Editing Psilocybin (section)

==Natural occurrence==
{{Main|Psilocybin-containing mushroom}}
{| class="wikitable" style="max-width:16em; float:right; margin:0.5em;"
|+ Maximum reported psilocybin concentrations (%&nbsp;dry weight) in 12 ''Psilocybe'' species<ref name="Stamets_1996" />{{rp|39}}
! scope="col" | Species
! scope="col" | % psilocybin
|-
|''[[Psilocybe azurescens|P. azurescens]]''
| style="text-align: center;" | 1.78
|-
| ''[[Psilocybe serbica|P. serbica]]''
| style="text-align: center;" | 1.34
|-
| ''[[Psilocybe semilanceata|P. semilanceata]]''
| style="text-align: center;" | 0.98
|-
| ''[[Psilocybe baeocystis|P. baeocystis]]''
| style="text-align: center;" | 0.85
|-
| ''[[Psilocybe cyanescens|P. cyanescens]]''
| style="text-align: center;" | 0.85
|-
| ''[[P. tampanensis]]''
| style="text-align: center;" | 0.68
|-
| ''[[P. cubensis]]''
| style="text-align: center;" | 0.63
|-
| ''[[Psilocybe weilii|P. weilii]]''
| style="text-align: center;" | 0.61
|-
| ''[[Psilocybe hoogshagenii|P. hoogshagenii]]''
| style="text-align: center;" | 0.60
|-
| ''[[Psilocybe stuntzii|P. stuntzii]]''
| style="text-align: center;" | 0.36
|-
| ''[[Psilocybe cyanofibrillosa|P. cyanofibrillosa]]''
| style="text-align: center;" | 0.21
|-
| ''[[Psilocybe liniformans|P. liniformans]]''
| style="text-align: center;" | 0.16
|}

Psilocybin is present in varying concentrations in over 200 species of [[Basidiomycota]] mushrooms. In a 2000 review on the worldwide distribution of hallucinogenic mushrooms, [[Gastón Guzmán]] and colleagues considered these to be distributed amongst the following [[genera]]: ''[[Psilocybe]]'' (116&nbsp;species), ''[[Gymnopilus]]'' (14), ''[[Panaeolus]]'' (13), ''[[Copelandia]]'' (12), ''[[Hypholoma]]'' (6), ''[[Pluteus]]'' (6), ''[[Inocybe]]'' (6), ''[[Conocybe]]'' (4), ''[[Panaeolina]]'' (4), ''[[Gerronema]]'' (2), and ''[[Galerina]]'' (1&nbsp;species).<ref name=Guzman2000/> Guzmán increased his estimate of the number of psilocybin-containing ''Psilocybe'' to 144 species in a 2005 review. The majority of these are found in Mexico (53 species), with the remainder distributed in the United States and Canada (22), Europe (16), Asia (15), Africa (4), and Australia and associated islands (19).<ref name=Guzman2005/> The diversity of psilocybin mushrooms is reported to have been increased by horizontal transfer of the psilocybin [[Metabolic gene cluster|gene cluster]] between unrelated mushroom species.<ref>{{Cite news |date=24 August 2017 |title=How Mushrooms Became Magic |language=en-US |work=The Atlantic |url=https://www.theatlantic.com/science/archive/2017/08/how-mushrooms-became-magic/537789/ |url-status=live |access-date=March 15, 2018 |archive-url=https://web.archive.org/web/20180316084829/https://www.theatlantic.com/science/archive/2017/08/how-mushrooms-became-magic/537789/ |archive-date=March 16, 2018 |vauthors=Yong E}}</ref><ref name=Reynolds2018/> In general, psilocybin-containing species are dark-spored, [[lamella (mycology)|gilled]] mushrooms that grow in meadows and woods of the [[subtropic]]s and [[tropics]], usually in soils rich in [[humus]] and plant debris.<ref name = Wurst2002 />{{rp|5}} Psilocybin mushrooms occur on all continents, but the majority of species are found in [[Tropical and subtropical moist broadleaf forests|subtropical humid forests]].<ref name=Guzman2000/> ''Psilocybe'' species commonly found in the tropics include ''[[Psilocybe cubensis|P.&nbsp;cubensis]]'' and ''[[Psilocybe subcubensis|P.&nbsp;subcubensis]]''. ''[[Psilocybe semilanceata|P.&nbsp;semilanceata]]''—considered by Guzmán to be the world's most widely distributed psilocybin mushroom<ref name=Guzman1983/>—is found in Europe, North America, Asia, South America, Australia and New Zealand, but is entirely absent from Mexico.<ref name=Guzman2005/> Although the presence or absence of psilocybin is not of much use as a [[chemotaxonomy|chemotaxonomical]] marker at the [[family (biology)|familial]] level or higher, it is used to classify [[taxa]] of lower taxonomic groups.<ref name=Saupe1981/>

