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.

Abstract of The entropic brain

“Entropy is a dimensionless quantity that is used for measuring uncertainty about the state of a system but it can also imply physical qualities, where high entropy is synonymous with high disorder. Entropy is applied here in the context of states of consciousness and their associated neurodynamics, with a particular focus on the psychedelic state. The psychedelic state is considered an exemplar of a primitive or primary state of consciousness that preceded the development of modern, adult, human, normal waking consciousness. Based on neuroimaging data with psilocybin, a classic psychedelic drug, it is argued that the defining feature of “primary states” is elevated entropy in certain aspects of brain function, such as the repertoire of functional connectivity motifs that form and fragment across time. Indeed, since there is a greater repertoire of connectivity motifs in the psychedelic state than in normal waking consciousness, this implies that primary states may exhibit “criticality,” i.e., the property of being poised at a “critical” point in a transition zone between order and disorder where certain phenomena such as power-law scaling appear. Moreover, if primary states are critical, then this suggests that entropy is suppressed in normal waking consciousness, meaning that the brain operates just below criticality. It is argued that this entropy suppression furnishes normal waking consciousness with a constrained quality and associated metacognitive functions, including reality-testing and self-awareness. It is also proposed that entry into primary states depends on a collapse of the normally highly organized activity within the default-mode network (DMN) and a decoupling between the DMN and the medial temporal lobes (which are normally significantly coupled). These hypotheses can be tested by examining brain activity and associated cognition in other candidate primary states such as rapid eye movement (REM) sleep and early psychosis and comparing these with non-primary states such as normal waking consciousness and the anaesthetized state.”

Authors: Robin L. Carhart-Harris, Robert Leech, Peter J. Hellyer, Murray Shanahan, Amanda Feilding, Enzo Tagliazucchi, Dante R. Chialvo & and David Nutt

Notes on The entropic brain

  • Introduction of the entropic brain model (measuring how ordered or disordered/chaotic the brain is)
  • Psychedelics may put the brain in a ‘primary state’, where it exhibits ‘criticality’, i.e. being on the cusp between order and disorder
  • During the use of psychedelics, the default-mode network (DMN) and contact between it and the medial temporal lobes are suppressed

This paper/theory is built upon and expanded in Carhart-Harris (2018) – the entropic brain revisited, and Carhart-Harris & Friston (2019) – REBUS.

“The main aim of this paper is to introduce a new theory of conscious states that incorporates principles of physics, neurobiology, and psychoanalysis. The theory is intended to assist our understanding of the makeup of the human mind, addressing such questions as: “how does the normal waking consciousness of healthy adult humans relate to other states of consciousness?” “how does the human brain maintain its normal state of waking consciousness?” and “what happens to the human brain’s functionality when non-ordinary states such as rapid eye movement (REM) sleep/dreaming, early psychosis and the psychedelic state occur?””

“At its core, the entropic brain hypothesis proposes that the quality of any conscious state depends on the system’s entropy1 measured via key parameters of brain function. Entropy is a powerful explanatory tool for cognitive neuroscience since it provides a quantitative index of a dynamic system’s randomness or disorder while simultaneously describing its informational character, i.e., our uncertainty about the system’s state if we were to sample it at any given time-point. When applied in the context of the brain, this allows us to make a translation between mechanistic and qualitative properties. Thus, according to this principle increased subjective uncertainty or “puzzlement” accompanies states of increased system entropy.”

So, if there is more entropy, the brain is less organized, more confused, less structured. This (later in the paper) is also linked to the psychedelic state of mind and psychosis. When there is less entropy, it means more organization, less flexibility, more rigidity. A lack of creativity, OCD, PTSD (looping through a bad memory) are all examples of this state.

“The present article takes this latter view and argues that the most realistic way forward for psychoanalysis as a science is for its most tangible hypotheses to be simplified and applied within the framework of cognitive neuroscience.”

This is in contrast to saying that psychoanalysis has no testable hypothesis (as Karl Popper has remarked about Sigmund Freud). The authors do believe that psychoanalysis (or maybe more broadly talk therapy) has value. It only needs to ground itself in cognitive neuroscience to have a stronger base to stand on and make better (simplified) hypotheses. And so also bridge the gap with cognitive psychology (which normally only looks at what can be observed/tested).

“By definition, all classic psychedelic drugs are agonists at the serotonin 2A receptor (5-HT2AR). There is a strong positive correlation between a psychedelic’s affinity for the 5-HT2AR and its psychedelic potency.”

Here the authors quickly explain how psychedelics work. They also note that stimulation of the serotonin 2A receptor makes them more likely to fire (demonstrated in rodents in layer 5 pyramid neurons).

