In brief
- A retrospective preprint includes 2,363 regulated-service records; two-week PHQ-9 and GAD-7 score changes of −49% and −51% come from 138 and 181 paired responses, respectively.
- Doses ranged from 1 to 95 mg, averaging 28.8 mg. No significant outcome difference was found between 30 mg or less and above 30 mg; this does not prove equivalence or an optimal dose.
- The preprint notes 94 mild adverse events, five more serious ones, and potential evidence of increased suicidal ideation that the authors urge investigating further.
Oregon and Colorado were the first two US states to establish a legal framework for supervised psilocybin outside clinical trials. An analysis of those services provides observational data outside the laboratory: a team led by Scott M. Thompson at the University of Colorado Anschutz, alongside clinical management company Althea PBC, posted on medRxiv an analysis of these services covering 2,363 participants.
What they measured
Clients and facilitators completed standardized questionnaires before and after sessions: depression (PHQ-9), anxiety (GAD-7), well-being (WHO-5), and mystical experience (MEQ-30). 66% of 1,476 respondents reported depression or anxiety history. Two-week mean changes were −49% in PHQ-9 (n = 138), −51% in GAD-7 (n = 181) and +22% in WHO-5 (n = 600), using paired pre/post responses.
Dose comparison without significant differences
The finding that defies common intuition lies in the dosing. Doses ranged from 1 to 95 mg, with an overall average of 28.8 mg. While the intensity of the mystical experience increased with dosage, no significant differences in depression and anxiety changes were observed between 30 mg or less and above 30 mg; an equivalence test was not designed. Furthermore, the correlation between how mystical the session felt and subsequent clinical improvement was weak. In other words, an intense experience and clinical benefit do not necessarily go hand in hand, contradicting one of the most frequently repeated assumptions in the field.
What went wrong
The study also tracks adverse events, which is part of its real value. There were 94 mild adverse events during or after dosing and five more serious events whose relationship to psilocybin remains unclear: two emergency service calls (one for suspected cardiac issues, another for renal colic), one request for help with acute emotional distress without confirmation that an emergency call was made, a possible heart attack reported days later, and a fall without injuries. Added to this is what the authors describe as evidence of a potential risk of increased suicidal ideation in part of the sample, a signal they emphasize warrants thorough investigation.
What it means
It is best read with the caveats the paper itself outlines: it is retrospective, open-label (no placebo, no blinding), relies on self-reported data, loses participants to follow-up, and cuts off at two weeks. It has also not yet undergone peer review. Furthermore, there is a declared conflict of interest worth noting: CU Anschutz held an equity stake in Althea, the study’s co-sponsor, and several co-authors are founders or employees of the company. Even with all that, it remains one of the few large-scale portraits of legal access in practice, complementing the three-month follow-up published in JAMA Network Open without allowing a direct comparison of the outcome samples. The most actionable takeaway is not the percentage of improvement, but the rest: higher doses guarantee nothing, and a supervised setting does not eliminate the need to screen for cardiac history or provide post-session psychological support. That is vital information for anyone considering psilocybin, and it aligns with what any rigorous approach to harm reduction has long demanded: data, not promises.
Source
- Thompson SM, et al. Real-world use, safety, and mental health efficacy of regulated psilocybin services in Oregon and Colorado. medRxiv (preprint, not peer-reviewed), August 12, 2026.
Educational content written from a harm reduction perspective and with respect for individual freedom. It is not a substitute for advice from a healthcare professional and is not intended to encourage or condemn any drug use.
