Depressive DisordersAnxiety DisordersObsessive-Compulsive Disorder (OCD)Substance Use Disorders (SUD)Set & Setting

How Psychedelic-Assisted Treatment Works in the Bayesian Brain

The paper proposes that psychedelics attenuate the precision of high-level predictions (REBUS), thereby amplifying psychotherapy’s common factors (set and setting) so that bottom-up input more readily revises maladaptive beliefs, accelerating therapeutic change and symptom relief.

Authors

  • Villiger, D.

Published

Frontiers in Psychiatry
meta Study

Abstract

Psychedelics are experiencing a renaissance in clinical research. In recent years, an increasing number of studies on psychedelic-assisted treatment have been conducted. So far, the results are promising, suggesting that this new (or rather, rediscovered) form of therapy has great potential. One particular reason for that appears to be the synergistic combination of the pharmacological and psychotherapeutic interventions in psychedelic-assisted treatment. But how exactly do these two interventions complement each other? This paper provides the first account of the interaction between pharmacological and psychological effects in psychedelic-assisted treatment. Building on the relaxed beliefs under psychedelics (REBUS) hypothesis of Carhart-Harris and Friston and the contextual model of Wampold, it argues that psychedelics amplify the common factors and thereby the remedial effects of psychotherapy. More precisely, psychedelics are assumed to attenuate the precision of high-level predictions, making them more revisable by bottom-up input. Psychotherapy constitutes an important source of such input. At best, it signalizes a safe and supportive environment (cf. setting) and induces remedial expectations (cf. set). During treatment, these signals should become incorporated when high-level predictions are revised: a process that is hypothesized to occur as a matter of course in psychotherapy but to get reinforced and accelerated under psychedelics. Ultimately, these revisions should lead to a relief of symptoms.

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Research Summary of 'How Psychedelic-Assisted Treatment Works in the Bayesian Brain'

Introduction

Psychedelic research has undergone a marked revival over recent decades, with rising numbers of clinical trials and renewed public and academic interest. After an early flowering in the 1950s and 1960s that was curtailed by regulatory prohibition, contemporary studies have investigated psychedelics such as LSD, psilocybin and DMT across conditions including depression, OCD, anxiety and substance use. Despite promising clinical signals, understanding remains incomplete because psychedelic administration is typically embedded within psychotherapeutic programmes, blurring the boundary between pharmacological and psychological mechanisms of change. This paper sets out to integrate two explanatory frameworks: the relaxed beliefs under psychedelics (REBUS) hypothesis, which is grounded in the free-energy principle and predictive processing, and Wampold's contextual model of psychotherapy, which emphasises common factors such as the therapeutic relationship and expectations. Aaronson and colleagues aim to provide a first comprehensive account of how the pharmacological actions of psychedelics and psychotherapeutic elements interact to produce remedial effects, and they outline testable hypotheses that follow from this integrative perspective.

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Study Details

References (26)

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Show all 26 references
Hallucinogens

Nichols, D. E. · Pharmacology and Therapeutics (2004)

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)

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Timmermann, C., Roseman, L., Williams, L. et al. · Frontiers in Psychology (2018)

The paradoxical psychological effects of lysergic acid diethylamide (LSD)

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

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Wittmann, M., Hasler, F., Vollenweider, F. X. · Neuroscience Letters (2008)

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Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance

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Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action

Vollenweider, F. X., Vollenweider-Scherpenhuyzen, M. F. I., Bäbler, A. et al. · NeuroReport (1998)

Patients’ accounts of increased “Connectedness” and “Acceptance” after psilocybin for treatment-resistant depression

Watts, R., Day, C. M., Krzanowski, J. et al. · Journal of Humanistic Psychology (2017)

Blinding and Expectancy Confounds in Psychedelic Randomised Controlled Trials

Muthukumaraswamy, S., Forsyth, B., Lumley, T. · Expert Review of Clinical Pharmacology (2021)

Tripping on nothing: placebo psychedelics and contextual factors

Olson, J. A., Suissa-Rocheleau, L., Lifshitz, M. et al. · Psychopharmacology (2020)

Psilocybin-induced changes in brain network integrity and segregation correlate with plasma psilocin level and psychedelic experience

Madsen, M. K., Stenbaek, D. S., Arvidsson, A. et al. · European Neuropsychopharmacology (2021)

LSD alters dynamic integration and segregation in the human brain

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

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

LSD modulates music-induced imagery via changes in parahippocampal connectivity

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

Positive expectations predict improved mental-health outcomes linked to psychedelic microdosing

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