Neuroimaging & Brain MeasuresSet & Setting

Neural Mechanisms and Psychology of Psychedelic Ego Dissolution

This review (2022) investigates the neural mechanisms, 5HT2A receptor agonism at the top of the cortical hierarchy, that lead to ego dissolution and long-term neural plasticity. This study uses the hierarchical predictive coding framework to understand the neural mechanisms of consciousness (and psychedelics to test the model).

Authors

  • Adeel Razi
  • Devon Stoliker
  • Gary Egan

Published

Pharmacological Reviews
meta Study

Abstract

Neuroimaging studies of psychedelics have advanced our understanding of hierarchical brain organisation and the mechanisms underlying their subjective and therapeutic effects. The primary mechanism of action of classic psychedelics is binding to serotonergic 5HT2A receptors. Agonist activity at these receptors leads to neuromodulatory changes in synaptic efficacy that can have a profound effect on hierarchical message passing in the brain. Here, we review the cognitive and neuroimaging evidence for the effects of psychedelics; in particular, their influence on selfhood and subject-object boundaries-known as ego dissolution-surmised to underwrite their subjective and therapeutic effects. Agonist of 5HT2A receptors, located at the apex of the cortical hierarchy may have a particularly powerful effect on sentience and consciousness. These effects can endure well after the pharmacological half life, suggesting that psychedelics may have long-term effects on neural plasticity - that may play a role in their therapeutic efficacy. Psychologically, this may be accompanied by a surrender of ego resistance that increases the repertoire of perceptual hypotheses, including those that undergird selfhood. We consider the interaction between serotonergic neuromodulation and sentience through the lens of hierarchical predictive coding, which speaks to the value of psychedelics in understanding how we make sense of the world-and specific predictions about effective connectivity in cortical hierarchies that can be tested using functional neuroimaging.

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Research Summary of 'Neural Mechanisms and Psychology of Psychedelic Ego Dissolution'

Introduction

Stoliker and colleagues frame classic serotonergic psychedelics as tools that both perturb and reveal the hierarchical organisation of the brain. They review a broad literature linking 5-HT2A receptor agonism to neuromodulatory changes in synaptic efficacy, altered hierarchical message‑passing, and profound subjective effects—most notably ego dissolution, the transient breakdown of the sense of a bounded, narrativised self. The introduction situates this literature historically (ancient ritual use, mid‑20th century research and subsequent hiatus, renewed clinical work in the 2000s) and conceptually, emphasising the value of modern neuroimaging (PET, fMRI, EEG, MEG) to trace how receptor‑level action may cascade to network‑level changes in perception, selfhood, and therapeutic outcomes. The authors set out to synthesise neuroimaging, pharmacological, and psychological evidence for how psychedelics alter brain connectivity and subjective experience, with a special focus on ego dissolution. They adopt hierarchical predictive‑coding and the free energy principle as an organising theoretical framework, proposing testable predictions about effective connectivity in cortical hierarchies and highlighting the role of context (set and setting), plasticity, and clinical relevance. The review intends to bridge molecular action (5‑HT2A agonism) through neuronal and network mechanisms to phenomenology and therapeutic implications.

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Study Details

References (117)

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