Feel unwell? You take some medicine; you feel better. Although this is how most traditional prescription drugs tend to work, the transformative effects of psychedelics go far beyond the dose itself. The outcome of the psychedelic experience is almost entirely dependent on who you are as you enter the trip and how you spend the experience – better known as the “set and setting”. It is an integral feature of the experience and the basis of harm reduction, but how exactly does the set and setting of a psychedelic trip predict who we will be on the other side? What is set and setting? The idea that context can change a psychedelic experience has been recognised for centuries. Take ancient ayahuasca rituals, for instance. Indigenous shamans have long been known to incorporate songs, smoke, and whistles to shape the user's trip and facilitate spiritual healing. The concept of set and setting was first introduced to Western medicine in the ‘50s by Alfred Matthew Hubbard, the “Johnny Appleseed of LSD”, who suggested that LSD’s therapeutic results could be manipulated by the surrounding environment. The term “set and setting” was then coined by Timothy Leary, first published in a 1961 paper. “Set” refers to the mindset of the individual when taking psychedelics. It encompasses their personality, mood, religious or spiritual beliefs, and expectations – their mental state. Whether you’re stressed, angry, or feeling carefree, this will ultimately predict what the trip will be like. “Setting” is an individual’s external environment. It can be physical – who you’re with, where you are, what surrounds you, the smells, sounds, weather, and so on – or it can be influenced by more cultural and societal factors. Our social environment, whether political, racial, or religious, can also shift how we perceive the psychedelic experience. Beyond individual experience, there is also the idea of “collective set and setting,” detailed by Dr Ido Hartoghson in his 2013 paper. This is where the wider society can shape a psychedelic experience. “Different societies in different times in history would have different set-and-setting conditions,” Hartoghson writes. A particularly prevalent example of this was the use of LSD in 1960s America, where psychedelics fuelled a collective countercultural force. Effectively, set and setting is the reason why you could take the same psychedelic drug, at the same dose, in two completely different places and have two wildly different experiences. How context shapes a trip Our psychological mindset and our position in society – our day-to-day ‘set and setting’ – act as lenses through which we perceive the world. Our perception of reality becomes altered under the influence of a psychedelic drug, but these lenses remain in place. Set and setting, therefore, help to shape this experience. Hartoghson offered a similar analogy in his 2013 paper, where he claimed that “ acts as a mirror and magnifying glass to its user’s state of mind. If the state of that mind is anxious, LSD could easily function as an anxiety-inducing drug. If it is creative, then it could equally serve as a creativity enhancer. Should it be spiritual, then spirituality will be enhanced.” Set and setting go beyond the bounds of consciousness; your conscious mind might feel ‘ready’ for a trip, but you can never really predict what thoughts, emotions, or images will surface during the psychedelic experience. Countless subconscious factors can alter your inner and outer climate and, in turn, shape how you respond to the challenging aspects of a trip. There are, however, things a person can do to prepare for a positive trip. By journaling, setting intentions, or speaking with a therapist, you can check in with yourself and ensure that you are ‘mentally ready’. The best setting for a trip is a familiar and safe environment, surrounded by trustworthy, supportive people and with added comforts, such as calming music. For those who use psychedelics in pursuit of enjoyment, set and setting could be the difference between a positive, unforgettable experience and an anxiety-filled nightmare of a bad trip. However, in the flourishing field of psychedelic psychotherapy, someone’s entire mental state could be in the hands of their psychedelic experience. Their set and setting may, therefore, be a crucial predictor of inner healing. Set and setting: the science Classic psychedelics, such as LSD, DMT and psilocybin, activate serotonin 2A (5-HT2A) receptors in the brain. This triggers a cascade of neurobiological changes that generate a hallucinogenic state, where the brain becomes more flexible, chaotic, and disorganised. During a psychedelic trip, the brain systems involved in rigid, negative thinking are broken down. What remains can be likened to a mystical experience, a strong sense of unity that exists without the restraints of the ego. Previous psychedelic research has even established that stronger feelings of mysticism result in