Hallucinogen

A hallucinogen is a psychoactive agent that often or ordinarily causes hallucinations, perceptual anomalies, and other substantial subjective changes in thought, emotion, and 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, dissociatives and deliriants. Although hallucinogens all can induce altered states of consciousness with some overlap in effects, there are quantifiable as well as vast qualitative differences in the induced subjective experiences between the different classes of hallucinogens due to differing and distinct pharmacological mechanisms. Contemporarily, certain potentially hallucinogenic GABAergic drugs such as 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.[1] 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."[2]

Characteristics

Leo Hollister's five criteria for establishing that a drug is [classically] hallucinogenic were as follows:[3][4]

  • 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.[4] 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 and deliriant 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.[5] In this article, they are referred to as hallucinogens and divided into psychedelics (classical hallucinogens), dissociatives, and deliriants, 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.[6] 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:

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.[6]

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, 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."[7]

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:[8]

Class I Phantastica roughly correspond to the psychedelics. 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; 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:

Effects by type

Psychedelics (classical hallucinogens)

One "Blotter" sheet of 900 LSD doses.

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 effects such as LSD and other ergotamine derivatives, 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.[9] 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.[4] 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.[6]

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.[10] 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

Salvia divinorum

Dissociatives produce analgesia, amnesia and catalepsy at anesthetic doses.[11] 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."[12] Dissociative symptoms include the disruption or compartmentalization of "...the usually integrated functions of consciousness, memory, identity or perception."[13]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.[14][15][16] 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;...."[17]

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.[18][19][20] 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.[21]

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.[22]

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.[23] The argument was criticized on the basis of lack of evidence[24] and White retracted his claim.[25] 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.[26] 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.[27] LSD and DOB have also been found to prevent NAN.[28]

Deliriants

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.[29]

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.[30]

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.[31] [32] 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.[33]

Uncured tobacco is also a deliriant due to its intoxicatingly high levels of nicotine.[34]

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.

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.[35] Many designer drugs and research chemicals are hallucinogenic in nature, such as those in the 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 reputation for being heavily connected with magic and folklore both in Western and 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, 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 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 ethnic minorities such as the Native American Church and the Santo Daime Church. Recently the União do Vegetal, a 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.[36]

Traditional religious and shamanic use

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.[37] 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.[38]

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.[39]

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."[40]

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.[41] 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.[42][43] 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.[44] 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.[45]

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)."[6]

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,[46] drug addiction,[47][48][49] 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.

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.[6] 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.[50] 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 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.[51]

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.[52]

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 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.[53]

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.[54]

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%.[55]

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.[56] 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.[56]

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.[57] 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.[58][59][60] 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.[61] 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."[61]

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.

