hallucinogen
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A hallucinogen is a psychoactive agent that often or ordinarily causes
hallucinations A hallucination is a perception Perception (from the Latin ''perceptio'', meaning gathering or receiving) is the organization, identification, and interpretation of Sense, sensory information in order to represent and understand the pr ...
,
perceptual Perception (from the Latin Latin (, or , ) is a classical language belonging to the Italic languages, Italic branch of the Indo-European languages. Latin was originally spoken in the area around Rome, known as Latium. Through the powe ...

perceptual
anomalies, and other substantial subjective changes in
thought In their most common sense, the terms thought and thinking refer to conscious cognitive processes that can happen independently of sensory stimulation. Their most paradigmatic forms are judging, reasoning, concept formation, problem solving, and ...

thought
,
emotion Emotions are mental state, psychological states brought on by neurophysiology, neurophysiological changes, variously associated with thoughts, feelings, behavioural responses, and a degree of pleasure or suffering, displeasure. There is currentl ...

emotion
, and
consciousness , an English Paracelsian Paracelsianism (also Paracelsism; German: ') was an early modern History of medicine, medical movement based on the theories and therapies of Paracelsus. It developed in the second half of the 16th century, during the ...

consciousness
that are not typically experienced to such degrees with other drug classifications. The term hallucinogen almost invariably refers to any drug which causes what is called a "trip". The common classifications for hallucinogens are
psychedelics Psychedelics are a subset of hallucinogenic drugs whose primary effect is to trigger non-ordinary states of consciousness (known as psychedelic experiences or "trips" ) via serotonin 2A receptor agonism. This causes specific psychological, v ...
,
dissociative Dissociatives are a class of hallucinogen A hallucinogen is a psychoactive drug, psychoactive agent that often or ordinarily causes hallucinations, perception, perceptual anomalies, and other substantial subjective changes in thought, emotion, ...
s and
deliriant Deliriants are a class of hallucinogen. The term was coined in the early 1980s to distinguish these drugs from psychedelic drug, psychedelics and dissociatives such as lysergic acid diethylamide, LSD and ketamine, due to their primary effect of ca ...
s. Although hallucinogens all can induce
altered states of consciousness An altered state of consciousness (ASC), also called altered state of mind or mind alteration, is any condition which is significantly different from a normal waking state. By 1892, the expression was in use in relation to hypnosis File: ...
with some overlap in effects, there are quantifiable as well as vast qualitative differences in the induced
subjective experience In philosophy Philosophy (from , ) is the study of general and fundamental questions, such as those about reason, Metaphysics, existence, Epistemology, knowledge, Ethics, values, Philosophy of mind, mind, and Philosophy of language, lang ...
s between the different classes of hallucinogens due to differing and distinct
pharmacological Pharmacology is a branch of medicine Medicine is the Art (skill), art, science, and Praxis (process) , practice of caring for a patient and managing the diagnosis, prognosis, Preventive medicine, prevention, therapy, treatment or Palliative ...
mechanisms. Contemporarily, certain potentially hallucinogenic
GABAergic In molecular biology and physiology, something is GABAergic if it pertains to or affects the neurotransmitter A neurotransmitter is a signaling molecule In biology, cell signaling (cell signalling in British English), or cell-cell communicati ...
drugs such as
muscimol Muscimol (also known as agarin or pantherine) is one of the principal psychoactive constituents of ''Amanita muscaria'' and related species of mushroom. Muscimol is a potent, selective agonist for the GABAA receptor, GABAA receptors and displays ...

muscimol
, gaboxadol and zolpidem may be grouped into a distinct, separate or new category of hallucinogens that may be referred to as hypnotics despite many hypnotic and GABAergic drugs not being hallucinogenic like the three previously mentioned compounds. Additionally, cannabinergic compounds (such as THC) may also be considered distinct from the other categories as well despite sharing characteristics; specifically with both the psychedelic and dissociative classes.


Etymology

The word ''hallucinogen'' is derived from the word ''hallucination''. The term ''hallucinate'' dates back to around 1595–1605, and is derived from the Latin ''hallūcinātus'', the past participle of ''(h)allūcināri'', meaning "to wander in the mind."


Characteristics

Leo Hollister's five criteria for establishing that a drug is [classically] hallucinogenic were as follows: * in proportion to other effects, changes in thought, perception, and mood should predominate; * intellectual or memory impairment should be minimal; * stupor, narcosis, or excessive stimulation should not be an integral effect; * autonomic nervous system side effects should be minimal; and * addictive craving should be absent. This definition is broad enough to include a wide range of substances (mostly psychedelics) with different effects and characteristics. It should however also be noted that some of these criteria such as “minimal impairment of memory”, limited side effects of the nervous system or an “absence of addictiveness and cravings” only seems to directly apply to psychedelic substances or “classical hallucinogens” considering that drugs from both the
dissociative Dissociatives are a class of hallucinogen A hallucinogen is a psychoactive drug, psychoactive agent that often or ordinarily causes hallucinations, perception, perceptual anomalies, and other substantial subjective changes in thought, emotion, ...
and
deliriant Deliriants are a class of hallucinogen. The term was coined in the early 1980s to distinguish these drugs from psychedelic drug, psychedelics and dissociatives such as lysergic acid diethylamide, LSD and ketamine, due to their primary effect of ca ...
classes can exert memory impairment or addictiveness quite prominently. The most notable, distinguishing quality for the various types of hallucinogens appears to be a substantial change in thought, perception and mood. Although hallucinations are a common symptom of amphetamine psychosis, amphetamines are not considered hallucinogens as the hallucinations are not a primary effect of the drugs themselves.


Debate over nomenclature and taxonomy

Because of the multi-faceted phenomenology brought on by the class of drugs described in this article, efforts to create a consensus around their nomenclature and classification have not so far succeeded. In this article, they are referred to as ''hallucinogens'' and divided into Psychedelic drug, psychedelics (classical hallucinogens),
dissociative Dissociatives are a class of hallucinogen A hallucinogen is a psychoactive drug, psychoactive agent that often or ordinarily causes hallucinations, perception, perceptual anomalies, and other substantial subjective changes in thought, emotion, ...
s, and
deliriant Deliriants are a class of hallucinogen. The term was coined in the early 1980s to distinguish these drugs from psychedelic drug, psychedelics and dissociatives such as lysergic acid diethylamide, LSD and ketamine, due to their primary effect of ca ...
s, but the reader is well advised to consider that this system of classification is not universally accepted.


Nomenclature

The term ''hallucinogen'' sometimes refers only to classical hallucinogens, while sometimes it refers to a very broad class of pharmacological agents. It is therefore important to consult the definitions given in individual sources. The words ''entactogen'', ''empathogen'', ''dissociative'' and ''deliriant'' have all been coined to refer to classes of drugs which give hallucinatory experiences and/or show some resemblance or crossover with psychedelic drugs, albeit still with clear and important differences.


Psychedelics/classical hallucinogens

Psychedelics or classical hallucinogens in particular have been described by a profusion of names, most of which are associated with a particular theory of their nature. Regarding their nomenclature, David E. Nichols wrote in 2004: Louis Lewin started out in 1924 by using the word ''phantastica'' as the title of his ground-breaking monograph about plants that, in his words, "bring about evident cerebral excitation in the form of hallucinations, illusions and visions [...] followed by unconsciousness or other symptoms of altered cerebral functioning". But no sooner had the term been invented, or Lewin complained that the word "does not cover all that I should wish it to convey", and indeed with the proliferation of research following the discovery of LSD came numerous attempts to improve on it, such as ''hallucinogen'', ''phanerothyme'', ''Psychedelic drug, psychedelic'', ''psychotomimetic'', ''psychogenic'', ''schizophrenogenic'', ''cataleptogenic'', ''mysticomimetic'', ''psychodysleptic'', and ''entheogenic''. The word ''psychotomimetic'', meaning "mimicking psychosis", reflects the hypothesis of early researchers that the effects of psychedelic drugs are similar to naturally occurring symptoms of schizophrenia (see below). The word ''psychedelic'' was coined by Humphrey Osmond and has the rather mysterious but at least somewhat value-neutral meaning of "mind manifesting". The word ''entheogen'', on the other hand, which is often used to describe the religious and ritual use of psychedelic drugs in anthropological studies, is associated with the idea that it could be relevant to religion. Robin Carhart-Harris and Guy Goodwin write that the term ''psychedelic'' is preferable to ''hallucinogen'' for describing classical psychedelics because of the term ''hallucinogen''s "arguably misleading emphasis on these compounds' hallucinogenic properties."


Taxonomy

Hallucinogens can be classified by their subjective effects, mechanisms of action or chemical structure. These classifications often correlate to some extent.


Lewin's classes

A traditional classification, mainly of historical interest, is that of Lewin in his 1924 book ''Phantastica'': :''Class I Phantastica'' roughly correspond to the
psychedelics Psychedelics are a subset of hallucinogenic drugs whose primary effect is to trigger non-ordinary states of consciousness (known as psychedelic experiences or "trips" ) via serotonin 2A receptor agonism. This causes specific psychological, v ...
. Here the term is used to discriminate one particular class of hallucinogens which it seems to describe best. They typically have no sedative effects (sometimes the opposite) and there is usually a clearcut memory to their effects. These drugs have also been referred to as the "classical" hallucinogens. :''Class II Phantastica'' correspond to the other classes of hallucinogens. They tend to sedate in addition to their hallucinogenic properties and there often is an impaired memory trace after the effects wear off.


