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The classical hallucinogens are considered to be the representative psychedelics and LSD is generally considered the prototypical psychedelic.<ref name = "Freedman1969">{{cite journal | vauthors = Freedman DX | title = The psychopharmacology of hallucinogenic agents | journal = Annual Review of Medicine | volume = 20 | pages = 409–18 | year = 1969 | pmid = 4894506 | doi = 10.1146/annurev.me.20.020169.002205 }}</ref> 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.<ref name="glennon-1999"/> 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.<ref name="Nichols, David 2004">{{cite journal | vauthors = Nichols DE | title = Hallucinogens | journal = Pharmacology & Therapeutics | volume = 101 | issue = 2 | pages = 131–81 | date = February 2004 | pmid = 14761703 | doi = 10.1016/j.pharmthera.2003.11.002 }}</ref>
The classical hallucinogens are considered to be the representative psychedelics and LSD is generally considered the prototypical psychedelic.<ref name = "Freedman1969">{{cite journal | vauthors = Freedman DX | title = The psychopharmacology of hallucinogenic agents | journal = Annual Review of Medicine | volume = 20 | pages = 409–18 | year = 1969 | pmid = 4894506 | doi = 10.1146/annurev.me.20.020169.002205 }}</ref> 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.<ref name="glennon-1999"/> 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.<ref name="Nichols, David 2004">{{cite journal | vauthors = Nichols DE | title = Hallucinogens | journal = Pharmacology & Therapeutics | volume = 101 | issue = 2 | pages = 131–81 | date = February 2004 | pmid = 14761703 | doi = 10.1016/j.pharmthera.2003.11.002 }}</ref>

Despite several attempts that have been made, starting in the 19th and 20th centuries, to define common [[Phenomenology (psychology)|phenomenological]] structures of the effects produced by classic psychedelics, a universally accepted taxonomy does not yet exist.<ref name="bnsd-phenom">{{Cite book|last1=Preller|first1=Katrin H.|title=Behavioral Neurobiology of Psychedelic Drugs|last2=Vollenweider|first2=Franz X.|date=2016|publisher=Springer Berlin Heidelberg|isbn=978-3-662-55878-2|editor1=Adam L. Halberstadt |editor2=Franz X. Vollenweider |editor3=David E. Nichols |volume=36|location=Berlin, Heidelberg|pages=221–256|chapter=Phenomenology, Structure, and Dynamic of Psychedelic States|journal=Current Topics in Behavioral Neurosciences|doi=10.1007/7854_2016_459|pmid=28025814}}</ref><ref name="swanson">{{Cite journal|last=Swanson|first=Link R.|date=2018-03-02|title=Unifying Theories of Psychedelic Drug Effects|journal=Frontiers in Pharmacology|volume=9|pages=172|doi=10.3389/fphar.2018.00172|pmid=29568270|pmc=5853825|issn=1663-9812|doi-access=free}}</ref> A prominent element of psychedelic experiences is visual alteration.<ref name="bnsd-phenom"/> Psychedelic visual alteration often includes spontaneous formation of complex flowing geometric visual patterning in the visual field.<ref name="swanson"/> When the eyes are open, the visual alteration is overlaid onto the objects and spaces in the physical environment; when the eyes are closed the visual alteration is seen in the "inner world" behind the eyelids.<ref name="swanson"/> These visual effects increase in complexity with higher dosages, and also when the eyes are closed.<ref name="swanson"/> The visual alteration does not normally constitute [[hallucination]]s, because the person undergoing the experience can still distinguish between real and imagined visual phenomena, though in some cases, true hallucinations are present.<ref name="bnsd-phenom"/> More rarely, psychedelic experiences can include complex hallucinations of objects, animals, people, or even whole landscapes.<ref name="bnsd-phenom"/>


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]]''.<ref>{{cite book |last=Huxley |first=Aldous |title=The Doors of Perception |url=http://mescaline.com/huxley.htm |access-date=8 March 2006 |year=1954 |publisher=Harper & Bros |location=London |page=63 |isbn=978-0-09-945820-3 |url-status=live |archive-url=https://web.archive.org/web/20060308033309/http://www.mescaline.com/huxley.htm |archive-date=8 March 2006 }}</ref> 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.
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]]''.<ref>{{cite book |last=Huxley |first=Aldous |title=The Doors of Perception |url=http://mescaline.com/huxley.htm |access-date=8 March 2006 |year=1954 |publisher=Harper & Bros |location=London |page=63 |isbn=978-0-09-945820-3 |url-status=live |archive-url=https://web.archive.org/web/20060308033309/http://www.mescaline.com/huxley.htm |archive-date=8 March 2006 }}</ref> 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.

