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REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics
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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. Significance Statement 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 how 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, hierarchical predictive coding, with an often-cited model of the acute action of psychedelics, the entropic brain hypothesis. 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.
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“Another model of psychedelic actions on brain-wide circuits is the”
From Psychedelics and Neural Plasticity: Therapeutic Implications (2022) · cites this paper as Carhart-Harris and Friston, 2019
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“Carhart-Harris and Friston (2020) distinguish between ‘complete ego-dissolution’—a state of ‘complete surrender, associated bliss, and union with all things’ (Carhart-Harris and Friston 2019, 321); and ‘incomplete’ ego-dissolution—a state characterized by intense fear, anxiety and distress.”
From Consciousness in active inference: Deep self-models, other minds, and the challenge of psychedelic-induced ego-dissolution (2021) · cites this paper as Carhart-Harris and Friston 2019
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“It suggests that psychedelics “relax” high-level cortical cognitive structures, or “priors” - deep-seated beliefs and assumptions that shape how individuals perceive and interpret the world.”
From Psychoanalytically informed MDMA-assisted therapy for pathological narcissism: a novel theoretical approach (2025) · cites this paper as [101]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“The altered state of consciousness induced by psychedelics is characterized by high sensitivity to the immediate and previous context, which can help actualize of the person’s belief system with bottom-up information (56).”
From Ayahuasca-assisted meaning reconstruction therapy for grief: a non-randomized clinical trial protocol (2025) · cites this paper as [56]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“The ayahuasca experience, therefore, could bring new information to the foreground to enrich the therapeutic process, providing an opportunity to transform maladaptive narratives about oneself, other people (including the deceased) or the world (56, 57).”
From Ayahuasca-assisted meaning reconstruction therapy for grief: a non-randomized clinical trial protocol (2025) · cites this paper as [56]
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“Thus, increased long-ranging cortical connexions and harmony between mutually exclusive brain networks may underlie the beneficial effects elicited by mindfulness meditation and psychedelic-assisted therapy, in isolation as well as in combination (102).”
From Examining the Potential Synergistic Effects Between Mindfulness Training and Psychedelic-Assisted Therapy (2021) · cites this paper as [102]
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“This notion is supported by Carhart-Harris and Friston’s (2019) relaxed beliefs under psychedelics model, which proposes that psychedelics precipitate a freer and less constrained states of consciousness.”
From Prospective examination of the therapeutic role of psychological flexibility and cognitive reappraisal in the ceremonial use of ayahuasca (2022) · cites this paper as Carhart-Harris and Friston, 2019
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“At lower doses, this manifests as the phenomenological effects of psychedelics—e.g. walls may have the appearance of ‘breathing’ (Carhart-Harris and Friston 2019).”
From Consciousness in active inference: Deep self-models, other minds, and the challenge of psychedelic-induced ego-dissolution (2021) · cites this paper as Carhart-Harris and Friston 2019
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“Specifically, relaxed beliefs under psychedelics (the REBUS model) [115] states that psychedelics serve to relax prior beliefs.”
From Mindfulness meditation and psychedelics: potential synergies and commonalities (2023) · cites this paper as [115]
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“Such “tightening of beliefs” functions as a defensive response to intolerable stress and uncertainty and may affect mental health in a transdiagnostic manner [160].”
