Norbaeocystin – An Active Component in Magic Mushrooms?

Norbaeocystin – An Ignored Psilocybin Derivative

Norbaeocystin is a psilocybin derivative, i.e., an analogue of the psychedelic prodrug psilocybin. It is also described by the chemical name 3-(2-ammonioethyl)-1H-indol-4-yl dihydrogen phosphate and the molecular formula C10H13N2O4P. It has a molecular mass of 256.2 grams per mole.

Norbaeocystin has a primary amino group on the ethyl amine group shared by the psilocybin derivatives.  However, unlike baeocystin, aeruginascin, or psilocybin, it has no methylation on the ethylamine group. By contrast Baeocystin has a single methyl group at this position; psilocybin has two methyl groups; and aeruginascin has three methyl groups.

Structural formula of norbaeocystin

Norbaeocystin Ocurrs Naturally in some Magic Mushrooms.

Norbaeocystin was first isolated from submerged cultures of psilocybe baeocystis (Leung and Paul, 1968).  Solvent extraction provided material enriched in psilocybin derivatives. Those chemicals were further separated by chromatography to provide pure fractions of norbaeocystin, baeocystin, and psilocybin.

Thin Layer Chromatogram showing several different molecules.

Recently, it was demonstrated that norbaeocystin could be an intermediate in the biosynthesis of psilocybin (Fricke et al., 2017). In vitro tests have demonstrated that L-tryptophan is converted to tryptamine by the enzyme PsiD, which is then converted to 4-hydroxytryptamine by the enzyme PsiH. PsiD can also synthesize 4-hydroxytryptamine directly from the substrate 4-hydroxy-L-tryptophan. Norbaeocystin is then synthesized by the enzyme PsiK.

Researchers propose that additional methyl groups are added by the enzyme PsiM, generating baeocystin (one methylation) and psilocybin (two methylations). The research by Fricke et al. provides the foundation for in vitro enzymatic synthesis of psilocybin and psilocybin derivatives. Alternatively, the desired compounds could be produced by biotechnological production through genetic engineering of suitable fermentation hosts.

Never Studied and Poorly Understood.

For the most part, norbaeocystin has been ignored by the scientific community. It is almost never discussed. And, the biological effects are not well documented.

Researchers have hypothesized that norbaeocystin is generally found at lower concentrations than psilocybin.  Documented chemotyping of psychoactive mushrooms support this hypothesis, showing considerably higher amounts of psilocybin vis-a-vis other (unspecified) psilocybin derivatives.

Norbaeocystin is generally regarded as non-psychedelic. However, there is no evidence to support this belief.  Furthermore, the absence of psychedelic properties does not exclude it’s potential for therapeutic uses — for example in modulating the properties of drugs and/or endogenous neurotransmitters (e.g, serotonin) — without an intoxicating effect.

If we draw an analogy to the accepted metabolic pathway for psilocybin, we would infer that norbaeocystin is dephosphorylated in the body to form 4-hydroxytryptamine, which is further metabolized. Notably, the proposed 4-hydroxytryptamine compound would differ from serotonin (5-hydroxytryptamine) only by the position of the hydroxy- group.  Norbaeocystin is hydroxylated at the 4 position whereas serotonin is hydroxylated at the 5 position.

Different Effects from Different Mushrooms?

Many anecdotal reports suggest that different species of magic mushrooms result in different effects for the user.  However, almost all discussions of magic mushrooms focus on just one molecule: psilocybin. Some molecules in magic mushrooms have never been formally studied.

DifferEnt Molecule = Different Drug

Structurally different molecules almost certainly provide different effects when ingested by the user.  They are different drugs.

Understanding how each psilocybin derivative contributes to the overall effect of a magic mushroom experience would allow researchers to create targeted formulations.  Such formulations could be optimized to provide certain properties without undesired side-effects.  See, e.g., Wood Lover Paralysis arising from certain species of psilocybin containing mushrooms.

Potentially, particular psilocybin derivatives could be used for treating people without intoxicating them.  For example, some assert that norbaeocystin is non-psychedelic.  But, the scientific community has yet to study whether it provides any of the benefits attributed to psilocybin.

References

1. https://pubchem.ncbi.nlm.nih.gov/compound/9795063

2. Leung AY and Paul AG (1968) “Baeocystin and Norbaeocystin: New Analogs of Psilocybin from Psilocybe baeocystis.” Journal of Pharmaceutical Sciences 57, 10: 1667-1671.

4. Fricke J, Blei F, and Hoffmeister D (2017) “Enzymatic Synthesis of Psilocybin.” Angew. Chem. Int. Ed., 56: 12352-12355.