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Cognitive outcomes following psilocybin-assisted therapy in treatment-resistant depression: A post-hoc analysis of a randomized, waitlist-controlled trial

Shakila Meshkat, Noah Chisamore, Zoe Doyle, Jordan Bawks, Jeremy Riva-Cambrin, Orly Lipsitz, Roger S McIntyre, Danica E. Johnson, Erica Kaczmarek, Jennifer S. Rabin, Ryan M Brudner, Rodrigo B. Mansur, Krista L. Lanctôt, Joshua D. Rosenblat

Progress in Neuro-psychopharmacology and Biological Psychiatry November 22, 2025 DOI: 10.1016/j.pnpbp.2025.111565 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Preprint Randomized Peer reviewed
Population Individuals with treatment-resistant depression
Intervention Psilocybin-assisted therapy
Topics Depression Psilocybin
Keywords Cognition Mood Test biology Schizophrenia object-oriented programming Randomized controlled trial Executive functions Cognitive remediation therapy Clinical psychology Affect linguistics
Key points Psilocybin was associated with modest, short-term improvements in processing speed and executive function that did not consistently exceed expected practice effects.

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.