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Psilocybin

Psilocybin

Overview
Psilocybin is a naturally occurring psychedelic
Psychedelic drug
A psychedelic substance is a psychoactive drug whose primary action is to alter cognition and perception. Psychedelics are part of a wider class of psychoactive drugs known as hallucinogens, a class that also includes related substances such as dissociatives and deliriants...

 prodrug
Prodrug
A prodrug is a pharmacological substance administered in an inactive form. Once administered, the prodrug is metabolised in vivo into an active metabolite, a process termed bioactivation. The rationale behind the use of a prodrug is generally for absorption, distribution, metabolism, and...

, with mind-altering effects similar to those of LSD
LSD
Lysergic acid diethylamide, abbreviated LSD or LSD-25, also known as lysergide and colloquially as acid, is a semisynthetic psychedelic drug of the ergoline family, well known for its psychological effects which can include altered thinking processes, closed and open eye visuals, synaesthesia, an...

 and mescaline
Mescaline
Mescaline or 3,4,5-trimethoxyphenethylamine is a naturally occurring psychedelic alkaloid of the phenethylamine class used mainly as an entheogen....

, after it is converted to psilocin
Psilocin
Psilocin , an aromatic compound, sometimes also spelled psilocine, psilocyn, or psilotsin, is a psychedelic mushroom alkaloid. It is found in most psychedelic mushrooms together with its phosphorylated counterpart psilocybin...

. The effects can include altered thinking processes, perceptual distortions, an altered sense of time, and spiritual experiences, as well as adverse reactions such as nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...

 and panic attack
Panic attack
Panic attacks are periods of intense fear or apprehension that are of sudden onset and of relatively brief duration. Panic attacks usually begin abruptly, reach a peak within 10 minutes, and subside over the next several hours...

s. Psilocybin is produced by over 200 species of mushroom
Mushroom
A mushroom is the fleshy, spore-bearing fruiting body of a fungus, typically produced above ground on soil or on its food source. The standard for the name "mushroom" is the cultivated white button mushroom, Agaricus bisporus; hence the word "mushroom" is most often applied to those fungi that...

s, collectively known as psilocybin mushrooms. The most potent are members of the genus Psilocybe
Psilocybe
Psilocybe is a genus of small mushrooms growing worldwide. This genus is best known for its species with psychedelic or hallucinogenic properties, widely known as "magic mushrooms", though the majority of species do not contain hallucinogenic compounds...

, such as P. cubensis
Psilocybe cubensis
Psilocybe cubensis is a species of psychedelic mushroom whose principal active compounds are psilocybin and psilocin. Commonly called Boomers, Cubes or Gold Caps, it belongs to the Strophariaceae family of fungi and was previously known as Stropharia cubensis.-Taxonomy and naming:The species was...

, P. semilanceata
Psilocybe semilanceata
Psilocybe semilanceata, commonly known as the liberty cap, is a psychedelic mushroom that contains the psychoactive compounds psilocybin and baeocystin. Of the world's psychoactive mushrooms, it is the most common in nature, and one of the most potent...

, and P. cyanescens
Psilocybe cyanescens
Psilocybe cyanescens is a species of potent psychedelic mushroom. The main compounds responsible for its psychedelic effects are psilocybin and psilocin. It belongs to the family Strophariaceae...

, but psilocybin has also been isolated from about a dozen other genera
Genera
Genera is a commercial operating system and development environment for Lisp machines developed by Symbolics. It is essentially a fork of an earlier operating system originating on the MIT AI Lab's Lisp machines which Symbolics had used in common with LMI and Texas Instruments...

.

In Mexico, Central America, and South America, psilocybin-containing mushrooms have been ingested for thousands of years in spiritual ceremonies.
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Encyclopedia
Psilocybin is a naturally occurring psychedelic
Psychedelic drug
A psychedelic substance is a psychoactive drug whose primary action is to alter cognition and perception. Psychedelics are part of a wider class of psychoactive drugs known as hallucinogens, a class that also includes related substances such as dissociatives and deliriants...

 prodrug
Prodrug
A prodrug is a pharmacological substance administered in an inactive form. Once administered, the prodrug is metabolised in vivo into an active metabolite, a process termed bioactivation. The rationale behind the use of a prodrug is generally for absorption, distribution, metabolism, and...

, with mind-altering effects similar to those of LSD
LSD
Lysergic acid diethylamide, abbreviated LSD or LSD-25, also known as lysergide and colloquially as acid, is a semisynthetic psychedelic drug of the ergoline family, well known for its psychological effects which can include altered thinking processes, closed and open eye visuals, synaesthesia, an...

 and mescaline
Mescaline
Mescaline or 3,4,5-trimethoxyphenethylamine is a naturally occurring psychedelic alkaloid of the phenethylamine class used mainly as an entheogen....

, after it is converted to psilocin
Psilocin
Psilocin , an aromatic compound, sometimes also spelled psilocine, psilocyn, or psilotsin, is a psychedelic mushroom alkaloid. It is found in most psychedelic mushrooms together with its phosphorylated counterpart psilocybin...

. The effects can include altered thinking processes, perceptual distortions, an altered sense of time, and spiritual experiences, as well as adverse reactions such as nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...

 and panic attack
Panic attack
Panic attacks are periods of intense fear or apprehension that are of sudden onset and of relatively brief duration. Panic attacks usually begin abruptly, reach a peak within 10 minutes, and subside over the next several hours...

s. Psilocybin is produced by over 200 species of mushroom
Mushroom
A mushroom is the fleshy, spore-bearing fruiting body of a fungus, typically produced above ground on soil or on its food source. The standard for the name "mushroom" is the cultivated white button mushroom, Agaricus bisporus; hence the word "mushroom" is most often applied to those fungi that...

s, collectively known as psilocybin mushrooms. The most potent are members of the genus Psilocybe
Psilocybe
Psilocybe is a genus of small mushrooms growing worldwide. This genus is best known for its species with psychedelic or hallucinogenic properties, widely known as "magic mushrooms", though the majority of species do not contain hallucinogenic compounds...

, such as P. cubensis
Psilocybe cubensis
Psilocybe cubensis is a species of psychedelic mushroom whose principal active compounds are psilocybin and psilocin. Commonly called Boomers, Cubes or Gold Caps, it belongs to the Strophariaceae family of fungi and was previously known as Stropharia cubensis.-Taxonomy and naming:The species was...

, P. semilanceata
Psilocybe semilanceata
Psilocybe semilanceata, commonly known as the liberty cap, is a psychedelic mushroom that contains the psychoactive compounds psilocybin and baeocystin. Of the world's psychoactive mushrooms, it is the most common in nature, and one of the most potent...

, and P. cyanescens
Psilocybe cyanescens
Psilocybe cyanescens is a species of potent psychedelic mushroom. The main compounds responsible for its psychedelic effects are psilocybin and psilocin. It belongs to the family Strophariaceae...

, but psilocybin has also been isolated from about a dozen other genera
Genera
Genera is a commercial operating system and development environment for Lisp machines developed by Symbolics. It is essentially a fork of an earlier operating system originating on the MIT AI Lab's Lisp machines which Symbolics had used in common with LMI and Texas Instruments...

.

In Mexico, Central America, and South America, psilocybin-containing mushrooms have been ingested for thousands of years in spiritual ceremonies. In a 1957 Life
Life (magazine)
Life generally refers to three American magazines:*A humor and general interest magazine published from 1883 to 1936. Time founder Henry Luce bought the magazine in 1936 solely so that he could acquire the rights to its name....

magazine article, American banker and ethnomycologist
Ethnomycology
Ethnomycology is the study of the historical uses and sociological impact of fungi , and can be considered a subfield of ethnobotany or ethnobiology...

  described his experiences ingesting psilocybin-containing mushrooms during a traditional ceremony in Mexico, introducing the drug to popular culture. Shortly afterward, the Swiss chemist Albert Hofmann
Albert Hofmann
Albert Hofmann was a Swiss scientist known best for being the first person to synthesize, ingest and learn of the psychedelic effects of lysergic acid diethylamide . He authored more than 100 scientific articles and a number of books, including LSD: My Problem Child...

 purified the active principle psilocybin from the mushroom Psilocybe mexicana
Psilocybe mexicana
Psilocybe mexicana is a psychedelic mushroom. It is from this species that Dr. Albert Hofmann first isolated and named the active compounds, psilocybin and psilocin in 1958. It was first used by the early natives of Central America and North America over 2,000 years ago, known to theAztecs as...

, and developed a method to produce the drug synthetically
Organic synthesis
Organic synthesis is a special branch of chemical synthesis and is concerned with the construction of organic compounds via organic reactions. Organic molecules can often contain a higher level of complexity compared to purely inorganic compounds, so the synthesis of organic compounds has...

. Hofmann's employer Sandoz
Sandoz
Founded in 2003, Sandoz presently is the generic drug subsidiary of Novartis, a multinational pharmaceutical company. The company develops, manufactures and markets generic drugs as well as pharmaceutical and biotechnological active ingredients....

 marketed and sold pure psilocybin to physicians and clinicians worldwide for use in psychedelic psychotherapy.

Enthusiasts for the drug consider it an entheogen
Entheogen
An entheogen , in the strict sense, is a psychoactive substance used in a religious, shamanic, or spiritual context. Historically, entheogens were mostly derived from plant sources and have been used in a variety of traditional religious contexts...

 (spirituality-enhancing agent) and a tool to supplement practices for transcendence
Transcendence (religion)
In religion transcendence refers to the aspect of God's nature which is wholly independent of the physical universe. This is contrasted with immanence where God is fully present in the physical world and thus accessible to creatures in various ways...

, including meditation
Meditation
Meditation is any form of a family of practices in which practitioners train their minds or self-induce a mode of consciousness to realize some benefit....

 and psychonautics
Psychonautics
Psychonautics refers both to a methodology for describing and explaining the subjective effects of altered states of consciousness, including those induced by mind altering substances, and to a research paradigm in which the researcher voluntarily immerses him/herself into an altered...

. The intensity and duration of the effects of psilocybin are variable, depending on species or cultivar
Cultivar
A cultivar'Cultivar has two meanings as explained under Formal definition. When used in reference to a taxon, the word does not apply to an individual plant but to all those plants sharing the unique characteristics that define the cultivar. is a plant or group of plants selected for desirable...

 of mushrooms, dosage, individual physiology, and set and setting
Set and setting
Set and setting describes the context for psychoactive and particularly psychedelic drug experiences: one's mindset and the setting in which the user has the experience. This is especially relevant for psychedelic or hallucinogenic experiences...

, as was shown in experiments led by Timothy Leary
Timothy Leary
Timothy Francis Leary was an American psychologist and writer, known for his advocacy of psychedelic drugs. During a time when drugs like LSD and psilocybin were legal, Leary conducted experiments at Harvard University under the Harvard Psilocybin Project, resulting in the Concord Prison...

 at Harvard University
Harvard University
Harvard University is a private Ivy League university located in Cambridge, Massachusetts, United States, established in 1636 by the Massachusetts legislature. Harvard is the oldest institution of higher learning in the United States and the first corporation chartered in the country...

 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; however, to individuals under the influence of psilocybin, the effects may seem to last much longer, since the drug can distort the perception of time
Time perception
Time perception is a field of study within psychology and neuroscience. It refers to the sense of time, which differs from other senses since time cannot be directly perceived but must be reconstructed by the brain. Humans can perceive relatively short periods of time, in the order of milliseconds,...

