Psychedelic drug

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Synthetic mescaline. Normally biosynthesized from peyote and some other cacti, mescaline was the first psychedelic compound to be extracted and isolated. Synthetic mescaline powder i2001e0151 ccby3.jpg
Synthetic mescaline. Normally biosynthesized from peyote and some other cacti, mescaline was the first psychedelic compound to be extracted and isolated.

Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states (known as psychedelic experiences or psychedelic "trips") and/or an apparent expansion of consciousness. [2] [3] [4] Sometimes, they are called classic hallucinogens, serotonergic hallucinogens, or serotonergic psychedelics, and the term psychedelic is sometimes used more broadly to include various types of hallucinogens or those which are atypical or adjacent to psychedelia such as MDMA or cannabis; this article uses the narrower definition of psychedelics. True psychedelics cause specific psychological, visual, and auditory changes, and oftentimes a substantially altered state of consciousness. [5] [6] [3] [7] Psychedelic states are often compared to meditative, psychodynamic or transcendental types of alterations of mind. [4] [5] [8] The "classical" psychedelics, the psychedelics with the largest scientific and cultural influence, are mescaline, LSD, psilocybin, and DMT. [5] [9] [10] [4] LSD in particular has long been considered the paradigmatic psychedelic compound, to which all other psychedelics are often or usually compared.

Contents

Most psychedelic drugs fall into one of the three families of chemical compounds: tryptamines, phenethylamines, or lysergamides (LSD is considered both a tryptamine and lysergamide). They act via serotonin 2A receptor agonism. [2] [11] [12] [13] When compounds bind to serotonin 5-HT2A receptors, [14] they modulate the activity of key circuits in the brain involved with sensory perception and cognition, however, the exact nature of how psychedelics induce changes in perception and cognition via the 5-HT2A receptor is still unknown, although reduction in default mode network activity and increased functional connectivity between regions in the brain as a result may be one of the most relevant pharmacological mechanisms underpinning the psychedelic experience, [15] [16] particularly ego death. [17] The psychedelic experience is often compared to non-ordinary forms of consciousness such as those experienced in meditation, [18] [3] mystical experiences, [8] [7] and near-death experiences, [7] which also appear to be partially underpinned by altered default mode network activity. [19] [20] The phenomenon of ego death is often described as a key feature of the psychedelic experience. [18] [3] [7]

Many psychedelic drugs are illegal worldwide under the UN conventions, with occasional exceptions for religious use or research contexts. Despite these controls, recreational use of psychedelics is common. [21] [22] Legal barriers have made the scientific study of psychedelics more difficult. Research has been conducted, however, and studies show that psychedelics are physiologically safe and rarely lead to addiction. [23] [24] Studies conducted using psilocybin in a psychotherapeutic setting reveal that psychedelic drugs may assist with treating depression, alcohol addiction, and nicotine addiction. [13] [25] Although further research is needed, existing results suggest that psychedelics could be effective treatments for certain forms of psychopathology. [26] [27] [28] [22] A 2022 survey found that 28% of Americans had used a psychedelic at some point in their life. [29]

Etymology and nomenclature

5-HT2A receptor 5ht2a.jpg
5-HT2A receptor

The term psychedelic was coined by the psychiatrist Humphrey Osmond during written correspondence with author Aldous Huxley and presented to the New York Academy of Sciences by Osmond in 1957. [30] It is irregularly [31] derived from the Greek words ψυχή psychḗ 'soul, mind' and δηλείν dēleín 'to manifest', with the intended meaning "mind manifesting," the implication being that psychedelics can reveal unused potentials of the human mind. [32] The term was loathed by American ethnobotanist Richard Schultes but championed by American psychologist Timothy Leary. [33]

Aldous Huxley had suggested his own coinage phanerothyme (Greek phaneroein- "visible" and Greek thymos "soul", thus "visible soul") to Osmond in 1956. [34] Recently, the term entheogenic has come into use to denote the use of psychedelic drugs, as well as various other types of psychoactive substances, in a religious, spiritual, and mystical context. [35]

