SchizophreniaNeuroimaging & Brain Measures

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.

Authors

  • Enzo Tagliazucchi
  • Robin Carhart-Harris
  • David Nutt

Published

Frontiers in Human Neuroscience
meta Study

Abstract

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.

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

Introduction

Carhart-Harris and colleagues present a synthetic theory—the entropic brain hypothesis—that links principles from physics, neurobiology and psychoanalysis to explain differences between normal adult waking consciousness and a class of regressive or ‘‘primary’’ conscious states (for example, the psychedelic state, REM sleep and early psychosis). The paper frames entropy, in the information-theoretical sense, as a quantitative index of a brain's uncertainty or disorder, and proposes that subjective experiences of puzzlement or loosened reality-testing accompany increased system entropy. It positions self-organised criticality and Friston's free-energy ideas as conceptual scaffolding for relating dynamical brain properties to conscious style. The study sets out to argue that the psychedelic state exemplifies a high-entropy or near-critical mode of brain function, and to map candidate neural correlates of the ‘‘ego’’ or self-boundary—notably activity, synchrony and coupling within the default mode network (DMN) and between the DMN and the medial temporal lobes (MTLs). Using previously published neuroimaging findings (ASL, BOLD fMRI and MEG) with psilocybin alongside theoretical argument, the authors propose testable hypotheses about how DMN integrity, DMN–MTL coupling, oscillatory activity (especially PCC alpha) and measures of network metastability and entropy distinguish primary from secondary consciousness. A secondary aim is to show how psychedelics can serve as an experimental tool to probe psychoanalytic constructs within cognitive neuroscience.

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Study Details

References (25)

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Kettner, H., Rosas, F. E., Timmermann, C. et al. · Frontiers in Pharmacology (2021)

157 cited
Neural Correlates of the Shamanic State of Consciousness

Pasquini, L., Luke, D., Harris, R. E. et al. · Frontiers in Human Neuroscience (2021)

Psychedelic Experiences and Mindfulness are Associated with Improved Wellbeing

Qiu, T. T., Minda, J. P. · Psyarxiv (2021)

Psilocin acutely disrupts sleep and affects local but not global sleep homeostasis in laboratory mice

Thomas, C. W., Blanco-Duque, C., Breant, B. et al. · Translational Psychiatry (2021)

Effects of ketamine on brain function during metacognition of episodic memory

Lehmann, M., Neumann, C., Wasserthal, S. et al. · Neuroscience of Consciousness (2021)

11 cited
Neural and subjective effects of inhaled N,N-dimethyltryptamine in natural settings

Pallavicini, C., Cavanna, F., Zamberlan, F. et al. · Journal of Psychopharmacology (2021)

LSD alters dynamic integration and segregation in the human brain

Luppi, A. I., Carhart-Harris, R. L., Roseman, L. et al. · NeuroImage (2021)

141 cited
EEG Gamma Band Alterations and REM-like Traits Underpin the Acute Effect of the Atypical Psychedelic Ibogaine in the Rat

González, J., Cavelli, M., Castro-Zaballa, S. et al. · ACS Pharmacology and Translational Science (2021)

17 cited
The entropic tongue: Disorganization of natural language under LSD

Sanz, C., Pallavicini, C., Carrillo, F. et al. · Consciousness and Cognition (2021)

24 cited
The potential synergistic effects between psychedelic administration and nature contact for the improvement of mental health

Gandy, S., Forstmann, M., Carhart-Harris, R. L. et al. · Health Psychology Open (2020)

Pivotal Mental States

Brouwer, A., Carhart-Harris, R. L. · Journal of Psychopharmacology (2020)

Improved colour blindness symptoms associated with recreational psychedelic use: Results from the Global Drug Survey 2017

Ferris, J. A., Nutt, D. J. · Drug Science Policy and Law (2020)

7 cited
The Acute Effects of the Atypical Dissociative Hallucinogen Salvinorin A on Functional Connectivity in the Human Brain

Doss, M. K., May, D. G., Johnson, M. W. et al. · Scientific Reports (2020)

Serotonergic psychedelics LSD & psilocybin increase the fractal dimension of cortical brain activity in spatial and temporal domains

Varley, T. F., Carhart-Harris, R., Roseman, L. et al. · NeuroImage (2020)

Psychedelic drugs: neurobiology and potential for treatment of psychiatric disorders

Vollenweider, F. X., Preller, K. H. · Nature Reviews Neuroscience (2020)

