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

The REBUS and the anarchic brain hypothesis paper (2019) argues that psychedelics relax the precision of high-level priors or beliefs, thereby liberating bottom-up information flow, particularly via intrinsic sources such as the limbic system.

Abstract of REBUS and the Anarchic Brain

“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.”

Authors: Robin L. Carhart-Harris & Karl J. Friston

Notes on REBUS and the Anarchic Brain

This paper is included in our ‘Top 10 Articles for Psychedelic Novices

  • Formulation of REBUS – relaxed beliefs under psychedelics – which combines the entropic brain hypothesis and the free-energy principle
  • Makes explicit a model for therapeutic use that shows how prior beliefs may be relaxed
  • Discussion ventures wider into (speculative) areas such as politics and possible benefits in those contexts

This paper builds on the previous work by Carhart-Harris, et al. (2014) and Carhart-Harris (2018) that first proposed the entropic brain hypothesis.

It is also reviewed on Slate Star Codex (September 2019). And has been commented on by Adam Safron in ‘Strenghtened beliefs under psychedelics (SEBUS)?‘.

“[T]o marry insights from the free-energy principle with those of the entropic brain hypothesis to account for the acute and longer-term brain and mind effects of psychedelics.”

The paper brings together two bright minds (the authors) and makes a bridge between their respective theories.

“The model takes inspiration from two formulations of brain function, namely: 1) the free-energy principle and 2) the entropic brain hypothesis.”

The two formulations are from Friston and Carhart-Harris respectively. In brief, they state the following:

The Entropic Brain hypothesis – Within upper and lower bounds (the critical zone) we experience consciousness from the entropy of spontaneous brain activity, psychedelics increase this.

The Free-Energy principle – “The free-energy principle tries to explain how (biological) systems maintain their order (non-equilibrium steady-state) by restricting themselves to a limited number of states. It says that biological systems minimise a free energy function of their internal states, which entail beliefs about hidden states in their environment.” (wiki) and “[I]f we look closely at what is optimized, the same quantity keeps emerging, namely value (expected reward, expected utility) or its complement, surprise (prediction error, expected cost).” (Nature)

“The entropic brain measures the uncertainty of neuronal fluctuations across time, whereas free-energy measures the uncertainty of beliefs encoded by neuronal fluctuations. The entropic brain hypothesis proposes that a principal action of psychedelics is to increase the entropy of spontaneous brain activity, and that such effects are mirrored at the subjective level by an increase in the richness of conscious experience …”

Psychedelics relax the effect (precision weighting) of prior beliefs and thus make bottom-up information more accessible.

“It is proposed in this work that dissolving high-level priors has implications for the functioning of the rest of the hierarchy—and indeed the integrity of the hierarchy itself. More specifically, we propose that the general (entropic) action of psychedelics is to render the brain/mind’s (variational free) energy landscape flattened or opened up.”

This model argues that it can explain the whole psychedelic experience. From being able to ‘break’ free from old thought-patterns, to having more uncertainty about what you experience to the visuals usually associated with psychedelics. It also tries to explain the experiences like ego dissolution, the peak experience, near-death-like experience, anxiety, insight, and more.

“Within the transient hot state of a psychedelic experience, a flattened landscape implies that attracting brain states (and accompanying mind states) encoding beliefs are less stable and influential, implying that interstate transitions can occur more freely. Thus, rather than the mind and brain being constrained to a small number of gravitationally dominant attractors (i.e., states or sequence of states), the mind and brain spontaneously transition between states with greater freedom—and in a less predictable way.”

This implies that less top-down control allows for more connections between different neurons (and even brain regions). It also hints as to explaining the uncertainty that many people feel when doing psychedelics.

“[O]ur proposal is that psychedelics disrupt functioning at a level of the system (sensitivity of deep-layer pyramidal neurons, power of low-frequency rhythms, and integrity of large-scale networks) that encodes the precision of priors, beliefs, or assumptions. At low doses, subjective effects may be felt most tangibly at the perceptual level and particularly within the visual domain [serotonin 2A receptor (5-HT2ARs) are richly expressed within the visual cortex], but at higher doses, effects will become more profound as the functioning of higher levels of the global hierarchy become significantly disrupted, potentially accounting for phenomena such as the dissolution of ego boundaries and potential (long-term) revision of high-level priors, perspectives, or beliefs.”

“We propose that many, if not most, psychopathologies develop via the gradual (or rapid—in the case of acute trauma) entrenchment of pathologic thoughts and behaviors, plus aberrant beliefs held at a high level, e.g., in the form of negative self-perception and/or fearful, pessimistic, and sometimes paranoid outlooks. We also propose that these pathologic beliefs are ascribed excessive precision, weight, or influence in many psychiatric disorders.”

During the psychedelic experience, the weights of these prior beliefs are lowered and it’s proposed that a participant is freer to reinterpret the past experience/life events.