In 2004, David E. Nichols wrote the following about the nomenclature used for psychedelic drugs: [35]

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." [36]

While the term psychedelic is most commonly used to refer only to serotonergic hallucinogens, [13] [12] [37] [38] it is sometimes used for a much broader range of drugs, including empathogen–entactogens, dissociatives, and atypical hallucinogens/psychoactives such as Amanita muscaria , Cannabis sativa , Nymphaea nouchali and Salvia divinorum . [27] [39] Thus, the term serotonergic psychedelic is sometimes used for the narrower class. [40] [41] It is important to check the definition of a given source. [35] This article uses the more common, narrower definition of psychedelic.

Examples

Doses of lysergic acid diethylamide (LSD) Adams-hand-net.jpg
Doses of lysergic acid diethylamide (LSD)

Uses

Traditional

Preparation of Ayahuasca, Province of Pastaza, Ecuador. Ayahuasca prep.JPG
Preparation of Ayahuasca, Province of Pastaza, Ecuador.

A number of frequently mentioned or traditional psychedelics such as Ayahuasca (which contains DMT), San Pedro, Peyote, and Peruvian torch (which all contain mescaline), Psilocybe mushrooms (which contain psilocin/psilocybin) and Tabernanthe iboga (which contains the unique psychedelic ibogaine) all have a long and extensive history of spiritual, shamanic and traditional usage by indigenous peoples in various world regions, particularly in Latin America, but also Gabon, Africa in the case of iboga. [52] Different countries and/or regions have come to be associated with traditional or spiritual use of particular psychedelics, such as the ancient and entheogenic use of psilocybe mushrooms by the native Mazatec people of Oaxaca, Mexico [53] or the use of the ayahuasca brew in the Amazon basin, particularly in Peru for spiritual and physical healing as well as for religious festivals. [54] Peyote has also been used for several thousand years in the Rio Grande Valley in North America by native tribes as an entheogen.[ citation needed ] In the Andean region of South America, the San Pedro cactus ( Echinopsis pachanoi ) has a long history of use, possibly as a traditional medicine. Archaeological studies have found evidence of use going back two thousand years, to Moche culture, [55] Nazca culture, [56] and Chavín culture. Although authorities of the Roman Catholic church attempted to suppress its use after the Spanish conquest, [57] this failed, as shown by the Christian element in the common name "San Pedro cactus" – Saint Peter cactus. The name is attributed[ by whom? ] to the belief that just as St Peter holds the keys to heaven, the effects of the cactus allow users "to reach heaven while still on earth." [58] In 2022, the Peruvian Ministry of Culture declared the traditional use of San Pedro cactus in northern Peru as cultural heritage. [59]

Although people of western culture have tended to use psychedelics for either psychotherapeutic or recreational reasons, most indigenous cultures, particularly in South America have seemingly tended to use psychedelics for more supernatural reasons such as divination. This can often be related to “healing” or health as well but typically in the context of finding out what is wrong with the individual; such as using psychedelic states to “identify” a disease and/or its cause, locate lost objects, and identify a victim or even perpetrator of sorcery. [60] In some cultures and regions, even psychedelics themselves, such as ayahuasca and the psychedelic lichen of eastern Ecuador ( Dictyonema huaorani ) that supposedly contains both 5-MeO-DMT and psilocybin, have also been used by witches and sorcerers to conduct their malicious magic, similarly to nightshade deliriants like brugmansia and latua . [60] [ citation needed ]

Psychedelic therapy

Psychedelic therapy (or psychedelic-assisted therapy) is the proposed use of psychedelic drugs to treat mental disorders. [27] [38] As of 2021, psychedelic drugs are controlled substances in most countries and psychedelic therapy is not legally available outside clinical trials, with some exceptions. [38] [61]

