Psilocin, also known as 4-hydroxy-''N'',''N''-dimethyltryptamine (4-HO-DMT), is a substituted tryptamine

alkaloid Alkaloids are a broad class of natural product, naturally occurring organic compounds that contain at least one nitrogen atom. Some synthetic compounds of similar structure may also be termed alkaloids. Alkaloids are produced by a large varie ...

and a serotonergic psychedelic. It is present in most psychedelic mushrooms together with its phosphorylated counterpart

psilocybin Psilocybin, also known as 4-phosphoryloxy-''N'',''N''-dimethyltryptamine (4-PO-DMT), is a natural product, naturally occurring tryptamine alkaloid and Investigational New Drug, investigational drug found in more than List of psilocybin mushroom ...

. Psilocybin, as well as synthetic

ester In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...

s such as 4-AcO-DMT (psilacetin; ''O''-acetylpsilocin) and 4-PrO-DMT (''O''-propionylpsilocin), are prodrugs of psilocin. Acting on the

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

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 Lysergic acid diethylamide, commonly known as LSD (from German ; often referred to as acid or lucy), is a Semisynthesis, semisynthetic, Hallucinogen, hallucinogenic compound derived from ergot, known for its powerful psychological effects and ...

(LSD) and ''N'',''N''-dimethyltryptamine (DMT). Psilocin is a Schedule I drug under the Convention on Psychotropic Substances.

Uses

Psilocin is used recreationally,

spirituality The meaning of ''spirituality'' has developed and expanded over time, and various meanings can be found alongside each other. Traditionally, spirituality referred to a religious process of re-formation which "aims to recover the original shape o ...

or shamanically, and medically. It is most commonly used in the form of its prodrugs such as

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). This is related to psilocin's lack of

prodrug moiety, which results in its

molecular weight A molecule is a group of two or more atoms that are held together by Force, attractive forces known as chemical bonds; depending on context, the term may or may not include ions that satisfy this criterion. In quantum physics, organic chemi ...

being about 40% lower than that of psilocybin (204.273g/mol and 284.252g/mol, respectively). The human dosage of psilocin has been given as 10 to 20mg.

Effects

The effects observed after ingestion of psilocin 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 ...

, dilated pupils, 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 Open or OPEN may refer to: Music * Open (band), Australian pop/rock band * The Open (band), English indie rock band * ''Open'' (Blues Image album), 1969 * ''Open'' (Gerd Dudek, Buschi Niebergall, and Edward Vesala album), 1979 * ''Open'' (Go ...

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 with sy ...

(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 A headache, also known as cephalalgia, 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 (mood), depression in those with severe ...

, sweating and chills, and

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...

. Psilocin acts as a

5-HT_2A, 5-HT_2C, and 5-HT_1A receptor

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

partial agonist In pharmacology, partial agonists are drugs that bind to and activate a given Receptor (biochemistry), receptor, but have only partial Intrinsic activity, efficacy at the receptor relative to a full agonist. They may also be considered Ligand (bio ...

. Such receptors are claimed to significantly regulate visual processing,

decision making In psychology, decision-making (also spelled decision making and decisionmaking) is regarded as the cognitive process resulting in the selection of a belief or a course of action among several possible alternative options. It could be either ra ...

, mood,

blood pressure Blood pressure (BP) is the pressure of Circulatory system, circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term ...

, and

heart rate Heart rate is the frequency of the cardiac cycle, heartbeat measured by the number of contractions of the heart per minute (''beats per minute'', or bpm). The heart rate varies according to the body's Human body, physical needs, including the nee ...

. There has been no direct

lethality Lethality (also called deadliness or perniciousness) is how capable something is of causing death. Most often it is used when referring to diseases, chemical weapons, biological weapons, or their toxic chemical components. The use of this term ...

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 Mescaline, also known as mescalin or mezcalin, and in chemical terms 3,4,5-trimethoxyphenethylamine, is a natural product, naturally occurring psychedelic drug, psychedelic alkaloid, protoalkaloid of the substituted phenethylamine class, found ...

(LSD), and other psychedelics due to

downregulation In biochemistry, in the biology, biological context of organisms' regulation of gene expression and production of gene products, downregulation is the process by which a cell (biology), cell decreases the production and quantities of its cellular ...

of these receptors.

Interactions

Pharmacology

Pharmacodynamics

Psilocin is the pharmacologically 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 receptor

. Psilocin exhibits functional selectivity in that it activates phospholipase A2 instead of activating phospholipase C as the

endogenous Endogeny, in biology, refers to the property of originating or developing from within an organism, tissue, or cell. For example, ''endogenous substances'', and ''endogenous processes'' are those that originate within a living system (e.g. an ...

ligand In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's el ...

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 Nitrogen is a chemical element; it has Symbol (chemistry), symbol N and atomic number 7. Nitrogen is a Nonmetal (chemistry), nonmetal and the lightest member of pnictogen, group 15 of the periodic table, often called the Pnictogen, pnictogens. ...

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

prefrontal cortex In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. It is the association cortex in the frontal lobe. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, ...

