Psilocin (also known as 4-HO-DMT, 4-hydroxy DMT, psilocine, psilocyn, or psilotsin) is a

substituted tryptamine Substituted tryptamines, or serotonin analogues, are organic compounds which may be thought of as being derived from tryptamine itself. The molecular structures of all tryptamines contain an indole ring, joined to an amino group, amino (NH2) group ...

alkaloid Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of similar ...

and a serotonergic psychedelic substance. It is present in most

psychedelic mushroom Psilocybin mushrooms, commonly known as magic mushrooms, are a polyphyletic informal group of mushroom, fungi that contain psilocybin which turns into psilocin upon ingestion. Biological genera containing psilocybin mushrooms include ''Psilocyb ...

s together with its

phosphorylated In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, whi ...

counterpart

psilocybin Psilocybin ( , ) is a naturally occurring psychedelic prodrug compound produced by more than 200 species of fungi. The most potent are members of the genus ''Psilocybe'', such as '' P. azurescens'', '' P. semilanceata'', and '' P.&nbs ...

. Psilocin is a Schedule I drug under the

Convention on Psychotropic Substances The Convention on Psychotropic Substances of 1971 is a United Nations treaty designed to control psychoactive drugs such as #Amphetamine-type stimulants, amphetamine-type stimulants, barbiturates, benzodiazepines, and Psychedelic drug, psychede ...

. Acting on the 5-HT_2A receptors, psilocin modulates the production and reuptake of

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...

. The mind-altering effects of psilocin are highly variable and subjective and resemble those of

LSD Lysergic acid diethylamide (LSD), also known colloquially as acid, is a potent psychedelic drug. Effects typically include intensified thoughts, emotions, and sensory perception. At sufficiently high dosages LSD manifests primarily mental, vi ...

and

DMT ''N'',''N''-Dimethyltryptamine (DMT or ''N'',''N''-DMT, SPL026) is a substituted tryptamine that occurs in many plants and animals, including human beings, and which is both a derivative and a structural analog of tryptamine. It is used as a ...

Chemistry

Psilocin and its phosphorylated cousin,

, were first isolated and named in 1958 by Swiss chemist

Albert Hofmann Albert Hofmann (11 January 1906 – 29 April 2008) was a Swiss chemist known for being the first to synthesize, ingest, and learn of the psychedelic effects of lysergic acid diethylamide (LSD). Hofmann's team also isolated, named and synthesiz ...

. Hofmann obtained the chemicals from laboratory-grown specimens of the

entheogenic Entheogens are psychoactive substances that induce alterations in perception, mood (psychology), mood, consciousness, cognition, or behavior for the purposes of engendering spiritual development or otherwiseRätsch, Christian, ''The Encyclop ...

mushroom A mushroom or toadstool is the fleshy, spore-bearing fruiting body of a fungus, typically produced above ground, on soil, or on its food source. ''Toadstool'' generally denotes one poisonous to humans. The standard for the name "mushroom" is t ...

Psilocybe mexicana ''Psilocybe mexicana'' is a psychedelic mushroom. Its first known usage was by the natives of North and Central America over 2,000 years ago. Known to the Aztecs as teotlnanácatl, from the Nahuatl ''teotl'' ("god") + ''nanácatl'' ("fungus"). T ...

''. Hofmann also succeeded in finding synthetic routes to these chemicals. Psilocin can be obtained by

dephosphorylation In biochemistry, dephosphorylation is the removal of a phosphate (PO43−) group from an organic compound by hydrolysis. It is a reversible post-translational modification. Dephosphorylation and its counterpart, phosphorylation, activate and deac ...

of natural psilocybin under strongly

acid In computer science, ACID ( atomicity, consistency, isolation, durability) is a set of properties of database transactions intended to guarantee data validity despite errors, power failures, and other mishaps. In the context of databases, a sequ ...

ic or under

alkaline In chemistry, an alkali (; from ar, القلوي, al-qaly, lit=ashes of the saltwort) is a base (chemistry), basic, ionic compound, ionic salt (chemistry), salt of an alkali metal or an alkaline earth metal. An alkali can also be defined as ...

conditions (

hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...

