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Psychedelics are a subclass of Hallucinogen whose primary effect is to trigger non-ordinary mental states (known as psychedelic experiences or "trips") and a perceived "expansion of consciousness". Also referred to as classic hallucinogens or serotonergic hallucinogens, the term psychedelic is sometimes used more broadly to include various other types of hallucinogens as well, such as those which are atypical or adjacent to psychedelia like Salvia divinorum and MDMA, respectively.
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.McKenna, Terence (1992). Food of the Gods: The Search for the Original Tree of Knowledge A Radical History of Plants, Drugs, and Human EvolutionW. Davis (1996), One River: Explorations and Discoveries in the Amazon Rain Forest. New York, Simon and Schuster, Inc. p. 120. There are a large number of both natural product and synthetic serotonergic psychedelics.
Most psychedelic drugs fall into one of the three families of chemical compounds: tryptamines, phenethylamines, or lysergamides. They produce their psychedelic effects by agonist a receptor in the brain called the serotonin 5-HT2A receptor. By activating serotonin 5-HT2A receptors, 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 serotonin 5-HT2A receptor is still unknown. The psychedelic experience is often compared to non-ordinary forms of consciousness such as those experienced in meditation, mystical experiences, and near-death experiences, which also appear to be partially underpinned by altered default mode network activity. The phenomenon of ego death is often described as a key feature of the psychedelic experience.
Many psychedelic drugs are illegal to possess without lawful authorisation, exemption or license worldwide under the UN conventions, with occasional exceptions for religious use or research contexts. Despite these controls, recreational use of psychedelics is common. There is also a long history of use of naturally occurring psychedelics as dating back thousands of years. Legal barriers have made the scientific study of psychedelics more difficult. Research has been conducted, however, and studies show that psychedelics are physiologically drug safety and rarely lead to addiction. Studies conducted using psilocybin in a Psychotherapy setting reveal that psychedelic drugs may assist with treating depression, anxiety, alcohol addiction, and nicotine addiction. Although further research is needed, existing results suggest that psychedelics could be effective treatments for certain mental health conditions. A 2022 survey by YouGov found that 28% of Americans had used a psychedelic at some point in their life.
MDMA ("ecstasy") is sometimes said to also have weak psychedelic effects, but it acts and is classified mainly as an entactogen rather than as a hallucinogen. Certain related drugs like MDA and MMDA have greater psychedelic effects however. (1991). 9780963009609, Transform Press. ISBN 9780963009609
A June 2024 report by the RAND Corporation suggests psilocybin mushrooms may be the most prevalent psychedelic drug among adults in the United States. The RAND national survey indicated that 3.1% of U.S. adults reported using psilocybin in the past year. Roughly 12% of respondents acknowledged lifetime use of psilocybin, while a similar percentage reported having used LSD at some point in their lives. MDMA, also known as ecstasy, showed a lower prevalence of use at 7.6%. Notably, less than 1% of U.S. adults reported using any psychedelic drugs within the past month. A recent nationwide survey of 11,299 adults in Germany suggests that 5.0% of respondents reported lifetime psychedelic use (0.7% in the past six months). Approximately 3% of individuals used LSD, LSD analogues, psilocybin, or other substances at least once in their lifetime, and 0.5% used these substances within the past six months. The lifetime prevalence of medium-to-high dosing (3.9%) was higher than that of microdosing (2.7%). Usage patterns varied across sociodemographic groups such as sex, age, place of residence, income, and marital status.
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. 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.
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. The therapeutic team prepares the patient for the experience beforehand and helps them integrate insights from the drug experience afterwards. 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.
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. On the basis of favorable early results, ongoing research is examining proposed psychedelic therapies for conditions including major depressive disorder, and anxiety and depression linked to terminal illness. The United States Food and Drug Administration has granted breakthrough therapy status, which expedites the assessment of promising drug therapies for potential approval, to psilocybin therapy for treatment-resistant depression and major depressive disorder.
It has been proposed that psychedelics used for therapeutic purposes may act as active placebo "super ".
