The first written description of a hallucinogenic experience in the Western world appeared in 1511, yet the substance itself had been used by indigenous peoples for thousands of years before that. In 1496, Western explorers like Christopher Columbus observed the use of hallucinogenic snuffs by indigenous South American people, but it was not until 1519 that Spanish explorers documented the use of psilocybin-containing mushrooms, known as teonanacatl, in Mexico following Hernán Cortés's arrival. The earliest known written account of a psychedelic experience was published by Ramon Pane in 1511, describing the effects of cohoba, a snuff made from the seeds of the Anadenanthera tree. Despite these early observations, the scientific community remained largely unaware of these substances until the late 19th century. The first known published description of a hallucinogenic peyote experience was by American neurologist Silas Weir Mitchell in December 1896, which sparked interest among other scientists and writers. German pharmacologist Louis Lewin obtained mescal buttons from Parke-Davis during a trip to the United States in 1887 and began studying them, leading to the isolation of mescaline by German pharmacologist Arthur Heffter in 1897. The first known published description of a hallucinogenic peyote experience was by American neurologist Silas Weir Mitchell in December 1896, which sparked interest among other scientists and writers. German pharmacologist Louis Lewin obtained mescal buttons from Parke-Davis during a trip to the United States in 1887 and began studying them, leading to the isolation of mescaline by German pharmacologist Arthur Heffter in 1897. The first known published description of a hallucinogenic peyote experience was by American neurologist Silas Weir Mitchell in December 1896, which sparked interest among other scientists and writers. German pharmacologist Louis Lewin obtained mescal buttons from Parke-Davis during a trip to the United States in 1887 and began studying them, leading to the isolation of mescaline by German pharmacologist Arthur Heffter in 1897.
The Accidental Discovery
On the 16th of April 1943, Swiss chemist Albert Hofmann accidentally discovered the hallucinogenic effects of lysergic acid diethylamide, or LSD, when minute amounts of the potent psychedelic absorbed through his skin. Three days later, on the 19th of April 1943, Hofmann conducted a self-experiment with LSD, an event now celebrated as Bicycle Day. The psychedelic effects of synthesized DMT were described by Hungarian chemist and psychiatrist Stephen Szára in 1956, while the psychedelic effects of morning glory seeds were first described by Hofmann in 1963. In 1952, couple and amateur ethnomycologists 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, and in mid-1955, the Wassons participated in a mushroom ceremony with Mazatec curandera Maria Sabina in Huautla de Jiménez, Oaxaca, Mexico. Gordon Wasson published his experience in an article for Life 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 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. 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 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 chemist and pharmacologist Vittorio Erspamer in 1967. A 1984 pamphlet by Albert Most (real name Ken Nelson), titled Bufo Alvarius: the Psychedelic Toad of the Sonoran Desert, described how to obtain and use Colorado River toad secretions as a psychedelic drug, and this started its recreational use.
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. The term psychedelic 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 derived from the Greek words ψυχή (psychē, 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. The term was loathed by American ethnobotanist Richard Schultes but championed by American psychologist Timothy Leary. Aldous Huxley had suggested his own coinage phanerothyme (Greek phaneroein-). English 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 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. 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.
The Chemical Architects
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 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. The synthetic mescaline analogue 2,6-dibromomescaline was described by Arthur Heffter in 1901, although he is not known to have tested it and its psychedelic effects weren't reported until much later. 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 chemist and pharmacologist Gordon Alles in 1930, but weren't subsequently published 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 entactogens, were marketed and clinically used at non-hallucinogenic doses as antidepressants in the early 1960s, but were quickly withdrawn due to physical toxicity. Numerous synthetic psychedelic tryptamines were known by the mid-1970s.
The Modern 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 100 clinical trials of four major psychedelics, including psilocybin, LSD, ayahuasca, and MDMA, were identified as being underway in 2024. 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 super placebos. As of 2021, psychedelic drugs are controlled substances in most countries and psychedelic therapy is not legally available outside clinical trials, with some exceptions. 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. A 2022 survey by YouGov found that 28% of Americans had used a psychedelic at some point in their life. A 2013 survey found that 13.4% of American adults had used a psychedelic at some point in their lives. A June 2024 report by the RAND Corporation indicated that psilocybin mushrooms are currently the most widely used psychedelic drug among U.S. adults. According to the RAND national survey, 3.1% of adults reported psilocybin use in the past year, while about 12% reported lifetime use. Similar lifetime prevalence was reported for LSD, whereas MDMA (ecstasy) showed lower lifetime use at 7.6%. Fewer than 1% of adults reported using any psychedelic in the past month. A nationwide survey of 11,299 adults in Germany, published in 2025, found that 5.0% of respondents reported lifetime psychedelic use, with 0.7% reporting use within the past six months. Approximately 3% of respondents had used LSD, LSD analogues, psilocybin, or related substances at least once in their lifetime, and 0.5% had done so within the past six months. Lifetime prevalence of medium-to-high dosing (3.9%) was higher than microdosing (2.7%). Usage patterns varied by sociodemographic characteristics, including sex, age, residence, income, and marital status.