Set & SettingImplementation & Service Delivery

Psychedelics and the essential importance of context

This opinion article (2018) argues that context (set and setting) are of upmost important when working with psychedelics and proposes ways of optimising context/treatment models.

Authors

  • Robin Carhart-Harris
  • Leor Roseman
  • David Erritzoe

Published

Journal of Psychopharmacology
meta Study

Abstract

Psychedelic drugs are making waves as modern trials support their therapeutic potential and various media continue to pique public interest. In this opinion piece, we draw attention to a long-recognised component of the psychedelic treatment model, namely ‘set’ and ‘setting’ - subsumed here under the umbrella term ‘context’. We highlight: (a) the pharmacological mechanisms of classic psychedelics (5-HT2A receptor agonism and associated plasticity) that we believe render their effects exceptionally sensitive to context, (b) a study design for testing assumptions regarding positive interactions between psychedelics and context, and (c) new findings from our group regarding contextual determinants of the quality of a psychedelic experience and how acute experience predicts subsequent long-term mental health outcomes. We hope that this article can: (a) inform on good practice in psychedelic research, (b) provide a roadmap for optimising treatment models, and (c) help tackle unhelpful stigma still surrounding these compounds, while developing an evidence base for long-held assumptions about the critical importance of context in relation to psychedelic use that can help minimise harms and maximise potential benefits.

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Research Summary of 'Psychedelics and the essential importance of context'

Introduction

Carhart-Harris and colleagues frame their paper within the contemporary resurgence of scientific interest in psychedelics, noting historical and indigenous use and two earlier waves of research in the mid-20th century. They highlight the longstanding idea that the psychological and environmental context—summarised by the terms 'set' (the individual’s mindset, expectations and pre-existing psychological state) and 'setting' (the physical and social environment)—shapes acute psychedelic experiences and their longer-term consequences. The authors argue that insufficient appreciation of context may help explain both rare instances of harm and the enduring stigma around these drugs, whereas careful attention to context appears to have accompanied promising outcomes in modern clinical trials. This article sets out to articulate and defend the central hypothesis that the therapeutic action of psychedelics is fundamentally reliant on context. It reviews historical and contemporary evidence, reports preliminary empirical observations from the authors’ own work (including laboratory manipulations and a large web-based survey), and proposes research designs to test context–drug interactions. The piece serves as a conceptual and practical call to foreground extra‑pharmacological factors in future research, clinical implementation and policy discussions about psychedelic medicine.

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Study Details

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Safety, tolerability, pharmacokinetics, and subjective effects of 50, 75, and 100 µg LSD in healthy participants within a novel intervention paradigm: A proof-of-concept study

Family, N., Hendricks, P. S., Williams, L. T. J. et al. · Journal of Psychopharmacology (2022)

Presence, Trust, and Empathy: Preferred Characteristics of Psychedelic Carers

Thal, S., Engels, L. B., Bright, S. J. · Journal of Humanistic Psychology (2022)

Virtual Reality as a Moderator of Psychedelic-Assisted Psychotherapy

Sekula, A. D., Downey, L., Puspanathan, P. · Frontiers in Psychology (2022)

19 cited
Beating Pain with Psychedelics: Matter over Mind?

Elman, I., Borsook, D., Pustilink, A. · Neuroscience and Biobehavioral Reviews (2022)

Exploring protective associations between the use of classic psychedelics and cocaine use disorder: a population-based survey study

Jones, G. M., Nock, M. K. · Scientific Reports (2022)

Psychedelic Therapy's Transdiagnostic Effects: A Research Domain Criteria (RDoC) Perspective

Dursun, S. M., Kelly, J. R., Gillan, C. M. et al. · Frontiers in Psychiatry (2021)

Right-Wing Psychedelia: Case Studies in Cultural Plasticity and Political Pluripotency

Pace, B. A., Devenot, N. · Frontiers in Psychology (2021)

A Spectrum of Selves Reinforced in Multilevel Coherence: A Contextual Behavioural Response to the Challenges of Psychedelic-Assisted Therapy Development

Whitfield, H. J. · Frontiers in Psychiatry (2021)

Microevidence for microdosing with psilocybin mushrooms: a double-blind placebo-controlled study of subjective effects, behavior, creativity, perception, cognition, and brain activity

