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History Early There is evidence to suggest that psychoactive mushrooms have been used by humans in religious ceremonies for thousands of years. Murals dated 9000 to 7000 BCE found in the Sahara desert in southeast Algeria depict horned beings dressed as dancers, clothed in garb decorated with geometrical designs, and holding mushroom-like objects. Parallel lines extend from the mushroom shapes to the center of the dancers’ heads. 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. 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. 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 16th 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), and described how some merchants would celebrate upon returning from a successful business trip by consuming mushrooms to evoke revelatory visions. 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. Although dozens of species of psychedelic mushrooms are found in Europe, there is little documented usage of these species in Old World history. 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. 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. Modern American banker and amateur ethnomycologist R. Gordon Wasson and his wife Valentina studied the ritual use of psychoactive mushrooms by the native population in the Mazatec village Huautla de Jiménez. 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. 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. Heim cultivated the mushrooms in France, and sent samples for analysis to Albert Hofmann, a chemist employed by the Swiss multinational pharmaceutical company Sandoz (now Novartis). Hofmann, who had in 1938 created LSD, led a research group that isolated and identified the psychoactive compounds from Psilocybe mexicana. Hofmann was aided in the discovery process by his willingness to ingest mushroom extracts to help verify the presence of the active compounds. He and his colleagues later synthesized a number of compounds chemically related to the naturally occurring psilocybin, to see how structural changes would affect psychoactivity. The new molecules differed from psilocybin in the position of the phosphoryl or hydroxyl group at the top of the indole ring, and in the numbers of methyl groups (CH3) and other additional carbon chains. Two diethyl analogs (containing two ethyl groups in place of the two methyl groups) of psilocybin and psilocin were synthesized by Hofmann: 4-phosphoryloxy-N,N-diethyltryptamine, called CEY-19, and 4-hydroxy-N,N-diethyltryptamine, called CZ-74. Because their physiological effects last only about three and a half hours (about half as long as psilocybin), they proved more manageable in European clinics using “psycholytic therapy”—a form of psychotherapy involving the controlled use of psychedelic drugs. Sandoz marketed and sold pure psilocybin under the name Indocybin to physicians and clinicians worldwide. 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 pharmaceutical. 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. Further backlash against LSD usage swept psilocybin along with it into the Schedule I category of illicit drugs in 1970. Subsequent restrictions on the use of these drugs in human research made funding for such projects difficult to obtain, and scientists who worked with psychedelic drugs faced being “professionally marginalized”. Despite the legal restrictions on psilocybin use, the 1970s witnessed the emergence of psilocybin as the “entheogen of choice”. 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.” Because of a lack of clarity about laws about psilocybin mushrooms, retailers in the late 1990s and early 2000s (decade) commercialized and marketed them in smartshops in the Netherlands and the UK, and online. Several websites 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.