[[File:Pschoactive Psilocybe distribution.svg|class=skin-invert-image|thumb|center|upright=2.5|Global distribution of over 100 psychoactive species of genus ''Psilocybe'' mushrooms.<ref name="Guzmán 1998">{{Cite journal |vauthors=Guzmán G, Allen JW, Gartz J |year=1998 |title=A worldwide geographical distribution of the neurotropic fungi, an analysis and discussion |url=http://www.magic-mushrooms.net/World_Wide_Distribution_of_Magic_Mushrooms.pdf |url-status=dead |journal=Annali del Museo Civico di Rovereto |volume=14 |page=207 |archive-url=https://web.archive.org/web/20100626050845/http://www.magic-mushrooms.net/World_Wide_Distribution_of_Magic_Mushrooms.pdf |archive-date=June 26, 2010 |access-date=September 17, 2017}}</ref>]]

{{Multiple image| align = right| direction = vertical| width = 165| image1 = Psilocybe mexicana 313748.jpg| alt1 = The mushroom ''Psilocybe mexicana''| caption1 = Psilocybin was first isolated from ''[[Psilocybe mexicana]]''.| image2 = Psilocybe semilanceata 6514.jpg| alt2 = The mushroom ''Psilocybe semilanceata''| caption2 = ''[[Psilocybe semilanceata|P.&nbsp;semilanceata]]'' is common in Europe, Canada, and the United States.}}

Both the [[pileus (mycology)|caps]] and the [[stipe (mycology)|stems]] contain psychoactive compounds, although the caps consistently contain more. The [[spore]]s of these mushrooms do not contain psilocybin or psilocin.<ref name=Keller1999/><ref name=Wurst1984/><ref name=Kysilka1989/> The total [[potency (pharmacology)|potency]] varies greatly between species and even between specimens of a species collected or grown from the same strain.<ref name=Bigwood1982/> Because most psilocybin biosynthesis occurs early in the formation of [[basidiocarp|fruit bodies]] or [[sclerotia]], younger, smaller mushrooms tend to have a higher concentration of the drug than larger, mature mushrooms.<ref name=Gartz1992/> In general, the psilocybin content of mushrooms is quite variable (ranging from almost nothing to 2.5% of the [[dry matter|dry weight]])<ref>{{cite journal | vauthors = Laussmann T, Meier-Giebing S | title = Forensic analysis of hallucinogenic mushrooms and khat (Catha edulis Forsk) using cation-exchange liquid chromatography | journal = Forensic Science International | volume = 195 | issue = 1–3 | pages = 160–164 | date = February 2010 | pmid = 20047807 | doi = 10.1016/j.forsciint.2009.12.013 }}</ref><ref name=Stafford1992/>{{rp|248}} and depends on species, strain, growth and drying conditions, and mushroom size.<ref name="Stamets_1996" />{{rp|36–41, 52}} Cultivated mushrooms have less variability in psilocybin content than wild mushrooms.<ref name="urlEMCDDA" /> The drug is more stable in dried than fresh mushrooms; dried mushrooms retain their potency for months or even years,<ref name="Stamets_1996" />{{rp|51–5}} while mushrooms stored fresh for four weeks contain only traces of the original psilocybin.<ref name=Amsterdam2011/>