Integrating psychotherapy and psychopharmacology: psychedelic-assisted psychotherapy and other combined treatments

Greenway, K. T., Garel, N., Jerome, L. et al. · Expert Review of Clinical Pharmacology (2020)

Updating the dynamic framework of thought: Creativity and psychedelics

Girn, M., Mills, C., Roseman, L. et al. · NeuroImage (2020)

Ethics and ego dissolution: the case of psilocybin

Smith, W. R., Sisti, D. · Journal of Medical Ethics (2020)

Me, myself, bye: regional alterations in glutamate and the experience of ego dissolution with psilocybin

Mason, N. L., Kuypers, K. P. C., Reckweg, J. et al. · Neuropsychopharmacology (2020)

Chronic pain and psychedelics: a review and proposed mechanism of action

Castellanos, J. P., Woolley, C., Bruno, K. A. et al. · Regional Anesthesia and Pain Medicine (2020)

101 cited
LSD flattens the functional hierarchy of the human brain

Girn, M., Roseman, L., Bernhardt, B. et al. · Biorxiv (2020)

Isness: Using Multi-Person VR to Design Peak Mystical Type Experiences Comparable to Psychedelics

Glowacki, D. R., Wonnacott, M. D., Freire, R. et al. · Association for Computing Machinery (2020)

32 cited
Decreased directed functional connectivity in the psychedelic state

Barnett, L., Muthukumaraswamy, S., Carhart-Harris, R. L. · NeuroImage (2020)

Depression, Mindfulness, and Psilocybin: Possible Complementary Effects of Mindfulness Meditation and Psilocybin in the Treatment of Depression. A Review

Heuschkel, K., Kuypers, K. P. C. · Frontiers in Psychiatry (2020)

63 cited
Long-term effects of psychedelic drugs: A systematic review

Aday, J. S., Mitzkovitz, C. M., Bloesch, E. K. et al. · Neuroscience and Biobehavioral Reviews (2020)

Psychedelics and Psychedelic-Assisted Psychotherapy

Reiff, C. M., Richman, E. E., Nemeroff, C. B. et al. · American Journal of Psychiatry (2020)

Emotions and brain function are altered up to one month after a single high dose of psilocybin

Barrett, F. S., Doss, M. K., Sepeda, N. D. et al. · Scientific Reports (2020)

Ayahuasca’s ‘afterglow’: improved mindfulness and cognitive flexibility in ayahuasca drinkers.

Murphy-Beiner, A., Soar, K. · Psychopharmacology (2020)

99 cited
Neuropharmacological modulation of the aberrant bodily self through psychedelics

Ho, J. T., Preller, K. H., Lenggenhager, B. · Neuroscience and Biobehavioral Reviews (2020)

Psilocybin-assisted therapy of major depressive disorder using Acceptance and Commitment Therapy as a therapeutic frame

Sloshower, J., Guss, J., Krause, R. et al. · Journal of Contextual Behavioral Science (2020)

Psychological flexibility mediates the relations between acute psychedelic effects and subjective decreases in depression and anxiety

Davis, A. K., Barrett, F. S., Griffiths, R. R. · Journal of Contextual Behavioral Science (2020)

From Egoism to Ecoism: Psychedelics Increase Nature Relatedness in a State-Mediated and Context-Dependent Manner

Kettner, H., Gandy, S., Haijen, E. C. H. M. et al. · International Journal of Environmental Research and Public Health (2019)

131 cited
Neural correlates of the DMT experience assessed with multivariate EEG

Timmermann, C., Roseman, L., Schartner, M. et al. · Scientific Reports (2019)

Dynamical exploration of the repertoire of brain networks at rest is modulated by psilocybin

Lord, L. D., Expert, P., Atasoy, S. et al. · NeuroImage (2019)

183 cited
Spectral signatures of serotonergic psychedelics and glutamatergic dissociatives

Pallavicini, C., Vilas, M. G., Villarreal, M. et al. · NeuroImage (2019)

51 cited
Toward a contextual psychedelic-assisted therapy: Perspectives from Acceptance and Commitment Therapy and contextual behavioral science

Luoma, J. B., Sabucedo, P., Eriksson, J. et al. · Journal of Contextual Behavioral Science (2019)

Psilocybin-assisted mindfulness training modulates self-consciousness and brain default mode network connectivity with lasting effects

Smigielski, L., Scheidegger, M., Kometer, M. et al. · NeuroImage (2019)

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

Carhart-Harris, R. L., Friston, K. J. · Pharmacological Reviews (2019)

