Hallucinogen

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

Contents

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 gave five criteria for classifying a drug as hallucinogenic. [5] [6] This definition is broad enough to include a wide range of drugs and has since been shown to encompass a number of categories of drugs with different pharmacological mechanisms and behavioral effects. [6] Richard Glennon has thus given an additional two criteria that narrow the category down to classical hallucinogens. [6] Hollister's criteria for hallucinogens were as follows: [5] [6]

Glennon's additional criteria for classical hallucinogens are that the drugs in question must also: [6]

Nomenclature and taxonomy

Most hallucinogens can be categorized based on their pharmacological mechanisms as psychedelics (which are serotonergic), dissociatives (which are generally antiglutamatergic), or deliriants (which are generally anticholinergic). [2] However, the pharmacological mechanisms of some hallucinogens, such as salvinorin A and ibogaine, do not fit into any of 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: [8]

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.

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)

One "Blotter" sheet of 900 LSD doses Ruby Slippers LSD Sheet.jpg
One "Blotter" sheet of 900 LSD doses

Despite several attempts that have been made, starting in the 19th and 20th centuries, to define common phenomenological structures (i.e., patterns of experience) brought on by classical psychedelics, a universally accepted taxonomy does not yet exist. [13] [14]

A prominent element of psychedelic experiences is visual alteration. [13] Psychedelic visual alteration often includes spontaneous formation of complex flowing geometric visual patterning in the visual field. [14] 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. [14] These visual effects increase in complexity with higher dosages, and also when the eyes are closed. [14] The visual alteration does not normally constitute hallucinations, because the person undergoing the experience can still distinguish between real and internally generated visual phenomena, though in some cases, true hallucinations are present. [13] More rarely, psychedelic experiences can include complex hallucinations of objects, animals, people, or even whole landscapes. [13]

A number of studies by Roland R. Griffiths and other researchers have concluded that high doses of psilocybin and other classic psychedelics trigger mystical experiences in most research participants. [15] [16] [17] [18] Mystical experiences have been measured by a number of psychometric scales, including the Hood Mysticism Scale, the Spiritual Transcendence Scale, and the Mystical Experience Questionnaire. [18] The revised version of the Mystical Experience Questionnaire, for example, asks participants about four dimensions of their experience, namely the "mystical" quality, positive mood such as the experience of amazement, the loss of the usual sense of time and space, and the sense that the experience cannot be adequately conveyed through words. [18] The questions on the "mystical" quality in turn probe multiple aspects: the sense of "pure" being, the sense of unity with one's surroundings, the sense that what one experienced was real, and the sense of sacredness. [18] Some researchers have questioned the interpretation of the results from these studies and whether the framework and terminology of mysticism are appropriate in a scientific context, while other researchers have responded to those criticisms and argued descriptions of mystical experiences are compatible with a scientific worldview. [19] [20] [21]

Link R. Swanson divides overarching scientific frameworks for understanding psychedelic experiences into two waves. In the first wave, encompassing nineteenth- and twentieth-century frameworks, he includes model psychosis theory (the psychotomimetic paradigm), filtration theory, and psychoanalytic theory. [14] In the second wave of theories, encompassing twenty-first-century frameworks, Swanson includes entropic brain theory, integrated information theory, and predictive processing. [14] It is from the paradigm of filtration theory that the term psychedelic derives. [14] Aldous Huxley and Humphrey Osmond applied the pre-existing ideas of filtration theory, which held that the brain filters what enters into consciousness, to explain psychedelic experiences; Huxley believed that the brain was filtering reality itself and that psychedelics granted conscious access to "Mind at Large", whereas Osmond believed that the brain was filtering aspects of the mind out of consciousness. [14] Swanson writes that Osmond's view seems "less radical, more compatible with materialist science, and less epistemically and ontologically committed" than Huxley's. [14]

Dissociatives

Salvia divinorum Salviadivinorum.jpg
Salvia divinorum

Dissociatives produce analgesia, amnesia and catalepsy at anesthetic doses. [22] 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." [23] Dissociative symptoms include the disruption or compartmentalization of "...the usually integrated functions of consciousness, memory, identity or perception." [24] 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. [25] In a 2004 paper, Daphne Simeon 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;...." [26]