Cavanna, F., Muller, S., de la Fuente, L. A. et al. · Translational Psychiatry (2021)

5 cited
Ketamine as a Treatment for Anorexia Nervosa: A Narrative Review

Keeler, J. L., Treasure, J., Juruena, M. F. et al. · Nutrients (2021)

Psychedelic experience dose-dependently modulated by cannabis: results of a prospective online survey

Kuc, J., Kettner, H., Rosas, F. E. et al. · Psychopharmacology (2021)

Translating Psychedelic Therapies From Clinical Trials to Community Clinics: Building Bridges and Addressing Potential Challenges Ahead

Williams, M. L., Korevaar, D., Harvey, R. et al. · Frontiers in Psychiatry (2021)

16 cited
Psilocybin in the treatment of anorexia nervosa: The English transition of a French 1959 case study

Verroust, V., Zafar, R., Spriggs, M. J. · Annales Médico-Psychologiques (2021)

Perspectives on psychedelic treatment and research in eating disorders: a web-based questionnaire study of people with eating disorders

Harding, F., Seynaeve, M., Keeler, J. et al. · Journal of Integrative Neuroscience (2021)

Novel Treatment Approaches for Substance Use Disorders: Therapeutic Use of Psychedelics and the Role of Psychotherapy

Johnson, M. W., Gründer, G., Betzler, F. et al. · Current Addiction Reports (2021)

Psychedelics, sociality, and human evolution

Rodríguez Arce, J. M., Winkelman, M. J. · Frontiers in Psychology (2021)

Do Psychedelics Change Beliefs?

McGovern, H., Leptourgos, P., Hutchinson, B. et al. · Psyarxiv (2021)

Attitudes and Beliefs about the Therapeutic Use of Psychedelic Drugs among Psychologists in the United States

Davis, A. K., Agin-Liebes, G. I., España, M. et al. · Journal of Psychoactive Drugs (2021)

On Revelations and Revolutions: Drinking Ayahuasca Among Palestinians Under Israeli Occupation

Roseman, L., Karkabi, N. · Frontiers in Psychology (2021)

This Is Something That Changed My Life: A Qualitative Study of Patients' Experiences in a Clinical Trial of Ketamine Treatment for Alcohol Use Disorders

Mollaahmetoglu, O. M., Keeler, J., Ashbullby, K. J. et al. · Frontiers in Psychiatry (2021)

The socialization of hallucinations. Cultural priors, social interactions and contextual factors in the use of psychedelics

Dupuis, D. · Transcultural Psychiatry (2021)

69 cited
Moral Psychopharmacology Needs Moral Inquiry: The Case of Psychedelics

Earp, B. D., Repantis, D., Langlitz, N. et al. · Frontiers in Psychiatry (2021)

28 cited
Turn on, Tune in, and Drop out: Predictors of Attrition in a Prospective Observational Cohort Study on Psychedelic Use

Hübner, S., Haijen, E. C. H. M., Kaelen, M. et al. · Journal of Medical Internet Research (2021)

Safer Tripping: Serotonergic Psychedelics and Drug Checking. Submission and Detection Rates, Potential Harms, and Challenges for Drug Analysis

Hirschfeld, T., Smit-Rigter, L., Van Der Gouwe, D. et al. · Current Addiction Reports (2021)

Does psychedelic therapy have a transdiagnostic action and prophylactic potential?

Kočárová, C., Horacek, J., Carhart-Harris, R. L. · Frontiers in Psychiatry (2021)

73 cited
Using Psychedelics With Therapeutic Intent Is Associated With Lower Shame and Complex Trauma Symptoms in Adults With Histories of Child Maltreatment

Healy, C. J., Lee, K. A. · Chronic Stress (2021)

Sustained, multifaceted improvements in mental well-being following psychedelic experiences in a prospective opportunity sample

Mans, K., Kettner, H., Erritzoe, D. et al. · Frontiers in Psychiatry (2021)

Psychedelics alter metaphysical beliefs

Timmermann, C., Kettner, H., Letheby, C. et al. · Scientific Reports (2021)

Protocol for Outcome Evaluation of Ayahuasca-Assisted Addiction Treatment: The Case of Takiwasi Center

