Psilocybin and other psychedelic compounds are being studied for therapeutic use, but little is known about norbaeocystin, a pathway intermediate, due to difficulties obtaining it. Researchers developed a new E. coli platform to produce gram-scale amounts of norbaeocystin, finding that even minor genetic changes required reoptimization of production. In vivo tests on Long-Evans rats showed a dose response to psilocybin, but norbaeocystin did not elicit any pharmacological response, suggesting it and its metabolites may not strongly bind to the serotonin 2A receptor. This work enables future studies of norbaeocystin in animal models and supports the safety of using cell broth as a drug delivery vehicle.
Psilocybin, a recreational psychedelic, is being studied as a therapy for depression, anxiety, and addiction. Recent advances include biosynthesis using microorganisms. This work demonstrates production of approximately 300 mg/L of psilocybin in less than 2 days using a recombinant E. coli strain in a simple, homebrew-style setup with easily sourced equipment. The finding raises regulatory questions about preventing clandestine synthesis while allowing pharmaceutical development. The authors present their results and suggestions for addressing these regulatory concerns.