REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics

This theoretical paper (2019) introduces the ‘REBUS’ (Relaxed Beliefs Under Psychedelics) model, integrating the free-energy principle with the entropic brain hypothesis. It proposes that psychedelics relax the precision weighting of high-level beliefs (priors), thereby liberating bottom-up information flow and enabling the revision of pathological or rigid thought patterns.

Authors

  • Robin Carhart-Harris
  • Karl John Friston

Published

Pharmacological Reviews
meta Study

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.

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Research Summary of 'REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics'

Introduction

Psychedelics such as LSD and psilocybin are regaining widespread scientific and public attention, yet a unifying account of how they alter brain function and consciousness remains lacking. Carhart-Harris and colleagues position their work at the intersection of two contemporary frameworks: the free-energy principle (and its operationalisation in hierarchical predictive coding) and the entropic brain hypothesis. The free-energy principle frames brain function as the minimisation of surprise via probabilistic internal models (priors), whereas the entropic brain hypothesis links the entropy of spontaneous neural activity to the richness of subjective experience; both approaches are naturally expressed in information-theoretic terms and are therefore amenable to empirical study. This paper sets out to synthesise those frameworks into a single mechanistic proposal, labelled REBUS (RElaxed Beliefs Under pSychedelics) and its complement the anarchic brain. The core claim is that psychedelics, via agonism at the serotonin 2A receptor (5-HT2AR), relax the precision weighting (felt confidence) of high-level priors encoded in deep cortical hierarchies. This relaxation flattens the brain’s free-energy landscape, increases spontaneous cortical entropy, and liberates bottom-up information flow—changes that may explain the phenomenology of the psychedelic state and, when combined with appropriate context, promote revision of pathologically over-weighted beliefs relevant to psychiatric disorders.

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Study Details

  • Study Type
    meta
  • Journal
  • Authors
  • APA Citation

    Carhart-Harris, R., & Friston, K. (2019). REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics. Pharmacological Reviews, 71(3), 316-344. https://doi.org/10.1124/pr.118.017160

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How does psilocybin therapy work? An exploration of experiential avoidance as a putative mechanism of change

Zeifman, R. J., Wagner, A. C., Monson, C. M. et al. · Journal of Affective Disorders (2023)

47 cited
Therapeutic mechanisms of psychedelics and entactogens

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N, N-Dimethyltryptamine (DMT)-Occasioned Familiarity and the Sense of Familiarity Questionnaire (SOF-Q)

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Spatial correspondence of LSD-induced variations of brain functioning at rest with serotonin receptor expression

Pizzi, S. D., Chiacchiaretta, P., Sestieri, C. et al. · Biological Psychiatry (2023)

Sub-acute effects of psilocybin on EEG correlates of neural plasticity in major depression: Relationship to symptoms

Skosnik, P. D., Sloshower, J., Safi-Aghdam, H. et al. · Journal of Psychopharmacology (2023)

Prevalence and therapeutic impact of adverse life event reexperiencing under ceremonial ayahuasca

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Dosing and Therapeutic Conduct in Administration Sessions in Substance-Assisted Psychotherapy: A Systematized Review

Thal, S. B., Wieberneit, M., Sharbanee, J. M. et al. · Journal of Humanistic Psychology (2023)

4 cited
A complex systems perspective on psychedelic brain action

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Self-reported effects of classic psychedelics on stuttering

Gold, N. D., Goldway, N., Gerlach-Houck, H. et al. · Biorxiv (2023)

A whole-brain model of the neural entropy increase elicited by psychedelic drugs

Herzog, R., Mediano, P. A. M., Rosas, F. E. et al. · Scientific Reports (2023)

LSD microdosing attenuates the impact of temporal priors in time perception

Sadibolova, R., Murray-Lawson, C., Family, N. et al. · Biorxiv (2023)

Information parity increases on functional brain networks under influence of a psychedelic substance

Viol, A., Viswanathan, G. M., Soldatkina, O. et al. · Journal of Physiology (2023)

Human brain effects of DMT assessed via EEG-fMRI

Timmermann, C., Roseman, L., Haridas, S. et al. · PNAS (2023)

158 cited
Canalization and plasticity in psychopathology

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Can psychedelics enhance group psychotherapy? A discussion on the therapeutic factors

Ponomarenko, P., Seragnoli, F., Calder, A. et al. · Journal of Psychopharmacology (2023)

N,N-dimethyltryptamine affects EEG response in a concentration dependent manner - a pharmacokinetic/pharmacodynamic analysis

