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
ChemSpider 10178
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  ?

Psilocybin (pronounced [saɪləˈsaɪbɪn], sye-lə-SYE-bin) (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 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. 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.

Contents

[edit] Chemistry

Psilocybin (O-phosphoryl-4-hydroxy-N,N-dimethyltryptamine) 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. Mushroom caps tend to contain more of the psychoactive compounds than the stems.[4][5][6] The total potency varies greatly between species and even between specimens of one species in the same batch.[7] Younger, smaller mushrooms are relatively higher in alkaloids and have a milder taste than larger, mature mushrooms. Mature mycelium contains some psilocybin, while young mycelium (recently germinated from spores) does not contain appreciable amounts of alkaloids.[8] Many species of mushrooms containing psilocybin also contain small amounts of the psilocybin analogs baeocystin and norbaeocystin.[9][10][11] Most species of psilocybin-containing mushrooms bruise blue when handled or damaged[12] 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-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.[13]

[edit] Medicine

Psilocybin has no recognized medical uses. However, it has been investigated as an experimental 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.

A pilot study led by Francisco Moreno and supported by Multidisciplinary Association for Psychedelic Studies (MAPS) studied the effects of psilocybin on nine patients with obsessive-compulsive disorder.[14] The study found that psilocybin could be safely given to patients with OCD but, due to the study design, it was unable to confirm or deny that psilocybin was effective in relieving obsessive compulsive disorder symptoms.[15]

Two current studies are investigating the possibility that psilocybin can ease the psychological suffering associated with cancer. One study, led by Charles Grob, involves 12 subjects with terminal cancer being administered the hallucinogen or a placebo in two separate sessions.[16][17][18] A second study, led by Roland Griffiths at Johns Hopkins, will administer psilocybin on two occasions to people "with a current or past diagnosis of cancer who have some anxiety or are feeling down about their cancer".[19]

[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[20] (however rabbits are extremely intolerant to the effects of most psychoactive drugs). The lethal dose from psilocybin toxicity alone is unknown at recreational or medicinal levels, and has never been documented. Psilocybin makes up roughly 1% of the weight of Psilocybe cubensis 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] Physiology

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.[21] A typical recreational dosage is from 10–50 mg psilocybin. However, 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 play 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.

[edit] Effects

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 disoriented, 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 hallucination 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 introspective or entheogenic. Open-eye visuals are more common, and may be very detailed although rarely confused with reality.

Distortions in the experience of time in psilocybin-induced states have been subjectively reported [22], and objectively measured [23]. In these studies, psilocybin significantly decreased subjects’ reproduction of time intervals longer than 2.5 s, impaired their ability to synchronize to inter-beat intervals longer than 2 s, and reduced their preferred tapping rate. Recent studies into the effects of psilocybin on time interval reproduction may shed light on qualitative alterations of time experience in experimentally-induced altered states of consciousness, mystical states, or in psychopathology.[24]

Users having a pleasant experience can feel ecstatic, a sense of connection to others, nature, the universe, and other feelings/emotions are often intensified. Difficult experiences or bad trips occur due to a variety of reasons. Tripping during an emotional/physical low, or in a non-supportive/inadequate/etc. environment (see: set and setting) could possibly cause anxiety. Latent psychological issues may be triggered by the strong emotional components of the experience. [25]

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.

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.[26] Further measures at 14 months after the psilocybin experience confirmed that participants continued to attribute deep personal meaning to the experience. This research was widely covered in the major media outlets.[27] The research team cautions that if hallucinogens are used in less well supervised settings, the possible fear or anxiety responses could lead to harmful behaviors.[28] Further studies by this group have investigated the relationship of psilocybin dose to likelihood of mystical experience in healthy volunteers[29] and whether mystical experiences in volunteers given psilocybin can help with anxiety and poor mood due to cancer.[30]

The National Institute on Drug Abuse states psilocybin "can produce muscle relaxation or weakness, ataxia, excessive pupil dilation, nausea, vomiting, and drowsiness. Individuals who abuse psilocybin mushrooms also risk poisoning if one of the many existing varieties of poisonous mushrooms is incorrectly identified as a psilocybin mushroom."[31]

In rare cases, psilocybin use can cause Hallucinogen Persisting Perception Disorder. [32]

[edit] Social and legal aspects

Psilocybin and psilocin are listed as Schedule I drugs under the United Nations 1971 Convention on Psychotropic Substances.[33] 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.

