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.

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.”

Authors: Robin L. Carhart-Harris, Leor Roseman, Eline Haijen, David Erritzoe, Rosalind Watts, Igor Branchi & Mendel Kaelen

Summary

The therapeutic action of psychedelics is fundamentally reliant on context, both in the psychological and environmental sense. Neglect of context could render a psychedelic experience not only clinically ineffective but also potentially harmful.

Indigenous peoples have historically placed great emphasis on environmental context and psychological factors brought to the experience, and have a strong animistic belief in the plant(s) used, the guiding shaman, and the chants sung to the recipient(s).

In the 1950s and 60s, the importance of context was quickly appreciated when scientific research on psychedelics began. The terms ‘set’ and ‘setting’ were embraced by Timothy Leary, and refer to the various psychological and environmental influences on a psychedelic drug experience.

Psychedelic drugs are making waves as modern trials support their therapeutic potential. This article discusses the importance of context in relation to psychedelic use, and how a positive interaction between psychedelics and context can help minimise harms and maximise potential benefits.

In the 1950s and 1960s, therapeutic applications of LSD were impressive, with reassuring safety and promising efficacy data. In contrast, military experiments with psychedelics in the 1950s and 1960s were considerably less positive.

If the media and public opinion turn against psychedelics, as occurred in the mid to late 1960s, this could feed into a negative cultural context loop that could damage the wider therapeutic agenda.

Several recent trials have demonstrated promising outcomes with psychologically and environmentally supported psychedelics sessions for psychological distress, mood disorders and addiction.

Modern psychedelic trials typically have two compassionate mental health professionals to help prepare the patient for their upcoming experience, support them during it, and help them integrate its content and meaning afterwards. Such intensive support is unusual in conventional mental health-care services.

Psychedelics require a strong therapeutic bond between the patient and his/her guide, and this could resurrect the care element that some service-users have found lacking in current mental healthcare practice.

Recent clinical trials with psychedelics have reported significantly favourable outcomes. This suggests that favourable context has contributed significantly to these outcomes, and that this effect may be amplified by the plasticity-promoting effects of serotonin 2A receptor signalling.

In recent years, comprehensive approaches to drug action have been gaining traction in psychopharmacology. This paper argues that the same degree of emphasis needs to be placed on extra-pharmacological factors in relation to psychedelics, and that this could lead to risky and potentially harmful applications.

Few controlled studies have ever been performed to test the assumed relationship between psychedelics and context. However, studies that have been performed have found that music, positive autobiographical memory scripts and creative imagery/suggestibility all enhance the psychedelic experience.

Psychedelics increase serotonin 2A receptor signalling, which mediates cortical plasticity and an associated sensitivity to internal and external influence. This sensitivity is dependent on the level at which a given contextual factor captures and resonates with an individual’s underlying emotional and cognitive state.

The quality of an acute psychedelic experience is predictive of its longer-term effects, and a proper acknowledgement of the importance of context and experience would represent a positive paradigm shift in pharmacological care in psychiatry.

Previous research has shown that the dose of a psychedelic is a reliable predictor of the nature of the subsequent psychological response. Spatially confined neuroimaging settings can also increase the likelihood of challenging experiences with psychedelics.

Other than dose-response studies and retrospective analyses, controlled studies to isolate and test key contextual variables assumed to influence the quality of a psychedelic experience have not yet been carried out.

There has been an emerging interest in psychedelic ‘microdosing’ in recent years, with claims that it can improve mood, well-being and creative thinking.

A controlled study would add value by testing the association between serotonin 2A receptor signalling and sensitivity to context, and by back-translating positive findings from human research to non-human animals.

There may be many factors impinging on a psychedelic experience. We propose testing those elements we hold particularly strong prior hypotheses about.

Psychedelics are an anomaly among drugs of potential misuse, because people who want to have a psychedelic experience often plan ahead for it. We set up a web-based survey system to test the process of change related to a psychedelic experience.

Preliminary results show that having a clear intention for the experience, taking a higher dose, and feeling ready to ‘surrender’ to the experience are all predictive of having a ‘peak’ experience. Having a peak psychedelic experience predicts an improvement in psychological well-being 2 weeks after the experience, whereas having a challenging experience predicts a deflation of this effect. Higher doses may not strongly predict a challenging experience.

Based on additional measures included in this project, we are presently working towards resolving putative inconsistencies between our data and previous findings. We believe that challenging experiences can be therapeutically beneficial, but only if personal insight and/or an emotional catharsis follows the relevant experience(s) of psychological struggle.

In summary, this article has sought to highlight the importance of context in determining the quality of a psychedelic experience and its longer-term outcomes. A careful management of context may serve to minimise harm and maximise the therapeutic potential of psychedelics.

The future success of psychedelic medicine depends on how scientists, clinicians, investors and policy makers receive this complex, composite and paradigm-challenging treatment model. However, factoring in context may actually be a cost-saving measure due to the potential long-term duration of clinical response.