The procedure for psychedelic therapy differs from that of therapies using conventional psychiatric medications. While conventional medications are usually taken without supervision at least once daily, in contemporary psychedelic therapy the drug is administered in a single session (or sometimes up to three sessions) in a therapeutic context. [62] The therapeutic team prepares the patient for the experience beforehand and helps them integrate insights from the drug experience afterwards. [63] [64] After ingesting the drug, the patient normally wears eyeshades and listens to music to facilitate focus on the psychedelic experience, with the therapeutic team interrupting only to provide reassurance if adverse effects such as anxiety or disorientation arise. [63] [64]

As of 2022, the body of high-quality evidence on psychedelic therapy remains relatively small and more, larger studies are needed to reliably show the effectiveness and safety of psychedelic therapy's various forms and applications. [26] [27] On the basis of favorable early results, ongoing research is examining proposed psychedelic therapies for conditions including major depressive disorder, [26] [65] and anxiety and depression linked to terminal illness. [26] [66] The United States Food and Drug Administration has granted "breakthrough therapy" status, which expedites the assessment of promising drug therapies for potential approval, [note 1] to psilocybin therapy for treatment-resistant depression and major depressive disorder. [38]

Recreational

Recreational use of psychedelics is common. [21] [22] A survey published in 2013 found that 13.4% of American adults had used a psychedelic. [68]

Microdosing

Psychedelic microdosing is the practice of using sub-threshold doses (microdoses) of psychedelics in an attempt to improve creativity, boost physical energy level, emotional balance, increase performance on problems-solving tasks and to treat anxiety, depression and addiction. [69] [70] The practice of microdosing has become more widespread in the 21st century with more people claiming long-term benefits from the practice. [71] [72]

A 2022 study recognized signatures of psilocybin microdosing in natural language and concluded that low amount of psychedelics have potential for application, and ecological observation of microdosing schedules. [73] [74]

Pharmacology

While the method of action of psychedelics is not fully understood, they are known to show affinities for various 5-HT (serotonin) receptors in different ways and levels, and may be classified by their activity at different 5-HT sub-types, particularly 5-HT1A, 5-HT2A, and 5-HT2C. [35] It is almost unanimously agreed that psychedelics produce their effect by acting as strong partial agonists at the 5-HT2A receptors. [2] [75] [12] [13] How this produces the psychedelic experience is unclear, but it is likely that it acts by increasing excitation in the cortex, possibly by specifically facilitating input from the thalamus, the major relay for sensory information input to the cortex. [35] Additionally, researchers discovered that many psychedelics are potent psychoplastogens, compounds capable of promoting rapid and sustained neural plasticity. [76] [77]

Tryptamines

N,N-DMT DMT.svg
N,N-DMT

Tryptamine, along with other trace amines, is found in the central nervous system of mammals. It is hypothesized to play a role as a neuromodulator on classical monoamine neurotransmitters, such as dopamine, serotonin, and norepinephrine (epinephrine). Tryptamine acts as a non-selective serotonin receptor agonist to activate serotonin receptors, and a serotonin–norepinephrine–dopamine releasing agent (SNDRA) to release more monoamine neurotransmitter, with a preference for evoking serotonin and dopamine release over norepinephrine (epinephrine) release. [78] [79] [80] Psychedelic tryptamines found in nature include psilocin, DMT, 5-MeO-DMT, and tryptamines that have been synthesized in the laboratory include 4-HO-MET, [81] 4-HO-MiPT, [45] and 5-MeO-DALT. [82]

Mescaline Mescaline Structural Formula.svg
Mescaline

Phenethylamines

Phenethylamine is also a trace amine but to a lesser extent acts as a neurotransmitter in the human central nervous system (CNS). Phenethylamine instead regulates monoamine neurotransmission by binding to trace amine-associated receptor 1 (TAAR1), which plays a significant role in regulating neurotransmission in dopamine, norepinephrine, and serotonin neurons in the CNS and inhibiting vesicular monoamine transporter 2 (VMAT2) in monoamine neurons. [83] [84] When VMAT2 is inhibited monoamine neurotransmitters such as dopamine cannot be released into the synapse via typical release mechanisms. [85] Mescaline is a naturally occurring psychedelic protoalkaloid of the substituted phenethylamine class.