Pharmacological classes

One possible way of classifying the hallucinogens is by their chemical structure and that of the receptors they act on. A problem with structure-based frameworks is that the same structural motif can include a wide variety of drugs which have substantially different effects. For example, both methamphetamine and MDMA are substituted amphetamines, but methamphetamine has a much stronger stimulant action than MDMA, with none of the latter's empathogenic effects. Also, drugs commonly act on more than one receptor; dextromethorphan, DXM, for instance, is primarily dissociative in high doses, but also acts as a serotonin reuptake inhibitor, similar to many phenethylamines. Even so, in many cases structure-based frameworks are still very useful, and the identification of a biologically active pharmacophore and synthesis of analogues of known active substances remains an integral part of modern medicinal chemistry. In this vein, the following categories are often used: * ''Psychedelic drug, Psychedelics'' ** Serotonergics (5-HT2A receptor, 5-HT2A receptor agonists or serotonergic psychedelic, classical psychedelics) such as mescaline from peyote ''(Lophophora williamsii)'' *** Indoles / Tryptamines such as psilocybin from "magic" mushrooms (''Psilocybe'') **** Ergolines such as lysergol from morning glory (Convolvulaceae) ***** Lysergamides such as lysergic acid diethylamide, LSD ("acid"), derived from ergot (''Claviceps purpurea'') **** Beta-carbolines (monoamine oxidase inhibitors or MAOIs, specifically reversible inhibitors of monoamine oxidase A or RIMAs) such as harmala alkaloids such as norharman from ayahuasca (''Banisteriopsis caapi'') **** Complexly substituted tryptamines such as ibogaine from iboga (''Tabernanthe iboga'') *** Phenethylamines such as mescaline **** ''Empathogen–entactogens'' such as 3,4-methylenedioxyamphetamine, MDA ***** Substituted methylenedioxyphenethylamines (serotonin releasing agents) such as MDMA ("ecstasy") ** Cannabinoidergics (Cannabinoid receptor type 1, CB-1 receptor agonists or atypical psychedelics) such as THC from cannabis (''Cannabis'') * ''Dissociative drug, Dissociatives'' ** Antiglutamatergics (NMDA receptor antagonists or classical dissociatives) such as "laughing gas" (nitrous oxide) and ketamine ** Opioidergics (sometimes regarded as atypical psychedelics) (κ-Opioid receptor agonists or atypical dissociatives) such as salvinorin A from ''Salvia divinorum'' and pentazocine * ''Deliriants'' ** Anticholinergics (muscarine, muscarinic acetylcholine receptor antagonists or classical deliriants) such as tropane alkaloids such as atropine from deadly nightshade (''Atropa belladonna'') and diphenhydramine (Benadryl) **
GABAergic In molecular biology and physiology, something is GABAergic if it pertains to or affects the neurotransmitter A neurotransmitter is a signaling molecule In biology, cell signaling (cell signalling in British English), or cell-cell communicati ...
s (sometimes regarded as atypical dissociatives) (GABA A receptor, GABAA receptor agonists, and some allosteric modulator, positive allosteric modulators of the GABAA receptor, hypnotics, or atypical deliriants) such as
muscimol Muscimol (also known as agarin or pantherine) is one of the principal psychoactive constituents of ''Amanita muscaria'' and related species of mushroom. Muscimol is a potent, selective agonist for the GABAA receptor, GABAA receptors and displays ...

muscimol
from fly agaric (''Amanita muscaria'') and zolpidem (Ambien)


Effects by type


Psychedelics (classical hallucinogens)

The word ''psychedelic'' (From Ancient Greek ψυχή (psychê) ''mind, soul'' + δηλος (dêlos) ''manifest, reveal'' + -ic) was coined to express the idea of a drug that may manifest a hidden but real aspect of the mind or soul. It is commonly applied to any drug with perception-altering Psychedelic experience, psychedelic effects such as LSD and other ergotamine derivatives, Dimethyltryptamine, DMT and other tryptamines including the alkaloids of ''Psilocybe spp.'', mescaline and other phenethylamines. The classical hallucinogens are considered to be the representative psychedelics and LSD is generally considered the prototypical psychedelic. In order to refer to the LSD-like psychedelics, scientific authors have used the term "classical hallucinogen" in the sense defined by Glennon (1999): "The classical hallucinogens are agents that meet Hollister's original definition, but are also agents that: (a) bind at 5-HT2 serotonin receptors, and (b) are recognized by animals trained to discriminate 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) from vehicle. Otherwise, when the term 'psychedelic' is used to refer only to the LSD-like psychedelics (a.k.a. the classical hallucinogens), authors explicitly point that they intend 'psychedelic' to be understood according to this more restrictive interpretation. One explanatory model for the experiences provoked by psychedelics is the "reducing valve" concept, first articulated in Aldous Huxley's book ''The Doors of Perception''. In this view, the drugs disable the brain's "filtering" ability to selectively prevent certain perceptions, emotions, memories and thoughts from ever reaching the conscious mind. This effect has been described as ''mind expanding'', or ''consciousness expanding'', for the drug "expands" the realm of experience available to conscious awareness.


