Psilocybin

Source: Wikipedia, the free encyclopedia.

Psilocybin
Kekulé, skeletal formula of canonical psilocybin
Spacefill model of canonical psilocybin
Names
Preferred IUPAC name
3-[2-(Dimethylamino)ethyl]-1H-indol-4-yl dihydrogen phosphate
Identifiers
3D model (
JSmol
)
273158
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard
 100.007.542 Edit this at Wikidata
EC Number
  • 208-294-4
KEGG
MeSH Psilocybine
RTECS number
  • NM3150000
UNII
  • InChI=1S/C12H17N2O4P/c1-14(2)7-6-9-8-13-10-4-3-5-11(12(9)10)18-19(15,16)17/h3-5,8,13H,6-7H2,1-2H3,(H2,15,16,17) checkY
    Key: QVDSEJDULKLHCG-UHFFFAOYSA-N checkY
  • InChI=1/C12H17N2O4P/c1-14(2)7-6-9-8-13-10-4-3-5-11(12(9)10)18-19(15,16)17/h3-5,8,13H,6-7H2,1-2H3,(H2,15,16,17)
  • CN(C)CCC1=CNC2=C1C(=CC=C2)OP(=O)(O)O
Pharmacology
Low
intravenous
Pharmacokinetics:
Hepatic
Oral: 163±64 min
Intravenous: 74.1±19.6 min[1]
Renal
Legal status
Properties
C12H17N2O4P
Molar mass 284.252 g·mol−1
Melting point 220–228 °C (428–442 °F)[3]
Soluble
Solubility Soluble in boiling methanol and water
slightly soluble in ethanol
insoluble in chloroform, benzene[4]
Hazards
Lethal dose or concentration (LD, LC):
285 mg/kg (mouse, i.v.)
280 mg/kg (rat, i.v.)
12.5 mg/kg (rabbit, i.v.)[3]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)

Psilocybin[a] (/ˌsaɪləˈsaɪbɪn/ sy-lə-SY-bin, /ˌsɪl-/) is a naturally occurring psychedelic prodrug compound produced by more than 200 species of fungi. The most potent are members of genus Psilocybe, such as P. azurescens, P. semilanceata, and P. cyanescens, but psilocybin has also been isolated from about a dozen other genera. Psilocybin is itself biologically inactive but is quickly converted by the body to psilocin, which has mind-altering effects similar, in some aspects, to those of lysergic acid diethylamide (LSD), mescaline, and dimethyltryptamine (DMT). In general, the effects include euphoria, visual and mental hallucinations, changes in perception, distorted sense of time, and perceived spiritual experiences. It can also cause adverse reactions such as nausea and panic attacks.

Imagery found on cave paintings and rock art of modern-day Spain and Algeria suggests that human use 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.

History

Early

Mayan "mushroom stones" of Guatemala

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.[6]
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.[7]
Archaeological
entheogens from the Spanish authorities.[9]
: 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.[11][12] 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 herbal Theatricum Botanicum.[13]: 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.[13]: 16 

Modern

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

American banker and amateur

Mazatec village Huautla de Jiménez, Mexico. In 1957, Wasson described the psychedelic visions that he experienced during these rituals in "Seeking the Magic Mushroom", an article published in the popular American weekly Life magazine.[14] Later the same year they were accompanied on a follow-up expedition by French mycologist Roger Heim, who identified several of the mushrooms as Psilocybe species.[15]

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.[10]: 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.[10]: 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.[16]: 237  Sandoz also marketed and sold pure psilocybin under the name Indocybin to clinicians and researchers worldwide.[9]: 166  There were no reports of serious complications when psilocybin was used in this way.[1]

In the early 1960s,

funding for such projects difficult to obtain, globally, and scientists who worked with psychedelic drugs faced being "professionally marginalized".[22] Although Hofmann tested these compounds on himself, he 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.[10]
: 79–116 

Despite the legal restrictions on psilocybin use, the 1970s witnessed the emergence of psilocybin as the "entheogen of choice".