See also

References

  1. ↑ "hallucinogen". Merriam-Webster. Retrieved 31 May 2020.
  2. ↑ "Hallucinate". Dictionary.com. Retrieved 26 June 2020.
  3. ↑ Glennon RA. Classical drugs: an introductory overview. In Lin GC and Glennon RA (eds). Hallucinogens: an update Archived 2015-07-23 at the Wayback Machine. National Institute on Drug Abuse: Rockville, MD, 1994.
  4. 1 2 3 Glennon RA (October 1999). "Arylalkylamine drugs of abuse: an overview of drug discrimination studies". Pharmacology Biochemistry and Behavior. 64 (2): 251–6. doi:10.1016/S0091-3057(99)00045-3. PMID 10515299. S2CID 10221368.
  5. ↑ Hermle, Leo; Kraehenmann, Rainer (2017). "Experimental Psychosis Research and Schizophrenia—Similarities and Dissimilarities in Psychopathology". Current Topics in Behavioral Neurosciences. 36: 313–332. doi:10.1007/7854_2016_460. ISBN 978-3-662-55878-2. PMID 28444578.
  6. 1 2 3 4 5 Nichols DE (February 2004). "Hallucinogens". Pharmacology & Therapeutics. 101 (2): 131–81. doi:10.1016/j.pharmthera.2003.11.002. PMID 14761703.
  7. ↑ Carhart-Harris, Robin; Guy, Goodwin (2017). "The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future". Neuropsychopharmacology. 42 (11): 2105–2113. doi:10.1038/npp.2017.84. PMC 5603818. PMID 28443617.
  8. ↑ Lewin, L. Phantastica. Die betäubenden und erregenden Genussmittel. Für Ärzte und Nichtärzte. Berlin: Verlag von Georg Stilke, 1924.
  9. ↑ Freedman DX (1969). "The psychopharmacology of hallucinogenic agents". Annual Review of Medicine. 20: 409–18. doi:10.1146/annurev.me.20.020169.002205. PMID 4894506.
  10. ↑ Huxley, Aldous (1954). The Doors of Perception. London: Harper & Bros. p. 63. ISBN 978-0-09-945820-3. Archived from the original on 8 March 2006. Retrieved 8 March 2006.
  11. ↑ Pender JW (November 1970). "Dissociative anesthesia". California Medicine. 113 (5): 73. PMC 1501800. PMID 18730444.
  12. ↑ Pender JW (October 1972). "Dissociative anesthesia". California Medicine Some Dissociatives Have General Depressant Effects as Well, Which is Why Doctors Prescribe Them to Sedate Patients Who Are in Pain or to Help Maintain General Anesthesia During an Operation. Common Dissociative Drugs Include: PCP (Phencyclidine). 117 (4): 46–7. PMC 1518731. PMID 18730832.
  13. ↑ American Psychiatric Association. Diagnostic and statistical manual of mental disorders (4th ed., text revision). Washington, DC: American Psychiatric Association, 2000.
  14. ↑ Simeon D, Gross S, Guralnik O, Stein DJ, Schmeidler J, Hollander E (August 1997). "Feeling unreal: 30 cases of DSM-III-R depersonalization disorder". The American Journal of Psychiatry. 154 (8): 1107–13. doi:10.1176/ajp.154.8.1107. PMID 9247397.
  15. ↑ Nathan. Mostly not regretful Archived 17 October 2010 at the Wayback Machine. Erowid Experience Vaults. 29 October 2006.
  16. ↑ Keil. Like nothing else in the world Archived 17 October 2010 at the Wayback Machine. Erowid Experience Vaults. 11 August 2003.
  17. ↑ Simeon D (2004). "Depersonalisation disorder: a contemporary overview". CNS Drugs. 18 (6): 343–54. doi:10.2165/00023210-200418060-00002. PMID 15089102. S2CID 18506672.
  18. ↑ Herling S, Coale EH, Hein DW, Winger G, Woods JH (1981). "Similarity of the discriminative stimulus effects of ketamine, cyclazocine, and dextrorphan in the pigeon". Psychopharmacology. 73 (3): 286–91. doi:10.1007/BF00422419. hdl:2027.42/46423. PMID 6787651. S2CID 2369250.
  19. ↑ Herling S, Woods JH (April 1981). "Discriminative stimulus effects of narcotics: evidence for multiple receptor-mediated actions" (PDF). Life Sciences. 28 (14): 1571–84. doi:10.1016/0024-3205(81)90311-8. hdl:2027.42/24399. PMID 6264253.