Dissociatives

''Dissociatives'' produce analgesia, amnesia and catalepsy at anesthetic doses. They also produce a sense of detachment from the surrounding environment, hence "the state has been designated as dissociative anesthesia since the patient truly seems disassociated from his environment." Dissociative symptoms include the disruption or compartmentalization of "...the usually integrated functions of consciousness, memory, identity or perception."p. 523 Dissociation of sensory input can cause derealization, the perception of the outside world as being dream-like, vague or unreal. Other dissociative experiences include depersonalization, which includes feeling dissociated from one's personality; feeling unreal; feeling able to observe one's actions but not actively take control; being unable to associate with one's self in the mirror while maintaining rational awareness that the image in the mirror is the same person. Simeon (2004) offered "...common descriptions of depersonalisation experiences: watching oneself from a distance (similar to watching a movie); candid out-of-body experiences; a sense of just going through the motions; one part of the self acting/participating while the other part is observing;...." The classical dissociatives achieve their effect through blocking the signals received by the NMDA receptor set (NMDA receptor antagonist, NMDA receptor antagonism) and include ketamine, methoxetamine (MXE), phencyclidine (PCP), dextromethorphan (DXM), and nitrous oxide. However, dissociation is also remarkably administered by salvinorin A's (the active constituent in ''Salvia divinorum'' shown to the left) potent kappa Opioid receptor, κ-opioid receptor agonism, though usually described as a very ''atypical'' dissociative. Some dissociatives can have central nervous system, CNS depressant effects, thereby carrying similar risks as opioids, which can slow breathing or heart rate to levels resulting in death (when using very high doses). DXM in higher doses can increase heart rate and blood pressure and still depress respiration. Inversely, PCP can have more unpredictable effects and has often been classified as a stimulant and a depressant in some texts along with being as a dissociative. While many have reported that they "feel no pain" while under the effects of PCP, DXM and Ketamine, this does not fall under the usual classification of anesthetics in recreational doses (anesthetic doses of DXM may be dangerous). Rather, true to their name, they process pain as a kind of "far away" sensation; pain, although present, becomes a disembodied experience and there is much less emotion associated with it. As for probably the most common dissociative, nitrous oxide, the principal risk seems to be due to Hypoxia (medical), oxygen deprivation. Injury from falling is also a danger, as nitrous oxide may cause sudden loss of consciousness, an effect of oxygen deprivation. Because of the high level of physical activity and relative imperviousness to pain induced by PCP, some deaths have been reported due to the release of myoglobin from ruptured muscle cells. High amounts of myoglobin can induce Kidney, renal shutdown. Many users of dissociatives have been concerned about the possibility of NMDA antagonist neurotoxicity (NAN). This concern is partly due to William E. White, the author of the DXM FAQ, who claimed that dissociatives definitely cause brain damage. The argument was criticized on the basis of lack of evidence and White retracted his claim. White's claims and the ensuing criticism surrounded original research by John Olney. In 1989, John Olney discovered that neuronal vacuolation and other cytotoxic changes ("lesions") occurred in brains of rats administered NMDA antagonists, including Phencyclidine, PCP and ketamine. Repeated doses of NMDA antagonists led to cellular tolerance and hence continuous exposure to NMDA antagonists did not lead to cumulative neurotoxic effects. Antihistamines such as diphenhydramine, barbiturates and even diazepam have been found to prevent NAN. Lysergic acid diethylamide, LSD and 2,5-Dimethoxy-4-bromoamphetamine, DOB have also been found to prevent NAN.


