Single Dose of Synthetic Psilocybin Reduces Chronic Suicidal Ideation in Open-Label Trial

The Journal of Clinical Psychiatry reported an open-label trial of 20 adults (12 men, 8 women) with major depressive disorder and chronic suicidal thoughts, all treatment-resistant. After tapering existing meds, participants received a single 25 mg oral dose of synthetic psilocybin, preceded by three preparatory therapy sessions and followed by three integration sessions. Suicidal ideation was measured with the Modified Scale for Suicidal Ideation (MSSI) at baseline, week 1, week 3, and week 12.

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At week 3 the mean MSSI score fell by 14 points. Seventy-five percent achieved at least a 50 % reduction (anti-suicidal response) and 45 % reached full remission. Depression severity on the Montgomery-Åsberg Depression Rating Scale declined in parallel and stayed low through week 12. Fourteen of 20 participants maintained remission or near-remission at three months.

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No severe adverse events occurred; all participants completed the study. Nausea, headache and anxiety were common; one required an anti-anxiety dose for a panic attack. Two participants showed temporary increases in suicidal ideation; one remained elevated at week 12, which investigators attributed to loss of support. The open-label design lacks a placebo control. The small sample (N = 20) limits power and generalizability from a single site. Screening may have under-reported baseline suicidality. Over half resumed standard medications after week 3, confounding durability. Funding from Compass Pathways, the drug’s manufacturer, poses a conflict of interest.

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The investigators said the trial fills a gap left by earlier psychedelic studies that excluded suicidal patients. They reported a favorable safety profile and durable anti-suicidal effects over 12 weeks. The authors emphasized that Compass Pathways had no role in design, data collection, or interpretation and called for larger, randomized, placebo-controlled trials. If replicated, a single psilocybin dose could provide rapid, lasting relief for treatment-resistant depression with chronic suicidal thoughts, a need unmet by antidepressants and ketamine.

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• “Patients with suicidal ideation are generally excluded from all depression trials,” — Scott T. Aaronson

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• “Given the amount of attention psychedelics have had and the concern that there may be a signal for increased suicidality after psychedelic dosing, it seemed critical that we should look at this population and provide careful monitoring and support.” — Scott T. Aaronson

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• “We did not expect to see such a high remission rate,” — Scott T. Aaronson

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• “There was no significant evidence for a pattern of increased risk of suicidal ideation after a single psychedelic dose of a synthetic psilocybin,” — Scott T. Aaronson

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Two participants showed increased suicidal ideation after dosing; one remained elevated at week 12, contrary to the overall remission pattern. Screening may have missed baseline severity, and the lack of a placebo arm prevents clear attribution of effects. Durability beyond three months is unknown.

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