Oregon Psilocybin Program Shows Mental Health Improvements, Few Serious Reactions
Key Clinical Summary:
- A cohort study of 346 adults receiving state-regulated psilocybin services in Oregon found that serious adverse reactions were uncommon, although their rates were statistically significant.
- At 3 months, participants had lower risks of moderate-to-severe depression, anxiety, and posttraumatic stress disorder (PTSD) symptoms compared with baseline, alongside improved mental well-being and life satisfaction.
- Four participants (1.2%), all psychedelic-naive, experienced adverse behavioral reactions requiring medical attention; 2.3% reported their experience as harmful at 3 months.
Most participants in Oregon’s state-regulated psilocybin program reported improvements in depression, anxiety, PTSD symptoms, mental well-being, and life satisfaction over 3 months, according to findings from the Open Psychedelic Evaluation Nexus (OPEN). Published in JAMA Network Open, the multisite cohort study evaluated safety and participant outcomes in the first US state-regulated psilocybin program, including individuals who did not necessarily seek services to address mental health concerns.
Study Findings
The study included 346 adults enrolled from November 2024 through March 2026 at 24 of Oregon’s 26 actively licensed psilocybin service centers, with follow-up through June 2026. Participants received services supervised by 83 licensed facilitators and completed assessments at baseline and 1 week, 1 month, and 3 months after their psilocybin sessions.
Participants had a mean age of 49.5 years, 52.5% were women, and 86.7% were White. Overall, 44.2% were psychedelic-naive, and the mean psilocybin dose was 31.9 mg.
Retention remained above 90% through 3 months. Four participants (1.2%), all psychedelic-naive, experienced adverse behavioral reactions requiring medical attention. Participant-reported harm was also uncommon, ranging from 1.6% at 1 week to 2.3% at 3 months.
At 1 month, 92.2% of participants reported benefiting from the experience, while 58.6% ranked it among the 10 most meaningful experiences of their lives.
At 3 months, the risk of moderate-to-severe depression symptoms was lower compared with baseline (relative risk [RR], 0.40; 95% CI, 0.32-0.50), as were risks of anxiety (RR, 0.29; 95% CI, 0.22-0.38) and PTSD symptoms (RR, 0.35; 95% CI, 0.27-0.45). Mental well-being improved by a mean of 3.21 points (95% CI, 2.66-3.76), and life satisfaction increased (RR, 1.31; 95% CI, 1.19-1.44).
Clinical Implications
These longitudinal findings provide real-world data on the potential therapeutic effect and safety profile of psilocybin outside of a controlled trial.
“Safety was very similar to what we’ve seen with psychedelics in clinical settings,” said lead author Todd Korthuis, MD, MPH, Oregon Health & Science University, Portland, in a news release. “That’s important because there was a big question around whether or not safety in carefully controlled psilocybin clinical trials would translate into real-world use.”
Because the findings also indicated improvement in patients not specifically seeking mental health treatment, the study further suggests that “psilocybin services can evoke changes beyond the presenting concerns.”
Expert Commentary
“In this cohort study, people receiving state-regulated psilocybin services in Oregon experienced few safety events, high satisfaction with services, and overall improvements in mental health, well-being, and life satisfaction in the 3 months following a psilocybin experience,” the researchers wrote.
They concluded that the findings “provide a foundational evidence base for clinician, facilitator, and public education to support accurate expectations about potential benefits and risks and strengthen informed consent.”
