Psilocybin is an indole alkaloid derived from the monoamine alkaloid tryptamine, which, in turn, is derived from the amino acid tryptophan.4 After ingestion, psilocybin is metabolized to the active compound psilocin, which is also present in psilocybin mushrooms, but in smaller amounts.5 Psilocin is pharmacologically similar to lysergic acid diethylamide (LSD; a semisynthetic derivative of ergotamine, which is produced by the ergot fungus Claviceps purpurea [Clavicipitaceae] and related fungi) and the neurotransmitter serotonin (5-hydroxytryptamine [5-HT]).4,5 It has been shown that activation of the serotonin receptor subtype 5-HT2A is responsible for most of the psychedelic (i.e., consciousness-expanding and hallucinatory) effects of the compound.6
A 1998 review by Guzmán et al. identified 186 fungal species that contain psilocybin and related indoles, or that are likely to contain these substances, with the majority (116, or 62%) of these species belonging to the genus Psilocybe (Hymenogastraceae) and the rest belonging to 12 different fungal genera.7
Human use of psilocybin mushrooms likely dates back thousands of years. Prehistoric murals from Tassili n’Ajjer in the Sahara Desert in southeastern Algeria, which are thought to be between 7,000 and 9,000 years old, may depict Psilocybe mairei. Additionally, a portion of the Selva Pascuala mural, which is located in the municipality of Villar del Humo in Cuenca, Spain, may depict P. hispanica. This portion of the mural may be about 6,000 years old, which makes it the oldest known evidence of psilocybin mushroom use in Europe.8
In Mesoamerica, the native use of hallucinogenic mushrooms dates back to pre-Columbian times. In his multivolume Historia General de las Cosas de Nueva España, Franciscan friar Bernardino de Sahagún (1499-1590) recorded the ritualistic use by the Aztecs of psilocybin mushrooms that they called teonanácatl (which translates approximately to “God’s flesh” in Náhuatl). De Sahagún reportedly wrote that mushroom intoxication gave the Aztecs the ability to seemingly change themselves into animals and have powerful visions during which they heard voices they believed to be from God.9
After participating in a Mazatec ritual in Oaxaca, Mexico, which involved psilocybin mushrooms, the amateur mycologists Robert Gordon Wasson, a vice president of J.P. Morgan and Co., and his wife Valentina published a 1957 article in Life magazine titled “Seeking the Magic Mushroom.” This article sparked widespread interest in psilocybin mushrooms and reportedly inspired some, including Harvard psychologist Timothy Leary, PhD, to study and popularize psilocybin and other entheogens (i.e., substances that produce an unordinary state of consciousness for religious or spiritual purposes; in Greek, entheogen means “generating the divine within”).9
In 1959, Swiss chemist Albert Hoffman (who was the first to synthesize LSD in 1938) isolated the active principle psilocybin from Psilocybe mexicana. In the 1960s and 1970s, hallucinogens, including psilocybin and LSD, were the subjects of multiple studies, but this research stopped for almost three decades after the US Controlled Substances Act of 1970 placed these substances into Schedule I, the most restrictive and punitive schedule. This was done because of concerns about widespread non-medical use of these compounds.1,2
Psilocybin is not known to be addictive and may have anti-addictive properties. It also has a well-established safety profile in human laboratory and clinical trial research. According to Ross et al., since the early 1990s, about 2,000 varying doses of psilocybin have been safely administered to humans in the United States and Europe, in carefully controlled clinical settings.1
Psilocybin mushrooms can induce a sense of exhilaration, hallucinations that include vivid and bright colors and shapes, euphoria, distorted perception of time, and impaired judgment. Stationary objects may appear mobile. In addition, although visual hallucinations are more common, auditory hallucinations can also occur. Hallucinations typically do not last longer than four or five hours.4
Ross S, Bossis A, Guss J, et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. Journal of Psychopharmacology. 2016;30(12):1165-1180. doi: 10.1177/0269881116675512.
Griffiths RR, Johnson MW, Carducci MA, et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial. Journal of Psychopharmacology. 2016;30(12):1181-1197. doi: 10.1177/0269881116675513.
Supplement to: Ross S, Bossis A, Guss J, et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J Psychopharmacol. 2016;30(12):1165-1180. Available at: journals.sagepub.com/doi/suppl/10.1177/0269881116675512/suppl_file/JOP675512_Appendix.pdf. Accessed April 26, 2017.
Psilocybine. Toxicology Data Network website. Available at: toxnet.nlm.nih.gov/cgi-bin/sis/search2/r?dbs+hsdb:@term+@rn+@rel+520-52-5. Accessed April 19, 2017.
Hallucinogenic mushrooms drug profile. European Monitoring Centre for Drugs and Drug Addiction website. Available at: www.emcdda.europa.eu/publications/drug-profiles/mushrooms. Accessed April 19, 2017.
Lee H-M, Roth BL. Hallucinogen actions on human brain revealed. Proceedings of the National Academy of Sciences. 2012;109(6):1820-1821. doi: 10.1073/pnas.1121358109.
Guzmán G, Allen JW, Gartz J. A Worldwide Geographical Distribution of the Neurotropic Fungi, an Analysis and Discussion. Annali del Museo Civico di Rovereto: Sezione: Archeologia, Storia, Scienze Naturali. 1998;14:189-280. Available at: www.museocivico.rovereto.tn.it/UploadDocs/104_art09-Guzman%20&%20C.pdf.
Akers BP, Ruiz JF, Piper A, Ruck CAP. A prehistoric mural in Spain depicting neurotropic Psilocybe mushrooms? Economic Botany. 2011;65(2):121-128. doi:10.1007/s12231-011-9152-5.
Rush JA, ed. Entheogens and the Development of Culture. Berkeley, CA: North Atlantic Books; 2013.