The neural basis of psychedelic action

Psychedelics are serotonin 2A receptor agonists that can lead to profound changes in perception, cognition and mood. In this review, we focus on the basic neurobiology underlying the action of psychedelic drugs. We first discuss chemistry, highlighting the diversity of psychoactive molecules and the principles that govern their potency and pharmacokinetics. We describe the roles of serotonin receptors and their downstream molecular signaling pathways, emphasizing key elements for drug discovery. We consider the impact of psychedelics on neuronal spiking dynamics in several cortical and subcortical regions, along with transcriptional changes and sustained effects on structural plasticity. Finally, we summarize neuroimaging results that pinpoint effects on association cortices and thalamocortical functional connectivity, which inform current theories of psychedelic action. By synthesizing knowledge across the chemical, molecular, neuronal, and network levels, we hope to provide an integrative perspective on the neural mechanisms responsible for the acute and enduring effects of psychedelics on behavior.

Automated summary

This review focuses on the basic neurobiology of the action of psychedelic drugs. It covers the chemistry and potency of psychoactive molecules, the role of serotonin receptors and their signaling pathways, the impact on neuronal spiking dynamics, transcriptional changes, and structural plasticity. This review also summarizes neuroimaging results that highlight the effects on association cortices and thalamocortical functional connectivity, providing insights into the neural mechanisms responsible for the acute and enduring effects of psychedelics on behavior.