  20. ↑ Nicholson KL, Hayes BA, Balster RL (September 1999). "Evaluation of the reinforcing properties and phencyclidine-like discriminative stimulus effects of dextromethorphan and dextrorphan in rats and rhesus monkeys". Psychopharmacology. 146 (1): 49–59. doi:10.1007/s002130051087. PMID 10485964. S2CID 28576850.
  21. ↑ Roth BL, Baner K, Westkaemper R, Siebert D, Rice KC, Steinberg S, Ernsberger P, Rothman RB (September 2002). "Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist". Proceedings of the National Academy of Sciences of the United States of America. 99 (18): 11934–9. Bibcode:2002PNAS...9911934R. doi:10.1073/pnas.182234399. PMC 129372. PMID 12192085.
  22. ↑ Price, William A.; Giannini, Matthew C.; Giannini, A. James (1984). "Antidotal Strategies in Phencyclidine Intoxication". The International Journal of Psychiatry in Medicine. 14 (4): 315–21. doi:10.2190/KKAW-PWGF-W7RQ-23GN. S2CID 72401949.
  23. ↑ White W. (1998) This is your brain on dissociatives Archived 17 October 2010 at the Wayback Machine (accessed 23 October 2010)
  24. ↑ Anderson C. (2003) The bad news isn't in Archived 17 December 2008 at the Wayback Machine (Accessed 23 October 2010)
  25. ↑ White W. (2004) Response to "The Bad News Isn't In": Please Pass the Crow Archived 17 October 2010 at the Wayback Machine (accessed 23 October 2010)
  26. ↑ Olney JW, Labruyere J, Price MT (June 1989). "Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs". Science. 244 (4910): 1360–2. Bibcode:1989Sci...244.1360O. doi:10.1126/science.2660263. PMID 2660263.
  27. ↑ Farber NB, Kim SH, Dikranian K, Jiang XP, Heinkel C (2002). "Receptor mechanisms and circuitry underlying NMDA antagonist neurotoxicity". Molecular Psychiatry. 7 (1): 32–43. doi:10.1038/sj/mp/4000912. PMID 11803444.
  28. ↑ Farber NB, Hanslick J, Kirby C, McWilliams L, Olney JW (January 1998). "Serotonergic agents that activate 5HT2A receptors prevent NMDA antagonist neurotoxicity". Neuropsychopharmacology. 18 (1): 57–62. doi:10.1016/S0893-133X(97)00127-9. PMID 9408919.
  29. ↑ Gold, David Duncan; Robert (1982). Drugs and the whole person. New York u.a.: Wiley. ISBN 978-0471041207.
  30. ↑ Grinspoon, Lester; Bakalar, James B. (1998). Psychedelic drugs reconsidered (2. print ed.). New York: Lindesmith Cemter. ISBN 978-0964156852.
  31. ↑ Schultes, Richard Evans; Hofmann, Albert (1979). The Botany and Chemistry of Hallucinogens (2nd ed.). Springfield Illinois: Charles C. Thomas.
  32. ↑ Emboden, William, Narcotic Plants – Hallucinogens, stimulants, inebriants, and hypnotics, their origins and uses 2nd edition, revised and enlarged, pub. Macmillan Publishing Co., Inc., New York 1979, ISBN 0-02-535480-9.
  33. ↑ Beaver, Kathleen M; Gavin, Thomas J (1998). "Treatment of acute anticholinergic poisoning with physostigmine". The American Journal of Emergency Medicine. 16 (5): 505–507. doi:10.1016/S0735-6757(98)90003-1. PMID 9725967.
  34. ↑ Winter, Joseph C. (2000). Tobacco Use by Native North Americans: Sacred Smoke and Silent Killer. University of Oklahoma Press. p. 354. ISBN 9780806132624.
  35. ↑ Wohlfarth A, Weinmann W (May 2010). "Bioanalysis of new designer drugs". Bioanalysis. 2 (5): 965–79. doi:10.4155/bio.10.32. PMID 21083227.
  36. ↑ Da Silveira DX, Grob CS, de Rios MD, Lopez E, Alonso LK, Tacla C, Doering-Silveira E (June 2005). "Ayahuasca in adolescence: a preliminary psychiatric assessment". Journal of Psychoactive Drugs. 37 (2): 129–33. doi:10.1080/02791072.2005.10399792. PMID 16149324. S2CID 16236951.
  37. ↑ Schultes, Richard Evans (1976). Hallucinogenic Plants. Illustrated by Elmer W. Smith. New York: Golden Press. pp. 5, 7, 9, 102. ISBN 0-307-24362-1.