“These studies provide some useful clues about the mechanisms by which psychedelics alter brain function to alter consciousness. They imply that cerebral blood flow, BOLD signal, functional connectivity and oscillatory power are decreased in brain regions that are normally highly metabolically active, functionally connected and synchronous/organized in their activity.”

A number of studies with fMRI scanners show that activity in the default mode network (DMN, especially the posterior cingulate cortex (PCC)) is downregulated. This part of the brain is normally responsible for organization/high-level functions, or being a central conductor/orchestrator of global brain function. The theory is that this downregulation adds to the disorganization of the brain.

This article proposes that states such as the psychedelic state, REM sleep, the onset-phase of psychosis and the dreamy-state of temporal lobe epilepsy are examples of a regressive style of cognition that is qualitatively different to the normal waking consciousness of healthy adult humans. We will refer to this mode of cognition as “primary consciousness” and the states themselves as “primary states.” To enter a primary state from normal waking consciousness, it is proposed that the brain must undergo a “phase transition”

This is in contrast to ‘secondary consciousness’, our normal waking state that we are in most of our lives. This state is where we try and limit our surprise and uncertainty about the world (in other words, high entropy). This secondary consciousness is what makes us great planners, but also limits our creativity/diversity of conscious experiences.

The ‘primary consciousness’ (or state) is one where you can expect more magical thinking, like wishful beliefs and -inferences and paranoia. All types where you jump to (positive or negative) conclusions prematurely.

[C]oupling between the MTLs and the cortical regions of the DMN is necessary for the maintenance of adult normal waking consciousness, with its capacity for metacognition. Moreover, a breakdown in hippocampal-DMN coupling is necessary for a regression to primary consciousness.

The medial temporal lobe (MLT) and the DMN are decoupled during the psychedelic state. In the article, a variety of interesting studies are quoted to support this hypothesis.

[W]e recently found a highly significant positive correlation between the magnitude of alpha power decreases in the PCC after psilocybin and ratings of the item “I experienced a disintegration of my ‘self’ or ‘ego’.”

The alpha waves are argued to be related to secondary consciousness and reducing entropy. When it’s there are fewer alpha waves, some characteristics of the secondary state seem to fall away (e.g. ‘ego’). And characteristics of the primary state, like magical thinking, appear.

Results revealed significantly increased network variance in high-level association networks after psilocybin but not in sensory specific and motor networks, and there were no changes after placebo. These results imply that activity in high-level networks becomes relatively disorganized under psilocybin, consistent with the entropic brain hypothesis.”

More brain studies show that entropy increases and the brain patterns become harder to predict under the influence of psilocybin (or psychedelics in general).

[I]t is the ability of psychedelics to disrupt stereotyped patterns of thought and behavior by disintegrating the patterns of activity upon which they rest that accounts for their therapeutic potential. This principle implies that a brain at criticality may be a “happier” brain.

Here the authors make a link to depression and why psychedelics are having such a large positive effect (in combination with therapy). The brain of a depressed person is hyperactive in the DMT, and sub-critical. “Psychedelics may be therapeutic because they work to normalize pathologically subcritical styles of thought (such as is seen in depression, OCD or addiction/craving for example) thereby returning the brain to a more critical mode of operating.”

Indeed, if the principle holds that a critical brain is a happy brain, then it would follow that psychedelics could be used to enhance well-being and divergent thinking, even in already healthy individuals. One negative consequence of this however could be the neglect of accurate reality-testing.”

Not only for people who suffer from mental disorders but also ‘healthy normals’ may benefit from using psychedelics.

[I]t is hypothesized that there is a basic mechanism by which psychedelics can be helpful in psychiatry, whether they be used to treat depression, OCDbor addiction. Specifically, it is proposed that psychedelics work by dismantling reinforced patterns of negative thought and behavior by breaking down the stable spatiotemporal patterns of brain activity upon which they rest.

A caveat is placed here, that you do need the proper guidance to integrate such an experience.

[T]he mechanics underlying the onset of true primary states (for which the spiritual experiences is an example) can be viewed in relation to the second law of thermodynamics. Explicitly, in the absence of a regular driving input, the system (i.e., self-organized brain activity) will inevitably degrade or collapse toward formlessness or maximum entropy.

The spiritual experiences on psychedelics are compared to what is normally associated with this experience, the characteristics strongly overlap. The authors then go on to compare the entropy of the brain to the second law of thermodynamics (“…the total entropy of an isolated system can never decrease over time, and is constant if and only if all processes are reversible. Isolated systems spontaneously evolve towards thermodynamic equilibrium, the state with maximum entropy.”.

The regular MLT activity and/or the clock-like firing of serotonin neurons are argued to be mechanisms that keep the brain organized (low entropy).