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.
| + Doses of major serotonergic psychedelics and MDMA (2025). 9783031121838 ISBN 9783031121838 | |||||||
| 25–50 mg | |||||||
| 125–200 mg | |||||||
| Notes: (1) All doses are for oral administration unless otherwise indicated. (2) For the psychedelics, doses are considered to be roughly equivalent in terms of peak or overall response. Footnotes: a = As LSD free base (100μg LSD base = 146μg LSD tartrate). b = As mescaline hydrochloride. c = As DMT fumarate given as constant infusions for >30minutes. d = As MDMA hydrochloride. | |||||||
In the case of dried psilocybin-containing mushrooms, microdoses are 0.1g to 0.3g and psychedelic doses are 1.0g to 3.5–5.0g. The preceding 1.0 to 5.0g range corresponds to psilocybin doses of about 10 to 50mg. Psilocybin-containing mushrooms vary in their psilocybin and psilocin content, but are typically around 1% of the dried weight of the mushrooms (in terms of total or combined psilocybin and psilocin content). Psilocybin and psilocin are similar in potency and dose but psilocin is about 1.4-fold more active, this being related to the difference in molecular weight between the two compounds.
Some psychedelics, such as 2C-B, 2C-E, and 4-HO-DiPT, have been said to have steep dose–response curves, meaning that the difference in dose between a light experience and an overwhelming disconnection from reality can be small.
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. 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. 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. 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.
Psychedelics include natural product tryptamines like psilocybin and DMT, the naturally occurring phenethylamine mescaline, and naturally occurring like ergine (lysergic acid amide; LSA), as well as synthetic analogues and derivatives like LSD and 2C-B. Many of these psychedelics cause remarkably similar effects, despite their different chemical structures. However, many users anecdotally report that the three major families have subjectively different qualities in the "feel" of the experience, which are difficult to describe. There can also be very substantial differences between the drugs; for instance, 5-MeO-DMT rarely produces the visual effects typical of other psychedelics. As additional examples, DiPT is said to primarily affect the hearing sense, 2C-T-17 and ASR-3001 (5-MeO-iPALT) are said to produce psychedelic effects on thinking or "head space" with few or no visuals, and N-methyltryptamine (NMT) has been said to be a primarily spatial psychedelic.
The visuals of psychedelics have been reproduced in video and image form using artificial intelligence.
Some rare individuals do not experience hallucinogenic effects with serotonergic psychedelics.
Some drugs, such as MDxx compounds like MDMA and MDA as well as α-alkyltryptamines like α-methyltryptamine (AMT), are entactogens and/or stimulants acting at monoamine transporters in addition to having varying degrees of psychedelic effects.
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. The term "psychedelic afterglow" was first formally coined in the 1960s. Albert Hofmann, the discoverer of LSD, said the following about the aftermath of his first full LSD experience in his 1980 book LSD: My Problem Child:
During a speech on his 100th birthday in 2006, Hofmann additionally said of LSD:
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. In some cases, individuals taking psychedelics have performed dangerous or fatal acts because they believed they possessed superhuman powers.
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. 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. 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. In any case, induction of psychosis has been associated with psychedelics in small percentages of individuals, and the rates appear to be higher in people with schizophrenia.
Using psychedelics poses certain risks of re-experiencing of the drug's effects, including flashbacks and hallucinogen persisting perception disorder (HPPD). These non-psychotic effects are poorly studied, but the permanent symptoms (also called "endless trip") are considered to be rare.
Serotonergic psychedelics are not only of the serotonin 5-HT2A receptor but also of the serotonin 5-HT2B receptor and other serotonin receptors. A potential risk of frequent repeated use of serotonergic psychedelics is cardiac fibrosis and valvulopathy caused by serotonin 5-HT2B receptor activation. However, single high doses or widely spaced doses (e.g., months) are widely thought to be safe and concerns about cardiac toxicity apply more to chronic psychedelic microdosing or very frequent use (e.g., weekly). Selective serotonin 5-HT2A receptor agonists that do not activate the serotonin 5-HT2B receptor or other serotonin receptors, such as 25CN-NBOH, DMBMPP, and LPH-5, have been developed and are being studied. Selective serotonin 5-HT2A receptor agonists are expected to avoid the cardiac risks of serotonin 5-HT2B receptor activation.
The serotonin 5-HT1A receptor partial agonist buspirone has been found to markedly reduce the hallucinogenic effects of psilocybin in humans. Conversely, the serotonin 5-HT1A receptor antagonist pindolol has been found to potentiate the hallucinogenic effects of DMT by 2- to 3-fold in humans. Serotonin 5-HT1A receptor agonism may modify and self-inhibit the effects of psychedelics that possess this property. A particularly notable example is 5-methoxytryptamine derivatives such as 5-MeO-DMT, which are more potent serotonin 5-HT1A receptor agonists than other psychedelics and have qualitatively unique and differing hallucinogenic effects.
