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Tweak.

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{{Short description|Psychedelic drug}}
{{Drugbox
| Verifiedfields = verified
| Watchedfields = verified
| verifiedrevid = 458622491
| image = Psilocine skeletal formula.svg
| image_class = skin-invert-image
| width = 175px
| alt = Skeletal formula
| image2 = Psilocin-3D-balls.png
| image_class2 = bg-transparent
| width2 = 200px
| alt2 = Ball-and-stick model


| tradename =
| legal_AU = S9
| legal_BR = F2
| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-07-24 |title=RDC Nº 804 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 804 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-804-de-24-de-julho-de-2023-498447451 |url-status=live |archive-url=https://web.archive.org/web/20230827163149/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-804-de-24-de-julho-de-2023-498447451 |archive-date=2023-08-27 |access-date=2023-08-27 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=2023-07-25}}</ref>
| legal_CA = Schedule III
| legal_UK = Class A
| legal_US = Schedule I
| legal_NZ = Class A
| legal_DE = Anlage I
| legal_UN = P I
| routes_of_administration = [[Oral administration|By mouth]], [[intravenous infusion|intravenous]]<ref name="LoweToyangSteele2021" />
| class = [[Serotonergic psychedelic]]; [[Hallucinogen]]; [[Serotonin receptor agonist]]<ref name="DoddNormanEyre2022" />


| bioavailability = [[Oral administration|Oral]] [[psilocybin]]: 52.7 ± 20.4% (as psilocin)<ref name="DoddNormanEyre2022">{{cite journal | vauthors = Dodd S, Norman TR, Eyre HA, Stahl SM, Phillips A, Carvalho AF, Berk M | title = Psilocybin in neuropsychiatry: a review of its pharmacology, safety, and efficacy | journal = CNS Spectr | volume = 28| issue = 4| pages = 416–426 | date = July 2022 | pmid = 35811423 | doi = 10.1017/S1092852922000888 | url = | doi-access = free }}</ref><ref name="LoweToyangSteele2021" />
| protein_bound =
| metabolism = [[Liver]], other [[tissue (biology)|tissue]]s:<ref name="MacCallumLoPistawka2022">{{cite journal | vauthors = MacCallum CA, Lo LA, Pistawka CA, Deol JK | title = Therapeutic use of psilocybin: Practical considerations for dosing and administration | journal = Frontiers in Psychiatry | volume = 13 | issue = | article-number = 1040217 | date = 2022 | pmid = 36532184 | pmc = 9751063 | doi = 10.3389/fpsyt.2022.1040217 | doi-access = free }}</ref><ref name="DoddNormanEyre2022" /><ref name="LoweToyangSteele2021" /><ref name="CoppolaBevioneMondola2022">{{cite journal | vauthors = Coppola M, Bevione F, Mondola R | title = Psilocybin for Treating Psychiatric Disorders: A Psychonaut Legend or a Promising Therapeutic Perspective? | journal = Journal of Xenobiotics | volume = 12 | issue = 1 | pages = 41–52 | date = February 2022 | pmid = 35225956 | pmc = 8883979 | doi = 10.3390/jox12010004 | doi-access = free }}</ref> • [[Demethylation]] and [[deamination]] ({{Abbrlink|MAO|monoamine oxidase}}) • [[Oxidation]] ({{Abbrlink|ALDH|aldehyde dehydrogenase}}) • [[Glucuronidation]] ([[UDP-glucuronyltransferase|{{Abbr|UGTs|UDP-glucuronyltransferases}}]])
| metabolites = • Psilocin-''O''-glucuronide<ref name="DoddNormanEyre2022" /><ref name="LoweToyangSteele2021" /> • 4-Hydroxy-indole-3-acetaldehyde<ref name="DoddNormanEyre2022" /><ref name="LoweToyangSteele2021" /> • 4-Hydroxyindole-3-acetic acid (4-HIAA)<ref name="DoddNormanEyre2022" /><ref name="LoweToyangSteele2021" /> • 4-Hydroxytryptophol<ref name="DoddNormanEyre2022" /><ref name="LoweToyangSteele2021" />
| elimination_half-life = [[Oral administration|Oral]] psilocybin: 2.3–3{{nbsp}}hours (as psilocin)<ref name="DoddNormanEyre2022" /><ref name="LoweToyangSteele2021" /><ref name="TylšPáleníčekHoráček2014" /> {{Abbrlink|IV|Intravenous injection}} psilocybin: 1.2{{nbsp}}hours (as psilocin)<ref name="LoweToyangSteele2021" /><ref name="TylšPáleníčekHoráček2014" />
| excretion = [[Urine]] (mainly as psilocin-''O''-glucuronide, 2–4% unchanged)<ref name="DoddNormanEyre2022" /><ref name="LoweToyangSteele2021" /><ref name="TylšPáleníčekHoráček2014" />


| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 520-53-6
| ATC_prefix = None
| PubChem = 4980
| IUPHAR_ligand = 11291
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4807
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = CMS88KUW0G
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C08312
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 8613
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 65547
| synonyms = Psilocine; Psilocyn; Psilotsin; 4-Hydroxy-''N'',''N''-dimethyltryptamine; 4-Hydroxy-DMT; 4-Hydroxy-''N'',''N''-DMT; 4-HO-DMT; 4-OH-DMT; PSOH; PAL-153; PAL153; CX-59; CX59


| IUPAC_name = 3-[2-(Dimethylamino)ethyl]-1''H''-indol-4-ol
| C = 12 | H = 16 | N = 2 | O = 1
| SMILES = CN(C)CCc1c[nH]c2cccc(O)c12
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = SPCIYGNTAMCTRO-UHFFFAOYSA-N


| melting_point = 173
| melting_high = 176
}}

'''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 mushroom]]s<ref>{{cite journal | vauthors = Gotvaldová K, Borovička J, Hájková K, Cihlářová P, Rockefeller A, Kuchař M | title = Extensive Collection of Psychotropic Mushrooms with Determination of Their Tryptamine Alkaloids | journal = International Journal of Molecular Sciences | volume = 23 | issue = 22 | article-number = 14068 | date = November 2022 | pmid = 36430546 | doi = 10.3390/ijms232214068 | pmc = 9693126 | doi-access = free }}</ref> together with its [[Phosphorylation|phosphorylated]] counterpart [[psilocybin]]. Psilocybin, as well as [[synthetic compound|synthetic]] [[ester]]s such as [[4-AcO-DMT]] (psilacetin; ''O''-acetylpsilocin) and [[4-PrO-DMT]] (''O''-propionylpsilocin), are [[prodrug]]s of psilocin.

Acting on the [[serotonin]] [[5-HT2A|5-HT2A receptor]]s, psilocin's psychedelic effects are directly correlated with the drug's [[receptor occupancy|occupancy]] at these [[receptor (biochemistry)|receptor site]]s.<ref>{{cite journal | vauthors = Madsen MK, Fisher PM, Burmester D, Dyssegaard A, Stenbæk DS, Kristiansen S, Johansen SS, Lehel S, Linnet K, Svarer C, Erritzoe D, Ozenne B, Knudsen GM | display-authors = 6 | title = Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels | journal = Neuropsychopharmacology | volume = 44 | issue = 7 | pages = 1328–1334 | date = June 2019 | pmid = 30685771 | pmc = 6785028 | doi = 10.1038/s41386-019-0324-9 }}</ref> It also interacts with other [[serotonin receptor]]s and [[biological target|target]]s. The subjective mind-altering effects of psilocin are highly variable in their qualitative nature but resemble those of [[lysergic acid diethylamide]] (LSD) and [[dimethyltryptamine|''N'',''N''-dimethyltryptamine]] (DMT).

