REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics
2019/06/20 by Robin Carhart‐Harris, R.L. Carhart-Harris, Karl Friston +1 · 1,183 citations
Neuroscience · Nursing · Psychology · #Action (physics) #Artificial intelligence #Bayesian probability #Biochemical Analysis and Sensing Techniques #Cognitive psychology #Computer science #Consciousness #Epistemology #Hallucinogen #Neuroscience #Neurotransmitter Receptor Influence on Behavior #Philosophy #Prior probability #Psilocybin #Psychedelics and Drug Studies #Psychology
paper · pdf · doi:10.1124/pr.118.017160
published in Pharmacological Reviews 71(3), 316-344 (American Society for Pharmacology and Experimental Therapeutics)
openalex publication_date 2019/06/20 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/05
Abstract
This paper formulates the action of psychedelics by integrating the free-energy principle and entropic brain hypothesis. We call this formulation relaxed beliefs under psychedelics (REBUS) and the anarchic brain, founded on the principle that—via their entropic effect on spontaneous cortical activity—psychedelics work to relax the precision of high-level priors or beliefs, thereby liberating bottom-up information flow, particularly via intrinsic sources such as the limbic system. We assemble evidence for this model and show how it can explain a broad range of phenomena associated with the psychedelic experience. With regard to their potential therapeutic use, we propose that psychedelics work to relax the precision weighting of pathologically overweighted priors underpinning various expressions of mental illness. We propose that this process entails an increased sensitization of high-level priors to bottom-up signaling (stemming from intrinsic sources), and that this heightened sensitivity enables the potential revision and deweighting of overweighted priors. We end by discussing further implications of the model, such as that psychedelics can bring about the revision of other heavily weighted high-level priors, not directly related to mental health, such as those underlying partisan and/or overly-confident political, religious, and/or philosophical perspectives. <h3>Significance Statement</h3> Psychedelics are capturing interest, with efforts underway to bring psilocybin therapy to marketing authorisation and legal access within a decade, spearheaded by the findings of a series of phase 2 trials. In this climate, a compelling unified model of <i>how</i> psychedelics alter brain function to alter consciousness would have appeal. Towards this end, we have sought to integrate a leading model of global brain function, <i>hierarchical predictive coding</i>, with an often-cited model of the acute action of psychedelics, <i>the entropic brain hypothesis</i>. The resulting synthesis states that psychedelics work to relax high-level priors, sensitising them to liberated bottom-up information flow, which, with the right intention, care provision and context, can help guide and cultivate the revision of entrenched pathological priors.
Citations
Cited by
- Existential feelings as a phenomenological framework for psychedelic therapy
- Beyond the reducing valve: towards a computational neurophenomenology of altered states via deep neural networks
- Psilocybin alters visual contextual computations
- Naturalistic psychedelic experiences and gender-based self-acceptance in transgender and gender-expansive people
- Complex slow waves in the human brain under 5-MeO-DMT
- How Layer-Specific fMRI Can Contribute to Understanding Perceptual Disturbances Across Psychiatric Disorders
- Cellular mechanisms of serotonergic psychedelics - apical hypercontextualisation
- Dissolving yourself in connection to others: shared experiences of ego attenuation and connectedness during group VR experiences can be comparable to psychedelics
- Navigating groundlessness: An interview study on dealing with ontological shock and existential distress following psychedelic experiences
- Immersive exposure to simulated visual hallucinations modulates high-level human cognition
- The phenomenology of psychedelic temporality: current knowledge, open questions, and clinical applications
- Experiencing timelessness and the phenomenology of temporal flow
- A landscape of consciousness: Toward a taxonomy of explanations and implications
- Reframing psychedelic regulation: Tools, not treatments