, for example diazepam, alprazolam, clonazepam, and lorazepam, as well as alcohol, which act as GABAA receptor positive allosteric modulators, have been limitedly studied in combination with psychedelics and are not currently known to directly interact with them. However, these GABAergic drugs produce effects such as anxiolytic, sedation, and amnesia, and in relation to this, may diminish or otherwise oppose the effects of psychedelics. As a result of this, benzodiazepines and alcohol are often used by recreational users as "trip killers" to manage difficult hallucinogenic experiences with psychedelics, for instance experiences with prominent anxiety. The drug safety of this strategy is not entirely clear and might have risks. However, benzodiazepines have been used clinically to manage the adverse psychological effects of psychedelics, for instance in clinical studies and in the emergency department. (2025). 9781441903372, Springer New York. ISBN 9781441903372 A clinical trial of psilocybin and midazolam coadministration found that midazolam clouded the effects of psilocybin and impaired memory of the experience. Benzodiazepines might interfere with the therapeutic effects of psychedelics, such as sustained antidepressant effects.
Some serotonergic psychedelics, for instance dimethyltryptamine (DMT) and 5-MeO-DMT, are highly susceptible substrates for monoamine oxidase (MAO), specifically MAO-A, and hence can be greatly potentiated by monoamine oxidase inhibitors (MAOIs). An example of this is ayahuasca, in which plants containing both DMT and acting as MAOIs such as harmine and harmaline are combined. This allows DMT to become orally active and to have a much longer duration of action than usual. The 2C psychedelics, such as 2C-B, 2C-I, and 2C-E, are also substrates of both MAO-A and MAO-B, and may likewise be greatly potentiated by MAOIs. Examples of MAOIs that may potentiate psychedelics behaving as MAO-A and/or MAO-B substrates include phenelzine, tranylcypromine, isocarboxazid, moclobemide, and selegiline. Combination of MAO-substrate psychedelics with MAOIs can result in overdose and serious toxicity, including death. Other psychedelics, such as LSD, are not substrates of MAO and are not potentiated by MAOIs. The extent to which psilocin (and by extension psilocybin) is metabolized by MAO, specifically MAO-A, is not fully clear, but has ranged from 4% to 33% in different studies based on metabolite excretion. However, circulating levels of the deaminated metabolite of psilocin are far higher than those of free unmetabolized psilocin with psilocybin administration. An early clinical study of psilocybin in combination with short-term tranylcypromine pretreatment found that tranylcypromine marginally potentiated the human body effects of psilocybin, including pressor effects and mydriasis, but overall did not significantly modify the psychoactive and hallucinogenic effects of the psilocybin, although some of its emotional effects were said to be reduced and some of its perceptual effects were said to be amplified.
Some psychedelics are substrates of cytochrome P450 (CYP450) , for instance LSD being a substrate of CYP2D6 as well as of several other CYP450 enzymes. As such, CYP450 enzyme inhibitor may increase exposure to CYP450-substrate psychedelics such as LSD and thereby potentiate their effects as well as risks. A clinical study found that administration of LSD to people taking paroxetine, a selective serotonin reuptake inhibitor (SSRI) and strong CYP2D6 inhibitor, increased LSD exposure by about 1.5-fold. The combination was well-tolerated and did not modify the pleasant subjective effects or physiological effects of LSD, whereas negative effects of LSD, including "bad drug effect", anxiety, and nausea, were reduced. Similarly to the findings with a strong CYP2D6 inhibitor, a pharmacogenomic clinical study with LSD found that LSD levels were 75% higher in people with non-functional CYP2D6 () compared to those with functional CYP2D6.
Serotonin syndrome can be caused by combining psychedelics with other serotonergic drugs, including certain , , (e.g. MDMA), serotonin 5-HT1 agonists (e.g. ), or supplements, and others.
A high rate of has been reported when people on lithium have taken serotonergic psychedelics. In an analysis of online reports, 47% of 62accounts reported seizures when a psychedelic was taken while on lithium. The mechanism underlying this apparent interaction is unclear.
