wine used in the Eucharist must contain alcohol. Canon 924 of the presentCode of Canon Law (1983)states:

§3 The wine must be natural, made from grapes of the vine, and not corrupt.[53]

Psychoactive use

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Entheogen
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See also:EntheogenandList of substances used in rituals
Timothy Learywas a leading proponent of spiritual hallucinogen use.

Certain psychoactives, particularly hallucinogens, have been used for religious purposes since prehistoric times. Native Americans have usedpeyotecacti containingmescalinefor religious ceremonies for as long as 5700 years.[54]Themuscimol-containingAmanita muscariamushroom was used for ritual purposes throughout prehistoric Europe.[55]

The use of entheogens for religious purposes resurfaced in the West during thecounterculture movementsof the 1960s and 70s. Under the leadership ofTimothy Leary,new spiritual and intention-based movements began to useLSDand 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 theNative American Church,which is allowed to cultivate and distributepeyote.However, the genuine religious use of peyote, regardless of one's personal ancestry, is protected in Colorado, Arizona, New Mexico, Nevada, and Oregon.[56]

Psychedelic therapy
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Main article:Psychedelic therapy

Psychedelic therapy(orpsychedelic-assisted therapy) refers to the proposed use ofpsychedelic drugs,such aspsilocybin,MDMA,[note 2]LSD,andayahuasca,to treatmental disorders.[58][59]As of 2021, psychedelic drugs are controlled substances in most countries and psychedelic therapy is not legally available outside clinical trials, with some exceptions.[59][60]

Psychonautics
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Main article:Psychonautics

The aims and methods of psychonautics, when state-altering substances are involved, is commonly distinguished fromrecreational drug useby research sources.[61]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.[62]

Self-medication

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Main article:Self-medication

Self-medication,sometime called do-it-yourself (DIY) medicine, is ahuman behaviorin which an individual uses a substance or any exogenous influence to self-administer treatment for physical or psychological conditions, for exampleheadachesorfatigue.

The substances most widely used in self-medication areover-the-counterdrugs and dietary supplements, which are used to treat common health issues at home. These do not require adoctor'sprescriptionto obtain and, in some countries, are available in supermarkets and convenience stores.[63]

Sex

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Main article:Sex and drugs

Sexanddrugsdate back to ancient humans and have been interlocked throughout human history. Both legal and illegal, the consumption ofdrugsand their effects onthe human bodyencompasses all aspects of sex, includingdesire,performance,pleasure,conception,gestation,anddisease.

There are many different types of drugs that are commonly associated with their effects on sex, includingalcohol,cannabis,cocaine,MDMA,GHB,amphetamines,opioids,antidepressants,and many others.

Social movements

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Cannabis

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In the US, NORML (National Organization for the Reform of Marijuana Laws) has led since the 1970s a movement to legalize cannabis nationally.[64]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 internationalcountercultureholidaybased on the celebration and consumption of cannabis;[65][66][67]4:20 pm on any day is a time to consume cannabis.[68][69]

Operation Overgrow
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Main article:Operation Overgrow

Operation Overgrowis the name, given bycannabisactivists, of an "operation" to spreadmarijuana seedswildly "so it grows like weed".[70]The thought behind the operation is to draw attention to the debate about legalization/decriminalization of marijuana.

Suicide

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See also:Suicide methods § Drug_overdose,andsuicide pill

Adrug overdoseinvolves taking a dose of adrugthat exceeds safe levels. In the UK (England and Wales) until 2013, a drug overdose was the most common suicide method in females.[71]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.[72]The risk of death in suicide attempts involving overdose is about 2%.[72][verification needed]

Most people are under the influence ofsedative-hypnotic drugs(such asalcoholor benzodiazepines) when they die by suicide,[73]with alcoholism present in between 15% and 61% of cases.[74]Countries that have higher rates of alcohol use and a greater density of bars generally also have higher rates of suicide.[75]About 2.2–3.4% of those who have been treated for alcoholism at some point in their life die by suicide.[75]Alcoholics who attempt suicide are usually male, older, and have tried to take their own lives in the past.[74]In adolescents who misuse alcohol, neurological and psychological dysfunctions may contribute to the increased risk of suicide.[76]

Overdose attempts usingpainkillersare among the most common, due to their easy availability over-the-counter.[77]

Route of administration

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Main article:Route of administration

Psychoactive drugs are administered via oralingestionas a tablet, capsule, powder, liquid, and beverage; viainjectionbysubcutaneous,intramuscular,andintravenousroute; via rectum bysuppositoryandenema;and via inhalation bysmoking,vaporizing,and snorting. The efficiency of each method of administration varies from drug to drug.[78]

The psychiatric drugsfluoxetine,quetiapine,andlorazepamareingestedorally intabletorcapsuleform.Alcoholandcaffeineare ingested in beverage form;nicotineandcannabisare smoked orvaporized;peyoteandpsilocybin mushroomsare ingested in botanical form or dried; and crystalline drugs such ascocaineandmethamphetamineare usually inhaled or snorted.

