Psilocybin therapy linked to reduced suicidal thoughts in people with psychiatric disorders

A new study published in Therapeutic Advances in Psychopharmacology provides evidence that psilocybin therapy may reduce suicidal ideation in adults with psychiatric conditions. The findings come from a systematic review and meta-analysis of clinical trials and suggest that the psychedelic compound, when paired with psychological support, may have a modest but measurable impact on decreasing thoughts of suicide. Although suicide attempts and deaths were not observed in these trials, the results point to the possibility that psilocybin could play a role in mental health treatment strategies aimed at reducing suicide risk.

Psilocybin is a naturally occurring psychedelic compound found in certain mushrooms, sometimes called “magic mushrooms.” It affects the brain by stimulating serotonin receptors, particularly one known to play a role in mood regulation and emotional processing. When administered in controlled clinical settings alongside therapy, psilocybin has been shown to help relieve symptoms of depression, anxiety, and some forms of addiction.

Interest in psilocybin as a therapeutic agent has grown rapidly in recent years, especially for people who do not respond to standard treatments like antidepressants or talk therapy. Some smaller studies have suggested that psilocybin therapy might also reduce suicidal ideation, a symptom common in many psychiatric conditions.

Given suicide’s widespread toll on public health, researchers wanted to evaluate whether these early signs held up across multiple trials. To do this, they examined all available randomized controlled trials that reported on suicide-related outcomes in people undergoing psilocybin therapy.

“I was inspired to investigate the usage of psilocybin therapy to help treat my patients who suffer from treatment resistant depression. As I was reading the latest clinical trials at the time, there were some reports of increasing suicidal ideation. Increasing suicidal ideation would be a risk in this vulnerable population. When I was reviewing the literature, there was not much synthesized evidence which inspired me to pursue this study,” explained study author Stanley Wong, a general psychiatry resident at the University of Toronto.

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To assess the potential impact of psilocybin therapy on suicidal ideation and behaviors, the research team carried out a systematic review and meta-analysis. A systematic review collects and evaluates all relevant studies on a specific topic using a structured and transparent process. A meta-analysis goes a step further by statistically combining results from multiple studies to estimate an overall effect. This method is often used in medicine to determine how well a treatment works by comparing evidence across different settings, sample sizes, and trial designs.

The team searched four major scientific databases for randomized controlled trials involving adults with psychiatric disorders who received psilocybin therapy and for whom suicide-related outcomes were reported. They identified nine studies with a total of 593 participants: 335 received psilocybin therapy, while 258 were assigned to control conditions. Seven of these studies provided usable data for the meta-analysis.

The researchers found that, on average, participants who received psilocybin therapy experienced a small reduction in suicidal ideation compared to those in the control groups. There was no evidence of publication bias, which suggests that the results were not skewed by the selective reporting of positive outcomes.

“We found a small but significant reduction in suicidal ideation in adults receiving psilocybin therapy compared to control,” Wong told PsyPost. “Clinically, this could mean a potential reduction in the frequency or intensity of suicidal thoughts, and people living with treatment resistant depression, which could greatly enhance their well-being in quality of life.”

Importantly, none of the studies reported suicide attempts or deaths during the course of the trials. However, one study did observe suicidal behavior in a small number of participants who received a higher dose of psilocybin. The difference was not statistically significant when compared to other groups.

“I was surprised and glad that there was no death by suicide in any of the trials conducted,” Wong said. “All the studies used standardized scales to follow the suicidal thoughts of their participants. This speaks to the degree of importance these studies placed on the safety of participants of not just physical adverse outcomes but also psychological ones as well.”

The analysis also explored whether factors like funding source, study location, or the use of blinding (in which participants and staff are kept unaware of who received the active drug) affected the results. No clear differences emerged between subgroups. Interestingly, studies that used a single dose of psilocybin showed a more consistent reduction in suicidal ideation than those using multiple doses, although the sample sizes for multiple-dose studies were smaller, making the findings harder to interpret.

While most trials were able to maintain the blind design on paper, two studies assessed whether staff could guess who had received psilocybin based on participants’ behavior. In nearly every case, they guessed correctly, raising concerns about the potential for bias. This issue is common in psychedelic trials, where the effects are often obvious to both participants and researchers, even when a placebo or active control is used.

The study provides a useful snapshot of the current evidence but also highlights several limitations. Most trials included small numbers of participants, which can make findings less reliable and more vulnerable to overestimating the benefits of treatment.

None of the trials were designed specifically to study suicide prevention, so suicide-related outcomes were often recorded as secondary measures or adverse events. There was also considerable variation in how suicidal ideation was measured across trials, with some using dedicated suicide assessment tools and others relying on a single item within broader depression scales.

Another important issue is that people with high levels of suicidal ideation or a history of suicide attempts were often excluded from participating in these trials. This makes it difficult to generalize the findings to individuals at the highest risk, who may have the most to gain or lose from a new treatment. Additionally, while psilocybin therapy appeared to reduce suicidal thoughts in the short term, long-term follow-up data were limited, leaving questions about whether the benefits last over time.

“In adults with psychiatric diagnoses (mainly treatment resistant depression), psilocybin therapy may reduce suicidal ideation through its antidepressive effects,” Wong said. “However, further research is required to understand the long-term effects of psilocybin therapy on suicidal thoughts.”

There is also the issue of how psilocybin therapy exerts its effects. Researchers suspect that the reduction in suicidal ideation is likely tied to the therapy’s broader antidepressant properties. Psilocybin interacts with serotonin systems in the brain, modulates activity in regions involved in emotion, and may promote neural plasticity.

Some scientists also believe the experience itself—often described as intense, emotional, or personally meaningful—may help people shift their perspective and find new meaning in life. Others point to the possibility that psilocybin reduces hopelessness, a known risk factor for suicide. However, none of these explanations have been specifically tested in the context of suicide-related outcomes.

Future research could explore these potential mechanisms more directly, perhaps by examining brain scans, molecular markers, or psychological changes before and after treatment. Studies could also include participants with higher baseline risk for suicide and follow them for longer periods to better understand safety and durability.

“Psilocybin therapy, like most emergent therapies being invested gained, are conducted in smaller sample sizes for many reasons, including safety and cost,” Wong told PsyPost. “As such, the true effect size of the reduction in suicidal ideation is still yet to be determined. However, the findings from our study points towards a positive finding for those suffering from treatment resistant depression.”

“I would like to further investigate whether or not the reduction in suicidal ideation is maintained in long-term follow up studies. I would also like to investigate the neurobiological mechanisms in which psilocybin therapy reduces suicidal ideation.”

“Psilocybin therapy has really opened doors for potential treatment options for those who suffer from treatment resistant depression – I am excited to see what the future has in store for this emerging field of psychedelic psychiatry,” Wong added.

The study, “Effect of psilocybin therapy on suicidal ideation, attempts, and deaths in people with psychiatric diagnoses: a systematic review and meta-analysis,” was authored by Stanley Wong, Gray Meckling, Nicholas Fabiano, Sanghun Lee, Brett D. M. Jones, Risa Shorr, Aroldo Dargel, Alan K. Davis, Jess G. Fiedorowicz, Marco Solmi, Joshua D. Rosenblat, Benoit H. Mulsant, Daniel M. Blumberger, and Muhammad Ishrat Husain.