- Neural mechanisms of psychedelic visual imagery
- Realization experiences: a convergent account of insight and mystical experiences
- N,N-dimethyltryptamine effects on connectome harmonics, subjective experience and comparative psychedelic experiences
- An encounter with death: a comparative thematic and content analysis of naturalistic DMT experiences and the near-death experience
- Cross-Frequency Coupling as a Neural Substrate for Prediction Error Evaluation: A Laminar Neural Mass Modeling Approach
- A causal pluralist theory of the interaction of substance, set and setting in psychedelic experience
- Contemplating contradiction: speculative mysticism and the entropic brain
- Exploring the Role of Psychedelic Experiences on Wellbeing and Symptoms of Disordered Eating
- The serotonergic psychedelic DOI impairs deviance detection in the auditory cortex
- Understanding mystical experiences through the lens of entropy: introduction to the special issue on ‘mystical entropy’
- The role of self-transcendent emotions in psychedelic experiences: a two-process proposal
- Cyberdelics: Virtual reality hallucinations modulate cognitive-affective processes
- Network control energy reductions under DMT relate to serotonin receptors, signal diversity, and subjective experience
- Learning from Boundlessness: Psychedelic induced awe and epistemic shifts towards a holistic worldview
- Hemispheric annealing and lateralization under psychedelics (HEALS): A novel hypothesis of psychedelic action in the brain
- DMT-Induced Shifts in Criticality Correlate with Self-Dissolution
- Psychedelic experiences in psychedelic-assisted therapy for depression
- Psychedelic-assisted therapy, metacognition, and the problem of integration: a tri-phasic approach
- Behavioural investigations of psilocybin in non-human animals 1962–2021: A scoping review
- A beautiful loop: An active inference theory of consciousness
- Fearful symmetry in altered states: a bi-logic account of psychedelic action
- Natural language analysis of the structure of altered states of consciousness
- A qualitative analysis of the psychedelic mushroom come-up and come-down
- Recalled childhood trauma and post-psychedelic trajectories of change in a mixed-methods study
- Sensing the darkness: Dark therapy, authority, and spiritual experience
- Clarifying the ethical landscape of psychedelic-assisted psychotherapy
- On the social epistemology of psychedelic experience
- Edging thermodynamic equilibrium : mystical experiences as “mirror” encounters between the entropic brain and the entropic world
- From flow to mystical experiences: Connecting entropy and fluency along the unifying framework of cognitive continuum
- MASSAG model: Towards an integrative neuroscience framework linking emotional trauma, pain, and mechanisms of force-based manipulations
- Eigenmodes of the deep unconscious: the neuropsychology of Jungian archetypes and psychedelic experience
- Set and setting: The missing factors in Chris Letheby’s psychedelic philosophy
- Unveiling Reality: Psychedelics, Neural Filtering, and the Future of Psychiatric Medicine
- Meditation expertise influences response bias and prestimulus alpha activity in the somatosensory signal detection task
- Modeled Long‐Term Effects of Psilocybin on Dynamic Activity and Effective Connectivity of Fronto‐Striatal‐Thalamic Circuits
- An international mega-analysis of psychedelic drug effects on brain circuit function
- The science of psychedelic medicine
- How to Change Minds Ethically: Doxastic Vulnerability, Epistemic Harm Reduction, and the Role of Therapists in Psychedelic Therapy
- This is your brain on death: a comparative analysis of a near-death experience and subsequent 5-Methoxy-DMT experience
- Psychedelic therapies and belief change: are there risks of epistemic harm or epistemic injustice?
- A complexity-science framework for studying flow: using media to probe brain-phenomenology dynamics
- Oceanic states of consciousness—an existential-neuroscience perspective
- An encounter with the self: A thematic and content analysis of the DMT experience from a naturalistic field study
- Apophenia, absorption and anxiety: Evidence for individual differences in positive and negative experiences of Hallucinogen Persisting Perceptual Disorder
- The renaissance of psychedelics in modern psychiatry: a new breakthrough or the myth of a “magic bullet”?