Lysergamides

Lysergic acid diethylamide (LSD) Lysergsaurediethylamid (LSD).svg
Lysergic acid diethylamide (LSD)

Amides of lysergic acid are collectively known as lysergamides, and include a number of compounds with potent agonist and/or antagonist activity at various serotonin and dopamine receptors. Lysergamides contain both Tryptamine and Phenethylamine structure although it is class as a complex Tryptamine. LSD (Lysergic Acid Diethylamide) is one of many lysergamides. A wide range of lysergamides have emerged in recent years, inspired by existing scientific literature. Others, have appeared from chemical research. [86] 1P-LSD is a derivative and functional analogue of LSD and a homologue of ALD-52. It modifies the LSD molecule by adding a propionyl group to the nitrogen molecule of LSD's indole. [87]

Psychedelic experiences

Although several attempts 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. [88] [89] At lower doses, features of psychedelic experiences include sensory alterations, such as the warping of surfaces, shape suggestibility, pareidolia and color variations. Users often report intense colors that they have not previously experienced, and repetitive geometric shapes or form constants are common as well. Higher doses often cause intense and fundamental alterations of sensory (notably visual) perception, such as synesthesia or the experience of additional spatial or temporal dimensions. [90] Tryptamines are well documented to cause classic psychedelic states, such as increased empathy, visual distortions (drifting, morphing, breathing, melting of various surfaces and objects), auditory hallucinations, ego dissolution or ego death with high enough dose, mystical, transpersonal and spiritual experiences, autonomous "entity" encounters, time distortion, closed eye hallucinations and complete detachment from reality with a high enough dose. [91] Luis Luna describes psychedelic experiences as having a distinctly gnosis-like quality, and says that they offer "learning experiences that elevate consciousness and can make a profound contribution to personal development." [92] Czech psychiatrist Stanislav Grof studied the effects of psychedelics like LSD early in his career and said of the experience, that it commonly includes "complex revelatory insights into the nature of existence… typically accompanied by a sense of certainty that this knowledge is ultimately more relevant and 'real' than the perceptions and beliefs we share in everyday life."[ citation needed ] Traditionally, the standard model for the subjective phenomenological effects of psychedelics has typically been based on LSD, with anything that is considered "psychedelic" evidently being compared to it and its specific effects.[ citation needed ]

During a speech on his 100th birthday, the inventor of LSD, Albert Hofmann said of the drug: "It gave me an inner joy, an open mindedness, a gratefulness, open eyes and an internal sensitivity for the miracles of creation... I think that in human evolution it has never been as necessary to have this substance LSD. It is just a tool to turn us into what we are supposed to be." [93] With certain psychedelics and experiences, a user may also experience an "afterglow" of improved mood or perceived mental state for days or even weeks after ingestion in some cases. [94] In 1898, the English writer and intellectual Havelock Ellis reported a heightened perceptual sensitivity to "the more delicate phenomena of light and shade and color" for a prolonged period of time after his exposure to mescaline. [95] Good trips are reportedly deeply pleasurable, and typically involve intense joy or euphoria, a greater appreciation for life, reduced anxiety, a sense of spiritual enlightenment, and a sense of belonging or interconnectedness with the universe. [96] [97] Negative experiences, colloquially known as "bad trips," evoke an array of dark emotions, such as irrational fear, anxiety, panic, paranoia, dread, distrustfulness, hopelessness, and even suicidal ideation. [98] While it is impossible to predict when a bad trip will occur, one's mood, surroundings, sleep, hydration, social setting, and other factors can be controlled (colloquially referred to as "set and setting") to minimize the risk of a bad trip. [99] [100] The concept of “set and setting” also generally appears to be more applicable to psychedelics than to other types of hallucinogens such as deliriants, hypnotics and dissociative anesthetics.[ citation needed ]

