Imagery found on cave paintings and rock art of modern-day Spain and Algeria suggests that human usage of psilocybin mushrooms predates recorded history. In Mesoamerica, the mushrooms had long been consumed in spiritual and divinatory ceremonies before Spanish chroniclers first documented their use in the sixteenth century. In 1958, the Swiss chemist Albert Hofmann isolated psilocybin and psilocin from the mushroom Psilocybe mexicana. Hofmann's employer Sandoz marketed and sold pure psilocybin to physicians and clinicians worldwide for use in psychedelic therapy. Although the increasingly restrictive drug laws of the 1960s and the 1970s curbed scientific research into the effects of psilocybin and other hallucinogens, its popularity as an entheogen (spirituality-enhancing agent) grew in the next decade, owing largely to the increased availability of information on how to cultivate psilocybin mushrooms.
The intensity and duration of the effects of psilocybin are variable, depending on species or cultivar of mushrooms, dosage, individual physiology, and set and setting, as was shown in experiments led by Timothy Leary at Harvard University in the early 1960s. Once ingested, psilocybin is rapidly metabolized to psilocin, which then acts on serotonin receptors in the brain. The mind-altering effects of psilocybin typically last from two to six hours, although to individuals under the influence of psilocybin, the effects may seem to last much longer, since the drug can distort the perception of time. Possession of psilocybin-containing mushrooms has been outlawed in most countries, and psilocybin has been classified as a Schedule I controlled substance under the 1971 United Nations Convention on Psychotropic Substances.
American psychologist and counterculture figure Timothy Leary conducted early experiments into the effects of psychedelic drugs, including psilocybin (1989 photo)
The effects of psilocybin are highly variable and depend on the mindset and environment in which the user has the experience, factors commonly referred to as set and setting. In the early 1960s, Timothy Leary and colleagues at Harvard University investigated the role of set and setting on the effects of psilocybin. They administered the drug to 175 volunteers from various backgrounds in an environment intended to be similar to a comfortable living room. Ninety-eight of the subjects were given questionnaires to assess their experiences and the contribution of background and situational factors. Individuals who had experience with psilocybin prior to the study reported more pleasant experiences than those for whom the drug was novel. Group size, dosage, preparation, and expectancy were important determinants of the drug response. In general, those in groups of more than eight felt that the groups were less supportive, and their experiences less pleasant. Conversely, smaller groups (fewer than six) were seen as more supportive and reported more positive reactions to the drug in those groups. Leary and colleagues proposed that psilocybin heightens suggestibility, making an individual more receptive to interpersonal interactions and environmental stimuli. These findings were affirmed in a later review by Jos ten Berge (1999), who concluded that dosage, set, and setting were fundamental factors in determining the outcome of experiments that tested the effects of psychedelic drugs on artists' creativity.
After ingesting psilocybin, a wide range of subjective effects may be experienced: feelings of disorientation, lethargy, giddiness, euphoria, joy, and depression. In one study, 31% of volunteers given a high dose reported feelings of significant fear and 17% experienced transient paranoia. In studies at Johns Hopkins among those given a moderate dose (but still enough to "give a high probability of a profound and beneficial experience"), negative experiences were rare, whereas 1/3 of those given the high dose experienced anxiety or paranoia. Low doses can induce hallucinatory effects. Closed-eye hallucinations may occur, where the affected individual sees multicolored geometric shapes and vivid imaginative sequences. Some individuals report synesthesia, such as tactile sensations when viewing colors.: 175 At higher doses, psilocybin can lead to "intensification of affective responses, enhanced ability for introspection, regression to primitive and childlike thinking, and activation of vivid memory traces with pronounced emotional undertones". Open-eye visual hallucinations are common, and may be very detailed although rarely confused with reality.
A 2011 prospective study by Roland R. Griffiths and colleagues suggests that a single high dosage of psilocybin can cause long-term changes in the personality of its users. About half of the study participants—described as healthy, "spiritually active", and many possessing postgraduate degrees—showed an increase in the personality dimension of openness (assessed using the Revised NEO Personality Inventory), and this positive effect was apparent more than a year after the psilocybin session. According to the study authors, the finding is significant because "no study has prospectively demonstrated personality change in healthy adults after an experimentally manipulated discrete event". A further study by Griffiths in 2017 found that doses of 20 to 30 mg/70 kg psilocybin inducing mystical-type experiences brought more lasting changes to traits including altruism, gratitude, forgiveness and feeling close to others when they were combined with a regular meditation practice and an extensive spiritual practice support program. Although other researchers have described instances of psychedelic drug usage leading to new psychological understandings and personal insights, it is not known whether these experimental results can be generalized to larger populations.
Common responses include pupil dilation (93%); changes in heart rate (100%), including increases (56%), decreases (13%), and variable responses (31%); changes in blood pressure (84%), including hypotension (34%), hypertension (28%), and general instability (22%); changes in stretch reflex (86%), including increases (80%) and decreases (6%); nausea (44%); tremor (25%); and dysmetria (16%) (inability to properly direct or limit motions).[b] The temporary increases in blood pressure caused by the drug can be a risk factor for users with pre-existing hypertension. These qualitative somatic effects caused by psilocybin have been corroborated by several early clinical studies. A 2005 magazine survey of clubgoers in the UK found that nausea or vomiting was experienced by over a quarter of those who had used psilocybin mushrooms in the last year, although this effect is caused by the mushroom rather than psilocybin itself. In one study, administration of gradually increasing dosages of psilocybin daily for 21 days had no measurable effect on electrolyte levels, blood sugar levels, or liver toxicity tests.
The ability of psilocybin to cause perceptual distortions is linked to its influence on the activity of the prefrontal cortex
Psilocybin is known to strongly influence the subjective experience of the passage of time. Users often feel as if time is slowed down, resulting in the perception that "minutes appear to be hours" or "time is standing still". Studies have demonstrated that psilocybin significantly impairs subjects' ability to gauge time intervals longer than 2.5 seconds, impairs their ability to synchronize to inter-beat intervals longer than 2 seconds, and reduces their preferred tapping rate. These results are consistent with the drug's role in affecting prefrontal cortex activity, and the role that the prefrontal cortex is known to play in time perception. However, the neurochemical basis of psilocybin's effects on the perception of time are not known with certainty.