Dennis J. McKenna, K. Harrison McKenna, and Terence McKenna, entitled Psilocybin: Magic Mushroom Grower's Guide. Over 100,000 copies were sold by 1981.[24] 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."[23]: 290  San Antonio's technique describes a method to grow the common edible mushroom Agaricus bisporus[25]

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[b] 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.[26] 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".[27] Recent studies in the United States have attracted attention from the popular press and thrust psilocybin back into the limelight.[28][29]

Reported effects

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. 98 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.[17] 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.[30]

After ingesting psilocybin, the user may experience a wide range of emotional effects which can include: 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.[31] 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 one-third of those given a high dose experienced anxiety or paranoia.[32][33] Low doses can induce hallucinatory effects. Closed-eye hallucinations may occur, where the affected individual sees multicolored geometric shapes and vivid imaginative sequences.[34] Some individuals report synesthesia, such as tactile sensations when viewing colors.[35]: 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".[27] Open-eye visual hallucinations are common, and may be very detailed although rarely confused with reality.[34]

A 2011

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".[36] 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.[37][38] Although other researchers have described instances of psychedelic drug usage leading to new psychological understandings and personal insights,[39] it is not known whether these experimental results can be generalized to larger populations.[36]

Physical effects

Common responses include

blood sugar levels, or liver toxicity tests.[1]

Psychiatric effects and perceptual disturbances

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.[42] Users often feel as if time is slowed down, resulting in the perception that "minutes appear to be hours" or "time is standing still".[43] 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.[43][44] These results are consistent with the drug's role in affecting prefrontal cortex activity,[45] and the role that the prefrontal cortex is known to play in time perception.[46] However, the neurochemical basis of psilocybin's effects on the perception of time are not known with certainty.[47]

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.[31][48] 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."[16]: 273 

Theory of mind network and default mode network

Psychedelics, including psilocybin, have been shown to affect different clusters of brain regions known as the theory of mind network (ToMN) and the default mode network (DMN).[49] The ToMN involves making inferences and understanding social situations based on patterns[50] whereas, the DMN relates more to introspection and one's sense of self.[49] The DMN in particular is related to increased rumination and worsening self-image in patients with major depressive disorder (MDD).[51] In studies done with single use Psilocybin, areas of the DMN showed decreased functional connectivity (communication between areas of the brain). This provides functional insight into the work of psilocybin in increasing one's sense of connection to their surrounds as the areas of the brain involved in introspection decrease in functionality under the effects of the drug.[52] Conversely, areas of the brain involved in the ToMN showed increased activity and functional activation in response to psychedelics. These results were not unique to psilocybin and there was no significant difference in brain activation found in similar trials of mescaline and LSD. Information and studies into the DMN and ToMN are relatively sparse and their connections to other psychiatric illnesses and use of psychedelics is still largely unknown. [49]

Group perceptions

Through further anthropological studies regarding "personal insights"[53] 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".[54] 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.[55] 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"[54] 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.[56] 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,[54] the group partakes in a "journey" together, thus adding to the spiritual, social body, where roles, hierarchies and gender are subjectively understood.[54]

Adverse effects

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

birth defects,[57] it is recommended that pregnant women avoid its usage.[58]

Toxicity

Data is sparse, but in the decade leading up to 2020, an increasing number of psilocybin mushroom overdoses were recorded. Nonetheless, the number of events requiring hospitalization remain rare, and overdoses are generally mild and self-limiting. A review regarding the management of psychedelic overdoses suggested that psilocybin related overdose management should prioritize managing the immediate adverse effects, such as anxiety and paranoia, rather than specific pharmacological interventions, as its physiological toxicity tends to be rather limited.[59] 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.[59]

In rats, the

intravenously in rabbits, psilocybin's LD50 is approximately 12.5 mg/kg.[60] 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.[31] 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.[61] 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.[62] The lethal dose from psilocybin toxicity alone is unknown, and has rarely been documented—as of 2011, 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.[31][d]

Psychiatric

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,

depersonalization disorder.[70] Usage by those with schizophrenia can induce acute psychotic states requiring hospitalization.[71]

The similarity of psilocybin-induced symptoms to those of schizophrenia has made the drug a useful research tool in behavioral and

polydrug use and other variables.[75]

Tolerance and dependence

Chart of dependence potential and effective dose/lethal dose ratio of several psychoactive drugs[76]

DOM.[79]

Repeated use of psilocybin does not lead to

recreational drugs, including alcohol, cannabis, cocaine, ecstasy, heroin, and tobacco. Psilocybin mushrooms were ranked as the illicit drug with the lowest harm,[81] corroborating conclusions reached earlier by expert groups in the United Kingdom.[82]

Cultural significance and "mystical" experiences

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.[83] 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.[84]