Determinants of effects

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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 colleaguesRalph Metzner,andRichard Alpert(Ram Dass) in the 1960s.[79]

Dosage

The first factor, dosage, has been a truism since ancient times, or at least sinceParacelsuswho 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.[80]

Effects

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Main article:Neuropsychopharmacology
Illustration of the major elements ofneurotransmission.Depending on its method of action, a psychoactive substance may block the receptors on the post-synaptic neuron (dendrite), or block reuptake or affect neurotransmitter synthesis in the pre-synaptic neuron (axon).

Psychoactive drugs operate by temporarily affecting a person'sneurochemistry,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 moreneurotransmitterorneuroreceptorin the brain.

Drugs that increase activity in particular neurotransmitter systems are calledagonists.They act by increasing thesynthesisof one or more neurotransmitters, by reducing itsreuptakefrom thesynapses,or by mimicking the action by binding directly to the postsynaptic receptor. Drugs that reduce neurotransmitter activity are calledantagonists,and operate by interfering with synthesis or blocking postsynaptic receptors so that neurotransmitters cannot bind to them.[81]

Exposure to a psychoactive substance can cause changes in the structure and functioning ofneurons,as the nervous system tries to re-establish thehomeostasisdisrupted 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 calledsensitization.Conversely, overstimulation of receptors for a particular neurotransmitter may cause a decrease in both number and sensitivity of these receptors, a process calleddesensitizationortolerance.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.[82]Physical dependenceon antidepressants or anxiolytics may result in worse depression or anxiety, respectively, as withdrawal symptoms. Unfortunately, becauseclinical depression(also calledmajor depressive disorder) is often referred to simply asdepression,antidepressants are often requested by and prescribed for patients who are depressed, but not clinically depressed.

Affected neurotransmitter systems

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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.[83]