The classical dissociatives achieve their effect through blocking binding of the neurotransmitter glutamate to NMDA receptors (NMDA receptor antagonism) and include ketamine, methoxetamine (MXE), phencyclidine (PCP), dextromethorphan (DXM), and nitrous oxide. [27] [28] [29] 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. [30]

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. [31]

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. [32] The argument was criticized on the basis of lack of evidence [33] and White retracted his claim. [34] 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. [35] 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. [36] LSD and DOB have also been found to prevent NAN. [37]

Deliriants

Datura innoxia in flower Datura wrightii flower.jpg
Datura innoxia in flower
Attractive but highly toxic berry of Atropa belladonna IMG 8023 Atropa belladonna L. Single fruit.jpg
Attractive but highly toxic berry of Atropa belladonna
Flowers and foliage of Nicotiana tabacum, the cultivated tobacco Tabak P9290021.JPG
Flowers and foliage of Nicotiana tabacum , the cultivated tobacco
Single fruiting body of Amanita muscaria Fly Agaric mushroom 05.jpg
Single fruiting body of Amanita muscaria
Myristica fragrans fruit, halved, showing within the red seed (nutmeg) enclosed in its brown aril (mace) Nutmeg fruit seed and aril.jpg
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. [38] [ 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. [39] [ page needed ]

Typical or classical deliriants are those which are anticholinergic, meaning they block the muscarinic acetylcholine receptors. 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. [40] [41] 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. [42]

Uncured tobacco is also a deliriant due to its intoxicatingly high levels of nicotine. [43]

History of use

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. [44] 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. [45]

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. [46]

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." [47]

Early scientific investigations

In an 1860 book, the mycologist Mordecai Cubitt Cooke differentiated a class of drugs roughly corresponding to hallucinogens from opiates, and in 1924 the toxicologist Louis Lewin described hallucinogens in depth under the name phantastica. From the 1920s on, work in psychopharmacology and ethnobotany resulted in more detailed knowledge of various hallucinogens. In 1943, Albert Hofmann discovered the hallucinogenic properties of lysergic acid diethylamide (LSD), which raised the prospect of hallucinogens becoming more broadly available. [48]

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. [49]

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 major social changes initiated in the 1960s. [50] [51] 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. [52] 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. [53]

As early as the 1960s, research into the medicinal properties of LSD was being conducted. "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 have received extensive attention in the Western world. They have been and are being explored as potential therapeutic agents in treating alcoholism, [54] and other forms of drug addiction. [55] [56] [57]

In the United States, classical hallucinogens (psychedelics) are in the most strictly prohibited class of drugs, known as Schedule 1 drugs. [8] This classification was created for drugs that meet the three following characteristics: 1) they have no currently accepted medical use, 2) there is a lack of safety for their use under medical supervision, and 3) they have a high potential for abuse. [8] However, pharmacologist David E. Nichols argues that hallucinogens were placed in this class for political rather than scientific reasons. [8] In 2006, Albert Hofmann, the chemist who discovered LSD, said he believed LSD could be valuable when used in a medical rather than recreational context, and said it should be regulated in the same way as morphine rather than more strictly. [58]

The Netherlands previously allowed psilocybin mushrooms to be sold, but in October 2007 the Dutch government moved to ban their sale following several widely publicized incidents involving tourists. [59] In November 2020, Oregon became the first U.S. state to both decriminalize psilocybin and legalize it for therapeutic use, after Ballot Measure 109 passed. [60]

Effects

Relationship between long-term use and mental illness

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, [61] although the underlying cause and pathology remains unclear. [62]

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. [63]

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%. [64]

Effects on the brain

Different classes of hallucinogens have different pharmacological mechanisms of action. [2] [65] Psychedelics are 5-HT2A receptor agonists (serotonin 2A receptor agonists). [66] [65]

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. [67] 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. [67]

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. [68] 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. [69] [70] [71] 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. [72] 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." [72]

Chemistry

Classical hallucinogens (psychedelics) can be divided into three main chemical classes: tryptamines (such as psilocin and DMT), ergolines (such as LSD), and phenethylamines (such as mescaline). [65] Tryptamines closely resemble serotonin chemically. [65]

See also

Related Research Articles

<i>N</i>,<i>N</i>-Dimethyltryptamine Chemical compound

N,N-Dimethyltryptamine is a substituted tryptamine that occurs in many plants and animals, including humans, and which is both a derivative and a structural analog of tryptamine. DMT is used as a psychedelic drug and prepared by various cultures for ritual purposes as an entheogen.

