Psilocybin, cognitive stability and drinking reduction in co-occurring alcohol use disorder and depression: a pilot secondary analysis of a randomized, placebo-controlled trial

In a placebo-controlled trial subset of patients with co-occurring alcohol use disorder and major depression, psilocybin slowed cued task switching about one week post-dose (d=1.01–1.12).

• Why it matters: Cognitive control changes are proposed mechanisms for psychedelic therapy, but competing accounts predict different effects on flexibility, inhibition, working memory, and willingness to exert control.
• What they did: In 25 participants (placebo n=13, psilocybin n=12), five cognitive tasks were completed pre-dose and again about 6.7 days later; 34 retest measures plus demand avoidance and correlations with drinking and PHQ-9 were analyzed using effect sizes and Bayes factors.
• The result: Psilocybin showed inconsistent feedback-driven effects and no detectable change in demand avoidance (BF01=2.0), while drinking reduction tracked increased cognitive stability (stability composite rho=-.64, BF10=29) and lower baseline working-memory span predicted larger reductions (BF10=19-25). Depressive symptoms improved more with psilocybin (PHQ-9 d=-0.88, BF10=2.7) but cognitive change did not explain or predict that improvement.

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