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Psychedelics and the essential importance of context
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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In the citing paper
“The psychedelic experience comes with an increased sensitivity to internal and external stimuli.”
In the citing paper
“It follows that the general context of psychedelic administration fundamentally shapes drug response and hence safety, as well as potentially therapeutic efficacy [9, 88].”
In the citing paper
“This highlights the frequent clinical observation that patients may need particularly intensive supportive care during, as well as after psychedelic experiences (Carhart-Harris et al., 2018).”
From Naturalistic psychedelic therapy: The role of relaxation and subjective drug effects in antidepressant response (2024) · cites this paper as Carhart-Harris et al., 2018
In the citing paper
“Psychedelic experiences vary depending not only on individual characteristics, such as health status, but also on the type of preparation available, intentions agreed upon before the experience, and the environment in which the experience takes place (Carhart-Harris et al., 2018; Golden et al., 2022).”
From Naturalistic psychedelic therapy: The role of relaxation and subjective drug effects in antidepressant response (2024) · cites this paper as Carhart-Harris et al., 2018
In the citing paper
“It has long been recognised that both set (the mindset of the participant, including their expectations, assumptions and intentions for the psychedelic experience, as well as stable variables such as personality and the presence of psychopathology) and setting (the physical, social and cultural environment in which the experience occurs) have the potential to greatly impact the outcomes of the Psy”
From The psychological processes of classic psychedelics in the treatment of depression: a systematic review protocol (2022) · cites this paper as [43]
In the citing paper
“Contextual factors, such as the environment in which the experience takes place (setting), the mindset of the individual (set), and the support available after the experience (integration and setting), have a huge impact on the effects of psychedelics (85–88).”
From Potential therapeutic effects of an ayahuasca-inspired N,N-DMT and harmine formulation: a controlled trial in healthy subjects (2024) · cites this paper as [85]
In the citing paper
“Differences in set and setting, which involve factors such as opportunity for preparation, guidance and integration by a trained guide, have been extensively shown to greatly influence the acute psychedelic experience (136, 137).”
From Examining the Potential Synergistic Effects Between Mindfulness Training and Psychedelic-Assisted Therapy (2021) · cites this paper as [136]
In the citing paper
“Changes in the ratings of subjective measures that were observed in the present study are not necessarily related to a pharmacological effect of 5-MeO-DMT, but could have resulted from uncontrolled variables such as response expectancy of the participants prior to and after the session or the set and setting of drug administration (Carhart-Harris et al. 2018; Hartogsohn 2016).”
From Prospective examination of synthetic 5-methoxy-N,N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment (2020) · cites this paper as Carhart-Harris et al. 2018
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“Therapeutic alliance is already known to be a major predictor of response in mental healthcare (Kazdin, 2007) and if the present thesis is correct, its influence is likely to be greater still in the context of psychedelics (see Carhart-Harris and Nutt, 2017).”
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“Indirect support for this may be found in the not inconsiderable (before-versus-after treatment) effects sizes observed in control conditions in recent double-blind randomised control trials of psilocybin for end-of-life distress, for example (Griffiths et al., 2016).”
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Metadata
- Authors
- Carhart-Harris, R. L., Roseman, L., Haijen, E., Erritzoe, D., Watts, R., Branchi, I., & Kaelen, M.
- Affiliations
- Imperial College London (GB)
- Psychedelic Research Group, Neuropsychopharmacology Unit, Centre for Psychiatry, Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK
- Istituto Superiore di Sanità (IT)
- Corresponding author
- Carhart-Harris, Robin L
- Venue
- Journal of Psychopharmacology
- Publisher
- SAGE Publications
- Published
- 2018-02-15
- Volume
- 32
- Issue
- 7
- Pages
- 725-731
- ISSN
- 0269-8811 (ISSN-L)
- 1461-7285
- OpenAlex
- W2788854095
- Cited by
- 657
- References
- 62
- Citations by year
- 2026: 83 · 2025: 102 · 2024: 112 · 2023: 105 · 2022: 97 · 2021: 72 · 2020: 49 · 2019: 24 · 2018: 13
- FWCI
- 46.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute for Health and Care Research (ACF-2013-21-501)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
- Social Sciences › Health › Religion, Spirituality, and Psychology
- Keywords
- psychedelics, set and setting, context effects, 5-HT2A receptor agonism, neuroplasticity, long-term mental health outcomes, harm reduction
- MeSH terms
- Animals, Clinical Trials as Topic, Hallucinogens, Humans, Research Design, Serotonin 5-HT2 Receptor Agonists
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