Psychedelic drug

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Synthetic mescaline, the first psychedelic compound to be extracted and isolated[1]

Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states (known as psychedelic experiences or "trips") and an apparent expansion of consciousness.[2][3] 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.[4]

Classic psychedelics generally cause specific psychological, visual, and auditory changes, and oftentimes a substantially

LSD, psilocybin, and DMT.[7][8]

Most psychedelic drugs fall into one of the three families of chemical compounds:

mystical experiences,[6][5] and near-death experiences,[5] which also appear to be partially underpinned by altered default mode network activity.[15] The phenomenon of ego death is often described as a key feature of the psychedelic experience.[14][3][5]

Many psychedelic drugs are illegal worldwide under the

nicotine addiction.[11][20] Although further research is needed, existing results suggest that psychedelics could be effective treatments for certain forms of psychopathology.[21][22][23][17] A 2022 survey found that 28% of Americans had used a psychedelic at some point in their life.[24]

Etymology and nomenclature

5-HT2A receptor

The term

Richard Schultes but championed by American psychologist Timothy Leary.[28]

Aldous Huxley had suggested his own coinage phanerothyme (Greek phaneroein- "to make manifest or visible" and Greek thymos "soul", thus "to reveal the soul") to Osmond in 1956.[29] Recently, the term entheogen (meaning "that which produces the divine within") 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.[30]

In 2004, David E. Nichols wrote the following about the nomenclature used for psychedelic drugs:[30]

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."[31]

While the term psychedelic is most commonly used to refer only to serotonergic hallucinogens,[11][10][32][33] 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.[22][34] Thus, the term serotonergic psychedelic is sometimes used for the narrower class.[35][36] It is important to check the definition of a given source.[30] This article uses the more common, narrower definition of psychedelic.

Examples

lysergic acid diethylamide
(LSD)
Mimosa hostilis
 root bark (left); vape cartridge made with freebase N,N-DMT extract (right)
Main article: List of psychedelic drugs
  • 2C-B (2,5-dimethoxy-4-bromophenethylamine) is a substituted phenethylamine first synthesised in 1974 by Alexander Shulgin.[37][page needed] 2C-B is both a psychedelic and a mild entactogen, with its psychedelic effects increasing and its entactogenic effects decreasing with dosage. 2C-B is the most well known compound in the 2C family, their general structure being discovered as a result of modifying the structure of mescaline.[37][page needed]
  • DMT (N,N-dimethyltryptamine) is an indole alkaloid found in various species of plants. Traditionally it is consumed by tribes in South America in the form of ayahuasca. A brew is used that consists of DMT-containing plants as well as plants containing MAOIs, specifically harmaline, which allows DMT to be consumed orally without being rendered inactive by monoamine oxidase enzymes in the digestive system.[38] In the Western world DMT is more commonly consumed via the vaporisation of freebase DMT. Whereas Ayahuasca typically lasts for several hours, inhalation has an onset measured in seconds and has effects measured in minutes, being significantly more intense.[39] Particularly in vaporised form, DMT has the ability to cause users to enter a hallucinatory realm fully detached from reality, being typically characterised by hyperbolic geometry, and described as defying visual or verbal description.[40] Users have also reported encountering and communicating with entitites within this hallucinatory state.[41] DMT is the archetypal substituted tryptamine, being the structural scaffold of psilocybin and – to a lesser extent – the lysergamides.
  • LSD (Lysergic acid diethylamide) is a derivative of lysergic acid, which is obtained from the hydrolysis of ergotamine. Ergotamine is an alkaloid found in the fungus Claviceps purpurea, which primarily infects rye. LSD is both the prototypical psychedelic and the prototypical lysergamide. As a lysergamide, LSD contains both a tryptamine and phenethylamine group within its structure. As a result of containing a phenethylamine group LSD agonises dopamine receptors as well as serotonin receptors,[42] making it more energetic in effect in contrast to the more sedating effects of psilocin, which is not a dopamine agonist.[43]
  • Echinopsis pachanoi). Mescaline has effects comparable to those of LSD and psilocybin, albeit with a greater emphasis on colors and patterns.[44][page needed] Ceremonial San Pedro use seems to be characterized by relatively strong spiritual experiences, and low incidence of challenging experiences.[45]
  • 4-HO-MIPT and 4-HO-MET, respectively.[47]

