A18: Enzymatic Conversion of Psilocybin and Related Tryptamines by Alkaline Phosphatase and Monoamine Oxidase A

The McMurray lab is a behavioral neuroscience lab that focuses on the study of tryptamines commonly found in “magic” mushrooms. The main tryptamine found in these mushrooms is psilocybin, and this has been extensively studied as a therapeutic because of its promising antidepressant effects. The leading theory for why psilocybin possesses this antidepressant efficacy is its binding affinity for the 5-HT2A receptor. Current depression treatments include the administration of SSRIs which inhibit the reuptake of serotonin. This inhibition leads to an increase in serotonin levels in the brain and thus an increase in binding of 5-HT2A receptors. Psilocybin and its related tryptamines may produce similar antidepressant effects through a similar mechanism. Although promising, the FDA has been reluctant to approve psilocybin as a treatment partially due to its hallucinogenic effects. Previous studies have shown that tryptamines of psilocybin (i.e. norbaeocystin, baeocystin, and aeruginascin) may not elicit hallucinations and also have pharmacological potential. Our study aimed to assess the enzyme kinetics of the aforementioned compounds to determine whether they have similar mechanisms compared to psilocybin. First, each tryptamine was dephosphorylated to mimic natural metabolic processes. We then examined how they interact with the MAO enzyme, because we know from previous studies that many antidepressant medications are MAO inhibitors. The Michaelis-Menten plots from both assays revealed that all of the tryptamines behave similarly. This suggests that norbaeocystin, baeocystin, and aeruginascin are comparable to psilocybin with regards to their enzymatic activity, and further studies are needed to determine whether these compounds are more efficacious than psilocybin as an antidepressant. Overall, this project has helped us to prepare for careers in research.

Author(s): Grace Runge, Biology, Data Analytics, and Neuroscience Major

William Hortz, Biochemistry Major

Advisor(s): Matthew McMurray, Department of Psychology