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Psilocybin (also known as psilocybine) is a psychedelic alkaloid of the tryptamine family. It is present in hundreds of species of fungi, including those of the genus Psilocybe, such as Psilocybe cubensis and Psilocybe semilanceata, but also reportedly isolated from a dozen or so other genera. Psilocybin-containing mushrooms are commonly called magic mushrooms or more simply "shrooms". The intensity and duration of recreational and entheogenic use of psilocbyin mushrooms vary depending on species of mushroom, dosage, individual physiology, and set and setting.
ChemistryPsilocybin is a prodrug that is converted into the pharmacologically active compound psilocin in the body by dephosphorylation.[1] This chemical reaction takes place under strongly acidic conditions or enzymatically by phosphatases in the body. Psilocybin is a zwitterionic alkaloid that is soluble in water, moderately soluble in methanol and ethanol, and insoluble in most organic solvents. Albert Hofmann was the first to recognize the importance and chemical structure of the pure compounds psilocybin and psilocin. Hofmann was aided in this process by his willingness to ingest extracts isolated from Psilocybe. Hofmann's colleagues at the University of Delaware were also trying to isolate the active principle, but were unsuccessful.[1] Biology
PharmacologyPsilocybin is rapidly dephosphorylated in the body to psilocin which then acts as a partial agonist at the 5-HT2A serotonin receptor in the brain where it mimics the effects of serotonin (5-HT). Psilocybin is an 5-HT1A and 5-HT2A/2C agonist. MedicinePsilocybin has been studied as a treatment for several disorders. In 1961, Timothy Leary and Richard Alpert ran the Harvard Psilocybin Project, carrying out a number of experiments concerning the use of psilocybin in the treatment of personality disorders and other uses in psychological counseling. More recently, in the US, an FDA-approved study supported by Multidisciplinary Association for Psychedelic Studies (MAPS) began in 2001 to study the effects of psilocybin on patients with obsessive-compulsive disorder.[2] MAPS has also proposed studying psilocybin's potential application for the treatment of cluster headaches based on anecdotal evidence presented to them by a group of cluster headache sufferers.[3]
In a current study of psilocybin, 12 subjects are being administered with either the hallucinogen or a placebo in two separate sessions. Dr. Gob and Dr. Hagerty are currently working with a patient from New Mexico that is in the last stages of metastasize rectal cancer. [4] "Lewis, Judith. "The Hallucinogenic Way to Die." LA Weekly. Mar. 2004:AlterNet ToxicityThe toxicity of psilocybin is relatively low; when administered intravenously in rabbits, Psilocybin's LD50 is approximately 12.5mg/kg. In rats, the LD50 is 280mg/kg -- almost one and a half times that of caffeine.[5] Death from psilocybin intake alone is unknown at most recreational or medicinal levels. The psilocybin content of psychoactive mushrooms is quite variable and depends on species, growth and drying conditions, and mushroom size, but averages around 5mg/g of dried mushroom, or 1mg/2g of fresh mushroom.[citation needed] EffectsPsilocybin is absorbed through the lining of the mouth and stomach. Effects begin 10-60 minutes after ingestion of psilocybin-containing mushrooms, and last from 2-6 hours depending on dose, species, and individual metabolism. Typical recreational dosage is from 10-50mg Psilocybin, or approximately 2-5g dried mushroom. The effects of psilocybin are often pleasant, even ecstatic, including a deep sense of connection to others, confusion, hilarity, and a general feeling of connection to nature and the universe. Difficult trips may occur when psychedelic compounds are taken in a non-supportive or inadequate environment, by an inexperienced person, or in an unexpectedly high dose (see: set and setting). At low doses, hallucinatory effects occur, including walls that seem to breathe, a vivid enhancement of colors and the animation of organic shapes. At higher doses, experiences tend to be less social and more entheogenic, often catalyzing intense spiritual experiences. For example, in the Marsh Chapel Experiment, which was run by a graduate student at Harvard Divinity School under the supervision of Timothy Leary, almost all of the graduate degree divinity student volunteers who received psilocybin reported profound religious experiences. (A brief video about the Marsh Chapel experiment can be viewed here.) In 2006, a group of researchers from Johns Hopkins School of Medicine led by Roland R Griffiths conducted an experiment assessing the degree of mystical experience and attitudinal effects of the psilocybin experience; this report was published in the journal Psychopharmacology. Thirty-six volunteers without prior experience with hallucinogens were given psilocybin and methylphenidate (Ritalin) in separate sessions, the methylphenidate sessions serving as a control and active placebo; the tests were double-blind, with neither the subject nor the administrator knowing which drug was being administered. The degree of mystical experience was measured using a questionnaire on mystical experience 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 (eg, a “bad trip”) 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. [2] This research was widely covered in the major media outlets.[3] A very small number of people are unusually sensitive to psilocybin's effects, where doses as little as 0.25 grams of dried Psilocybe cubensis mushrooms (normally a threshold dose of around 2 mg psilocybin) can result in effects usually associated with medium and high doses. Likewise, there are some people who require relatively high doses of psilocybin to gain low-dose effects. Individual brain chemistry and metabolism plays a large role in determining a person's response to psilocybin. Psilocybin is metabolized mostly in the liver where it becomes psilocin. It is broken down by the enzyme monoamine oxidase. MAO inhibitors have been known to sustain the effects of psilocybin for longer periods of time; people who are taking an MAOI for a medical condition (or are seeking to potentiate the mushroom experience) should be careful. Mental and physical tolerance to psilocybin builds and dissipates quickly. Taking psilocybin more than three or four times in a week (especially two days in a row) can result in diminished effects. Tolerance dissipates after a few days, so frequent users often keep doses spaced five to seven days apart to avoid the effect. Adverse effectsThe consumption may cause Hallucinogen persisting perception disorder (HPPD).[6] While some claim that a user will take foolish risks, such as driving a vehicle, there is no evidence to support this assertion. Indeed most users find themselves in a heightened state of self preservation.[citation needed] It is this heightened state of caution or concern that can result in what is commonly known as a "bad trip", a state of intense concern over one's well being that in extreme cases can result in a state of panic or anxiety. As a drug, alcohol is far more likely to induce "foolish behavior".[citation needed] Social and legal aspectsPsilocybin and psilocin are listed as Schedule I drugs under the United Nations 1971 Convention on Psychotropic Substances.[4] 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 have been amended to reflect this convention (for example, the US Psychotropic Substances Act, the UK Misuse of Drugs Act 1971, and the Canadian Controlled Drugs and Substances Act), 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 in some places. For more details on the legal status of psilocybin mushrooms and Psilocybe spores, see: Psilocybe: Social and legal aspects. Because of the ease of cultivating psilocybin mushrooms or gathering wild species, purified psilocybin is practically nonexistent on the illegal drug market. See also
References
2006 Johns Hopkins experiment
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