Physics

Neuroscience

Action (physics)

Central nervous system

Psychology

Oligodendrocyte

Neuroscientist

Myelin

Quantum mechanics

Neural activity

Nature Neuroscience

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. Psychedelics are serotonergic drugs that have therapeutic potential. This Review article provides an integrative perspective on the basic neurobiology underlying the actions of psychedelics and highlights open questions in the field.

The neural basis of psychedelic action