Psilocybin detailed information

Psilocybin (also known as psilocybine) is a psychedelic alkaloid of the tryptamine family, found in psilocybin mushrooms. It is considered mostly to be an entheogen and a tool in use to supplement various types of practices for transcendence including in meditation, psychonautics, and illicit psychedelic psychotherapy whether self administered or not. It can also be used as a recreational drug. Though Psilocybin rarely attracts much attention from mainstream media, when it does, the focus tends to be on the recreational use to the exclusion of any other purpose. 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 mushrooms are commonly called "magic mushrooms" or more simply "shrooms". The intensity and duration of entheogenic and recreational use of psilocybin mushrooms vary depending on species of mushrooms, dosage, individual physiology, and set and setting.

Chemistry
Psilocybin is a prodrug that is converted into the pharmacologically active compound psilocin in the body by dephosphorylation. 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.

Biology
Psilocybin is a naturally-occurring compound found in high concentrations in some species of Psilocybe and Panaeolus (collectively called "psilocybin mushrooms" or "psilocybian mushrooms"), and at low levels in a large number of species of the Agaricales. The spores of these mushrooms are completely free of both psilocybin and psilocin. The total potency varies greatly between species and even between specimens of one species in the same batch. Younger, smaller mushrooms are relatively higher in alkaloids and have a milder taste than larger, mature mushrooms. Mature mycelium contains some amount of psilocybin, which can be extracted with an acidic solution, usually of citric acid or ascorbic acid (Vitamin C). Young mycelium (recently germinated from spores) does not contain appreciable amounts of alkaloids. Most species of hallucinogenic mushrooms also contain small amounts of the psilocybin analogs baeocystin and norbaeocystin. Many types of psilocybin mushrooms bruise blue when handled or damaged — this is due to the oxidization of active compounds though bruising is not a definitive method of determining a mushrooms potency.

Pharmacology
Psilocybin 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). Psilocin is an 5-HT1A and 5-HT2A/2C agonist.

Medicine
Psilocybin 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.

In the United States, 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. 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. In 2006, the MAPS study found psilocybin effective in relieving obsessive compulsive disorder symptoms, in some cases for more than a few days.

In a current study of psilocybin, led by Charles Grob, 12 subjects are being administered with either the hallucinogen or a placebo in two separate sessions. Grob hopes to reduce the psychological distress that is associated with death by treating patients with psilocybin. "Lewis, Judith. "The Hallucinogenic Way to Die." LA Weekly. Mar. 2004:AlterNet

Toxicity
The toxicity of psilocybin is relatively low; in rats, the oral LD50 is 280mg/kg — almost one and a half times that of the LD50 of caffeine. When administered intravenously in rabbits, Psilocybin's LD50 is approximately 12.5mg/kg. Death from psilocybin intake alone is unknown at recreational or medicinal levels.

The psilocybin content of psychoactive mushrooms is quite variable and depends on species, growth and drying conditions, and mushroom size.

Effects
Psilocybin is absorbed through the lining of the mouth and stomach. Effects begin 10-40 minutes after ingestion of psilocybin-containing mushrooms if held in mouth for 20-60 minutes or if swallowed on an empty stomach, and last from 2-6 hours depending on dose, species, and individual metabolism. Typical recreational dosage is from 10-50mg psilocybin, approximately 1-5g dried mushroom or 10-50g wet mushrooms.

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. Bad trips may occur when psychedelic compounds are taken in a non-supportive or inadequate environment, by an inexperienced person, in an unexpectedly high dose (see: set and setting), or when the substance triggers difficult areas of one's psyche.

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 (I.E. 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. This research was widely covered in the major media outlets.. Most people who have used psilocybin report that if you believe you will have a "bad trip" then you will. The same people, also report the best way to have a "good trip" is respect the mushroom, believe it will be a "good trip", and use it more for spiritual enhancement, rather than taking the psilocybin just to get "messed up".

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 effects
Individuals that have relatives with schizophrenia should be very careful about consuming psilocybin or any hallucinogenic drug at all due to the risk of triggering a psychosis.

In extremely rare cases the use of hallucinogens may trigger a malady called Hallucinogen persisting perception disorder. (HPPD).

Social and legal aspects
Psilocybin and psilocin are listed as Schedule I drugs under the United Nations 1971 Convention on Psychotropic Substances. 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.

2006 Johns Hopkins experiment

 * Griffiths RR, Richards WA, McCann U, Jesse R. (2006). Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology (online edition): July 11, 2006. (PDF) – Original paper.
 * Schuster C; Kleber H; Snyder S; Nichols D; de Wit H. (2006). Commentaries and Editorial on Article by Griffiths et al. Psychopharmacology (online edition): July 11, 2006. (PDF)
 * "Hopkins Scientists Show Hallucinogen in Mushrooms Creates Universal 'Mystical' Experience", Johns Hopkins Medicine news release, July 11, 2006.
 * "Q&A is with Roland Griffiths, the study’s lead researcher", Johns Hopkins Medicine news release, July 11, 2006.
 * "Psilocybin Viewed as Therapy or Research Tool" by Michael Smith, Medpagetoday.com, July 12, 2006.
 * "Magic mushrooms really cause 'spiritual' experiences" by Roxanne Khamsi, NewScientist.com news service, July 11, 2006.
 * "Drug's Mystical Properties Confirmed" by David Brown, Washington Post, July 11, 2006.
 * "Mushroom Drug Produces Mystical Experience", Associated Press, July 11, 2006.
 * "Counterculture Drug Provides Spiritual Boost" by Denise Gellene, Los Angeles Times, July 11, 2006.
 * "Tripping Out: Scientists Study Mystical Effects of Mushrooms" by Joy Victory, Bharathi Radhakrishnan, and Andrea Carter, ABC News (online), July 11, 2006.