). Another

synthetic Synthetic things are composed of multiple parts, often with the implication that they are artificial. In particular, 'synthetic' may refer to: Science * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic o ...

route uses the Speeter–Anthony tryptamine synthesis procedure. 4-hydroxyindole is

acylated In chemistry, acylation (or alkanoylation) is the chemical reaction in which an acyl group () is added to a compound. The compound providing the acyl group is called the acylating agent. Because they form a strong electrophile when treated with ...

with oxalyl chloride. The compound is further reacted with an

amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituen ...

, yielding indole-3-yl-glyoxalyamide. Finally, the product amide is reduced using lithium aluminum hydride yielding psilocin. Psilocin is relatively unstable in solution due to its

phenolic Phenolic is an adjective and a substantive (noun) that may apply to : * Phenol (or carbolic acid), a colorless crystalline solid and aromatic compound * Phenols, a class of chemical compounds that include phenol * Phenolic content in wine * Phenol ...

hydroxy (-OH) group. In the presence of

oxygen Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as wel ...

, it readily forms bluish and dark black degradation products. Similar products are also formed under acidic conditions in the presence of oxygen and Fe³⁺

ion An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conven ...

s (

Keller's reagent Keller's reagent can refer to either of two different mixtures of acids. In metallurgy, Keller's reagent is a mixture of nitric acid, hydrochloric acid, and hydrofluoric acid, used to etch aluminum alloys to reveal their grain boundaries and or ...

Structural analogs

Sulfur Sulfur (or sulphur in British English) is a chemical element with the symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms form cyclic octatomic molecules with a chemical formula ...

analogs are known with a benzothienyl replacement as well as 4- SH-DMT.

1-Methylpsilocin 1-Methylpsilocin is a tryptamine derivative which acts as a selective agonist for the 5-HT2C receptor (IC50 of 12 nM, vs 633 nM at 5-HT2A), and an inverse agonist at 5-HT2B (Ki of 38 nM). While 1-methylpsilocin does have higher ...

is a functionally 5-HT_2C receptor preferring agonist. 4-Fluoro-''N'',''N''-dimethyltryptamine is known. ''O''-Acetylpsilocin (4-AcO-DMT) is an acetylated analog of psilocin. Additionally, replacement of a methyl group at the dimethylated

nitrogen Nitrogen is the chemical element with the symbol N and atomic number 7. Nitrogen is a nonmetal and the lightest member of group 15 of the periodic table, often called the pnictogens. It is a common element in the universe, estimated at se ...

with an isopropyl or ethyl group yields

4-HO-MIPT 4-HO-MiPT (miprocin, 4-hydroxy-''N''-methyl-''N''-isopropyltryptamine) is a synthetic substituted aromatic compound and a lesser-known psychedelic tryptamine. It is thought to be a serotonergic psychedelic, similar to magic mushrooms, LSD and ...

(4-hydroxy-''N''-methyl-''N''-isopropyltryptamine) and

4-HO-MET 4-HO-MET (4-hydroxy-''N''-methyl-''N''-ethyltryptamine, metocin, or methylcybin), is a lesser-known psychedelic drug. It is a structural− and functional analog of psilocin as well as the 4-hydroxyl analog of methylethyltryptamine (MET). 4-HO-M ...

(4-hydroxy-''N''-methyl-''N''-ethyltryptamine), 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.

Pharmacology

Psilocin is the

pharmacological Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemica ...

ly active agent in the body after ingestion of

or some species of psychedelic mushrooms. Psilocybin is rapidly dephosphorylated in the body to psilocin which acts as a 5-HT_2A, 5-HT_2C and 5-HT_1A

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

partial agonist In pharmacology, partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. They may also be considered ligands which display both agonistic and antagonistic e ...