In animals, potency for stimulus generalization to the psychedelic DOM in drug discrimination tests is strongly correlated with serotonin 5-HT2A receptor affinity. Non-selective serotonin 5-HT2A receptor antagonists, like ketanserin and pirenperone, and selective serotonin 5-HT2A receptor antagonists, like volinanserin (MDL-100907), abolish the stimulus generalization of psychedelics in drug discrimination tests. Conversely, serotonin 5-HT2B and 5-HT2C receptor antagonists are ineffective. The potencies of serotonin 5-HT2 receptor antagonists in blocking psychedelic substitution are strongly correlated with their serotonin 5-HT2A receptor affinities. Highly selective serotonin 5-HT2A receptor agonists have recently been developed and show stimulus generalization to psychedelics, whereas selective serotonin 5-HT2C receptor agonists do not do so. The head-twitch response (HTR) is induced by serotonergic psychedelics and is a behavioral proxy of psychedelic-like effects in animals. (2025). 9781461441205, Springer New York. ISBN 9781461441205 The HTR is invariably induced by serotonergic psychedelics, is blocked by selective serotonin 5-HT2A receptor antagonists, and is abolished in serotonin 5-HT2A receptor knockout mice. In addition, there is a strong correlation between hallucinogenic potency in humans and potency in the HTR assay. Moreover, the HTR paradigm is one of the only animal tests that can distinguish between hallucinogenic serotonin 5-HT2A receptor agonists and non-hallucinogenic serotonin 5-HT2A receptor agonists, such as lisuride. In accordance with the preceding animal and human findings, it has been said that the evidence that the serotonin 5-HT2A receptor mediates the hallucinogenic effects of serotonergic psychedelics is overwhelming.
The serotonin 5-HT2A receptor activates several downstream cell signaling. These include the Gq protein, β-arrestin2, and other pathways. Activation of both the Gq and β-arrestin2 pathways have been implicated in mediating the hallucinogenic effects of serotonergic psychedelics. However, subsequently, activation of the Gq pathway and not β-arrestin2 has been implicated. Interestingly, Gq signaling appeared to mediate hallucinogenic-like effects, whereas β-arrestin2 mediated receptor downregulation and tachyphylaxis. The lack of psychedelic effects with non-hallucinogenic serotonin 5-HT2A receptor agonists may be due to partial agonism of the serotonin 5-HT2A receptor with efficacy insufficient to produce psychedelic effects or may be due to biased agonism of the serotonin 5-HT2A receptor. There appears to be a threshold level of Gq activation (in terms of intrinsic activity, with >70%) required for production of hallucinogenic effects. and above this threshold are psychedelic 5-HT2A receptor agonists, whereas partial agonists below this threshold, such as lisuride, 2-bromo-LSD, 6-fluoro-DET, 6-MeO-DMT, and Ariadne, are non-hallucinogenic 5-HT2A receptor agonists. In addition, biased agonists that activate β-arrestin2 signaling but not Gq signaling, such as ITI-1549, IHCH-7086, and 25N-N1-Nap, are non-hallucinogenic serotonin 5-HT2A receptor agonists.
The hallucinogenic effects of serotonergic psychedelics may be critically mediated by serotonin 5-HT2A receptor activation in the medial prefrontal cortex (mPFC). Layer V pyramidal cell in this area are especially discussed. (2025). 9783662558782 ISBN 9783662558782 Activation of serotonin 5-HT2A receptors in the mPFC results in marked excitatory and inhibitory effects as well as increased release of glutamate and GABA. Direct injection of serotonin 5-HT2A receptor agonists into the mPFC produces the HTR. Drugs that suppress glutamatergic activity in the mPFC, including AMPA receptor antagonists, metabotropic glutamate mGlu2/3 receptor agonists, μ-opioid receptor agonists, and adenosine A1 receptor agonists, block or suppress many of the neurochemical and behavioral effects of serotonergic psychedelics, including the HTR. Metabotropic glutamate mGlu2 receptors are primarily expressed as presynaptic and have inhibitory effects on glutamate release. Serotonergic psychedelics have been found to produce frontal cortex hyperactivity in humans in PET and single-photon emission computed tomography (SPECT) imaging studies. The PFC projects to many other cortical and subcortical brain areas, such as the locus coeruleus, nucleus accumbens, and amygdala, among others, and activation of the PFC by serotonergic psychedelics may thereby indirectly modulate these areas. In addition to the PFC, there is moderate to high expression of serotonin 5-HT2A receptors in the primary visual cortex (V1), as well as expression of the serotonin 5-HT2A receptor in other visual areas, and activation of these receptors may contribute to or mediate the visual effects of serotonergic psychedelics. Serotonergic psychedelics also directly or indirectly modulate a variety of other brain areas, like the claustrum, and this may be involved in their effects as well.
