About Psilocybin
Psilocybin is a prodrug for the classical hallucinogen - more specifically, psychedelic - psilocin, or 4-HO-DMT , the active metabolite of psilocybin, responsible for all of the psychoactive effect of the drug. Both drugs are members of the indole and tryptamine classes. Psilocybin-containing mushrooms are used both recreationally, and traditionally, for spiritual purposes, as entheogens, with a history of use spanning millennia. It is produced by hundreds of species of fungi, including those of the genus Psilocybe, such as Psilocybe cubensis, Psilocybe semilanceata and Psilocybe cyanescens, and has also been reportedly isolated from about a dozen other genera. Collectively known as psilocybin mushrooms, these are commonly called "boomers," "sacred mushrooms," "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. 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 or cultivar of mushrooms, dosage, individual physiology, and set and setting.
Once ingested, psilocybin is rapidly metabolised to psilocin, which then acts as a partial agonist at the 5-HT2A and 5-HT1A serotonin receptors in the brain. The mind-altering effects of psilocybin typically last anywhere from 3 to 8 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.
The American banker and amateur mycologist R. Gordon Wasson and his wife Valentina discovered that the ancient religious practices of the Indians in a remote village of Mexico included ingestion of mushrooms. In 1957, they published an article in Life magazine , where they described the occurrence of hallucinatory experiences during these rituals. They were accompanied on a later expedition by the French mycologist Roger Heim, director of the musée national d'histoire naturelle, when it was possible to identify several of the fungi as Psilocybe species. Heim was able to successfully cultivate the mushroom in France, and sent samples to the Swiss chemist Albert Hofmann for analysis. Hofmann, who had in 1938 created LSD in his Sandoz laboratory, was the first to recognize the importance and chemical structure of the pure compounds he called psilocybin and psilocin. Leading a research group that was able to isolate and identify the compounds from Psilocybe mexicana, Hofmann was aided in the discovery process by his willingness to ingest mushroom extracts. He and his colleagues later synthesized a number of compounds chemically related to the naturally occurring psilocybin:
Two diethyl analogs of psilocybin and psilocin were synthesized by Hofmann, 4-phosphoryloxy-N,N-diethyltryptamine, called CY-19, and 4-hydroxy-N,N-diethyltryptamine, called CZ-74. Because their effects last only about three and a half hours , they proved more manageable in European clinics using "psycholytic therapy"—psychotherapy in conjunction with the controlled use of psychedelics.
In the early 1960s, Harvard University became the testing ground of psilocybin, through the efforts of Timothy Leary and his associate Richard Alpert . Leary was able to obtain synthesized psilocybin from Hofmann through Hofmann's employer, Sandoz pharmaceutical . Although a number of experiments in the early 1960s demonstrated positive results using psilocybin in clinical psychiatry, the LSD hysteria of the times swept psilocybin along with it into the Schedule I category of illicit drugs in 1970. The 1970s would witness 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 even included fictional works such as those by Carlos Castaneda, and several books that taught the technique of growing one's own psilocybin mushrooms. One of the most popular of these books was produced under the pseudonyms O.T. Oss and O.N. Oeric by J. Bigwood, D.J. McKenna, K. Harrison McKenna and T.K. McKenna, entitled Psilocybin: Magic Mushroom Grower's Guide. Over 100,000 copies had been sold by 1981:
Psilocybin is a naturally occurring compound found in varying concentrations in over 200 species of Basidiomycota mushrooms, distributed amongst the following genera: Psilocybe , Gymnopilus , Panaeolus , Copelandia , Hypholoma , Pluteus Inocybe , Conocybe , Panaeolina , Gerronema and Agrocybe, Galerina and Mycena . The spores of these mushrooms do not contain psilocybin or psilocin. Mushroom caps tend to contain more of the psychoactive compounds than the stems. The total potency varies greatly between species and even between specimens of one species in the same batch. Younger, smaller mushrooms have a higher concentration of alkaloids and have a milder taste than larger, mature mushrooms. In general, the psilocybin content of mushrooms is quite variable and depends on species, growth and drying conditions, and mushroom size. Mature mycelium contains some psilocybin, while young mycelium does not contain appreciable amounts of alkaloids. Many species of mushrooms containing psilocybin also contain small amounts of the psilocybin analogs baeocystin and norbaeocystin. Most species of psilocybin-containing mushrooms bruise blue when handled or damaged due to the oxidization of phenolic compounds. This reaction, however, is not a definitive method of identification or determining a mushroom's potency.
Psilocybin is a prodrug that is converted into the pharmacologically active compound psilocin in the body by a dephosphorylation reaction. This chemical reaction takes place under strongly acidic conditions, or under physiological conditions in the body, through the action of enzymes called phosphatases. Psilocybin is a tryptamine compound having a chemical structure derived from tryptophan and containing a ring configuration called an indole linked to an ethylamine substituent. It bears a close structural resemblance to the neurotransmitter serotonin . Psilocybin is a zwitterionic alkaloid that is soluble in water, moderately soluble in methanol and ethanol, and insoluble in most organic solvents. Exposure to light is detrimental to the stability of aqueous solutions of psilocybin, and will cause it to rapidly oxidize—an important consideration when using it as an analytical standard. A method for the large-scale synthesis of psilocybin was reported by a Japanese group in 2003.
Many analytical techniques have been used to identify and evaluate the quantity of psilocybin in mushroom material. These techniques include thin layer chromatography,gas chromatography coupled to mass spectrometry ,ion mobility spectrometry,capillary zone electrophoresis, ultraviolet spectroscopy,infrared spectroscopy, high performance liquid chromatography with ultraviolet, fluorescence, electrochemical, or electrospray mass spectrometric detection methods. The earliest techniques used gas chromatography, however, a problem with this method is that psilocybin dephosphorylates to psilocin prior to analysis, complicating the analysis.
Various chromatographic methods have been developed to detect psilocin in body fluids: the rapid emergency drug identification system , 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, the analysis in plasma or serum requires a preliminary extraction, followed by derivatization of the extracts in the case of GC-MS. A specific immunoassay has also been developed to detect psilocin in whole blood samples.
Psilocin concentrations in the plasma of adult volunteers averaged about 8 µg/L within 2 hours after ingestion of a single 15 mg oral psilocybin dose. A young man arrested for driving under the influence of psilocybin mushrooms had serum and urine psilocin levels of 18 and 52 µg/L, respectively.