Psilocybin-assisted therapy may reduce chronic suicidal thoughts in treatment-resistant depression. Digest
Chronic suicidal thoughts can persist despite multiple antidepressant treatments, and effective options remain limited for many patients. Researchers have now tested whether a single dose of psilocybin could provide a new treatment option.
The study included 20 adults aged 18 to 65 who had experienced active suicidal thoughts on most days for at least three months and had not improved after at least two antidepressant trials. People with a recent active suicide plan and imminent intent were excluded. After tapering psychiatric medications, all participants received a 25-milligram dose of psilocybin as part of a structured treatment program that included meetings with therapists before and after the dosing session. There was no placebo, comparison group, or blinding. Before treatment and again 1, 3, and 12 weeks later, clinicians rated suicidal thoughts using a 0–54 scale and depression using a 0–60 scale, with higher scores indicating more severe symptoms.
- Suicidal thoughts dropped sharply within three weeks. The average score fell from 18.5 at the start of the study to 4.6. Fifteen of the 20 participants had their scores cut by at least half.
- Most participants still had few or no suicidal thoughts 12 weeks later. The average score was 5.5, and 14 of the 20 participants scored between 0 and 2 on the suicidal thought scale, including seven who scored 0.
- Depression symptoms also improved. The average depression score fell from 35.3 at the start of the study to 14.8 after three weeks and was 17.7 after 12 weeks.
- Most adverse events were mild, but not everyone improved. Two of the 20 participants experienced worsening suicidal thought scores. The score of one participant increased only temporarily before falling below its starting point by week 12, while the other participant's score rose from 17 to 23 by the end of the study.
Psilocybin activates serotonin 5-HT2A receptors in the brain. The researchers suggest that this may temporarily disrupt brain activity tied to rigid, self-focused thinking and support greater neural flexibility, potentially allowing shifts in perspective, meaning, and connectedness that mitigate hopelessness and repetitive suicidal thinking. Preparing participants beforehand and helping them reflect afterward may also have contributed. In psychedelic-assisted therapy, this support is considered crucial because it helps people enter the session with trust and clear expectations, then connect the experience to daily life.
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The main limitation is that everyone received the same treatment, making it impossible to separate the effects of psilocybin from therapist support, expectations, or natural symptom changes. Still, psilocybin-assisted therapy could offer a new option for people with chronic suicidal thoughts whose depression has not responded to standard treatment. In this clip, the late Dr. Roland Griffiths describes new findings that suggest psilocybin may be useful in managing the symptoms of treatment-resistant depression.
If you or someone you know is struggling with suicidal thoughts, support is available worldwide through local crisis helplines, which can be found here.