Users having a pleasant experience can feel a sense of connection to others, nature, and the universe; other perceptions and emotions are also often intensified. Users having an unpleasant experience (a "bad trip") describe a reaction accompanied by fear, other unpleasant feelings, and occasionally by dangerous behavior. In general, the phrase "bad trip" is used to describe a reaction that is characterized primarily by fear or other unpleasant emotions, not just transitory experience of such feelings. A variety of factors may contribute to a psilocybin user experiencing a bad trip, including "tripping" during an emotional or physical low or in a non-supportive environment (see: set and setting). Ingesting psilocybin in combination with other drugs, including alcohol, can also increase the likelihood of a bad trip. Other than the duration of the experience, the effects of psilocybin are similar to comparable dosages of lysergic acid diethylamide (LSD) or mescaline. However, in the Psychedelics Encyclopedia, author Peter Stafford noted, "The psilocybin experience seems to be warmer, not as forceful and less isolating. It tends to build connections between people, who are generally much more in communication than when they use LSD.": 273
Through further anthropological studies regarding "personal insights" and the psycho-social effects of psilocybin, it can be seen in many traditional societies that powerful mind-active substances such as psilocybin are regularly "consumed ritually for therapeutic purposes or for transcending normal, everyday reality". Positive effects that psilocybin has on individuals can be observed by taking on an anthropological approach and moving away from the Western bio-medical society; this is aided by the studies done by Leary. Within certain traditional societies where the use of psilocybin is frequent for shamanic healing rituals, group collectives praise their guide, healer and shaman for helping alleviate them of pains, aches and hurt. They do this through a group ritual practice where participants, or just the guide, ingests psilocybin to help extract any "toxic psychic residues or sorcerous implants" found in one's body. Group therapies using classic psychedelics are becoming more commonly used in the Western world in clinical practice. This may continue to grow as long providing the evidence remains indicative of safety and efficacy. In social sense, the group is shaped by their experiences surrounding psilocybin and how they view the plant collectively. As mentioned in the anthropology article, the group partakes in a "journey" together, thus adding to the spiritual, social body, where roles, hierarchies and gender are subjectively understood.
In their studies on the psilocybin experience, Johns Hopkins researchers use peaceful music and a comfortable room to help ensure a comfortable setting, and experienced guides to monitor and reassure the volunteers
Psilocybin mushrooms have been and continue to be used in indigenous New World cultures in religious, divinatory, or spiritual contexts. Reflecting the meaning of the word entheogen ("the god within"), the mushrooms are revered as powerful spiritual sacraments that provide access to sacred worlds. Typically used in small group community settings, they enhance group cohesion and reaffirm traditional values.Terence McKenna documented the worldwide practices of psilocybin mushroom usage as part of a cultural ethos relating to the Earth and mysteries of nature, and suggested that mushrooms enhanced self-awareness and a sense of contact with a "Transcendent Other"—reflecting a deeper understanding of our connectedness with nature.
Psychedelic drugs can induce states of consciousness that have lasting personal meaning and spiritual significance in individuals who are religious or spiritually inclined; these states are called mystical experiences. Some scholars have proposed that many of the qualities of a drug-induced mystical experience are indistinguishable from mystical experiences achieved through non-drug techniques, such as meditation or holotropic breathwork. In the 1960s, Walter Pahnke and colleagues systematically evaluated mystical experiences (which they called "mystical consciousness") by categorizing their common features. These categories, according to Pahnke, "describe the core of a universal psychological experience, free from culturally determined philosophical or theological interpretations", and allow researchers to assess mystical experiences on a qualitative, numerical scale.
In the 1962 Marsh Chapel Experiment, which was run by Pahnke at the Harvard Divinity School under the supervision of Timothy Leary, almost all of the graduate degree divinity student volunteers who received psilocybin reported profound religious experiences. One of the participants was religious scholar Huston Smith, author of several textbooks on comparative religion; he later described his experience as "the most powerful cosmic homecoming I have ever experienced." In a 25-year followup to the experiment, all of the subjects given psilocybin described their experience as having elements of "a genuine mystical nature and characterized it as one of the high points of their spiritual life".: 13 Psychedelic researcher Rick Doblin considered the study partially flawed due to incorrect implementation of the double-blind procedure, and several imprecise questions in the mystical experience questionnaire. Nevertheless, he said that the study cast "a considerable doubt on the assertion that mystical experiences catalyzed by drugs are in any way inferior to non-drug mystical experiences in both their immediate content and long-term effects".: 24 This sentiment was echoed by psychiatrist William A. Richards, who in a 2007 review stated "[psychedelic] mushroom use may constitute one technology for evoking revelatory experiences that are similar, if not identical, to those that occur through so-called spontaneous alterations of brain chemistry."
A group of researchers from Johns Hopkins School of Medicine led by Roland Griffiths conducted a study to assess the immediate and long-term psychological effects of the psilocybin experience, using a modified version of the mystical experience questionnaire and a rigorous double-blind procedure. When asked in an interview about the similarity of his work with Leary's, Griffiths explained the difference: "We are conducting rigorous, systematic research with psilocybin under carefully monitored conditions, a route which Dr. Leary abandoned in the early 1960s." The National Institute of Drug Abuse-funded study, published in 2006, has been praised by experts for the soundness of its experimental design.[c] In the experiment, 36 volunteers without prior experience with hallucinogens were given psilocybin and methylphenidate (Ritalin) in separate sessions; the methylphenidate sessions served as a control and psychoactive placebo. The degree of mystical experience was measured using a questionnaire developed by Ralph W. Hood; 61% of subjects reported a "complete mystical experience" after their psilocybin session, while only 13% reported such an outcome after their experience with methylphenidate. Two months after taking psilocybin, 79% of the participants reported moderately to greatly increased life satisfaction and sense of well-being. About 36% of participants also had a strong to extreme "experience of fear" or dysphoria (i.e., a "bad trip") at some point during the psilocybin session (which was not reported by any subject during the methylphenidate session); about one-third of these (13% of the total) reported that this dysphoria dominated the entire session. These negative effects were reported to be easily managed by the researchers and did not have a lasting negative effect on the subject's sense of well-being.
