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 via OpenAlex
Summary
AI-generated from the abstractA single dose of psilocybin was linked to small, temporary gains in processing speed and executive function in people with treatment-resistant depression. These cognitive improvements seemed unrelated to mood changes but did not consistently surpass the improvements expected from simply retaking the tests. The findings underscore the need for larger, controlled studies to determine whether psilocybin genuinely enhances cognition or if the observed changes stem from practice effects or mood shifts.
Study at a glance
| Characteristics | Preprint Randomized Peer reviewed |
|---|---|
| Population | Individuals with treatment-resistant depression |
| Intervention | Psilocybin-assisted therapy |
| Keywords | Cognition Mood Test biology Schizophrenia object-oriented programming Randomized controlled trial |
| Key finding | 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.