Neurotransmitter/receptor Classification Examples
Acetylcholine
 Cholinergics(acetylcholine receptor agonists) arecoline,nicotine,piracetam
Muscarinic antagonists(acetylcholine receptor antagonists) scopolamine,benzatropine,dimenhydrinate,diphenhydramine,trihexiphenidyl,doxylamine,atropine,quetiapine,olanzapine,mosttricyclics
Nicotinic antagonists(acetylcholine receptor antagonists) memantine,bupropion
Adenosine
 Adenosine receptor antagonists[84] caffeine,theobromine,theophylline
Dopamine
 Dopamine reuptake inhibitors cocaine,bupropion,methylphenidate,St John's wort,and certainTAAR1 agonistslikeamphetamine,phenethylamine,andmethamphetamine
Dopamine releasing agents Cavendishbananas,[85]TAAR1 agonistslikeamphetamine,phenethylamine,andmethamphetamine
Dopamine agonists pramipexole,Ropinirole,L-DOPA(prodrug),memantine
Dopamine antagonists haloperidol,droperidol,manyantipsychotics(e.g.,risperidone,olanzapine,quetiapine)
Dopamine partial agonists LSD,aripiprazole
gamma-Aminobutyric acid(GABA)
 GABA reuptake inhibitors tiagabine,St John's wort,vigabatrin,deramciclane
GABAA receptor agonists ethanol,niacin,[86]barbiturates,diazepam,clonazepam,lorazepam,temazepam,alprazolamand otherbenzodiazepines,zolpidem,eszopiclone,zaleplonand othernonbenzodiazepines,muscimol,phenibut
GABAA receptor positive allosteric modulators
GABA receptor antagonists thujone,bicuculline
GABAA receptor negative allosteric modulators
Norepinephrine
 Norepinephrine reuptake inhibitors St John's wort,[87]most non-SSRIantidepressantssuch asamoxapine,atomoxetine,bupropion,venlafaxine,quetiapine,thetricyclics,methylphenidate,SNRIssuch asduloxetine,venlafaxine,cocaine,tramadol,and certainTAAR1 agonistslikeamphetamine,phenethylamine,methamphetamine.
Norepinephrine releasing agents ephedrine,PPA,pseudoephedrine,amphetamine,phenethylamine,methamphetamine
Adrenergic agonists clonidine,guanfacine,phenylephrine
Adrenergic antagonists carvedilol,metoprolol,mianserin,prazosin,propranolol,trazodone,yohimbine,olanzapine
Serotonin
 Serotonin receptor agonists triptans(e.g.sumatriptan,eletriptan),psychedelics(e.g.lysergic acid diethylamide,psilocybin,mescaline), ergolines (e.g.lisuride,bromocriptine)
Serotonin reuptake inhibitors mostantidepressantsincludingSt John's wort,tricyclicssuch asimipramine,SSRIs(e.g.fluoxetine,sertraline,escitalopram),SNRIs(e.g.duloxetine,venlafaxine)
Serotonin releasing agents fenfluramine,MDMA(ecstasy),tryptamine
Serotonin receptor antagonists ritanserin,mirtazapine,mianserin,trazodone,cyproheptadine,memantine,atypical antipsychotics(e.g.,risperidone,olanzapine,quetiapine)
AMPA receptor
 AMPA receptor positive allosteric modulators aniracetam,CX717,piracetam
AMPA receptor antagonists kynurenic acid,NBQX,topiramate
Anandamide(Endocannabinoid system)
 Cannabinoid receptor agonists JWH-018
Cannabinoid receptor partial agonists Anandamide,THC,cannabidiol,cannabinol
Cannabinoid receptor inverse agonists Rimonabant
Anandamide reuptake inhibitors LY 2183240,VDM 11,AM 404
FAAHenzyme inhibitors MAFP,URB597,N-Arachidonylglycine
NMDA receptor
 NMDA receptor antagonists ethanol,ketamine,deschloroketamine,2-Fluorodeschloroketamine,PCP,DXM,Nitrous Oxide,memantine
GHB receptor
 GHB receptor agonists GHB,T-HCA
Sigma receptor Sigma-1 receptor agonists cocaine,DMT,DXM,fluvoxamine,ibogaine,opipramol,PCP,methamphetamine
Sigma-2 receptor agonists methamphetamine
Opioid receptor μ-opioid receptor agonists Narcotic opioids (e.g.codeine,morphine,hydrocodone,hydromorphone,oxycodone,oxymorphone,heroin,fentanyl)
μ-opioid receptor partial agonists buprenorphine
μ-opioid receptorinverse agonists naloxone
μ-opioid receptor antagonists naltrexone
κ-opioid receptor agonists salvinorin A,butorphanol,nalbuphine,pentazocine,ibogaine[88]
κ-opioid receptor antagonists buprenorphine
Histamine receptor
 H1receptor antagonists diphenhydramine,doxylamine,mirtazapine,mianserin,quetiapine,olanzapine,meclozine,mosttricyclics
H3receptor antagonists pitolisant
Indirect histamine receptor agonists modafinil[89]
Monoamine oxidase
 Monoamine oxidase inhibitors(MAOIs) phenelzine,iproniazid,tranylcypromine,selegiline,rasagiline,moclobemide,isocarboxazid,Linezolid,benmoxin,St John's wort,coffee,[90]garlic[91]
Melatonin receptor
 Melatonin receptoragonists agomelatine,melatonin,ramelteon,tasimelteon
Imidazoline receptor
 Imidazoline receptoragonists apraclonidine,clonidine,moxonidine,rilmenidine
Orexin receptor InderictOrexin receptoragonists modafinil[92]
Orexin receptorantagonists SB-334,867,SB-408,124,TCS-OX2-29,suvorexant

Addiction and dependence

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Main articles:AddictionandΔFosB
Addiction and dependence glossary[93][94][95]
  • addiction– abiopsychosocialdisorder characterized by persistent use of drugs (includingalcohol) despite substantial harm and adverse consequences
  • addictive drug– psychoactive substances that with repeated use are associated with significantly higher rates of substance use disorders, due in large part to the drug's effect on brainreward systems
  • dependence– an adaptive state associated with a withdrawal syndrome upon cessation of repeated exposure to a stimulus (e.g., drug intake)
  • drug sensitizationorreverse tolerance– the escalating effect of a drug resulting from repeated administration at a given dose
  • drug withdrawal– symptoms that occur upon cessation of repeated drug use
  • physical dependence– dependence that involves persistent physical–somaticwithdrawal symptoms (e.g., fatigue anddelirium tremens)
  • psychological dependence– dependence socially seen as being extremely mild compared to physical dependence (e.g., with enough willpower it could be overcome)
  • reinforcingstimuli– stimuli that increase the probability of repeating behaviors paired with them
  • rewardingstimuli– stimuli that the brain interprets as intrinsically positive and desirable or as something to approach
  • sensitization– an amplified response to a stimulus resulting from repeated exposure to it
  • substance use disorder– a condition in which the use of substances leads to clinically and functionally significant impairment or distress
  • tolerance– the diminishing effect of a drug resulting from repeated administration at a given dose
Comparison of the perceived harm for various psychoactive drugs from a poll among medical psychiatrists specialized in addiction treatment (David Nuttet al. 2007)[96]