Uses

Traditional

Preparation of Ayahuasca, province of Pastaza, Ecuador
Religious statues involving Psilocybe Mushrooms
Echinopsis pachanoi in Peru

A number of frequently mentioned or traditional psychedelics such as

Moche culture,[52] Nazca culture,[53] and Chavín culture. Although authorities of the Roman Catholic church attempted to suppress its use after the Spanish conquest,[54] this failed, as shown by the Christian element in the common name "San Pedro cactus" – Saint Peter cactus. The name has its origin in 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."[55] In 2022, the Peruvian Ministry of Culture declared the traditional use of San Pedro cactus in northern Peru as cultural heritage.[56]

Although people of

deliriants like brugmansia and latua.[57][citation needed
]

Psychedelic therapy

Main article: Psychedelic therapy

Psychedelic therapy (or psychedelic-assisted therapy) is the proposed use of psychedelic drugs to treat mental disorders.[58] As of 2021, psychedelic drugs are controlled substances in most countries and psychedelic therapy is not legally available outside clinical trials, with some exceptions.[33][59]

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.[60] The therapeutic team prepares the patient for the experience beforehand and helps them integrate insights from the drug experience afterwards.[61][62] 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.[61][62]

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.[21][22] On the basis of favorable early results, ongoing research is examining proposed psychedelic therapies for conditions including major depressive disorder,[21][63] and anxiety and depression linked to terminal illness.[21][64] 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.[33]

Recreational

Further information: Recreational drug use § Hallucinogens

Recreational use of psychedelics has been common since the psychedelic era of the mid 1960s, and continues to play a role in various festivals and events, including Burning Man.[16][17] A survey published in 2013 found that 13.4% of American adults had used a psychedelic.[66]

Microdosing

Main article: Psychedelic 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.[67][68] The practice of microdosing has become more widespread in the 21st century with more people claiming long-term benefits from the practice.[69][70]

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.[71][72]

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.

neural plasticity.[74][75]

Tryptamines

N,N-DMT

DMT, 5-MeO-DMT, and tryptamines that have been synthesized in the laboratory include 4-HO-MET,[79] 4-HO-MiPT,[47] and 5-MeO-DALT.[80]

Mescaline

Phenethylamines

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.[81][82] When VMAT2 is inhibited monoamine neurotransmitters such as dopamine cannot be released into the synapse via typical release mechanisms.[83] Mescaline is a naturally occurring psychedelic protoalkaloid of the substituted phenethylamine
class.

Lysergamides

Lysergic acid diethylamide (LSD)

indole.[85]

Psychedelic experiences

Main article: Psychedelic experience

Although several attempts have been made, starting in the 19th and 20th centuries, to define common

its specific effects.[91]

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."[92] 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.[93] 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.[94] 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.[95][96] 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.[97] 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.[98][99] 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.[100]

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.[11]

Potential adverse effects

See also: Bad trip and Trip sitter

Despite the contrary perception of much of the public, psychedelic drugs are not addictive and are physiologically safe.[18][19][11] As of 2016, there have been no known deaths due to overdose of LSD, psilocybin, or mescaline.[11]

Risks do exist during an unsupervised psychedelic experience, however;

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.[11]

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

Further information: Psychedelic therapy
Psilocybin session at Johns Hopkins

Psychedelic substances which may have therapeutic uses include psilocybin, LSD, and mescaline.

cluster headaches.[17]

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
Main article: Psychedelia

Psychedelic culture includes manifestations such as

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]

Legal status

See also: Legal status of psilocybin mushrooms, Psilocybin decriminalization in the United States, and Legal status of ayahuasca by country

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 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

Psychedelic drugs
Drug classes defined by psychological effects
Drugs by psychological effects
Psychoactive drugs

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)."[65]

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Further reading

External links

Wikimedia Commons has media related to Psychedelics.
Look up psychedelic in Wiktionary, the free dictionary.

Psychedelic Timeline by Tom Frame, Psychedelic Times

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