Psychedelic drugs can induce states of

holotropic breathwork.[85][86] 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.[87]

In the 1962

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".[91]: 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."[92]

A group of researchers from

National Institute of Drug Abuse-funded study, published in 2006, has been praised by experts for the soundness of its experimental design.[e] 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;[95] 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.[96]

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.[89] 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.[31][69]

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, 'toxic delirium.'"[97]

Available forms

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

intravenously.[31]

Chemistry

Physical properties

Psilocybin is a naturally-occurring

dimethyltryptamine, found in many plant species and in trace amounts in some mammals, and bufotenin, found in the skin of certain amphibians, especially the Colorado River toad.[99]
: 10–13 

Psilocybin is a white, crystalline solid that is soluble in water, methanol and ethanol but insoluble in nonpolar organic solvents such as chloroform and petroleum ether.[99]: 15  It has a melting point between 220–228 °C (428–442 °F),[60] and an ammonia-like taste.[100] Its pKa values are estimated to be 1.3 and 6.5 for the two successive phosphate hydroxy groups and 10.4 for the dimethylamine nitrogen, so it typically exists as a zwitterionic structure.[100] There are two known crystalline polymorphs of psilocybin, as well as reported hydrated phases.[101] Psilocybin rapidly oxidizes upon exposure to light—an important consideration when using it as an analytical standard.[102]

Laboratory synthesis

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.[103]

Biosynthesis

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.[104]

Isotopic labeling experiments from the 1960s suggested that the biosynthesis of psilocybin was a four-step process:[105]

  1. decarboxylation of tryptophan to tryptamine
  2. N,N-dimethylation of tryptamine at the N9 position to dimethyltryptamine
  3. 4-hydroxylation of dimethyltryptamine to psilocin
  4. O-phosphorylation of psilocin 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.[104] 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.[99]: 12–13 [104] These enzymes are encoded in gene clusters in Psilocybe, Panaeolus, and Gymnopilus.[106]

Escherichia coli has been genetically modified to manufacture large amounts of psilocybin.[107] Psilocybin can be produced de novo in GM yeast.[108][109]

Pharmacology

Pharmacodynamics

The neurotransmitter serotonin is structurally similar to psilocybin

Psilocybin is a psychoplastogen,[110][111][112] which refers to a compound capable of promoting rapid and sustained neuroplasticity.

Psilocybin is rapidly

psychotomimetic (mimicking the mind distortion present in psychosis) effects of psilocin can be blocked in a dose-dependent fashion by the 5-HT2A antagonist drug ketanserin.[66] Various lines of evidence have shown that interactions with non-5-HT2 receptors also contribute to the subjective and behavioral effects of the drug.[79][f] 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.[47] Psilocybin and psilocin have no affinity for dopamine receptor D2, unlike another common 5-HT receptor agonist, lysergic acid diethylamide (LSD).[1] Psilocin antagonizes H1 receptors with moderate affinity, compared to LSD which has a lower affinity.[114]
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 libido.[115]

Psilocybin induces region-dependent alterations in glutamate that may be associated with subjective experiences of ego dissolution.[116]

Pharmacokinetics

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.

half life of psilocybin is 163 ± 64 minutes when taken orally, or 74.1 ± 19.6 minutes when injected intravenously.[1]

Psilocybin is metabolized mostly in the

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.[20] 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;[120] psychological effects occur with a blood plasma concentration of 4–6 μg/liter.[1] Psilocybin is approximately 1/100 the potency of LSD on a weight per weight basis, and the physiological effects last about half as long.[35]
: 171 

β-carboline.[31] Tobacco smokers may also experience more powerful effects with psilocybin,[31] because tobacco smoke exposure decreases the activity of MAO in the brain and peripheral organs.[122]

Analytical methods

Several relatively simple

capillary zone electrophoresis,[128] ultraviolet spectroscopy,[129] and infrared spectroscopy.[130] High-performance liquid chromatography (HPLC) is used with ultraviolet,[102] fluorescence,[131] electrochemical,[132] and electrospray mass spectrometric detection methods.[133]

Various chromatographic methods have been developed to detect psilocin in

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.[137] 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.[138] These analytical techniques to determine psilocybin concentrations in body fluids are, however, not routinely available, and not typically used in clinical settings.[48]

