Naturally Derived Psilocybin for Therapeutic Use: A Six-Criterion Framework for Evidence, Safety, and Benefit–Risk Considerations in Policy and Clinical Development
Biomolecules July 3, 2026 Stefanie Enriquez‐geppert, Lisa Bevers, Arvid Rosander et al.
A review of naturally derived psilocybin finds perceived therapeutic benefits for mental health, but evidence of causal efficacy is mixed. Safety profiles are favorable yet context-dependent, with risks for vulnerable populations. Preliminary preclinical evidence suggests possible entourage effects, but human validation is lacking. Dose precision varies: purified psilocybin is most reliable, followed by standardized extracts, then alcoholic, aqueous, and whole biomass preparations. Scalable cultivation is feasible but faces sustainability challenges. Key gaps include a lack of controlled trials, longitudinal safety evaluations, and standardization. The review proposes a phased research roadmap for short-term safety studies, mid-term mechanistic and standardization efforts, and long-term integration into therapeutic, cultural, and ecological systems.