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Temporal dynamics in neuroimaging as correlates of therapeutic response to psilocybin in major depressive disorder: A systematic review and critical appraisal

Sami George Sabbah, Sophie Li, Sabrina Wong, Gia Han Le, Sebastian Badulescu, Colin Hawco, Joshua D. Rosenblat, Roger S. McIntyre

Journal of Affective Disorders September 16, 2025 DOI: 10.1016/j.jad.2025.120335 via OpenAlex

Summary

AI-generated from the abstract

Psilocybin is linked to dynamic and temporally distinct neuroplastic changes that are associated with clinical improvement in depression. However, many studies reused overlapping datasets, had high exploratory flexibility, and risk of bias, which limits the generalizability of the results. Future research should use independent datasets, pre-registered imaging endpoints, and longitudinal designs to better understand the mechanisms of psychedelic therapy for depression.

Study at a glance

Characteristics Review Longitudinal Preregistered Peer reviewed
Citations 2
Key finding Psilocybin is associated with dynamic and temporally distinct neuroplastic changes linked to clinical improvement in depression, but generalizability is constrained by overlapping datasets and high risk of bias.

Abstract

Although these findings suggest psilocybin is associated with dynamic and temporally distinct neuroplastic changes linked to clinical improvement, several limitations must be acknowledged. Many studies reused overlapping datasets with high exploratory flexibility and risk of bias. The generalizability of results is therefore constrained. Future research should emphasize independent datasets, pre-registered imaging endpoints, and longitudinal designs to clarify the mechanisms underlying psychedelic therapy for depression.

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