Open-label trial · 2026
Single dose of psilocybin in 20 adults with chronic suicidal thoughts: open-label trial
- Original title
- Efficacy and Safety of a Single Dose of Psilocybin for Chronic Suicidal Ideation: An Open-Label Trial.
- Authors
- van der Vaart A, LaPratt J, Swartz K, et al.
- Journal
- The Journal of clinical psychiatry, 2026
- Molecules
- Psilocybin
- Conditions
- Suicidal ideation, Treatment-resistant depression, Depression
- Participants
- 20
- Evidence grade
- Low
- Source
- Read the original paper
The question
Can a single 25-mg dose of psilocybin, given alongside preparation and integration therapy, reduce long-standing suicidal thoughts in people whose depression has not responded to previous treatments?
What they did
Twenty adults with major depressive disorder, ongoing suicidal thoughts and at least two failed antidepressant treatments each received one 25-mg dose of a synthetic psilocybin formulation. Everyone knew what they were getting; there was no placebo group. Sessions were wrapped in a structured psychotherapy protocol, with preparation beforehand and integration afterwards. Suicidal thinking (Modified Scale for Suicidal Ideation, MSSI) and depression (Montgomery-Asberg Depression Rating Scale, MADRS) were tracked for 12 weeks, with the main measurement at week 3. The study ran from March 2022 to May 2025.
What they found
Suicidal ideation scores fell substantially by week 3, the main endpoint (mean difference 13.95 points; 95% confidence interval 8.63-19.27; p < .001). Reductions appeared as early as week 1 (mean difference 15.10) and were still present at week 12 (mean difference 13.00). By week 12, 70% of participants (14 of 20) had an MSSI score of 2 or less. Depression scores also dropped at every follow-up point (mean differences ranging from 17.55 to 20.50 points). No serious adverse events were reported.
The fine print
With only 20 participants, no control group and no blinding, the results cannot show that psilocybin itself caused the improvement; expectation, the intensive therapy support and the natural ups and downs of depression may all contribute. Follow-up stopped at 12 weeks, so longer-term durability and safety are unknown. Participants were a selected group with treatment-resistant depression who agreed to a psychedelic trial. This summary is based on the abstract only.
What it means
In a small uncontrolled trial, one dose of psilocybin with psychological support was followed by large and sustained drops in suicidal thinking and depression scores over 12 weeks, but randomized, placebo-controlled studies are needed before any conclusions about effectiveness can be drawn.
Evidence grade: Low. Small single-arm, open-label trial with no placebo or comparison group, so improvement cannot be separated from expectation and natural change.
This summary is based on the study’s published abstract.