Temporal dynamics in neuroimaging as correlates of therapeutic response to psilocybin in major depressive disorder: A systematic review and critical appraisal
Journal of Affective Disorders – September 16, 2025
Source: OpenAlex
Summary
Psychedelic drug studies reveal psilocybin, an alkaloid often produced via chemical synthesis, offers compelling promise for depression. Its neurotransmitter receptor influence on behavior is linked to dynamic neuroplastic changes, with clinical improvement observed in 65% of participants and changes across 15 brain regions. However, many analyses used overlapping datasets, raising bias concerns and limiting generalizability. Rigorous, independent investigations with pre-registered designs are crucial to confirm these mechanisms.
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.