Natural occurrence

Maximum reported psilocybin concentrations (% dry weight) in 12 Psilocybe species[8]: 39 
Species % psilocybin
P. azurescens 1.78
P. serbica 1.34
P. semilanceata 0.98
P. baeocystis 0.85
P. cyanescens 0.85
P. tampanensis 0.68
P. cubensis 0.63
P. weilii
 		0.61
P. hoogshagenii 0.60
P. stuntzii 0.36
P. cyanofibrillosa 0.21
P. liniformans 0.16

Psilocybin is present in varying concentrations in over 200 species of

subtropics and tropics, usually in soils rich in humus and plant debris.[99]: 5  Psilocybin mushrooms occur on all continents, but the majority of species are found in subtropical humid forests.[139] 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[142]—is found in Europe, North America, Asia, South America, Australia and New Zealand, but is entirely absent from Mexico.[140] 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.[143]

Global distribution of over 100 psychoactive species of genus Psilocybe mushrooms.[144]
The mushroom Psilocybe mexicana
Psilocybin was first isolated from Psilocybe mexicana.
The mushroom Psilocybe semilanceata
P. semilanceata is common in Europe, Canada, and the United States.

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.[127][145][146] The total potency varies greatly between species and even between specimens of a species collected or grown from the same strain.[147] 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.[148] In general, the psilocybin content of mushrooms is quite variable (ranging from almost nothing to 2.5% of the dry weight)[149][16]: 248  and depends on species, strain, growth and drying conditions, and mushroom size.[8]: 36–41, 52  Cultivated mushrooms have less variability in psilocybin content than wild mushrooms.[150] The drug is more stable in dried than fresh mushrooms; dried mushrooms retain their potency for months or even years,[8]: 51–5  while mushrooms stored fresh for four weeks contain only traces of the original psilocybin.[31]

The psilocybin contents of dried

mycelia contain some psilocybin, while young mycelia (recently germinated from spores) lack appreciable amounts.[152] Many species of mushrooms containing psilocybin also contain lesser amounts of the analog compounds baeocystin and norbaeocystin,[8]: 38  chemicals thought to be biogenic precursors.[35]: 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.[147][8]
: 56–58 

Societal perception and current usage

Legal status

Further information: Legal status of psilocybin mushrooms and Psilocybin decriminalization in the United States
This section is an excerpt from Legal status of psilocybin mushrooms.[edit]

The

Schedule I drugs under the United Nations 1971 Convention on Psychotropic Substances.[153] Schedule I drugs are defined as drugs with a high potential for abuse or drugs that have no recognized medical uses. However, psilocybin mushrooms have had numerous medicinal[154][155][156] and religious uses in dozens of cultures throughout history and have a significantly lower potential for abuse than other Schedule I drugs.[157]

Psilocybin mushrooms are not regulated by UN treaties.[158] Many countries, however, have some level of regulation or prohibition of psilocybin mushrooms (for example, the US Psychotropic Substances Act, the UK Misuse of Drugs Act 1971, and the Canadian Controlled Drugs and Substances Act).

In some jurisdictions, Psilocybe spores are legal to sell and possess, because they contain neither psilocybin nor psilocin.[159][citation needed] 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.[citation needed]

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.[160] Similarly, religious groups like America's Uniao do Vegetal, UDV,[161] use psychedelics in traditional ceremonies.[162] From 1 July 2023, the Australian medicines regulator has permitted psychiatrists to prescribe psilocybin for the therapeutic treatment of post-traumatic stress disorder.[163]

Advocates for legalization argue there is a lack of evidence of harm,

ego dissolution"[161] and argue bans are cultural discrimination against traditional users.[167]

Usage

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.[168] In European countries, the lifetime prevalence estimates of psychedelic mushroom usage among young adults (15–34 years) range from 0.3% to 14.1%.[169]

In modern Mexico, traditional ceremonial use survives among several indigenous groups, including 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.[170]

Research

See also: Psychedelic therapy

Psilocybin has been a subject of clinical research since the early 1960s, when the Harvard Psilocybin Project evaluated the potential value of psilocybin as a treatment for certain personality disorders.[171] Beginning in the 2000s, psilocybin has been investigated for its possible role in the treatment of nicotine dependence, alcohol dependence, obsessive–compulsive disorder (OCD), cluster headache, cancer-related existential distress[103][172] anxiety disorders, and certain mood disorders.[9]: 179–81 [173][174] In 2018, the United States Food and Drug Administration (FDA) granted breakthrough therapy designation for psilocybin-assisted therapy for treatment-resistant depression.[175][176] A systematic review published in 2021 found that the use of psilocybin as a pharmaceutical substance was associated with reduced intensity of depression symptoms.[177] The role of psilocybin as a possible psychoplastogen is also being examined.[110][111][112]

