Cognitive outcomes following psilocybin-assisted therapy in treatment-resistant depression: A post-hoc analysis of a randomized, waitlist-controlled trial
Progress in Neuro-Psychopharmacology and Biological Psychiatry – November 22, 2025
Source: OpenAlex
Summary
Psilocybin-assisted therapy was linked to modest, short-term improvements in mental quickness and problem-solving for individuals with severe depression resistant to other treatments. These cognitive gains appeared independent of mood changes. Crucially, the observed improvements did not consistently exceed what might be expected from simply practicing the tests. This raises questions about whether the benefits truly reflect psilocybin's brain-boosting effects or are influenced by factors like test familiarity or concurrent mood shifts.
Abstract
PAP was associated with modest, short-term improvements in performance on measures of processing speed and executive function among individuals with TRD. While these changes appeared independent of mood, they did not consistently exceed expected practice effects. These findings highlight the need for adequately powered, controlled trials to clarify whether observed cognitive changes reflect genuine procognitive effects of psilocybin or are attributable to non-specific influences such as test familiarity or concurrent mood improvements.