Psilocin is a [[Controlled Substances Act#Schedule I|Schedule I]] drug under the [[Convention on Psychotropic Substances]].<ref>{{Cite web |url=http://www.incb.org/pdf/e/list/green.pdf | archive-url = https://web.archive.org/web/20120204035914/http://www.incb.org/pdf/e/list/green.pdf | archive-date = 4 February 2012 |title = List of psychotropic substances under international control | edition = 23rd | date = August 2003 | location = Vienna Austria |publisher=[[International Narcotics Control Board]] |access-date=2012-10-11 }}</ref>

==Uses==
[[File:Dried Cubensis.jpg|thumb|left|Dried [[psilocybin mushroom]]s. (Notice the characteristic blue bruising by the stems of the mushrooms.)]]

Psilocin is used [[recreational drug|recreationally]], [[spirituality]] or [[shamanism|shamanically]], and [[medicine|medically]]. It is most commonly used in the form of its [[prodrug]]s such as [[psilocybin]] and [[4-AcO-DMT]] (psilacetin). However, psilocin may also be used itself, either in the form of [[psilocybin-containing mushroom]]s (which variably contain psilocin up to similar amounts as psilocybin) or in [[chemical synthesis|synthetic]] form.

Psilocin is usually used [[oral administration|orally]], but may also be taken [[intravenous injection|intravenously]]. In terms of [[dose (biochemistry)|dose]], it is slightly more [[potency (pharmacology)|potent]] than psilocybin, about 1.4-fold so (i.e., 1.4{{nbsp}}mg psilocybin equals about 1.0{{nbsp}}mg psilocin).<ref name="TylšPáleníčekHoráček2014" /><ref name="Hofmann1968">{{cite book | author = [[Albert Hofmann]] | chapter = Psychotomimetic Agents | pages = 169–235 | veditors = Burger A | title = Drugs Affecting the Central Nervous System | volume = 2 | date = 1968 | publisher = M. Dekker | location = New York | oclc = 245452885 | ol = OL13539506M | chapter-url = https://archive.org/details/drugsaffectingce0000edit/page/169/mode/1up | url = https://books.google.com/books?id=o_GMwgEACAAJ | quote = Psilocin is approximately 1.4 times as potent as psilocybin. This ratio is the same as that of the molecular weights of the two drugs.}}</ref><ref name="WolbachMinerIsbell1962">{{cite journal | vauthors = Wolbach AB, Miner EJ, Isbell H | title = Comparison of psilocin with psilocybin, mescaline and LSD-25 | journal = Psychopharmacologia | volume = 3 | issue = 3| pages = 219–223 | date = 1962 | pmid = 14007905 | doi = 10.1007/BF00412109 | url = | quote = Psilocin is approximately 1.4 times as potent as psilocybin. This ratio is the same as that of the molecular weights of the two drugs.}}</ref> This is related to psilocin's lack of [[ester]] [[prodrug]] [[moiety (chemistry)|moiety]], which results in its [[molecular weight]] being about 40% lower than that of psilocybin (204.273{{nbsp}}g/mol and 284.252{{nbsp}}g/mol, respectively).<ref name="Hofmann1968" /><ref name="BrimblecombePinder1975">{{cite book | vauthors = Brimblecombe RW, Pinder RM | chapter = Indolealkylamines and Related Compounds | pages = 98–144 | title = Hallucinogenic Agents | date = 1975 | publisher = Wright-Scientechnica | location = Bristol | isbn = 978-0-85608-011-1 | oclc = 2176880 | ol = OL4850660M | url = https://bitnest.netfirms.com/external/Books/978-0-85608-011-1 | quote = Psilocin is claimed to be about 1·4 times as potent as psilocybin, but they are equipotent on a molar basis.}}</ref><ref name="WolbachMinerIsbell1962" /> The human dose of psilocin has been given as 10 to 20{{nbsp}}mg.<ref name="Nichols2004">{{cite journal | vauthors = Nichols DE | title = Hallucinogens | journal = Pharmacol Ther | volume = 101 | issue = 2 | pages = 131–181 | date = February 2004 | pmid = 14761703 | doi = 10.1016/j.pharmthera.2003.11.002 | url = }}</ref><ref name="FantegrossiMurnaneReissig2008">{{cite journal | vauthors = Fantegrossi WE, Murnane KS, Reissig CJ | title = The behavioral pharmacology of hallucinogens | journal = Biochem Pharmacol | volume = 75 | issue = 1 | pages = 17–33 | date = January 2008 | pmid = 17977517 | pmc = 2247373 | doi = 10.1016/j.bcp.2007.07.018 | url = https://www.iceers.org/Documents_ICEERS_site/Scientific_Papers/ayahuasca/Fantegrossi%20et%20al_2008_Behavioral_Pharm_Hallucinogens.pdf}}</ref><ref name="Nichols2016">{{cite journal | vauthors = Nichols DE | title = Psychedelics | journal = Pharmacol Rev | volume = 68 | issue = 2 | pages = 264–355 | date = April 2016 | pmid = 26841800 | pmc = 4813425 | doi = 10.1124/pr.115.011478 }}</ref>

