Key Takeaways
Extended Takeaways
- The primary antisuicidal signal was substantial by week 3, with a mean MSSI reduction of 13.95 points and Cohen d = 1.73 after a single 25-mg dose delivered with structured preparation and integration.
- Clinical improvement appeared early and then plateaued: the mean MSSI score was 3.4 at week 1, 4.6 at week 3, and 5.5 at week 12, which may help clinicians frame expectations about strong early benefit with some later symptom return.
- Suicidal ideation and depressive symptoms improved together but not perfectly, with baseline-to-week 3 change scores strongly correlated (r = 0.70, P < .001), suggesting SI tracking should remain a distinct target rather than inferred from mood response alone.
- Durability should be interpreted cautiously because 12 of 20 participants (60%) restarted or initiated at least 1 psychotropic medication for MDD at or after week 3, so longer-term outcomes were not attributable to psilocybin alone.
- Safety monitoring remains essential even in a supported setting: 2 of 20 participants (10%) had increased MSSI relative to baseline, including 1 participant whose score rose from 17 at baseline to 23 at week 12, although no serious AEs, psychosis, or sustained manic/hypomanic symptoms were observed.
- Exploratory signals suggest baseline hopelessness may moderate response; nonresponders had higher CHRT-SR ratings for “Things will never get better” at baseline (4.6 vs 3.9; P = .042) and day 1 (3.6 vs 1.9; P = .008) and for “No future” at baseline (5.0 vs 3.6; P = .020) and day 1 (4.0 vs 1.9; P = .003).
