Psychedelics as potent anti-inflammatory therapeutics

Introduction

Psychedelics have historically been studied for their profound effects on perception and consciousness, and research over many decades largely focused on central nervous system actions. Nichols and colleagues note that this brain-centric emphasis left peripheral biology relatively unexplored, even though the principal molecular target of classic psychedelics, the serotonin 2A receptor (5-HT2A), is widely expressed across tissues. Earlier physiological work had also shown that serotonin can be pro-inflammatory at sites of tissue injury and inflammation, and that 5-HT2A antagonists can block some of those pro-inflammatory effects. This paper presents a narrative review of work that identifies certain psychedelics as potent peripheral anti-inflammatories and immunomodulators. The aim is to describe the discovery pathway from in vitro assays to animal disease models, to report key efficacy and selectivity findings, and to outline translational implications including the possibility of developing sub‑behavioural or peripherally restricted 5-HT2A agonists for inflammatory diseases.