Classic psychedelics are considered to be those found in nature like psilocybin, DMT, mescaline, and LSD which is derived from naturally occurring ergotamine, and non-classic psychedelics are considered to be newer analogs and derivatives of pharmacophore lysergamides, tryptamine, and phenethylamine structures like 2C-B. Many of these psychedelics cause remarkably similar effects, despite their different chemical structure. However, many users report that the three major families have subjectively different qualities in the "feel" of the experience, which are difficult to describe. Some compounds, such as 2C-B, have extremely tight "dose curves", meaning the difference in dose between a non-event and an overwhelming disconnection from reality can be very slight. There can also be very substantial differences between the drugs; for instance, 5-MeO-DMT rarely produces the visual effects typical of other psychedelics. [13]

Potential adverse effects

Despite the contrary perception of much of the public, psychedelic drugs are not addictive and are physiologically safe. [23] [24] [13] As of 2016, there have been no known deaths due to overdose of LSD, psilocybin, or mescaline. [13]

Risks do exist during an unsupervised psychedelic experience, however; Ira Byock wrote in 2018 in the Journal of Palliative Medicine that psilocybin is safe when administered to a properly screened patient and supervised by a qualified professional with appropriate set and setting. However, he called for an "abundance of caution" because in the absence of these conditions a range of negative reactions is possible, including "fear, a prolonged sense of dread, or full panic." He notes that driving or even walking in public can be dangerous during a psychedelic experience because of impaired hand-eye coordination and fine motor control. [101] In some cases, individuals taking psychedelics have performed dangerous or fatal acts because they believed they possessed superhuman powers. [13]

Psilocybin-induced states of mind share features with states experienced in psychosis, and while a causal relationship between psilocybin and the onset of psychosis has not been established as of 2011, researchers have called for investigation of the relationship. [102] Many of the persistent negative perceptions of psychological risks are unsupported by the currently available scientific evidence, with the majority of reported adverse effects not being observed in a regulated and/or medical context. [103] A population study on associations between psychedelic use and mental illness published in 2013 found no evidence that psychedelic use was associated with increased prevalence of any mental illness. [104]

Using psychedelics poses certain risks of re-experiencing of the drug's effects, including flashbacks and hallucinogen persisting perception disorder (HPPD). [102] These non-psychotic effects are poorly studied, but the permanent symptoms (also called "endless trip") are considered to be rare. [105]

Serotonin syndrome can be caused by combining psychedelics with other serotonergic drugs, including certain antidepressants, opioids, CNS stimulants (e.g. MDMA), 5-HT1 agonists (e.g. triptans), herbs and others. [106] [107] [108] [109]

Potential therapeutic effects

Psilocybin session at Johns Hopkins Johns Hopkins psilocybin session room-SessionRm 2176x.jpg
Psilocybin session at Johns Hopkins

Psychedelic substances which may have therapeutic uses include psilocybin, LSD, and mescaline. [28] During the 1950s and 1960s, lack of informed consent in some scientific trials on psychedelics led to significant, long-lasting harm to some participants. [28] Since then, research regarding the effectiveness of psychedelic therapy has been conducted under strict ethical guidelines, with fully informed consent and a pre-screening to avoid people with psychosis taking part. [28] Although the history behind these substances has hindered research into their potential medicinal value, scientists are now able to conduct studies and renew research that was halted in the 1970s. Some research has shown that these substances have helped people with such mental disorders as obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), alcoholism, depression, and cluster headaches. [22]

It has long been known that psychedelics promote neurite growth and neuroplasticity and are potent psychoplastogens. [110] [111] [112] There is evidence that psychedelics induce molecular and cellular adaptations related to neuroplasticity and that these could potentially underlie therapeutic benefits. [113] [114] Psychedelics have also been shown to have potent anti-inflammatory activity and therapeutic effects in animal models of inflammatory diseases including asthma, [115] and cardiovascular disease and diabetes. [116]

Surrounding culture

Psychedelic rock band Jefferson Airplane in 1967 Jefferson Airplane photo 1967.JPG
Psychedelic rock band Jefferson Airplane in 1967

