Baeocystin

Baeocystin, also known as norpsilocybin or 4-phosphoryloxy-N-methyltryptamine (4-PO-NMT), is a zwitterionic alkaloid and analogue of psilocybin. It is found as a minor compound in most psilocybin mushrooms together with psilocybin, norbaeocystin, aeruginascin, and psilocin.<ref>Template:Cite journal</ref> Baeocystin is the N-demethylated derivative of psilocybin and the 4-phosphorylated derivative of 4-HO-NMT (4-hydroxy-N-methyltryptamine). The structures at right illustrate baeocystin in its zwitterionic form.

History

Baeocystin was first isolated from the mushroom Psilocybe baeocystis,<ref name="Leung 1968"/> and later from P. semilanceata,<ref name="Repke 1977"/> Panaeolus renenosus, Panaeolus subbalteatus, and Copelandia chlorocystis.<ref name="Brossi 1988"/> It was first synthesized by Troxler et al. in 1959.<ref name="Troxer 1959"/>

Pharmacology

Baeocystin is thought to be a prodrug of norpsilocin, analogously to how psilocybin is a prodrug of psilocin.<ref name="RakoczyRungeSen2024">Template:Cite journal</ref> Norpsilocin is a potent and centrally penetrant agonist of the serotonin 5-HT_2A receptor and also interacts with other serotonin receptors.<ref name="RakoczyRungeSen2024" />

Baeocystin and norpsilocin have been found to be inactive in terms of hallucinogen-like effects in rodents in multiple studies published in the 2020s.<ref name="SherwoodHalberstadtKlein2020">Template:Cite journal</ref><ref name="GlatfelterPottiePartilla2022">Template:Cite journal</ref><ref name="RakoczyRungeSen2024" /> More specifically, they were unable to produce the head-twitch response (HTR), a well-established behavioral proxy of psychedelic effects, and this was in contrast to psilocybin.<ref name="SherwoodHalberstadtKlein2020" /><ref name="GlatfelterPottiePartilla2022" /><ref name="RakoczyRungeSen2024" /> In one of the papers, the researchers concluded that "...baeocystin alone would likely not induce hallucinogenic effects in vivo".<ref name="SherwoodHalberstadtKlein2020" /> As with baeocystin and norpsilocin, norbaeocystin, aeruginascin, 4-hydroxytryptamine (4-HT), and 4-HO-TMT also all failed to induce the HTR in rodents.<ref name="SherwoodHalberstadtKlein2020" /><ref name="GlatfelterPottiePartilla2022" /><ref name="RakoczyRungeSen2024" /> However, these compounds have not necessarily been inactive in terms of behavioral effects in general.<ref name="GlatfelterPottiePartilla2022" /><ref name="RakoczyRungeSen2024" />

Chemist and mycologist Jochen Gartz reported in the 1990s that baeocystin is active as a psychedelic in humans.<ref name="GartzAppeliusTaake1996">Template:Cite book</ref><ref name="Gartz1999">Template:Cite book</ref><ref name="Gartz1992">Template:Cite journal</ref><ref name="Ott1996">Template:Cite book</ref><ref name="Trout2007">Template:Cite book</ref><ref name="MorrisOtt2023">Template:Cite podcast</ref> He has stated that 4Template:Nbspmg produced a "threshold" or "gentle hallucinogenic experience" with "mild hallucinations for three hours" and that "10Template:Nbspmg of baeocystin [was] found to be about as psychoactive as a similar amount of psilocybin".<ref name="GartzAppeliusTaake1996" /><ref name="Gartz1999" /><ref name="Gartz1992" /><ref name="Ott1996" /><ref name="Trout2007" /> Gartz also personally communicated these findings to Jonathan Ott, who has reproduced the claims.<ref name="Ott1996" /><ref name="Trout2007" /><ref name="MorrisOtt2023" /> Hamilton Morris has expressed surprise and skepticism about the reported psychoactivity of baeocystin however.<ref name="MorrisOtt2023" />

Gartz has also claimed that mushrooms with high baeocystin content, such as Psilocybe semilanceata, are more frequently associated with dysphoric experiences.<ref name="PepeHesamidelaCerda2023">Template:Cite journal</ref><ref name="Gartz1989">Template:Cite journal</ref> Conversely, he has claimed that accidental ingestion of Inocybe aeruginascens, which contains high levels of both aeruginascin and baeocystin, is usually associated with euphoric experiences, in contrast to the dysphoric experiences that can occur with mushrooms containing only high levels of psilocybin.<ref name="PepeHesamidelaCerda2023" /><ref name="Gartz1989" /> However, more research is needed on the effects of baeocystin and aeruginascin in humans.<ref name="PepeHesamidelaCerda2023" /><ref name="Gartz1989" />

In contrast to Gartz, mycologist Paul Stamets has reported that he tried 10Template:Nbspmg pure baeocystin and it didn't produce hallucinogenic effects but did produce pupil dilation and apparent anxiolysis.<ref name="Mandrake2021">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="Rogan2019">Template:Cite podcast</ref><ref name="Bauer2020">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

The reasons for the apparently non-hallucinogenic nature of norpsilocin, baeocystin, and related compounds in animals (and possibly in humans), in spite of norpsilocin and others being potent serotonin 5-HT_2A receptor agonists and producing other centrally mediated behavioral effects in animals, remain unknown.<ref name="RakoczyRungeSen2024" /><ref name="GlatfelterPottiePartilla2022" /> One possibility however is that these compounds may be biased agonists of the serotonin 5-HT_2A receptor and may not sufficiently activate the intracellular signaling cascades responsible for psychedelic effects.<ref name="RakoczyRungeSen2024" /><ref name="GlatfelterPottiePartilla2022" />

Development

Baeocystin is being evaluated by Pilz Bioscience ("pilz" being German for "mushroom") under the developmental code name PLZ-1019 for the possible treatment of pervasive developmental disorders like autism in children.<ref name="AdisInsight">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

References

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