Psilocin

Psilocin, also known as 4-hydroxy-N,N-dimethyltryptamine (4-HO-DMT), is a substituted tryptamine alkaloid and a serotonergic psychedelic. It is present in most psychedelic mushrooms together with its phosphorylated counterpart psilocybin. Psilocybin, as well as synthetic esters such as 4-AcO-DMT (psilacetin; O-acetylpsilocin) and 4-PrO-DMT (O-propionylpsilocin), are prodrugs of psilocin.

Acting on the serotonin 5-HT_2A receptors, psilocin's psychedelic effects are directly correlated with the drug's occupancy at these receptor sites. It also interacts with other serotonin receptors and targets. The subjective mind-altering effects of psilocin are highly variable in their qualitative nature but resemble those of lysergic acid diethylamide (LSD) and N,N-dimethyltryptamine (DMT).

Psilocin is a Schedule I drug under the Convention on Psychotropic Substances.

Uses

File:Dried Cubensis.jpg

Dried psilocybin mushrooms. (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.

Psilocin is usually used orally, but may also be taken intravenously. In terms of dosage, it is slightly more potent than psilocybin, about 1.4-fold so (i.e., 1.4Template:Nbspmg psilocybin equals about 1.0Template:Nbspmg psilocin). 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 (204.273Template:Nbspg/mol and 284.252Template:Nbspg/mol, respectively). The human dosage of psilocin has been given as 10 to 20Template:Nbspmg.

Effects

The effects observed after ingestion of psilocin can include but are not limited to tachycardia, dilated pupils, restlessness or arousal, euphoria, open and closed eye visuals (common at medium to high doses), synesthesia (e.g. hearing colours and seeing sounds), increased body temperature, headache, sweating and chills, and nausea. Psilocin acts as a serotonin 5-HT_2A, 5-HT_2C, and 5-HT_1A receptor agonist or partial agonist. Such receptors are claimed to significantly regulate visual processing, decision making, mood, blood pressure, and heart rate.

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.

Pharmacology

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-HT_2A, 5-HT_2C and 5-HT_1A 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-HT_2A receptors in the prefrontal cortex. Psilocin has no significant effect on dopamine receptors only affects the noradrenergic system at very high doses.

The cryo-EM structures of the serotonin 5-HT_2A receptor with psilocin, as well as with various other psychedelics and serotonin 5-HT_2A receptor agonists, have been solved and published by Bryan L. Roth and colleagues.

Pharmacokinetics

Psilocin's elimination half-life ranges from 1 to 3Template:Nbsphours 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 is closely structurally related to the neurotransmitter serotonin (which is 5-hydroxytryptamine, also known as 5-HT or 5-HO-T), as well as to the naturally occurring psychedelics dimethyltryptamine (N,N-dimethyltryptamine; DMT) and bufotenin (5-hydroxy-N,N-DMT; 5-HO-DMT). Psilocybin is psilocin's O-phosphate ester (4-phosphoryloxy-N,N-DMT; 4-PO-DMT).

Synthesis

Psilocin can be obtained by dephosphorylation of natural 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

A number of ester prodrugs of psilocin are known, such as psilocybin (4-PO-DMT), 4-AcO-DMT, and 4-PrO-DMT. Psilocybin is the O-phosphate ester of psilocin, while 4-AcO-DMT is the O-acetyl ester and 4-PrO-DMT is the O-propionyl ester.

Bufotenin (5-hydroxy-DMT) and 6-hydroxy-DMT are positional isomers of psilocin.

Additionally, replacement of a methyl group of psilocin at the dimethylated nitrogen with an isopropyl or ethyl group yields 4-HO-MiPT (4-hydroxy-N-methyl-N-isopropyltryptamine; Miprocin) and 4-HO-MET (4-hydroxy-N-methyl-N-ethyltryptamine; metocin), respectively. 4-Acetoxy-MET (4-acetoxy-N-methyl-N-ethyltryptamine), also known as 4-AcO-MET, is the acetate ester of 4-HO-MET, and a homologue of 4-AcO-DMT.

1-Methylpsilocin is a functionally 5-HT_2C receptor-preferring agonist. 4-Fluoro-DMT is known. 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.

History

Psilocin and its phosphorylated cousin, psilocybin, were first isolated and named in 1958 by Swiss chemist Albert Hofmann. He obtained the chemicals from laboratory-grown specimens of the entheogenic mushroom Psilocybe mexicana. Hofmann also succeeded in finding synthetic routes to these chemicals.

Society and culture

Legal status

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 50Template:Nbspmg.

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.

External links

• Psilocin - Isomer Design
• 4-HO-DMT (Psilocin) - TiHKAL - Erowid
• 4-HO-DMT (Psilocin) - TiHKAL - Isomer Design