. Psilocybin has a low toxicity
Toxicity
Toxicity is the degree to which a substance can damage a living or non-living organisms. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell or an organ , such as the liver...

 and a relatively low harm potential, and reports of lethal doses of the drug are rare. Several modern bioanalytical
Bioanalysis
Bioanalysis is a sub-discipline of analytical chemistry covering the quantitative measurement of xenobiotics and biotics in biological systems.-Modern bioanalytical chemistry:Many scientific endeavors are dependent upon...

 methods have been adapted to rapidly and accurately screen the levels of psilocybin in mushroom samples and body fluids. In the 2000s, there has been a revival of scientific research into the potential usefulness of psilocybin for treating a variety of medical and psychological conditions including obsessive compulsive disorder, cluster headache
Cluster headache
Cluster headache, nicknamed "suicide headache", is a neurological disease that involves, as its most prominent feature, an immense degree of pain in the head. Cluster headaches occur periodically: spontaneous remissions interrupt active periods of pain. The cause of the disease is currently unknown...

s, and anxiety related to terminal
Terminal illness
Terminal illness is a medical term popularized in the 20th century to describe a disease that cannot be cured or adequately treated and that is reasonably expected to result in the death of the patient within a short period of time. This term is more commonly used for progressive diseases such as...

 cancer. Possession of psilocybin-containing mushrooms has been outlawed in most countries, and it has been classified as scheduled by many national drug laws.

History


There is evidence to suggest that psychoactive mushrooms have been used by man in religious ceremonies for thousands of years. Rock art
Rock art
Rock art is a term used in archaeology for any human-made markings made on natural stone. They can be divided into:*Petroglyphs - carvings into stone surfaces*Pictographs - rock and cave paintings...

 discovered near the town of Villar del Humo
Villar del Humo
Villar del Humo is a municipality located in the province of Cuenca, Castile-La Mancha, Spain. According to the 2004 census , the municipality has a population of 372 inhabitants.It is an important location for prehistoric rock art...

 in Spain offers evidence that Psilocybe hispanica
Psilocybe hispanica
Psilocybe hispanica is a species of fungus in the Strophariaceae family. It produces small brown mushrooms with conical to convex caps up to in diameter and stems long by thick. Reported as new to science in 2000, it is only known from the Pyrenees mountain range in northern Spain and...

was used in religious rituals 6000 years ago; similarly, murals dated 7000 to 9000 BCE found in the Sahara desert in southeast Algeria
Algeria
Algeria , officially the People's Democratic Republic of Algeria , also formally referred to as the Democratic and Popular Republic of Algeria, is a country in the Maghreb region of Northwest Africa with Algiers as its capital.In terms of land area, it is the largest country in Africa and the Arab...

 suggest prehistoric usage of psilocybin mushrooms. In the Mayan
Maya civilization
The Maya is a Mesoamerican civilization, noted for the only known fully developed written language of the pre-Columbian Americas, as well as for its art, architecture, and mathematical and astronomical systems. Initially established during the Pre-Classic period The Maya is a Mesoamerican...

 and Aztec
Aztec
The Aztec people were certain ethnic groups of central Mexico, particularly those groups who spoke the Nahuatl language and who dominated large parts of Mesoamerica in the 14th, 15th and 16th centuries, a period referred to as the late post-classic period in Mesoamerican chronology.Aztec is the...

 cultures, psilocybin mushrooms were used for rituals and ceremonies; in Nahuatl
Nahuatl
Nahuatl is thought to mean "a good, clear sound" This language name has several spellings, among them náhuatl , Naoatl, Nauatl, Nahuatl, Nawatl. In a back formation from the name of the language, the ethnic group of Nahuatl speakers are called Nahua...

, the language of the Aztecs, the mushrooms were called teonanácatl, or "God's flesh". Following the arrival of Spanish explorers to the New World
New World
The New World is one of the names used for the Western Hemisphere, specifically America and sometimes Oceania . The term originated in the late 15th century, when America had been recently discovered by European explorers, expanding the geographical horizon of the people of the European middle...

 in the 16th century, chroniclers reported the use of mushrooms by the natives for ceremonial and religious purposes. According to the Dominican
Dominican Order
The Order of Preachers , after the 15th century more commonly known as the Dominican Order or Dominicans, is a Catholic religious order founded by Saint Dominic and approved by Pope Honorius III on 22 December 1216 in France...

 friar Diego Durán
Diego Durán
Diego Durán was a Dominican friar best known for his authorship of one of the earliest Western books on the history and culture of the Aztecs, The History of the Indies of New Spain, a book that was much criticized in his lifetime for helping the "heathen" maintain their culture.Also known as the...

 in The History of the Indies of New Spain (published circa 1581), mushrooms were eaten in festivities conducted on the occasion of the accession to the throne of Aztec emperor Moctezuma II
Moctezuma II
Moctezuma , also known by a number of variant spellings including Montezuma, Moteuczoma, Motecuhzoma and referred to in full by early Nahuatl texts as Motecuhzoma Xocoyotzin, was the ninth tlatoani or ruler of Tenochtitlan, reigning from 1502 to 1520...

 in 1502. The Franciscan
Franciscan
Most Franciscans are members of Roman Catholic religious orders founded by Saint Francis of Assisi. Besides Roman Catholic communities, there are also Old Catholic, Anglican, Lutheran, ecumenical and Non-denominational Franciscan communities....

 friar Bernardino de Sahagún
Bernardino de Sahagún
Bernardino de Sahagún was a Franciscan friar, missionary priest and pioneering ethnographer who participated in the Catholic evangelization of colonial New Spain . Born in Sahagún, Spain, in 1499, he journeyed to New Spain in 1529, and spent more than 50 years conducting interviews regarding Aztec...

 wrote of witnessing mushroom usage in his Florentine Codex
Florentine Codex
The Florentine Codex is the common name given to a 16th century ethnographic research project in Mesoamerica by Franciscan friar Bernardino de Sahagún. Bernardino originally titled it: La Historia General de las Cosas de Nueva Espana...

 (published 1545–1590). In the following passage, he described how some merchants would celebrate upon returning from a successful business trip:
Coming at the very first, at the time of feasting, they ate mushrooms when, as they said, it was the hour of the blowing of the flutes. Not yet did they partake of food; they drank only chocolate during the night. And they ate mushrooms with honey. When already the mushrooms were taking effect, there was dancing, there was weeping.... Some saw in a vision that they would die in war. Some saw in a vision that they would be devoured by wild beasts.... Some saw in a vision that they would become rich, wealthy. Some saw in a vision that they would buy slaves, would become slave owners. Some saw in a vision that they would commit adultery [and so] would have their heads bashed in, would be stoned to death.... Some saw in a vision that they would perish in the water. Some saw in a vision that they would pass to tranquility in death. Some saw in a vision that they would fall from the housetop, tumble to their death ... All such things they saw.... And when [the effects of] the mushroom ceased, they conversed with one another, spoke of what they had seen in the vision.
After the defeat of the Aztecs, the Spanish conquerors forbade traditional religious practices and rituals, including ceremonial mushroom use. For the next four centuries, the Indians of Mesoamerica hid their use of entheogens from their Spanish conquerors.

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, they published an article in Life
Life (magazine)
Life generally refers to three American magazines:*A humor and general interest magazine published from 1883 to 1936. Time founder Henry Luce bought the magazine in 1936 solely so that he could acquire the rights to its name....

magazine (Seeking the Magic Mushroom) in which they described the occurrence of hallucinatory experiences during these rituals. Later the same year they were accompanied on a followup expedition by French mycologist Roger Heim
Roger Heim
Roger Heim was a French botanist specialising in mycology and tropical phytopathology. He was known for his studies describing the anatomy of the mushroom hymenium, the systematics and phylogeny of higher fungi , the mycology of tropical fungi such as...

, who identified several of the mushrooms as Psilocybe species. Heim cultivated the mushrooms in France, and sent samples for analysis to the chemist Albert Hofmann
Albert Hofmann
Albert Hofmann was a Swiss scientist known best for being the first person to synthesize, ingest and learn of the psychedelic effects of lysergic acid diethylamide . He authored more than 100 scientific articles and a number of books, including LSD: My Problem Child...

, who was employed by the Swiss multinational pharmaceutical company Sandoz
Sandoz
Founded in 2003, Sandoz presently is the generic drug subsidiary of Novartis, a multinational pharmaceutical company. The company develops, manufactures and markets generic drugs as well as pharmaceutical and biotechnological active ingredients....

 (now Novartis). Hofmann, who had in 1938 created LSD
LSD
Lysergic acid diethylamide, abbreviated LSD or LSD-25, also known as lysergide and colloquially as acid, is a semisynthetic psychedelic drug of the ergoline family, well known for its psychological effects which can include altered thinking processes, closed and open eye visuals, synaesthesia, an...

, led a research group that isolated and identified the psychoactive compounds from Psilocybe mexicana
Psilocybe mexicana
Psilocybe mexicana is a psychedelic mushroom. It is from this species that Dr. Albert Hofmann first isolated and named the active compounds, psilocybin and psilocin in 1958. It was first used by the early natives of Central America and North America over 2,000 years ago, known to theAztecs as...

. Hofmann was aided in the discovery process by his willingness to ingest mushroom extracts
Liquid-liquid extraction
Liquid–liquid extraction, also known as solvent extraction and partitioning, is a method to separate compounds based on their relative solubilities in two different immiscible liquids, usually water and an organic solvent. It is an extraction of a substance from one liquid phase into another liquid...

 to help verify the presence of the active compounds. He and his colleagues later synthesized
Chemical synthesis
In chemistry, chemical synthesis is purposeful execution of chemical reactions to get a product, or several products. This happens by physical and chemical manipulations usually involving one or more reactions...

 a number of compounds chemically related to the naturally occurring psilocybin:
In essence, these were the same molecules except that: (1) the phosphoryl or hydroxy group at the top of the indole ring was moved around to other ring positions, and (2) different numbers of methyl groups (CH3) and other carbon chains were added to the side-chains and to the nitrogen on the indole ring to see how these changes would affect psychoactivity.


Two diethyl analogs (containing two ethyl
Ethyl group
In chemistry, an ethyl group is an alkyl substituent derived from ethane . It has the formula -C2H5 and is very often abbreviated -Et.Ethylation is the formation of a compound by introduction of the ethyl functional group, C2H5....

 groups in place of the two methyl groups) of psilocybin and psilocin were synthesized by Hofmann, 4-phosphoryloxy-N,N-diethyltryptamine
Ethocybin
Ethocybin is a homologue of the mushroom alkaloid psilocybin, and a semi-synthetic psychedelic alkaloid of the tryptamine family...

, called CEY-19, and 4-hydroxy-N,N-diethyltryptamine
4-HO-DET
4-HO-DET, also known as 4-hydroxy-diethyl-tryptamine, CZ-74, or ethocin, is a hallucinogenic drug and psychedelic compound of moderate duration. 4-HO-DET is a substituted tryptamine, structurally related to psilocin and 4-HO-DIPT.-Analogs:...

, 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
Psychotherapy
Psychotherapy is a general term referring to any form of therapeutic interaction or treatment contracted between a trained professional and a client or patient; family, couple or group...