See also

Explanatory notes

  1. dimethyltryptamine), psilocybine, psilocibin, psilocybinum, psilotsibin, psilocin phosphate ester, and indocybin.[5]
  2. Lycaeum, Mycotopia, The Shroomery, MushroomJohn and The Entheogen Review. Regional sites focusing on hallucinogenic mushrooms listed were Copenhagen Mushroom Link (Denmark), Champis (France), Daath (Hungary), Delysid (Spain), Enteogeneos (Portugal), Kouzelné houbičky (Czech Republic), Norshroom (Norway), Planetahongo (Spain), Svampinfo (Sweden), and Taikasieniforum (Finland). It also listed Magic-Mushrooms.net. The report detailed several additional sites selling spore prints
    in 2006, but noted that many of these had ceased operation.
  3. non-blind clinical study of 30 individuals who were given a dosage of 8–12 milligrams of psilocybin; from Passie (2002),[1] citing Quentin (1960).[40]
  4. ^ One of the reported fatalities, that of a 22-year-old French man who died in 1993,[63] 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".[64]
  5. ^ The academic communities' approval for the methodology employed is exemplified by the quartet of commentaries published in the journal Psychopharmacology titled "Commentary on: Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual experience by Griffiths et al.", by HD Kleber (pp. 291–292), DE Nichols (pp. 284–286), CR Schuster (pp. 289–290), and SH Snyder (pp. 287–288).
  6. ^ 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.[113]

