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
Acting on the serotonin 5-HT2A receptors, psilocin's psychedelic effects are directly correlated with the drug's occupancy at these receptor sites.
Psilocin is a Schedule I drug under the Convention on Psychotropic Substances.
Uses
Psilocin is used recreationally,
spirituality or
shamanism, and
medicine. It is most commonly used in the form of its
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., 1.4mg psilocybin equals about 1.0mg psilocin).
Effects
The effects observed after ingestion of psilocin can include but are not limited to
tachycardia,
pupil dilation, restlessness or
arousal,
euphoria,
open-eye visual 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.
Interactions
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
methyl group 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
noradrenaline 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).
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 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
natural product 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
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
Phenols hydroxyl (-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
iron .
Analogues
A number of
ester 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-HT2C receptor-preferring agonist.
Sulfur analogues of psilocin are known with a benzothiophene replacement[; CA 68:95680n]
History
Psilocin and its
phosphorylation 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 50mg.
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