The psilocybin contents of dried [[herbarium]] specimens of ''Psilocybe semilanceata'' in one study were shown to decrease with the increasing age of the sample: collections dated 11, 33, or 118 years old contained 0.84%, 0.67%, and 0.014% (all dry weight), respectively.<ref name=Ohenoja1987/> Mature [[mycelia]] contain some psilocybin, while young mycelia (recently [[germinated]] from spores) lack appreciable amounts.<ref name=Gross2000/> Many species of mushrooms containing psilocybin also contain lesser amounts of the analog compounds [[baeocystin]] and [[norbaeocystin]],<ref name="Stamets_1996" />{{rp|38}} chemicals thought to be biogenic [[precursor (chemistry)|precursors]].<ref name="Ballesteros_2006" />{{rp|170}} Although most species of psilocybin-containing mushrooms bruise blue when handled or damaged due to the [[Redox|oxidization]] of phenolic compounds, this reaction is not a definitive method of identification or determining a mushroom's potency.<ref name=Bigwood1982/><ref name="Stamets_1996" />{{rp|56–58}}

===Biosynthesis===
[[Isotopic labeling]] experiments from the 1960s suggested that the [[biosynthesis]] of psilocybin was a four-step process:<ref name="Agurell1968" />

# [[Decarboxylation]] of [[tryptophan]] to [[tryptamine]]
# ''N'',''N''-Dimethylation of tryptamine at the N<sup>9</sup> position to [[dimethyltryptamine]]
# 4-[[Hydroxylation]] of dimethyltryptamine to [[psilocin]]
# ''O''-[[Phosphorylation]] of psilocin to psilocybin

This process can be seen in the following diagram:<ref name=Fricke2017/>

[[File:Biosynthesis of psilocybin.svg|class=skin-invert-image|thumb|upright=2.5|center|Biosynthetic route previously thought to lead to psilocybin. It has recently been shown that 4-hydroxylation and O-phosphorylation immediately follow decarboxylation, and neither dimethyltryptamine nor psilocin are intermediates, although spontaneously generated psilocin can be converted back to psilocybin.<ref name=Fricke2017/>]]{{clear left}}

More recent research has demonstrated that—at least in ''P. cubensis''—''O''-phosphorylation is in fact the third step, and that neither dimethyltryptamine nor psilocin are intermediates.<ref name=Fricke2017/> The sequence of the intermediate steps has been shown to involve four enzymes (PsiD, PsiH, PsiK, and PsiM) in ''P. cubensis'' and ''P. cyanescens'', although it is possible that the biosynthetic pathway differs between species.<ref name = Wurst2002 />{{rp|12–13}}<ref name=Fricke2017/> These enzymes are encoded in [[Metabolic gene cluster|gene clusters]] in ''Psilocybe, Panaeolus,'' and ''Gymnopilus''.<ref name=Reynolds2018/>

''[[Escherichia coli]]'' has been genetically modified to manufacture large amounts of psilocybin.<ref>{{Cite journal |vauthors=Satyanarayana M |date=7 October 2019 |title=Modified ''E. coli'' pump out psilocybin |url=https://cen.acs.org/biological-chemistry/biotechnology/Modified-E-coli-pump-magic/97/i39 |url-status=live |journal=[[Chemical & Engineering News]] |volume=97 |issue=39 |page=11 |doi=10.1021/cen-09739-scicon9 |archive-url=https://web.archive.org/web/20191203042315/https://cen.acs.org/biological-chemistry/biotechnology/Modified-E-coli-pump-magic/97/i39 |archive-date=December 3, 2019 |access-date=December 3, 2019 |s2cid=208747979}}</ref> Psilocybin can be produced ''de novo'' in GM yeast.<ref name=Milne2020/><ref name=Wong2022/>