The Importance of Set and Setting in Psychedelic Therapy

The context of the psychedelic experience plays a critical role in determining positive outcomes for patients.


In a 2018 review and opinion piece, “Psychedelics and the essential importance of context”, Dr. Robin Carhart-Harris and his research team propose good practices for psychedelic research and suggest a new roadmap for optimizing patient treatment models.1 They also discuss the unhelpful stigma that follows psychedelic drugs, how to maximize benefits and minimize harms in the therapeutic use of psychedelics, and lay out the evidence that supports the critical importance of set and setting in psychedelic therapy.

Dr. Robin Carhart-Harris is the head of the Imperial Psychedelic Research Group in the Department of Medicine at Imperial College London. He is one of the premier researchers in the world who are studying the therapeutic benefits of psychedelics (particularly psilocybin and LSD) and how they work in the brain.

In this article, Dr. Carthart-Harris introduces the term ‘context’ as an umbrella term for ‘set and setting’ used in the current psychedelic treatment model. Context is used as a general term but can include environmental and psychological aspects related to a psychedelic experience.

Context and the 5-HT2A Receptor

Scientists understand that psychedelic effects in the brain happen when compounds like LSD and psilocin (the metabolically active drug produced in the body by prodrug psilocybin) bind to the serotonin 5-HT2A receptor. These psychedelic compounds don’t block receptor function (antagonism); they cause a different physiological response than serotonin does (agonism), which is the psychedelic experience.

Research has also demonstrated that psilocin promotes structural and functional neuroplasticity in the brain as does serotonin.2 Dr. Carhart-Harris proposes in the paper that the pro-plasticity effects of serotonin and the agonism of the 5-HT2A receptor in particular, “renders the psychedelic experience exceptionally sensitive to context.” He goes on to say;

Insufficient appreciation of this principle may lead to risky and potentially harmful applications of psychedelics – which could jeopardise the healthy progress of psychedelic research – as well as the mental health of anyone who misuses these drugs.1

A New Psychedelic Study Design Using Context

Dr. Carhart-Harris points out that research into isolating and understanding key variables relating to context and the psychedelic experience has not been done.1 He explains that this is probably due to the raising of ethical and practical challenges if study patients were given sub-optimal context combined with a full-dose psychedelic experience. Imagine the issues that would arise with treatment groups subjected to an adverse or negative context for comparison.

One solution to these practical and ethical issues could lie in a study design using only low doses of a psychedelic (microdosing). In this case, the use of sub-optimal context is feasible and less controversial because, as Dr. Carhart-Harris explains, it is unclear how important context is in microdosing.1 Therefore, designing a controlled study to test the impact of context on microdosing outcomes would be valuable as a first step, he says.

Variables Affecting the Outcome of Psychedelic Experiences is a website run by the Psychedelic Research Group at Imperial College London. The site launched on April 19, 2018 (known formally as Bicycle Day), the anniversary date of Albert Hofmann‘s first LSD trip and subsequent experience riding his bicycle home from work while still under the influence.

People planning on taking a psychedelic drug can sign up on the website to receive surveys at strategic time points before and after their experience. By gathering this type of data, the research team gained valuable insight into how people prepared for their psychedelic experience (the context) and what short and long-term experiences they had. In describing the purpose of the surveys, Dr. Carhart-Harris said, “In this way we sought to test the process of change related to the psychedelic experience, assessing a large number of potentially salient factors and their relevant contributions to acute and longer-term outcomes in a large sample.”

The paper published by Dr. Carhart-Harris and his team details some of the findings they have made from the data collected in the surveys, promising a complete account of the results in a forthcoming publication. Two of the key findings they shared were:1

  • The following factors were all predictive for having a ‘peak’ psychedelic experience (synonymous with a ‘mystical’ experience):
    • Feeling ready to ‘surrender’ to the experience.
    • Having a clear intention for the experience.
    • Having the experience in a therapeutic setting.
    • Taking a higher dose.
  • All of the factors above plus “being in the company of well-trusted individuals” was protective against a ‘challenging’ psychological experience (some call it a ‘bad trip’).


With the encouraging results from psychedelic therapy trials and growing interest in how psychedelics work, Dr. Carhart-Harris and his research team point out the importance of context to the psychedelic experience. He cautions that moving too quickly to establish treatment programs before the role of context is better understood could be disastrous for patients and the future of psychedelic drug research. In the paper, Dr. Carhart-Harris eloquently sums up his argument saying, “For the sake of science and healthcare over politics, we must hope that the future be [sic] allowed to properly test and tell.”

Barb Bauer Headshot

Barb is the former Editor and one of the founders of Psychedelic Science Review. She is currently a contributing writer. Her goal is making accurate and concise psychedelic science research assessable so that researchers and private citizens can make informed decisions.


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  1. Carhart-Harris RL, Roseman L, Haijen E, et al. Psychedelics and the essential importance of context. J Psychopharmacol (Oxford). 2018;32(7):725-731. doi:10.1177/0269881118754710
  2. Branchi I. The double edged sword of neural plasticity: Increasing serotonin levels leads to both greater vulnerability to depression and improved capacity to recover. Psychoneuroendocrinology. 2011;36(3):339-351. doi:10.1016/j.psyneuen.2010.08.011