 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
Harvard University
Harvard University is a private Ivy League university located in Cambridge, Massachusetts, United States, established in 1636 by the Massachusetts legislature. Harvard is the oldest institution of higher learning in the United States and the first corporation chartered in the country...

 became a testing ground for psilocybin, through the efforts of Timothy Leary
Timothy Leary
Timothy Francis Leary was an American psychologist and writer, known for his advocacy of psychedelic drugs. During a time when drugs like LSD and psilocybin were legal, Leary conducted experiments at Harvard University under the Harvard Psilocybin Project, resulting in the Concord Prison...

 and his associates Ralph Metzner
Ralph Metzner
Ralph Metzner Ph.D. , is an American psychologist, writer and researcher, who participated in psychedelic research at Harvard University in the early 1960s with Timothy Leary and Richard Alpert . Dr...

 and Richard Alpert (who later changed his name to Ram Dass
Ram Dass
Ram Dass is an American contemporary spiritual teacher and the author of the seminal 1971 book Be Here Now. He is known for his personal and professional associations with Timothy Leary at Harvard University in the early 1960s, for his travels to India and his relationship with the Hindu guru Neem...

). Leary was able to obtain synthesized psilocybin from Hofmann through Sandoz pharmaceutical. Some studies in the early 1960s, such as the Concord Prison Experiment
Concord Prison Experiment
The Concord Prison Experiment was designed to evaluate whether the experiences produced by the psychoactive drug psilocybin, derived from psilocybin mushrooms, combined with psychotherapy, could inspire prisoners to leave their antisocial lifestyles behind once they were released...

, suggested promising results using psilocybin in clinical psychiatry. However, according to a 2008 review of safety guidelines in human hallucinogenic research, 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, the 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
Research funding
Research funding is a term generally covering any funding for scientific research, in the areas of both "hard" science and technology and social science. The term often connotes funding obtained through a competitive process, in which potential research projects are evaluated and only the most...

 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
Carlos Castaneda
Carlos Castaneda was a Peruvian-born American anthropologist and author....

, and several books that taught the technique of growing psilocybin mushrooms. One of the most popular of these books 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
Terence McKenna
Terence Kemp McKenna was an Irish-American philosopher, psychonaut, researcher, teacher, lecturer and writer on many subjects, such as human consciousness, language, psychedelic drugs, the evolution of civilizations, the origin and end of the universe, alchemy, and extraterrestrial beings.-Early...

, entitled Psilocybin: Magic Mushroom Grower's Guide. Over 100,000 copies had been sold by 1981. As ethnobiologist Jonathan Ott
Jonathan Ott
Jonathan Ott is an ethnobotanist, writer, translator, publisher, natural products chemist and botanical researcher in the area of entheogens and their cultural and historical uses, and helped coin the term "entheogen".-Writings:...

 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 commercialized and marketed them in smartshops in the Netherlands and the UK, and on the internet. 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 regarding 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
Neuropharmacology
Neuropharmacology is the study of how drugs affect cellular function in the nervous system. There are two main branches of neuropharmacology: behavioral and molecular. Behavioral neuropharmacology focuses on the study of how drugs affect human behavior , including the study of how drug dependence...

 and neuropsychology
Neuropsychology
Neuropsychology studies the structure and function of the brain related to specific psychological processes and behaviors. The term neuropsychology has been applied to lesion studies in humans and animals. It has also been applied to efforts to record electrical activity from individual cells in...

, and the availability of brain imaging
Neuroimaging
Neuroimaging includes the use of various techniques to either directly or indirectly image the structure, function/pharmacology of the brain...

 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.

Occurrence



Psilocybin is a naturally occurring compound found in varying concentrations in over 200 species of Basidiomycota
Basidiomycota
Basidiomycota is one of two large phyla that, together with the Ascomycota, comprise the subkingdom Dikarya within the Kingdom Fungi...

 mushrooms. In a 2000 review on the worldwide distribution of hallucinogenic mushrooms, Gastón Guzmán
Gastón Guzmán
Gastón Guzmán is a Mexican mycologist and anthropologist. He is considered the world's foremost authority on the genus Psilocybe.He was born in Xalapa, Veracruz, in 1932....

 and colleagues considered these to be distributed amongst the following genera
Genus
In biology, a genus is a low-level taxonomic rank used in the biological classification of living and fossil organisms, which is an example of definition by genus and differentia...

: Psilocybe
Psilocybe
Psilocybe is a genus of small mushrooms growing worldwide. This genus is best known for its species with psychedelic or hallucinogenic properties, widely known as "magic mushrooms", though the majority of species do not contain hallucinogenic compounds...

(116 species), Gymnopilus
Gymnopilus
Gymnopilus is a genus of gilled mushrooms within the fungal family Strophariaceae containing about 200 rusty-orange spored mushroom species formerly divided among Pholiota and the defunct genus Flammula. The fruiting body is typically reddish brown to rusty orange to yellow, medium to large,...

(14), Panaeolus
Panaeolus
Panaeolus is a genus of small, black-spored, saprotrophic agarics. The word Panaeolus is Greek for "all variegated", alluding to the spotted gills of the mushrooms produced.- Characteristics :...

(13), Copelandia
Copelandia
Copelandia is a genus of mushrooms consisting of at least 12 species. Most Copelandia species have a long, thin fragile stem and are delicate, growing in grasslands on dead moss, dead grass, sand dunes, decayed wood, and dung. They are found in the tropics and neotropics of both hemispheres...

(12), Hypholoma
Hypholoma
Fungi of the genus Hypholoma are quite well known due to the commonness of Sulphur Tuft on stumps in temperate woodlands. This species is easily recognizable because the dark spores create a distinctive greenish effect on the yellow cap underside...

(6), Pluteus
Pluteus
Pluteus is a large genus of fungi with over 100 species. They are wood rotting saprobes with pink spore prints and gills that are free from the stem.Pluteus means shed or penthouse.-Characteristics of the genus :...

(6) Inocybe
Inocybe
Inocybe is a large, complex genus of mushrooms. Members of Inocybe are mycorrhizal, and some evidence shows that the high degree of speciation in the genus is due to adaptation to different trees and perhaps even local environments.-Description:...

(6), Conocybe
Conocybe
The genus Conocybe is a genus of mushrooms consisting of Conocybe tenera and at least 243 other species, with at least 50 species in North America....

(4), Panaeolina
Panaeolina
Panaeolina is a small genus of small mushrooms, containing only about four species. They are a subgroup of Panaeolus which have dark brown spores. The type species is Panaeolina foenisecii, a common lawn mushroom...

(4), Gerronema
Gerronema
Gerronema is a genus of small- to medium-sized lignicolous agarics with white, nonamyloid, basidiospores and decurrent lamellae. The genus, first described by American mycologist Rolf Singer in 1951, contains 13 species.-Description:...

(2) and Agrocybe
Agrocybe
Agrocybe, including edible fungi such as the Agrocybe cylindracea, is a genus of mushroom with similar characteristics to the Tricholoma matsutake, Agrocybe aegerita and Agrocybe parasitica. Some are poisonous mushrooms...

, Galerina
Galerina
Galerina is a genus of small brown-spored saprobic mushrooms, with over 300 species found throughout the world, from the far north to remote Macquarie Island in the Southern Ocean. Species are typically small and hygrophanous, with a slender and brittle stem. They are often found growing on wood,...

and Mycena
Mycena
Mycena is a large genus of small saprotrophic mushrooms that are rarely more than a few centimeters in width. They are characterized by a white spore print, a small conical or bell-shaped cap, and a thin fragile stem. Most are gray or brown, but a few species have brighter colors. Most have a...

(1 species each). 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 US and Canada (22), Europe (16), Asia (15), Africa (4), and Australia and associated islands (19). In general, psilocybin-containing species are dark-spored, gilled mushrooms that grow in meadows and woods of the subtropics and tropics
Tropics
The tropics is a region of the Earth surrounding the Equator. It is limited in latitude by the Tropic of Cancer in the northern hemisphere at approximately  N and the Tropic of Capricorn in the southern hemisphere at  S; these latitudes correspond to the axial tilt of the Earth...

, usually in soils rich in humus and plant debris. Psilocybin mushrooms occur on all continents, but the majority of species are found in subtropical humid forests
Tropical and subtropical moist broadleaf forests
Tropical and subtropical moist broadleaf forests , also known as tropical moist forests, are a tropical and subtropical forest biome....

. Psilocybe species commonly found in the tropics include P. cubensis
Psilocybe cubensis
Psilocybe cubensis is a species of psychedelic mushroom whose principal active compounds are psilocybin and psilocin. Commonly called Boomers, Cubes or Gold Caps, it belongs to the Strophariaceae family of fungi and was previously known as Stropharia cubensis.-Taxonomy and naming:The species was...

and P. subcubensis
Psilocybe subcubensis
Psilocybe subcubensis is a species of mushroom in the Strophariaceae family. The mushroom contains the medicinal compound psilocybin....

. P. semilanceata
Psilocybe semilanceata
Psilocybe semilanceata, commonly known as the liberty cap, is a psychedelic mushroom that contains the psychoactive compounds psilocybin and baeocystin. Of the world's psychoactive mushrooms, it is the most common in nature, and one of the most potent...

is common in Europe, Canada, and the United States, but is not found in Mexico. Although the presence or absence of psilocybin is not of much use as a chemotaxonomical
Chemotaxonomy
Chemotaxonomy , also called chemosystematics, is the attempt to classify and identify organisms , according to demonstrable differences and similarities in their biochemical compositions. The compounds studied in most of the cases are mostly proteins, amino acids and peptides...

 marker at the familial
Family (biology)
In biological classification, family is* a taxonomic rank. Other well-known ranks are life, domain, kingdom, phylum, class, order, genus, and species, with family fitting between order and genus. As for the other well-known ranks, there is the option of an immediately lower rank, indicated by the...

 level or higher, it is used to classify taxa
Taxon
|thumb|270px|[[African elephants]] form a widely-accepted taxon, the [[genus]] LoxodontaA taxon is a group of organisms, which a taxonomist adjudges to be a unit. Usually a taxon is given a name and a rank, although neither is a requirement...

 of lower taxonomic groups.

Mushroom caps
Pileus (mycology)
The pileus is the technical name for the cap, or cap-like part, of a basidiocarp or ascocarp that supports a spore-bearing surface, the hymenium. The hymenium may consist of lamellae, tubes, or teeth, on the underside of the pileus...

 tend to contain more of the psychoactive compounds than the stems
Stipe (mycology)
thumb|150px|right|Diagram of a [[basidiomycete]] stipe with an [[annulus |annulus]] and [[volva |volva]]In mycology a stipe refers to the stem or stalk-like feature supporting the cap of a mushroom. Like all tissues of the mushroom other than the hymenium, the stipe is composed of sterile hyphal...

