Psilocin

Last updated
Psilocin
Psilocine skeletal formula.svg
Psilocin-3D-balls.png
Clinical data
Other namesPsilocine; Psilocyn; Psilotsin; 4-Hydroxy-N,N-dimethyltryptamine; 4-Hydroxy-DMT; 4-Hydroxy-N,N-DMT; 4-OH-DMT; 4-HO-DMT
Routes of
administration 		By mouth, intravenous [1]
Drug class Serotonergic psychedelic (hallucinogen) [2]
ATC code
  • None
Legal status
Legal status
Pharmacokinetic data
Bioavailability Oral psilocybin: 52.7 ± 20.4% (as psilocin) [2] [1]
Metabolism Liver, other tissues: [4] [2] [1] [5]
• Demethylation and deamination (MAO Tooltip monoamine oxidase)
• Oxidation (ALDH Tooltip aldehyde dehydrogenase)
• Glucuronidation (UGTs)
Metabolites • Psilocin-O-glucuronide [2] [1]
• 4-Hydroxy-indole-3-acetaldehyde [2] [1]
• 4-Hydroxyindole-3-acetic acid (4-HIAA) [2] [1]
• 4-Hydroxytryptophol [2] [1]
Elimination half-life Oral psilocybin: 2.3–3 hours (as psilocin) [2] [1] [6]
IV Tooltip Intravenous injection psilocybin: 1.2 hours (as psilocin) [1] [6]
Excretion Urine (mainly as psilocin-O-glucuronide, 2–4% unchanged) [2] [1] [6]
Identifiers
  • 3-[2-(Dimethylamino)ethyl]-1H-indol-4-ol
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.007.543 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C12H16N2O
Molar mass 204.273 g·mol−1
3D model (JSmol)
Melting point 173 to 176 °C (343 to 349 °F)
  • CN(C)CCc1c[nH]c2cccc(O)c12
  • InChI=1S/C12H16N2O/c1-14(2)7-6-9-8-13-10-4-3-5-11(15)12(9)10/h3-5,8,13,15H,6-7H2,1-2H3 Yes check.svgY
  • Key:SPCIYGNTAMCTRO-UHFFFAOYSA-N Yes check.svgY
   (verify)

Psilocin, also known as 4-hydroxy-N,N-dimethyltryptamine (4-OH-DMT), is a substituted tryptamine alkaloid and a serotonergic psychedelic. It is present in most psychedelic mushrooms [7] together with its phosphorylated counterpart psilocybin. Psilocin is a Schedule I drug under the Convention on Psychotropic Substances. [8] Acting on the serotonin 5-HT2A receptors, psilocin's psychedelic effects are directly correlated with the drug's occupancy at these receptor sites. [9] The subjective mind-altering effects of psilocin are highly variable and are said to resemble those of lysergic acid diethylamide (LSD) and N,N-dimethyltryptamine (DMT).

Contents

Effects

Dried psilocybin mushrooms. (Notice the characteristic blue bruising by the stems of the mushrooms.) Dried Cubensis.jpg
Dried psilocybin mushrooms. (Notice the characteristic blue bruising by the stems of the mushrooms.)

Its physiological effects are similar to a sympathetic arousal state. Specific effects observed after ingestion 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-HT2A, 5-HT2C, and 5-HT1A receptor agonist or partial agonist. Such receptors are claimed to significantly regulate visual processing, decision making, mood, blood pressure, and heart rate. [10]

There has been no direct lethality associated with psilocin. [10] [11] There has been no reported withdrawal syndrome when chronic use of this drug is ceased. [10] [12] There is cross tolerance among psilocin, mescaline, lysergic acid diethylamide (LSD), [10] [13] and other 5-HT2A, 5-HT2C, and 5-HT1A receptor agonists due to downregulation of these receptors.

Pharmacology

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), [10] 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 has no significant effect on dopamine receptors (unlike lysergic acid diethylamide (LSD)) and only affects the noradrenergic system at very high doses. [14]

Psilocin's elimination half-life ranges from 1 to 3 hours depending on route of administration of psilocybin. [6]

Chemistry

Psilocin and its phosphorylated cousin, psilocybin, were first isolated and named in 1958 by Swiss chemist Albert Hofmann. Hofmann obtained the chemicals from laboratory-grown specimens of the entheogenic mushroom Psilocybe mexicana . Hofmann also succeeded in finding synthetic routes to these chemicals. [15]

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. [16]

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. [17] Similar products are also formed in the presence of oxygen and Fe3+ ions.

