In brief
- A pilot trial at the University of California, San Francisco (UCSF) tested psilocybin in 14 people with bipolar II depression, a profile typically excluded from these studies.
- Depressive symptoms dropped markedly after the session, with both 10 mg and 25 mg doses.
- Three participants experienced notable psychiatric episodes (suicidal ideation or hypomania) that were resolved with clinical support; there were no serious adverse events.
A team at the University of California, San Francisco, has published the first clinical trial administering psilocybin in an open-label format to people with bipolar II depression (BD-II)—a group most psychedelic trials exclude due to fears of triggering mania or psychosis. The study, led by Amanda E. Downey and Josh D. Woolley, appears in The Journal of Clinical Psychiatry and concludes that the substance was generally well tolerated.
A design intended to minimize risk
The trial, registered as NCT05065294 and conducted between 2022 and 2025, included 14 people diagnosed with depression in the context of bipolar II disorder, using adapted criteria that required at least two consecutive days of hypomanic symptoms. Each participant first received a 10 mg dose of psilocybin; only if depressive symptoms persisted did they move on to a second session with 25 mg. Everyone received psychotherapy before, during, and after the sessions and was actively monitored for signs of decompensation.
Clear improvement, with safety nuances
After the 10 mg dose, scores on the MADRS scale (the most commonly used to measure depression severity) dropped by an average of 12.7 points (p<0.001), and 28.5% of participants (4 of 14) met remission criteria, meaning they did not receive the second dose. Of the 9 who did move on to the 25 mg dose, the improvement at 21 days was even greater: an average of 18.6 points (p<0.001). Quality of life, measured with the QoL-BD questionnaire, also improved significantly 90 days after the final dose (31.2 points, p=0.004). Regarding safety, the most common effects were mild to moderate anxiety, nausea, and headache, along with transient increases in heart rate and blood pressure. There were no serious adverse events, but three participants went through relevant psychiatric episodes (suicidal ideation or hypomania) that the authors describe as resolved with the support of the clinical team.
What this implies
This is a pilot trial—open-label (without a placebo group or blinding) and with a very small sample size—so the results are preliminary. They serve to explore whether psilocybin can be administered with reasonable safety in this patient profile, not to confirm that it works better than other options. The authors themselves call for randomized controlled trials to confirm efficacy and refine the protocol, especially regarding the monitoring of hypomanic episodes. For those living with bipolar II disorder, the relevant takeaway is that this group, historically sidelined from psychedelic research, is beginning to have its own data to rely on instead of extrapolating from unipolar depression. More context on this substance, its pharmacology, and its history can be found in Psiconáutica’s psilocybin and magic mushrooms guide, and on another psychedelic tested for treatment-resistant bipolar depression in this previous news article on ketamine.
Source
- Downey AE, Szigeti B, Bradley ER, et al. An Open-Label, Dose-Escalation Trial of Psilocybin-Assisted Therapy for Bipolar II Depression. The Journal of Clinical Psychiatry, September 21, 2026.
Educational content written from a harm reduction perspective and with respect for individual freedom. It is not a substitute for advice from a healthcare professional and is not intended to encourage or condemn any drug use.