<span class="mw-page-title-main">LSD</span> Hallucinogenic drug

Lysergic acid diethylamide, commonly known as LSD, and known colloquially as acid or lucy is a potent psychedelic drug. Effects typically include intensified thoughts, emotions, and sensory perception. At sufficiently high dosages LSD manifests primarily mental, visual, and auditory hallucinations. Dilated pupils, increased blood pressure, and increased body temperature are typical. Effects typically begin within half an hour and can last for up to 20 hours. LSD is also capable of causing mystical experiences and ego dissolution. It is used mainly as a recreational drug or for spiritual reasons. LSD is both the prototypical psychedelic and one of the "classical" psychedelics, being the psychedelic with the greatest scientific and cultural significance. LSD is synthesized as a solid compound, typically in the form of a powder or a crystalline material. This solid LSD is then dissolved in a liquid solvent, such as ethanol or distilled water, to create a solution. The liquid serves as a carrier for the LSD, allowing for accurate dosage and administration onto small pieces of blotter paper called tabs. LSD is typically either swallowed or held under the tongue. In pure form, LSD is clear or white in color, has no smell, and is crystalline. It breaks down with exposure to ultraviolet light.

<span class="mw-page-title-main">Phencyclidine</span> Dissociative hallucinogenic drug, mostly used recreationally

Phencyclidine or phenylcyclohexyl piperidine (PCP), also known in its use as a street drug as angel dust among other names, is a dissociative anesthetic mainly used recreationally for its significant mind-altering effects. PCP may cause hallucinations, distorted perceptions of sounds, and violent behavior. As a recreational drug, it is typically smoked, but may be taken by mouth, snorted, or injected. It may also be mixed with cannabis or tobacco.

<span class="mw-page-title-main">Recreational drug use</span> Use of drugs with the primary intention to alter the state of consciousness

Recreational drug use is the use of one or more psychoactive drugs to induce an altered state of consciousness, either for pleasure or for some other casual purpose or pastime. When a psychoactive drug enters the user's body, it induces an intoxicating effect. Recreational drugs are commonly divided into three categories: depressants, stimulants, and hallucinogens.

<span class="mw-page-title-main">Psilocybin</span> Chemical compound found in some species of mushrooms

Psilocybin is a naturally occurring psychedelic prodrug compound produced by more than 200 species of fungi. The most potent are members of genus Psilocybe, such as P. azurescens, P. semilanceata, and P. cyanescens, but psilocybin has also been isolated from about a dozen other genera. Psilocybin is itself biologically inactive but is quickly converted by the body to psilocin, which has mind-altering effects similar, in some aspects, to those of lysergic acid diethylamide (LSD), mescaline, and dimethyltryptamine (DMT). In general, the effects include euphoria, visual and mental hallucinations, changes in perception, distorted sense of time, and perceived spiritual experiences. It can also cause adverse reactions such as nausea and panic attacks.

<span class="mw-page-title-main">Psychopharmacology</span> Study of the effects of psychoactive drugs

Psychopharmacology is the scientific study of the effects drugs have on mood, sensation, thinking, behavior, judgment and evaluation, and memory. It is distinguished from neuropsychopharmacology, which emphasizes the correlation between drug-induced changes in the functioning of cells in the nervous system and changes in consciousness and behavior.