Analogues

Sulfur analogs are known with a benzothienyl replacement [18] as well as 4-SH-DMT. [19] 1-Methylpsilocin is a functionally 5-HT2C receptor preferring agonist. [20] 4-Fluoro-N,N-dimethyltryptamine is known. [20] O-Acetylpsilocin (4-AcO-DMT) is the ester of acetic acid with psilocin. Additionally, replacement of a methyl group at the dimethylated nitrogen with an isopropyl or ethyl group yields 4-HO-MIPT (4-hydroxy-N-methyl-N-isopropyltryptamine) and 4-HO-MET (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.

Society and culture

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). [21] 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. [21]

Russia

Psilocin and psilocybin are banned in Russia, due to their status as narcotic drugs, with a criminal penalty for possession of more than 50 mg. [22]

Research

Psilocin is being evaluated under the developmental code name PLZ-1015 for the treatment of pervasive developmental disorders like autism in children. [23]

See also

Related Research Articles

<i>N</i>,<i>N</i>-Dimethyltryptamine Chemical compound

N,N-Dimethyltryptamine is a substituted tryptamine that occurs in many plants and animals, including humans, and which is both a derivative and a structural analog of tryptamine. DMT is used as a psychedelic drug and prepared by various cultures for ritual purposes as an entheogen.

<span class="mw-page-title-main">Psilocybin</span> Chemical compound found in some species of mushrooms

Psilocybin, also known as 4-phosphoryloxy-N,N-dimethyltryptamine (4-PO-DMT), and formerly sold under the brand name Indocybin, is a naturally occurring psychedelic prodrug compound produced by more than 200 species of fungi. Psilocybin is itself biologically inactive but is quickly converted by the body to psilocin, which has mind-altering effects similar, in some aspects, to those of other classical psychedelics. Effects include euphoria, hallucinations, changes in perception, a distorted sense of time, and perceived spiritual experiences. It can also cause adverse reactions such as nausea and panic attacks.

<span class="mw-page-title-main">Psychedelic drug</span> Hallucinogenic class of psychoactive drug

Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states and a perceived "expansion of consciousness". Also referred to as classic hallucinogens or serotonergic hallucinogens, the term psychedelic is sometimes used more broadly to include various types of hallucinogens, such as those which are atypical or adjacent to psychedelia like salvia and MDMA, respectively.

<span class="mw-page-title-main">5-MeO-DMT</span> Chemical compound

5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine), also known as O-methylbufotenin or mebufotenin, is a naturally occurring psychedelic of the tryptamine family. It is found in a wide variety of plant species, and is also secreted by the glands of at least one toad species, the Colorado River toad. It may occur naturally in humans as well. Like its close relatives dimethyltryptamine (DMT) and bufotenin (5-HO-DMT), it has been used as an entheogen in South America. Slang terms include Five-methoxy, the power, bufo, and toad venom.

<span class="mw-page-title-main">Bufotenin</span> Psychedelic drug found in toads, mushrooms and plants

Bufotenin, also known as dimethylserotonin or as 5-hydroxy-N,N-dimethyltryptamine (5-HO-DMT), is a tryptamine derivative, more specifically, a dimethyltryptamine (DMT) analogue, related to the neurotransmitter serotonin. It is an alkaloid found in some species of mushrooms, plants and toads, especially the skin. It is also found naturally in the human body in small amounts.

<span class="mw-page-title-main">4-HO-MiPT</span> Chemical compound

4-HO-MiPT 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 mescaline. Its molecular structure and pharmacological effects somewhat resemble those of the tryptamine psilocin, which is the primary psychoactive chemical in magic mushrooms.

<span class="mw-page-title-main">LSM-775</span> Chemical compound

N-Morpholinyllysergamide, also known as lysergic acid morpholide, is a derivative of ergine (lysergamide). It is less potent than lysergic acid diethylamide (LSD) but is reported to have some LSD-like effects at doses ranging from 75 to 700 micrograms and a shorter duration. LSM-775 may only produce weak or threshold psychedelic effects in humans.