Psychedelic culture includes manifestations such as psychedelic music, [117] psychedelic art, [118] psychedelic literature, [119] psychedelic film, [120] and psychedelic festivals. [121] Examples of psychedelic music would be rock bands like the Grateful Dead, Jefferson Airplane and The Beatles. Many psychedelic bands and elements of the psychedelic subculture originated in San Francisco during the mid to late 1960s. [122]

Many psychedelics are classified under Schedule I of the United Nations Convention on Psychotropic Substances of 1971 as drugs with the greatest potential to cause harm and no acceptable medical uses. [123] In addition, many countries have analogue laws; for example, in the United States, the Federal Analogue Act of 1986 automatically forbids any drugs sharing similar chemical structures or chemical formulas to illicit or prohibited substances if sold for human consumption. [124]

U.S. states such as Oregon and Colorado have also instituted decriminalization and legalization measures of psychedelics [125] and states like New Hampshire and others are attempting to do the same. [126] J.D. Tuccille argues that increasing rates of use of psychedelics in defiance of the law are likely to result in more widespread legalization and decriminalization of the substances in the United States (as has happened with alcohol and cannabis). [127]

See also

Categories

Notes

  1. ↑ The Food and Drug Administration describes the designation of breakthrough therapy as "a process designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s)." [67]

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 human beings, and which is both a derivative and a structural analog of tryptamine. It is used as a psychedelic drug and prepared by various cultures for ritual purposes as an entheogen.

<span class="mw-page-title-main">Lysergic acid diethylamide</span> Hallucinogenic drug

Lysergic acid diethylamide (LSD), also known colloquially as acid, is a potent psychedelic drug. Effects typically include intensified thoughts, emotions, and sensory perception. At sufficiently high dosages LSD manifests primarily mental, visual, as well as 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 psychedelics with the greatest scientific and cultural significance. LSD is typically either swallowed or held under the tongue. It is most often sold on blotter paper and less commonly as tablets, in a watery solution or in gelatin squares called panes.

<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 the 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 LSD, mescaline, and DMT. In general, the effects include euphoria, visual and mental hallucinations, changes in perception, a 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">Mescaline</span> Chemical compound

Mescaline or mescalin (3,4,5-trimethoxyphenethylamine) is a naturally occurring psychedelic protoalkaloid of the substituted phenethylamine class, known for its hallucinogenic effects comparable to those of LSD and psilocybin.

<span class="mw-page-title-main">5-MeO-DMT</span> Chemical compound

5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine) or O-methyl-bufotenin is a psychedelic of the tryptamine class. It is found in a wide variety of plant species, and also is secreted by the glands of at least one toad species, the Colorado River toad. Like its close relatives DMT and bufotenin (5-HO-DMT), it has been used as an entheogen in South America. Slang terms include Five-methoxy, The power, and Toad venom.

<span class="mw-page-title-main">Empathogen–entactogen</span> Class of psychoactive drugs that produce empathic experiences

Empathogens or entactogens are a class of psychoactive drugs that produce experiences of emotional communion, oneness, relatedness, emotional openness—that is, empathy or sympathy—as particularly observed and reported for experiences with 3,4-methylenedioxymethamphetamine (MDMA). This class of drug is distinguished from the classes of hallucinogen or psychedelic, and amphetamine or stimulants. Major members of this class include MDMA, MDA, MDEA, MDOH, MBDB, 5-APB, 5-MAPB, 6-APB, 6-MAPB, methylone, mephedrone, GHB, αMT, and αET, MDAI among others. Most entactogens are phenethylamines and amphetamines, although several, such as αMT and αET, are tryptamines. When referring to MDMA and its counterparts, the term MDxx is often used. Entactogens are sometimes incorrectly referred to as hallucinogens or stimulants, although many entactogens such as ecstasy exhibit psychedelic or stimulant properties as well.

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.

