Mental health outcomes following a psilocybin session within Oregon’s state-regulated model: A naturalistic study

Abstract Background In 2020, Oregon became the first U.S. state to establish a regulated framework for adults to access psilocybin services using naturally-derived mushroom products. No studies have examined mental health outcomes among individuals receiving psilocybin in this context. Aims To evaluate changes in self-reported symptoms of depression, anxiety, and well-being 30-days post-psilocybin session under the Oregon state-regulated model , and document session-related adverse events and doses consumed. Methods This was a naturalistic study (March 2024-April 2025) among adults ≥21 years participating in a legal psilocybin services program. Online surveys were completed pre-session, 1-day, and 30-days post-session. Primary outcomes were change in depression, anxiety, and well-being symptoms pre-session to 30-days post-session evaluated using linear mixed-effects models (random effect: timepoint; fixed effects: sex, concurrent psychiatric medication use, age, session dose [total psilocybin equivalents, TPE, mg: psilocybin mg + 1.39 * psilocin mg]). Adverse events (e.g., hallucinogen persisting perception disorder [HPPD]) were assessed at 1-day and 30-days post-session. Results Participants (n=88; median age 43 years; 52% male) were predominantly Oregon residents (53.4%), psychedelic-experienced (64.8%), and concurrently using psychiatric medication (46.6%). All outcomes improved significantly at 30-days post-session (p<0.001), including in sensitivity analyses stratified by concurrent psychiatric medication usage (p<0.001 all outcomes, both groups). Two participants (2.3%) reported symptoms consistent with HPPD at 1-day post-session, but none at 30-days. Mean dose was 27.8 mg (SD 8.2) TPE. Conclusions Psilocybin sessions delivered under the Oregon regulatory model were associated with clinically meaningful improvements in depression, anxiety, and well-being 30-days post-session, supporting therapeutic effectiveness of legal psilocybin services.