Serotonin, as well as drugs that increase serotonin levels, like the serotonin precursor 5-hydroxytryptophan (5-HTP), serotonin reuptake inhibitors, and serotonin releasing agents, are non-hallucinogenic in humans despite increasing activation of serotonin 5-HT2A receptors. Serotonin is a hydrophilic molecule which cannot easily cross biological membranes without active transport, and the serotonin 5-HT2A receptor is usually expressed as a cell surface receptor that is readily accessible to extracellular serotonin. The HTR, a behavioral proxy of psychedelic-like effects, appears to be mediated by activation of gene expression serotonin 5-HT2A receptors in a population of mPFC neurons that do not also express the serotonin transporter (SERT) and hence cannot be activated by serotonin. In contrast to serotonin, serotonergic psychedelics are more lipophilic than serotonin and are able to readily enter these neurons and activate the serotonin 5-HT2A receptors within them. Artificial expression of the SERT in this population of neurons in animals resulted in a serotonin releasing agent that doesn't normally produce the HTR being able to do so. Although serotonin itself is non-hallucinogenic, at very high concentrations achieved pharmacologically (e.g., injected into the brain or with massive doses of 5-HTP) it can produce psychedelic-like effects in animals by being drug metabolism by indolethylamine N-methyltransferase (INMT) into more lipophilic N-methyl group tryptamines like N-methylserotonin and bufotenin ( N, N-dimethylserotonin). (2025). 9783319704722, Springer International Publishing. ISBN 9783319704722 (2025). 9783662558782 ISBN 9783662558782
In addition to their hallucinogenic effects, serotonergic psychedelics may also produce a variety of other effects, including (i.e., neuroplasticity-enhancing), antidepressant, anxiolytic, empathy-enhancing or prosocial effects, anti-obsessional, (2025). 9783031121838 ISBN 9783031121838 anti-addictive, anti-inflammatory and effects, (2025). 9783031121838 ISBN 9783031121838 analgesic effects, and/or antimigraine effects. (2025). 9783031121838 ISBN 9783031121838 While psychedelics themselves are also being clinically evaluated for these potential therapeutic benefits, non-hallucinogenic serotonin 5-HT2A receptor agonists, which are often analogues of serotonergic psychedelics, have been developed and are being studied for potential use in medicine in an attempt to provide some such benefits without hallucinogenic effects.
Although the hallucinogenic effects of serotonergic psychedelics are thought to be mediated by serotonin 5-HT2A receptor activation, interactions with other receptors, such as the serotonin 5-HT1A, 5-HT1B, 5-HT2B, and 5-HT2C receptors among many others, may additionally contribute to and modulate their effects. Certain psychedelics, including LSD and psilocin, have been reported to act as highly potent positive allosteric modulators of the tropomyosin receptor kinase B (TrkB), one of the signaling receptors of brain-derived neurotrophic factor (BDNF). However, subsequent studies failed to reproduce these findings and instead found no interaction of LSD or psilocin with TrkB. Moreover, the psychoplastogenic effects of serotonergic psychedelics, including dendrite, dendritic spine, and synaptogenesis, appear to be mediated by activation of serotonin 5-HT2A receptors, whereas psychedelics do not generally stimulate neurogenesis.
The factors responsible for differences in psychoactive and hallucinogenic effects between different psychedelics are incompletely understood but may include (1) differences in selectivity for the serotonin 5-HT2A receptor or off-target activity; (2) differences in functional selectivity for different serotonin 5-HT2A receptor downstream signaling pathways; and (3) differences in patterns or balances of distribution to different brain areas.
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The first known published description of a hallucinogenic peyote experience was by American neurologist Silas Weir Mitchell in December 1896. After reading Mitchell's article, others, including psychologist and sexologist Havelock Ellis, American psychologist William James, and German pharmacologist, chemist, and Lewin rival Arthur Heffter, among others, tried peyote and described their experiences. Heffter isolated and ingested mescaline from peyote, experiencing psychedelic effects with the pure compound, in 1897, and published his findings in 1898.
Austrian people chemist Ernst Späth synthesized mescaline for the first time in 1919. The German pharmaceutical company Merck Group then began distributing pharmaceutical mescaline in 1920. The German psychiatrist Kurt Beringer, a student of Lewin and an acquaintance of Hermann Hesse and Carl Jung, became the father of psychedelic psychiatry and conducted experiments with mescaline in more than 60people starting in 1921. He published his monograph on the subject, Der Meskalinrausch ( Mescaline Intoxication), in 1927. German–American people psychologist Heinrich Klüver published his monograph, Mescal: The Divine Plant and Its Psychological Effects, in English in 1928. He is said to have been the first to attempt to provide a phenomenological description of the psychedelic experience.
Ergine (lysergic acid amide; LSA) and isoergine (isolysergic acid amide; iso-LSA) were first identified from hydrolysis of in 1932 and 1936, respectively. In 1938, Swiss people chemist Albert Hofmann, working at Sandoz Laboratories, synthesized lysergic acid diethylamide (LSD), a synthetic derivative of ergine, while developing new oxytocic derived from ergot. LSD was not further investigated and was placed in storage for 5years. In 1943 however, Hofmann worked with LSD again and accidentally discovered its hallucinogenic effects when minute amounts of the potent psychedelic absorbed through his skin. His subsequent self-experiment with LSD three days later on April 19 is the psychedelic holiday Bicycle Day. Hofmann and his colleague, psychiatrist Werner Stoll, first described LSD in 1943 and first described its psychedelic effects in 1947. LSD began being distributed by Sandoz Laboratories for research purposes under the brand name Delysid in 1949.
