Psilocybin

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Psilocybin
Systematic (IUPAC) name
[3-(2-dimethylaminoethyl)-1H-indol-4-yl] dihydrogen phosphate
Identifiers
CAS number	520-52-5
ATC code	?
PubChem	10624
Chemical data
Formula	C₁₂H₁₇N₂O₄P
Mol. mass	284.25 g/mol
SMILES	eMolecules & PubChem
Pharmacokinetic data
Bioavailability	?
Metabolism	?
Half life	?
Excretion	?
Therapeutic considerations
Pregnancy cat.	?
Legal status	Prohibited (S9)(AU) Schedule III(CA) Class A(UK) Schedule I(US)
Routes	?

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Psilocybin (IPA: /saɪləˈsaɪbɪn/)(also known as psilocybine) is a psychedelic indole of the tryptamine family, found in psilocybin mushrooms. 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". Possession, and in some cases usage, of psilocybin or psilocin has been outlawed in many if not most countries across the globe.^[1]. Proponents of its usage consider it to be an entheogen and a tool to supplement various types of practices for transcendence, including in meditation, psychonautics, and psychedelic psychotherapy^{[citation needed]}. The intensity and duration of entheogenic effects of psilocybin mushrooms are highly variable, depending on species/cultivar of mushrooms, dosage, individual physiology, and set and setting. Though psilocybin rarely attracts much attention from mainstream media, when it does the focus tends to be on the recreational use, generally excluding any other uses of the drug.

1 Chemistry
2 Biology
3 Pharmacology
4 Medicine
5 Toxicity
6 Effects
7 Social and legal aspects
8 See also
9 References
- 9.1 2006 Johns Hopkins experiment
10 External links

[edit] Chemistry

Psilocybin is a prodrug that is converted into the pharmacologically active compound psilocin in the body by dephosphorylation.^[2] 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, the well-known chemist who discovered and experimented with LSD, 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.^[3]

[edit] Biology

Psilocybin is a naturally-occurring compound found in varying concentrations in some species of the genera of Psilocybe spp. and Panaeolus spp. (fungal Phylum Basidiomycota). 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.^{[citation needed]} Mature mycelium contains some psilocybin. Young mycelium (recently germinated from spores) does not contain appreciable amounts of alkaloids. Many species of mushrooms containing psilocybin also contain small amounts of the psilocybin analogs baeocystin and norbaeocystin. Some species of psilocybin mushrooms bruise blue when handled or damaged due to the oxidization of phenolic compounds. This is not a definitive method of identification or determining a mushroom's potency.

[edit] Pharmacology

Psilocybin is rapidly dephosphorylated in the body to psilocin which then acts as a partial agonist at the 5-HT_2A serotonin receptor in the brain where it mimics the effects of serotonin (5-HT). Psilocin is an 5-HT_1A and 5-HT_2A/2C agonist.^{[citation needed]}

[edit] 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 counselling.

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.^[4] 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.^[5] In 2006, the MAPS study found psilocybin effective in relieving obsessive compulsive disorder symptoms, in some cases for more than a few days.^[6]

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.^[7]^[8]^[9]

[edit] Toxicity

The toxicity of psilocybin is relatively low; in rats, the oral LD₅₀ is 280mg/kg, approximately one and a half times that of caffeine. When administered intravenously in rabbits, psilocybin's LD₅₀ is approximately 12.5mg/kg^[10] (However rabbits are extremely intolerant to the effects of most psychoactive drugs). The lethal dose from psilocybin intake alone is unknown at recreational or medicinal levels, and has never been documented; psilocybin makes up roughly 1% of the weight of Psilocybe mushrooms, and so nearly 1.7 kilograms of dried mushrooms, or 17 kilograms of fresh mushrooms, would be required for a 60kg person to reach the 280mg/kg LD50 rate of rats.

[edit] Effects

Psilocybin is absorbed through the lining of the mouth and stomach. Effects begin 10–40 minutes after ingestion of psilocybin-containing mushrooms, and last from 2–6 hours depending on dose, species, and individual metabolism.^[11] A typical recreational dosage is from 10–50 mg psilocybin.

The effects of psilocybin are highly variable, and dependent on the current mood and overall sense of well-being by the individual. Initially the subject may begin to feel somewhat disorientated, lethargic, and euphoric or sometimes depressed. At low doses, hallucinatory effects may occur, including enhancement of colors and the animation of geometric shapes. Closed-eye visuals may occur, where the affected individual may see multi-coloured geometric shapes and vivid imaginative sequences. At higher doses, hallucinatory effects increase and experiences tend to be less social and more introspectic or entheogenic. Open-eye visuals are more common, and may be very detailed although rarely confused with reality.

Users having a pleasant experience may feel ecstatic, including a deep sense of connection to others, confusion, hilarity, and a general feeling of connection to nature and the universe. Difficult experiences or bad trips may occur in some individuals, often when consumed during emotional turmoil, in a non-supportive or inadequate environment, by an inexperienced person, or in an unexpectedly high dose (see: set and setting). Latent psychological issues may be triggered by the strong emotional components of the experience.^{[citation needed]}

Some of these individuals report that they have experienced a 'spiritual' episode. 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 psychoactive placebo; the tests were double-blind. 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.^[12] This research was widely covered in the major media outlets.^[13]

A very small number of people are unusually sensitive to psilocybin's effects, where a normally threshold dose of around 2 mg of 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 may experience highly potentiated effects.

Mental and physical tolerance to psilocybin builds and dissipates quickly. Taking psilocybin more than three or four times in a week (especially on consecutive days) 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.

Psilocybin use can cause Hallucinogen Persisting Perception Disorder.

[edit] Social and legal aspects

Psilocybin and psilocin are listed as Schedule I drugs under the United Nations 1971 Convention on Psychotropic Substances.^[14] 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 often extremely difficult to find on the market.