4 Psychedelics: therapeutic mechanisms

Psychedelics like LSD, psilocybin, MDMA, and DMT work in the brain through a multi-level mechanism. Classic serotonergic psychedelics act on the serotonin 2A receptor, whose function and evolutionary purpose are illuminated by this pharmacology. Brain imaging reveals acute effects that increase entropy, supporting the entropic brain hypothesis. The REBUS model explains how psychedelics relax prior beliefs, allowing for predictive processing changes that map onto the acute experience and therapeutic outcomes. Current evidence supports psychedelic therapy, including a clinical trial of psilocybin for treatment-resistant depression and an ongoing comparison with escitalopram for major depressive disorder.

Study at a glance

Abstract

Robin Carhart-Harris moved to Imperial College London in 2008 after obtaining a PhD in Psychopharmacology from the University of Bristol and an MA in Psychoanalysis from Brunel University. At Imperial, he has designed and/or carried out brain imaging studies involving LSD, psilocybin, MDMA and DMT, plus a clinical trial of psilocybin for treatment-resistant depression, and an ongoing study comparing psilocybin with escitalopram for major depressive disorder. In 2019, he set-up the Centre for Psychedelic Research at Imperial and he also an honorary position with the University of Oxford. The talk takes a multi-level approach to the question of how psychedelics work in the brain. Key themes include: the pharmacology of classic serotonergic psychedelics, what this tells us about the function and evolutionary purpose of the serotonin 2A receptor, the acute brain effects of psychedelics as determined by functional brain imaging, the entropic brain hypothesis, current evidence for psychedelic therapy, the ‘REBUS’ hierarchical predictive processing model of the action of psychedelics, and how this maps on to the phenomenology of the acute psychedelic experience and therapeutic outcomes.