<i>O</i>-Acetylpsilocin Semi-synthetic psychoactive drug

Psilacetin, also known as O-acetylpsilocin or as 4-acetoxy-N,N-dimethyltryptamine, is a semi-synthetic serotonergic psychedelic drug that has been suggested by David Nichols to be a potentially useful alternative to psilocybin for pharmacological studies, as they are both believed to be prodrugs of psilocin. However, some users report that O-acetylpsilocin's subjective effects differ from those of psilocybin and psilocin. Additionally, some users prefer 4-AcO-DMT to natural psilocybin mushrooms due to feeling fewer adverse side effects such as nausea and heavy body load, which are more frequently reported in experiences involving natural mushrooms. It is the acetylated form of the psilocybin mushroom alkaloid psilocin and is a lower homolog of 4-AcO-MET, 4-AcO-DET, 4-AcO-MiPT and 4-AcO-DiPT.

<span class="mw-page-title-main">Serotonin receptor agonist</span> Neurotransmission-modulating substance

A serotonin receptor agonist is an agonist of one or more serotonin receptors. They activate serotonin receptors in a manner similar to that of serotonin, a neurotransmitter and hormone and the endogenous ligand of the serotonin receptors.

<span class="mw-page-title-main">Aeruginascin</span> Chemical compound

Aeruginascin, also known as 4-phosphoryloxy-N,N,N-trimethyltryptamine (4-PO-TMT), is an indoleamine derivative which occurs naturally within the mushrooms Inocybe aeruginascens, Pholiotina cyanopus, and Psilocybe cubensis.

<span class="mw-page-title-main">Substituted tryptamine</span> Class of indoles

Substituted tryptamines, or simply tryptamines, also known as serotonin analogues (i.e., 5-hydroxytryptamine 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 (NH2) group via an ethyl (−CH2–CH2−) sidechain. In substituted tryptamines, the indole ring, sidechain, and/or amino group are modified by substituting another group for one of the hydrogen (H) atoms.

<span class="mw-page-title-main">Head-twitch response</span> Head movement in rodents upon 5-HT2A receptor activation

The head-twitch response (HTR), also sometimes known as wet dog shakes (WDS) in rats, is a rapid side-to-side head movement that occurs in mice and rats when the serotonin 5-HT2A receptor is activated. Serotonergic psychedelics, including lysergic acid diethylamide (LSD), induce the HTR, and so the HTR is widely used as an animal behavioral model of hallucinogen effects and to discover new psychedelic drugs. HTR-like effects are also induced by psychedelics in other animal species, for instance cats and stump-tailed macaque monkeys. Other related behaviors to head twitches induced by serotonergic agents include limb jerks and body scratches. The only other behavioral paradigms for assessment of psychedelic-like effects in animals are drug discrimination (DD), prepulse inhibition (PPI), and time perception.

<span class="mw-page-title-main">Psilocybin therapy</span> Experimental use of psilocybin to treat anxiety & depression

Psilocybin therapy is the use of psilocybin in treating a range of mental health conditions, such as depression, anxiety, addictions, obsessive compulsive disorder (OCD), and psychosis. It is one of several forms of psychedelic therapy under study. Psilocybin was popularized as a psychedelic recreational drug in the 1970s and was classified as a Schedule I drug by the DEA. Research on psilocybin as a medical treatment was restricted until the 1990s because of the sociocultural fear of dependence on this drug. As of 2022, psilocybin is the most commonly researched psychedelic due to its safety and low potential for abuse and dependence. Clinical trials are being conducted at universities and there is evidence confirming the use of psilocybin in the treatment of depression, post-traumatic stress disorder (PTSD) and end of life anxiety.

<span class="mw-page-title-main">4-PrO-DMT</span> Chemical compound

4-Propionoxy-N,N-dimethyltryptamine is a synthetic psychedelic drug from the tryptamine family with psychedelic effects, and is believed to act as a prodrug for psilocin. It produces a head-twitch response in mice. It has been sold online as a designer drug since May 2019. It was first identified as a new psychoactive substance in Sweden, in July 2019. A number of related derivatives have been synthesized as prodrugs of psilocin for medical applications.

