Psychedelics in magic mushrooms and 6 hallucinogens beyond psilocybin
Psilocybe and Inocybe mushrooms offer many options for clinicians, patients, and chemists. Psilocybin, at the heart of the psychedelic mushroom literature, shares properties 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 metabolites.
However, there are few research laboratories that can legally quantify this group of tryptamines with accuracy and demystify the chemistry in psychedelic mushrooms. However, a few laboratories in Canada have accepted Health Canada exemptions for the analysis of mushrooms containing psilocybin.
Psilocin and psilocybin
Tryptamines are a large class of drugs that were once loved by the late Alexander Shulgin. And psilocybin is an analog of tryptamine discovered in 1958 by the Swiss chemist and father of LSD, Albert Hofmann. Rather, psilocin is the active hallucinogen that psilocybin is converted to during metabolism and processing.
Research is focused on these two ingredients and that manic attention has made our knowledge of psilocybin very weak in comparison. For starters, where does psilocybin come from and what other psychedelics or active ingredients are in these mysterious mushrooms?
A 136 gram mutant Melmac, a variety of the Albino Penis Envy (APE), a Psilocybe cubensis phenotype. Photo by Chris Pesto.
4-Hydroxytryptamine – A source of psychedelics
Psilocybin, psilocin, DMT, serotonin, and melatonin are all related molecules. Magic mushrooms, however, are unique and consist of a novel metabolic pathway that is responsible for the production of psilocybin. Instead of taking the typical root of serotonin, tryptamine in psychedelic mushrooms is more likely to be metabolized to psilocybin. 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 is converted to before turning into psilocybin (4-PO-DMT). However, the exact route wild mushrooms take has been an area of interest to research laboratories since Shulgin’s early research. In any case, in the classic production of psilocin and psilocybin, n-DMT is not formed despite their relationship.
Baeocystin
Baeocystin is a potential intermediate between 4-hydroxytryptamine and psilocybin. Though little discussed, baeocystin is a common tryptamine of interest found in psychedelic mushrooms, including the common Psilocybe cubensis (Cubes). Dr. Albert Leung and Ara G. Paul discovered the natural analog in 1967. Poorly quantified in any sample, although its roles in hallucinogens and therapeutic effects are likely as indirect as psilocybin.
Baeocystin was found in the species Psilocybe baeocystis.
Is norbaeocystin the mother of phosphorylated tryptamines?
A year later, Dr. Leung and Ara G. Paul discovered the demethylated version of baeocystin in 1968. The new molecule was embossed with the prefix and was not responsible for a missing methyl group. And then there was a gap. Psilocybin was listed as a Schedule I drug in the United States in 1970. After that, the next study to appear in Pubmed that mentions norbaeocystin wasn’t published until 2018. In fact, there are only six studies in Pubmed’s database that refer to this phosphorylated tryptamine. Interestingly, four of these publications describe only the synthetic or in vitro production of the compound and only two discuss naturally occurring fungi.
It is therefore not surprising that there is no study on the pharmacological properties of norbaeocystin and that analytical workflows to quantify the substance are still in progress. Still, norbaeocystin has been viewed as the primary precursor to 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 of the Friedrich Schiller University Jena discovered the metabolite of baeocystin, norpsilocin. Using an NMR test, the team found this potent indole alkaloid in cubes. And suddenly viability was revived in the culture of psychedelic chemistry. Norpsilocyin was found to be even more effective than psilocin, suggesting that baeocystin might be just as important as psilocybin. Perhaps alternative pathways can be discovered that also facilitate psilocybin synthesis.
Photo from the Hans Knöll Institute.
Hopefully chemists can find out if the activation (dephosphorylation) applies to baeocystin and norpsilocin. Finally, baeocystin (4-PO-NMT) and norpsilocin (4-HO-NMT) only differ in one phosphate group, similar to psilocybin and psilocin.
Aeruginascin and its unknown metabolite
Finally, a single species of psychedelic mushroom produces a promising but rare indoltryptamine. Dr. In 1989, Jochen Gartz documented the first discovery of a rare psilocybin-related molecule that was contained in the fruiting body of Inocybe aeruginascens. Instead of one or two methyl groups, the methyl group in aeruginascin (air-oh-gen-oh-sin) is tripled.
In essence, the metabolite (and a possible precursor) of baecystin has not been identified for half a century after its discovery. Well, jump forward three decades after Dr. Gartz teased Aeruginascin at the German Academy of Sciences in Berlin, and we still haven’t fully characterized its derivative.
Aeruginascin’s metabolite is the eighth and as yet unidentified tryptamine. Despite its still elusive status, candidates for this molecule have been synthesized and studied to some extent. Similar to psilocin, 4-HO-TMT is active on serotonin receptors. Otherwise, methylated psilocin with a different positional structure was synthesized by Hoffman and colleagues in 1959. Even so, more research is needed to filter out the metabolites naturally formed after digestion of aeruginascin and to discover its role in some rare species.
Aeruginascin is also produced in the fruiting body of Pholiotina Cyanopus (pictured). Photo by R. Rutkowski courtesy of Researchgate.
Quantification of the entire suite
Tryptamines, despite the central position of psilocybin, are just one group of psychedelics in magic mushrooms. When you look at the bigger picture, there is a potential symphony of therapeutic entheogens and botanical molecules. Fresh mushrooms, for example, have terpenes, and some mushrooms have glowing beta-carbolines in the dark. And for this reason, psychedelic research institutes divide their approach into a few segments beyond psilocybin and six other hallucinogens.
Let us know in the comments if you were surprised that psilocybin has psychedelic 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. In contrast to Wikipedia, however, they did not synthesize baeocystin. The only monomethyl analog of psilocybin synthesized by Troxler was linked to a benzyl group. Otherwise, norpsilocin with an additional oxygen atom 18 was mentioned in the publication. (3)
sources
- Leung, AY, & Paul, AG (1967). Baeocystin, a monomethyl analog of psilocybin from the saprophyte culture of Psilocybe baeocystis. Journal of Pharmaceutical Sciences, 56 (1), 146. Mk
- 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:
- Troxler F, Seemann F, Hofmann A. Modification products of psilocybin and psilocin. 2. Communication on synthetic indole compounds. Helvetica Chimica Acta. 1959; 42 (6): 2073-2103.
- Halama, Marek & Poliwoda, Anna & Jasicka-Misiak, Izabela & Wieczorek, Piotr & Rutkowski, Ryszard. (2014). Pholiotina cyanopus, a rare mushroom that produces psychoactive tryptamines. Open life sciences. 10. 40-51. 10.1515 / biol-2015-0005.
Post a comment: