Real-world psilocybin study finds short-term mental health score improvements, with safety questions remaining

The study examined records from 2,363 people who received psilocybin at regulated service centers in Oregon and Colorado. These states allow eligible adults to use psilocybin with licensed facilitators in supervised settings.

Researchers used a retrospective observational design. That means they looked back at information collected during regular services rather than assigning people at random to receive psilocybin or a comparison treatment. Clients and facilitators entered information before and after sessions.

The group included people with a range of mental health histories. Sixty-six percent had preexisting mental health concerns. Psilocybin doses ranged from 1 to 95 milligrams, with an average total dose of 28.8 milligrams.

Two weeks after dosing, average scores on commonly used self-report questionnaires changed. Depression scores on the Patient Health Questionnaire-9 were 49% lower on average. Anxiety scores on the Generalized Anxiety Disorder-7 were 51% lower. Scores on the World Health Organization’s five-question well-being measure improved by 22%.

These changes show an association: people who reported outcomes two weeks after regulated psilocybin services also reported better average mental health scores. They do not prove that psilocybin caused the changes. There was no control group, such as people receiving another approach or no psilocybin, to separate the possible effects of the drug from expectations, the facilitated setting, or other changes in participants’ lives.

The researchers also measured mystical-type experiences with a 30-question survey. Higher psilocybin doses were linked with higher scores on that measure. However, improvements in depression and anxiety scores were not different between people receiving 30 milligrams or less and those receiving more than 30 milligrams. Changes in those scores were only weakly connected with mystical-experience scores.

Safety was a central part of the report. The researchers recorded 94 mild adverse events during or after dosing. They also recorded five more serious events, though these were not clearly related to treatment. The study reported evidence of a possible risk of increased suicidality and said more robust monitoring is needed.

The findings apply to regulated service centers in Oregon and Colorado, not to all psilocybin use. These systems include screening and licensed facilitators. Oregon and Colorado use different eligibility and safety-screening processes, and facilitators may decline clients for health or safety reasons.

The paper is a preprint, meaning it had not yet been through peer review based on the supplied material. Its authors also noted important limits: sessions were open label, so clients knew they were receiving psilocybin; outcomes were self-reported; some participants were lost to follow-up; and the follow-up period was only two weeks.

Longer-term studies with comparison groups and complete follow-up would be needed to better understand benefits, risks, and which people may have different experiences in regulated settings.