<i>O</i>-Acetylbufotenine Psychedelic tryptamine

O-Acetylbufotenine, or bufotenine O-acetate, also known as 5-acetoxy-N,N-dimethyltryptamine (5-AcO-DMT) or O-acetyl-N,N-dimethylserotonin, is a synthetic tryptamine derivative and putative serotonergic psychedelic. It is the O-acetylated analogue of the naturally occurring peripherally selective serotonergic tryptamine bufotenine and is thought to act as a centrally penetrant prodrug of bufotenine.

<span class="mw-page-title-main">4-HO-TMT</span> Serotonergic compound

4-HO-TMT, or 4-OH-TMT, also known as 4-hydroxy-N,N,N-trimethyltryptammonium or as dephosphorylated aeruginascin, is a substituted tryptamine derivative and the active form of aeruginascin (4-PO-TMT), analogously to how psilocin (4-HO-DMT) is the active form of psilocybin (4-PO-DMT). 4-HO-TMT is closely related to bufotenidine, the N-trimethyl analogue of serotonin.

A trip killer, or hallucinogen antidote, is a drug that aborts or reduces the effects of a hallucinogenic drug experience. As there are different types of hallucinogens that work in different ways, there are different types of trip killers. They can completely block or reduce the effects of hallucinogens or they can simply provide anxiety relief and sedation. Examples of trip killers, in the case of serotonergic psychedelics, include serotonin receptor antagonists, like antipsychotics and certain antidepressants, and benzodiazepines. Trip killers are sometimes used by recreational psychedelic users as a form of harm reduction to manage so-called bad trips, for instance difficult experiences with prominent anxiety. They can also be used clinically to manage effects of hallucinogens, like anxiety and psychomotor agitation, for instance in the emergency department.

<span class="mw-page-title-main">6-MeO-DMT</span> Non-hallucinogenic 5-HT2A agonist

6-MeO-DMT, or 6-methoxy-N,N-dimethyltryptamine, also known as 6-OMe-DMT, is a serotonergic drug of the tryptamine family. It is the 6-methoxy derivative of the serotonergic psychedelic N,N-dimethyltryptamine (DMT) and is a positional isomer of the serotonergic psychedelic 5-MeO-DMT.

<span class="mw-page-title-main">4-Hydroxytryptamine</span> Serotonin receptor agonist

4-Hydroxytryptamine, also known as N,N-didesmethylpsilocin, is a naturally occurring tryptamine alkaloid. It is closely related chemically to the neurotransmitter serotonin, the psychedelic psilocin, and is the active form of the tryptamine alkaloid norbaeocystin.

