Prospective real-world evidence of mental health outcomes following supervised psilocybin services within the Oregon state-regulated model

Background: In 2020, Oregon established the first regulated framework for adult psilocybin services using naturally-derived mushroom products. No studies have examined mental health outcomes among individuals receiving psilocybin in this real-world, state-regulated context. Aims: To evaluate the effects of supervised psilocybin services under the Oregon model on self-reported symptoms of depression, anxiety, and well-being, and document session-related aftereffects and doses consumed. Methods: This was a prospective, naturalistic study (March 2024-April 2025) among adults 21 years or older 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: participant; fixed effects: timepoint, sex, concurrent psychiatric medication use, age, dose [total psilocybin equivalents, TPE]). Post-session visual perceptual or psychological aftereffects were assessed at follow-up. Results: Participants (n=88; median age 43 years; 52% male) were predominantly Oregon residents (53.4%), psychedelic-experienced (64.8%), and using psychiatric medication (46.6%). All outcomes showed significant within-person improvements 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 session-related distressing visual perceptual aftereffects 1-day post-session, resolved at 30-days; three (3.4%) reported psychological aftereffects 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 significant improvements in depression, anxiety, and well-being. As other U.S. jurisdictions explore similar models, this initial real-world evidence supports the potential utility of legal psilocybin services for improved mental health.