. The spore
Spore
In biology, a spore is a reproductive structure that is adapted for dispersal and surviving for extended periods of time in unfavorable conditions. Spores form part of the life cycles of many bacteria, plants, algae, fungi and some protozoa. According to scientist Dr...

s of these mushrooms do not contain psilocybin or psilocin. The total potency
Potency (pharmacology)
In the field of pharmacology, potency is a measure of drug activity expressed in terms of the amount required to produce an effect of given intensity. A highly potent drug evokes a larger response at low concentrations, while a drug of lower potency evokes a small response at low concentrations...

 varies greatly between species and even between specimens of one species collected from the same fungus. Because most psilocybin biosynthesis occurs early in the formation of fruit bodies
Basidiocarp
In fungi, a basidiocarp, basidiome or basidioma , is the sporocarp of a basidiomycete, the multicellular structure on which the spore-producing hymenium is borne. Basidiocarps are characteristic of the hymenomycetes; rusts and smuts do not produce such structures...

 or sclerotia
Sclerotium
A sclerotium is a compact mass of hardened fungal mycelium containing food reserves. One role of sclerotia is to survive environmental extremes. In some higher fungi such as ergot, sclerotia become detached and remain dormant until a favorable opportunity for growth. Other fungi that produce...

, 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 1.5% of the dry weight
Dry matter
The dry matter is a measurement of the mass of something when completely dried.The dry matter of plant and animal material would be its solids, i.e. all its constituents excluding water. The dry matter of food would include carbohydrates, fats, proteins, vitamins, minerals, and antioxidants...

) and depends on species, growth and drying conditions, and mushroom size. The drug is more stable in dried than fresh mushrooms; dried mushrooms retain their potency for months or even years, while mushrooms stored fresh for four weeks contain only traces of the original psilocybin. Mature mycelia contain some psilocybin, while young mycelia (recently germinated
Germination
Germination is the process in which a plant or fungus emerges from a seed or spore, respectively, and begins growth. The most common example of germination is the sprouting of a seedling from a seed of an angiosperm or gymnosperm. However the growth of a sporeling from a spore, for example the...

 from spores) lack appreciable amounts. Many species of mushrooms containing psilocybin also contain small amounts of the analog compounds baeocystin
Baeocystin
Baeocystin is a mushroom alkaloid and analog of the psychedelic hallucinogenic drug psilocybin, a tryptamine derivative. It is found as a minor compound in most psychoactive mushrooms together with psilocybin, norbaeocystin, and psilocin...

 and norbaeocystin
Norbaeocystin
Norbaeocystin is a mushroom alkaloid and analog of the psychedelic hallucinogenic drug psilocybin. It is found as a minor compound in most psilocybin mushrooms together with psilocin, psilocybin and baeocystin....

, chemicals thought to be biogenic precursors
Precursor (chemistry)
In chemistry, a precursor is a compound that participates in the chemical reaction that produces another compound. In biochemistry, the term "precursor" is used more specifically to refer to a chemical compound preceding another in a metabolic pathway....

. Most species of psilocybin-containing mushrooms bruise blue when handled or damaged due to the oxidization
Redox
Redox reactions describe all chemical reactions in which atoms have their oxidation state changed....

 of phenolic compounds. This reaction, however, is not a definitive method of identification or determining a mushroom's potency.

Chemistry


Psilocybin (O-phosphoryl-4-hydroxy-N,N-dimethyltryptamine
Dimethyltryptamine
N,N-Dimethyltryptamine is a naturally occurring psychedelic compound of the tryptamine family. DMT is found in several plants, and also in trace amounts in humans and other mammals, where it is originally derived from the essential amino acid tryptophan, and ultimately produced by the enzyme INMT...

 or 4-PO-DMT) is a prodrug
Prodrug
A prodrug is a pharmacological substance administered in an inactive form. Once administered, the prodrug is metabolised in vivo into an active metabolite, a process termed bioactivation. The rationale behind the use of a prodrug is generally for absorption, distribution, metabolism, and...

 that is converted into the pharmacologically
Pharmacology
Pharmacology is the branch of medicine and biology concerned with the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function...

 active compound psilocin
Psilocin
Psilocin , an aromatic compound, sometimes also spelled psilocine, psilocyn, or psilotsin, is a psychedelic mushroom alkaloid. It is found in most psychedelic mushrooms together with its phosphorylated counterpart psilocybin...

 in the body by a dephosphorylation
Dephosphorylation
Dephosphorylation is the essential process of removing phosphate groups from an organic compound by hydrolysis. Its opposite is phosphorylation...

 reaction. This chemical reaction
Chemical reaction
A chemical reaction is a process that leads to the transformation of one set of chemical substances to another. Chemical reactions can be either spontaneous, requiring no input of energy, or non-spontaneous, typically following the input of some type of energy, such as heat, light or electricity...

 takes place under strongly acidic conditions, or under physiological conditions in the body, through the action of enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

s called phosphatase
Phosphatase
A phosphatase is an enzyme that removes a phosphate group from its substrate by hydrolysing phosphoric acid monoesters into a phosphate ion and a molecule with a free hydroxyl group . This action is directly opposite to that of phosphorylases and kinases, which attach phosphate groups to their...

s. Oxidization of psilocin by the enzyme hydroxyindole oxidase yields the deep blue-colored compound ortho-quinone
1,2-Benzoquinone
1,2-Benzoquinone, also called ortho-benzoquinone or cyclohexa-3,5-diene-1,2-dione, is a ketone, with formula C6H4O2. It is one of the two isomers of quinone, the other being 1,4-benzoquinone....

. This compound readily undergoes electron transfer
Electron transfer
Electron transfer is the process by which an electron moves from an atom or a chemical species to another atom or chemical species...

, a chemical feature that contributes to the biochemical effects of psilocybin.

Psilocybin is a tryptamine
Tryptamine
Tryptamine is a monoamine alkaloid found in plants, fungi, and animals. It is based around the indole ring structure, and is chemically related to the amino acid tryptophan, from which its name is derived...

 compound having a chemical structure
Chemical structure
A chemical structure includes molecular geometry, electronic structure and crystal structure of molecules. Molecular geometry refers to the spatial arrangement of atoms in a molecule and the chemical bonds that hold the atoms together. Molecular geometry can range from the very simple, such as...

 derived from the amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

 tryptophan
Tryptophan
Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...

 and containing an indole
Indole
Indole is an aromatic heterocyclic organic compound. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered nitrogen-containing pyrrole ring. Indole is a popular component of fragrances and the precursor to many pharmaceuticals. Compounds that contain an...

 linked to an ethylamine
Ethylamine
Ethylamine is an organic compound with the formula CH3CH2NH2. This colourless gas has a strong ammonia-like odor. It is miscible with virtually all solvents and is considered to be a weak base, as is typical for amines. Ethylamine is widely used in chemical industry and organic...

 substituent
Substituent
In organic chemistry and biochemistry, a substituent is an atom or group of atoms substituted in place of a hydrogen atom on the parent chain of a hydrocarbon...

; psilocybin bears a close structural resemblance to the neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...

 serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

 (5-hydroxytryptamine). Biosynthetically, the biochemical transformation from tryptophan to psilocybin involves several enzyme reactions: decarboxylation
Decarboxylation
Decarboxylation is a chemical reaction that releases carbon dioxide . Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is the first chemical step in photosynthesis, is called carbonation, the addition of CO2 to...

, methylation
Methylation
In the chemical sciences, methylation denotes the addition of a methyl group to a substrate or the substitution of an atom or group by a methyl group. Methylation is a form of alkylation with, to be specific, a methyl group, rather than a larger carbon chain, replacing a hydrogen atom...

 at the N9 position, 4-hydroxylation
Hydroxylation
Hydroxylation is a chemical process that introduces a hydroxyl group into an organic compound. In biochemistry, hydroxylation reactions are often facilitated by enzymes called hydroxylases. Hydroxylation is the first step in the oxidative degradation of organic compounds in air...

, and O-phosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....

. Isotopic labeling
Isotopic labeling
Isotopic labeling is a technique for tracking the passage of a sample of substance through a system. The substance is 'labeled' by including unusual isotopes in its chemical composition...

 experiments suggest that tryptophan decarboxylation is the first biosynthetic step and that O-phosphorylation is the final step. The precise sequence of the intermediate steps is not known with certainty, and the biosynthetic pathway may differ between species.

Psilocybin is a zwitterion
Zwitterion
In chemistry, a zwitterion is a neutral molecule with a positive and a negative electrical charge at different locations within that molecule. Zwitterions are sometimes also called inner salts.-Examples:...

ic alkaloid
Alkaloid
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...

 that is soluble
Solubility
Solubility is the property of a solid, liquid, or gaseous chemical substance called solute to dissolve in a solid, liquid, or gaseous solvent to form a homogeneous solution of the solute in the solvent. The solubility of a substance fundamentally depends on the used solvent as well as on...

 in water, moderately soluble in methanol
Methanol
Methanol, also known as methyl alcohol, wood alcohol, wood naphtha or wood spirits, is a chemical with the formula CH3OH . It is the simplest alcohol, and is a light, volatile, colorless, flammable liquid with a distinctive odor very similar to, but slightly sweeter than, ethanol...

 and ethanol
Ethanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...

, and insoluble in most organic solvents. Exposure to light is detrimental to the stability of aqueous solution
Aqueous solution
An aqueous solution is a solution in which the solvent is water. It is usually shown in chemical equations by appending aq to the relevant formula, such as NaCl. The word aqueous means pertaining to, related to, similar to, or dissolved in water...

s of psilocybin, and will cause it to rapidly oxidize—an important consideration when using it as an analytical standard
Standard solution
In analytical chemistry, a standard solution is a solution containing a precisely known concentration of an element or a substance i.e, a known weight of solute is dissolved to make a specific volume. It is prepared using a standard substance, such as a primary standard. Standard solutions are used...

. Osamu Shirota and colleagues reported a method for the large-scale synthesis of psilocybin without chromatographic
Chromatography
Chromatography is the collective term for a set of laboratory techniques for the separation of mixtures....

 purification in 2003. Starting with 4-hydroxyindole, they generated psilocybin from psilocin at an 85% yield, a marked improvement over yields reported from previous syntheses. Purified psilocybin is a white, needle-like crystalline powder with a melting point
Melting point
The melting point of a solid is the temperature at which it changes state from solid to liquid. At the melting point the solid and liquid phase exist in equilibrium. The melting point of a substance depends on pressure and is usually specified at standard atmospheric pressure...

 between 220 –, and a slightly ammonia
Ammonia
Ammonia is a compound of nitrogen and hydrogen with the formula . It is a colourless gas with a characteristic pungent odour. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to food and fertilizers. Ammonia, either directly or...

-like taste.

Analytical methods


Several relatively simple chemical test
Chemical test
In chemistry, a chemical test is a qualitative or quantitative procedure designed to prove the existence of, or to quantify, a chemical compound or chemical group with the aid of a specific reagent...

s—commercially available as reagent testing kits—can be used to assess the presence of psilocybin in mushroom extract
Extract
An extract is a substance made by extracting a part of a raw material, often by using a solvent such as ethanol or water. Extracts may be sold as tinctures or in powder form....

s. The drug reacts in the Marquis test
Marquis reagent
The Marquis reagent is used as a simple spot-test to presumptively identify alkaloids as well as other compounds. It is composed of a mixture of formaldehyde and concentrated sulfuric acid, which is dripped onto the substance being tested...

 to produce a yellow color, and a green color in the Mandelin test. Neither of these tests, however, is specific for psilocybin; for example, the Marquis test will react with many classes of controlled drugs, such as those containing primary amino groups and unsubstituted benzene rings, including amphetamine
Amphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...

 and methamphetamine
Methamphetamine
Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...