. Psilocin has no significant effect on dopamine receptors only affects the noradrenergic system at very high doses. The cryo-EM

structure A structure is an arrangement and organization of interrelated elements in a material object or system, or the object or system so organized. Material structures include man-made objects such as buildings and machines and natural objects such as ...

s 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 Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the blood plasma. ...

ranges from 1 to 3hours depending on

route of administration In pharmacology and toxicology, a route of administration is the way by which a medication, drug, fluid, poison, or other substance is taken into the body. Routes of administration are generally classified by the location at which the substance ...

Chemistry

Psilocin, also known as 4-hydroxy-''N'',''N''-dimethyltryptamine (4-HO-DMT), is a tryptamine

derivative In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...

. It is closely structurally related to the

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

(which is 5-hydroxytryptamine, also known as 5-HT or 5-HO-T), as well as to the

naturally occurring A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical ...

psychedelics

dimethyltryptamine Dimethyltryptamine (DMT), also known as ''N'',''N''-dimethyltryptamine (''N'',''N''-DMT), is a Psychedelic drug, serotonergic hallucinogen and Investigational New Drug, investigational drug of the substituted tryptamine, tryptamine family tha ...

(''N'',''N''-dimethyltryptamine; DMT) and bufotenin (5-hydroxy-''N'',''N''-DMT; 5-HO-DMT).

Psilocybin Psilocybin, also known as 4-phosphoryloxy-''N'',''N''-dimethyltryptamine (4-PO-DMT), is a natural product, naturally occurring tryptamine alkaloid and Investigational New Drug, investigational drug found in more than List of psilocybin mushroom ...

is psilocin's ''O''-

phosphate Phosphates are the naturally occurring form of the element phosphorus. In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthop ...

(4-phosphoryloxy-''N'',''N''-DMT; 4-PO-DMT).

Synthesis

Psilocin can be obtained by dephosphorylation of natural psilocybin under strongly

acid An acid is a molecule or ion capable of either donating a proton (i.e. Hydron, hydrogen cation, H+), known as a Brønsted–Lowry acid–base theory, Brønsted–Lowry acid, or forming a covalent bond with an electron pair, known as a Lewis ...

ic or under

alkaline In chemistry, an alkali (; from the Arabic word , ) is a basic salt of an alkali metal or an alkaline earth metal. An alkali can also be defined as a base that dissolves in water. A solution of a soluble base has a pH greater than 7.0. The ...

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 ...

). 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 Dimethylamine is an organic compound with the formula (CH3)2NH. This secondary amine is a colorless, flammable gas with an ammonia-like odor. Dimethylamine is commonly encountered commercially as a solution in water at concentrations up to around ...

, 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 Oxygen is a chemical element; it has chemical symbol, symbol O and atomic number 8. It is a member of the chalcogen group (periodic table), group in the periodic table, a highly reactivity (chemistry), reactive nonmetal (chemistry), non ...

, 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

prodrugs of psilocin are known, such as

(4-PO-DMT), 4-AcO-DMT, and 4-PrO-DMT. Psilocybin is the ''O''-

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 In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula (whereas normal methane has the formula ). In formulas, the group is often abbreviated a ...

of psilocin at the dimethylated

with an isopropyl or

ethyl group In organic chemistry, an ethyl group (abbr. Et) is an alkyl substituent with the formula , derived from ethane (). ''Ethyl'' is used in the International Union of Pure and Applied Chemistry The International Union of Pure and Applied ...

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 Sulfur ( American spelling and the preferred IUPAC name) or sulphur ( Commonwealth spelling) is a chemical element; it has symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms ...

analogues of psilocin are known with a benzothienyl replacement as well as 4-SH-DMT.; CA 68:95680n

History

Psilocin and its phosphorylated cousin,

, were first isolated and named in 1958 by Swiss chemist Albert Hofmann. He obtained the chemicals from laboratory-grown specimens of the entheogenic

mushroom A mushroom or toadstool is the fleshy, spore-bearing Sporocarp (fungi), fruiting body of a fungus, typically produced above ground on soil or another food source. ''Toadstool'' generally refers to a poisonous mushroom. The standard for the n ...

'' 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 Autism, also known as autism spectrum disorder (ASD), is a neurodevelopmental disorder characterized by differences or difficulties in social communication and interaction, a preference for predictability and routine, sensory processing d ...

in children. Its prodrug

is also being studied for treatment of depression and a variety of other conditions.

References

External links

Psilocin - Isomer Design

4-HO-DMT (Psilocin) - TiHKAL - Erowid

4-HO-DMT (Psilocin) - TiHKAL - Isomer Design
{{Tryptamines 5-HT1A agonists 5-HT1B agonists 5-HT2A agonists 5-HT2B agonists 5-HT2C agonists N,N-Dialkyltryptamines Dimethylamino compounds Entheogens Experimental hallucinogens Human drug metabolites 4-Hydroxytryptamines Mycotoxins Partial monoamine releasing agents Psilocybin Psychedelic tryptamines Serotonin receptor agonists Serotonin releasing agents TAAR1 agonists Tryptamine alkaloids