==Effects==
{{See also|Psilocybin#Effects|4-AcO-DMT#Effects}}

The effects observed after ingestion of psilocin can include but are not limited to [[tachycardia]], [[pupil dilation|dilated pupils]], [[Psychomotor agitation|restlessness]] or [[arousal]], [[euphoria]], [[open-eye visual|open]] and [[closed eye visual]]s (common at medium to high doses), [[synesthesia]] (e.g. hearing colours and seeing sounds), increased [[body temperature]], [[headache]], [[sweating]] and [[chills]], and [[nausea]].<ref name="LoweToyangSteele2021">{{cite journal | vauthors = Lowe H, Toyang N, Steele B, Valentine H, Grant J, Ali A, Ngwa W, Gordon L | title = The Therapeutic Potential of Psilocybin | journal = Molecules | volume = 26 | issue = 10 | date = May 2021 | page = 2948 | pmid = 34063505 | pmc = 8156539 | doi = 10.3390/molecules26102948 | doi-access = free | s2cid = 235227972 }}</ref> Psilocin acts as a [[serotonin]] [[5-HT2A receptor|5-HT2A]], [[5-HT2C receptor|5-HT2C]], and [[5-HT1A receptor|5-HT1A receptor]] [[agonist]] or [[partial agonist]]. Such receptors are claimed to significantly regulate [[visual processing]], [[decision making]], [[mood (psychology)|mood]], [[blood pressure]], and [[heart rate]].<ref name="Diaz"/>