. Ehrlich's reagent
Ehrlich's reagent
para-Dimethylaminobenzaldehyde is an organic compound containing amine and aldehyde moieties which is used in Ehrlich's reagent for determination of hydrazine.-Urobilinogen determination:...

 and DMACA reagent
DMACA reagent
DMACA is an histological dye used to detect indole production in cells. It is used for the rapid identification of bacteria containing tryptophanase enzyme systems....

 are used as sprays to detect the drug after thin layer chromatographic
Thin layer chromatography
Thin layer chromatography is a chromatography technique used to separate mixtures. Thin layer chromatography is performed on a sheet of glass, plastic, or aluminum foil, which is coated with a thin layer of adsorbent material, usually silica gel, aluminium oxide, or cellulose...

 analysis. Many modern analytical
Analytical chemistry
Analytical chemistry is the study of the separation, identification, and quantification of the chemical components of natural and artificial materials. Qualitative analysis gives an indication of the identity of the chemical species in the sample and quantitative analysis determines the amount of...

 techniques have been adapted to determine the quantity of psilocybin in mushroom material. The earliest techniques used gas chromatography; however, a problem with this method is that psilocybin dephosphorylates to psilocin prior to analysis, making it difficult to discriminate between the two drugs. In forensic toxicology
Forensic toxicology
Forensic toxicology is the use of toxicology and other disciplines such as analytical chemistry, pharmacology and clinical chemistry to aid medical or legal investigation of death, poisoning, and drug use...

, techniques involving gas chromatography coupled to mass spectrometry
Gas chromatography-mass spectrometry
Gas chromatography–mass spectrometry is a method that combines the features of gas-liquid chromatography and mass spectrometry to identify different substances within a test sample. Applications of GC-MS include drug detection, fire investigation, environmental analysis, explosives investigation,...

 (GC–MS) are the most widely used due to their high sensitivity and ability to separate compounds in complex biological mixtures. These techniques include ion mobility spectrometry, capillary zone electrophoresis, ultraviolet spectroscopy, and infrared spectroscopy
Infrared spectroscopy
Infrared spectroscopy is the spectroscopy that deals with the infrared region of the electromagnetic spectrum, that is light with a longer wavelength and lower frequency than visible light. It covers a range of techniques, mostly based on absorption spectroscopy. As with all spectroscopic...

. High performance liquid chromatography
High performance liquid chromatography
High-performance liquid chromatography , HPLC, is a chromatographic technique that can separate a mixture of compounds and is used in biochemistry and analytical chemistry to identify, quantify and purify the individual components of the mixture.HPLC typically utilizes different types of stationary...

 (HPLC) is used with ultraviolet, fluorescence, electrochemical, and electrospray
Electrospray ionization
Electrospray ionization is a technique used in mass spectrometry to produce ions. It is especially useful in producing ions from macromolecules because it overcomes the propensity of these molecules to fragment when ionized...

 mass spectrometric detection methods.

Various chromatographic methods have been developed to detect psilocin in body fluids
Bodily fluid
Body fluid or bodily fluids are liquids originating from inside the bodies of living people. They include fluids that are excreted or secreted from the body as well as body water that normally is not.Body fluids include:-Body fluids and health:...

: 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
Liquid-liquid extraction
Liquid–liquid extraction, also known as solvent extraction and partitioning, is a method to separate compounds based on their relative solubilities in two different immiscible liquids, usually water and an organic solvent. It is an extraction of a substance from one liquid phase into another liquid...

, followed by derivatization
Derivatization
Derivatization is a technique used in chemistry which transforms a chemical compound into a product of similar chemical structure, called a derivative....

 of the extracts in the case of GC–MS. A specific immunoassay
Immunoassay
An immunoassay is a biochemical test that measures the presence or concentration of a substance in solutions that frequently contain a complex mixture of substances. Analytes in biological liquids such as serum or urine are frequently assayed using immunoassay methods...

 has also been developed to detect psilocin in whole blood samples. A 2009 publication reported using HPLC to obtain a high-speed separation of forensically important illicit drugs including psilocybin and psilocin, which were identifiable within 0.5 min of analysis. These analytical techniques to determine psilocybin concentrations in body fluids are, however, not routinely available, and not typically used in clinical settings.

Pharmacology



Psilocybin is rapidly dephosphorylated in the body to psilocin, which then acts as a partial agonist
Partial agonist
Partial agonists bind and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist...

 to several receptors involved with the neurotransmission
Neurotransmission
Neurotransmission , also called synaptic transmission, is the process by which signaling molecules called neurotransmitters are released by a neuron , and bind to and activate the receptors of another neuron...

 of serotonin. Psilocin has a high affinity for the 5-HT2A
5-HT2A receptor
The mammalian 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor . This is the main excitatory receptor subtype among the GPCRs for serotonin , although 5-HT2A may also have an inhibitory effect on certain areas such...

 serotonin receptor in the brain, where it mimics the effects of serotonin (5-hydroxytryptamine, or 5-HT). Psilocin binds less tightly to other serotonergic receptors 5-HT1A
5-HT1A receptor
The 5-HT1A receptor is a subtype of 5-HT receptor that binds the endogenous neurotransmitter serotonin . It is a G protein-coupled receptor that is coupled to Gi/Go and mediates inhibitory neurotransmission...

, 5-HT1D
5-HT1D receptor
5-hydroxytryptamine receptor 1D, also known as HTR1D, is a 5-HT receptor, but also denotes the human gene encoding it. 5-HT1D acts on the central nervous system, and affects locomotion and anxiety...

, and 5-HT2C
5-HT2C receptor
The 5-HT2C receptor is a subtype of 5-HT receptor that binds the endogenous neurotransmitter serotonin . It is a G protein-coupled receptor that is coupled to Gq/G11 and mediates excitatory neurotransmission. HTR2C denotes the human gene encoding for the receptor, that in humans is located at the...

. Serotonin receptors are located in numerous parts of the brain including the cerebral cortex
Cerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...

, and are involved in a wide range of functions, including regulation of mood and motivation. The psychotomimetic
Psychotomimetic
A drug with psychotomimetic actions mimics the symptoms of psychosis, including delusions and/or delirium, as opposed to just hallucinations. Some drugs of the opioid class have psychotomimetic effects, such as pentazocine and butorphanol....

 (psychosis-mimicking) effects of psilocin can be blocked in a dose-dependent fashion by the 5-HT2A antagonist
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...

 drugs ketanserin
Ketanserin
Ketanserin is a drug with affinity for multiple G protein-coupled receptors . Initially it was believed to be a highly selective antagonist for serotonin 5-HT2A receptors, however this is not true. Ketanserin only has moderate selectivity for 5-HT2A receptors over 5-HT2C receptors...

 and risperidone
Risperidone
Risperidone is a second generation or atypical antipsychotic, sold under the trade name . It is used to treat schizophrenia , schizoaffective disorder, the mixed and manic states associated with bipolar disorder, and irritability in people with autism...

. Although the 5-HT2A receptor is responsible for most of the effects of psilocybin, various lines of evidence have shown that interactions with non-5-HT2A receptors also contribute to the subjective and behavioral effects of the drug. For example, psilocybin indirectly increases the concentration of the neurotransmitter dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 in the basal ganglia
Basal ganglia
The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...

, and some psychomimetic symptoms of psilocybin are reduced by haloperidol
Haloperidol
Haloperidol is a typical antipsychotic. It is in the butyrophenone class of antipsychotic medications and has pharmacological effects similar to the phenothiazines....

, an antagonist of dopamine receptor D2
Dopamine receptor D2
Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the DRD2 gene.- Function :This gene encodes the D2 subtype of the dopamine receptor. This G protein-coupled receptor inhibits adenylyl cyclase activity...

. Taken together, these suggest that there may be an indirect dopaminergic
Dopaminergic
Dopaminergic means related to the neurotransmitter dopamine. For example, certain proteins such as the dopamine transporter , vesicular monoamine transporter 2 , and dopamine receptors can be classified as dopaminergic, and neurons which synthesize or contain dopamine and synapses with dopamine...

 contribution to psilocybin's psychotic effects.

The chemical structures of psilocybin and related analogs have been used in computational biology
Computational biology
Computational biology involves the development and application of data-analytical and theoretical methods, mathematical modeling and computational simulation techniques to the study of biological, behavioral, and social systems...

 to help model
Molecular modelling
Molecular modelling encompasses all theoretical methods and computational techniques used to model or mimic the behaviour of molecules. The techniques are used in the fields of computational chemistry, computational biology and materials science for studying molecular systems ranging from small...

 the structure
Protein structure prediction
Protein structure prediction is the prediction of the three-dimensional structure of a protein from its amino acid sequence — that is, the prediction of its secondary, tertiary, and quaternary structure from its primary structure. Structure prediction is fundamentally different from the inverse...

, function, and ligand
Ligand (biochemistry)
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. In a narrower sense, it is a signal triggering molecule, binding to a site on a target protein.The binding occurs by intermolecular forces, such as ionic bonds, hydrogen...

-binding properties of the 5-HT2C G-protein-coupled receptor. In contrast to LSD, psilocybin and psilocin have no affinity for the dopamine D2
Dopamine receptor D2
Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the DRD2 gene.- Function :This gene encodes the D2 subtype of the dopamine receptor. This G protein-coupled receptor inhibits adenylyl cyclase activity...

 receptor.

Toxicity and harm potential



The toxicity
Toxicity
Toxicity is the degree to which a substance can damage a living or non-living organisms. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell or an organ , such as the liver...

 of psilocybin is low; in rats, the oral is 280 milligrams per kilogram (mg/kg), approximately one and a half times that of caffeine
Caffeine
Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...

. When administered intravenously in rabbits, psilocybin's LD50 is approximately 12.5 mg/kg. Based on the results of animal studies, the lethal dose
Lethal dose
A lethal dose is an indication of the lethality of a given substance or type of radiation. Because resistance varies from one individual to another, the 'lethal dose' represents a dose at which a given percentage of subjects will die...

 of psilocybin has been extrapolated to be 6 grams, 1000 times greater than the effective dose
Effective dose (pharmacology)
An effective dose in pharmacology is the dose or amount of drug that produces a therapeutic response or desired effect in some fraction of the subjects taking it....

 of 6 milligrams. The Registry of Toxic Effects of Chemical Substances assigns psilocybin a relatively high therapeutic index
Therapeutic index
The therapeutic index is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes death or toxicity ....

 of 641 (higher values correspond to a better safety profile); for comparison, the therapeutic indices of aspirin
Aspirin
Aspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...

 and nicotine
Nicotine
Nicotine is an alkaloid found in the nightshade family of plants that constitutes approximately 0.6–3.0% of the dry weight of tobacco, with biosynthesis taking place in the roots and accumulation occurring in the leaves...

 are 199 and 21, respectively. The lethal dose from psilocybin toxicity alone is unknown at recreational or medicinal levels, and has rarely been documented—as of 2011, only two cases attributed to overdosing on hallucinogenic mushrooms (without simultaneous use of other drugs) have been reported in the scientific literature. Psilocybin makes up roughly 1% of the weight of Psilocybe cubensis mushrooms, and so nearly 1.7 kilograms (3.7 lb) of dried mushrooms, or 17 kilograms (37.5 lb) of fresh mushrooms, would be required for a 60 kilograms (132.3 lb) person to reach the 280 mg/kg LD50 value of rats. Although no studies have indicated that the drug causes birth defects, it is recommended that pregnant women avoid its usage.