Eckernäs, E., Timmermann, C., Carhart-Harris, R. et al. · Philosophy and the Mind Sciences (2023)

LSD-induced increase of Ising temperature and algorithmic complexity of brain dynamics

Ruffini, G., Damiani, G., Lozano-Soldevilla, D. et al. · PLOS ONE (2023)

Effective connectivity of functionally anticorrelated networks under LSD

Stoliker, D., Novelli, L., Vollenweider, F. X. et al. · Biological Psychiatry (2023)

23 cited
Distributed harmonic patterns of structure-function dependence orchestrate human consciousness

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32 cited
Psychedelic Identity Shift: A Critical Approach to Set And Setting

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28 cited
ARC: a framework for access, reciprocity and conduct in psychedelic therapies

Spriggs, M. J., Murphy-Beiner, A., Murphy, R. et al. · Psychological Medicine (2022)

35 cited
A Psychoanalytic Perspective on Psychedelic Experience

Guss, J. · Psychoanalytic Dialogues (2022)

Psychedelics and schizophrenia: Distinct alterations to Bayesian inference

Rajpal, H., Mediano, P. A. M., Rosas, F. E. et al. · NeuroImage (2022)

The effect of lysergic acid diethylamide (LSD) on whole-brain functional and effective connectivity

Bedford, P., Hauke, D. J., Wang, Z. et al. · Neuropsychopharmacology (2022)

Low doses of lysergic acid diethylamide (LSD) increase reward-related brain activity

Glazer', J., Murray, C. H., Nusslock', R. et al. · Neuropsychopharmacology (2022)

The neural basis of psychedelic action

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Default Mode Network Modulation by Psychedelics: A Systematic Review

Gattuso, J. J., Perkins, D., Ruffell, S. G. D. et al. · International Journal of Neuropsychopharmacology (2022)

Receptor-informed network control theory links LSD and psilocybin to a flattening of the brain’s control energy landscape

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Neural Mechanisms and Psychology of Psychedelic Ego Dissolution

Stoliker, D., Egan, G. F., Friston, K. J. et al. · Pharmacological Reviews (2022)

Effects of psilocybin versus escitalopram on rumination and thought suppression in depression

Barba, T., Buehler, S., Kettner, H. et al. · BJPsych Open (2022)

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

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4 cited
Pattern Breaking: A Complex Systems Approach to Psychedelic Medicine

Hipólito, I., Mago, J., Rosas, F. E. et al. · Psyarxiv (2022)

Belief changes associated with psychedelic use

Nayak, S., Singh, M., Yaden, D. B. et al. · Journal of Psychopharmacology (2022)

Psychedelic-Assisted Psychotherapy-A Systematic Review of Associated Psychological Interventions

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Group VR experiences can produce ego attenuation and connectedness comparable to psychedelics

Glowacki, D. R., Wonnacott, M. D., Freire, R. et al. · Scientific Reports (2022)

31 cited
Psychedelic Therapy for Body Dysmorphic Disorder

Johnson, S., Letheby, C. · Journal of Psychedelic Studies (2022)

The Psychedelic Integration Scales: Tools for Measuring Psychedelic Integration Behaviors and Experiences

Whitney, S., Yaden, D. B., Lipson, J. et al. · Frontiers in Psychology (2022)

Psychedelic Resting-state Neuroimaging: A Review and Perspective on Balancing Replication and Novel Analyses

McCulloch, D. E-W., Knudsen, G. M., Barrett, F. S. et al. · Neuroscience and Biobehavioral Reviews (2022)

Increased global integration in the brain after psilocybin therapy for depression

Daws, R. E., Timmermann, C., Giribaldi, B. et al. · Nature Medicine (2022)

Therapeutic Alliance and Rapport Modulate Responses to Psilocybin Assisted Therapy for Depression

Murphy, R., Murphy-Beiner, A., Kettner, H. et al. · Frontiers in Pharmacology (2022)

162 cited
Differential contributions of serotonergic and dopaminergic functional connectivity to the phenomenology of LSD

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40 cited
How Psychedelic-Assisted Treatment Works in the Bayesian Brain

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Classic Psychedelic Drugs: Update on Biological Mechanisms

Vollenweider, F. X., Smallridge, J. W. · Pharmacopsychiatry (2022)

71 cited
Effective Connectivity of LSD-induced Ego Dissolution

Stoliker, D., Novelli, L., Vollenweider, F. X. et al. · MedRvix (2021)