. Psilocin exhibits

functional selectivity Functional selectivity (or “agonist trafficking”, “biased agonism”, “biased signaling”, "ligand bias" and “differential engagement”) is the ligand-dependent selectivity for certain signal transduction pathways relative to a referen ...

in that it activates

phospholipase A2 The enzyme phospholipase A2 (EC 3.1.1.4, PLA2, systematic name phosphatidylcholine 2-acylhydrolase) catalyse the cleavage of fatty acids in position 2 of phospholipids, hydrolyzing the bond between the second fatty acid “tail” and the glyce ...

instead of activating

phospholipase C Phospholipase C (PLC) is a class of membrane-associated enzymes that cleave phospholipids just before the phosphate group (see figure). It is most commonly taken to be synonymous with the human forms of this enzyme, which play an important role ...

as the endogenous ligand serotonin does. Psilocin is structurally similar to

(5-HT), differing only by the

hydroxyl In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy ...

group being on the 4-position rather than the 5 and the dimethyl groups on the

. Its effects are thought to come from its agonist activity at 5-HT_2A

serotonin receptor 5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in the central and peripheral nervous systems. They mediate both excitatory and inhibitory neur ...

s in the

prefrontal cortex In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, BA13, BA14, BA24, BA25, BA32, BA44, BA45, BA46, ...

. Psilocin has no significant effect on

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...

receptors (unlike

) and only affects the

noradrenergic Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...

system at very high dosages. Psilocin's half-life ranges from 1 to 3 hours.

Behavioral and non-behavioral effects

Its physiological effects are similar to a sympathetic arousal state. Specific effects observed after

ingestion Ingestion is the consumption of a substance by an organism. In animals, it normally is accomplished by taking in a substance through the mouth into the gastrointestinal tract, such as through eating or drinking. In single-celled organisms ingest ...

can include but are not limited to

tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal (su ...

, dilated

pupil The pupil is a black hole located in the center of the iris of the eye that allows light to strike the retina.Cassin, B. and Solomon, S. (1990) ''Dictionary of Eye Terminology''. Gainesville, Florida: Triad Publishing Company. It appears black ...

s, restlessness or arousal,

euphoria Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and da ...

, open and closed eye visuals (common at medium to high doses),

synesthesia Synesthesia (American English) or synaesthesia (British English) is a perceptual phenomenon in which stimulation of one sensory or cognitive pathway leads to involuntary experiences in a second sensory or cognitive pathway. People who re ...

(e.g. hearing colours and seeing sounds), increased

body temperature Thermoregulation is the ability of an organism to keep its body temperature within certain boundaries, even when the surrounding temperature is very different. A thermoconforming organism, by contrast, simply adopts the surrounding temperature ...

headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...

sweat Perspiration, also known as sweating, is the production of fluids secreted by the sweat glands in the skin of mammals. Two types of sweat glands can be found in humans: eccrine glands and apocrine glands. The eccrine sweat glands are distribut ...

ing and chills, and

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

. Psilocin acts as a 5-HT2A, 5-HT2C, and 5-HT1A receptor

or partial agonist. Such receptors are claimed to significantly regulate visuals, decision making, mood, decreased blood pressure, and heart rate. There is virtually no direct lethality associated with psilocin. There is virtually no withdrawal syndrome when chronic use of this

drug A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via insuffla ...

is ceased. There is

cross tolerance Cross-tolerance is a phenomenon that occurs when tolerance to the effects of a certain drug produces tolerance to another drug. It often happens between two drugs with similar functions or effects—for example, acting on the same cell receptor ...

among psilocin,

mescaline Mescaline or mescalin (3,4,5-trimethoxyphenethylamine) is a naturally occurring psychedelic protoalkaloid of the substituted phenethylamine class, known for its hallucinogenic effects comparable to those of LSD and psilocybin. Biological sou ...

, and other 5-HT_2A, 5-HT_2C, and 5-HT_1A agonists due to down-regulation of these receptors.

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).Poisons Standard October 2015 https://www.comlaw.gov.au/Details/F2015L01534 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 as narcotic drugs with a criminal penalty for possession of at least 50 mg.

References

External links

4-HO-DMT
entry in

TiHKAL ''TIHKAL: The Continuation'' is a 1997 book written by Alexander Shulgin and Ann Shulgin about a family of psychoactive drugs known as tryptamines. A sequel to '' PIHKAL: A Chemical Love Story'', ''TIHKAL'' is an acronym that stands for "Tryp ...

{{DEFAULTSORT:Psilocin Dimethylamino compounds Entheogens Hydroxyarenes Mycotoxins Psilocybin Psychedelic drugs Psychedelic tryptamines Serotonin receptor agonists Tryptamine alkaloids