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

K J Friston,R L Carhart-Harris,Eric L Barker

doi:10.1124/pr.118.017160

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.Significance StatementPsychedelics 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.

Highlights

Psychedelic drugs such as d-lysergic acid diethylamide (LSD) and psilocybin are capturing people’s imagination and permeating popular culture on a scale not seen since the 1960s (Hanks, 2010; Keshavan and Sudarshan, 2017; Bayne and Carter, 2018; Pollan, 2018)
To aid the testing of the relaxed beliefs under psychedelics (REBUS)/anarchic brain model, we propose a number of specific indices of priors and bottom-up signaling such as the functional integrity and dynamics of high-level brain networks (REBUS) and effective connectivity applied to relevant circuitry, such as circuitry connecting the hippocampus/parahippocampus with cortical nodes of the default-mode network (DMN)
We propose that mechanisms of Bayesian model selection (BMS) and Bayesian model reduction (BMR) are catalyzed by the time-limited entropic state induced by psychedelics, such that model redundancy can be minimized, and high-level priors refined or “spring-cleaned.”

Summary

Introduction

Psychedelic (mind-manifesting) drugs such as d-lysergic acid diethylamide (LSD) and psilocybin are capturing people’s imagination and permeating popular culture on a scale not seen since the 1960s (Hanks, 2010; Keshavan and Sudarshan, 2017; Bayne and Carter, 2018; Pollan, 2018). We integrate the entropic brain hypothesis and the free-energy principle framework, and in particular, exploit the latter’s close links with predictive processing or coding and the so-called Bayesian brain hypothesis Put these closely related perspectives on brain and mind function maintain that the brain instantiates, within its hierarchical architecture, best-guess statistical approximations (generative models) of the causes of its sensorium based on Bayesian principles of empirically informed belief updating (Rao and Ballard, 1999). We hope to explain how a potential relaxation of the precision weighting of high-level priors or beliefs and subsequent opening up of mental content under a psychedelic is logically implied by our two main guiding formulations: the entropic brain hypothesis and the free-energy principle. We conclude by focusing on recent evidence supporting the therapeutic potential of psychedelics and offer a unified account of their acute and therapeutic mechanisms based on an integration of the entropic brain hypothesis and free-energy principle

The Basic Neuropharmacology of Psychedelics

Behavioral Evidence of Relaxed Priors under Psychedelics

Comparisons with Other Altered States and Traits

Psychedelics and Insight

The Anarchic Brain

Summary

Conclusions