How do psychedelics work?
This review (2019), for a psychiatry audience, summarizes our current understanding of how psychedelics work, from 5HT2a agonism to more bottom-up processing.
Authors
- Robin Carhart-Harris
Published
Abstract
Purpose of review Psychedelics are reawakening interest from psychiatry, cognitive neuroscience and the general public with impressive outcomes in small-scale clinical trials, intriguing human brain imaging work and high-impact journalism. Recent findings This brief opinion piece offers a perspective on how psychedelics work in the brain that may help contextualize these developments. It attempts to link various scales of action, from the molecular (serotonin 2A receptor agonism) through to the anatomical and functional (heightened plasticity) and up to the dynamic (increased brain entropy), systems level (network disintegration and desegregation) and experiential. Summary It is proposed that psychedelics initiate a cascade of neurobiological changes that manifest at multiple scales and ultimately culminate in the relaxation of high-level beliefs. The purpose of psychedelic therapy is to harness the opportunity afforded by this belief-relaxation to achieve a healthy revision of pathological beliefs.
Research Summary of 'How do psychedelics work?'
Introduction
Psychedelics such as LSD, psilocybin and DMT have re-attracted attention across psychiatry, cognitive neuroscience and other disciplines, driven by promising small clinical trials, human brain imaging studies and renewed public interest. Carhart-Harris frames these compounds as unusual brain drugs that historically influenced culture and psychiatry and poses a central scientific question: by what mechanisms do psychedelics exert their characteristic experiential and therapeutic effects? This brief opinion piece aims to offer a multi-scale perspective linking known molecular actions to anatomical, physiological, network-level and experiential phenomena. The paper proposes that psychedelics trigger a cascade—from serotonin 2A receptor agonism through heightened plasticity and increased neural entropy to network disintegration and, ultimately, a relaxation of high‑level beliefs—and that psychedelic therapy seeks to use this transient belief‑relaxation to enable adaptive revision of pathological beliefs.
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Study Details
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Carhart-Harris, R. L. (2019). How do psychedelics work?. Current Opinion in Psychiatry, 32(1), 16-21. https://doi.org/10.1097/YCO.0000000000000467
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