A follow-up study conducted 14 months after the original psilocybin session confirmed that participants continued to attribute deep personal meaning to the experience. Almost one-third of the subjects reported that the experience was the single most meaningful or spiritually significant event of their lives, and over two-thirds reported it among their five most spiritually significant events. About two-thirds indicated that the experience increased their sense of well-being or life satisfaction. Even after 14 months, those who reported mystical experiences scored on average 4 percentage points higher on the personality trait of Openness/Intellect; personality traits are normally stable across the lifespan for adults. Likewise, in a recent (2010) web-based questionnaire study designed to investigate user perceptions of the benefits and harms of hallucinogenic drug use, 60% of the 503 psilocybin users reported that their use of psilocybin had a long-term positive impact on their sense of well-being.
While many recent studies have concluded that psilocybin can cause mystical-type experiences having substantial and sustained personal meaning and spiritual significance, not all the medical community agree. Paul R. McHugh, formerly director of the Department of Psychiatry and Behavioral Science at Johns Hopkins, responded as follows in a book review: "The unmentioned fact in The Harvard Psychedelic Club is that LSD, psilocybin, mescaline, and the like produce not a "higher consciousness" but rather a particular kind of "lower consciousness" known well to psychiatrists and neurologists—namely, 'toxicdelirium.'"
Although psilocybin may be prepared synthetically, outside of the research setting it is not typically used in this form. The psilocybin present in certain species of mushrooms can be ingested in several ways: by consuming fresh or dried fruit bodies, by preparing an herbal tea, or by combining with other foods to mask the bitter taste. In rare cases people have injected mushroom extracts intravenously.
Most of the comparatively few fatal incidents reported in the literature that are associated with psychedelic mushroom usage involve the simultaneous use of other drugs, especially alcohol. Probably the most common cause of hospital admissions resulting from psychedelic mushroom usage involves "bad trips" or panic reactions, in which affected individuals become extremely anxious, confused, agitated, or disoriented. Accidents, self-injury, or suicide attempts can result from serious cases of acute psychotic episodes. Although no studies have linked psilocybin with birth defects, it is recommended that pregnant women avoid its usage.
Data is sparse, but in the decade leading up to 2020 an increasing number of psilocybin mushroom overdoses have been recorded. One analysis of mushrooms used by people hospitalized from psilocybin poisoning found high concentrations of phenethylamine (PEA), which has also been detected in the urine of people who have used psilocybin mushrooms. It is hypothesized that PEA may intensify the effect of psilocybin poisoning.
In rats, the median lethal dose (LD50) when administered orally is 280 milligrams per kilogram (mg/kg), approximately one and a half times that of caffeine. When administered intravenously in rabbits, psilocybin's LD50 is approximately 12.5 mg/kg. Psilocybin comprises approximately 1% of the weight of Psilocybe cubensis mushrooms, and so nearly 1.7 kilograms (3.7 lb) of dried mushrooms, or 17 kilograms (37 lb) of fresh mushrooms, would be required for a 60-kilogram (130 lb) person to reach the 280 mg/kg LD50 value of rats. Based on the results of animal studies, the lethal dose of psilocybin has been extrapolated to be 6 grams, 1000 times greater than the effective dose of 6 milligrams. The Registry of Toxic Effects of Chemical Substances assigns psilocybin a relatively high therapeutic index of 641 (higher values correspond to a better safety profile); for comparison, the therapeutic indices of aspirin and nicotine are 199 and 21, respectively. The lethal dose from psilocybin toxicity alone is unknown, and has rarely been documented—as of 2011[update], only two cases attributed to overdosing on hallucinogenic mushrooms (without concurrent use of other drugs) have been reported in the scientific literature and may involve other factors aside from psilocybin.[d]
Panic reactions can occur after consumption of psilocybin-containing mushrooms, especially if the ingestion is accidental or otherwise unexpected. Reactions characterized by violent behavior, suicidal thoughts, schizophrenia-like psychosis, and convulsions have been reported in the literature. A 2005 survey conducted in the United Kingdom found that almost a quarter of those who had used psilocybin mushrooms in the past year had experienced a panic attack.[failed verification] Other adverse effects less frequently reported include paranoia, confusion, prolonged derealization (disconnection from reality), and mania. Psilocybin usage can temporarily induce a state of depersonalization disorder. Usage by those with schizophrenia can induce acute psychotic states requiring hospitalization.
The similarity of psilocybin-induced symptoms to those of schizophrenia has made the drug a useful research tool in behavioral and neuroimaging studies of this psychotic disorder. In both cases, psychotic symptoms are thought to arise from a "deficient gating of sensory and cognitive information" in the brain that ultimately lead to "cognitive fragmentation and psychosis".Flashbacks (spontaneous recurrences of a previous psilocybin experience) can occur long after having used psilocybin mushrooms. Hallucinogen persisting perception disorder (HPPD) is characterized by a continual presence of visual disturbances similar to those generated by psychedelic substances. Neither flashbacks nor HPPD are commonly associated with psilocybin usage, and correlations between HPPD and psychedelics are further obscured by polydrug use and other variables.
Tolerance to psilocybin builds and dissipates quickly; ingesting psilocybin more than about once a week can lead to diminished effects. Tolerance dissipates after a few days, so doses can be spaced several days apart to avoid the effect. A cross-tolerance can develop between psilocybin and the pharmacologically similar LSD, and between psilocybin and phenethylamines such as mescaline and DOM.
Repeated use of psilocybin does not lead to physical dependence. A 2008 study concluded that, based on US data from the period 2000–2002, adolescent-onset (defined here as ages 11–17) usage of hallucinogenic drugs (including psilocybin) did not increase the risk of drug dependence in adulthood; this was in contrast to adolescent usage of cannabis, cocaine, inhalants, anxiolytic medicines, and stimulants, all of which were associated with "an excess risk of developing clinical features associated with drug dependence". Likewise, a 2010 Dutch study ranked the relative harm of psilocybin mushrooms compared to a selection of 19 recreational drugs, including alcohol, cannabis, cocaine, ecstasy, heroin, and tobacco. Psilocybin mushrooms were ranked as the illicit drug with the lowest harm, corroborating conclusions reached earlier by expert groups in the United Kingdom.