[edit] See also

[edit] References

  1. ^ Erowid Psilocybin Mushroom Vault : Legal Status
  2. ^ Horita, A. and L.J. Weber. "Dephosphorylation of psilocybin to psilocin by alkaline phosphatase." Proceedings of the Society for Experimental Biology 106(1): 32-33 (1961)
  3. ^ Dr. Albert Hofmann | Psilocybin | Psilocin
  4. ^ Wurst M, M. Semerdzieva M, J. Vokoun, Analysis of psychotropic compounds in fungi of the genus Psilocybe by reversed-phase high performance liquid chromatography, J. Chromatogr. 286 ( 1984) 229 – 235.
  5. ^ Kysilka R, Wurst M (March 1989). "High-performance liquid chromatographic determination of some psychotropic indole derivatives". J. Chromatogr. 464 (2): 434–7. PMID 2722990. 
  6. ^ Keller T, Schneider A, Regenscheit P, et al (January 1999). "Analysis of psilocybin and psilocin in Psilocybe subcubensis Guzmán by ion mobility spectrometry and gas chromatography-mass spectrometry". Forensic Sci. Int. 99 (2): 93–105. PMID 10077856. http://linkinghub.elsevier.com/retrieve/pii/S0379073898001686. 
  7. ^ Bigwood J, Beug MW (May 1982). "Variation of psilocybin and psilocin levels with repeated flushes (harvests) of mature sporocarps of Psilocybe cubensis (Earle) Singer". J Ethnopharmacol 5 (3): 287–91. PMID 7201054. 
  8. ^ Gross ST (May 2000). "Detecting psychoactive drugs in the developmental stages of mushrooms". J. Forensic Sci. 45 (3): 527–37. PMID 10855955. 
  9. ^ Gartz J (June 1987). "Occurrence of Psilocybin and Baeocystin in Fruit Bodies of Pluteus salicinus". Planta Med. 53 (3): 290–291. doi:10.1055/s-2006-962710. PMID 17269025. 
  10. ^ Stijve T, Kuyper TW (October 1985). "Occurrence of psilocybin in various higher fungi from several European countries". Planta Med. 51 (5): 385–7. doi:10.1055/s-2007-969526. PMID 17342589. 
  11. ^ Repke DB, Leslie DT, Guzmán G (1977). "Baeocystin in psilocybe, conocybe and panaeolus". Lloydia 40 (6): 566–78. PMID 600026. 
  12. ^ Singer R, Smith AH. (1958). Mycological Investigations on Teonanácatl, the Mexican Hallucinogenic Mushroom. Part II. A Taxonomic Monograph of Psilocybe, Section Caerulescentes. Mycologia 50(2) :262-303.
  13. ^ Passie T, Seifert J, Schneider U, Emrich HM. (2002). "The pharmacology of psilocybin.". Addict Biol. 7 (4): 357–64. doi:10.1080/1355621021000005937. PMID 14578010. 
  14. ^ http://www.maps.org/research/psilo/azproto.html Effects of psilocybin in Obsessive-Compulsive Disorder
  15. ^ Moreno FA, Wiegand CB, Taitano EK, Delgado PL. (2006). "Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder". J Clin Psychiatry 67 (11): 1735–40. PMID 17196053. 
  16. ^ Psychopharmacology of Psilocybin in Cancer Patients - ClinicalTrials.gov
  17. ^ hhtp://http://psychedelics.com/psilocybe/psilocybin.html The Hallucinogenic Way of Dying
  18. ^ Lewis, Judith. "The Hallucinogenic Way to Die." LA Weekly. Mar. 2004:AlterNet
  19. ^ http://www.bpru.org/cancer/ recruitment notice for psilocybin clinical trial
  20. ^ NLM (click on "toxicity" on the left side)
  21. ^ Erowid Psilocybin Mushroom Vault : Dosage
  22. ^ Fischer R, England SM, Archer RC, Dean RK (February 1966). "Psilocybin reactivity and time contraction as measured by psychomotor performance". Arzneimittelforschung 16 (2): 180–5. PMID 6014013. 
  23. ^ Wittmann M, Carter O, Hasler F, et al (January 2007). "Effects of psilocybin on time perception and temporal control of behaviour in humans". J. Psychopharmacol. (Oxford) 21 (1): 50–64. doi:10.1177/0269881106065859. PMID 16714323. http://jop.sagepub.com/cgi/pmidlookup?view=long&pmid=16714323. 
  24. ^ Wackermann J, Wittmann M, Hasler F, Vollenweider FX (April 2008). "Effects of varied doses of psilocybin on time interval reproduction in human subjects". Neurosci. Lett. 435 (1): 51–5. doi:10.1016/j.neulet.2008.02.006. PMID 18325673. http://linkinghub.elsevier.com/retrieve/pii/S0304-3940(08)00179-1. 
  25. ^ AJ Giannini. Drugs of Abuse--Second Edition. Los Angeles, Medical Examination Publishing Co., 1997.
  26. ^ "Medical News: Psilocybin Viewed as Therapy or Research Tool - in Psychiatry, Addictions from MedPage Today". http://www.medpagetoday.com/Psychiatry/GeneralPsychiatry/tb/3721. 
  27. ^ "Drugs & God: The Magic Mushroom Study - 2006". http://www.yoism.org/?q=node/219. 
  28. ^ Spiritual Effects of Hallucinogens Persist Newswise, Retrieved on July 6, 2008.
  29. ^ Griffiths R, Richards W, Johnson M, McCann U, Jesse R. (2008). "Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later". J Psychopharmacol 22 (6): 621–32. doi:10.1177/0269881108094300. PMID 18593735. 
  30. ^ Recruitment page for Hopkins cancer study
  31. ^ NIDA InfoFacts: Hallucinogens - LSD, Peyote, Psilocybin, and PCP NIDA
  32. ^ Espiard ML, Lecardeur L, Abadie P, Halbecq I, Dollfus S. (2005). "Hallucinogen persisting perception disorder after psilocybin consumption: a case study". Eur Psychiatry 20 (5-6): 458–60. doi:10.1016/j.eurpsy.2005.04.008. PMID 15963699. 
  33. ^ "List of psychotropic substances under international control (International Narcotics Control Board)" (PDF). http://www.incb.org/pdf/e/list/green.pdf. 

[edit] 2006 Johns Hopkins experiment

[edit] 2008 Follow-up to Johns Hopkins experiment

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