This open-label single-arm trial (n=20) found that a single 25 mg dose of psilocybin with psychological support was linked to rapid and lasting reductions in chronic suicidal thoughts and depression over 12 weeks. No serious adverse events were reported.
Papers cited by this study that are also in Blossom
Aaronson, S. T., Van Der Vaart, A., Miller, T. et al. · American Journal of Psychiatry (2025)
Objectives
To evaluate the efficacy, safety, and durability of a single 25-mg dose of a proprietary, synthetic formulation of psilocybin with psychological support for reducing chronic suicidal ideation in a treatment-resistant population.
Methods
This was an open-label, single-arm study with a 12-week follow-up conducted between March 2022 and May 2025. Twenty adults with chronic suicidal ideation, major depressive disorder (DSM-5), and ≥2 prior antidepressant treatment failures received a single 25-mg dose of psilocybin administered within a structured preparatory and integration psychotherapy protocol. The primary outcome was change from baseline in the Modified Scale for Suicidal Ideation (MSSI) at week 3. Secondary outcomes included change in MSSI at weeks 1 and 12 and change in Montgomery-Asberg Depression Rating Scale (MADRS) scores at weeks 1, 3, and 12. Outcomes were analyzed using 1-way repeated-measures analysis of variance with Bonferroni-adjusted pairwise comparisons.
Results
Significant reductions in MSSI scores were observed from baseline to week 3 (primary end point: mean difference [MD] = 13.95; 95% CI, 8.63–19.27; P < .001; d = 1.73). Improvements were rapid and durable, with significant reductions at week 1 (MD = 15.10; P < .001; d = 2.11) and week 12 (MD = 13.00; P < .001; d = 1.46). By week 12, 70% (n=14) of participants achieved MSSI ≤2. MADRS scores showed similar significant reductions at all postbaseline time points (MD range: 17.55–20.50; all P < .001; d = 1.63–1.97). No serious adverse events occurred.
Conclusions
In this open-label single-arm study of adults with chronic suicidal ideation and prior treatment failures, a single administration of psilocybin with psychological support was associated with rapid, large-magnitude, and durable reductions in suicidal ideation and depressive symptoms through 12 weeks. These preliminary findings support further evaluation in larger randomized controlled trials.
Suicidal ideation that persists for months or years can remain severe despite antidepressants, psychotherapy, or other standard treatments. The paper frames this as a major unmet need because many available interventions are slow to work, may not help in the acute phase of suicidal distress, or have limited durability. Although psilocybin has shown rapid antidepressant effects in earlier studies, people with significant suicidality have usually been excluded from psychedelic trials, leaving uncertainty about whether psilocybin can be used safely and effectively in this population. Vaart and colleagues set out to address that gap by studying whether a single 25-mg dose of psilocybin, given with structured psychological support, could reduce chronic suicidal ideation in adults with major depressive disorder who had not responded adequately to previous antidepressant treatment. They also aimed to assess durability of any benefit over 12 weeks, examine changes in depressive symptoms, and monitor safety and tolerability in this high-risk group.
This was an open-label, single-arm pilot study conducted between March 2022 and May 2025. The researchers enrolled 20 adults with chronic suicidal ideation, major depressive disorder, and at least two prior antidepressant treatment failures. Participants were required to have recent and sustained suicidal ideation on the Columbia-Suicide Severity Rating Scale, but those with very acute imminent risk were excluded. Other exclusions included personal or first-degree family history of psychotic or bipolar I disorder, active substance use disorder within 12 months, and unstable medical illness that would make psilocybin unsafe. Before dosing, participants tapered and washed out psychotropic medication for at least 2 weeks or five half-lives, whichever was longer. The intervention combined a single oral 25-mg dose of proprietary synthetic psilocybin with a structured psychotherapy model. This included three preparatory sessions with two trained therapists, the dosing session in a supportive room with eyeshades and music, and three integration sessions afterwards to help participants reflect on the experience and apply it to daily life. Outcomes were assessed at baseline and at weeks 1, 3, and 12. The primary endpoint was change in the clinician-rated Modified Scale for Suicidal Ideation (MSSI) from baseline to week 3. Secondary outcomes included MSSI change at weeks 1 and 12, changes in Montgomery-Asberg Depression Rating Scale (MADRS) scores across follow-up, response and remission rates, and the correlation between changes in suicidal ideation and depressive symptoms. Safety monitoring used the C-SSRS at each visit and systematic recording of adverse events, which were coded with MedDRA and reviewed for severity and relationship to treatment. The primary analysis included all participants who received psilocybin and completed the week 3 assessment. Repeated-measures analysis of variance was used to test changes over time, with Bonferroni-corrected pairwise comparisons against baseline. Effect sizes were calculated using Cohen d, and Pearson correlations examined the relationship between changes in suicidal ideation and depression. The authors also carried out exploratory comparisons between week 3 responders and nonresponders using t tests and Fisher exact tests.