Deliriants

''Deliriants'', as their name implies, induce a state of delirium in the user, characterized by extreme confusion and an inability to control one's actions. They are called deliriants because their subjective effects are similar to the experiences of people with delirious fevers. The term was introduced by David F. Duncan and Robert S. Gold to distinguish these drugs from
psychedelics Psychedelics are a subset of hallucinogenic drugs whose primary effect is to trigger non-ordinary states of consciousness (known as psychedelic experiences or "trips" ) via serotonin 2A receptor agonism. This causes specific psychological, v ...
and
dissociative Dissociatives are a class of hallucinogen A hallucinogen is a psychoactive drug, psychoactive agent that often or ordinarily causes hallucinations, perception, perceptual anomalies, and other substantial subjective changes in thought, emotion, ...
s, such as lysergic acid diethylamide, LSD and ketamine respectively, due to their primary effect of causing delirium, as opposed to the more lucid states produced by the other hallucinogens. Despite the fully legal status of several common deliriant plants, deliriants are largely unpopular as recreational drug use, recreational drugs due to the severe, generally unpleasant and often dangerous nature of the hallucinogenic effects produced. Typical or classical deliriants are those which block the Muscarinic acetylcholine receptor, muscarinic acetylcholine Acetylcholine receptor, receptors (Receptor antagonist, antagonism). These are said to be anticholinergic. Many of these compounds are produced naturally by plant genera belonging to the nightshade family Solanaceae, such as ''Datura'', ''Brugmansia'' and ''Latua'' in the New World and ''Atropa'', ''Hyoscyamus'' and ''Mandragora (genus), Mandragora'' in the Old World. These tropane alkaloids are poisonous and can cause death due to tachycardia-induced heart failure and hyperthermia even in small doses. Additionally, over-the-counter antihistamines such as diphenhydramine (brand name Benadryl) and dimenhydrinate (brand name Dramamine) also have an anticholinergic effect. Curing of tobacco, Uncured tobacco is also a deliriant due to its Nicotine poisoning, intoxicatingly high levels of nicotine. The fly agaric mushroom, ''Amanita muscaria'', is often informally lumped with the nightshade plants as a ''deliriant'', though regarded as a ''hypnotic'' with some regularity as well. This may be explained by the familiarity of both ''A. muscaria'' and ''Atropa belladonna'' to European culture, their formal statuses as poisons, and their generally undesirable, unpleasant, and dangerous nature, with the potential for death from physical and behavioral toxicity a possibility even when dosages are carefully considered. Nutmeg has deliriant and hallucinogenic effects as well due to some of its psychoactive chemicals, such as myristicin, which may be anticholinergic like the tropane alkaloids of the nightshade plants, or as suggested by Alexander Shulgin, partially metabolized into the ''empathogen-entactogen'' MMDA (drug), MMDA.


Research chemicals and designer drugs

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 at the same time avoid being classified as illegal (by specification as a research chemical) and/or avoid detection in standard drug tests. Many designer drugs and research chemicals are hallucinogenic in nature, such as those in the 2C (psychedelics), 2C and 25-NB (NBOMe) families.


History of use

Psychedelics, dissociatives, and deliriants have a long history of use within medicinal and religious traditions around the world including shamanic forms of ritual healing and divination, initiation rites, and rituals of syncretistic movements such as União do Vegetal, Santo Daime, and the Native American Church. In the context of religious practice, psychedelic drug use, as well as other substances such as tobacco (atypical deliriant), are referred to as entheogens. In some places peyote is classified as 'sacrament' for part of religious ceremonies, and is legally condoned for such use. Additionally, plant deliriants also have a long-standing Deliriants#Occultism and folklore, reputation for being heavily connected with magic and folklore both in Western world, Western and Indigenous peoples, Indigenous cultures, with certain anticholinergic nightshades traditionally regarded as being integral to various practices in witchcraft. Hallucinogenic substances are among the oldest drugs used by human kind, as hallucinogenic substances naturally occur in mushrooms, cactus, cacti and a variety of other plants. Numerous cultures worldwide have endorsed the use of hallucinogens in medicine, religion and recreation, to varying extents, while some cultures have regulated or outright prohibited their use. In most developed countries today, the possession of many hallucinogens, even those found commonly in nature, is considered a crime punishable by fines, imprisonment or even capital punishment, death. In some countries, such as the United States and the Netherlands, partial deference may be granted to traditional religious use by members of Indigenous peoples, Indigenous ethnic minorities such as the Native American Church and the Santo Daime Church. Recently the União do Vegetal, a Christianity, Christian-based religious sect whose composition is not primarily ethnicity-based, won a United States Supreme Court decision authorizing its use of ayahuasca. However, in Brazil, ayahuasca use in a religious context has been legal since 1987. In fact, it is a common belief among members of the União do Vegetal that ayahuasca presents no risk for adolescents within the church, as long as they take it within a religious context.


