Psilocybin therapy for bipolar II depression: a small open-label dose-escalation trial

The question

Can psilocybin-assisted therapy be given safely to people with bipolar II disorder who are depressed, and does it show early signs of helping? People with bipolar disorder are usually excluded from psilocybin trials because of worries about triggering hypomania or psychosis.

What they did

Researchers ran an open-label pilot trial between 2022 and 2025, meaning everyone knew they were getting psilocybin and there was no placebo group. Fourteen adults with bipolar II depression received a 10 mg dose of psilocybin, and those whose symptoms persisted were then offered a 25 mg dose. All participants had psychotherapy sessions before, during and after the dosing sessions, and were monitored for side effects. Depression was measured with a standard clinician rating scale (MADRS) 21 days after each person’s final dosing session, alongside a bipolar-specific quality of life questionnaire.

What they found

Psilocybin was generally well tolerated, with only short-lived rises in heart rate and blood pressure and no serious adverse events. Common side effects were mild-to-moderate anxiety, nausea and headache. Three participants had notable psychiatric events, either suicidal thoughts or hypomania, which resolved with support. After the 10 mg session, depression scores fell by 12.7 points (P<.001) and 4 participants (28.5%) met remission criteria, so they did not go on to the higher dose; 9 people received 25 mg, and their depression scores fell by 18.6 points 21 days later (P<.001). Quality of life scores also improved at 90 days after the final dose (31.2 points, P=.004).

The fine print

This was a very small pilot of 14 people with no control group and no blinding, so the improvements cannot be attributed to psilocybin itself rather than to the psychotherapy, the attention received, or expectation. Three of 14 participants experienced suicidal thoughts or hypomania, which is an important safety signal in this group even though they resolved. Follow-up was short, and this summary is based on the published abstract only.

What it means

In a carefully monitored research setting, psilocybin therapy appeared tolerable for a small group with bipolar II depression and was followed by improved mood and quality of life scores, but the study design cannot show that psilocybin caused the change. The authors say randomized controlled trials are needed.

Evidence grade: Very low. A single-arm, open-label pilot with only 14 participants and no placebo or comparison group, so improvements cannot be separated from expectation and natural course.

This summary is based on the study’s published abstract.