Repeated use of psilocybin does not lead to physical dependence on the drug. 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
Substance dependence
The section about substance dependence in the Diagnostic and Statistical Manual of Mental Disorders does not use the word addiction at all. It explains:...

 in adulthood; this was in contrast to adolescent usage of cannabis
Cannabis
Cannabis is a genus of flowering plants that includes three putative species, Cannabis sativa, Cannabis indica, and Cannabis ruderalis. These three taxa are indigenous to Central Asia, and South Asia. Cannabis has long been used for fibre , for seed and seed oils, for medicinal purposes, and as a...

, cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...

, inhalant
Inhalant
Inhalants are a broad range of drugs whose volatile vapors are taken in via the nose and trachea. They are taken by volatilization, and do not include drugs that are inhaled after burning or heating...

s, anxiolytic
Anxiolytic
An anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...

 medicines, and stimulant
Stimulant
Stimulants are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include enhanced alertness, wakefulness, and locomotion, among others...

s, all of which were associated with "an excess risk of developing clinical features associated with drug dependence". Similarly, a 2010 Dutch study ranked the relative harm of psilocybin mushrooms compared to a selection of 19 recreational drugs, including alcohol
Ethanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...

, cannabis, cocaine, ecstasy, heroin, and tobacco
Tobacco
Tobacco is an agricultural product processed from the leaves of plants in the genus Nicotiana. It can be consumed, used as a pesticide and, in the form of nicotine tartrate, used in some medicines...

. Experts rated the drugs for their acute and chronic toxicity, addictive potency, and social harm. Magic mushrooms were ranked as the illicit drug with the lowest harm, corroborating conclusions reached earlier by expert groups in the United Kingdom.

Physiology


The effects of the drug begin 10–40 minutes after ingestion of psilocybin-containing mushrooms, and last 2–6 hours depending on dose, species, and individual metabolism. A dosage of 4–10 mg, corresponding roughly to 50–300 microgram
Microgram
In the metric system, a microgram is a unit of mass equal to one millionth of a gram , or 1/1000 of a milligram. It is one of the smallest units of mass commonly used...

s per kilogram (µg/kg) of body weight, is required to induce psychedelic effects. A typical recreational dosage is 10–50 mg psilocybin. However, a small number of people are unusually sensitive to psilocybin's effects, such that a normally threshold-level dose of about 2 mg of psilocybin can result in effects usually associated with medium or high doses. Conversely, there are some who require relatively high doses of psilocybin to experience noticeable effects. Individual brain chemistry and metabolism play a large role in determining a person's response to psilocybin.

Based on studies using animals
Animal model
An animal model is a living, non-human animal used during the research and investigation of human disease, for the purpose of better understanding the disease without the added risk of causing harm to an actual human being during the process...

, 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
Bile
Bile or gall is a bitter-tasting, dark green to yellowish brown fluid, produced by the liver of most vertebrates, that aids the process of digestion of lipids in the small intestine. In many species, bile is stored in the gallbladder and upon eating is discharged into the duodenum...

 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. Psilocybin is metabolized mostly in the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

, where it becomes psilocin, which is broken down by the enzyme monoamine oxidase
Monoamine oxidase
L-Monoamine oxidases are a family of enzymes that catalyze the oxidation of monoamines. They are found bound to the outer membrane of mitochondria in most cell types in the body. The enzyme was originally discovered by Mary Bernheim in the liver and was named tyramine 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
Glucuronide
A glucuronide, also known as glucuronoside, is any substance produced by linking glucuronic acid to another substance via a glycosidic bond...

; this is a biochemical mechanism animals use to eliminate toxic substances by linking them with glucuronic acid
Glucuronic acid
Glucuronic acid is a carboxylic acid. Its structure is similar to that of glucose. However, glucuronic acid's sixth carbon is oxidized to a carboxylic acid...

, which can then be excreted in the urine. 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.

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
Cross-tolerance
Cross-tolerance refers to a pharmacological phenomenon, in which a patient being treated with a drug exhibits a physiological resistance to that medication as a result of tolerance to a pharmacologically similar drug. In other words, there is a decrease in response to one drug due to exposure to...

 can develop between psilocybin and the pharmacologically similar LSD; further, cross-tolerance also develops between psilocybin and phenylethylamines such as mescaline
Mescaline
Mescaline or 3,4,5-trimethoxyphenethylamine is a naturally occurring psychedelic alkaloid of the phenethylamine class used mainly as an entheogen....

 and 2,5-dimethoxy-4-methylamphetamine
2,5-Dimethoxy-4-methylamphetamine
2,5-Dimethoxy-4-methylamphetamine is a psychedelic and a substituted amphetamine...

. Monoamine oxidase inhibitor
Monoamine oxidase inhibitor
Monoamine oxidase inhibitors are a class of antidepressant drugs prescribed for the treatment of depression. They are particularly effective in treating atypical depression....

s (MAOI) have been known to sustain the effects of psilocybin for longer periods; people who are taking an MAOI for a medical condition may experience enhanced effects. Acetaldehyde
Acetaldehyde
Acetaldehyde is an organic chemical compound with the formula CH3CHO or MeCHO. It is one of the most important aldehydes, occurring widely in nature and being produced on a large scale industrially. Acetaldehyde occurs naturally in coffee, bread, and ripe fruit, and is produced by plants as part...

, one of the primary breakdown metabolites of consumed alcohol, reacts with biogenic amines present in the body to produce MAOIs related to tetrahydroisoquinoline
Tetrahydroisoquinoline
Tetrahydroisoquinoline is a secondary amine with the chemical formula C9H11N.-Reactions:Like other secondary amines, tetrahydroisoquinoline can be oxidized to the corresponding nitrone using hydrogen peroxide, catalyzed by selenium dioxide....

 and β-carboline
Beta-carboline
β-Carboline is an organic amine that is the prototype of a class of compounds known as β-carbolines.-Pharmacology:...

, and thus enhance the psychoactive effects of psilocybin. A similar effect has been suggested for tobacco users.

Effects



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
Set and setting
Set and setting describes the context for psychoactive and particularly psychedelic drug experiences: one's mindset and the setting in which the user has the experience. This is especially relevant for psychedelic or hallucinogenic experiences...

. In the early 1960s, Timothy Leary
Timothy Leary
Timothy Francis Leary was an American psychologist and writer, known for his advocacy of psychedelic drugs. During a time when drugs like LSD and psilocybin were legal, Leary conducted experiments at Harvard University under the Harvard Psilocybin Project, resulting in the Concord Prison...

 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 a warm, supportive environment free from distractions, 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. Those placed in groups of more than eight individuals generally felt that the groups were less supportive, and their experiences were less pleasant. Conversely, smaller groups (fewer than six individuals) were seen as more supportive and participants reported having more positive reactions to the drug. Leary and colleagues proposed that psilocybin heightens suggestibility
Suggestibility
Suggestibility is the quality of being inclined to accept and act on the suggestions of others.A person experiencing intense emotions tends to be more receptive to ideas and therefore more suggestible. Generally, suggestibility decreases as age increases...

, 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
Euphoria
Euphoria is an emotional and mental state defined as a sense of great elation and well being.Euphoria may also refer to:* Euphoria , a genus of scarab beetles* Euphoria, a genus name previously used for the longan and other trees...

, joy, and depression
Depression (mood)
Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...

. About a third of users report feelings of anxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

 or paranoia
Paranoia
Paranoia [] is a thought process believed to be heavily influenced by anxiety or fear, often to the point of irrationality and delusion. Paranoid thinking typically includes persecutory beliefs, or beliefs of conspiracy concerning a perceived threat towards oneself...

. At low doses, hallucinatory effects may occur, including enhancement of colors and the animation of geometric shapes. Closed-eye hallucination
Closed-eye hallucination
Closed-eye hallucinations and closed-eye visualizations are a distinct class of hallucination. These types of hallucinations generally only occur when one's eyes are closed or when one is in a darkened room. They are a form of phosphene....

 may occur, in which the affected individual sees multicolored geometric shapes and vivid imaginative sequences. Some individuals report experiencing synesthesia
Synesthesia
Synesthesia , from the ancient Greek , "together," and , "sensation," is a neurologically based condition in which stimulation of one sensory or cognitive pathway leads to automatic, involuntary experiences in a second sensory or cognitive pathway...

, such as tactile sensations when viewing colors. At higher doses, the altered state of consciousness afforded by psilocybin can lead to "Intensification of affective
Affect (psychology)
Affect refers to the experience of feeling or emotion. Affect is a key part of the process of an organism's interaction with stimuli. The word also refers sometimes to affect display, which is "a facial, vocal, or gestural behavior that serves as an indicator of affect" .The affective domain...

 responses, enhanced ability for introspection, regression
Regression (psychology)
Regression, according to psychoanalyst Sigmund Freud, is a defense mechanism leading to the temporary or long-term reversion of the ego to an earlier stage of development rather than handling unacceptable impulses in a more adult way...

 to primitive and childlike thinking, and activation of vivid memory traces with pronounced emotional undertones". Open-eye visuals are more common, and may be very detailed although rarely confused with reality.

A 2011 study by Roland R. Griffiths and colleagues suggests that a single high dosage of psilocybin can cause long-term changes in the personality
Personality psychology
Personality psychology is a branch of psychology that studies personality and individual differences. Its areas of focus include:* Constructing a coherent picture of the individual and his or her major psychological processes...

 of its users. Changes in personality were assessed using the Revised NEO Personality Inventory
Revised NEO Personality Inventory
The Revised NEO Personality Inventory, or NEO PI-R, is a psychological personality inventory; a 240-item measure of the Five Factor Model: Extraversion, Agreeableness, Conscientiousness, Neuroticism, and Openness to Experience. Additionally, the test measures six subordinate dimensions of each of...

, which describes people's personalities according to five factors: neuroticism
Neuroticism
Neuroticism is a fundamental personality trait in the study of psychology. It is an enduring tendency to experience negative emotional states. Individuals who score high on neuroticism are more likely than the average to experience such feelings as anxiety, anger, guilt, and depressed mood...

, extroversion, conscientiousness
Conscientiousness
Conscientiousness is the trait of being painstaking and careful, or the quality of acting according to the dictates of one's conscience. It includes such elements as self-discipline, carefulness, thoroughness, organization, deliberation , and need for achievement. It is an aspect of what has...

, agreeableness
Agreeableness
Agreeableness is a tendency to be pleasant and accommodating in social situations. In contemporary personality psychology, agreeableness is one of the five major dimensions of personality structure, reflecting individual differences in concern for cooperation and social harmony. People who score...

, and openness
Openness
Openness is the quality of being open. It sometimes refers to a very general philosophical position from which some individuals and organizations operate, often highlighted by a decision-making process recognizing communal management by distributed stakeholders rather than a centralized authority...

. In the study, about half of the participants—described as healthy, "spiritually active", and many possessing postgraduate degrees
Postgraduate diploma
A postgraduate diploma is a postgraduate qualification awarded typically after a bachelor's degree. It can be contrasted with a graduate diploma...

—showed an increase in the personality dimension of "openness", 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." It is not known whether these results can be generalized to larger populations.