Traditional religious and shamanic use

Historically, hallucinogens have been commonly used in religious or shamanism, shamanic rituals. In this context they are referred to as entheogens, and are used to facilitate healing, divination, communication with spirits, and coming-of-age ceremonies. Evidence exists for the use of entheogens in prehistory, prehistoric times, as well as in numerous ancient cultures, including Ancient Egyptian, History of Mycenaean Greece, Mycenaean, History of Ancient Greece, Ancient Greek, Vedic civilization, Vedic, Maya civilization, Maya, Inca and Aztec cultures. The Upper Amazon is home to the strongest extant entheogenic tradition; the Urarina of the Peruvian Amazon, for instance, continue to practice an elaborate system of ayahuasca shamanism, coupled with an animistic belief system. Shamans consume hallucinogenic substances in order to induce a trance. Once in this trance, shamans believe that they are able to communicate with the spirit world, and can see what is causing their patients' illness. The Aguaruna of Peru believe that many illnesses are caused by the darts of sorcerers. Under the influence of Ayahuasca, yaji, a hallucinogenic drink, Aguaruna shamans try to discover and remove the darts from their patients. In the 1970s, Frida G. Surawicz and Richard Banta published a review of two case studies where hallucinogenic drug-use appeared to play a role in "delusions of being changed into a wolf" (sometimes referred to as "lycanthropy," or being a "werewolf"). They described a patient whose delusion was thought to be caused by an altered state of consciousness "brought on by LSD and strychnine and continued casual marijuana use." The review was published in the Canadian Psychiatric Association Journal. While both central cases described white male patients from contemporary Appalachia, Surawicz and Banta generalized their conclusions about a link between hallucinogens and "lycanthropy," based on historical accounts that reference myriad types of pharmacologically-similar drug-use alongside descriptions of "lycanthropes."


Early scientific investigations

Although natural hallucinogenic drugs have been known to mankind for millennia, it was not until the early 20th century that they received extensive attention from Western world, Western science. Earlier beginnings include scientific studies of nitrous oxide in the late 18th century, and initial studies of the constituents of the peyote cactus in the late 19th century. Starting in 1927 with Kurt Beringer's ''Der Meskalinrausch'' (The Mescaline Intoxication), more intensive effort began to be focused on studies of psychoactive plants. Around the same time, Louis Lewin published his extensive survey of psychoactive plants, ''Phantastica'' (1928). Important developments in the years that followed included the re-discovery of Mexico, Mexican psilocybin mushrooms (in 1936 by Robert J. Weitlaner) and Turbina corymbosa, Christmas vine (in 1939 by Richard Evans Schultes). Arguably the most important pre-World War II development was by Albert Hofmann's 1938 discovery of the semi-Chemical synthesis, synthetic drug LSD, which was later discovered to produce hallucinogenic effects in 1943.


Hallucinogens after World War II

After World War II there was an explosion of interest in hallucinogenic drugs in psychiatry, owing mainly to the invention of LSD. Interest in the drugs tended to focus on either the potential for psychotherapy, psychotherapeutic applications of the drugs (see ''psychedelic psychotherapy''), or on the use of hallucinogens to produce a "controlled psychosis", in order to understand psychotic disorders such as schizophrenia. By 1951, more than 100 articles on LSD had appeared in medical journals, and by 1961, the number had increased to more than 1000 articles. Hallucinogens were also researched in several countries for their potential as agents of chemical warfare. Most famously, several incidents associated with the Central Intelligence Agency, CIA's MK-ULTRA mind control research project have been the topic of media attention and lawsuits. At the beginning of the 1950s, the existence of hallucinogenic drugs was virtually unknown to the general public in the Western World, West. However this soon changed as several influential figures were introduced to the hallucinogenic experience. Aldous Huxley's 1953 essay ''The Doors of Perception'', describing his experiences with mescaline, and R. Gordon Wasson's 1957 Life magazine article (''Seeking the Magic Mushroom'') brought the topic into the public limelight. In the early 1960s, counterculture icons such as Jerry Garcia, Timothy Leary, Allen Ginsberg and Ken Kesey advocated the drugs for their psychedelic drug, psychedelic effects, and a large subculture of psychedelic drug users was spawned. Psychedelic drugs played a major role in catalyzing the vast social changes initiated in the 1960s. As a result of the growing popularity of LSD and disdain for the hippies with whom it was heavily associated, LSD was banned in the United States in 1967. This greatly reduced the clinical research about LSD, although limited experiments continued to take place, such as those conducted by Reese Jones in San Francisco. As early as the 1960s, research into the medicinal properties of LSD was being conducted. It has been found that LSD is a fairly effective treatment for mental disorders such as obsessive compulsive disorder (OCD). "Savage et al. (1962) provided the earliest report of efficacy for a hallucinogen in OCD, where after two doses of LSD, a patient who suffered from depression and violent obsessive sexual thoughts experienced dramatic and permanent improvement (Nichols 2004: 164)." Starting in the mid-20th century, psychedelic drugs has been the object of extensive attention in the Western world. They have been and are being explored as potential therapeutic agents in treating clinical depression, depression, posttraumatic stress disorder, obsessive–compulsive disorder, alcoholism, drug addiction, cluster headaches, and other ailments. Early military research focused on their use as incapacitating agents. Intelligence agencies tested these drugs in the hope that they would provide an effective means of interrogation, with little success. 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. Despite prohibition, the recreational, spiritual, and medical use of psychedelics continues today. Organizations, such as Multidisciplinary Association for Psychedelic Studies, MAPS and the Heffter Research Institute, have arisen to foster research into their safety and efficacy, while advocacy groups such as the Center for Cognitive Liberty and Ethics push for their legalization. In addition to this activity by proponents, hallucinogens are also widely used in basic science research to understand the mind and brain. However, ever since hallucinogenic experimentation was discontinued in the late 1960s, research into the therapeutic applications of such drugs have been almost nonexistent, that is until this last decade where research has finally been allowed to resume.


