R L Carhart-Harris, K J Friston
5 min
The REBUS (Relaxed Beliefs Under pSychedelics) model integrates the free-energy principle—which posits that the brain functions to minimize uncertainty by updating internal models—with the entropic brain hypothesis, which suggests psychedelics increase the entropy of brain activity. The authors argue that psychedelics, through their action on 5-HT2AR receptors, specifically target the brain's high-level hierarchical structures. By reducing the 'precision weighting' (or felt confidence) of these high-level priors, the drug effectively 'flattens' the brain's energy landscape. This process releases the brain from the rigid, top-down constraints that normally govern perception and cognition, leading to a state of increased entropy and flexibility.
The 'anarchic brain' refers to the consequence of relaxing these high-level priors. In a normal state, the brain's highest levels (such as the Default Mode Network) exert a compressive, top-down influence that suppresses lower-level information. Under the influence of psychedelics, this hierarchy is disrupted. As top-down control weakens, bottom-up information—particularly from intrinsic sources like the limbic system—is liberated. This allows for a more chaotic, or 'anarchic,' state of information processing, which the authors argue is the neurobiological basis for the vivid, diverse, and often unitive experiences reported during a psychedelic trip.
The authors propose that many psychiatric disorders, such as depression and obsessive-compulsive disorder, are characterized by pathologically rigid, overweighted high-level priors that lock the individual into negative or restrictive patterns of thought. By temporarily relaxing these priors, psychedelic therapy creates a 'hot state' of heightened plasticity. This window of opportunity allows for the revision of these entrenched beliefs. When combined with proper psychological support, this process can lead to long-term therapeutic benefits, as the individual is able to recalibrate their internal models to be more flexible and better aligned with reality.
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.
Sam: So the system moves away from a deep, narrow attractor toward something much broader and shallower. It becomes hypersensitive to incoming data rather than filtering everything through a fixed model.
Alex: The authors use the analogy of simulated annealing. You heat the system — raise its entropy — so it can escape local minima and explore the broader energy landscape. Then as the drug clears, the system cools back down and, ideally, settles into a more adaptive configuration. That's the mechanistic story behind the afterglow effect clinicians observe: the days or weeks of increased psychological flexibility after a session aren't just residual pharmacology — they reflect a genuine structural recalibration of the generative model.
Sam: That's a tidy story. Where does it strain?
Alex: The authors are candid about the central limitation: the "high-level" attribution is still largely abstract. The framework predicts that psychedelics selectively flatten precision at the top of the hierarchy, but mapping that claim onto specific neuronal populations with sufficient resolution to test it rigorously is still out of reach. Ego dissolution is a well-characterized phenomenological state, but pinning it to a precise computational signature in identified circuits — rather than gesturing at association cortex broadly — remains an open problem. The model is generative and internally consistent, but it's running ahead of what the empirical methods can currently resolve.
Sam: So it's a framework that organizes existing findings and generates predictions, rather than a model that's been directly confirmed at the mechanistic level.
Alex: That's the right read. What it does well is unify two previously separate accounts — the free-energy principle and the entropic brain hypothesis — into a single computational story that makes contact with both the pharmacology and the phenomenology. It gives researchers a shared vocabulary and a set of testable predictions. If precision weighting of high-level priors is the operative variable, you'd expect the therapeutic signal to correlate with measures of prior relaxation, not just with the intensity of the acute experience. Some early data points in that direction, but the causal chain hasn't been closed.
Sam: It also reframes what psychedelics are doing at a conceptual level — not disrupting the brain indiscriminately, but selectively modulating the confidence the system places in its most entrenched beliefs.
Alex: Which is what makes the model worth taking seriously as a research scaffold, even before the mechanistic details are nailed down. The question it poses — how do you therapeutically update a prior that's too precisely weighted to revise through ordinary experience? — is a genuinely important one, and REBUS offers a principled computational answer. Whether that answer survives contact with the next generation of circuit-level data is the experiment worth watching.
Sam: Thanks for walking through that, Alex.
Alex: Thanks for listening to ResearchPod.