Physical effects


The physical side effect
Side effect
In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequences of the use of a drug.Occasionally, drugs are...

s resulting from psilocybin usage are generally not considered significant. Common responses include: pupil dilation (93%); changes in heart rate
Heart rate
Heart rate is the number of heartbeats per unit of time, typically expressed as beats per minute . Heart rate can vary as the body's need to absorb oxygen and excrete carbon dioxide changes, such as during exercise or sleep....

 (100%), including increases (56%), decreases (13%), and variable responses (31%); changes in blood pressure
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...

 (84%), including hypotension
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...

 (34%), hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

 (28%), and general instability (22%); changes in stretch reflex
Stretch reflex
The stretch reflex is a muscle contraction in response to stretching within the muscle. It is a monosynaptic reflex which provides automatic regulation of skeletal muscle length....

 (86%), including increases (80%) and decreases (6%); nausea (44%); tremor
Tremor
A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving to-and-fro movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, face, head, vocal folds, trunk, and legs. Most tremors occur in the...

 (25%); and dysmetria
Dysmetria
Dysmetria refers to a lack of coordination of movement typified by the undershoot or overshoot of intended position with the hand, arm, leg, or eye...

 (16%) (inability to properly direct or limit motions). The temporary increases in blood pressure caused by the drug can be a risk factor
Risk factor
In epidemiology, a risk factor is a variable associated with an increased risk of disease or infection. Sometimes, determinant is also used, being a variable associated with either increased or decreased risk.-Correlation vs causation:...

 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 club
Nightclub
A nightclub is an entertainment venue which usually operates late into the night...

 goers in the UK found that nausea or vomiting was experienced by over a quarter of those who had used hallucinogenic 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
Electrolyte
In chemistry, an electrolyte is any substance containing free ions that make the substance electrically conductive. The most typical electrolyte is an ionic solution, but molten electrolytes and solid electrolytes are also possible....

 levels, blood sugar
Blood sugar
The blood sugar concentration or blood glucose level is the amount of glucose present in the blood of a human or animal. Normally in mammals, the body maintains the blood glucose level at a reference range between about 3.6 and 5.8 mM , or 64.8 and 104.4 mg/dL...

 levels, or liver toxicity tests
Liver function tests
Liver function tests , are groups of clinical biochemistry laboratory blood assays designed to give information about the state of a patient's liver. The parameters measured include PT/INR, aPTT, albumin, billirubin and others...

.

Perceptual distortions



Psilocybin is known to strongly influence the subjective experience of the passage of time
Time perception
Time perception is a field of study within psychology and neuroscience. It refers to the sense of time, which differs from other senses since time cannot be directly perceived but must be reconstructed by the brain. Humans can perceive relatively short periods of time, in the order of milliseconds,...

. Users often feel as if time is slowed down, resulting in the perception that "minutes appear to be hours" or "time is standing still". These effects can be tested experimentally with timing tasks, in which subjects are tested on their ability to accurately reproduce time intervals of different durations, or to synchronize movements to a sequence of regularly repeated tones. 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
Tapping rate
The tapping rate is a psychological test given to assess the integrity of the neuromuscular system and examine motor control. The finger tapping test has the advantage of being a relatively pure neurologically driven motor task because the inertial and intersegmental interactions are so small that...

. These results are consistent with the drug's role in affecting prefrontal cortex
Prefrontal cortex
The prefrontal cortex is the anterior part of the frontal lobes of the brain, lying in front of the motor and premotor areas.This brain region has been implicated in planning complex cognitive behaviors, personality expression, decision making and moderating correct social behavior...

 activity, and the role that the prefrontal cortex is known to play in time perception. However, the neurochemical
Neurochemical
A neurochemical is an organic molecule, such as serotonin, dopamine, or nerve growth factor, that participates in neural activity. The science of neurochemistry studies the functions of neurochemicals.-Prominent neurochemicals:...

 basis of psilocybin's effects on the perception of time are not known with certainty.

Users having a pleasant experience can feel an ecstatic 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
Bad trip
Bad trip is a disturbing experience sometimes associated with use of a psychedelic drug such as LSD, Salvinorin A, DXM, mescaline, psilocybin, DMT and sometimes even other drugs including cannabis, alcohol and MDMA....

") describe a reaction accompanied by fear, other unpleasant feelings, and occasionally by dangerous behavior. In general, "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
Set and setting
Set and setting describes the context for psychoactive and particularly psychedelic drug experiences: one's mindset and the setting in which the user has the experience. This is especially relevant for psychedelic or hallucinogenic experiences...

). Ingesting psilocybin in combination with other drugs or with 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 LSD or mescaline. In the Psychedelics Encyclopedia, author Peter Stafford
Peter Stafford
Peter Stafford was an American writer and author of the Psychedelics Encyclopedia . Stafford is also co-author with Bonnie Golightly of LSD: The Problem-solving Psychedelic, as well as other books on psychedelics. He was the editor of Crawdaddy! from 1969 to 1970...

 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."

Possible adverse psychiatric effects


Panic reactions can occur after consumption of psilocybin-containing mushrooms, especially if the ingestion is accidental or otherwise unexpected. Reactions characterized by violence, aggression, homicidal and suicidal attempts, prolonged schizophrenia-like psychosis
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...

, and convulsion
Convulsion
A convulsion is a medical condition where body muscles contract and relax rapidly and repeatedly, resulting in an uncontrolled shaking of the body. Because a convulsion is often a symptom of an epileptic seizure, the term convulsion is sometimes used as a synonym for seizure...

s have been reported in the literature. A 2005 survey of users in the United Kingdom found that almost a quarter of those who had used the drug in the past year had experienced a panic attack
Panic attack
Panic attacks are periods of intense fear or apprehension that are of sudden onset and of relatively brief duration. Panic attacks usually begin abruptly, reach a peak within 10 minutes, and subside over the next several hours...

. Other adverse effects less frequently reported include paranoia
Paranoia
Paranoia [] is a thought process believed to be heavily influenced by anxiety or fear, often to the point of irrationality and delusion. Paranoid thinking typically includes persecutory beliefs, or beliefs of conspiracy concerning a perceived threat towards oneself...

, confusion
ConFusion
ConFusion is an annual science fiction convention organized by the Stilyagi Air Corps and its parent organization, the Ann Arbor Science Fiction Association. Commonly, it is held the third weekend of January. It is the oldest science fiction convention in Michigan, a regional, general SF con...

, derealization
Derealization
Derealization is an alteration in the perception or experience of the external world so that it seems unreal. Other symptoms include feeling as though one's environment is lacking in spontaneity, emotional coloring and depth. It is a dissociative symptom of many conditions, such as psychiatric and...

, disconnection from reality, and mania
Mania
Mania, the presence of which is a criterion for certain psychiatric diagnoses, is a state of abnormally elevated or irritable mood, arousal, and/ or energy levels. In a sense, it is the opposite of depression...

. Consumption of psilocybin by those with schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...

 can induce acute psychotic states requiring hospitalization.

The similarity of psilocybin-induced symptoms to those of schizophrenia has led to the drug being used in both behavioral and neuroimaging
Neuroimaging
Neuroimaging includes the use of various techniques to either directly or indirectly image the structure, function/pharmacology of the brain...

 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". There has been one case report of psilocybin and cannabis possibly causing hallucinogen persisting perception disorder
Hallucinogen persisting perception disorder
Hallucinogen persisting perception disorder is a disorder characterized by a continual presence of visual disturbances that are reminiscent of those generated by the ingestion of hallucinogenic substances. Previous use of hallucinogens by the person is needed, though not sufficient, for...

 (HPPD) (which at worst can last five years or more). However, the claimed association between HPPD and psychedelics is obscured by polydrug use and other variables.

Mystical experiences



Psychedelic drugs can induce states of consciousness
Consciousness
Consciousness is a term that refers to the relationship between the mind and the world with which it interacts. It has been defined as: subjectivity, awareness, the ability to experience or to feel, wakefulness, having a sense of selfhood, and the executive control system of the mind...

 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
Meditation
Meditation is any form of a family of practices in which practitioners train their minds or self-induce a mode of consciousness to realize some benefit....

 or holotropic breathwork
Holotropic Breathwork
Holotropic Breathwork is a practice that uses breathing and other elements to allow access to non-ordinary states for the purpose of self-exploration. It was developed by Stanislav Grof, M.D., Ph.D. and Christina Grof, Ph.D. . Holotropic breathing has some similarities to rebirthing-breathwork,...

. In the 1960s, Walter Pahnke
Walter Pahnke
Walter N. Pahnke M.D., Ph.D. was a minister, physician, and psychiatrist who attended Harvard in the early 1960s. He earned an MD from Harvard Medical School, a BD from Harvard Divinity School, a PhD from Harvard Graduate School of Arts and Sciences, and a Harvard psychiatric residency.He was a...

 and colleagues sought to more systematically evaluate 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
Marsh Chapel Experiment
The Marsh Chapel Experiment was run by Walter N. Pahnke, a graduate student in theology at Harvard Divinity School, under the supervision of Timothy Leary and the Harvard Psilocybin Project. The goal was to see if in religiously predisposed subjects, psilocybin would act as reliable entheogen...

, which was run by Pahnke at the Harvard Divinity School
Harvard Divinity School
Harvard Divinity School is one of the constituent schools of Harvard University, located in Cambridge, Massachusetts, in the United States. The School's mission is to train and educate its students either in the academic study of religion, or for the practice of a religious ministry or other public...

 under the supervision of Timothy Leary, almost all of the graduate degree divinity
Seminary
A seminary, theological college, or divinity school is an institution of secondary or post-secondary education for educating students in theology, generally to prepare them for ordination as clergy or for other ministry...

 student volunteers who received psilocybin reported profound religious experiences. One of the participants was religious scholar Huston Smith
Huston Smith
Huston Cummings Smith is a religious studies scholar in the United States. His book The World's Religions remains a popular introduction to comparative religion.-Education:...

, author of several textbooks on comparative religion
Comparative religion
Comparative religion is a field of religious studies that analyzes the similarities and differences of themes, myths, rituals and concepts among the world's religions...

; 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". Psychedelic researcher Rick Doblin
Rick Doblin
Rick Doblin is the president and founder of the Multidisciplinary Association for Psychedelic Studies .He co-founded Earth Metabolic Design Laboratories in 1984 to support psychedelic research and Multidisciplinary Association for Psychedelic Studies in 1986 with the goal of making MDMA an...

 considered the study partially flawed due to incorrect implementation of the double-blind
Double-blind
A blind or blinded experiment is a scientific experiment where some of the people involved are prevented from knowing certain information that might lead to conscious or subconscious bias on their part, invalidating the results....

 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". 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
Johns Hopkins School of Medicine
The Johns Hopkins School of Medicine , located in Baltimore, Maryland, U.S., is the academic medical teaching and research arm of Johns Hopkins University. Hopkins has consistently been the nation's number one medical school in the amount of competitive research grants awarded by the National...

 led by 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. In the experiment, 36 volunteers without prior experience with hallucinogens were given psilocybin and methylphenidate
Methylphenidate
Methylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...

 (Ritalin) in separate sessions; the methylphenidate sessions served as a control
Scientific control
Scientific control allows for comparisons of concepts. It is a part of the scientific method. Scientific control is often used in discussion of natural experiments. For instance, during drug testing, scientists will try to control two groups to keep them as identical and normal as possible, then...

