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Safety and Clinical Outcomes of State-Regulated Psilocybin Services: Findings From the OPEN Cohort Study
Based on findings from the Open Psychedelic Evaluation Nexus (OPEN) longitudinal cohort study published in JAMA Network Open.
Following Oregonโs 2020 ballot initiative legalizing state-monitored, licensed access to psilocybin, investigators initiated the Open Psychedelic Evaluation Nexus (OPEN) cohort study to evaluate participant safety, clinical outcomes, and subjective experiences.
Highlighting the public health imperative driving the investigation, P. Todd Korthuis, MD, MPH, professor of medicine at the Oregon Health & Science University School of Medicine, stated:
โWhen Oregon voters passed a ballot initiative in 2020 to permit state-licensed access to psilocybin services, our group of interdisciplinary researchers talked about the need to learn about the safety and outcomes of this first-in-the-nation initiative.โ
Study Cohort and Intervention Design
The OPEN study recruited 346 individuals receiving state-regulated psilocybin administration across 24 licensed service centers in Oregon between November 2024 and March 2026. Administered psilocybin doses averaged 31.9 mg (range, 2โ50 mg). The cohort demonstrated high longitudinal retention: 93.1% at 1 week, 92.8% at 1 month, and 90.2% at 3 months.
Table 1. Baseline Demographics, Pre-Treatment Substance Use, and Motivations ($N = 346$)
| Parameter | Specification / Distribution |
| Demographics | |
| Mean age (years) | 49.5 |
| Sex: Female | 52.5% |
| Race: White | 86.7% |
| Psychedelic Background | |
| Psychedelic-naรฏve | 44.2% |
| Prior psychedelic experience | 55.8% |
| Substance Use (Prior 30 Days) | |
| Alcohol | 58.7% |
| Cannabis | 36.7% |
| Nicotine / Tobacco | 11.0% |
| Primary Motivations for Participation* | |
| Self-improvement | 68.5% |
| Managing mental health symptoms | 64.5% |
| Navigating psychological trauma | 51.4% |
| Greater connection with people, Earth, or nature | 45.1% |
*Categories were not mutually exclusive.
Psychiatric Symptom Trajectories and Well-Being
Assessment of moderate-to-severe psychiatric symptoms demonstrated marked decreases across all evaluated symptom domains from baseline through 3 months of follow-up. Concurrent improvements were identified in psychological well-being and life satisfaction.
Table 2. Psychiatric Symptoms, Well-Being Scores, and Quality of Life Measures
| Clinical Endpoint / Metric | Baseline Rate / Score | 1-Month Follow-Up | 3-Month Follow-Up | Statistical Metric (vs Baseline) |
| Moderate-to-Severe Depression | 42.2% | โ | 16.5% | RR = 0.40 (95% CI, 0.32โ0.50) |
| Moderate-to-Severe Anxiety | 45.1% | โ | 13.2% | RR = 0.29 (95% CI, 0.22โ0.38) |
| Moderate-to-Severe PTSD Symptoms | 48.0% | โ | 16.8% | RR = 0.35 (95% CI, 0.27โ0.45) |
| Mean Mental Well-Being Score | 22.1 | 26.2 | 25.3 | Mean Difference = 3.21 (95% CI, 2.66โ3.76) |
| Life Satisfaction Rate | 63.0% | 83.4% | 82.3% | RR = 1.31 (95% CI, 1.19โ1.44) |
Participant Satisfaction, Perceptions, and Safety Signals
At 1 month post-administration, participants reported high satisfaction with facilitator and facility care, as well as positive appraisals of overall value.
Safety surveillance revealed no serious adverse medical events. However, 4 participants experienced severe behavioral adverse reactions during administration sessions, 1 of which required acute healthcare intervention. All 4 individuals were psychedelic-naรฏve, had enrolled specifically to address treatment-refractory psychiatric symptoms, and 2 were actively prescribed psychiatric medications. Perceptions of personal harm remained low throughout observation (1.6% at 1 week; 1.9% at 1 month; 2.3% at 3 months).
Reflecting on the acute safety profile, Dr. Korthuis noted:
โWe were struck by the low incidence of serious adverse reactions.โ
He summarized the overall findings:
โOregon-regulated psilocybin services appear to be safe and associated with improved mental health and wellbeing. While promising, these early results need to be confirmed by comparing groups receiving psilocybin services with a control group of people who donโt access state psilocybin services.โ
Table 3. Self-Reported Satisfaction, Valuation, and Adverse Safety Events
| Outcome Domain | Evaluated Parameter | Reported Rate (%) |
| Provider & Facility Evaluation (1 Month) | Endorsed session facilitator | 96.0% |
| Endorsed state-licensed service center | 95.6% | |
| Personal & Life Appraisals (1 Month) | Achieved a broader life perspective | 89.4% |
| Accomplished self-made goals | 81.6% | |
| Perceived overall personal benefit | 92.2% | |
| Meaningful / comparable to highly valued life events | 58.6% | |
| Economic Perceptions | Reported service cost caused financial strain | 32.1% |
| Endorsed intervention as worth the financial cost | 81.0% | |
| Adverse Events & Perceived Harm | Serious medical adverse events | 0.0% ($n = 0$) |
| Serious behavioral adverse reactions | 1.15% ($n = 4$) | |
| Behavioral reactions requiring healthcare intervention | 0.29% ($n = 1$) | |
| Experience perceived as harmful at 1 week | 1.6% | |
| Experience perceived as harmful at 1 month | 1.9% | |
| Experience perceived as harmful at 3 months | 2.3% |
Invited Commentary: Diagnostic Validity and Selection Bias
In an accompanying perspective, Walter S. Dunn, MD, PhD (UCLA Department of Psychiatry; Co-Director, UCLA Psychiatry Residency Neuromodulation Program), emphasized key methodological caveats regarding generalizability to true clinical psychiatric populations:
- Absence of Formal Psychiatric Diagnoses: Participants were not verified through formal diagnostic evaluations. Reductions on screening scales (such as PHQ-9 or PCL-5) do not confirm DSM-defined major depressive disorder or PTSD. The clearest indicators of formal psychiatric illness were restricted to the 4 patients who developed acute behavioral reactions (two of whom were prescribed psychotropic drugs). If the broader cohort comprised largely non-clinical individuals seeking wellness, reported safety and efficacy metrics cannot be extrapolated directly to psychiatric cohorts.
- Positive Selection Bias via Prior Exposure: More than half of participants had prior psychedelic experience. Individuals who have had severe, frightening, or destabilizing reactions to psychedelics in the past are unlikely to voluntarily pay for state-licensed sessions. Consequently, the cohort was enriched with individuals preselected for biological and psychological tolerability.
- Recommendations for Future Studies: Future evaluations must systematically stratify clinical endpoints based on baseline diagnostic verification and psychedelic-naรฏve versus psychedelic-experienced status.
