Norbaeocystin

Psilocybin is just one of several compounds that naturally occur in psychedelic mushrooms (aka magic mushrooms). One of these other compounds, norbaeocystin, is present at lower concentrations than psilocybin in some mushroom species.1–3 Norbaeocystin is virtually unknown to most people (including many researchers) and is its effects are not well documented.

The Chemistry of Norbaeocystin

Norbaeocystin is a derivative and analog of psilocybin. It was first isolated from Psilocybe baeocystis by Leung and Paul in 1968.4 In the study, solvent extractions provided material enriched in psilocybin derivatives. Those chemicals were further separated by chromatography to provide pure fractions of norbaeocystin, baeocystin, and psilocybin. Chemically, norbaeocystin is an N-demethylated derivative of baeocystin (and baeocystin is the N-demethylated derivative of psilocybin) (Figure 1).

Recently, researchers demonstrated that norbaeocystin could be an intermediate in the biosynthesis of psilocybin.5 In vitro tests showed 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. The researchers propose that additional methyl groups are added by the enzyme PsiM, generating baeocystin (one methylation) and psilocybin (two methylations).

Figure 1: The chemical structures of baeocystin, norbaeocystin, and psilocybin.

The Pharmacology of Norbaeocystin

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 its potential for therapeutic uses — for example, in modulating the properties of drugs and/or endogenous neurotransmitters (e.g. serotonin) — without an intoxicating effect.

Drawing an analogy to the accepted metabolic pathway for psilocybin, one 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 4th position in the molecule, whereas serotonin is hydroxylated at the 5th position.

No one has quantified the effects of this molecule on its own or in combination with other active magic mushroom compounds. Accordingly, progress towards understanding the properties of pure norbaeocystin will likely come from better access to the molecule via separation techniques, synthetic methods, or both.

The Applications and Potential of Norbaeocystin

Nothing is known about the possible therapeutic effects of norbaeocystin either by itself or in combination with other magic mushroom compounds. And on top of this, scientists are not actively studying norbaeocystin, which results in an empty research pipeline. Future research in this area will benefit from shifting the focus from magic mushrooms to the active molecules within them. It is conceivable that norbaeocystin could have therapeutic applications that come without intoxicating properties.

Based on what is known from studying the compounds in other naturally-occurring organisms such as cannabis, it is conceivable that there is also an entourage effect with magic mushrooms. Norbaeocystin may play an essential role in generating and modulating specific psychedelic effects. The current state of the art for norbaeocystin (and psilocybin) can be improved by isolating each of the individual molecules and studying how they affect cellular receptors (e.g., serotonin) alone and in combination with other molecules.

    References
  1. Stamets P, Weil A. Psilocybin Mushrooms of the World: An Identification Guide. First Edition. Berkeley, Calif: Ten Speed Press; 1996.
  2. Gartz J. New aspects of the occurrence, chemistry and cultivation of European hallucinogenic mushrooms. Supplemento agli Annali dei Musei Civici di Rovereto Sezione Archeologica, Storia e Scienze Naturali. 1992;8:107-124.
  3. Zhuk O, Jasicka-Misiak I, Poliwoda A, et al. Research on Acute Toxicity and the Behavioral Effects of Methanolic Extract from Psilocybin Mushrooms and Psilocin in Mice. Toxins. 2015;7(4):1018-1029. doi:10.3390/toxins7041018
  4. Leung AY, Paul AG. Baeocystin and norbaeocystin: New analogs of psilocybin from Psilocybe baeocystis. Journal of Pharmaceutical Sciences. 1968;57(10):1667-1671. doi:10.1002/jps.2600571007
  5. Fricke J, Blei F, Hoffmeister D. Enzymatic Synthesis of Psilocybin. Angewandte Chemie International Edition. 2017;56(40):12352-12355. doi:10.1002/anie.201705489