Key Takeaways
Extended Takeaways
- The dose-escalation design limited higher-dose exposure: 4 participants (28.5%) met remission criteria (MADRS ≤6) after the initial 10 mg session and did not proceed to 25 mg, suggesting some patients with bipolar II depression may improve before standard-dose administration is necessary.
- Psychiatric adverse events emerged after, not during, dosing sessions, including passive suicidal ideation at 11 days, worsening suicidal ideation with intent but no plan at 37 days, and hypomanic symptoms at 14 days after 25 mg; this timing supports structured follow-up for weeks after psilocybin administration rather than relying only on same-day monitoring.
- No serious adverse events were observed, and most of the 143 total adverse events were mild or moderate, with 83% of events mild, 15% moderate, and a single event severe; anxiety, nausea, and headache were the most common acute tolerability issues and did not require medication during sessions.
- Depression improvement was sustained beyond the acute treatment window, with MADRS change from baseline of −14.3 [2.8], n = 12, P < .001 at AB90; quality of life also remained improved at AB90 with QoL-BD change of 31.2 [10.2], P=.004.
- This sample had substantial trauma-related burden at baseline, with mean PCL-5 scores of 31.9 (20.9), and PTSD symptoms decreased by AB90 (−13.9 [6.1]; P=.048, Hedges g=−0.87); attachment avoidance also remained improved at AB90 (−5.9 [2.6]; P=.032), which may be relevant when bipolar II depression co-occurs with PTSD and attachment insecurity.
- Insomnia improved rather than worsened across follow-up, with ISI changes of −5 [1.4], P<.001 at A21, −7.0 [1.6], P<.001 at B21, and −3.1 [1.4], P=.036 at AB90; this is clinically useful because reduced sleep can complicate interpretation of emerging hypomanic symptoms in bipolar disorder.