Schultes described the indigenous and shamanic use of dimethyltryptamine (DMT)-containing psychedelic plants in 1954 and also described the use of hallucinogenic morning glories in the 1950s. The psychedelic effects of synthesized DMT were described by Hungarian people chemist and psychiatrist Stephen Szára in 1956. Osmond described the hallucinogenic and other effects of morning glory seeds in clinical studies in 1955. Hofmann identified and described ergine and isoergine as the active constituents of morning glory seeds in 1960. Their hallucinogenic effects were first described by Hofmann in 1963.
In 1952, couple and amateur R. Gordon Wasson and Valentina Wasson learned of the ritual use of hallucinogenic mushrooms in the 16th century in Mexico from the published work of Schultes. They made several trips to Mexico in search of the mushrooms. In mid-1955, the Wassons participated in a mushroom ceremony with Mazatec people curandera Maria Sabina in Huautla de Jiménez, Oaxaca, Mexico. Gordon Wasson published his experience in an article for Life Magazine magazine titled "Seeking the Magic Mushroom" in 1957, while Valentina Wasson published her experience as "I Ate the Sacred Mushroom" in This Week magazine the same year. Later in 1957, a second expedition was made by the Wassons to Mexico with French people mycologist Roger Heim. Heim identified several of the mushrooms as belonging to the genus Psilocybe. They collected samples of the mushrooms and Heim sent a sample to Hofmann. Hofmann identified psilocybin as the active constituent in 1958 and developed a chemical synthesis for it. Sandoz Pharmaceuticals began distributing tablets of psilocybin under the brand name Indocybin in 1960.
French scientists Césaire Phisalix and Gabriel Bertrand isolated bufotenin from Bufo toads in 1893 and named it.
Psychedelics became widely recreationally used by the public, for instance by the hippies, during the counterculture of the 1960s. Harvard psychologists Timothy Leary and Richard Alpert began studying LSD and psilocybin in the early 1960s and ended up being fired from the university in 1963. Sandoz Laboratories ceased distribution of Delysid in 1965. Psychedelics became controlled substances in the United States and internationally in the 1960s and 1970s. By the end of the 1960s, psychedelic clinical research throughout the world had largely ceased.
Besides public research, it was eventually learned that the United States government had also conducted research into psychedelics, as possible mind-control and truth-serum drugs, in the 1940s through the 1970s, for instance Project MKUltra by the Central Intelligence Agency (CIA) and the Edgewood Arsenal research by the U.S. Army.
Alexander Shulgin, an American chemist working at Dow Chemical Company, tried mescaline by 1960. This experience has been described as "the most consequential mescaline trip of the sixties", as it caused Shulgin to redirect his focus and life's work to psychedelic chemistry. Starting in the 1960s, Shulgin synthesized and gradually described hundreds of novel synthetic psychedelics as well as entactogens in scientific publications and published books such as PiHKAL (1991) and TiHKAL (1997). Notable major examples of these drugs have included the DOx psychedelic DOM, the 2C psychedelic 2C-B, and the MDxx entactogen MDMA, among others. However, MDMA was not an original creation of Shulgin's but had previously been first synthesized in 1912 and had surfaced as a recreational drug related to MDA by the mid- to late-1960s. Instead, Shulgin had merely served to help popularize and spread awareness about MDMA and its unique effects.
MDMA became outlawed in the mid-1980s. In response to this, the Multidisciplinary Association for Psychedelic Studies (MAPS) was founded by Rick Doblin in 1986 and began efforts to develop MDMA and other psychedelics as medicines. American chemist David E. Nichols has developed numerous novel psychedelics and entactogens from the 1970s to present. Swiss people chemist Daniel Trachsel, sometimes referred to as the "German Shulgin", has also developed and published numerous novel psychedelics as well as entactogens since the 1990s.
NBOMe psychedelics such as 25I-NBOMe, derived from structural modification of 2C psychedelics, were first described by Ralf Heim and colleagues by 2000. The NBOMe drugs were subsequently encountered as novel recreational drugs by 2010, and by 2012 had eclipsed other psychedelics like LSD and psilocybin-containing mushrooms in popularity, at least for a time.