Receptor-Enriched Analysis of functional connectivity by targets (REACT): A novel, multimodal analytical approach informed by PET to study the pharmacodynamic response of the brain under MDMA

Dipasquale, O., Selvaggi, P., Veronese, M. et al. · NeuroImage (2019)

Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function

Johnson, M. W., Hendricks, P. S., Barrett, F. S. et al. · Pharmacology and Therapeutics (2019)

States and traits related to the quality and consequences of psychedelic experiences

Russ, S. L., Carhart-Harris, R. L., Maruyama, G. et al. · Psychology of Consciousness Theory Research and Practice (2019)

A systematic study of microdosing psychedelics

Polito, V., Stevenson, R. J. · PLOS ONE (2019)

197 cited
Effective connectivity changes in LSD-induced altered states of consciousness in humans

Preller, K. H., Razi, A., Zeidman, P. et al. · PNAS (2019)

How do psychedelics work?

Carhart-Harris, R. L. · Current Opinion in Psychiatry (2019)

Current perspectives on psychedelic therapy: use of serotonergic hallucinogens in clinical interventions

Richards, W. A., Garcia-Romeu, A. · International Review of Psychiatry (2018)

Ketamine for the treatment of addiction: Evidence and potential mechanisms

Ezquerra-Romano, I. I., Lawn, W., Krupitsky, E. M. et al. · Neuropharmacology (2018)

LSD modulates effective connectivity and neural adaptation mechanisms in an auditory oddball paradigm

Timmermann, C., Spriggs, M. J., Kaelen, M. et al. · Neuropharmacology (2018)

The Varieties of the Psychedelic Experience: A Preliminary Study of the Association Between the Reported Subjective Effects and the Binding Affinity Profiles of Substituted Phenethylamines and Tryptamines

Zamberlan, F., Sanz, C., Pallavicini, C. et al. · Frontiers in Integrative Neuroscience (2018)

Exploring the effect of microdosing psychedelics on creativity in an open-label natural setting

Prochazkova, L., Lippelt, D. P., Colzato, L. S. et al. · Psychopharmacology (2018)

More realistic forecasting of future life events after psilocybin for treatment-resistant depression

Lyons, T., Carhart-Harris, R. L. · Frontiers in Psychology (2018)

49 cited
Awe: a putative mechanism underlying the effects of classic psychedelic-assisted psychotherapy

Hendricks, P. S. · International Review of Psychiatry (2018)

143 cited
Psychedelics and music: neuroscience and therapeutic implications

Barrett, F. S., Preller, K. H., Kaelen, M. · International Review of Psychiatry (2018)

Dimensions of consciousness and the psychedelic state

Bayne, T., Carter, O. · Neuroscience of Consciousness (2018)

106 cited
Psychedelics, meditation, and self-consciousness

Milliere, R., Carhart-Harris, R. L., Roseman, L. et al. · Frontiers in Psychology (2018)

Psychedelic-Assisted Psychotherapy: A Paradigm Shift in Psychiatric Research and Development

Schenberg, E. E. · Frontiers in Pharmacology (2018)

Positive psychology in the investigation of psychedelics and entactogens: A critical review

Jungaberle, H., Thal, S., Zeuch, A. et al. · Neuropharmacology (2018)

Role of the 5-HT2A Receptor in Self- and Other-Initiated Social Interaction in Lysergic Acid Diethylamide-Induced States: A Pharmacological fMRI Study

Preller, K. H., Schilbach, L., Pokorny, T. et al. · Journal of Neuroscience (2018)

The entropic brain - revisited

Carhart-Harris, R. L. · Neuropharmacology (2018)

Unifying theories of psychedelic drug effects

Swanson, L. R. · Frontiers in Pharmacology (2018)

The psychedelic debriefing in alcohol dependence treatment: illustrating key change phenomena through qualitative content analysis of clinical sessions

Kraehenmann, R., Nielson, E. M., May, D. G. et al. · Frontiers in Pharmacology (2018)

The Experience Elicited by Hallucinogens Presents the Highest Similarity to Dreaming within a Large Database of Psychoactive Substance Reports

Sanz, C., Zamberlan, F., Erowid, E. et al. · Frontiers in Neuroscience (2018)

Quality of acute psychedelic experience predicts therapeutic efficacy of psilocybin for treatment-resistant depression

Roseman, L., Nutt, D. J., Carhart-Harris, R. L. · Frontiers in Pharmacology (2018)