Legal status and attitudes

In Canada, mescaline is listed as prohibited under schedule III of the Controlled Drugs and Substances Acts, but peyote is specifically exempt and legally available. As of 2008, most well-known hallucinogens (aside from dextromethorphan, diphenhydramine and dimenhydrinate) are illegal in most Western countries. In the United States hallucinogens are classified as a schedule 1 drug. The 3-pronged test for schedule 1 drugs is as follows: the drug has no currently accepted medical use, there is a lack of safety for the use of the drug under medical supervision, and the substance has a high potential for abuse. One notable exception to the current criminalization trend is in parts of Western Europe, especially in the Netherlands, where cannabis is considered to be a "Drug harmfulness, soft drug". Previously included were hallucinogenic mushrooms, but as of October 2007 the Netherlands officials have moved to ban their sale following several widely publicized incidents involving tourists. While the possession of soft drugs is technically illegal, the Dutch government has decided that using law enforcement to combat their use is largely a waste of resources. As a result, public "coffeeshops" in the Netherlands openly sell cannabis for personal use, and "smart shops" sell drugs like ''Salvia divinorum'', and until the ban of psilocybin mushrooms took effect, they were still available for purchase in smartshops as well. (''See Drug policy of the Netherlands''). Despite being scheduled as a controlled substance in the mid-1980s, MDMA's popularity has been growing since that time in western Europe and in the United States. Attitudes towards hallucinogens other than cannabis have been slower to change. Several attempts to change the law on the grounds of freedom of religion have been made. Some of these have been successful, for example the Native American Church in the United States, and Santo Daime in Brazil. Some people argue that a religious setting should not be necessary for the legitimacy of hallucinogenic drug use, and for this reason also criticize the euphemistic use of the term "entheogen". Non-religious reasons for the use of hallucinogens including spirituality, spiritual, introspection, introspective, psychotherapy, psychotherapeutic, recreational drug, recreational and even hedonism, hedonistic motives, each subject to some degree of social disapproval, have all been defended as the legitimate exercising of civil liberties and freedom of thought. A movement to Psilocybin decriminalization in the United States, decriminalize psilocybin in the United States began in the late 2010s, with Denver, Colorado becoming the first city to decriminalize psilocybin in May 2019, and Oregon becoming the first U.S. state to both decriminalize psilocybin and also legalize it for therapeutic use in November 2020, after the 2020 Oregon Ballot Measure 109, Ballot Measure 109 passed. Several medical and scientific experts, including the late Albert Hofmann, advocate the drugs should not be banned, but should be strongly regulated and warn they can be dangerous without proper psychological supervision.


Effects


Relationship between long-term use and mental illness

Most psychedelics are not known to have long-term physical toxicity. However, entactogens such as MDMA that release neurotransmitters may stimulate increased formation of free radicals possibly formed from neurotransmitters released from the synaptic vesicle. Free radicals are associated with cell damage in other contexts, and have been Free radicals#In biology, suggested to be involved in many types of mental conditions including Parkinson's disease, senility, schizophrenia, and Alzheimer's. Research on this question has not reached a firm conclusion. The same concerns do not apply to psychedelics that do not release neurotransmitters, such as LSD, nor to dissociatives or deliriants. However, usage of anticholinergic deliriants in particular has been linked to histological patterns of neurodegeneration and dementia. No clear connection has been made between psychedelic drugs and organic brain damage. However, hallucinogen persisting perception disorder (HPPD) is a diagnosed condition wherein certain visual effects of drugs persist for a long time, sometimes permanently, although science and medicine have yet to determine what causes the condition. A large epidemiological study in the U.S. found that other than personality disorders and other substance use disorders, lifetime hallucinogen use was not associated with other mental disorders, and that risk of developing a hallucinogen use disorder was very low. A 2019 systematic review and meta-analysis by Murrie et al. found that the transition rate from a diagnosis of hallucinogen-induced psychosis to that of schizophrenia was 26% (CI 14%-43%), which was lower than cannabis-induced psychosis (34%) but higher than amphetamine (22%), opioid (12%), alcohol (10%) and sedative (9%) induced psychoses. Transition rates were not affected by sex, country of the study, hospital or community location, urban or rural setting, diagnostic methods, or duration of follow-up. In comparison, the transition rate for brief, atypical and not otherwise specified psychosis was found to be 36%.


