Psilocybin in Neuropsychiatric Disorders: Seeking Valuable Evidence in History, Pure Science, Clinical Trials and Real-World Data (RWD).
Brain sciences March 26, 2026 Piotr Skalski, Katarzyna Pękacka-falkowska, Agnieszka Pluto-Prądzyńska et al.
Psilocybin shows rapid and sustained antidepressant and anxiolytic effects, with benefits also observed in addiction treatment. However, conventional randomized controlled trials (RCTs) may not adequately capture the therapeutic complexity of psilocybin, which depends on pharmacological action as well as contextual, psychological, and interpersonal factors. This critical narrative review of the ten most cited clinical studies from 2015 to 2025 identified significant methodological limitations, including selection bias, challenges in placebo design and blinding, small sample sizes, and underrepresentation of diverse populations. Real-world evidence studies revealed heterogeneous response patterns and insights unattainable through RCTs alone. Comprehensive evaluation requires larger and more diverse trials, long-term follow-up, standardized psychotherapeutic protocols, and integration of real-world evidence.