Psilocybin disrupts sensory and higher order cognitive processing but not pre-attentive cognitive processing-study on P300 and mismatch negativity in healthy volunteers

Bravermanová, A., Viktorinová, M., Tylš, F. et al. · Psychopharmacology (2018)

Connectome-harmonic decomposition of human brain activity reveals dynamical repertoire re-organization under LSD

Atasoy, S., Leor, R., Kaelen, M. et al. · Scientific Reports (2017)

LSD Increases Primary Process Thinking via Serotonin 2A Receptor Activation

Sumiyoshi, T., Kraehenmann, R., Pokorny, D. et al. · Frontiers in Pharmacology (2017)

Double-blind comparison of the two hallucinogens psilocybin and dextromethorphan: similarities and differences in subjective experiences

Carbonaro, T. M., Hurwitz, E., Johnson, M. W. · Psychopharmacology (2017)

102 cited
Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms

Carhart-Harris, R. L., Roseman, L., Bolstridge, M. et al. · Scientific Reports (2017)

The Mechanisms of Psychedelic Visionary Experiences: Hypotheses from Evolutionary Psychology

Winkelman, M. J. · Frontiers in Neuroscience (2017)

Psychedelic Drugs in Biomedicine

Kyzar, E. J., Nichols, C. D., Gainetdinov, R. R. et al. · Trends in Pharmacological Sciences (2017)

Does psychedelic drug use reduce risk of suicidality? Evidence from a longitudinal community-based cohort of marginalised women in a Canadian setting

Argento, E., Strathdee, S. A., Tupper, K. et al. · BMJ Open (2017)

48 cited
Psychedelic pleasures: An affective understanding of the joys of tripping

Bøhling, F. · International Journal of Drug Policy (2017)

Serotonin and brain function: a tale of two receptors

Carhart-Harris, R. L., Nutt, D. J. · Journal of Psychopharmacology (2017)

Shannon entropy of brain functional complex networks under the influence of the psychedelic Ayahuasca

Viol, A., Palhano-Fontes, F., Onias, H. et al. · Scientific Reports (2017)

Psychedelics and connectedness

Carhart-Harris, R. L., Erritzoe, D., Haijen, E. C. H. M. et al. · Psychopharmacology (2017)

Psychedelic drug use in healthy individuals: A review of benefits, costs, and implications for drug policy

Elsey, J. W. B. · Drug Science Policy and Law (2017)

Qualitative and quantitative features of music reported to support peak mystical experiences during psychedelic therapy sessions

Slevc, L. R., Barrett, F. S., Robbins, H. et al. · Frontiers in Psychology (2017)

Self unbound: ego dissolution in psychedelic experience

Letheby, C., Gerrans, P. · Neuroscience of Consciousness (2017)

Effects of LSD on music-evoked brain activity

Kaelen, M., Lorenz, R., Barrett, F. S. et al. · Biorxiv (2017)

Looking for the Self: Phenomenology, Neurophysiology and Philosophical Significance of Drug-induced Ego Dissolution

Millière, R. · Frontiers in Human Neuroscience (2017)

Modern clinical research on LSD

Liechti, M. E. · Neuropsychopharmacology (2017)

Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin

Schartner, M., Carhart-Harris, R. L., Barrett, A. B. et al. · Scientific Reports (2017)

19 cited
The psychological and human brain effects of music in combination with psychedelic drugs

Kaelen, M. · Imperial College London (2017)

Psychedelics and the science of self-experience

Nour, M. R., Carhart-Harris, R. L. · British Journal of Psychiatry (2017)

Perception is in the Details: A Predictive Coding Account of the Psychedelic Phenomenon

Pink-Hashkes, S., Van Rooij, I., Kwisthout, J. · CogSci (2017)

Phenomenology, Structure, and Dynamic of Psychedelic States

Preller, K. H., Vollenweider, F. X. · Behavioral Neurobiology of Psychedelic Drugs (2016)

Classical hallucinogens and neuroimaging: A systematic review of human studies: hallucinogens and neuroimaging

Dos Santos, R. G., Osório, F. L., Crippa, J. A. et al. · Neuroscience and Biobehavioral Reviews (2016)

Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer

Griffiths, R. R., Johnson, M. W. · Journal of Psychopharmacology (2016)

Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: A randomized controlled trial

Ross, S., Bossis, A. P., Guss, J. et al. · Journal of Psychopharmacology (2016)

The Challenging Experience Questionnaire: Characterization of challenging experiences with psilocybin mushrooms