Another thing of note is that here, but also many other times in the paper, the authors mention Freud’s theories. They don’t bluntly state them as facts, but they try and pinpoint where good insights lay and which ones are corroborated by neural processes (thus lending possible rigorous scientific evidence for some claims of psychoanalysis, e.g. that the DMN might be the system that could repress memories and that on psychedelics they may thus surface).

During secondary consciousness, the brain can enter a multiplicity of different states and microstates but due to “winner-takes all,” or more strictly, “winnerless” competition between states … the global system only ever entertains one winning state at any one time. However, according to the entropic brain hypothesis, in primary states, the potential multiplicity of possible states is not obliterated but rather extended because the selectivity and conspicuity of a winning state is reduced, and so more transient states may be visited.

Some people describe the experience with psilocybin as having multiple thoughts at one time. In other cases, there is ‘ego’-loss, uncertainty, disorder, expansion. All words that describe or are typical of high entropy. In the article comparison to gas is made, in a larger container (vs half walled off) the entropy is higher.

To develop the construct validity of primary consciousness, it will be necessary to show that the identified parameters of primary consciousness have high internal and convergent validity (i.e., properties of primary consciousness must be shown to exist in a range of different primary states) and sufficient discriminant validity (i.e., these properties must be shown to be sufficiently specific to primary states, i.e., to be absent in non-primary states).

More studies need to be done. This work needs to focus on getting new and better measures of the experiences (e.g. new questionnaires), but also more brain-imaging studies on the different states (REM-sleep, psychedelics, meditation, etc).

Summary of The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs

This paper introduces a new theory of conscious states that incorporates principles of physics, neurobiology, and psychoanalysis. It addresses questions such as how the human brain maintains its normal state of waking consciousness.

The entropic brain hypothesis proposes that increased subjective uncertainty accompanies states of increased system entropy and that this uncertainty is minimized by the brain by minimizing free energy/surprise.

System entropy, as applied to the brain, is related to another current hot topic in cognitive neuroscience, namely “self-organized criticality”. There is growing evidence that brain activity displays characteristics of critical behaviour, and this raises the question of whether there are other states of consciousness in which these characteristics are even more pronounced.

This paper discusses the psychoanalytic model of the structure of the mind, with a special focus on the ego. The ego is a sensation of possessing an immutable identity or personality and is a fundamental system that works in competition and cooperation with other processes in the mind.

The psychedelic drug state is a prototypical high-entropy state of consciousness, and the brain exhibits more characteristics of criticality in the psychedelic state than are apparent during normal waking consciousness. The psychological counterpart of this process is the development of a mature ego and associated metacognitive functions.

The human brain exhibits greater entropy than other members of the animal kingdom, and thus the human mind possesses a greater repertoire of potential mental states than lower animals. The evolution of human consciousness may have occurred through a process of relatively rapid entropy-expansion followed by entropy-suppression.

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The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs

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Cite this paper (APA)

Carhart-Harris, R. L., Leech, R., Hellyer, P. J., Shanahan, M., Feilding, A., Tagliazucchi, E., ... & Nutt, D. (2014). The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs. Frontiers in human neuroscience, 20.

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Theory Building Bio/Neuro


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.

Amanda Feilding
Amanda is the Founder and Director of the Beckley Foundation. She's called the 'hidden hand' behind the renaissance of psychedelic science, and her contribution to global drug policy reform has also been pivotal and widely acknowledged.

Enzo Tagliazucchi
Enzo Tagliazucchi is the head of the Consciousness, Culture and Complexity Group at the Buenos Aires University, a Professor of Neuroscience at the Favaloro University, and a Marie Curie fellow at the Brain and Spine Institute in Paris. His main interest is the study of human consciousness as embedded within society and culture.

David Nutt
David John Nutt is a great advocate for looking at drugs and their harm objectively and scientifically. This got him dismissed as ACMD (Advisory Council on the Misuse of Drugs) chairman.


Institutes associated with this publication

Imperial College London
The Centre for Psychedelic Research studies the action (in the brain) and clinical use of psychedelics, with a focus on depression.

Linked Research Papers

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

LSD-induced increase of Ising temperature and algorithmic complexity of brain dynamics
This preprint (2022) uses the Ising model of brain phase transition to assess fMRI BOLD data from a study in LSD was administered (n=15). Several different concepts from statistical physics were applied to the fMRI data to analyze individualized Ising temperature increases under the influence of LSD and placebo, showing that LSD ingestion shifts the system away from the critical point between paramagnetic and ferromagnetic phases to a more disordered state. Overall findings suggest that LSD increases the complexity of brain dynamics.

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).

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.

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