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Effects of Psilocybin Treatment on Cognitive Effort Avoidance in Major Depressive Disorder and Co-Occurring Alcohol Use Disorder

Poster Session D - Monday, March 9, 2026, 8:00 – 10:00 am PDT, Fairview/Kitsilano Ballroom

Ceyda Sayali¹, Eli Weisman¹, Frederick Barrett¹; ¹Johns Hopkins University School of Medicine

Psilocybin has shown preliminary safety and efficacy in treating Major Depressive Disorder (MDD) and Alcohol Use Disorder (AUD), yet the mechanisms underlying its therapeutic effects remain unclear. While psychedelics acutely impair cognitive control performance, post-acute improvements have been observed. Importantly, cognitive control is not a unitary construct—it includes both the capacity to perform and the motivation to engage in cognitively demanding tasks. In this study, we examine whether psilocybin influences cognitive effort avoidance, a transdiagnostic feature across psychiatric conditions. This ongoing double-blind study evaluates the effects of a 25 mg dose of psilocybin on cognitive effort motivation in individuals with co-occurring MDD and AUD (MDD-AUD). We hypothesized that psilocybin would increase motivation for cognitive control post-acutely, reflected in greater selection of high-effort tasks, and that these changes would relate to symptom improvements. Participants were drawn from a placebo-controlled trial of psilocybin-assisted therapy for MDD-AUD. Cognitive effort motivation was measured using a task-switching paradigm embedded in a parametric Demand Selection Task at baseline and one week post-dosing. Depression symptoms were assessed at the same time points using the 9-item Patient Health Questionnaire (PHQ-9). Preliminary results indicate that greater reductions in PHQ-9 scores were associated with more frequent selection of high-effort tasks, despite no change in task performance. These preliminary findings suggest that psilocybin may reduce cognitive effort avoidance in individuals with MDD-AUD, potentially enhancing motivation for goal-directed behavior critical to recovery from both depression and addiction.

Topic Area: THINKING: Decision making