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

Summary

Psilocybin, a potent hallucinogen, shows immense promise in medicine for neuropsychiatric disorders. Despite growing interest, foundational neuroscience research in preclinical models remains limited. A review of 57 articles, a small fraction in the field of Psychedelics and Drug Studies, reveals most examine psilocybin's pharmacology and its neurotransmitter receptor influence on behavior. This alkaloid, naturally occurring but also subject to chemical synthesis, requires deeper understanding of its neuropsychopharmacology within a broader historical context, bridging ancient use with modern psychology and medicine.

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.

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