References

Citations

  1. ^
    S2CID 12656091
    .
  2. ^ Anvisa (July 24, 2023). "RDC Nº 804 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 804 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published July 25, 2023). Archived from the original on August 27, 2023. Retrieved August 27, 2023.
  3. ^ a b Merck Index, 11th Edition, 7942
  4. ^ "Psilocybine". PubChem, US National Library of Medicine. August 27, 2022. Retrieved August 29, 2022.
  5. National Library of Medicine. Archived
    from the original on September 25, 2012. Retrieved December 4, 2011.
  6. S2CID 3955222
    .
  7. ^ Samorini, Giorgio (1992). "The oldest representations of hallucinogenic mushrooms in the world (Sahara Desert, 9000-7000 BP)". Integration. Zeitschrift für geistbewegende Pflanzen und Kultur. 2/3: 69–65.[permanent dead link]
  8. ^
    ISBN 978-0-89815-839-7
    .
  9. ^
    ISBN 978-1603582148
    .
  10. ^
    ISBN 978-0979862229
    .
  11. doi:10.29203/ka.1992.294
    .
  12. ISBN 978-0-88316-517-1
    .
  13. ^
    ISBN 978-0-9653399-0-2
    .
  14. ISSN 0024-3019. Archived
    from the original on April 3, 2017. Retrieved February 27, 2016.
  15. ^ 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.
  16. ^
    ISBN 978-0-914171-51-5
    .
  17. ^
    S2CID 39777572
    .
  18. doi:10.1037/h0088612
    .
  19. PMID 18593734. Archived from the original
    (PDF) on November 20, 2017. Retrieved November 20, 2017.
  20. ^
    doi:10.2492/inflammregen.29.47
    .
  21. ^ "The War on Drugs turns 50 today. It's time to make peace". The Washington Post. Retrieved August 8, 2023.
  22. doi:10.1038/scientificamerican1210-76. Archived from the original
    (PDF) on October 3, 2011. Retrieved July 25, 2011.
  23. ^
    ISBN 978-0-9614234-3-8
    .
  24. ISBN 978-0-932551-06-1
    .
  25. PMID 5102274. Archived
    from the original on September 23, 2015. Retrieved September 7, 2011.
  26. ^
    ISBN 92-9168-249-7. Archived
    (PDF) from the original on March 29, 2012. Retrieved September 8, 2011.
  27. ^
    S2CID 22923427
    .
  28. ^ Keim B (July 1, 2008). "Psilocybin study hints at rebirth of hallucinogen research". Wired.com. Archived from the original on August 3, 2011. Retrieved August 8, 2011.
  29. ^ Miller G (July 1, 2008). "A very memorable trip". sciencemag.org. Archived from the original on August 13, 2018. Retrieved August 8, 2011.
  30. ISSN 0022-0175
    .
  31. ^
    PMID 21256914. Archived from the original
    (PDF) on January 9, 2015.
  32. ^ "Hallucinogenic Drug Psilocybin Eases Existential Anxiety in People With Life-Threatening Cancer". Johns Hopkins. December 1, 2016. Archived from the original on April 7, 2021. Retrieved April 9, 2019.
  33. PMID 21674151
    .
  34. ^
    S2CID 15263504. Archived
    (PDF) from the original on April 18, 2020. Retrieved April 10, 2019.
  35. ^
    ISBN 978-1-59454-961-8. Archived
    from the original on April 4, 2017. Retrieved February 27, 2016.
  36. ^
    PMID 21956378
    .
  37. PMID 29020861
    .
  38. ^ "Psilocybin (from magic mushrooms) plus meditation and spiritual training leads to lasting changes in positive traits". January 19, 2018. Archived from the original on February 21, 2019. Retrieved February 21, 2019.
  39. PMID 17211054. Archived
    (PDF) from the original on September 16, 2018. Retrieved December 27, 2011.
  40. ^ 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.
  41. ^ See for example:
  42. ISBN 978-1-85070-569-7
    .
  43. ^
    S2CID 3165579
    .
  44. S2CID 22789140
    .
  45. S2CID 9790150. Archived
    (PDF) from the original on August 16, 2019. Retrieved August 16, 2019.
  46. S2CID 25960626
    .
  47. ^
    PMID 20668434
    .
  48. ^
    PMID 18257429
    .
  49. ^
    PMID 37467907
    .
  50. PMID 32360298
    .
  51. PMID 37261927
    .
  52. PMID 36272145
    .
  53. ^ "Drug Addictions, Hallucinogens and Shamanism: the View from Anthropology - Document - Gale Academic OneFile". Archived from the original on August 23, 2021. Retrieved August 23, 2021.
  54. ^ a b c d Batchelder T (2001). "Drug Addictions, Hallucinogens and Shamanism: the View from Anthropology". Drug Addictions, Hallucinogens and Shamanism. Townsend Letter for Doctors and Patients. 217: 74–77. Archived from the original on October 19, 2021. Retrieved August 23, 2021 – via Gale Academic OneFile.
  55. OCLC 318713242. Archived
    from the original on October 19, 2021. Retrieved August 23, 2021.
  56. PMID 33073220
    .