Revision as of 16:19, 3 April 2022

Not to be confused with Hallucinogen (EP) or Hallucinogen (musician).

Hallucinogens are a large class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mood, and perception, among other changes.[1][2] Most hallucinogens can be categorized as psychedelics, dissociatives, or deliriants.[2]

Etymology

The word hallucinogen is derived from the word hallucination.[3] 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."[4]

Characteristics

Leo Hollister's five criteria for classifying a drug as [classically] hallucinogenic were as follows:[5][6]

  • 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, and it has since been shown to encompass a number of categories with different pharmacological mechanisms and behavioral effects.[6]

Nomenclature and taxonomy

Most hallucinogens can be categorized based on their pharmacological mechanisms as psychedelics (which are serotonergic), dissociatives (which are antiglutamatergic), or deliriants (which are anticholinergic).[2] Some hallucinogens, however, such as salvinorin A and ibogaine, have pharmacological mechanisms different from those of all those categories.[2] Entactogens and cannabinoids are also sometimes considered hallucinogens.[7] Nonetheless, while the term hallucinogen is often used to refer to the broad class of drugs covered in this article, sometimes it is used to mean only classical hallucinogens (that is, psychedelics).[8] Because of this, it is important to consult the definition given in a particular source.[8] Because of the multi-faceted phenomenology brought on by hallucinogens, efforts to create standardized terminology for classifying them based on their subjective effects have not succeeded to date.[9]

Classical hallucinogens or psychedelics have been described by many names. David E. Nichols wrote in 2004:

Many different names have been proposed over the years for this drug class. The famous German toxicologist Louis Lewin used the name phantastica earlier in this century, and as we shall see later, such a descriptor is not so farfetched. The most popular names—hallucinogen, psychotomimetic, and psychedelic ("mind manifesting")—have often been used interchangeably. Hallucinogen is now, however, the most common designation in the scientific literature, although it is an inaccurate descriptor of the actual effects of these drugs. In the lay press, the term psychedelic is still the most popular and has held sway for nearly four decades. Most recently, there has been a movement in nonscientific circles to recognize the ability of these substances to provoke mystical experiences and evoke feelings of spiritual significance. Thus, the term entheogen, derived from the Greek word entheos, which means "god within", was introduced by Ruck et al. and has seen increasing use. This term suggests that these substances reveal or allow a connection to the "divine within". Although it seems unlikely that this name will ever be accepted in formal scientific circles, its use has dramatically increased in the popular media and on internet sites. Indeed, in much of the counterculture that uses these substances, entheogen has replaced psychedelic as the name of choice and we may expect to see this trend continue.[8]

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."[10]

Certain hallucinogens are designer drugs, such as those in the 2C and 25-NB (NBOMe) families.[11] A designer drug is a structural or functional analog of a controlled substance (hallucinogenic or otherwise) 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.[12]

Effects by type

Psychedelics (classical hallucinogens)

Main article: Psychedelic drug
One "Blotter" sheet of 900 LSD doses.

The classical hallucinogens are considered to be the representative psychedelics and LSD is generally considered the prototypical psychedelic.[13] 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.[6] 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.[8]

Despite several attempts that have been made, starting in the 19th and 20th centuries, to define common phenomenological structures of the effects produced by classic psychedelics, a universally accepted taxonomy does not yet exist.[14][15] A prominent element of psychedelic experiences is visual alteration.[14] Psychedelic visual alteration often includes spontaneous formation of complex flowing geometric visual patterning in the visual field.[15] When the eyes are open, the visual alteration is overlaid onto the objects and spaces in the physical environment; when the eyes are closed the visual alteration is seen in the "inner world" behind the eyelids.[15] These visual effects increase in complexity with higher dosages, and also when the eyes are closed.[15] The visual alteration does not normally constitute hallucinations, because the person undergoing the experience can still distinguish between real and imagined visual phenomena, though in some cases, true hallucinations are present.[14] More rarely, psychedelic experiences can include complex hallucinations of objects, animals, people, or even whole landscapes.[14]

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.[16] 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

Main article: Dissociative
Salvia divinorum

Dissociatives produce analgesia, amnesia and catalepsy at anesthetic doses.[17] 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."[18] Dissociative symptoms include the disruption or compartmentalization of "...the usually integrated functions of consciousness, memory, identity or perception."[19]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.[20][21][22] 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;...."[23]

