Psilocybin: Chemical Foundations and Emerging Therapeutic Potential.
Mini reviews in medicinal chemistry March 24, 2026 Shivaputra A Patil, Holly C Hunsberger
Psilocybin, a naturally occurring psychedelic derived from Psilocybe mushrooms, is experiencing renewed interest for treating mental health disorders, addiction, and cancer-related depression, and its benefits are expanding into brain injury and lifespan due to its ability to enhance neuroplasticity. Its psychoactive effects arise from psilocin acting as a partial agonist at the 5-HT2A receptor. After the FDA's breakthrough therapy designation for treatment-resistant depression in 2018 and major depressive disorder in 2019, large-scale synthesis became a major challenge, requiring complex multi-step processes with strict temperature control and hazardous reagents. Modified versions of Hofmann's original method now enable kilogram-scale production for clinical trials. This mini review covers the history, chemistry, pharmacology, and therapeutic use of psilocybin in depression.