Barrett, F. S., Bradstreet, M. P., Leoutsakos, J. M. S. et al. · Journal of Psychopharmacology (2016)

Psychedelics as Medicines: An Emerging New Paradigm

Nichols, C. D., Nichols, D. E., Johnson, M. W. · Clinical Pharmacology and Therapeutics (2016)

Development of a Psychotherapeutic Model for Psilocybin-Assisted Treatment of Alcoholism

Bogenschutz, M. P., Forcehimes, A. A. · Journal of Humanistic Psychology (2016)

The Associations of Naturalistic Classic Psychedelic Use, Mystical Experience, and Creative Problem Solving

Sweat, N. W., Bates, L. W., Hendricks, P. S. · Journal of Psychoactive Drugs (2016)

Semantic activation in LSD: evidence from picture naming

Family, N., Vinson, D., Vigliocco, G. et al. · Language Cognition and Neuroscience (2016)

Clinical Applications of Hallucinogens: A Review

Garcia-Romeu, A., Kersgaard, B., Addy, P. H. · Experimental and Clinical Psychopharmacology (2016)

174 cited
LSD modulates music-induced imagery via changes in parahippocampal connectivity

Kaelen, M., Roseman, L., Kahan, J. et al. · European Neuropsychopharmacology (2016)

Ego-dissolution and psychedelics: validation of the ego-dissolution inventory (EDI)

Nour, M. R., Evans, J., Nutt, D. J. et al. · Frontiers in Human Neuroscience (2016)

The current state of research on ayahuasca: A systematic review of human studies assessing psychiatric symptoms, neuropsychological functioning, and neuroimaging

Dos Santos, R. G., Balthazar, F. M., Bouso, J. C. et al. · Journal of Psychopharmacology (2016)

LSD-induced entropic brain activity predicts subsequent personality change

Lebedev, A. V., Kaelen, M., L€ Ovd En, M. et al. · Human Brain Mapping (2016)

292 cited
Neural correlates of the LSD experience revealed by multimodal neuroimaging

Carhart-Harris, R. L., Muthukumaraswamy, S., Roseman, L. et al. · PNAS (2016)

Increased global functional connectivity correlates with LSD-induced ego dissolution

Tagliazucchi, E., Roseman, L., Kaelen, M. et al. · Current Biology (2016)

Psychedelics

Nichols, D. E. · Pharmacological Reviews (2016)

Lysergic acid diethylamide: a drug of ‘use’?

Das, S., Barnwal, P., Ramasamy, A. et al. · Therapeutic Advances in Psychopharmacology (2016)

Decreased mental time travel to the past correlates with default-mode network disintegration under lysergic acid diethylamide

Speth, J., Speth, C., Kaelen, M. et al. · Journal of Psychopharmacology (2016)

113 cited
The therapeutic potentials of ayahuasca: possible effects against various diseases of civilization

Frecska, E., Bokor, P., Winkelman, M. J. · Frontiers in Pharmacology (2016)

The paradoxical psychological effects of lysergic acid diethylamide (LSD)

Carhart-Harris, R. L., Kaelen, M., Bolstridge, M. et al. · Psychological Medicine (2016)

253 cited
New World Tryptamine Hallucinogens and the Neuroscience of Ayahuasca

McKenna, D., Riba, J. · Current Topics in Behavioral Neurosciences (2016)

Serotonergic Hallucinogen-Induced Visual Perceptual Alterations

Kometer, M., Vollenweider, F. X. · Behavioral Neurobiology of Psychedelic Drugs (2016)

Restructuring consciousness -the psychedelic state in light of integrated information theory

Gallimore, A. R. · Frontiers in Human Neuroscience (2015)

Finding the self by losing the self: Neural correlates of ego-dissolution under psilocybin

Lebedev, A. V., L€ Ovd En, M., Rosenthal, G. et al. · Human Brain Mapping (2015)

Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population

Hendricks, P. S., Thorne, C. B., Clark, B. et al. · Journal of Psychopharmacology (2015)

345 cited
LSD-assisted psychotherapy for anxiety associated with a life-threatening disease: a qualitative study of acute and sustained subjective effects

Kirchner, K. · Journal of Psychopharmacology (2014)

389 cited
Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction

Johnson, M. W., Garcia-Romeu, A., Cosimano, M. P. et al. · Journal of Psychopharmacology (2014)

The effects of psilocybin and MDMA on between-network resting state functional connectivity in healthy volunteers

Roseman, L., Leech, R., Feilding, A. et al. · Frontiers in Human Neuroscience (2014)

229 cited

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