Effects on the brain

LSD, mescaline, psilocybin, and PCP are drugs that cause hallucinations, which can alter a person's perception of reality. LSD, mescaline, and psilocybin cause their effects by initially disrupting the interaction of nerve cells and the neurotransmitter serotonin."DrugFacts: Hallucinogens – LSD, mescaline, Psilocybin, and PCP." Drugabuse.gov. National Institute on Drug Abuse, n.d. Web. 13 April 2014. . It is distributed throughout the brain and spinal cord, where the serotonin system is involved with controlling of the behavioral, perceptual, and regulatory systems. This also includes mood, hunger, body temperature, sexual behavior, muscle control, and sensory perception. Certain hallucinogens, such as PCP, act through a glutamate receptor in the brain which is important for perception of pain, responses to the environment, and learning and memory. Thus far, there have been no properly controlled research studies on the specific effects of these drugs on the human brain, but smaller studies have shown some of the documented effects associated with the use of hallucinogens.


Psychotomimetic paradigm

While early researchers believed certain hallucinogens mimicked the effects of schizophrenia, it has since been discovered that some hallucinogens resemble endogenous psychoses better than others. PCP and ketamine are known to better resemble endogenous psychoses because they reproduce both positive and negative symptoms of psychoses, while psilocybin and related hallucinogens typically produce effects resembling only the positive symptoms of schizophrenia. While the serotonergic psychedelics (LSD, psilocybin, mescaline, etc.) do produce subjective effects distinct from NMDA antagonist dissociatives (PCP, ketamine, dextrorphan), there is obvious overlap in the mental processes that these drugs affect and research has discovered that there is overlap in the mechanisms by which both types of psychedelics mimic psychotic symptoms. One double-blind study examining the differences between Dimethyltryptamine, DMT and ketamine hypothesized that ''Serotonergic psychedelic, classically psychedelic'' drugs most resemble paranoid schizophrenia while ''
dissociative Dissociatives are a class of hallucinogen A hallucinogen is a psychoactive drug, psychoactive agent that often or ordinarily causes hallucinations, perception, perceptual anomalies, and other substantial subjective changes in thought, emotion, ...
'' drugs best mimicked catatonic subtypes or otherwise undifferentiated schizophrenia. The researchers stated that their findings supported the view that "a heterogeneous disorder like schizophrenia is unlikely to be modeled accurately by a single pharmacological agent."


Chemistry

Almost all hallucinogens contain nitrogen and are therefore classified as alkaloids. Tetrahydrocannabinol, THC and salvinorin A are exceptions. Many hallucinogens have chemical structures similar to those of human neurotransmitters, such as serotonin, and temporarily modify the action of neurotransmitters and/or receptor sites.


See also

* Altered state of consciousness * Serotonergic psychedelic, Classical psychedelic * Closed-eye hallucination, Closed-eye visualization * Entheogen *Hallucinogenic plants in Chinese herbals * Out-of-body experience * Psychedelia * Psychedelic drug * Psychedelic experience * Psychonautics * Psychopharmacology * Visual perception


References

Works cited * Peter Stafford, Stafford, Peter. (2003). ''Psychedelics''. Ronin Publishing, Oakland, California. .


Further reading

The literature about psychedelics, dissociatives and deliriants is vast. The following books provide accessible and up-to-date introductions to this literature: * Ann & Alexander Shulgin: PIHKAL (Phenethylamines I Have Known And Loved), a Chemical Love Story * Ann & Alexander Shulgin: TIHKAL (Tryptamines I Have Known And Loved), the Continuation * Charles S. Grob, ed.: Hallucinogens, a reader * Winkelman, Michael J., and Thomas B. Roberts (editors) (2007).''Psychedelic Medicine: New Evidence for Hallucinogens as Treatments'' 2 Volumes. Westport, CT: Praeger/Greenwood.


External links


Erowid
is a web site dedicated entirely to providing information about psychoactive drugs, with an impressive collection of trip reports, materials collected from the web and usenet, and a bibliography of scientific literature.
Multidisciplinary Association for Psychedelic Studies
is a nonprofit research and educational organization which carries out clinical trials and other research in order to assess the potential medicinal uses of psychedelic drugs and develop them into medicines.
PsychonautWiki
is a wiki dedicated to documenting psychoactive drugs and their subjective effects, with an emphasis on hallucinogens and novel psychoactives. The site hosts experience reports, tutorials, and a curated collection of articles. {{Authority control Psychedelics, dissociatives and deliriants, * Hallucinations