Albert Hofmann et al. were the first team to synthesize psilocybin in 1958. Since that time, various chemists have improved the methods for the laboratory synthesis and purification of psilocybin. In particular, Shirota et al. reported a novel method in 2003 for the synthesis of psilocybin at the gram scale from 4-hydroxyindole that does not require chromatographic purification. Fricke et al. described an enzymatic pathway for the synthesis of psilocybin and psilocin, publishing their results in 2017. Sherwood et al. significantly improved upon Shirota's method (producing at the kilogram scale while employing less expensive reagents), publishing their results in 2020.
Biosynthetic route previously thought to lead to psilocybin. It has recently been shown that 4-hydroxylation and O-phosphorylation immediately follow decarboxylation, and neither dimethyltryptamine nor psilocin are intermediates, although spontaneously generated psilocin can be converted back to psilocybin.
More recent research has demonstrated that—at least in P. cubensis—O-phosphorylation is in fact the third step, and that neither dimethyltryptamine nor psilocin are intermediates. The sequence of the intermediate steps has been shown to involve four enzymes (PsiD, PsiH, PsiK, and PsiM) in P. cubensis and P. cyanescens, although it is possible that the biosynthetic pathway differs between species.: 12–13  These enzymes are encoded in gene clusters in Psilocybe, Panaeolus, and Gymnopilus.
Escherichia coli has been genetically modified to manufacture large amounts of psilocybin. Psilocybin can be produced de novo in yeast.
The neurotransmitter serotonin is structurally similar to psilocybin
Psilocybin is rapidly dephosphorylated in the body to psilocin, which is an agonist for several serotonin receptors, which are also known as 5-hydroxytryptamine (5-HT) receptors. In rats, psilocin binds with high affinity to 5-HT2A receptors and low affinity to 5-HT1 receptors, including 5-HT1A and 5-HT1D; effects are also mediated via 5-HT2C receptors. The psychotomimetic (psychosis-mimicking) effects of psilocin can be blocked in a dose-dependent fashion by the 5-HT2Aantagonist drug ketanserin. Various lines of evidence have shown that interactions with non-5-HT2 receptors also contribute to the subjective and behavioral effects of the drug.[e] For example, psilocin indirectly increases the concentration of the neurotransmitter dopamine in the basal ganglia, and some psychotomimetic symptoms of psilocin are reduced by haloperidol, a non-selective dopamine receptor antagonist. Taken together, these suggest that there may be an indirect dopaminergic contribution to psilocin's psychotomimetic effects. Psilocybin and psilocin have no affinity for dopamine receptor D2, unlike another common 5-HT receptor agonist, lysergic acid diethylamide (LSD). Psilocin antagonizes H1 receptors with moderate affinity, compared to LSD which has a lower affinity.
Serotonin receptors are located in numerous parts of the brain, including the cerebral cortex, and are involved in a wide range of functions, including regulation of mood, motivation, body temperature, appetite and sex.
Psilocybin is converted in the liver to the pharmacologically active psilocin, which is then either glucuronated to be excreted in the urine or further converted to various psilocin metabolites
The effects of the drug begin 10–40 minutes after ingestion, and last 2–6 hours depending on dose, species, and individual metabolism.: 36–41 The half life of psilocybin is 163 ± 64 minutes when taken orally, or 74.1 ± 19.6 minutes when injected intravenously.
Psilocybin is metabolized mostly in the liver. As it becomes converted to psilocin, it undergoes a first-pass effect, whereby its concentration is greatly reduced before it reaches the systemic circulation. Psilocin is broken down by the enzyme monoamine oxidase to produce several metabolites that can circulate in the blood plasma, including 4-hydroxyindole-3-acetaldehyde, 4-hydroxytryptophol, and 4-hydroxyindole-3-acetic acid. Some psilocin is not broken down by enzymes and instead forms a glucuronide; this is a biochemical mechanism animals use to eliminate toxic substances by linking them with glucuronic acid, which can then be excreted in the urine. Psilocin is glucuronated by the glucuronosyltransferase enzymes UGT1A9 in the liver, and by UGT1A10 in the small intestine. Based on studies using animals, about 50% of ingested psilocybin is absorbed through the stomach and intestine. Within 24 hours, about 65% of the absorbed psilocybin is excreted into the urine, and a further 15–20% is excreted in the bile and feces. Although most of the remaining drug is eliminated in this way within 8 hours, it is still detectable in the urine after 7 days. Clinical studies show that psilocin concentrations in the plasma of adults average about 8 μg/liter within 2 hours after ingestion of a single 15 mg oral psilocybin dose; psychological effects occur with a blood plasma concentration of 4–6 μg/liter. Psilocybin is about 100 times less potent than LSD on a weight per weight basis, and the physiological effects last about half as long.: 171
Monoamine oxidase inhibitors (MAOI) have been known to prolong and enhance the effects of DMT and one study assumed that the effect on psilocybin would be similar since it is a structural analogue of DMT. Alcohol consumption may enhance the effects of psilocybin, because acetaldehyde, one of the primary breakdown metabolites of consumed alcohol, reacts with biogenic amines present in the body to produce MAOIs related to tetrahydroisoquinoline and β-carboline. Tobacco smokers may also experience more powerful effects with psilocybin, because tobacco smoke exposure decreases the activity of MAO in the brain and peripheral organs.
Various chromatographic methods have been developed to detect psilocin in body fluids: the rapid emergency drug identification system (REMEDi HS), a drug screening method based on HPLC; HPLC with electrochemical detection; GC–MS; and liquid chromatography coupled to mass spectrometry. Although the determination of psilocin levels in urine can be performed without sample clean-up (i.e., removing potential contaminants that make it difficult to accurately assess concentration), the analysis in plasma or serum requires a preliminary extraction, followed by derivatization of the extracts in the case of GC–MS. A specific immunoassay has also been developed to detect psilocin in whole blood samples. A 2009 publication reported using HPLC to quickly separate forensically important illicit drugs including psilocybin and psilocin, which were identifiable within about half a minute of analysis time. These analytical techniques to determine psilocybin concentrations in body fluids are, however, not routinely available, and not typically used in clinical settings.
