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.

KEYWORDS:

• Psilocybin
• regulation
• homebrewed drugs
• recombinant DNA technology

Highlights:

• Homebrewed psilocybin is possible and economically competitive with mushrooms

• Simple E. coli fermentation setup is able to produce >300 mg/L of psilocybin

• Proposed regulation of recombinant microorganisms and key chemical precursors

Acknowledgements

This work was supported by Miami University start-up funds from the Department of Chemical, Paper, and Biomedical Engineering (JAJ), Undergraduate Summer Support from the College of Engineering and Computing (PJO), and a sponsored research grant from PsyBio Therapeutics (JAJ). Requests for strains and plasmids capable of producing controlled substances (e.g., psilocybin) will require proof of appropriate approvals and licenses from all necessary state and federal agencies prior to completion of a materials transfer agreement. The authors would also like to thank Dr. Kathryn E. Jones for helpful comments and discussions on the final draft. The graphical abstract and Figure 1 were created with BioRender.com

Disclosure statement

JAJ is the chairman of the scientific advisory board and a significant stakeholder at PsyBio Therapeutics. PsyBio Therapeutics has licensed psilocybin biosynthesis-related technology from Miami University. JAJ and WJGJ are co-inventors on a related provisional patent application.

Author Contribution Statement:

WJGJ and JAJ designed the study. WJGJ, BAB, MGM, and PJO performed experiments. JAJ secured the funding for the project. WJGJ, PJO, and JAJ analyzed data. All authors wrote and edited the manuscript. All authors reviewed the manuscript prior to submission.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work was supported by the Miami University [N/A]; PsyBio Therapeutics [N/A].