4 cited
Psychedelic Therapy's Transdiagnostic Effects: A Research Domain Criteria (RDoC) Perspective

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Models of psychedelic drug action: modulation of cortical-subcortical circuits

Doss, M. K., Madden, M. B., Gaddis, A. et al. · Brain (2021)

The readiness of psychiatrists to implement psychedelic-assisted psychotherapy

Page, L., Rehman, A., Syed, H. et al. · Frontiers in Psychiatry (2021)

30 cited
Bridging the Gap? Altered Thalamocortical Connectivity in Psychotic and Psychedelic States

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35 cited
Psilocybin in the treatment of anorexia nervosa: The English transition of a French 1959 case study

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Novel Treatment Approaches for Substance Use Disorders: Therapeutic Use of Psychedelics and the Role of Psychotherapy

Johnson, M. W., Gründer, G., Betzler, F. et al. · Current Addiction Reports (2021)

Psychedelics, sociality, and human evolution

Rodríguez Arce, J. M., Winkelman, M. J. · Frontiers in Psychology (2021)

Prefrontal contributions to the stability and variability of thought and conscious experience

Zamani, A., Carhart-Harris, R. L., Christoff, K. · Neuropsychopharmacology (2021)

Do Psychedelics Change Beliefs?

McGovern, H., Leptourgos, P., Hutchinson, B. et al. · Psyarxiv (2021)

Improving cognitive functioning in major depressive disorder with psychedelics: a dimensional approach

Kuiperes, Z., Schreiber, R. · Neurobiology of Learning and Memory (2021)

Psilocybin-induced changes in brain network integrity and segregation correlate with plasma psilocin level and psychedelic experience

Madsen, M. K., Stenbaek, D. S., Arvidsson, A. et al. · European Neuropsychopharmacology (2021)

Does psychedelic therapy have a transdiagnostic action and prophylactic potential?

Kočárová, C., Horacek, J., Carhart-Harris, R. L. · Frontiers in Psychiatry (2021)

73 cited
Trips and Neurotransmitters: Discovering Principled Patterns across 6,850 Hallucinogenic Experiences

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44 cited
Psychedelics alter metaphysical beliefs

Timmermann, C., Kettner, H., Letheby, C. et al. · Scientific Reports (2021)

Psilocybin as a Novel Pharmacotherapy for Treatment-Refractory Anorexia Nervosa

Rodan, S., Aouad, P., McGregor, I. S. et al. · OBM Neurobiology (2021)

Improvement of functional neurological disorder after administration of esketamine nasal spray: a case report

Vendrell-Serres, J., Soto-Angona, Ó., Rodríguez-Urrutia, A. et al. · Therapeutic Advances in Psychopharmacology (2021)

Psychedelics and health behaviour change

Teixeira, P. J., Johnson, M. W., Timmermann, C. et al. · Journal of Psychopharmacology (2021)

Future Directions for Clinical Psilocybin Research: The Relaxed Symptom Network

Lewis-Healey, E., Laukkonen, R., Van Elk, M. · Psyarxiv (2021)

1 cited
Protocol for Outcome Evaluation of Ayahuasca-Assisted Addiction Treatment: The Case of Takiwasi Center

Rush, B., Marcus, O., García, S. et al. · Frontiers in Pharmacology (2021)

19 cited
Relational Processes in Ayahuasca Groups of Palestinians and Israelis

Roseman, L., Ron, Y., Saca, A. et al. · Frontiers in Pharmacology (2021)

30 cited
Psychedelics and Consciousness: Distinctions, Demarcations, and Opportunities

Yaden, D. B., Johnson, M. W., Griffiths, R. R. et al. · International Journal of Neuropsychopharmacology (2021)

Moving Past Mysticism in Psychedelic Science

Sanders, J. W. · ACS Pharmacology and Translational Science (2021)

A continuum hypothesis of psychotomimetic rapid antidepressants

Haarsma, J., Harmer, C. J., Tamm, S. · Brain and Neuroscience Advances (2021)

Can pragmatic research, real-world data and digital technologies aid the development of psychedelic medicine?