“An important aspect of the present thesis is that the potential belief-revising effects of psychedelics occur via an action on the top end (or deepest aspect) of the brain’s functional architecture, with high-level cortex being particularly implicated. This high-end locus of action is supported by the especially dense expression of 5-HT2ARs within high-level cortex. Functional disintegration of the DMN [Default Mode Network] and changes in other high-level networks have been linked with the most abstract phenomenological features of the psychedelic experience, such as ego dissolution.”

“Crucially, psychedelics have been found to dramatically decrease prominent low-frequency and therefore high-level brain rhythms such as a and b, and this effect appears to be both reliable and closely related to the intensity of their subjective effects.”

“We propose that this dysregulation of the highest levels of the brain’s functional hierarchy is commensurate with a lightening of the precision weighting encoded by these levels and their associated dynamics. The effect of this, we propose, is to lighten the top heaviness of human cognition, by (temporarily) flattening the hierarchical organization that supports it. Although speculative, the alleged positive mood and procognitive effects of microdosing may depend on the same (temporary) antihierarchical effect, liberating brain and mind function, albeit with far greater subtlety than with higher doses.”

“… the brain enters an entropic hot state under psychedelics in which synaptic efficacy and plasticity are elevated. The result of this window of exceptionally high plasticity may be to leave a legacy of potentially enduring functional and perhaps anatomic change. As the acute drug effects begin to subside, the system (brain) will settle back into its default regimen of efficient free-energy minimization, mirrored by a renewed subjective sense of familiarity and assuredness, but may not return entirely as before.”

We propose that the action of psychedelics on the precision weighting of high-level priors is (one-half of) their definitive psychological action (the other half being increased bottom-up signaling, hence the anarchic brain component).”

This gives more substance to the claims above and provides more detail about how exactly the brain is more flexible in this state.

In a comparison with psychosis, the authors state “We speculate that reduced precision weighting on high-level priors may underlie these commonalities.” Why then do they differ? “1) unlike in psychosis, in the psychedelic state, the system (typically) begins from a baseline state of stable high-level priors (e.g., a stable ego) to which it returns as drug effects subside; 2) drug effects typically subside (e.g., after about 3–5 hours in the case of psilocybin); thus, there is insufficient opportunity or need for a delusional belief system to close out uncertainty; 3) increased prediction error (and accompanying increased uncertainty) in the psychedelic state is typically seen as an acceptable, expected, and even valued part of the drug experience … and thus is typically learned from, i.e., integrated rather defended against, possibly via the formation of delusional beliefs and flight from reality (as in schizophrenia); and 4) there is no evidence that prediction errors are overweighted in the psychedelic state; i.e., aberrant salient is not the rule.

Autism is another area where the authors believe faulty high-level priors play a role. They do state that it’s more trait than state-like phenomena. “In autism, the predictive coding architecture is skewed toward lower levels of the hierarchy, and critically, becomes set or fixed this way. It is hypothesized that lower levels of the functional hierarchy are ascribed greater precision in autism, which is often cast as a failure to attenuate sensory precision.”

A link is also made with meditation, some of the same brain-patterns can be seen, but the authors don’t do a deep dive into this topic.

The insight gained from the psychedelic experience can be observed from different lenses. Freudian and Jungian ones are common, but only just observing the outcomes/behavioural consequences is also a valid (albeit behaviourist) way of assessing (and predicting) the outcomes.

The mechanics of insight are still not totally clear (as they are for psychotherapy itself in many cases). The relaxation of prior beliefs is thought to be a component of creativity (and is what happens with psychedelics).

Insight often comes from seeing things from a new perspective (without adding/learning new information). Friston’s free-energy principle and the BMR and BMS models are used to possibly explain this. “BMR is the hypothesized mechanism via which high-level models are stripped of their redundancy so that simpler, more refined solutions may be revealed.” This makes me think of this Einstein quote “Everything should be made as simple as possible, but not simpler.” In this case, a less accurate/stringent model (relaxed prior beliefs) may be even more optimal/suited and lead to insight or ‘aha’ moments.

“[W]e suggest that the acute psychedelic “hot state” reflects the preconditions for subsequent insight; i.e., it reflects a key phase of the process by which insight occurs in which confidence in high-level models is first relinquished so that content previously hidden from consciousness by the occluding influence of overly confident priors is now allowed to emerge, thereby enabling fresh perspectives to be entertained. Under conditions of relaxed high-level priors, disinhibited information is allowed to travel up the hierarchy and impress on consciousness as it does. In this way, one may be granted a fresh opportunity to cultivate changes to the relevant assumptions instantiated by high hierarchical levels.”

Several factors support the notion that there exists a common mechanistic denominator underlying different expressions of mental illness. These include the following: 1) putatively high comorbidity, 2) the poor reliability of diagnoses across diagnosing clinicians, and 3) absence of specific and reliable biomarkers to bolster such diagnoses and the fact that the same category of drug can be used to treat a number of different disorders.” This fits nicely with the model proposed in the article, “…most, if not all, expressions of mental illness can be traced to aberrations in the normal mechanics of hierarchical predictive coding, particularly in the precision weighing of both high-level priors and prediction error. We also propose that, if delivered well, psychedelic therapy can be helpful for such a broad range of disorders precisely because psychedelics work pharmacologically (5-HT2AR agonism) and neurophysiologically (increased excitability of deep-layer pyramidal neurons) to relax the precision weighting of high-level priors (instantiated by high-level cortex) such that they become more sensitive to context (e.g., via sensitivity to bottom-up information flow intrinsic to the system) and amenable to revision.

