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PROTOCOL FOR REAL WORLD SAFETY AND EFFECTIVENESS STUDY OF PSILOCYBIN THERAPY

Alexandra Gordon — Hope Kronman2, Brennan Carrithers2, Noam Goldway3, Silver Liftin4, Stephen Ross2, Broc Pagni2, Richard Zeifman4 1NYU Langone Center for Psychedelic Medicine, 2NYU Langone Medical Center, 3King’s College London, 4New School for Social Research

2026 ASCP Annual Meeting

Background

Psilocybin therapy has demonstrated safety and efficacy in controlled clinical trials for a range of mental health conditions, but its real-world application remains largely unexplored. Clinical research has relied on tightly controlled studies with strict inclusion criteria, limiting generalizability. With the legalization of psilocybin services in Oregon and other U.S. states, there is an urgent need to examine its safety and effectiveness in broader, realworld populations, including individuals with comorbidities commonly excluded from most clinical trials. Therefore, this study aims to evaluate the real-world safety and effectiveness of psilocybin therapy delivered to a diverse population at licensed Oregon service centers and to identify demographic and psychological factors that predict both therapeutic outcomes and adverse events.

Methods

This prospective, longitudinal observational study collects data from individuals receiving psilocybin therapy at licensed service centers in Oregon. Participating centers recruit individuals via email invitation to complete surveys, assessing safety and effectiveness, administered at baseline, 3 days (acute measures only), 1 month (primary endpoint), 3 months, 6 months, and 12 months (long-term follow-up) post-treatment. Exclusion criteria are minimal to reflect real-world clinical diversity. Information is being collected about set and setting, such as number of facilitators, therapeutic rapport and therapeutic modality. All participating individuals complete validated measures of primary mental health outcomes [anxiety (GAD-7) , depression (PHQ-9), well-being (WHO-5), psychological flexibility (Psy-Flex), substance use (NIDAModified ASSIST and AUDIT-C)], adverse effects (SPSEI), and acute experience measures [mystical experience (MEQ-4), self-compassion (SCS-12), decentering (MPoD-S), emotional breakthrough (EBI), challenging experiences (CEQ-7), and psychological insight (PIQ)]. Participants may also complete additional validated assessments tailored to their presenting concern, in accordance with diagnoses stated in the DSM-5-TR (e.g., individuals with posttraumatic stress disorder complete the PCL-5). Proportions, means, and standard deviations will be presented for questions about effectiveness, safety, and key demographics. For safety data, means, proportions, and MCID changes will be presented. Pre-to-post changes on mental health outcomes will be evaluated using linear mixed models, and generalized linear models (GLM) will test baseline, acute, and psychological predictors of therapeutic response and adverse effects. Only mental health and psychological instruments that demonstrate significant changes from baseline to 1 month will be entered into the GLM.

Discussion

Findings from this study will clarify the real-world safety and effectiveness of psilocybin therapy, characterize the prevalence and nature of adverse outcomes, and identify individual-and treatment-level factors that minimize risk and promote positive and durable therapeutic outcomes. This study will gather critical evidence to inform public policy, minimize potential societal harm, and support the development of evidence-based guidelines for the safe, personalized, and optimized delivery of psilocybin therapy.