Homebrewed psilocybin: can new routes for pharmaceutical psilocybin production enable recreational use?

Abstract

Psilocybin, a drug most commonly recognized as a recreational psychedelic, is quickly gaining attention as a promising therapy for an expanding range of neurological conditions, including depression, anxiety, and addiction. This growing interest has led to many recent advancements in psilocybin synthesis strategies, including multiple in vivo fermentation-based approaches catalyzed by recombinant microorganisms. In this work, we show that psilocybin can be produced in biologically relevant quantities using a recombinant E. coli strain in a homebrew style environment. In less than 2 days, we successfully produced approximately 300 mg/L of psilocybin under simple conditions with easily sourced equipment and supplies. This finding raises the question of how this new technology should be regulated as to not facilitate clandestine biosynthesis efforts, while still enabling advancements in psilocybin synthesis technology for pharmaceutical applications. Here, we present our homebrew results, and suggestions on how to address the regulatory concerns accompanying this new technology.

“Biosynthesis of psilocybin and its nonnatural derivatives by a promiscuous psilocybin synthesis pathway in Escherichia coli”

“…More than 20 tryptamine analogs have also been produced utilizing engineered TrpBs from P. furiosus and the R. gnavus TDC (McDonald et al, 2019). Native E. coli TrpS, the combination of both α‐ and β‐subunits, was used previously in our lab, along with the psilocybin pathway enzymes PsiD, PsiK, and PsiM to produce psilocybin from 4‐hydroxyindole in E. coli (Adams et al, 2019; Gibbons et al, 2021). Recent characterization and modeling of the gateway decarboxylase, PsiD, has been reported (Schäfer et al, 2022), however, the ability of this complete pathway to utilize diverse substrates has not been extensively explored and is the primary focus of this study.…”