Recent research published in Journal of Clinical Psychiatry Our results suggest that a single dose of psilocybin combined with psychological support may quickly and safely reduce chronic suicidal ideation in adults with severe depression. The findings of this study provide evidence that psychedelic-assisted therapy tends to provide durable relief in individuals who have not responded to standard psychiatric treatment.
Chronic suicidal ideation is a serious challenge in psychiatric care. Symptoms often persist even when patients receive standard treatments and intensive drug trials. Traditional interventions, such as standard antidepressants and cognitive behavioral therapy, tend to be effective for many people, but usually require long treatment periods. In the acute phase of suicidal suffering, they may not provide immediate relief.
Other fast-acting treatments, such as ketamine, have shown promise in the acute phase, but have limited duration of effect. Past studies have shown that the anti-suicidal effects of these rapid treatments tend to wear off within days or weeks. This creates a need for interventions that produce more lasting psychological and behavioral changes.
Psilocybin is a psychoactive compound found in “magic mushrooms.” It has received considerable attention because it can induce rapid and lasting psychological changes when administered in a structured treatment setting. This substance works by stimulating specific serotonin receptors in the brain, causing temporary changes in brain network activity, particularly within the default mode network.
The default mode network is a collection of brain regions associated with introspection, mind wandering, and rumination. In people with severe depression, this network tends to become overly rigid, trapping people in repetitive negative thought patterns. Scientists propose that psilocybin can disrupt this rigid activity, allowing the brain to loosen deeply ingrained maladaptive beliefs. This temporary flexibility may help people break free from the ruminative thinking that characterizes chronic suicidal ideation.
Despite these theoretical benefits, previous clinical trials evaluating psychedelics have almost completely excluded participants with significant suicidal ideation. Medical professionals typically consider active suicidal tendencies to be a significant safety risk that precludes participation in experimental research. Because of this cautious approach, previous trials evaluating psychedelics have assessed suicidality only as a secondary safety measure rather than the primary goal of treatment.
Scott T. Aaronson, chief scientific officer of the Shepard Pratt Institute for Advanced Diagnostics and Treatments and adjunct professor of psychiatry at the University of Maryland, helped author the new study. He noted that the historical exclusion of this group has created a notable gap in scientific knowledge.
“Suicidal patients are typically excluded from all depression trials,” Aaronson said. “Given the high profile of psychedelic drugs and concerns that there may be signs of increased suicidality after psychedelic drug administration, it seemed important to focus on this population and provide careful monitoring and support.”
To address this gap, researchers organized an open-label study of 20 adults between the ages of 18 and 65. An open-label trial means that both researchers and participants know what substance is being administered, and no placebo is used. The sample consisted of 12 men and 8 women, with an average age of approximately 36 years. All participants had a confirmed diagnosis of major depressive disorder and experienced chronic suicidal ideation.
These people also had a history of treatment resistance, meaning their symptoms persisted despite completing at least two adequate trials of standard antidepressants. Prior to the experimental session, participants completed a supervised process to slowly discontinue all psychiatric medications they were currently taking. The intervention itself included a specialized synthetic formulation of psilocybin, alongside a structured psychological support program. The program included three preparatory therapy sessions aimed at building trust and setting intentions.
During the dosing session, participants received a single 25-milligram oral dose of psilocybin in a dedicated room designed with physical comfort and psychological safety in mind. They put on their eyeshades, reclined, and listened to a carefully selected music playlist for about eight hours. Two trained therapists remained in the room throughout the experience. Participants then participated in three integration sessions to process their experiences and incorporate the psychological insights into their daily lives.
To measure changes in suicidal ideation, the researchers used a clinical interview tool known as the Modified Suicidal Ideation Scale. They assessed participants before treatment and again one week, three weeks, and 12 weeks after the treatment session. They also tracked changes in overall depressive symptoms using the Montgomery-Asberg Depression Rating Scale.
Researchers found a statistically significant and significant reduction in suicidal ideation by the primary endpoint at week 3. Participants dropped an average of almost 14 points on a scale of suicidal ideation. The improvement was rapid, with significant reductions seen just one week after administration. These benefits were durable and remained significant through the final 12-week evaluation.
By the third week, 75% of participants met criteria for an anti-suicidal response. This means that the suicidal ideation score was reduced by at least half. Additionally, 45 percent of participants achieved complete remission of suicidal thoughts. Depression scores followed a similar trajectory, declining significantly and remaining low throughout the 12-week follow-up period.
Aaronson noted that these results exceeded initial expectations. “We didn’t expect to see such a high remission rate,” he says. He added that for many of those involved, the improvement in symptoms was long-lasting. “For many of the participants, the effects continued to be tracked for 12 weeks after administration,” Aaronson explained.