From Impact of Media-Induced Uncertainty on Mental Health: Narrative-Based Perspective. (2025) · cites this paper as [160]
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Mayer, A., Schwiedrzik, C. M., Wibral, M., Singer, W., & Melloni, L. (2016) · Cerebral Cortex · doi:10.1093/cercor/bhv146 · Cited by 119
Deep temporal models and active inference
Friston, K. J., Rosch, R., Parr, T., Price, C., & Bowman, H. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.04.004 · Cited by 119
Sensory Processing and the Rubber Hand Illusion—An Evoked Potentials Study
Zeller, D., Vladimir Litvak, A., Friston, K. J., & Claßen, J. (2014) · Journal of Cognitive Neuroscience · doi:10.1162/jocn_a_00705 · Cited by 118
Predictive Suppression of Cortical Excitability and Its Deficit in Schizophrenia
Lakatos, P., Schroeder, C. E., Leitman, D. I., & Javitt, D. C. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.0010-13.2013 · Cited by 118
Carter, O. L., Pettigrew, J. D., Hasler, F., Wallis, G. M., Liu, G. B., Hell, D., & Vollenweider, F. X. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300621 · Cited by 118
LTD-like molecular pathways in developmental synaptic pruning
Piochon, C., Kano, M., & Hansel, C. (2016) · Nature Neuroscience · doi:10.1038/nn.4389 · Cited by 118
Effect of Hallucinogens on Unconditioned Behavior
Halberstadt, A. L., & Geyer, M. A. (2016) · Current topics in behavioral neurosciences · doi:10.1007/7854_2016_466 · Cited by 117
Increased activation of indirect semantic associations under psilocybin
Spitzer, M., Thimm, M., Hermle, L., Holzmann-Erens, P., Kovar, K., Heimann, H., Gouzoulis‐Mayfrank, E., Kischka, U., & Schneider, F. W. (1996) · Biological Psychiatry · doi:10.1016/0006-3223(95)00418-1 · Cited by 115
Sacred Knowledge: Psychedelics and Religious Experiences
Richards, W. A. (2015) · doi:10.7312/rich17406 · Cited by 114
Mental time travel and default-mode network functional connectivity in the developing brain
Østby, Y., Walhovd, K. B., Tamnes, C. K., Grydeland, H., Westlye, L. T., & Fjell, A. M. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1210627109 · Cited by 109
Toward the neural implementation of structure learning
Tervo, D. G. R., Tenenbaum, J. B., & Gershman, S. J. (2016) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2016.01.014 · Cited by 106
Flagged first, then by citations
6 of the 283 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Bogenschutz, M. P., Ross, S., Bhatt, S., Baron, T., Forcehimes, A. A., Laska, E., Mennenga, S. E., O’Donnell, K., Owens, L. T., Podrebarac, S., et al. (2022) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2022.2096 · Cited by 711
Psychedelic drugs: neurobiology and potential for treatment of psychiatric disorders
Vollenweider, F. X., & Preller, K. H. (2020) · Nature Reviews Neuroscience · doi:10.1038/s41583-020-0367-2 · Cited by 570
Agin-Liebes, G. I., Malone, T., Yalch, M. M., Mennenga, S. E., Ponté, K. L., Guss, J., Bossis, A. P., Grigsby, J., Fischer, S., & Ross, S. (2020) · Journal of Psychopharmacology · doi:10.1177/0269881119897615 · Cited by 360
Andersen, K. A. A., Carhart‐Harris, R., Nutt, D. J., & Erritzoe, D. (2021) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.13249 · Cited by 347
Metadata
- Authors
- Carhart-Harris, R. L., & Friston, K. J.
- Affiliations
- Wellcome Centre for Human Neuroimaging (GB)
- Corresponding author
- Carhart-Harris, R.L.
- Venue
- Pharmacological Reviews
- Publisher
- Elsevier BV
- Published
- 2019-07
- Volume
- 71
- Issue
- 3
- Pages
- 316-344
- ISSN
- 0031-6997 (ISSN-L)
- PMC
- PMC6588209
- OpenAlex
- W2949457836
- Cited by
- 1,180
- References
- 283
- Citations by year
- 2026: 262 · 2025: 245 · 2024: 210 · 2023: 176 · 2022: 135 · 2021: 86 · 2020: 51 · 2019: 12
- FWCI
- 11.28
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Pharmacological Reviews (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Social Sciences › Psychology › Social Psychology › Paranormal Experiences and Beliefs
- Life Sciences › Neuroscience › Cognitive Neuroscience › Embodied and Extended Cognition
- Keywords
- psychedelics, rebus, free energy principle, hierarchical predictive coding, prior distributions, belief updating, spontaneous cortical activity, limbic system, mental illness, consciousness
- MeSH terms
- Animals, Brain, Culture, Hallucinogens, Humans, Models, Neurological
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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