Goodwin, G. M., Aaronson, S. T., Alvarez, O. et al. · New England Journal of Medicine (2022)
Goodwin, G. M. · Journal of Affective Disorders (2023)
Carhart-Harris, R. L., Friston, K. J. · Pharmacological Reviews (2019)
Shao, L-X,, Liao, C., Gregg, I. et al. · Neuron (2021)
Griffiths, R. R., Richards, W. A., Mccann, U. et al. · Journal of Psychopharmacology (2006)
Roseman, L., Nutt, D. J., Carhart-Harris, R. L. · Frontiers in Pharmacology (2018)
Krebs, T. S., Johansen, P. ˚. Ø. · PLOS ONE (2013)
All 20 enrolled participants received psilocybin and completed the 12-week study, with no dropout. The cohort was described as having severe suicidal ideation and moderate to severe depression, and most had experienced suicidal thoughts for years or most of adult life. At the primary endpoint, suicidal ideation improved substantially. Mean MSSI scores fell by 13.95 points from baseline to week 3, a large within-subject effect (Cohen d = 1.73; 95% CI for the mean difference 8.63 to 19.27; P < .001). Improvement was already evident at week 1, with a mean reduction of 15.10 points, and remained significant at week 12, with a mean reduction of 13.00 points; both were reported as P < .001. By week 12, 70% (14/20) of participants had very low suicidal ideation, defined as MSSI ≤2. Depressive symptoms improved in parallel. MADRS scores decreased significantly at weeks 1, 3, and 12, with mean reductions ranging from 17.55 to 20.50 points, all with P < .001 and large effect sizes (d = 1.63 to 1.97). Change in suicidal ideation and change in depressive symptoms were strongly correlated from baseline to week 3 (r = 0.70, P < .001). Response and remission rates were notable. At week 3, 15 of 20 participants (75%) met the criterion for suicidal ideation response, defined as at least a 50% reduction in MSSI, and 9 of 20 (45%) had full remission of suicidal ideation (MSSI = 0). For depression, 12 of 20 (60%) were MADRS responders and 9 of 20 (45%) met the remission threshold (MADRS ≤10). At week 12, 7 of 20 participants (35%) remained in suicidal ideation remission, and another 7 (35%) had minimal residual ideation. For depression at week 12, 10 of 20 (50%) remained antidepressant responders and 5 of 20 (25%) were in remission. Regarding safety, no serious adverse events were reported and no participant discontinued because of an adverse event. Most treatment-emergent adverse events were transient and mild to moderate. One participant required rescue lorazepam on the dosing day and short-term clonazepam afterwards for anxiety. Two participants (10%) showed an increase in MSSI relative to baseline; in one case this was transient, whereas in another suicidal ideation was higher at week 12 than at baseline (from 17 to 23). There was no evidence of treatment-emergent psychosis or sustained manic or hypomanic symptoms. In exploratory analyses, week 3 responders differed from nonresponders on a few baseline variables. Responders had slightly greater prior psilocybin exposure and were less likely to have a history of electroconvulsive therapy. Nonresponders endorsed more hopelessness and pessimism on specific suicide-risk questionnaire items such as “Things will never get better” and “No future”, suggesting that stronger negative expectancies may have been associated with weaker early response.
The authors interpret the findings as the first prospective evidence that psilocybin-assisted therapy may reduce chronic, treatment-resistant suicidal ideation. They argue that the intervention produced rapid, large, and sustained improvements in suicidal thoughts over 12 weeks, and that these improvements were accompanied by similarly strong reductions in depressive symptoms. They emphasise the speed of benefit, noting that the largest reduction was seen by week 1, which they consider clinically important for people at high suicide risk. Vaart and colleagues place the results in the context of earlier rapid-acting treatments such as esketamine, which may have short-lived effects, and suggest that psilocybin may offer a more durable response after a single administration. They also discuss the possibility that psilocybin could have direct antisuicidal effects rather than only reducing depression, although they state that the causal relationship between changes in depression and suicidal ideation cannot be determined from this study. They link the observed clinical effects to proposed mechanisms such as altered default mode network activity, reduced rigid self-referential thinking, increased psychological flexibility, and enhanced synaptic plasticity. The exploratory findings are presented as hypothesis-generating. The authors suggest that strong negative expectancies, reflected in beliefs such as “Things will never get better” and “No future”, may have attenuated response in nonresponders. They also note that prior psilocybin exposure was more common among responders and that prior electroconvulsive therapy was more common among nonresponders, but they do not overstate these associations. Safety is described as generally favourable, with mostly transient and mild adverse events. However, the authors highlight an anxiety/panic episode requiring benzodiazepine rescue in one participant with post-traumatic stress disorder, and they emphasise that two participants experienced worsening suicidal ideation, including one with clinically significant worsening at week 12. They present this as an important safety signal showing that negative outcomes can occur even in a carefully supported setting. The authors acknowledge several limitations. The open-label, single-arm design cannot separate treatment effects from placebo or expectancy effects. The sample was small, which limits generalisability and the ability to detect rare harms. The study took place at a specialised academic site with highly trained therapists, so the findings may not transfer directly to routine care. More than half of the participants restarted or began psychotropic medication after week 3, which complicates interpretation of durability over time. The small number of nonresponders also makes the exploratory comparisons unstable. The authors conclude that larger controlled trials with an adequate comparator are needed to disentangle specific psilocybin effects from nonspecific factors and to clarify long-term benefit.
The authors conclude that this pilot study provides a strong preliminary signal that psilocybin-assisted therapy deserves further testing for chronic suicidal ideation. They state that a single dose was associated with rapid, robust, and durable reductions in suicidal ideation and depression, and they recommend future studies with a suitable comparator group and longer follow-up to establish durability and interpretation of effects.