- Psychedelics and environmental virtues
- Psilocybin-assisted physiotherapy for refractory motor functional neurological disorder: protocol for a randomised dose-comparison pilot study
- Exploring aperiodic, complexity and entropic brain changes during non-ordinary states of consciousness
- Therapeutic (Sub)stance: Current practice and therapeutic conduct in preparatory sessions in substance-assisted psychotherapy—A systematized review
- With great power comes great vulnerability: an ethical analysis of psychedelics’ therapeutic mechanisms proposed by the REBUS hypothesis
- The Touched Body and the Experience of Self
- The Neuroscience and Psychology of the Alien Abduction Phenomenon: A Review
- Microdosing psilocybin and its effect on creativity: Lessons learned from three double-blind placebo controlled longitudinal trials
- Overmystifying the Psychedelic Experience
- Comforting delusions? How to evaluate the plausibility of mystical-type insights in psychedelic experiences
- Observing the mind under psychedelics: conceptual metaphors used following four once-weekly macrodoses of psilocybin
- Psychiatric risks for worsened mental health after psychedelic use
- Perceived Impact of Psychedelics on Sexual, Gender, and Intimate Relationship Dynamics: A Mixed-Methods Investigation
- Exploring 5-MeO-DMT as a pharmacological model for deconstructed consciousness
- How Level is the 'Cognitive Playing Field'?
- An Integrated theory of false insights and beliefs under psychedelics
- Models of psychedelic drug action: modulation of cortical-subcortical circuits
- Contemplative Agent
- Neural mechanisms underlying psilocybin’s therapeutic potential – the need for preclinical in vivo electrophysiology
- Microdosing psychedelics: Subjective benefits and challenges, substance testing behavior, and the relevance of intention
- Increased global integration in the brain after psilocybin therapy for depression
- Consciousness [wikipedia]
- Learning to Let Go: A Cognitive-Behavioral Model of How Psychedelic Therapy Promotes Acceptance. [europepmc]
- Post-Psychedelic Reductions in Experiential Avoidance Are Associated With Decreases in Depression Severity and Suicidal Ideation. [europepmc]
- DMT alters cortical travelling waves. [europepmc]
- Pivotal mental states. [europepmc]
- Ketamine and Serotonergic Psychedelics: Common Mechanisms Underlying the Effects of Rapid-Acting Antidepressants. [europepmc]
- LSD alters dynamic integration and segregation in the human brain. [europepmc]
- Positive expectations predict improved mental-health outcomes linked to psychedelic microdosing. [europepmc]
- Self-blinding citizen science to explore psychedelic microdosing. [europepmc]
- Psychedelic Harm Reduction and Integration: A Transtheoretical Model for Clinical Practice. [europepmc]
- Spontaneous and deliberate creative cognition during and after psilocybin exposure. [europepmc]
- Psychedelic Communitas: Intersubjective Experience During Psychedelic Group Sessions Predicts Enduring Changes in Psychological Wellbeing and Social Connectedness. [europepmc]
- Psychedelics and health behaviour change. [europepmc]
- Lasting effects of a single psilocybin dose on resting-state functional connectivity in healthy individuals. [europepmc]
- Does Psychedelic Therapy Have a Transdiagnostic Action and Prophylactic Potential? [europepmc]
- Psychedelics alter metaphysical beliefs. [europepmc]
- Models of psychedelic drug action: modulation of cortical-subcortical circuits. [europepmc]
- The self on its axis: a framework for understanding depression. [europepmc]
- Classic Psychedelic Drugs: Update on Biological Mechanisms. [europepmc]
- Therapeutic Alliance and Rapport Modulate Responses to Psilocybin Assisted Therapy for Depression. [europepmc]
- Psychedelic-Assisted Psychotherapy-A Systematic Review of Associated Psychological Interventions. [europepmc]
- Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder: A Randomized Clinical Trial. [europepmc]
- The neural basis of psychedelic action. [europepmc]
- Acute psilocybin enhances cognitive flexibility in rats. [europepmc]
- Human brain effects of DMT assessed via EEG-fMRI. [europepmc]
- History repeating: guidelines to address common problems in psychedelic science. [europepmc]
Related