Serotonin biology as a basis for explaining psychedelic drug action.
Cory A. Knox, Athena Li-Wu, Alex C. Kwan
Current Biology October 5, 2026 DOI: 10.1016/j.cub.2026.08.045 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Serotonin |
| Key findings | Argues that several major effects of psychedelics can be understood as perturbations to serotonergic signaling across reward learning, visual processing, and cerebrovascular function, while noting that some drug actions remain difficult to explain by existing serotonin biology. Proposes that viewing psychedelic drug action through the lens of serotonin provides a mechanistic framework linking molecular pharmacology to circuit dynamics and behavior. |
Abstract
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.
Comparable studies
Other narrative reviews on serotonin, most cited first.
Citations in the library
Cites 38
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
- Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels Neuropsychopharmacology January 26, 2019
- Single-Dose Psilocybin Treatment for Major Depressive Disorder JAMA August 31, 2023
- Lysergic Acid Diethylamide: Sensitive Neuronal Units in the Midbrain Raphe Science August 16, 1968
and 33 more in the library