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. iia700700.us.archive.org 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.
In 2004, David E. Nichols wrote the following about the nomenclature used for psychedelic drugs:
Robin Carhart-Harris and Guy Goodwin write that the term psychedelic is preferable to hallucinogen for describing classical psychedelics because of the term hallucinogens "arguably misleading emphasis on these compounds' hallucinogenic properties."
While the term psychedelic is most commonly used to refer only to serotonergic hallucinogens, it is sometimes used for a much broader range of drugs, including , , and atypical hallucinogens/psychoactives such as Amanita muscaria, Cannabis sativa, Nymphaea nouchali and Salvia divinorum. Thus, the term serotonergic psychedelic is sometimes used for the narrower class. It is important to check the definition of a given source. This article uses the more common, narrower definition of psychedelic.
In July 2022, though, under the United States Food and Drug Administration, the drug psilocybin was on track to be approved of as a treatment for depression, and MDMA as a treatment for post-traumatic stress disorder.
U.S. states such as Oregon and Colorado have also instituted decriminalization and legalization measures for accessing psychedelics and states like New Hampshire are attempting to do the same. 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 access to the substances in the United States (as has happened with alcohol and cannabis).
It has long been known that psychedelics promote neurite growth and neuroplasticity and are potent . There is evidence that psychedelics induce molecular and cellular adaptations related to neuroplasticity and that these could potentially underlie therapeutic benefits. Psychedelics have also been shown to have potent anti-inflammatory activity and therapeutic effects in animal models of inflammatory diseases including asthma, cardiovascular disease, and diabetes. They might also be useful for the treatment of neuroinflammation as well as post-COVID-19 syndrome (long COVID).
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/ref> The compound was first isolated to purity by Austrian chemist Hans Handovsky in 1920. Clinical studies assessed the effects of bufotenin and were published starting in 1956. However, the findings of these studies were conflicting, and bufotenin developed a long-standing reputation of being inactive and toxic. American ethnobotanist Jonathan Ott and colleagues subsequently showed in 2001 that bufotenin is in fact a psychedelic and does not necessarily produce major adverse effects, although marked nausea and vomiting are prominent. The related psychedelic 5-MeO-DMT was first synthesized by Japanese people chemists Toshio Hoshino and Kenya Shimodaira in 1935. It was later isolated from Dictyoloma incanescens in 1959. Subsequently, 5-MeO-DMT was isolated from numerous other plants and fungi. The compound was isolated from the skin of toads, specifically the Colorado River toad ( Incilius alvarius, formerly Bufo alvarius), by Italian people chemist and pharmacologist Vittorio Erspamer in 1967. A 1984 pamphlet by Albert Most (real name Ken Nelson), titled , described how to obtain and use Colorado River toad secretions as a psychedelic drug, and this started its recreational use.
Mid-20th-century research, popularization, and prohibition
Extensive clinical research on almost exclusively LSD, mescaline, and psilocybin was conducted in the 1950s and 1960s. However, the amount of research done on psilocybin was nowhere near that of LSD. Psychedelics like LSD started to become more visible in the mainstream sphere in the 1950s. English people writer Aldous Huxley tried mescaline, which he had obtained from English psychiatrist Humphry Osmond, in 1953, and described its effects in his 1954 book The Doors of Perception. British people politician Christopher Mayhew tried mescaline in 1955 and this was reported on in the media. Osmond, in correspondence with Huxley, coined the term "psychedelic", meaning "mind-manifesting", in 1956.
Creation of other synthetic psychedelics
The psychedelic effects of 3,4-methylenedioxyamphetamine (MDA), a synthetic analogue of mescaline that had been derived from amphetamine in 1910, were discovered by American people chemist and pharmacologist Gordon Alles in 1930, but weren't subsequently described by him until 1959. 3,4,5-Trimethoxyamphetamine (TMA), another synthetic mescaline analogue, was first described in 1947 and its psychedelic effects were described in 1955. 2,4,5-Trimethoxyphenethylamine (2C-O), a synthetic positional isomer of mescaline, was synthesized and claimed to be psychedelic similarly to mescaline in 1931, but later trials found it to be inactive. Various synthetic tryptamine psychedelics, such as diethyltryptamine (DET), 4-PO-DET (CEY-19), and 4-HO-DET (CZ-74), were developed in the late 1950s. In addition, the synthetic α-alkyltryptamine analogues α-methyltryptamine (AMT; Indopan) and α-ethyltryptamine (AET; Monase), which are psychedelics and/or , were marketed and clinically used at non-hallucinogenic doses as in the early 1960s, but were quickly withdrawn drug due to physical toxicity. Numerous synthetic psychedelic tryptamines were known by the mid-1970s.