Carhart-Harris, R. L., Wagner, A. C., Agrawal, M. et al. · Journal of Psychopharmacology (2021)

40 cited
Spontaneous and deliberate creative cognition during and after psilocybin exposure

Mason, N. L., Kuypers, K. P. C., Reckweg, J. T. et al. · Translational Psychiatry (2021)

86 cited
Increased sensitivity to strong perturbations in a whole-brain model of LSD

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A qualitative and quantitative account of patient’s experiences of ketamine and its antidepressant properties

Sumner, R. L., Chacko, E., Mcmillan, R. et al. · Journal of Psychopharmacology (2021)

51 cited
Psychedelic Harm Reduction and Integration: A Transtheoretical Model for Clinical Practice

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On the Relationship between Classic Psychedelics and Suicidality: A Systematic Review

Zeifman, R. J., Singhal, N., Breslow, L. et al. · ACS Pharmacology and Translational Science (2021)

Neural and subjective effects of inhaled N,N-dimethyltryptamine in natural settings

Pallavicini, C., Cavanna, F., Zamberlan, F. et al. · Journal of Psychopharmacology (2021)

Psychedelic drugs and perception: a narrative review of the first era of research

Aday, J. S., Bloesch, E. K., Wood, J. R. et al. · Reviews In The Neuroscience (2021)

LSD alters dynamic integration and segregation in the human brain

Luppi, A. I., Carhart-Harris, R. L., Roseman, L. et al. · NeuroImage (2021)

141 cited
Lasting effects of a single psilocybin dose on resting-state functional connectivity in healthy individuals

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Positive expectations predict improved mental-health outcomes linked to psychedelic microdosing

Kaertner, L. S., Steinborn, M. B., Kettner, H. et al. · Scientific Reports (2021)

112 cited
The entropic tongue: Disorganization of natural language under LSD

Sanz, C., Pallavicini, C., Carrillo, F. et al. · Consciousness and Cognition (2021)

24 cited
Effect of lysergic acid diethylamide (LSD) on reinforcement learning in humans

Kanen, J. W., Luo, Q., Kandroodi, M. R. et al. · Psychological Medicine (2020)

Ketamine and Serotonergic Psychedelics: Common Mechanisms Underlying the Effects of Rapid-Acting Antidepressants

Kadriu, B., Greenwald, M., Ba et al. · International Journal of Neuropsychopharmacology (2020)

Pivotal Mental States

Brouwer, A., Carhart-Harris, R. L. · Journal of Psychopharmacology (2020)

Therapeutic effects of classic serotonergic psychedelics: A systematic review of modern-era clinical studies

Andersen, K. A. A., Carhart-Harris, R. L., Nutt, D. J. et al. · Acta Psychiatrica Scandinavica (2020)

DMT alters cortical travelling waves

Alamia, A., Timmermann, C., Carhart-Harris, R. L. · eLife (2020)

Hallucinations Under Psychedelics and in the Schizophrenia Spectrum: An Interdisciplinary and Multiscale Comparison

Leptourgos, P., Fortier-Davy, M., Carhart-Harris, R. L. et al. · Schizophrenia Bulletin (2020)

Psychedelic drugs: neurobiology and potential for treatment of psychiatric disorders

Vollenweider, F. X., Preller, K. H. · Nature Reviews Neuroscience (2020)

Psychedelic science in post-COVID-19 psychiatry

Kelly, J. R., Crockett, M. T., Alexander, L. et al. · Irish Journal of Psychological Medicine (2020)

82 cited
Updating the dynamic framework of thought: Creativity and psychedelics

Girn, M., Mills, C., Roseman, L. et al. · NeuroImage (2020)

LSD flattens the functional hierarchy of the human brain

Girn, M., Roseman, L., Bernhardt, B. et al. · Biorxiv (2020)

Psychedelic Psychiatry’s Brave New World

Nutt, D. J., Erritzoe, D., Carhart-Harris, R. L. · Cell (2020)

Decreased directed functional connectivity in the psychedelic state

Barnett, L., Muthukumaraswamy, S., Carhart-Harris, R. L. · NeuroImage (2020)

Dissolving the self: Active inference, psychedelics, and ego-dissolution

Deane, G. · Philosophy and the Mind Sciences (2020)

Learning to Let Go: A Cognitive-Behavioral Model of How Psychedelic Therapy Promotes Acceptance

Wolff, M., Evens, R., Mertens, L. J. et al. · Frontiers in Psychiatry (2020)

292 cited
Neuropharmacological modulation of the aberrant bodily self through psychedelics

Ho, J. T., Preller, K. H., Lenggenhager, B. · Neuroscience and Biobehavioral Reviews (2020)

Dynamical exploration of the repertoire of brain networks at rest is modulated by psilocybin

Lord, L. D., Expert, P., Atasoy, S. et al. · NeuroImage (2019)

183 cited

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