 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
Dysphoria
Dysphoria is medically recognized as a mental and emotional condition in which a person experiences intense feelings of depression, discontent and indifference to the world around them.Mood disorders can induce dysphoria, often with a heightened risk of suicide, especially in...

 (i.e., a “bad trip
Bad trip
Bad trip is a disturbing experience sometimes associated with use of a psychedelic drug such as LSD, Salvinorin A, DXM, mescaline, psilocybin, DMT and sometimes even other drugs including cannabis, alcohol and MDMA....

”) at some point during the psilocybin session (which was not reported by any subject during the methylphenidate session), with about one-third of these (13% of the total) reporting 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 followup 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. Similarly, 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.

In 2011, Griffiths and colleagues published the results of further studies designed to learn more about the optimum psilocybin doses needed for positive life-changing experiences, while minimizing the chance of negative reactions. In a 14 month followup, the researchers found that 94% of the volunteers rated their experiences with the drug as one of the top 5 most spiritually significant of their lives (44% said it was the single most significant). None of the 90 sessions that took place throughout the study were rated as decreasing well-being or life satisfaction. Moreover, 89% reported positive changes in their behaviors as a result of the experiences. The conditions of the experimental design included a single drug experience a month, on a couch, in a living-room-like setting, with eye shades and carefully chosen music (classical and world music). As an additional precaution to guide the experience, the 2011 study included a "monitor" whom the volunteers supposedly trusted. The monitors provided gentle reassurance when the volunteers experienced times of anxiety. The volunteers, monitors, and observers all remained blind to the exact dosages for the sake of the experiment.

Medical research


Psilocybin has been a subject of medical research since the 1960s, when Leary and Alpert ran the Harvard Psilocybin Project
Harvard Psilocybin Project
The Harvard Psilocybin Project was a series of experiments in psychology conducted by Dr. Timothy Leary and Dr. Richard Alpert. The founding board of the project consisted of Leary, Aldous Huxley, John Spiegel , Leary's superior at Harvard University David McClelland, Frank Barron, Ralph Metzner,...

, in which they carried out a number of experiments to evaluate the therapeutic value of psilocybin in the treatment of personality disorders, or to augment psychological counseling. In the 2000s, there has been a resurgence of research concerning the use of psychedelic drugs for potential clinical applications, such as to address anxiety disorder
Anxiety disorder
Anxiety disorder is a blanket term covering several different forms of abnormal and pathological fear and anxiety. Conditions now considered anxiety disorders only came under the aegis of psychiatry at the end of the 19th century. Gelder, Mayou & Geddes explains that anxiety disorders are...

s, major depression, and various addiction
Addiction
Historically, addiction has been defined as physical and psychological dependence on psychoactive substances which cross the blood-brain barrier once ingested, temporarily altering the chemical milieu of the brain.Addiction can also be viewed as a continued involvement with a substance or activity...

s. In 2008, the Johns Hopkins research team published guidelines for responsibly conducting medical research trials
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...

 with psilocybin and other hallucinogens in humans. These included recommendations on how to screen potential study volunteers to exclude those with personal or family psychiatric histories
Psychiatric history
A psychiatric history is the result of a medical process where a clinician working in the field of mental health systematically records the content of an interview with a patient...

 that suggest a risk of averse reactions to hallucinogens. A 2010 study on the short- and long-term subjective effects of psilocybin administration in clinical settings concluded that despite a small risk of acute
Acute (medicine)
In medicine, an acute disease is a disease with either or both of:# a rapid onset, as in acute infection# a short course ....

 reactions such as dysphoria, anxiety, or panic, "the administration of moderate doses of psilocybin to healthy, high-functioning and well-prepared subjects in the context of a carefully monitored research environment is associated with an acceptable level of risk"; the authors note, however, that the safety of the drug "cannot be generalized to situations in which psilocybin is used recreationally or administered under less controlled conditions."

The first FDA-approved clinical study of psilocybin since 1970—led by Francisco Moreno at the University of Arizona
University of Arizona
The University of Arizona is a land-grant and space-grant public institution of higher education and research located in Tucson, Arizona, United States. The University of Arizona was the first university in the state of Arizona, founded in 1885...

 and supported by the Multidisciplinary Association for Psychedelic Studies
Multidisciplinary Association for Psychedelic Studies
The Multidisciplinary Association for Psychedelic Studies is a membership-based 501 non-profit research and educational organization working to develop psychedelics and marijuana into legal prescription drugs...

—studied the effects of psilocybin on nine patients with obsessive-compulsive disorder
Obsessive-compulsive disorder
Obsessive–compulsive disorder is an anxiety disorder characterized by intrusive thoughts that produce uneasiness, apprehension, fear, or worry, by repetitive behaviors aimed at reducing the associated anxiety, or by a combination of such obsessions and compulsions...

 (OCD). The pilot study found that, when administered by trained professionals in a medical setting, the use of psilocybin was associated with substantial reductions in OCD symptoms in several of the patients. This effect may be caused by psilocybin's ability to reduce the levels
Downregulation and upregulation
Downregulation is the process by which a cell decreases the quantity of a cellular component, such as RNA or protein, in response to an external variable...

 of the serotonin-2A receptor, resulting in decreased responsiveness to serotonin. Psilocybin has additionally shown promise to ease the pain caused by cluster headache
Cluster headache
Cluster headache, nicknamed "suicide headache", is a neurological disease that involves, as its most prominent feature, an immense degree of pain in the head. Cluster headaches occur periodically: spontaneous remissions interrupt active periods of pain. The cause of the disease is currently unknown...

s, often considered not only the most painful of all types of headaches but "one of the worst pain syndromes known to mankind." In a 2006 study, half of cluster headache patients reported that psilocybin aborted the attacks, and most reported extended remission periods; similar results were reported for LSD. A 2011 review of alternative
Alternative medicine
Alternative medicine is any healing practice, "that does not fall within the realm of conventional medicine." It is based on historical or cultural traditions, rather than on scientific evidence....

 headache treatments concluded that, despite flaws in the study design, these results suggest that LSD and psilocybin may warrant further study for use in the prevention of cluster headaches—only subhallucinogenic doses of the drugs are required for effective treatment, and no other medications have been reported to stop a cluster headache cycle.

Several modern studies have investigated the possibility that psilocybin can ease the psychological suffering associated with end-stage
Terminal illness
Terminal illness is a medical term popularized in the 20th century to describe a disease that cannot be cured or adequately treated and that is reasonably expected to result in the death of the patient within a short period of time. This term is more commonly used for progressive diseases such as...

 cancer. Preliminary results indicate that low doses of psilocybin can improve the mood and reduce the anxiety of patients with advanced cancer, and that the effects last from two weeks to six months. These results are comparable to those obtained from early studies that explored the use of LSD to improve the psychological well-being of terminally ill patients, but without the experimental rigor employed in modern clinical psychopharmacology
Psychopharmacology
Psychopharmacology is the scientific study of the actions of drugs and their effects on mood, sensation, thinking, and behavior...

 research.

Social and legal aspects



In the United States, psilocybin (and psilocin) were first subjected to federal regulation by the Drug Abuse Control Amendments of 1965, a product of a bill
Bill (proposed law)
A bill is a proposed law under consideration by a legislature. A bill does not become law until it is passed by the legislature and, in most cases, approved by the executive. Once a bill has been enacted into law, it is called an act or a statute....

 sponsored by Senator Thomas J. Dodd
Thomas J. Dodd
Thomas Joseph Dodd was a United States Senator and Representative from Connecticut, He was the first Senator censured by the US Senate since Joseph McCarthy in 1954, and was one of only six people censured by the Senate in the 20th century. He is the father of former U.S. Senator Christopher Dodd...

. The law—passed in July 1965 and taking effect on February 1, 1966—was an amendment to the federal Food, Drug and Cosmetic Act and was intended to regulate the unlicensed "possession, manufacture, or sale of depressant, stimulant and hallucinogenic drugs". The statute
Statute
A statute is a formal written enactment of a legislative authority that governs a state, city, or county. Typically, statutes command or prohibit something, or declare policy. The word is often used to distinguish law made by legislative bodies from case law, decided by courts, and regulations...

s themselves, however, did not list the "hallucinogenic drugs" that were being regulated. Instead the term "hallucinogenic drugs" was meant to refer to those substances believed to have a "hallucinogenic effect on the central nervous system".

Despite the seemingly strict provisions of the law, many people were exempt from prosecution. The statutes "permit[ted] … people to possess such drugs so long as they were for the personal use of the possessor, [for] a member of his household, or for administration to an animal". The federal law that specifically banned psilocybin and psilocin was enacted on October 24, 1968. The latter substances were said to have "a high potential for abuse", "no currently accepted medical use," and "a lack of accepted safety". On October 27, 1970, both psilocybin and psilocin became classified as Schedule I
Controlled Substances Act
The Controlled Substances Act was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. The CSA is the federal U.S. drug policy under which the manufacture, importation, possession, use and distribution of certain...

 and were simultaneously labeled "hallucinogens" under a section of the "Comprehensive Drug Abuse Prevention and Control Act" known as the "Controlled Substances Act". Schedule I drugs are illicit drugs that are claimed to have no known therapeutic benefit. Parties to the treaty are required to restrict use of the drug to medical and scientific research under strictly controlled conditions. Most national drug laws
Prohibition (drugs)
The prohibition of drugs through sumptuary legislation or religious law is a common means of attempting to prevent drug use. Prohibition of drugs has existed at various levels of government or other authority from the Middle Ages to the present....

 have been amended to reflect this convention (for example, the US Psychotropic Substances Act
Psychotropic Substances Act (United States)
The Psychotropic Substances Act of 1978 amended the Controlled Substances Act to ensure compliance with the Convention on Psychotropic Substances...

, the UK Misuse of Drugs Act 1971
Misuse of Drugs Act 1971
The Misuse of Drugs Act 1971 is an Act of Parliament which represents UK action in line with treaty commitments under the Single Convention on Narcotic Drugs, the Convention on Psychotropic Substances, and the United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic...

, and the Canadian Controlled Drugs and Substances Act
Controlled Drugs and Substances Act
The Controlled Drugs and Substances Act is Canada's federal drug control statute. Passed in 1996 by the Chrétien government, it repeals the Narcotic Control Act and Parts III and IV of the Food and Drug Act and establishes eight Schedules of controlled substances and two Classes of precursors...

), with possession and use of psilocybin and psilocin being prohibited under almost all circumstances, and often carrying severe legal penalties.

Possession and use of psilocybin mushrooms, including the bluing species of Psilocybe, is therefore prohibited by extension. However, in many national, state, and provincial drug laws, there is a great deal of ambiguity about the legal status of psilocybin mushrooms and the spores of these mushrooms, as well as a strong element of selective enforcement
Selective enforcement
Selective enforcement is the ability that executors of the law have to arbitrarily select choice individuals as being outside of the law...

 in some places. In addition, there has been a general shift in attitudes regarding research with psilocybin and other hallucingenic agents; after a long interruption in the use of these drugs, many countries are revising their positions and have started to approve studies to test the physiological and therapeutic effects of hallucinogens.

2006 Johns Hopkins experiment


2008 Follow-up to Johns Hopkins experiment


External links