  38. ↑ Bartholomew Dean 2009 Urarina Society, Cosmology, and History in Peruvian Amazonia, Gainesville: University Press of Florida ISBN 978-0-8130-3378-5 UPF.com Archived 17 July 2011 at the Wayback Machine
  39. ↑ "Shamanism and Its Discontents." Medical Anthropology Quarterly 2.2 (1988) 102-20.
  40. ↑ Surawicz, Fruda G.; Banta, Richard (November 1975). "Lycanthropy Revisited". Canadian Psychiatric Association Journal. 20:7 (7): 537–42. doi:10.1177/070674377502000706. PMID 1203837.
  41. ↑ Dyck, Erika (2005). "Flashback: Psychiatric Experimentation With LSD in Historical Perspective". The Canadian Journal of Psychiatry. 50 (7): 381–388. doi:10.1177/070674370505000703. PMID 16086535. S2CID 13894582.
  42. ↑ Ken Goffman. Counterculture through the Ages; from Abraham to Acid House. New York: Villard, 2004. Chapters 11–13.
  43. ↑ Brink Lindsey. The Age of Abundance; How Prosperity Transformed America's Politics and Culture. New York: Collins, 2007. p.156: "...pot and psychedelics revealed to their users wildly different visions of reality from the "straight" one everybody took for granted. ... Guided into those transcendent realms, many young andimpressionable minds were set aflame with visions of radical change. ... Antiwar protesters, feminists, student rebels, environmentalists, and gays all took their turns marching to the solemn strains of "We Shall Overcome"..."
  44. ↑ Goffman, ibidem, p.266–7: "By normative social standards, something unseemly was going on, but since LSD, the catalyst that was unleashing the celebratory chaos, was still legal [in 1966], there was little [the authorities] could do... [That year, a]cross the nation, states started passing laws prohibiting LSD. .... By their panic, as expressed through their prohibitionary legislation, the conservative forces teased out what was perhaps the central countercultural progression for this epoch."
  45. ↑ Francom P, Andrenyak D, Lim HK, Bridges RR, Foltz RL, Jones RT (January–February 1988). "Determination of LSD in urine by capillary column gas chromatography and electron impact mass spectrometry". Journal of Analytical Toxicology. 12 (1): 1–8. doi:10.1093/jat/12.1.1. PMID 3352236.
  46. ↑ Bogenschutz, M.P. (2013). Studying the Effects of Classic Hallucinogens in the Treatment of Alcoholism: Rationale, Methodology, and Current Research with Psilocybin. Curr Drug Abuse Rev. Jun 18;6(1):17–29.DOI: 10.2174/15733998113099990002 Michael, P. Bogenschutz (28 February 2013). "Studying the Effects of Classic Hallucinogens in the Treatment of Alcoholism: Rationale, Methodology, and Current Research with Psilocybin". Current Drug Abuse Reviews. 6 (1): 17–29. doi:10.2174/15733998113099990002. PMID 23627783. Archived from the original on 13 October 2013. Retrieved 1 July 2013.
  47. ↑ Vargas-Perez, H & Doblin, R. (2013) Editorial: The Potential of Psychedelics as a Preventative and Auxiliary Therapy for Drug Abuse Curr Drug Abuse Rev. Jun 18;6(1):1–2 Hector, Vargas-Perez; Rick, Doblin (28 February 2013). "Editorial (Hot Topic: The Potential of Psychedelics as a Preventative and Auxiliary Therapy for Drug Abuse)". Current Drug Abuse Reviews. 6 (1): 1–2. doi:10.2174/18744737112059990023. PMID 23773089. Archived from the original on 13 October 2013. Retrieved 1 July 2013.
  48. ↑ Thomas G, Lucas P, Capler NR, Tupper KW, Martin G. (2013) Ayahuasca-assisted therapy for addiction: results from a preliminary observational study in Canada. Curr Drug Abuse Rev. Jun 18;6(1):30–42. Gerald, Thomas; Philippe, Lucas; n., Rielle Capler; Kenneth, W. Tupper; Gina, Martin (28 February 2013). "Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada". Current Drug Abuse Reviews. 6 (1): 30–42. doi:10.2174/15733998113099990003. PMID 23627784. Archived from the original on 18 October 2013. Retrieved 26 December 2013.