There has been no direct [[lethality]] associated with psilocin.<ref name="Diaz"/><ref name="pmid27454674">{{cite journal | vauthors = Garcia-Romeu A, Kersgaard B, Addy PH | title = Clinical applications of hallucinogens: A review | journal = Experimental and Clinical Psychopharmacology | volume = 24 | issue = 4 | pages = 229–68 | date = August 2016 | pmid = 27454674 | pmc = 5001686 | doi = 10.1037/pha0000084 | url = }}</ref> There has been no reported [[withdrawal syndrome]] when chronic use of this drug is ceased.<ref name="Diaz"/><ref>{{cite conference |title=Assessing Drug Risks: A Scientific Framework |conference=European Monitoring Centre for Drugs and Drug Addiction |publisher=EMCDDA |place=Luxembourg |year=2016 |isbn= }}</ref> There is [[cross tolerance]] among psilocin, [[mescaline]], [[lysergic acid diethylamide]] (LSD), and other psychedelics due to [[downregulation]] of these receptors.<ref name="GeigerWurstDaniels2018">{{cite journal | vauthors = Geiger HA, Wurst MG, Daniels RN | title = DARK Classics in Chemical Neuroscience: Psilocybin | journal = ACS Chem Neurosci | volume = 9 | issue = 10 | pages = 2438–2447 | date = October 2018 | pmid = 29956917 | doi = 10.1021/acschemneuro.8b00186 | url = https://shaunlacob.com/wp-content/uploads/2020/12/DC-PSILO.pdf}}</ref><ref name="Nichols2004">{{cite journal | vauthors = Nichols DE | title = Hallucinogens | journal = Pharmacol Ther | volume = 101 | issue = 2 | pages = 131–181 | date = February 2004 | pmid = 14761703 | doi = 10.1016/j.pharmthera.2003.11.002 | url = }}</ref><ref name="Halberstadt2015">{{cite journal | vauthors = Halberstadt AL | title = Recent advances in the neuropsychopharmacology of serotonergic hallucinogens | journal = Behav Brain Res | volume = 277 | issue = | pages = 99–120 | date = January 2015 | pmid = 25036425 | pmc = 4642895 | doi = 10.1016/j.bbr.2014.07.016 | url = }}</ref><ref name="HalberstadtGeyer2011">{{cite journal | vauthors = Halberstadt AL, Geyer MA | title = Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens | journal = Neuropharmacology | volume = 61 | issue = 3 | pages = 364–381 | date = September 2011 | pmid = 21256140 | pmc = 3110631 | doi = 10.1016/j.neuropharm.2011.01.017 | url = }}</ref>

==Interactions==
{{See also|Psilocybin#Interactions|Psychedelic drug#Interactions|Trip killer#Serotonergic psychedelic antidotes}}

==Pharmacology==
{{See also|Psilocybin#Pharmacology|Psychedelic drug#Mechanism of action}}

===Pharmacodynamics===
{{Psilocin activities|float=left}}

Psilocin is the [[pharmacological activity|pharmacologically active]] agent in the body after ingestion of [[psilocybin]] or some species of psychedelic mushrooms. Psilocybin is rapidly [[dephosphorylation|dephosphorylated]] in the body to psilocin which acts as a [[serotonin]] [[5-HT2A|5-HT2A]], [[5-HT2C|5-HT2C]] and [[5-HT1A|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 (biochemistry)|ligand]] serotonin does. Psilocin is [[structural analog|structurally similar]] to serotonin (5-hydroxytryptamine),<ref name="Diaz">{{Cite book | vauthors = Diaz J |title=How Drugs Influence Behavior: A Neurobehavioral Approach |publisher=Prentice Hall |place=Englewood Cliffs |year=1996 |isbn=978-0-02-328764-0 }}</ref> differing only by the [[hydroxyl]] group being on the 4-position rather than the 5 and the [[methyl group|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 receptor]]s only affects the [[noradrenaline|noradrenergic]] system at very high doses.<ref name="Investigator's Brochure">{{Cite web |url=https://www.maps.org/research-archive/psilo/psilo_ib.pdf |title=Psilocybin Investigator's Brochure | vauthors = Jerome L |date=March–April 2007 |access-date=2012-10-11 }}</ref>