References

  1. 1 2 3 4 5 6 7 8 9 10 Lowe H, Toyang N, Steele B, Valentine H, Grant J, Ali A, Ngwa W, Gordon L (May 2021). "The Therapeutic Potential of Psilocybin". Molecules. 26 (10): 2948. doi: 10.3390/molecules26102948 . PMC   8156539 . PMID   34063505.
  2. 1 2 3 4 5 6 7 8 9 Dodd S, Norman TR, Eyre HA, Stahl SM, Phillips A, Carvalho AF, Berk M (July 2022). "Psilocybin in neuropsychiatry: a review of its pharmacology, safety, and efficacy". CNS Spectr. 28 (4): 416–426. doi: 10.1017/S1092852922000888 . PMID   35811423.
  3. ↑ Anvisa (2023-07-24). "RDC Nº 804 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 804 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-07-25). Archived from the original on 2023-08-27. Retrieved 2023-08-27.
  4. ↑ MacCallum CA, Lo LA, Pistawka CA, Deol JK (2022). "Therapeutic use of psilocybin: Practical considerations for dosing and administration". Frontiers in Psychiatry. 13: 1040217. doi: 10.3389/fpsyt.2022.1040217 . PMC   9751063 . PMID   36532184.
  5. ↑ Coppola M, Bevione F, Mondola R (February 2022). "Psilocybin for Treating Psychiatric Disorders: A Psychonaut Legend or a Promising Therapeutic Perspective?". Journal of Xenobiotics. 12 (1): 41–52. doi: 10.3390/jox12010004 . PMC   8883979 . PMID   35225956.
  6. 1 2 3 4 Tylš F, Páleníček T, Horáček J (March 2014). "Psilocybin--summary of knowledge and new perspectives". European Neuropsychopharmacology. 24 (3): 342–356. doi:10.1016/j.euroneuro.2013.12.006. PMID   24444771. S2CID   10758314.
  7. ↑ Gotvaldová K, Borovička J, Hájková K, Cihlářová P, Rockefeller A, Kuchař M (November 2022). "Extensive Collection of Psychotropic Mushrooms with Determination of Their Tryptamine Alkaloids". International Journal of Molecular Sciences. 23 (22): 14068. doi: 10.3390/ijms232214068 . PMC   9693126 . PMID   36430546.
  8. ↑ "List of psychotropic substances under international control" (PDF) (23rd ed.). Vienna Austria: International Narcotics Control Board. August 2003. Archived from the original (PDF) on 4 February 2012. Retrieved 2012-10-11.
  9. ↑ Madsen MK, Fisher PM, Burmester D, Dyssegaard A, Stenbæk DS, Kristiansen S, et al. (June 2019). "Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels". Neuropsychopharmacology. 44 (7): 1328–1334. doi:10.1038/s41386-019-0324-9. PMC   6785028 . PMID   30685771.
  10. 1 2 3 4 5 Diaz J (1996). How Drugs Influence Behavior: A Neurobehavioral Approach. Englewood Cliffs: Prentice Hall. ISBN   978-0-02-328764-0.
  11. ↑ Garcia-Romeu A, Kersgaard B, Addy PH (August 2016). "Clinical applications of hallucinogens: A review". Experimental and Clinical Psychopharmacology. 24 (4): 229–68. doi:10.1037/pha0000084. PMC   5001686 . PMID   27454674.
  12. ↑ Assessing Drug Risks: A Scientific Framework. European Monitoring Centre for Drugs and Drug Addiction. Luxembourg: EMCDDA. 2016.
  13. ↑ Nichols DE (April 2016). "Psychedelics". Pharmacological Reviews. 68 (2): 264–355. doi:10.1124/pr.115.011478. PMC   4813425 . PMID   26841800.
  14. ↑ Jerome L (March–April 2007). "Psilocybin Investigator's Brochure" (PDF). Retrieved 2012-10-11.
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  16. ↑ Kargbo RB, Sherwood A, Walker A, Cozzi NV, Dagger RE, Sable J, et al. (July 2020). "Direct Phosphorylation of Psilocin Enables Optimized cGMP Kilogram-Scale Manufacture of Psilocybin". ACS Omega. 5 (27): 16959–16966. doi:10.1021/acsomega.0c02387. PMC   7364850 . PMID   32685866. S2CID   220599227.
  17. ↑ Lenz C, Wick J, Braga D, García-Altares M, Lackner G, Hertweck C, et al. (January 2020). "Injury-Triggered Blueing Reactions of Psilocybe "Magic" Mushrooms". Angewandte Chemie. 59 (4): 1450–1454. doi:10.1002/anie.201910175. PMC   7004109 . PMID   31725937.
  18. ↑ Chapman NB, Scrowston RM, Sutton TM (1972). "Synthesis of the sulphur analogue of psilocin and some related compounds". Journal of the Chemical Society, Perkin Transactions 1: 3011–15. doi:10.1039/P19720003011.
  19. ↑ CH 421960,Hofmann A, Troxler F,issued 1967; CA 68:95680n
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  21. 1 2 "Poisons Standard". Therapeutics Goods Administration, Department of Health. Australian Government. October 2015.
  22. ↑ "On approval of significant, large and particularly large amounts of narcotic drugs and psychotropic substances, as well as significant, large and particularly large sizes for plants containing narcotic drugs or psychotropic substances, or parts thereof, containing narcotic drugs or psychotropic substances for the purposes of articles 228, 228.1, 229 and 229.1 of the Criminal Code of the Russian Federation (as amended) (translated)". Resolution of the Government of the Russian Federation. Criminal Code of the Russian Federation. 1 October 2012. 1002. Retrieved 1 April 2018.
  23. ↑ "Psilocin - Pilz Bioscience". AdisInsight.
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