<span class="mw-page-title-main">Psilocin</span> Psychedelic substance

Psilocin is a substituted tryptamine alkaloid and a serotonergic psychedelic substance. It is present in most psychedelic mushrooms together with its phosphorylated counterpart psilocybin. Psilocin is a Schedule I drug under the Convention on Psychotropic Substances. Acting on the 5-HT2A receptors, psilocin modulates the production and reuptake of serotonin. The mind-altering effects of psilocin are highly variable and subjective and resemble those of LSD and DMT.

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

DET, also known under its chemical name N,N-diethyltryptamine and as T-9, is a psychedelic drug closely related to DMT and 4-HO-DET. However, despite its structural similarity to DMT, its activity is induced by an oral dose of around 50–100 mg, without the aid of MAO inhibitors, and the effects last for about 2–4 hours.

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">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, 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">Indole alkaloid</span> Class of alkaloids

Indole alkaloids are a class of alkaloids containing a structural moiety of indole; many indole alkaloids also include isoprene groups and are thus called terpene indole or secologanin tryptamine alkaloids. Containing more than 4100 known different compounds, it is one of the largest classes of alkaloids. Many of them possess significant physiological activity and some of them are used in medicine. The amino acid tryptophan is the biochemical precursor of indole alkaloids.

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

ETH-LAD, 6-ethyl-6-nor-lysergic acid diethylamide is an analogue of LSD. Its human psychopharmacology was first described by Alexander Shulgin in the book TiHKAL. ETH-LAD is a psychedelic drug similar to LSD, and is slightly more potent than LSD itself, with an active dose reported at between 20 and 150 micrograms. ETH-LAD has subtly different effects to LSD, described as less demanding.

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

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.

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. Most hallucinogens can be categorized as either being psychedelics, dissociatives, or deliriants. However, others such as Fly agaric as well as other GABAergic hallucinogenics are more often considered to technically be hypnotics, therefore indicating another separate subcategory of drugs which can substantially alter visual perception.

<span class="mw-page-title-main">Substituted tryptamine</span> Class of indoles

Substituted tryptamines, or serotonin analogues, are organic compounds which may be thought of as being derived from tryptamine itself. The molecular structures of all tryptamines contain an indole ring, joined to an amino (NH2) group via an ethyl (−CH2–CH2−) sidechain. In substituted tryptamines, the indole ring, sidechain, and/or amino group are modified by substituting another group for one of the hydrogen (H) atoms.

<span class="mw-page-title-main">1-Methylpsilocin</span> Chemical compound

1-Methylpsilocin is a tryptamine derivative which acts as a selective agonist for the 5-HT2C receptor (IC50 of 12 nM, vs 633 nM at 5-HT2A), and an inverse agonist at 5-HT2B (Ki of 38 nM). While 1-methylpsilocin does have higher affinity for 5-HT2C than 5-HT2A, it does produce a head-twitch response in mice that are dependent on 5-HT2A, so it is not entirely free of effects on 5-HT2A in vivo. In contrast to psilocin, 1-methylpsilocin did not activate 5-HT1A receptors in mice. 1-Methylpsilocin has been investigated for applications such as treatment of glaucoma, OCD, and cluster headaches, as these conditions are amenable to treatment with psychedelic drugs but are not generally treated with such agents due to the hallucinogenic side effects they produce, which are considered undesirable. 1-Methylpsilocin therefore represents a potential alternative treatment to psilocin that may be less likely to produce hallucinogenic effects.

Psychedelic microdosing is the practice of using sub-threshold doses (microdoses) of serotonergic psychedelic drugs in an attempt to improve creativity, boost physical energy level, promote emotional balance, increase performance on problems-solving tasks and to treat anxiety, depression and addiction. The practice of microdosing has become more widespread in the 21st century with more people claiming long-term benefits from the practice.

<span class="mw-page-title-main">4-PrO-DMT</span> Chemical compound

4-Propionoxy-N,N-dimethyltryptamine is a synthetic psychedelic drug from the tryptamine family with psychedelic effects, and is theorized to act as a prodrug for psilocin. It has been sold online as a designer drug since May 2019. It was first identified as a new psychoactive substance in Sweden, in July 2019.

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 – the active metabolite of psilocybin, 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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