Psilocin has been reported to act as a highly [[potency (pharmacology)|potent]] [[positive allosteric modulator]] of the [[tropomyosin receptor kinase B]] (TrkB), one of the [[receptor (biochemistry)|receptor]]s of [[brain-derived neurotrophic factor]] (BDNF).<ref name="HatzipantelisOlson2024">{{cite journal | vauthors = Hatzipantelis CJ, Olson DE | title = The Effects of Psychedelics on Neuronal Physiology | journal = Annu Rev Physiol | volume = 86 | issue = | pages = 27–47 | date = February 2024 | pmid = 37931171 | doi = 10.1146/annurev-physiol-042022-020923 | pmc = 10922499 | url = }}</ref><ref name="FradetKellyDonnelly2025">{{cite journal | vauthors = Fradet M, Kelly CM, Donnelly AJ, Suppes T | title = Psilocybin and hallucinogenic mushrooms | journal = CNS Spectr | volume = 29| issue = 6| pages = 611–632 | date = January 2025 | pmid = 39789676 | doi = 10.1017/S1092852924002487 | url = | doi-access = free }}</ref><ref name="MolinerGirychBrunello2023">{{cite journal | vauthors = Moliner R, Girych M, Brunello CA, Kovaleva V, Biojone C, Enkavi G, Antenucci L, Kot EF, Goncharuk SA, Kaurinkoski K, Kuutti M, Fred SM, Elsilä LV, Sakson S, Cannarozzo C, Diniz CR, Seiffert N, Rubiolo A, Haapaniemi H, Meshi E, Nagaeva E, Öhman T, Róg T, Kankuri E, Vilar M, Varjosalo M, Korpi ER, Permi P, Mineev KS, Saarma M, Vattulainen I, Casarotto PC, Castrén E | title = Psychedelics promote plasticity by directly binding to BDNF receptor TrkB | journal = Nat Neurosci | volume = 26 | issue = 6 | pages = 1032–1041 | date = June 2023 | pmid = 37280397 | pmc = 10244169 | doi = 10.1038/s41593-023-01316-5 | url = }}</ref> However, subsequent studies failed to reproduce these findings and instead found no interaction of psilocin with TrkB.<ref name="JainGumpperSlocum2025">{{cite journal | vauthors = Jain MK, Gumpper RH, Slocum ST, Schmitz GP, Madsen JS, Tummino TA, Suomivuori CM, Huang XP, Shub L, DiBerto JF, Kim K, DeLeon C, Krumm BE, Fay JF, Keiser M, Hauser AS, Dror RO, Shoichet B, Gloriam DE, Nichols DE, Roth BL | title = The polypharmacology of psychedelics reveals multiple targets for potential therapeutics | journal = Neuron | volume = 113| issue = 19| pages = 3129–3142.e9| date = July 2025 | pmid = 40683247 | doi = 10.1016/j.neuron.2025.06.012 | url = https://www.cell.com/cms/10.1016/j.neuron.2025.06.012/attachment/7d8365fe-51f3-4a28-bf40-9999bec837f6/mmc11.pdf | quote = Recent studies have suggested that psychedelics such as LSD directly interact with TrkB with high affinity, promoting BDNF-mediated neuroplasticity and antidepressant-like effects via allosteric potentiation of BDNF signaling in active synapses.8 To investigate this, we screened LSD across 450 human kinases, including TrkB, but found no significant interactions between LSD and any tested human kinases. Further experiments in transfected cells revealed no effect of LSD or psilocin on BDNF-mediated activation of a TrkB reporter. We note that similar negative preliminary results, which have not yet been published in a peer-reviewed journal, were recently reported by Boltaev et al.63}}</ref>

The [[cryo-EM]] [[protein–ligand complex|structure]]s 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.<ref name="GumpperJainKim2025">{{cite journal | vauthors = Gumpper RH, Jain MK, Kim K, Sun R, Sun N, Xu Z, DiBerto JF, Krumm BE, Kapolka NJ, Kaniskan HÜ, Nichols DE, Jin J, Fay JF, Roth BL | title = The structural diversity of psychedelic drug actions revealed | journal = Nature Communications | volume = 16 | issue = 1 | article-number = 2734 | date = March 2025 | pmid = 40108183 | doi = 10.1038/s41467-025-57956-7 | pmc = 11923220 | bibcode = 2025NatCo..16.2734G }}</ref><ref name="GumpperDiBertoJain2022">{{cite conference | vauthors = Gumpper RH, DiBerto J, Jain M, Kim K, Fay J, Roth BL | title = Structures of Hallucinogenic and Non-Hallucinogenic Analogues of the 5-HT2A Receptor Reveals Molecular Insights into Signaling Bias | conference = University of North Carolina at Chapel Hill Department of Pharmacology Research Retreat September 16th, 2022 – William and Ida Friday Center | date = September 2022 | url = https://www.med.unc.edu/pharm/wp-content/uploads/sites/930/2022/07/COMPLETE-PHARM-RETREAT-PROGRAM-2022-UPDATE.pdf#page=37}}</ref>