Psychoactive drugs are often associated withaddictionordrug dependence.Dependence can be divided into two types:psychological dependence,by which a user experiences negative psychological or emotional withdrawal symptoms (e.g., depression) andphysical dependence,by which a user must use a drug to avoid physically uncomfortable or even medically harmful physicalwithdrawalsymptoms.[97]Drugs that are bothrewardingandreinforcingare addictive; these properties of a drug are mediated through activation of themesolimbic dopamine pathway,particularly thenucleus accumbens.Not all addictive drugs are associated with physical dependence, e.g.,amphetamine,and not all drugs that produce physical dependence areaddictive drugs,e.g.,oxymetazoline.

Globally, as of 2016,alcohol use disorderswere the most prevalent of all substance use disorders (SUD) worldwide; cannabis dependence and opioid dependence were the next most prevalent SUDs.[98]

Many professionals, self-help groups, and businesses specialize indrug rehabilitation,with varying degrees of success, and many parents attempt to influence the actions and choices of their children regarding psychoactives.[99]

Common forms ofrehabilitationincludepsychotherapy,support groupsandpharmacotherapy,which uses psychoactive substances to reduce cravings and physiologicalwithdrawalsymptoms while a user is going through detox.Methadone,itself anopioidand a psychoactive substance, is a common treatment forheroinaddiction, as is another opioid,buprenorphine.Recent research on addiction has shown some promise in usingpsychedelicssuch asibogaineto treat and even curedrug addictions,although this has yet to become a widely accepted practice.[100][101]

Legality

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Main article:Prohibition of drugs
Historical image of legalheroinbottle

The legality of psychoactive drugs has been controversial through most ofrecenthistory; theSecond Opium WarandProhibitionare two historical examples of legal controversy surrounding psychoactive drugs. However, in recent years, the most influential document regarding the legality of psychoactive drugs is theSingle Convention on Narcotic Drugs,an internationaltreatysigned in 1961 as an Act of theUnited Nations.Signed by 73 nations including the United States, theUSSR,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 torecreational drugsby combatting the sale, trafficking, and use of scheduled drugs.[102]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.[103]

In the United States, theFood and Drug Administration(FDA) has authority over all drugs, including psychoactive drugs. The FDA regulates which psychoactive drugs areover the counterand which are only available with aprescription.[104]However, certain psychoactive drugs, like alcohol, tobacco, and drugs listed in the Single Convention on Narcotic Drugs are subject to criminal laws. TheControlled Substances Actof 1970 regulates the recreational drugs outlined in the Single Convention on Narcotic Drugs.[105]Alcohol is regulated by state governments, but the federalNational Minimum Drinking Age Actpenalizes states for not following a national drinking age.[106]Tobacco is also regulated by all fifty state governments.[107]Most people accept such restrictions and prohibitions of certain drugs, especially the "hard" drugs, which are illegal in most countries.[108][109][110]

In the medical context, psychoactive drugs as a treatment for illness is widespread and generally accepted. Little controversy exists concerningover the counterpsychoactive medications inantiemeticsandantitussives.Psychoactive drugs are commonly prescribed to patients with psychiatric disorders. However, certain critics[who?]believe that certain prescription psychoactives, such asantidepressantsandstimulants,are overprescribed and threaten patients' judgement and autonomy.[111][112]

Effect on animals

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Further information:Effect of psychoactive drugs on animals,Recreational drug use in animals,andZoopharmacognosy

A number of animals consume different psychoactive plants, animals, berries and even fermented fruit, becoming intoxicated. An example of this is cats after consumingcatnip.Traditional legends of sacred plants often contain references to animals that introduced humankind to their use.[113]Animals and psychoactive plants appear to haveco-evolved,possibly explaining why these chemicals and their receptors exist within the nervous system.[114]

Widely used psychoactive drugs

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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).

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The most widely consumed psychotropic drugs worldwide are:[115]

Common prescribed drugs

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Common street drugs

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See also

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Notes

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  1. ^"New Psychoactive Substance", and "Novel Psychoactive Substance" (NPS) are often used interchangeably.
  2. ^MDMA and Ketamine are not a classical psychedelics but are sometimes discussed alongside classical psychedelics due to similarities in theirpsychoactiveand potentially therapeutic effects.[57]

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