Rush, B., Marcus, O., García, S. et al. · Frontiers in Pharmacology (2021)

19 cited
Relational Processes in Ayahuasca Groups of Palestinians and Israelis

Roseman, L., Ron, Y., Saca, A. et al. · Frontiers in Pharmacology (2021)

30 cited
From hallucinations to synaesthesia: a circular inference account of unimodal and multimodal erroneous percepts in clinical and drug-induced psychosis

Leptourgos, P., Bouttier, V., Denève, S. et al. · Psyarxiv (2021)

12 cited
The Potential Role of Psychedelic Drugs in Mental Health Care of the Future

Gründer, G., Jungaberle, H., Gründer, G. · Pharmacopsychiatry (2021)

Challenges in translational research: MDMA in the laboratory versus therapeutic settings

de Wit, H., Bershad, A. K., Grob, C. S. · Journal of Psychopharmacology (2021)

Set and Setting in the Santo Daime

Hartogsohn, I. · Frontiers in Pharmacology (2021)

A continuum hypothesis of psychotomimetic rapid antidepressants

Haarsma, J., Harmer, C. J., Tamm, S. · Brain and Neuroscience Advances (2021)

Trial of Psilocybin versus Escitalopram for Depression

Carhart-Harris, R. L., Giribaldi, B., Watts, R. et al. · New England Journal of Medicine (2021)

927 cited
Increased sensitivity to strong perturbations in a whole-brain model of LSD

Jobst, B. M., Atasoy, S., Ponce-Alvarez, A. et al. · NeuroImage (2021)

A qualitative and quantitative account of patient’s experiences of ketamine and its antidepressant properties

Sumner, R. L., Chacko, E., Mcmillan, R. et al. · Journal of Psychopharmacology (2021)

51 cited
Prediction of MDMA response in healthy humans: a pooled analysis of placebo-controlled studies

Studerus, E., Vizeli, P., Harder, S. et al. · Journal of Psychopharmacology (2021)

50 cited
Psychedelic Communitas: Intersubjective experience during psychedelic group sessions predicts enduring changes in psychological wellbeing and social connectedness

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

157 cited
Baseline power of theta oscillations predicts mystical-type experiences induced by DMT in a natural setting

Tagliazucchi, E., Zamberlan, F., Cavanna, F. et al. · Frontiers in Psychiatry (2021)

On the Relationship between Classic Psychedelics and Suicidality: A Systematic Review

Zeifman, R. J., Singhal, N., Breslow, L. et al. · ACS Pharmacology and Translational Science (2021)

Blinding and Expectancy Confounds in Psychedelic Randomised Controlled Trials

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

Predicting Reactions to Psychedelic Drugs: A Systematic Review of States and Traits Related to Acute Drug Effects

Aday, J. S., Davis, A. K., Mitzkovitz, C. M. et al. · ACS Pharmacology and Translational Science (2021)

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

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

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

Kaertner, L. S., Steinborn, M. B., Kettner, H. et al. · Scientific Reports (2021)

112 cited
The History of Psychedelics in Psychiatry

Nichols, D. E., Walter, H. · Pharmacopsychiatry (2020)

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)

Hallucinogens in Mental Health: Preclinical and Clinical Studies on LSD, Psilocybin, MDMA, and Ketamine

Hibicke, M., Gobbi, G. · Journal of Neuroscience (2020)

145 cited
Pivotal Mental States

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

Post-acute psychological effects of classical serotonergic psychedelics: A systematic review and meta-analysis

Goldberg, S. B., Shechet, B., Nicholas, C. R. et al. · Psychological Medicine (2020)

Hallucinations Under Psychedelics and in the Schizophrenia Spectrum: An Interdisciplinary and Multiscale Comparison

Leptourgos, P., Fortier-Davy, M., Carhart-Harris, R. L. et al. · Schizophrenia Bulletin (2020)

Are Psychedelics Something New in Teaching Psychopharmacology?