<span class="mw-page-title-main">Psychedelic drug</span> Hallucinogenic class of psychoactive drug

Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states and an apparent expansion of consciousness. Also referred to as classic hallucinogens or serotonergic hallucinogens, the term psychedelic is sometimes used more broadly to include various types of hallucinogens, such as those which are atypical or adjacent to psychedelia like salvia and MDMA, respectively. This article makes use of the narrower classical definition of psychedelics. Classic psychedelics generally cause specific psychological, visual, and auditory changes, and oftentimes a substantially altered state of consciousness. They have had the largest influence on science and culture, and include mescaline, LSD, psilocybin, and DMT.

A bad trip is a term describing an acute adverse psychological reaction to effects produced under the influence of psychoactive substances, namely psychedelics. To date, there is no clear definition of what constitutes a bad trip. Additionally, knowledge on the cause of bad trips and who may be vulnerable to such experiences are limited. Existing studies report that possible adverse reactions include, anxiety, panic, depersonalization, ego dissolution, paranoia, as well as physiological symptoms such as dizziness and heart palpitations. However, most studies indicate that the set and setting of substance use influence how people respond.

Dissociatives, colloquially dissos, are a subclass of hallucinogens that distort perception of sight and sound and produce feelings of detachment – dissociation – from the environment and/or self. Although many kinds of drugs are capable of such action, dissociatives are unique in that they do so in such a way that they produce hallucinogenic effects, which may include dissociation, a general decrease in sensory experience, hallucinations, dream-like states or anesthesia. Despite most dissociatives' main mechanism of action being tied to NMDA receptor antagonism, some of these substances, which are nonselective in action and affect the dopamine and/or opioid systems, may be capable of inducing more direct and repeatable euphoria or symptoms which are more akin to the effects of typical "hard drugs" or common drugs of abuse. This is likely why dissociatives are considered to be addictive with a fair to moderate potential for abuse, unlike psychedelics. Despite some dissociatives, such as phencyclidine (PCP) possessing stimulating properties, most dissociatives seem to have a general depressant effect and can produce sedation, respiratory depression, nausea, disorientation, analgesia, anesthesia, ataxia, cognitive and memory impairment as well as amnesia.

Psychedelic therapy refers to the proposed use of psychedelic drugs, such as psilocybin, MDMA, LSD, and ayahuasca, to treat mental disorders. As of 2021, psychedelic drugs are controlled substances in most countries and psychedelic therapy is not legally available outside clinical trials, with some exceptions.

A psychedelic experience is a temporary altered state of consciousness induced by the consumption of a psychedelic substance. For example, an acid trip is a psychedelic experience brought on by the use of LSD, while a mushroom trip is a psychedelic experience brought on by the use of psilocybin. Psychedelic experiences feature alterations in normal perception such as visual distortions and a subjective loss of self-identity, sometimes interpreted as mystical experiences. Psychedelic experiences lack predictability, as they can range from being highly pleasurable to frightening. The outcome of a psychedelic experience is heavily influenced by the person's mood, personality, expectations, and environment.

<span class="mw-page-title-main">Dizocilpine</span> Chemical compound

Dizocilpine (INN), also known as MK-801, is a pore blocker of the NMDA receptor, a glutamate receptor, discovered by a team at Merck in 1982. Glutamate is the brain's primary excitatory neurotransmitter. The channel is normally blocked with a magnesium ion and requires depolarization of the neuron to remove the magnesium and allow the glutamate to open the channel, causing an influx of calcium, which then leads to subsequent depolarization. Dizocilpine binds inside the ion channel of the receptor at several of PCP's binding sites thus preventing the flow of ions, including calcium (Ca2+), through the channel. Dizocilpine blocks NMDA receptors in a use- and voltage-dependent manner, since the channel must open for the drug to bind inside it. The drug acts as a potent anti-convulsant and probably has dissociative anesthetic properties, but it is not used clinically for this purpose because of the discovery of brain lesions, called Olney's lesions (see below), in laboratory rats. Dizocilpine is also associated with a number of negative side effects, including cognitive disruption and psychotic-spectrum reactions. It inhibits the induction of long term potentiation and has been found to impair the acquisition of difficult, but not easy, learning tasks in rats and primates. Because of these effects of dizocilpine, the NMDA receptor pore blocker ketamine is used instead as a dissociative anesthetic in human medical procedures. While ketamine may also trigger temporary psychosis in certain individuals, its short half-life and lower potency make it a much safer clinical option. However, dizocilpine is the most frequently used uncompetitive NMDA receptor antagonist in animal models to mimic psychosis for experimental purposes.