The classical dissociatives achieve their effect through blocking the signals received by the NMDA receptor set (NMDA receptor antagonism) and include ketamine, methoxetamine (MXE), phencyclidine (PCP), dextromethorphan (DXM), and nitrous oxide.[24][25][26] However, dissociation is also remarkably administered by salvinorin A's (the active constituent in Salvia divinorum shown to the left) potent κ-opioid receptor agonism, though usually described as a very atypical dissociative.[27]

Some dissociatives can have 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 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 renal shutdown.[28]

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.[29] The argument was criticized on the basis of lack of evidence[30] and White retracted his claim.[31] 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 PCP and ketamine.[32] 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.[33] LSD and DOB have also been found to prevent NAN.[34]

Deliriants

Main article: Deliriant
Datura innoxia in flower.
Attractive but highly toxic berry of Atropa belladonna
Flowers and foliage of Nicotiana tabacum, the cultivated tobacco.
Single fruiting body of Amanita muscaria
Myristica fragrans fruit, halved, showing within the red seed (nutmeg) enclosed in its brown aril (mace).

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 and dissociatives, such as LSD and ketamine respectively, due to their primary effect of causing delirium, as opposed to the more lucid states produced by the other hallucinogens.[35][page needed]

Despite the fully legal status of several common deliriant plants, deliriants are largely unpopular as recreational drugs due to the severe, generally unpleasant and often dangerous nature of the hallucinogenic effects produced.[36][page needed]

Typical or classical deliriants are those which block the muscarinic acetylcholine receptors (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 in the Old World.[37] [38] 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.[39]

Uncured tobacco is also a deliriant due to its intoxicatingly high levels of nicotine.[40]

History of use

Traditional religious and shamanic use

Main article: Entheogen

Historically, hallucinogens have been commonly used in religious or 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.[41] Evidence exists for the use of entheogens in prehistoric times, as well as in numerous ancient cultures, including Ancient Egyptian, Mycenaean, Ancient Greek, Vedic, 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.[42]

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 yaji, a hallucinogenic drink, Aguaruna shamans try to discover and remove the darts from their patients.[43]

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."[44]

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 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 Mexican psilocybin mushrooms (in 1936 by Robert J. Weitlaner) and 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-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 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.[45] Hallucinogens were also researched in several countries for their potential as agents of chemical warfare. Most famously, several incidents associated with the 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 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 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.[46][47] 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.[48] 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.[49]

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)."[8]

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 depression, posttraumatic stress disorder, obsessive–compulsive disorder, alcoholism,[50] drug addiction,[51][52][53] 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 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

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.[8] 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 "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.[54] 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).

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 spiritual, introspective, psychotherapeutic, recreational and even 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 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 Ballot Measure 109 passed.[55]

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.[56]

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.[citation needed] Free radicals are associated with cell damage in other contexts, and have been 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.[57]

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,[citation needed] 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.[58]

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%.[59]

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.[60] 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.[60]

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.[61] 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.[62][63][64] One double-blind study examining the differences between DMT and ketamine hypothesized that classically psychedelic drugs most resemble paranoid schizophrenia while dissociative drugs best mimicked catatonic subtypes or otherwise undifferentiated schizophrenia.[65] 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."[65]

Chemistry

Almost all hallucinogens contain nitrogen and are therefore classified as alkaloids. 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.[66][67]

See also

References

  1. ^ Vollenweider, Franz X. (2001). "Brain mechanisms of hallucinogens and entactogens". Dialogues in Clinical Neuroscience. 3 (4): 265–279. doi:10.31887/DCNS.2001.3.4/fxvollenweider. PMC 3181663. PMID 22033605.
  2. ^ a b c d Volgin, Andrey D.; Yakovlev, Oleg A.; Demin, Constantin A.; Alekseeva, Polina A.; Kyzar, Evan J.; Collins, Christopher; Nichols, David E.; Kalueff, Allan V. (2019). "Understanding Central Nervous System Effects of Deliriant Hallucinogenic Drugs through Experimental Animal Models". ACS Chemical Neuroscience. 10 (1): 143–154. doi:10.1021/acschemneuro.8b00433. PMID 30252437.
  3. ^ "hallucinogen". Merriam-Webster. Retrieved 31 May 2020.
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Works cited

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

Wikimedia Commons has media related to Hallucinogens.
  • 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.
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