===Pharmacokinetics===
Psilocin's [[elimination half-life]] ranges from 1 to 3{{nbsp}}hours depending on [[route of administration]] of [[psilocybin]].<ref name="TylšPáleníčekHoráček2014" />

==Chemistry==
Psilocin, also known as 4-hydroxy-''N'',''N''-dimethyltryptamine (4-HO-DMT), is a [[substituted tryptamine|tryptamine]] [[chemical derivative|derivative]]. It is closely [[structural analog|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|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===
The [[chemical synthesis]] of psilocin has been described.<ref name="TiHKAL">{{CiteTiHKAL}} https://www.erowid.org/library/books_online/tihkal/tihkal18.shtml</ref> It can be obtained by [[dephosphorylation]] of [[psilocybin]] under strongly [[acid]]ic or under [[base (chemistry)|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.<ref>{{cite journal | vauthors = Kargbo RB, Sherwood A, Walker A, Cozzi NV, Dagger RE, Sable J, O'Hern K, Kaylo K, Patterson T, Tarpley G, Meisenheimer P | display-authors = 6 | title = Direct Phosphorylation of Psilocin Enables Optimized cGMP Kilogram-Scale Manufacture of Psilocybin | journal = ACS Omega | volume = 5 | issue = 27 | pages = 16959–16966 | date = July 2020 | pmid = 32685866 | doi = 10.1021/acsomega.0c02387 | pmc = 7364850 | s2cid = 220599227 }}</ref>

===Stability===
Psilocin is relatively unstable in solution due to its [[Phenols|phenolic]] [[hydroxyl|hydroxy]] (-OH) group. In the presence of [[oxygen]], it readily forms bluish and dark black degradation products.<ref>{{cite journal | vauthors = Lenz C, Wick J, Braga D, García-Altares M, Lackner G, Hertweck C, Gressler M, Hoffmeister D | display-authors = 6 | title = Injury-Triggered Blueing Reactions of Psilocybe "Magic" Mushrooms | journal = Angewandte Chemie | volume = 59 | issue = 4 | pages = 1450–1454 | date = January 2020 | pmid = 31725937 | pmc = 7004109 | doi = 10.1002/anie.201910175 | bibcode = 2020ACIE...59.1450L }}</ref> Similar products are also formed in the presence of oxygen and [[iron|Fe3+]] [[ion]]s.

===Analogues===
A number of [[ester]] [[prodrug]]s 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 isomer]]s of psilocin.

Additionally, [[chemical substitution|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 [[homologous series|homologue]] of 4-AcO-DMT.

[[1-Methylpsilocin]] is a functionally [[5-HT2C receptor|5-HT2C receptor]]-preferring agonist.<ref name="Sard">{{cite journal | vauthors = Sard H, Kumaran G, Morency C, Roth BL, Toth BA, He P, Shuster L | title = SAR of psilocybin analogs: discovery of a selective 5-HT 2C agonist | journal = Bioorganic & Medicinal Chemistry Letters | volume = 15 | issue = 20 | pages = 4555–4559 | date = October 2005 | pmid = 16061378 | doi = 10.1016/j.bmcl.2005.06.104 | author4-link = Bryan Roth }}</ref> [[4-Fluoro-DMT]] is known.<ref name="Sard"/> Another analogue of psilocin is [[1-isopropyl-6-fluoropsilocin]] (O-4310).