<span class="mw-page-title-main">Deliriant</span> Class of psychoactive drugs

Deliriants are a subclass of hallucinogen. The term was coined in the early 1980s to distinguish these drugs from psychedelics such as LSD and dissociatives such as ketamine, due to their primary effect of causing delirium, as opposed to the more lucid and less disturbed states produced by other types of hallucinogens. The term generally refers to anticholinergic drugs, which are substances that inhibit the function of the neurotransmitter acetylcholine. Common examples of deliriants include plants of the genera Datura and Brugmansia as well as higher than recommended dosages of diphenhydramine (Benadryl). A number of plant deliriants such as that of the Solanaceae family, particularly in the Americas have been used by some indigenous cultures to reach delirious and altered states for traditions or rituals, such as rites of passage, divination or communicating with the ancestors. Despite their long history of use, deliriants are the least-studied class of hallucinogens in terms of their behavioral and neurological effects.

<span class="mw-page-title-main">Hallucinogen persisting perception disorder</span> Medical condition

Hallucinogen persisting perception disorder (HPPD) is a non-psychotic disorder in which a person experiences apparent lasting or persistent visual hallucinations or perceptual distortions after a previous use of drugs, including but not limited to psychedelics, dissociatives, entactogens, tetrahydrocannabinol (THC), and SSRIs. Despite being designated as a hallucinogen-specific disorder, the specific contributory role of psychedelic drugs is unknown.

<span class="mw-page-title-main">Serotonin receptor agonist</span> Neurotransmission-modulating substance

A serotonin receptor agonist is an agonist of one or more serotonin receptors. They activate serotonin receptors in a manner similar to that of serotonin, a neurotransmitter and hormone and the endogenous ligand of the serotonin receptors.

<span class="mw-page-title-main">NMDA receptor antagonist</span> Class of anesthetics

NMDA receptor antagonists are a class of drugs that work to antagonize, or inhibit the action of, the N-Methyl-D-aspartate receptor (NMDAR). They are commonly used as anesthetics for human and non-human animals; the state of anesthesia they induce is referred to as dissociative anesthesia.

<span class="mw-page-title-main">Etoxadrol</span> Chemical compound

Etoxadrol (CL-1848C) is a dissociative anaesthetic drug that has been found to be an NMDA antagonist and produce similar effects to PCP in animals. Etoxadrol, along with another related drug dexoxadrol, were developed as analgesics for use in humans, but development was discontinued in the late 1970s after patients reported side effects such as nightmares and hallucinations.

<span class="mw-page-title-main">2-Bromo-LSD</span> Chemical compound

2-Bromo-LSD, also known as BOL-148, is a derivative of lysergic acid invented by Albert Hofmann, as part of the original research from which the closely related compound LSD was also derived.

<span class="mw-page-title-main">Psychoactive drug</span> Chemical substance that alters nervous system function

A psychoactive drug, psychopharmaceutical, psychoactive agent, or psychotropic drug is a chemical substance that changes the function of the nervous system and results in alterations of perception, mood, cognition, and behavior. These substances may be used medically, recreationally, for spiritual reasons, or for research. Some categories of psychoactive drugs may be prescribed by physicians and other healthcare practitioners because of their therapeutic value.

Psychoplastogens are a group of small molecule drugs that produce rapid and sustained effects on neuronal structure and function, intended to manifest therapeutic benefit after a single administration. Several existing psychoplastogens have been identified and their therapeutic effects demonstrated; several are presently at various stages of development as medications including Ketamine, MDMA, Scopolamine, and the serotonergic psychedelics, including LSD, psilocin, DMT, and 5-MeO-DMT. Compounds of this sort are being explored as therapeutics for a variety of brain disorders including depression, addiction, and PTSD. The ability to rapidly promote neuronal changes via mechanisms of neuroplasticity was recently discovered as the common therapeutic activity and mechanism of action.

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