Maximum reported psilocybin concentrations (% dry weight) in 12 Psilocybe species: 39
Psilocybin is present in varying concentrations in over 200 species of Basidiomycota mushrooms. In a 2000 review on the worldwide distribution of hallucinogenic mushrooms, Gastón Guzmán and colleagues considered these to be distributed amongst the following genera: Psilocybe (116 species), Gymnopilus (14), Panaeolus (13), Copelandia (12), Hypholoma (6), Pluteus (6), Inocybe (6), Conocybe (4), Panaeolina (4), Gerronema (2), and Galerina (1 species). Guzmán increased his estimate of the number of psilocybin-containing Psilocybe to 144 species in a 2005 review. The majority of these are found in Mexico (53 species), with the remainder distributed in the United States and Canada (22), Europe (16), Asia (15), Africa (4), and Australia and associated islands (19). The diversity of psilocybin mushrooms is reported to have been increased by horizontal transfer of the psilocybin gene cluster between unrelated mushroom species. In general, psilocybin-containing species are dark-spored, gilled mushrooms that grow in meadows and woods of the subtropics and tropics, usually in soils rich in humus and plant debris.: 5 Psilocybin mushrooms occur on all continents, but the majority of species are found in subtropical humid forests.Psilocybe species commonly found in the tropics include P. cubensis and P. subcubensis. P. semilanceata—considered by Guzmán to be the world's most widely distributed psilocybin mushroom—is found in Europe, North America, Asia, South America, Australia and New Zealand, but is entirely absent from Mexico. Although the presence or absence of psilocybin is not of much use as a chemotaxonomical marker at the familial level or higher, it is used to classify taxa of lower taxonomic groups.
Global distribution of over 100 psychoactive species of genus Psilocybe mushrooms.
Both the caps and the stems contain psychoactive compounds, although the caps consistently contain more. The spores of these mushrooms do not contain psilocybin or psilocin. The total potency varies greatly between species and even between specimens of a species collected or grown from the same strain. Because most psilocybin biosynthesis occurs early in the formation of fruit bodies or sclerotia, younger, smaller mushrooms tend to have a higher concentration of the drug than larger, mature mushrooms. In general, the psilocybin content of mushrooms is quite variable (ranging from almost nothing to 2.5% of the dry weight): 248 and depends on species, strain, growth and drying conditions, and mushroom size.: 36–41, 52 Cultivated mushrooms have less variability in psilocybin content than wild mushrooms. The drug is more stable in dried than fresh mushrooms; dried mushrooms retain their potency for months or even years,: 51–5 while mushrooms stored fresh for four weeks contain only traces of the original psilocybin.
The psilocybin contents of dried herbarium specimens of Psilocybe semilanceata in one study were shown to decrease with the increasing age of the sample: collections dated 11, 33, or 118 years old contained 0.84%, 0.67%, and 0.014% (all dry weight), respectively. Mature mycelia contain some psilocybin, while young mycelia (recently germinated from spores) lack appreciable amounts. Many species of mushrooms containing psilocybin also contain lesser amounts of the analog compounds baeocystin and norbaeocystin,: 38 chemicals thought to be biogenic precursors.: 170 Although most species of psilocybin-containing mushrooms bruise blue when handled or damaged due to the oxidization of phenolic compounds, this reaction is not a definitive method of identification or determining a mushroom's potency.: 56–58
There is evidence to suggest that psychoactive mushrooms have been used by humans in religious ceremonies for thousands of years. 6,000-year-old pictographs discovered near the Spanish town of Villar del Humo illustrate several mushrooms that have been tentatively identified as Psilocybe hispanica, a hallucinogenic species native to the area.
The rock art was also discovered in Tassili, Algeria, and is believed to depict psychedelic mushrooms and the transformation of the user under their influence. The paintings are said to date back to 9000-7000 BC.
Archaeological artifacts from Mexico, as well as the so-called Mayan "mushroom stones" of Guatemala have also been interpreted by some scholars as evidence for ritual and ceremonial usage of psychoactive mushrooms in the Mayan and Aztec cultures of Mesoamerica.: 11 In Nahuatl, the language of the Aztecs, the mushrooms were called teonanácatl, or "God's flesh". Following the arrival of Spanish explorers to the New World in the sixteenth century, chroniclers reported the use of mushrooms by the natives for ceremonial and religious purposes. According to the Dominican friar Diego Durán in The History of the Indies of New Spain (published c. 1581), mushrooms were eaten in festivities conducted on the occasion of the accession to the throne of Aztec emperor Moctezuma II in 1502. The Franciscan friar Bernardino de Sahagún wrote of witnessing mushroom usage in his Florentine Codex (published 1545–1590),: 164 and described how some merchants would celebrate upon returning from a successful business trip by consuming mushrooms to evoke revelatory visions.: 118 After the defeat of the Aztecs, the Spanish forbade traditional religious practices and rituals that they considered "pagan idolatry", including ceremonial mushroom use. For the next four centuries, the Indians of Mesoamerica hid their use of entheogens from the Spanish authorities.: 165
Although dozens of species of psychedelic mushrooms are found in Europe, there is little documented usage of these species in Old World history besides the use of Amanita muscaria among Siberian peoples. The few existing historical accounts about psilocybin mushrooms typically lack sufficient information to allow species identification, and usually refer to the nature of their effects. For example, Flemish botanist Carolus Clusius (1526–1609) described the bolond gomba (crazy mushroom), used in rural Hungary to prepare love potions. English botanist John Parkinson included details about a "foolish mushroom" in his 1640 herbalTheatricum Botanicum.: 10–12 The first reliably documented report of intoxication with Psilocybe semilanceata—Europe's most common and widespread psychedelic mushroom—involved a British family in 1799, who prepared a meal with mushrooms they had picked in London's Green Park.: 16
Albert Hofmann (shown here in 1993) purified psilocybin and psilocin from Psilocybe mexicana in the late 1950s
The increasing availability of information on growing techniques made it possible for amateurs to grow psilocybin mushrooms (Psilocybe cubensis pictured) without access to laboratory equipment
Heim cultivated the mushrooms in France and sent samples for analysis to Albert Hofmann, a chemist employed by the Swiss pharmaceutical company Sandoz (now Novartis). Hofmann—who had synthesized lysergic acid diethylamide (LSD) in 1938—led a research group that isolated and identified the psychoactive alkaloids psilocybin and psilocin from Psilocybe mexicana, publishing their results in 1958.: 128 The team was aided in the discovery process by Hofmann's willingness to ingest mushroom extracts to help verify the presence of the active compounds.: 126–127
Next, Hofmann's team synthesized several structural analogs of these compounds to examine how these structural changes would affect psychoactivity. This research led to the development of ethocybin and CZ-74. Because the physiological effects of these compounds last only about three and a half hours (about half as long as psilocybin), they proved more manageable than the latter for use in psycholytic therapy.: 237 Sandoz also marketed and sold pure psilocybin under the name Indocybin clinicians and researchers worldwide.: 166 There were no reports of serious complications when psilocybin was used in this way.