Psychedelics, serotonin, and their actions
Serotonin, also known as 5-hydroxytryptamine (5-HT) and originally called enteramine, was discovered by Vittorio Erspamer in the 1930s and its structural identity was fully characterized in the late 1940s and early 1950s. Serotonin was discovered in the brain by Betty Twarog and Irvine Page in 1953. It was quickly noticed that LSD contains the serotonin-like tryptamine scaffold within its chemical structure. Shortly thereafter, it was found that LSD showed serotonin-like effects and could antagonize serotonin in certain bioassay. Studies in the 1960s and 1970s showed that various serotonin antagonists could block the behavioral effects of psychedelics in animals. The serotonin receptors, including the serotonin 5-HT2 receptors, were elucidated by the late 1970s. Mediation of the hallucinogenic effects of psychedelics by serotonin 5-HT2 receptor agonism was proposed by Richard Glennon and other researchers by the early 1980s. (2025). 9783662558782, Springer Berlin Heidelberg. ISBN 9783662558782 The human serotonin 5-HT2A receptor was first cloning in 1990. The hallucinogenic effects of psilocybin in humans were shown to be blocked by the selective serotonin 5-HT2A receptor antagonist ketanserin by Franz Vollenweider and colleagues in 1998, solidifying theoretical notions that agonism of the serotonin 5-HT2A receptor mediates the hallucinogenic effects of serotonergic psychedelics.
Psychedelic renaissance
Since the prohibition of the 1960s and 1970s, clinical research into psychedelics started to resume by the 1990s, for instance the studies of DMT by Rick Strassman, and they have once again started to be developed as pharmaceutical drugs for potential medical use. A so-called "psychedelic renaissance", in which interest in psychedelics has resurged, began in the late 2010s and early 2020s. Michael Pollan's 2018 book How to Change Your Mind, which was also adapted into a Netflix series in 2022, was especially impactful in terms of increasing mainstream awareness and interest in psychedelics. More than 100clinical trials of four major psychedelics, including psilocybin, LSD, ayahuasca, and MDMA, were identified as being underway in 2024.
Society and culture
Etymology and nomenclature
The term was coined by the psychiatrist Humphrey Osmond during written correspondence with author Aldous Huxley (written in a rhyme: "To fathom Hell or soar angelic/Just take a pinch of psychedelic.") and presented to the New York Academy of Sciences by Osmond in 1957. It is irregularly Oxford English Dictionary, 3rd edition, September 2007, s.v., Etymology derived from the Greek language words ψυχή ( psychḗ, meaning 'mind, soul') and δηλείν ( dēleín, meaning 'to manifest'), with the intended meaning "mind manifesting" or alternatively "soul manifesting", and the implication that psychedelics can reveal unused potentials of the human mind.A. Weil, W. Rosen. (1993), From Chocolate To Morphine: Everything You Need To Know About Mind-Altering Drugs. New York, Houghton Mifflin Company. p. 93 The term was loathed by American ethnobotanist Richard Schultes but championed by American psychologist Timothy Leary.W. Davis (1996), "One River: Explorations and Discoveries in the Amazon Rain Forest". New York, Simon and Schuster, Inc. p. 120.
Surrounding culture
Psychedelic culture includes manifestations such as psychedelic music, (2000). 9780252069154, University of Illinois Press. ISBN 9780252069154 psychedelic art, psychedelic literature, psychedelic film, and psychedelic Music festival.St John, Graham. "Neotrance and the Psychedelic Festival." Dancecult: Journal of Electronic Dance Music Culture, 1(1) (2009). Examples of psychedelic music are found in the work of 1960s rock bands like the Grateful Dead, Jefferson Airplane, The 13th Floor Elevators, and Syd Barrett-era Pink Floyd. Many psychedelic bands and elements of the psychedelic subculture originated in San Francisco during the mid to late 1960s.
Legal status
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. 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 prohibited substances if sold for human consumption.
Research
Therapeutic effects
Psychedelic substances which may have therapeutic uses include psilocybin, LSD, and mescaline. During the 1950s and 1960s, lack of informed consent in some scientific trials on psychedelics led to significant, long-lasting harm to some participants. 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. 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.
See also
Further reading
(2025). 9783662558782, Springer. ISBN 9783662558782
(2025). 9780300257502, Yale University Press. ISBN 9780300257502
(2025). 9780198843122, Oxford University Press. ISBN 9780198843122
External links
target="_blank" rel="nofollow"> Psychedelic drugs - Massviews Analysis - Wikipedia
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