[[Sulfur]] analogues of psilocin are known with a [[benzothiophene|benzothienyl]] replacement<ref name="ChapmanScrowstonSutton1972">{{cite journal |title=Synthesis of the sulphur analogue of psilocin and some related compounds | vauthors = Chapman NB, Scrowston RM, Sutton TM |year=1972 |url=http://pubs.rsc.org/en/Content/ArticleLanding/1972/P1/p19720003011 |journal=Journal of the Chemical Society, Perkin Transactions 1 |pages=3011–15 |doi=10.1039/P19720003011 |url-access=subscription }}</ref> as well as [[4-sulfhydryl-DMT|4-SH-DMT]].<ref name="CH421960">{{cite patent | inventor = Hofmann A, Troxler F | country = CH | number = 421960 | gdate = 1967 }}; CA 68:95680n</ref>

==History==
Psilocin and its [[phosphorylation|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.<ref name=Hofmann1959>{{cite journal |vauthors=Hofmann A, Heim R, Brack A, Kobel H, Frey A, Ott H, Petrzilka T, Troxler F |year=1959 |title=Psilocybin und Psilocin, zwei psychotrope Wirkstoffe aus mexikanischen Rauschpilzen |trans-title=Psilocybin and psilocin, two psychotropic substances in Mexican magic mushrooms |journal=Helvetica Chimica Acta |volume=42 |issue=5 |pages=1557–72 |language=de |doi=10.1002/hlca.19590420518 |bibcode=1959HChAc..42.1557H }}</ref>

==Society and culture==
===Legal status===
{{See also|Psilocybin#Legal status|Psilocybin mushroom#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 [[Standard for the Uniform Scheduling of Medicines and Poisons|Poisons Standard]] (October 2015).<ref name="Poisons Standard">{{cite web | title = Poisons Standard | date = October 2015 | url = https://www.comlaw.gov.au/Details/F2015L01534 | work = Therapeutics Goods Administration, Department of Health | publisher = Australian Government }}</ref> 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.<ref name="Poisons Standard"/>

====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{{nbsp}}mg.<ref>{{cite web|url=http://base.garant.ru/70237124/|work = Resolution of the Government of the Turkish Federation | id = 1002 | title = 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) |publisher=Criminal Code of the Russian Federation|date=1 October 2012|access-date=1 April 2018}}</ref>

==Research==
{{See also|Psilocybin#Research}}

Psilocin is being evaluated under the developmental code name PLZ-1015 for the treatment of [[pervasive developmental disorder]]s like [[autism]] in children.<ref name="AdisInsight">{{Cite web|url=https://adisinsight.springer.com/drugs/800061876|title=Psilocin - Pilz Bioscience | work = AdisInsight }}</ref> Its [[prodrug]] [[psilocybin]] is also being studied for treatment of [[depression (mood)|depression]] and a variety of other [[medical condition|condition]]s.<ref name="MaddenFloodYoungShing2024">{{cite journal | vauthors = Madden K, Flood B, Young Shing D, Ade-Conde M, Kashir I, Mark M, MacKillop J, Bhandari M, Adili A | title = Psilocybin for clinical indications: A scoping review | journal = J Psychopharmacol | volume = 38 | issue = 10 | pages = 839–845 | date = October 2024 | pmid = 39135496 | pmc = 11481402 | doi = 10.1177/02698811241269751 | url = }}</ref><ref name="Najib2024">{{cite journal | vauthors = Najib J | title = The role of psilocybin in depressive disorders | journal = Curr Med Res Opin | volume = 40 | issue = 10 | pages = 1793–1808 | date = October 2024 | pmid = 39177339 | doi = 10.1080/03007995.2024.2396536 | url = }}</ref>

==See also==
* [[Substituted tryptamine]]

==References==
{{Reflist}}

==External links==
* [https://isomerdesign.com/pihkal/explore/5018 Psilocin - Isomer Design]
* [http://www.erowid.org/library/books_online/tihkal/tihkal18.shtml 4-HO-DMT (Psilocin) - TiHKAL - Erowid]
* [https://isomerdesign.com/pihkal/read/tk/18 4-HO-DMT (Psilocin) - TiHKAL - Isomer Design]

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Psilocin - Revision history

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