In the early 1960s, Harvard University became a testing ground for psilocybin, through the efforts of Timothy Leary and his associates Ralph Metzner and Richard Alpert (who later changed his name to Ram Dass). Leary obtained synthesized psilocybin from Hofmann through Sandoz Pharmaceuticals. Some studies, such as the Concord Prison Experiment, suggested promising results using psilocybin in clinical psychiatry. According to a 2008 review of safety guidelines in human hallucinogenic research, however, Leary and Alpert's well-publicized termination from Harvard and later advocacy of hallucinogen use "further undermined an objective scientific approach to studying these compounds". In response to concerns about the increase in unauthorized use of psychedelic drugs by the general public, psilocybin and other hallucinogenic drugs suffered negative press and faced increasingly restrictive laws. In the United States, laws were passed in 1966 that prohibited the production, trade, or ingestion of hallucinogenic drugs; Sandoz stopped producing LSD and psilocybin the same year. In 1970, Congress passed "The Federal Comprehensive Drug Abuse Prevention and Control Act" that made LSD, peyote, psilocybin and other hallucinogens illegal to use for any and all purposes, including scientific research. United States politicians' agenda against LSD usage had swept psilocybin along with it into the Schedule I category of illicit drugs. Such restrictions on the use of these drugs in human research made funding for such projects difficult to obtain, globally, and scientists who worked with psychedelic drugs faced being "professionally marginalized". Although Hofmann tested these compounds on himself, never advocated their legalization or medical use. In his 1979 book LSD — mein Sorgenkind ("LSD — my problem child"), Hofmann described the problematic use of these hallucinogens as inebriants.: 79–116
Despite the legal restrictions on psilocybin use, the 1970s witnessed the emergence of psilocybin as the "entheogen of choice".: 276 This was due in large part to a wide dissemination of information on the topic, which included works such as those by author Carlos Castaneda, and several books that taught the technique of growing psilocybin mushrooms. One of the most popular of this latter group was published in 1976 under the pseudonyms O.T. Oss and O.N. Oeric by Jeremy Bigwood, Dennis J. McKenna, K. Harrison McKenna, and Terence McKenna, entitled Psilocybin: Magic Mushroom Grower's Guide. Over 100,000 copies were sold by 1981. As ethnobiologist Jonathan Ott explains, "These authors adapted San Antonio's technique (for producing edible mushrooms by casing mycelial cultures on a rye grain substrate; San Antonio 1971) to the production of Psilocybe [Stropharia] cubensis. The new technique involved the use of ordinary kitchen implements, and for the first time the layperson was able to produce a potent entheogen in his own home, without access to sophisticated technology, equipment or chemical supplies.": 290 San Antonio's technique describes a method to grow the common edible mushroom Agaricus bisporus
Because of a lack of clarity about laws about psilocybin mushrooms, specifically in the form of sclerotia (also known as "truffles"), European retailers in the late 1990s and early 2000s commercialized and marketed them in smartshops in the Netherlands and the UK, and online. Several websites[f] emerged that have contributed to the accessibility of information on description, use, effects and exchange of experiences among users. Since 2001, six EU countries have tightened their legislation on psilocybin mushrooms in response to concerns about their prevalence and increasing usage. In the 1990s, hallucinogens and their effects on human consciousness were again the subject of scientific study, particularly in Europe. Advances in neuropharmacology and neuropsychology, and the availability of brain imaging techniques have provided impetus for using drugs like psilocybin to probe the "neural underpinnings of psychotic symptom formation including ego disorders and hallucinations". Recent studies in the United States have attracted attention from the popular press and thrust psilocybin back into the limelight.
In some jurisdictions, Psilocybe spores are legal to sell and possess, because they contain neither psilocybin nor psilocin. In other jurisdictions, they are banned because they are items that are used in drug manufacture. A few jurisdictions (such as the US states of California, Georgia and Idaho) have specifically prohibited the sale and possession of psilocybin mushroom spores. Cultivation of psilocybin mushrooms is considered drug manufacture in most jurisdictions and is often severely penalized, though some countries and one US state (New Mexico) has ruled that growing psilocybin mushrooms does not qualify as "manufacturing" a controlled substance.
Advocacy for tolerance
Despite being illegal in many typically Western countries, such as the UK, Australia and some US states, less conservative governments opt to nurture the legal use of psilocybin and other psychedelic drugs. In Amsterdam, Netherlands, authorities provide education and promotion on the safe use of psychedelic drugs, such as psilocybin, in an aim to reduce public harm. Similarly, religious groups like America's Uniao do Vegetal, UDV, use psychedelics in traditional ceremonies.
Advocate for legalization argue there is a lack of evidence of harm, and potential use in treating certain mental health conditions. Research is difficult to conduct because of the legal status of psychoactive substances. Advocates for legalization also promote the utility of "ego dissolution" and argue bans are cultural discrimination against traditional users.
Dried Psilocybe mushrooms showing the characteristic blue bruising on the stems
A 2009 national survey of drug use by the US Department of Health and Human Services concluded that the number of first-time psilocybin mushroom users in the United States was roughly equivalent to the number of first-time users of cannabis. In European countries, the lifetime prevalence estimates of psychedelic mushroom usage among young adults (15–34 years) range from 0.3% to 14.1%.
In modern Mexico, traditional ceremonial use survives among several indigenous groups, including the Nahuas, the Matlatzinca, the Totonacs, the Mazatecs, Mixes, Zapotecs, and the Chatino. Although hallucinogenic Psilocybe species are abundant in low-lying areas of Mexico, most ceremonial use takes places in mountainous areas of elevations greater than 1,500 meters (4,900 ft). Guzmán suggests this is a vestige of Spanish colonial influence from several hundred years earlier, when mushroom use was persecuted by the Catholic Church.