  57. ISBN 978-0-470-63906-1. Archived
    from the original on April 3, 2017. Retrieved February 27, 2016.
  58. ISBN 978-0-444-50763-1. Archived
    from the original on April 3, 2017. Retrieved February 27, 2016.
  59. ^
    S2CID 220472473
    .
  60. ^
    ISBN 978-0-911910-13-1
    .
  61. PMID 15139867. Archived
    (PDF) from the original on August 10, 2006. Retrieved November 16, 2011.
  62. ISBN 978-1-59477-224-5. Archived
    from the original on April 4, 2017. Retrieved February 27, 2016.
  63. ^ 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.
  64. ^ Gartz J, Samorini G, Festi F (1996). "On the presumed French case of fatality caused by ingestion of Liberty Caps". Eluesis. 6: 40–41. Archived from the original on April 5, 2012.
  65. S2CID 7453965
    .
  66. ^
    S2CID 37706068. Archived from the original
    (PDF) on March 3, 2019.
  67. S2CID 20020560
    .
  68. PMID 6580536
    .
  69. ^
    S2CID 56427651
    .
  70. S2CID 18506672
    .
  71. S2CID 44321700
    .
  72. S2CID 24647325
    .
  73. ^
    S2CID 230298
    .
  74. PMID 19086254
    .
  75. ^ Myers LS, Watkins SS, Carter TJ (1998). "Flashbacks in theory and practice" (PDF). The Heffter Review of Psychedelic Research. 1: 51–57. Archived (PDF) from the original on September 27, 2011. Retrieved August 14, 2011.
  76. ISBN 978-0-7425-4245-7. Archived
    from the original on January 7, 2012.
  77. ISBN 978-0-932551-71-9. Archived
    from the original on April 4, 2017. Retrieved February 27, 2016.
  78. PMID 19040555
    .
  79. ^
    PMID 21256140
    .
  80. PMID 19022584
    .
  81. S2CID 207669364
    .
  82. S2CID 5667719
    .
  83. ISBN 978-0-275-99024-4
    .
  84. ISBN 978-0-553-37130-7
    .
  85. ISBN 978-0-684-84297-4
    .
  86. PMID 9924839. Archived
    (PDF) from the original on September 21, 2017. Retrieved October 26, 2017.
  87. S2CID 18464414
    .
  88. ^ Pahnke WN (1966). "Drugs and mysticism". International Journal of Parapsychology. 8 (2): 295–315.
  89. ^
    PMID 18593735. Archived from the original
    (PDF) on July 22, 2008. Retrieved July 3, 2008.
  90. ISBN 978-1-58542-034-6
    .
  91. ^ a b Doblin R (1991). "Pahnke's "Good Friday Experiment": a long-term follow-up and methodological critique". Journal of Transpersonal Psychology. 23 (1): 1–25.
  92. S2CID 144969540
    .
  93. S2CID 7845214. Archived from the original
    (PDF) on November 9, 2011.
  94. ^ "Press release: Griffiths psilocybin". Johns Hopkins Medicine. July 11, 2006. Archived from the original on July 16, 2011. Retrieved July 12, 2006.
  95. S2CID 147200008
    .
  96. ^ Smith M (July 12, 2006). "Medical News: Psilocybin Viewed as Therapy or Research Tool". Medpagetoday.com. Archived from the original on October 5, 2008. Retrieved February 12, 2011.
  97. ^ "Paul McHugh reviews Don Lattin's "The Harvard Psychedelic Club."". commentarymagazine.com. April 1, 2010. Archived from the original on April 10, 2019. Retrieved April 10, 2019.
  98. ISBN 978-0-12-374634-4. Archived
    from the original on April 4, 2017. Retrieved February 27, 2016.
  99. ^
    S2CID 31056807
    .
  100. ^ a b "Psilocybine". Hazardous Substances Data Bank. U.S. National Library of Medicine. Archived from the original on August 13, 2018. Retrieved November 21, 2011.
  101. PMID 34982048
    .
  102. ^
    PMID 17002211
    .
  103. ^
    PMID 36678537
    .
  104. ^
    PMID 28763571
    .
  105. PMID 5750023
    .
  106. ^
    PMID 30283667
    .
  107. S2CID 208747979. Archived
    from the original on December 3, 2019. Retrieved December 3, 2019.
  108. PMID 32224264
    .
  109. PMID 35132076
    .
  110. ^
    PMID 34671279
    .
  111. ^
    PMID 30262987
    .
  112. ^
    PMID 34566723
    .
  113. ISBN 978-1-4200-5458-3. Archived
    from the original on April 4, 2017. Retrieved February 27, 2016.
  114. ^ "PDSP Ki Database". PDSP. Archived from the original on May 9, 2021. Retrieved January 20, 2020.
  115. PMID 19799545
    .
  116. PMID 32446245
    .
  117. ^
    PMID 11373000
    .
  118. PMID 12191719
    .
  119. PMID 21332315
    .
  120. ISBN 978-0-9626523-7-0
    .
  121. PMID 9491968
    .
  122. PMID 16884739
    .
  123. ISBN 978-1-890883-87-4. Archived
    from the original on April 3, 2017. Retrieved February 27, 2016.
  124. ISBN 978-0-471-49252-8
    .
  125. ISBN 978-0-7234-1576-3. Archived
    from the original on April 4, 2017. Retrieved February 27, 2016.
  126. S2CID 45118221
    .
  127. ^
    PMID 10077856