There was a strong correlation between changes in depression severity and suicidal ideation. However, the initial reduction in suicidal ideation at week 1 was slightly greater than the reduction in overall depressive symptoms. This provides evidence that psilocybin may exert certain antisuicidal effects independent of its general antidepressant properties.
“Suicidal ideation tends to be a better target for treatment than symptoms of depression, but it’s a more individualized target,” Aaronson told SciPost.
The safety profile of this intervention was generally good. No serious adverse events occurred and no participants dropped out of the study. The most common side effects include temporary mild to moderate nausea, headache, and anxiety. One participant required taking standard anti-anxiety medications on the day of the dosing session to manage panic attacks.
Importantly, the study results provided evidence against the idea that the drug inherently worsens suicidal thoughts. “There was no significant evidence of a pattern of increased risk of suicidal ideation after a single dose of the synthetic psychedelic psilocybin,” Aaronson explained.
He added that the overall results were very positive for the majority of the group. “Overall, 14 of the 20 volunteers showed remission or near-remission of suicidal ideation three months after a single dose of psilocybin,” Aaronson said.
Exploratory analyzes revealed some interesting differences between those who responded well to treatment and those who did not. Participants who did not respond to psilocybin therapy tended to have strong feelings of hopelessness and pessimism before the trial began. People who strongly believe that things will never get better appear to be less likely to see an early reduction in suicidal ideation.
“Participants who were less pessimistic and/or hopeless at baseline and the day after dosing tended to be remitters,” Aaronson observed. “This suggests that expectations are a powerful force and that adequate preparation before administration can improve outcomes for the most pessimistic patients.”
The research team also found that the screening process may have completely missed the severity of some participants’ symptoms. “Some participants reported that they were actually more suicidal than they said at the screening,” Aaronson said. “They were afraid of being excluded. The main concern in studies like this is that they were trying not to include participants who reported immediate suicidal ideation.”
Although these findings are promising, there are several limitations that the reader should consider. Aaronson emphasized the preliminary nature of the trial. “This was an open-label, small-N study, and participants were carefully screened and followed,” he said.
An open-label design cannot exclude a placebo effect, and a small N means a small number of participants. Participants who volunteer in psychedelic clinical trials often have strong positive expectations about the treatment, which can significantly influence subjective outcomes. Without administering a placebo to a control group, it is difficult to accurately determine the extent to which the drug itself improves psychological expectations of cure.
The small sample size of 20 individuals limits the ability to generalize these results to the broader population. The small group size also makes it difficult to detect rare but potentially serious side effects. This study was conducted at a single academic center with highly specialized therapists and therefore may not reflect the care received in a standard psychiatric clinic.
Safety concerns also remain a priority, as two participants experienced an increase in suicidal ideation scores compared to baseline. For some individuals, this deterioration was temporary. Second, the increased suicidal ideation remained even after the 12-week study ended.
Aaronson provided the background for this particular case. “There was one participant who exited with slightly higher levels of suicidal ideation at 12 weeks, but he met remission criteria shortly after dosing, so we are likely looking at a response to the loss of psychedelic support rather than the cause of the psychedelic increase,” he said.
Another complicating factor involves restarting other medications. More than half of the participants resumed taking standard psychiatric medications three weeks into the study. Although major benefits were observed before these changes occurred, the reintroduction of the external drug makes it difficult to attribute the 12-week persistence strictly to a single dose of psilocybin.
The study was funded by Compass Pathways, the pharmaceutical company that developed the synthetic psilocybin formulation used in the trial. The authors noted that the company had no role in study design, data collection, or interpretation of final results. Several authors reported receiving personal fees, grants, or holding stock options from Compass Pathways or other pharmaceutical companies.
Future studies should employ larger sample sizes and randomized, placebo-controlled designs to better isolate the specific effects of psilocybin. The scientists hope to conduct a longer follow-up period to understand whether the treatment effects persist beyond three months. They also aim to test whether additional dosing sessions or ongoing integrative therapy can help strengthen and maintain positive improvements in mental health over time.
Aaronson indicated that continued research plans are already underway. “I’m currently looking for funding for larger studies,” he said. He stressed that supporting this particular group of patients remains a priority. “We hope this will help open the door to support further research into this often neglected population,” Aaronson concluded.
The study, “Efficacy and Safety of a Single Dose of Psilocybin for Chronic Suicidal Ideation: An Open-Label Study,” was authored by Andrew van der Vaart, Jeffrey LaPratt, Kimberly Swartz, Audrey Shoultz, Margo Lauterbach, Trisha Suppes, Harold A. Sackeim, and Scott T. Aaronson.