Louie, A. K., Beresin, E. V., Coverdale, J. et al. · Academic Psychiatry (2020)

Psychedelic Treatments for Psychiatric Disorders: A Systematic Review and Thematic Synthesis of Patient Experiences in Qualitative Studies

Breeksema, J. J., Niemeijer, A. R., Krediet, E. et al. · CNS Drugs (2020)

Psychedelics and virtual reality: parallels and applications

Aday, J. S., Davoli, C. C., Bloesch, E. K. · Therapeutic Advances in Psychopharmacology (2020)

Post-Psychedelic Reductions in Experiential Avoidance Are Associated With Decreases in Depression Severity and Suicidal Ideation

Zeifman, R. J., Wagner, A. C., Watts, R. et al. · Frontiers in Psychiatry (2020)

82 cited
LSD-induced increases in social adaptation to opinions similar to one's own are associated with stimulation of serotonin receptors

Schilbach, L., Stämpfli, P., Vollenweider, F. X. et al. · Scientific Reports (2020)

A potential role for psilocybin in the treatment of obsessive-compulsive disorder

Jacobs, E. · Journal of Psychedelic Studies (2020)

The Viability of Microdosing Psychedelics as a Strategy to Enhance Cognition and Well-being - An Early Review

Bornemann, J. · Journal of Psychoactive Drugs (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
Dissolving the self: Active inference, psychedelics, and ego-dissolution

Deane, G. · Philosophy and the Mind Sciences (2020)

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)

Tripping on nothing: placebo psychedelics and contextual factors

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

Natural Psychoplastogens As Antidepressant Agents

Benko, J., Vranková, S. · Molecules (2020)

Learning to Let Go: A Cognitive-Behavioral Model of How Psychedelic Therapy Promotes Acceptance

Wolff, M., Evens, R., Mertens, L. J. et al. · Frontiers in Psychiatry (2020)

Therapeutic Use of LSD in Psychiatry: A Systematic Review of Randomized-Controlled Clinical Trials

Fuentes, J. J., Fonseca, F., Elices, M. et al. · Frontiers in Psychiatry (2020)

Therapeutic mechanisms of psilocybin: Changes in amygdala and prefrontal functional connectivity during emotional processing after psilocybin for treatment-resistant depression

Mertens, L. J., Wall, M. B., Roseman, L. et al. · Journal of Psychopharmacology (2020)

155 cited
The use of the psychological flexibility model to support psychedelic assisted therapy

Watts, R., Luoma, J. B. · 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
Prospective examination of synthetic 5-methoxy-N,N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment

Uthaug, M. V., Lancelotta, R., Szabo, A. et al. · Psychopharmacology (2019)

86 cited
Embedding existential psychology within psychedelic science: reduced death anxiety as a mediator of the therapeutic effects of psychedelics.

Moreton, S. G., Szalla, L., Menzies, R. E. et al. · Psychopharmacology (2019)

47 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)

Emotional breakthrough and psychedelics: validation of the emotional breakthrough inventory

Roseman, L., Haijen, E. C. H. M., Idialu-Ikato, K. et al. · Journal of Psychopharmacology (2019)

Motives and side-effects of microdosing with psychedelics among users

Hutten, N. P. W., Mason, N. L., Dolder, P. C. et al. · International Journal of Neuropsychopharmacology (2019)

Cessation and reduction in alcohol consumption and misuse after psychedelic use

Garcia-Romeu, A., Davis, A. K., Fire Erowid et al. · Journal of Psychopharmacology (2019)

211 cited
Psychedelics as a treatment for disorders of consciousness

Scott, G., Carhart-Harris, R. L. · Neuroscience of Consciousness (2019)

Ayahuasca and Public Health: Health Status, Psychosocial Well-Being, Lifestyle, and Coping Strategies in a Large Sample of Ritual Ayahuasca Users

Ona, G., Kohek, M., Massaguer, T. et al. · Journal of Psychoactive Drugs (2019)

Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels

Madsen, M. K., Fisher, P. M., Burmester, D. et al. · Neuropsychopharmacology (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)

Predicting responses to psychedelics: a prospective study

Haijen, E. C. H. M., Kaelen, M., Roseman, L. et al. · Frontiers in Pharmacology (2018)

339 cited
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
Whole-brain multimodal neuroimaging model using serotonin receptor maps explains non-linear functional effects of LSD

Deco, G., Cruzat, J., Cabral, J. et al. · Current Biology (2018)

Psychedelics, meditation, and self-consciousness

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

DMT models the near-death experience

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

The entropic brain - revisited

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

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