Serotonin biology as a basis for explaining psychedelic drug action

Psychedelics exert their effects primarily through the serotonergic system. Like the endogenous neuromodulator, the drugs bind to many serotonin receptor subtypes. However, their receptor selectivity profiles and spatiotemporal patterns of action differ from those of serotonin and vary across compounds. In this review, we summarize studies that have established roles for serotonin in three domains: reward learning, visual processing, and cerebrovascular function. We contrast the neurophysiological and behavioral consequences of endogenous serotonin release with those produced by exogenous psychedelic administration. We propose that several major effects of psychedelics can be understood as perturbations to serotonergic signaling, while also noting some drug actions that remain difficult to explain by existing serotonin biology. Viewing psychedelic drug action through the lens of serotonin provides a mechanistic framework for linking molecular pharmacology to circuit dynamics and behavior.