^One of the reported fatalities, that of a 22-year-old French man who died in 1993, was later challenged in the literature by Jochen Gartz and colleagues, who concluded "the few reported data concerning the victim are insufficient to exclude other possible causes of the fatality".
^Subjective effects are "feelings, perceptions, and moods personally experienced by an individual"; they are often assessed using methods of self-report, including questionnaires. Behavioral effects, in contrast, can be observed directly.
^ abStuderus E, Kometer M, Hasler F, Vollenweider FX (2011). "Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies". Journal of Psychopharmacology. 25 (11): 1434–1452. doi:10.1177/0269881110382466. PMID20855349. S2CID22923427.
^Quentin AM (1960). La Psilocybine en Psychiatrie Clinique et Experimentale [Psilocybin in Clinical and Experimental Psychiatry] (PhD thesis) (in French). Paris, France: Paris University Medical Dissertation.
Rinkel M, Atwell CR, Dimascio A, Brown J (1960). "Experimental psychiatry. V. Psilocybine, a new psychotogenic drug". New England Journal of Medicine. 262 (6): 295–297. doi:10.1056/NEJM196002112620606. PMID14437505.
Parashos AJ (1976). "The psilocybin-induced "state of drunkenness" in normal volunteers and schizophrenics". Behavioral Neuropsychiatry. 8 (1–12): 83–86. PMID1052267.
^Heimann H (1994). "Experience of time and space in model psychoses". In Pletscher A, Ladewig D (eds.). 50 Years of LSD. Current Status and Perspectives of Hallucinogens. New York, New York: The Parthenon Publishing Group. pp. 59–66. ISBN978-1-85070-569-7.
^ abWittmann M, Carter O, Hasler F, Cahn BR, Grimberg U, Spring P, Hell D, Flohr H, Vollenweider FX (2007). "Effects of psilocybin on time perception and temporal control of behaviour in humans". Journal of Psychopharmacology. 21 (1): 50–64. doi:10.1177/0269881106065859. PMID16714323. S2CID3165579.
^ abAttema-de Jonge ME, Portier CB, Franssen EJ (2007). "Automutilatie na gebruik van hallucinogene paddenstoelen" [Automutilation after consumption of hallucinogenic mushrooms]. Nederlands Tijdschrift voor Geneeskunde (in Dutch). 151 (52): 2869–2872. PMID18257429.
^ abDoblin R (1991). "Pahnke's "Good Friday Experiment": a long-term follow-up and methodological critique". Journal of Transpersonal Psychology. 23 (1): 1–25.
^Richards WA (2008). "The phenomenology and potential religious import of states of consciousness facilitated by psilocybin". Archive for the Psychology of Religion. 30 (1): 189–199. doi:10.1163/157361208X317196. S2CID144969540.
^ abCarhart-Harris RL, Nutt DJ (2010). "User perceptions of the benefits and harms of hallucinogenic drug use: a web-based questionnaire study". Journal of Substance Abuse. 15 (4): 283–300. doi:10.3109/14659890903271624. S2CID56427651.
^Gérault A, Picart D (1996). "Intoxication mortelle à la suite de la consommation volontaire et en groupe de champignons hallucinogènes" [Fatal poisoning after a group of people voluntarily consumed hallucinogenic mushrooms]. Bulletin de la Société Mycologique de France (in French). 112: 1–14.
^Hyde C, Glancy P, Omerod P, Hall D, Taylor GS (1978). "Abuse of indigenous psilocybin mushrooms: a new fashion and some psychiatric complications". British Journal of Psychiatry. 132 (6): 602–604. doi:10.1192/bjp.132.6.602. PMID566144. S2CID20020560.
^Mack RB (1983). "Phenomenally phunny phungi – psilocybin toxicity". New Castle Medical Journal. 44 (10): 639–640. PMID6580536.
^van Amsterdam J, Opperhuizen A, Koeter M, van den Brink W (2010). "Ranking the harm of alcohol, tobacco and illicit drugs for the individual and the population". European Addiction Research. 16 (4): 202–207. doi:10.1159/000317249. PMID20606445. S2CID207669364.
^ abAnastos N, Barnett NW, Pfeffer FM (2006). "Investigation into the temporal stability of aqueous standard solutions of psilocin and psilocybin using high performance liquid chromatography". Science & Justice. 46 (2): 91–96. doi:10.1016/S1355-0306(06)71579-9. PMID17002211.
^Adams Jr JD (2009). "Chemical interactions with pyramidal neurons in layer 5 of the cerebral cortex: control of pain and anxiety". Current Medicinal Chemistry. 16 (27): 3476–3279. doi:10.2174/092986709789057626. PMID19799545.
^ abGrieshaber AF, Moore KA, Levine B (2001). "The detection of psilocin in human urine". Journal of Forensic Sciences. 46 (3): 627–630. doi:10.1520/JFS15014J. PMID11373000.
^Hasler F, Bourquin D, Brenneisen R, Vollenweider FX (2002). "Renal excretion profiles of psilocin following oral administration of psilocybin: a controlled study in man". Journal of Pharmaceutical and Biomedical Analysis. 30 (2): 331–339. doi:10.1016/S0731-7085(02)00278-9. PMID12191719.
^Meyer MR, Maurer HH (2011). "Absorption, distribution, metabolism and excretion pharmacogenomics of drugs of abuse". Pharmacogenomics. 12 (2): 215–233. doi:10.2217/pgs.10.171. PMID21332315.
^van Amsterdam J, Talhout R, Vleeming W, Opperhuizen A (2006). "Contribution of monoamine oxidase (MAO) inhibition to tobacco and alcohol addiction". Life Sciences. 79 (21): 1969–1973. doi:10.1016/j.lfs.2006.06.010. PMID16884739.
^Jenkins AJ (2003). "Hallucinogens". In Levine B (ed.). Principles of Forensic Toxicology (2nd ed.). Washington, D.C.: American Association for Clinical Chemistry Press. p. 281. ISBN978-1-890883-87-4. Archived from the original on April 3, 2017. Retrieved February 27, 2016.