But much brain imaging works still needs to be done. There are still many unanswered questions about how long the effects last (i.e. if there are effects that persist after the first day) and how they can be exactly studied.

The experiences that people have on psychedelics – according to the authors – are all ‘real’ and trustworthy (as perceived by the participant). The authors think they are useful, they serve a psychological function and explain things. But that doesn’t mean that they are reliable or honest repressed memories. We humans are notoriously bad at remembering (see work by Elisabeth Loftus – TED Talk).

What about woo-woo / beliefs in the supernatural? One part of the explanation is that people try and frame their extraordinary experience in a mystical way. This is then best correct afterward (not during the experience). “Reliable and robust models of natural phenomena, of the sort that science endeavors to discover and finesse, serve us best, as they are less likely to betray us, leaving us open to logical fallacies, dogmatism, absolutism, and an emotional and existential instability.”

The final part of the paper is concerned with a discussion about the anarchic brain principle. “The anarchic brain principle is a close complement to the entropic brain hypothesis. Both feature as part of their definition, the principle that psychedelics enhance brain entropy (e.g., as measured by Lempel–Ziv complexity) and bottom-up information flow (e.g., measurable via effective connectivity). Both principles are also intended to apply first and foremost to spontaneous brain activity—and are difficult to assess using classic stimulus–response paradigms …

It is natural to speculate from these findings that changes in brain function that may be defining of the psychedelic state, e.g., heightened brain entropy, modular disintegration, increased global integration, and increased bottom-up information flow from intrinsic sources, may be involved in the mediation of (potentially) fundamental transformations in beliefs, including changes in personality and outlook. Providing initial support for this, we previously found a relationship between increased brain entropy under LSD, as measured with functional magnetic resonance imaging, and subsequent increases in trait openness. Moreover, on a purely psychological level, we have found that ego dissolution mediates long-term increases in trait liberalism and decreased authoritarianism.”

As mentioned before, the evidence for long-term changes is promising, but much more study needs to be done.

“This paper has sought to marry insights from the free-energy principle with those of the entropic brain hypothesis to account for the acute and longer-term brain and mind effects of psychedelics. We have named this synthesis REBUS and the anarchic brain.” … “We propose that the REBUS/anarchic brain model can explain the full gamut of phenomena associated with the psychedelic experience, including the emergence of previously unconscious psychological material into conscious awareness.33 We also propose that high-level priors confer a broad summarization of the mind and world, effectively suppressing away (potential) content. It therefore follows that if this suppression is relaxed, as it is under psychedelics, content will necessarily be released. It is an ideal of psychedelic therapy that this newly available content be appropriately integrated and assimilated into existing mental models so that more of the inner and outer world can be processed.”

Summary of REBUS and the Anarchic Brain

Psychedelic drugs capture people’s imagination and permeate popular culture on a scale not seen since the 1960s. The relaxed beliefs under psychedelics (REBUS) model is a unified description of the brain mechanisms of psychedelics that takes inspiration from the free-energy principle and the entropic brain hypothesis.

The entropic brain hypothesis proposes that the entropy of spontaneous brain activity indexes the richness of subjective experience, and that psychedelics acutely increase both.

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

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Cite this paper (APA)

Carhart-Harris, R. L., & Friston, K. J. (2019). REBUS and the anarchic brain: toward a unified model of the brain action of psychedelics. Pharmacological reviews71(3), 316-344.

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Theory Building


Authors associated with this publication with profiles on Blossom

Robin Carhart-Harris
Dr. Robin Carhart-Harris is the Founding Director of the Neuroscape Psychedelics Division at UCSF. Previously he led the Psychedelic group at Imperial College London.

Linked Research Papers

Notable research papers that build on or are influenced by this paper

The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs
This seminal paper (2014) introduces the entropic brain hypothesis intending to build a bridge between neuroscience and psychoanalytic theories. The entropic brain hypothesis proposes two different forms of cognition, one being more 'critical' and unconstrained (whilst under psychedelics). It has become one of the major theories underlying our understanding of how psychedelics exert their therapeutic effects.

Pattern Breaking: A Complex Systems Approach to Psychedelic Medicine
This theory-building article (2022) further refines the REBUS model, using complex systems theory (CST) to propose that psychedelics act as destabilisers of stuck patterns of thinking ('attractors' or 'overweighted priors') which could explain both the acute (peak) and subsequent period in which psychedelics can help one get 'unstuck'.

The entropic brain - revisited
This theory-building article (2017) offers more evidence for the entropic brain hypothesis, a hypothesis that under psychedelics the brain reaches higher criticality and is more susceptible to set and setting (bottom-up information). The study serves as a (possible) framework for why psychedelics work so well for a variety of mental disorders (in combination with psychotherapy).

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