Psilocin

s. (Notice the characteristic blue bruising by the stems of the mushrooms.) Psilocin is used recreationally, spirituality or shamanically, and medically. It is most commonly used in the form of its prodrugs such as psilocybin and 4-AcO-DMT (psilacetin). However, psilocin may also be used itself, either in the form of psilocybin-containing mushrooms (which variably contain psilocin up to similar amounts as psilocybin) or in synthetic form. This is related to psilocin's lack of ester prodrug moiety, which results in its molecular weight being about 40% lower than that of psilocybin (204g/mol and 284g/mol, respectively). ==Contraindications==

There has been no direct lethality associated with psilocin. There has been no reported withdrawal syndrome when chronic use of this drug is ceased. There is cross tolerance among psilocin, mescaline, lysergic acid diethylamide (LSD), and other psychedelics due to downregulation of these receptors. ==Overdose==

Pharmacodynamics Psilocin is the pharmacologically active agent in the body after ingestion of psilocybin or some species of psychedelic mushrooms. Psilocybin is rapidly dephosphorylated in the body to psilocin which acts as a serotonin 5-HT2A, 5-HT2C and 5-HT1A receptor agonist or partial agonist. Psilocin exhibits functional selectivity in that it activates phospholipase A2 instead of activating phospholipase C as the endogenous ligand serotonin does. Psilocin is structurally similar to serotonin (5-hydroxytryptamine), differing only by the hydroxyl group being on the 4-position rather than the 5 and the dimethyl groups on the nitrogen. Its effects are thought to come from its agonist activity at 5-HT2A receptors in the prefrontal cortex. Psilocin's psychedelic effects are directly correlated with the drug's occupancy at these receptor sites. The drug shows pronounced biased agonism at the serotonin 5-HT2C receptor. Psilocin has no significant effect on dopamine receptors only affects the noradrenergic system at very high doses. Psilocin has been reported to act as a highly potent positive allosteric modulator of the tropomyosin receptor kinase B (TrkB), one of the receptors of brain-derived neurotrophic factor (BDNF). However, subsequent studies failed to reproduce these findings and instead found no interaction of psilocin with TrkB. The cryo-EM structures of the serotonin 5-HT2A receptor with psilocin, as well as with various other psychedelics and serotonin 5-HT2A receptor agonists, have been solved and published by Bryan L. Roth and colleagues. Pharmacokinetics Psilocin's elimination half-life ranges from 1 to 3hours depending on route of administration of psilocybin. ==Chemistry==

Psilocin, also known as 4-hydroxy-N,N-dimethyltryptamine (4-HO-DMT), is a tryptamine derivative. It can be obtained by dephosphorylation of psilocybin under strongly acidic or under alkaline conditions (hydrolysis). A synthetic route uses the Speeter–Anthony tryptamine synthesis procedure. First, 4-hydroxyindole is Friedel-Crafts-acylated with oxalyl chloride in position 3. The compound is further reacted with dimethylamine, yielding the indole-3-yl-glyoxamide. Finally, this 4-hydroxyindole-3-N,N-dimethylglyoxamide is reduced by lithium aluminum hydride yielding psilocin. Stability Psilocin is relatively unstable in solution due to its phenolic hydroxy (-OH) group. In the presence of oxygen, it readily forms bluish and dark black degradation products. Similar products are also formed in the presence of oxygen and Fe3+ ions. Analogues Analogues of psilocin (4-HO-DMT) include dimethyltryptamine (DMT), 4-hydroxytryptamine (4-HT or 4-HO-T), norpsilocin (4-HO-NMT), 4-HO-TMT, 4-HO-MET (metocin), 4-HO-DET (ethocin), 4-HO-MPT (meprocin), 4-HO-DPT (deprocin), 4-HO-MiPT (miprocin), 4-HO-DiPT (diprocin), 4-MeO-DMT, and 5-MeO-DMT, among others. Analogues of psilocin prodrugs include norbaeocystin (4-PO-T), baeocystin (4-PO-NMT), aeruginascin (4-PO-TMT), and ethocybin (4-PO-DET), among others. Bufotenin (5-HO-DMT), 6-HO-DMT, and 7-HO-DMT are positional isomers of psilocin. 1-Methylpsilocin is a serotonin 5-HT2C receptor-preferring agonist. 4-Fluoro-DMT Another analogue of psilocin is 1-isopropyl-6-fluoropsilocin (O-4310). Sulfur analogues of psilocin are known with a benzothienyl replacement as well as 4-SH-DMT. A deuterated isotopologue of psilocin is deupsilocin (d10-psilocin) or CYB003 (HLP003). ==History==

Psilocin and its phosphorylated cousin, psilocybin, were first isolated and named in 1958 by Swiss chemist Albert Hofmann. ==Society and culture==

Legal status United Nations Psilocin is a Schedule I drug under the Convention on Psychotropic Substances. The United Nations Convention on Psychotropic Substances (adopted in 1971) requires its members to prohibit psilocybin, and parties to the treaty are required to restrict the use of the drug to medical and scientific research under strictly controlled conditions. Australia Psilocin is considered a Schedule 9 prohibited substance in Australia under the Poisons Standard (October 2015). A Schedule 9 substance is a substance which may be abused or misused, the manufacture, possession, sale or use of which should be prohibited by law except when required for medical or scientific research, or for analytical, teaching or training purposes with approval of Commonwealth and/or State or Territory Health Authorities. Russia Psilocin and psilocybin are banned in Russia, due to their status as narcotic drugs, with a criminal penalty for possession of more than 50mg. United States Psilocin is a Schedule I controlled substance in the United States since 1971. ==Research==

Psilocin is being evaluated under the developmental code name PLZ-1015 for the treatment of pervasive developmental disorders like autism in children. Its prodrug psilocybin is also being studied for treatment of depression and a variety of other conditions. ==See also==