Psilocybe and inocybe mushrooms are a treasure cove of opportunity to clinicians, patients, and chemists. Psilocybin, the centrepiece of psychedelic mushroom literature, shares characteristics with a larger family of molecules. In fact, at least six other psychedelics in magic mushrooms form a matrix of hallucinogens beyond just psilocybin and its active metabolite.  

Few research labs, however, exist that can legally quantify this group of tryptamines with accuracy and demystify the chemistry within psychedelic mushrooms. A select few labs in Canada have exemptions accepted by Health Canada for the analysis of psilocybin-containing mushrooms, though.

Psilocin and psilocybin

Tryptamines are a large class of drugs once Loved by the late Alexander Shulgin. And psilocybin is an analogue of tryptamine discovered in 1958 by Swiss chemist and father of LSD, Albert Hofmann. Psilocin is rather the active hallucinogen that psilocybin converts into during metabolism and processing.

Research focuses on these two ingredients and that manic attention has left our knowledge beyond psilocybin sorely frail in comparison. For starters, where does psilocybin come from and what other psychedelics or active substances exist in these mysterious fungi?

A 136-gram mutated Melmac, a variety of the Albino Penis Envy (APE), a phenotype of Psilocybe Cubensis. Photo by Chris Pesto.

4-hydroxytryptamine – An origin of psychedelics

Psilocybin, psilocin, DMT, serotonin, and melatonin are all related molecules. Magic mushrooms are unique, however, consisting of a novel metabolic pathway that is responsible for psilocybin production. Rather than take the typical root to serotonin, tryptamine rather metabolizes into psilocybin in psychedelic fungi. And this unique metabolism is due to highly specific enzymes that require further analysis to properly map.

4-hydroxytryptamine is an isomer of serotonin and the first molecule that tryptamine changes into before it becomes psilocybin (4-PO-DMT). The exact pathway wild fungi take, however, has been an area of interest for research labs ever since Shulgin’s early investigations. In any case, n-DMT is not formed during the classic production of psilocin and psilocybin despite their relation.

Baeocystin

Baeocystin is one potential intermediate between 4-hydroxytryptamine and psilocybin. Although little discussed, baeocystin is a common tryptamine of interest found in psychedelic mushrooms, including common psilocybe cubensis (Cubes.) Dr. Albert Leung and Ara G Paul discovered the natural analogue in 1967. Poorly quantified in any sample, although its role in hallucinogenic and therapeutic effects are likely as indirect as psilocybin.

Baeocystin was found in the species, psilocybe baeocystis.

Is norbaeocystin the mother of phophorylated tryptamines?

One year later, Drs. Leung and Ara G. Paul discovered the demethylated version of baeocystin in 1968. The new molecule was coined with the prefix nor to account for one missing methyl group. And then, a gap occurred. Psilocybin was listed as a Schedule I drug in the US in 1970. Afterwards, the next study to appear in Pubmed mentioning norbaeocystin was not published until 2018. In fact, only six studies that reference this phosphorylated tryptamine can be found in Pubmed’s database. Interestingly, four of those papers exclusively detail synthetic or in-vitro production of the compound and only two discuss naturally occurring fungi.

Not surprisingly then, no study exists on the pharmacological properties of norbaeocystin and analytical workflows to quantify the substance are also still in progress. And yet, norbaeocystin has been regarded as a primary precursor for baeocystin and psilocybin — the mother of phosphate-containing tryptamines according to some literature.

A new form of psilocin discovered in a new millennium

In 2017, three scientists from the Hans-Knöll-Institute at Friedrich Schiller University Jena in Germany uncovered the metabolite of baeocystin, norpsilocin. With an NMR test, the team found this potent indole alkaloid in Cubes. And suddenly, viability was revitalized in the culture of psychedelic chemistry. Norpsilocyin was discovered to be even potent than psilocin, suggesting that baeocystin might be as important as psilocybin. Perhaps, alternate pathways can be uncovered that also facilate psilocybin synthesis.

Photo by Hans-Knöll-Institute.

Hopefully, chemists can discover if activation (dephosphorylation) applies to baeocystin and norpsilocin. After all, baeocystin (4-PO-NMT) and norpsilocin (4-HO-NMT) are only different by one phosphate group much like psilocybin and psilocin.

Aeruginascin and its unknown metabolite

Lastly, a single species of psychedelic mushroom produces a promising but rare indole tryptamine. Dr. Jochen Gartz documented the first discovery of a rare psilocybin-related molecule contained within the fruiting body of Inocybe aeruginascens in 1989. Rather than one or two methyl groups, the methyl group in aeruginascin (air-oh-gen-oh-sin) is tripled.

Essentially, the metabolite (and possible precursor) of baecystin was not identified for a half-century after its discovery. Well, jump forward three decades after Dr. Gartz teased out aeruginascin at the German Academy of Sciences at Berlin, and we still have not fully characterized its derivative.

Aeruginascin’s metabolite is the eighth and still unidentified tryptamine. Despite its still elusive status, candidates for this molecule have been synthesized and studied to an extent. Similar to psilocin, 4-HO-TMT is active at serotonin receptors. Otherwise, methylated psilocin with a different positional structure was synthesized by Hoffman and his colleagues in 1959. Despite all of this, more research is needed to tease out the metabolites naturally formed after aeruginascin is digested and discover its role in a few rare species.

Aeruginascin is also produced in the fruiting body of Pholiotina Cyanopus (pictured). Photo by R. Rutkowski courtesy of Researchgate.

Quantifying the full suite

Tryptamines, despite psilocybin’s pivotal position, are just one group of psychedelics in magic mushrooms. Looking at the bigger picture lies a potential symphony of therapeutic entheogens and botanical molecules. Fresh mushrooms, for example, have terpenes and some fungi have glow-in-the-dark beta-carbolines. And for that reason, psychedelic research facilities break their approach beyond psilocybin and six other hallucinogens down into a few segments.

Let us know in the comments if you were surprised to learn that psilocybin has psychedelics cousins? And stay tuned to learn more about a lab’s approach to myshroom testing.

Show your work

  • Hoffman and his colleagues, Franz Troxler and F. Seeman modified psilocybin into many conversion products in 1959. Contrary to Wikipedia, however, they did not synthesize baeocystin. The only monomethyl analogue of psilocybin synthesized by Troxler was attached to a benzyl group. Otherwise, norpsilocin with an added atom of oxygen-18 was mentioned in the paper. (3)

Sources

  1. Leung, A. Y., & Paul, A. G. (1967). Baeocystin, a mono-methyl analog of psilocybin from Psilocybe baeocystis saprophytic culture. Journal of pharmaceutical sciences56(1), 146. Mk
  2. J. Gartz (1989) Analysis of Aeruginascin in Fruit Bodies of the Mushroom Inocybe aeruginascens, International Journal of Crude Drug Research, 27:3, 141-144, DOI:
  3. Troxler F, Seemann F, Hofmann A. Abwandlungsprodukte von Psilocybin und Psilocin. 2. Mitteilung über synthetische Indolverbindungen. Helvetica Chimica Acta. 1959;42(6):2073-2103.
  4. Halama, Marek & Poliwoda, Anna & Jasicka-Misiak, Izabela & Wieczorek, Piotr & Rutkowski, Ryszard. (2014). Pholiotina cyanopus, a rare fungus producing psychoactive tryptamines. Open Life Sciences. 10. 40–51. 10.1515/biol-2015-0005.

Footnote(s)

https://doi.org/10.1002/jps.2600560132