State-regulated psilocybin services in Oregon were associated with decreases in moderate-to-severe depression, anxiety, and posttraumatic stress disorder symptoms through 3 months, while serious behavioral adverse reactions requiring medical attention occurred in 4 participants, according to a study published in JAMA Network Open.
Investigators conducted a longitudinal, prospective, single-arm cohort study of 346 adults who received psilocybin services at 24 of Oregon’s 26 active licensed service centers. Participants enrolled between November 2024 and March 2026, with follow-up through June 2026. Eighty-three licensed facilitators supervised the sessions.
Oregon’s program operates as a community-based wellness model in which adults 21 years or older may seek psilocybin services for any reason. Licensed facilitators supervised psilocybin experiences involving mushroom-derived products, although professional clinical training was not required. Oregon regulations exclude clients with active suicidal ideation or psychosis and those who used lithium within the prior 30 days.
Participants had a mean age of 50 years, 53% were women, and 87% were White. Overall, 56% reported lifetime psychedelic use, excluding microdosing. The mean psilocybin dose was 32 mg, with doses ranging from 2 to 50 mg. Follow-up rates were 93% at 1 week, 93% at 1 month, and 90% at 3 months.
Investigators measured depression using the Patient Health Questionnaire-9, anxiety using the Hospital Anxiety and Depression Scale, and posttraumatic stress disorder symptoms using the 6-item Posttraumatic Stress Disorder Checklist. Generalized estimating equations evaluated longitudinal within-group changes, with empirically estimated standard errors accounting for correlations between participants within facilitators and between measurements within participants. Psychiatric diagnostic status was unknown, and investigators analyzed changes in mental health scores regardless of participants’ reasons for seeking services rather than limiting the analysis to those with moderate-to-severe symptoms at baseline.
Moderate-to-severe depression symptoms decreased from 42% at baseline to 11% at 1 month and 17% at 3 months. Moderate-to-severe anxiety decreased from 45% to 12% and 13%, respectively, while moderate-to-severe posttraumatic stress disorder symptoms decreased from 48% to 19% and 17%. The proportion of participants who reported being very or somewhat satisfied with their lives increased from 63% at baseline to 83% at 1 month and 82% at 3 months.
“Many participants experienced decreases in anxiety, depression, and [posttraumatic stress disorder] symptoms within the first month of their psilocybin experience that were sustained at 3 months, although baseline symptoms were relatively low and psychiatric diagnostic status is unknown,” wrote lead author P. Todd Korthuis, MD, MPH, of Oregon Health & Science University in Portland, and colleagues.
Four participants, or 1%, experienced serious behavioral adverse reactions. All 4 were psychedelic-naive, had baseline mental health symptoms, and received psilocybin doses ranging from 25 to 50 mg. Investigators identified no serious medical adverse reactions. At 3 months, 5% of participants reported persistent worsening depression, 2% reported new thoughts of dying or suicide, and 9% reported hallucinogen persisting perception disorder symptoms; none of those reporting these perceptual symptoms at 3 months reported significant distress.
The investigators noted that the uncontrolled observational design precluded causal inference. The cohort represented approximately 5% of people receiving state-regulated psilocybin services in Oregon during the study period, raising the possibility of selection bias. They also noted that generalizability to people with lower income, less education, and historically marginalized populations remains uncertain and that the findings may not reflect experiences associated with unsupervised or religious psilocybin use.
Disclosures: The study was funded by the OHSU Addiction Program Development Account, the Substance Abuse and Mental Health Services Administration, the OHSU Foundation, and National Institutes of Health programs, including the National Institute on Drug Abuse, the Oregon Clinical and Translational Research Institute, and the National Center for Advancing Translational Sciences. The funders did not participate in the study design or conduct, data collection or analysis, interpretation of the findings, manuscript preparation or review, or the decision to submit the work for publication. Jason B. Luoma, PhD, disclosed personal fees from the OHSU Foundation during the study, as well as ownership of the Portland Institute for Psychedelic Science and personal fees from Atai Life Sciences outside the submitted work.
Source: JAMA Network Open