^Kamata T, Katagi M, Tsuchihashi H (2010). "Metabolism and toxicological analyses of hallucinogenic tryptamine analogues being abused in Japan". Forensic Toxicology. 28 (1): 1–8. doi:10.1007/s11419-009-0087-9. S2CID45118221.
^ abKeller T, Schneider A, Regenscheit P, Dirnhofer R, Rücker T, Jaspers J, Kisser W (1999). "Analysis of psilocybin and psilocin in Psilocybe subcubensis Guzmán by ion mobility spectrometry and gas chromatography-mass spectrometry". Forensic Science International. 99 (2): 93–105. doi:10.1016/S0379-0738(98)00168-6. PMID10077856.
^Pedersen-Bjergaard S, Sannes E, Rasmussen K, Tonneson F (1997). "Determination of psilocybin in Psilocybe semilanceata by capillary zone electrophoresis". Journal of Chromatography. 694 (2): 375–381. doi:10.1016/S0378-4347(97)00127-8. PMID9252052.
^Lee RE (1985). "A technique for the rapid isolation and identification of psilocin from psilocin/psilocybin-containing mushrooms". Journal of Forensic Sciences. 30 (3): 931–941. doi:10.1520/JFS11028J. PMID4040953.
^Wurst M, Kysilka R, Koza T (1992). "Analysis and isolation of indole alkaloids of fungi by high-performance liquid chromatography". Journal of Chromatography. 593 (1–2): 201–208. doi:10.1016/0021-9673(92)80287-5.
^Saito K, Toyo'oka T, Fukushima T, Kato M, Shirota O, Goda Y (2004). "Determination of psilocin in magic mushrooms and rat plasma by liquid chromatography with fluorimetry and electrospray ionization mass spectrometry". Analytica Chimica Acta. 527 (2): 149–156. doi:10.1016/j.aca.2004.08.071.
^ abLindenblatt H, Kramer E, Holzmann-Erens P, Gouzoulis-Mayfrank E, Kovar K (1998). "Quantitation of psilocin in human plasma by high performance liquid chromatography and electrochemical detection: comparison of liquid-liquid extraction with automated on-line solid-phase extraction". Journal of Chromatography. 709 (2): 255–263. doi:10.1016/S0378-4347(98)00067-X. PMID9657222.
^Kysilka R (1990). "Determination of psilocin in rat urine by high-performance liquid chromatography with electrochemical detection". Journal of Chromatography. 534: 287–290. doi:10.1016/S0378-4347(00)82176-3. PMID2094720.
^Kamata T, Nishikawa M, Katagi M, Tsuchihashi H (2003). "Optimized glucuronide hydrolysis for the detection of psilocin in human urine samples". Journal of Chromatography B. 792 (2): 421–427. doi:10.1016/j.jchromb.2003.08.030. PMID14581081.
^ abGuzmán G (2005). "Species diversity of the genus Psilocybe (Basidiomycotina, Agaricales, Strophariaceae) in the world mycobiota, with special attention to hallucinogenic properties". International Journal of Medicinal Mushrooms. 7 (1–2): 305–331. doi:10.1615/intjmedmushr.v7.i12.280.
^Guzmán G (1983). The Genus Psilocybe: A Systematic Revision of the Known Species Including the History, Distribution, and Chemistry of the Hallucinogenic Species. Beihefte Zur Nova Hedwigia. Heft 74. Vaduz, Liechtenstein: J. Cramer. pp. 361–362. ISBN978-3-7682-5474-8.
^Wurst M, Semerdžieva M, Vokoun J (1984). "Analysis of psychotropic compounds in fungi of the genus Psilocybe by reversed-phase high performance liquid chromatography". Journal of Chromatography A. 286: 229–235. doi:10.1016/S0021-9673(01)99190-3.
^ abBigwood J, Beug MW (1982). "Variation of psilocybin and psilocin levels with repeated flushes (harvests) of mature sporocarps of Psilocybe cubensis (Earle) Singer". Journal of Ethnopharmacology. 5 (3): 287–291. doi:10.1016/0378-8741(82)90014-9. PMID7201054.
^Gartz J (1992). "New aspects of the occurrence, chemistry and cultivation of European hallucinogenic mushrooms". Supplemento Agli Annali dei Musei Civici di Rovereto Sezione Archeologica, Storia e Scienze Naturali. 8: 107–124.
^Ohenoja E, Jokiranta J, Mäkinen T, Kaikkonen A, Airaksinen MM (1987). "The occurrence of psilocybin and psilocin in Finnish fungi". Journal of Natural Products. 50 (4): 741–744. doi:10.1021/np50052a030. PMID3430170.
^Heim R (1957). "Notes préliminaires sur les agarics hallucinogènes du Mexique" [Preliminary notes on the hallucination-producing agarics of Mexico]. Revue de Mycologie (in French). 22 (1): 58–79.
^Leary T, Metzner R, Presnell M, Weil G, Schwitzgebel R, Kinne S (1965). "A new behavior change program using psilocybin". Psychotherapy: Theory, Research & Practice. 2 (2): 61–72. doi:10.1037/h0088612.
^Schaepe, Herbert (September 13, 2001). "UN's INCB Psilocybin Mushroom Policy". Erowid.org. Retrieved January 7, 2012. As you are aware, mushrooms containing the above substances are collected and used for their hallucinogenic effects. As a matter of international law, no plants (natural material) containing psilocin and psilocybin are at present controlled under the Convention on Psychotropic Substances of 1971. Consequently, preparations made of these plants are not under international control and, therefore, not subject of the articles of the 1971 Convention [emphasis added]. Criminal cases are decided with reference to domestic law, which may otherwise provide for controls over mushrooms containing psilocine and psilocybin. As the Board can only speak as to the contours of the international drug conventions, I am unable to provide an opinion on the litigation in question. (Letter from Secretary of the UN International Narcotics Control Board to the Dutch Ministry of Health)
^Rodd R (September 2018). "It's all you! Australian ayahuasca drinking, spiritual development, and immunitary individualism". Critique of Anthropology. 38 (3): 325–45. doi:10.1177/0308275X18775818. S2CID149858755.
^Wark C, Galliher JF (2009). "Timothy Leary, Richard Alpert (Ram Dass) and the changing definition of psilocybin". The International Journal on Drug Policy. 21 (3): 234–239. doi:10.1016/j.drugpo.2009.08.004. PMID19744846.