Pharmacological, Neural, and Psychological Mechanisms underlying Psychedelics: A Critical Review

This review (2022) explores three analysis levels of psychedelic therapeutic mechanisms; 1) biochemical (e.g. neuroplasticity), 2) neural (e.g. less top-down signalling), and 3) psychological level (e.g. belief change). The review then maps out how the levels can be bridged and provide directions for future studies.


“This paper provides a critical review of several possible mechanisms at different levels of analysis underlying the effects and therapeutic potential of psychedelics. At the (1) biochemical level, psychedelics primarily affect the 5-HT2a receptor, increase neuroplasticity, offer a critical period for social reward learning and have anti-inflammatory properties. At the (2) neural level, psychedelics have been associated with reduced efficacy of thalamo-cortical filtering, the loosening of top-down predictive signaling and an increased sensitivity to bottom-up prediction errors, and activation of the claustro-cortical-circuit. At the (3) psychological level, psychedelics have been shown to induce altered and affective states, they affect cognition, induce belief change, exert social effects and can result in lasting changes in behavior. We outline the potential for a unifying account of the mechanisms underlying psychedelics and contrast this with a model of pluralistic causation. Ultimately, a better understanding of the specific mechanisms underlying the effects of psychedelics could allow for a more targeted therapeutic approach. We highlight current challenges for psychedelic research and provide a research agenda to foster insight in the causal-mechanistic pathways underlying the efficacy of psychedelic research and therapy.”

Authors: Michiel van Elk & David B. Yaden

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Pharmacological, Neural, and Psychological Mechanisms underlying Psychedelics: A Critical Review

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Published in
Neuroscience and Biobehavioral Reviews
July 22, 2022
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Authors associated with this publication with profiles on Blossom

David Yaden
David Bryce Yaden (Ph.D.) is a Research Fellow at Johns Hopkins University School of Medicine. His research focus is on the psychology, neuroscience, and psychopharmacology of psychedelics and other positively transformative experiences. Specifically, David is interested in understanding how brief experiences can result in such long-term changes to well-being.

Michiel van Elk
Michiel van Elk is an Assistant Professor at the unit Cognitive Psychology of the Institute of Psychology, at Leiden University.

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