Utility of preclinical models in the study of psilocybin – A comprehensive review

Interest in psilocybin's therapeutic potential is growing rapidly, but basic and translational studies remain scarce. A systematic search found 57 articles on psilocybin in rodent models. The review identifies four research areas: pharmacology, toxicity, effects on disease models, and molecular mechanisms, with pharmacology dominating. Despite the small literature, several conclusions and priorities for future work emerge.

Study at a glance

Abstract

Interest in the therapeutic potential of psilocybin across a broad range of neuropsychiatric disorders is rapidly expanding. Despite promising clinical data and tremendous public enthusiasm, complimentary basic and translational studies - which are critical for advancing our understanding of psilocybin's biological effects and promoting innovation - have been relatively few. As with all work involving the study of complex neuropsychopharmacology, the search for deeper understanding of biological mechanisms, and the need for nuanced behavioral analyses in the context of both normal and diseased states, the roles for preclinical models are clear. A systematic search of the literature identified 57 articles involving the study of psilocybin in preclinical rodent models. A comprehensive review and thematic analysis identified 4 broad areas of investigation - pharmacology, toxicity, effects on disease models, and molecular mechanisms - with pharmacology studies accounting for the majority. Though these papers represent a still remarkably small body of literature, several important conclusions can already be drawn, and several areas of high priority for future work can be identified.