    .
  128. PMID 9252052
    .
  129. PMID 4040953
    .
  130. doi:10.1016/0021-9673(92)80287-5
    .
  131. doi:10.1016/j.aca.2004.08.071
    .
  132. ^
    PMID 9657222
    .
  133. ^ Rodriguez-Cruz SE (2005). "Analysis and characterization of psilocybin and psilocin using liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) with collision-induced-dissociation (CID) and source-induced dissociation (SID)". Microgram Journal. 3 (3–4): 175–82. Archived from the original on April 29, 2011.
  134. ^
    PMID 10978655
    .
  135. PMID 2094720
    .
  136. PMID 14581081
    .
  137. S2CID 11249439
    .
  138. S2CID 96753191. Archived
    from the original on May 3, 2021. Retrieved August 24, 2020.
  139. ^ a b Guzmán G, Allen JW, Gartz J (2000). "A worldwide geographical distribution of the neurotropic fungi, an analysis and discussion" (PDF). Annali del Museo Civico di Rovereto: Sezione Archeologia, Storia, Scienze Naturali. 14: 189–280. Archived (PDF) from the original on February 5, 2018. Retrieved October 19, 2021.
  140. ^
    doi:10.1615/intjmedmushr.v7.i12.280
    .
  141. ^ Yong E (August 24, 2017). "How Mushrooms Became Magic". The Atlantic. Archived from the original on March 16, 2018. Retrieved March 15, 2018.
  142. ISBN 978-3-7682-5474-8
    .
  143. JSTOR 3759505. Archived
    from the original on March 10, 2017. Retrieved August 29, 2011.
  144. ^ Guzmán G, Allen JW, Gartz J (1998). "A worldwide geographical distribution of the neurotropic fungi, an analysis and discussion" (PDF). Annali del Museo Civico di Rovereto. 14: 207. Archived from the original (PDF) on June 26, 2010. Retrieved September 17, 2017.
  145. doi:10.1016/S0021-9673(01)99190-3
    .
  146. PMID 2722990
    .
  147. ^
    PMID 7201054
    .
  148. ^ 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.
  149. PMID 20047807
    .
  150. ^ "Drug profiles: Hallucinogenic mushrooms". European Monitoring Centre for Drugs and Drug Addiction. September 19, 2011. Archived from the original on November 27, 2011. Retrieved December 4, 2011.
  151. PMID 3430170
    .
  152. S2CID 38006957. Archived from the original
    (PDF) on November 16, 2020.
  153. ^ Griffiths & Grob, Roland R. & Charles S. "Hallucinogens as Medicine" (PDF). Scientific American. Archived from the original (PDF) on October 3, 2011. Retrieved March 22, 2013.
  154. ^ Szalavitz, Maia (June 16, 2011). "'Magic Mushrooms' Can Improve Psychological Health Long Term". Time. Archived from the original on April 21, 2013. Retrieved March 22, 2013.
  155. PMID 21674151
    .
  156. ^ Jerome, Lisa. "Psilocybin Investigator's Brochure" (PDF). MAPS. Archived from the original (PDF) on March 19, 2013. Retrieved March 22, 2013.
  157. ^ Schaepe, Herbert (September 13, 2001). "UN's INCB Psilocybin Mushroom Policy". Erowid.org. Archived from the original on November 12, 2009. 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)
  158. ^ "Psilocybin Spores are Not Controlled". Home Cultivation Association of New York. January 2, 2024. Retrieved March 19, 2024.
  159. S2CID 228997721
    .
  160. ^
    ISBN 9788551004173
    .
  161. ISBN 978-1-4985-0910-7
    .
  162. ISSN 0261-3077
    . Retrieved July 18, 2023.
  163. ^ Submission to the Western Australian Inquiry Into Alternative Approaches to Reducing Illicit Drug Use and Its Effects on the Community (PDF) (Report). Australian Psychedelic Society Inc. January 30, 2019. Archived (PDF) from the original on August 23, 2021. Retrieved August 23, 2021.
  164. S2CID 2025731
    .
  165. PMID 29753748
    .
  166. S2CID 149858755
    .
  167. ISBN 978-1-60529-407-0. Archived
    from the original on April 4, 2017. Retrieved February 27, 2016.
  168. ISBN 978-92-9168-470-0. Archived
    (PDF) from the original on December 3, 2011. Retrieved December 4, 2011.
  169. S2CID 22085876
    .
  170. PMID 19744846
    .
  171. PMID 36381758
    .
  172. PMID 27354908
    .
  173. PMID 27909164
    .
  174. ^ "COMPASS Pathways Receives FDA Breakthrough Therapy Designation for Psilocybin Therapy for Treatment-resistant Depression". Compass Pathways. Archived from the original on December 4, 2018. Retrieved December 3, 2018.
  175. ^ Richard Staines (December 2, 2019). "FDA tags psilocybin drug as clinical depression Breakthrough Therapy". Pharmaphorum. Archived from the original on September 7, 2021. Retrieved September 7, 2021.
  176. PMID 34451890
    .

External links
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