The neural basis of psychedelic action

This comprehensive review (2022) explains the neural basis of how psychedelics work. It covers serotonin receptors, changes in structural plasticity, and the long-term effects of psychedelics. The discussion covers the future of psychedelics, including non-hallucinogenic compounds.


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 signalling 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 behaviour.”

Authors: Alex C. Kwan, David E. Olson, Katrin H. Preller & Bryan L. Roth

Summary of The neural basis of psychedelic action

Psychedelics are potent molecules that can profoundly bend sensory processing, alter cognition and produce intense subjective experiences. They may also treat neuropsychiatric disorders, including depression, anxiety and substance-use disorders.

This review article focuses on the neuroscience of psychedelics. It covers the chemistry, receptors and molecular signalling of psychedelics, as well as recent insights into how psychedelics modulate neurons and neural circuits.

To access this content, you must purchase one of the following memberships: Business Membership, Business Membership Unlimited, Sprout Membership, Pro Membership, Pro Membership Unlimited or Insider Membership. The membership will give you access to exclusive data, including summaries of psychedelic research papers, extended company info, and our member-only visualisations. Save yourself multiple hours each week by accessing Blossom’s resource library.

Study details

Topics studied

Study characteristics
Literature Review Bio/Neuro


Authors associated with this publication with profiles on Blossom

David Olson
David Olson is the Chief Innovation Officer and Head of the Scientific Advisory Board at Delix Therapeutics. He is also an Associate Professor at UC Davis and his lab investigates the psychoplastogenic properties of psychedelic substances and other alkaloids, with respect to their ability to treat a wide variety of neuropsychiatric diseases, including depression, anxiety disorders, and addiction, by increasing neuroplasticity.

Katrin Preller
Katrin Preller is one of the upcoming researchers, currently at the University of Zurich and Yale University, and is focused on the neurobiology and pharmacology of psychedelics.

Alex Kwan
Dr. Alex Kwan is an Associate Professor for Neuroscience at the Yale School of Medicine.


Institutes associated with this publication

Yale University
The Yale Psychedelic Science Group was established in 2016.