  49. ↑ Brown, T.K. (2013) Ibogaine in the Treatment of Substance Dependence. Curr Drug Abuse Rev. Jun 18;6(1):3–16. DOI: 10.2174/15672050113109990001 Thomas, Kingsley Brown (28 February 2013). "Ibogaine in the Treatment of Substance Dependence". Current Drug Abuse Reviews. 6 (1): 3–16. doi:10.2174/15672050113109990001. PMID 23627782. Archived from the original on 13 October 2013. Retrieved 1 July 2013.
  50. ↑ "Netherlands bans magic mushrooms". BBC. 12 October 2007. Archived from the original on 13 November 2016. Retrieved 13 November 2016.
  51. ↑ Naftulin, Julia (4 November 2020). "Oregon has become the first state to legalize 'magic' mushrooms for therapeutic use. Here's what that means". Business Insider. Retrieved 27 May 2021.{{cite web}}: CS1 maint: url-status (link)
  52. ↑ Smith, Craig S. (7 January 2006). "The Saturday Profile; Nearly 100, LSD's Father Ponders His 'Problem Child'". The New York Times. Archived from the original on 20 May 2011. Retrieved 22 May 2010.
  53. ↑ "Study suggests link between long-term use of anticholinergics and dementia risk". Alzheimer's Society. 26 January 2015. Archived from the original on 12 November 2015. Retrieved 17 February 2015.
  54. ↑ Shalit N, Rehm J, Lev-Ran S (2019). "Epidemiology of hallucinogen use in the U.S. results from the National epidemiologic survey on alcohol and related conditions III". Addictive Behaviors. 89: 35–43. doi:10.1016/j.addbeh.2018.09.020. PMID 30245407. S2CID 52821352.
  55. ↑ Murrie, Benjamin; Lappin, Julia; Large, Matthew; Sara, Grant (16 October 2019). "Transition of Substance-Induced, Brief, and Atypical Psychoses to Schizophrenia: A Systematic Review and Meta-analysis". Schizophrenia Bulletin. 46 (3): 505–516. doi:10.1093/schbul/sbz102. PMC 7147575. PMID 31618428.
  56. 1 2 "DrugFacts: Hallucinogens – LSD, mescaline, Psilocybin, and PCP." Drugabuse.gov. National Institute on Drug Abuse, n.d. Web. 13 April 2014. <http://www.drugabuse.gov/publications/drugfacts/hallucinogens-lsd-mescaline-psilocybin-pcp%5B%5D>.
  57. ↑ Vollenweider FX, Geyer MA (November 2001). "A systems model of altered consciousness: integrating natural and drug-induced psychoses". Brain Research Bulletin. 56 (5): 495–507. doi:10.1016/S0361-9230(01)00646-3. PMID 11750795. S2CID 230298.
  58. ↑ Aghajanian GK, Marek GJ (March 2000). "Serotonin model of schizophrenia: emerging role of glutamate mechanisms". Brain Research. Brain Research Reviews. 31 (2–3): 302–12. doi:10.1016/S0165-0173(99)00046-6. PMID 10719157. S2CID 13040014.
  59. ↑ Svenningsson P, Tzavara ET, Carruthers R, Rachleff I, Wattler S, Nehls M, McKinzie DL, Fienberg AA, Nomikos GG, Greengard P (November 2003). "Diverse psychotomimetics act through a common signaling pathway". Science. 302 (5649): 1412–5. Bibcode:2003Sci...302.1412S. doi:10.1126/science.1089681. PMID 14631045. S2CID 84901005.
  60. ↑ Tsapakis, E. M. (2002). "Glutamate and psychiatric disorders". Advances in Psychiatric Treatment. 8 (3): 189–97. doi:10.1192/apt.8.3.189.
  61. 1 2 Gouzoulis-Mayfrank E, Heekeren K, Neukirch A, Stoll M, Stock C, Obradovic M, Kovar KA (November 2005). "Psychological effects of (S)-ketamine and N,N-dimethyltryptamine (DMT): a double-blind, cross-over study in healthy volunteers". Pharmacopsychiatry. 38 (6): 301–11. doi:10.1055/s-2005-916185. PMID 16342002.

Works cited

  • Stafford, Peter. (2003). Psychedelics. Ronin Publishing, Oakland, California. ISBN 0-914171-18-6.

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.
  • 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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