a better clinical outcome. In a paper published in the Journal of Psychopharmacology in 2018, Professor Robin Carhart-Harris and colleagues detailed that “5-HT2A receptor agonism and associated plasticity…renders exceptionally sensitive to context.” So if, as the paper suggests, context and intention are integral to the quality of the psychedelic experience, then it is also responsible for the intensity of mysticism and the subsequent psychological transformation. As put rather poetically by Timothy Leary in his book, The Psychedelic Experience, “Of course, the drug dose does not produce the transcendent experience. It merely acts as a chemical key – it opens the mind, frees the nervous system of its ordinary patterns and structures. The nature of the experience depends almost entirely on set and setting.” Prof Carhart-Harris and his team set out to assess just this. The researchers analysed survey data collected by the Psychedelic Survey at various points before and after using psychedelics to assess how various factors contributed to the short- and long-term outcomes of the trip. They found that the following variables were all key predictors of a mystical experience: \tFeeling ready to ‘surrender’ to the experience. \tHaving a clear intention for the experience. \tHaving the experience in a therapeutic setting. \tTaking a higher dose. All of the variables above plus “being in the company of well-trusted individuals” appeared to be protective against a bad trip. Using these findings, the paper then set out future intentions for the field of psychedelic medicine. The authors detailed how set and setting could be utilised to both reduce harm and promote psychological healing. The complexities of context in psychedelic medicine Although challenging trips are often seen as valuable experiences in the context of psychedelic therapy, harm reduction measures must also be taken to maximise the benefits and minimise the risks of the treatment and, ultimately, avoid worsening the patient’s psychological state. It is, therefore, essential that the setting is as calming for the patient as possible. So how exactly have psychedelic therapy trials created a warm, comfortable and safe environment for participants? Firstly, according to Prof Carhart-Harris’ 2018 paper, all trials have manipulated the therapeutic environment in some way, “with low lighting, carefully selected music playlists, aesthetically pleasing décor”. To ensure that the patient is in the ideal mindset, researchers provide “extensive psychological preparation” which often lasts “several hours and a number of repeat visits before and after the focal psychedelic experiences.” Finally, “patients enrolled within modern psychedelic trials typically have access to two compassionate mental health professionals.” Commonly termed “trip sitters”, these guides help to support the patient throughout the experience, as well as help them to integrate what comes up in therapy into their everyday lives. Due to the rigorous standards of testing in Western medicine, existing approaches to clinical psychiatry often overlook the fact that patients will come from diverse backgrounds, differ in their mental states, and therefore require unique treatment. However, by embracing the importance of set and setting, the practice of psychedelic therapy has the potential to transform psychiatric treatment as we know it. But if psychedelic therapy was to become mainstream, what could be improved about the way medical practitioners implement set and setting into their harm reduction measures? Since race and ethnicity heavily influence a person’s social setting, psychedelic medicine must prioritise patient and practitioner diversity. Research has shown that, in psychedelic trials between 1993 and 2018, 82.5% of participants were white. Counteracting this imbalance should be a priority, and it is essential psychedelic therapists are also well equipped to work through racial trauma. One researcher, Dr Michael Winkelman, believes that Western psychedelic medicine should take inspiration from ancient psychedelic rituals and adopt a more shamanic set and setting framework. In his 2021 paper, Winkelman proposes that psychedelic therapy should include “singing, drumming, dancing and dramatic displays” in their setting, to mimic the historic shamanic rituals. Similarly, he believes that the patient’s set should involve a more “animistic worldview,” the belief that where the natural world has properties of human consciousness. Winkelman claims that this framework would “enhance the efficacy of the therapeutic experiences”. Although there is much more to unearth about the complexities of psychedelic therapy, the concept of set and setting just goes to show that there are many variables to consider within psychedelic research. These drugs are powerful; the more we understand the factors that influence a psychedelic experience, the more we can utilise their therapeutic potential.