This commentary paper (pre-print) examines four common factors of psychedelic (healing) experiences and how those factors contribute, next to the molecules themselves, to the therapeutic effects. The factors are: 1) therapeutic relationship/alliance, 2) setting, 3) rationale/set, and 4) ritual.
Abstract
“Psychedelic-assisted treatment is at first glance markedly different in structure and approach from mainstream forms of psychotherapy in the West. A major criticism of clinical psychedelic research rests on the difficulty of executing placebo-controlled studies and distinguishing drug effects from those of the psychotherapeutic container in which psychedelics are typically presented. Detractors also tend to find fault in spiritual or mystical themes that often arise in the context of psychedelic use. Common factors theory of psychotherapy is a useful and extensively studied framework that can help make sense of these issues, and has much to contribute to our understanding of contextual effects that are often discussed in psychedelic literature as “set and setting.” In this paper we examine four major contextual “common factors” shared by various healing traditions-1) the therapeutic relationship, 2) the healing setting, 3) the rationale, conceptual scheme, or myth, and 4) the ritual. We explain how these factors show up in psychedelic-assisted treatment and how they may contribute to therapeutic effects. Lastly, we discuss implications of these factors for the concept of placebo, and for future research.”
Authors: Natalie Gukasyan & Sandeep Nayak
Notes
This paper offers more contextual information, or explanations, for other papers that investigate the placebo (-like) effects of psychedelics (set & setting) such as Uthaug and colleagues (2021).
Summary
ABSTRACT
Psychedelic-assisted treatment is markedly different in structure and approach from mainstream forms of psychotherapy in the West. Common factors theory of psychotherapy can help make sense of these issues, and has much to contribute to our understanding of contextual effects. The past two decades have seen a remarkable revival in scientific and public interest in psychedelics. This mini-review will highlight some relevant points that may help bridge the gap between psychedelic-assisted treatments, indigenous healing practices, and present-day mental healthcare in the West. Psychedelic drugs are those whose effects are mediated primarily by serotonin 2A (5-HT2A) receptor agonism. These include psilocybin, LSD, and DMT. Psychedelics can produce profound changes in perception and mood, and may even be associated with enduring changes in personality traits. Psilocybin, a plant brew containing DMT, has been shown to relieve symptoms of depression and anxiety in individuals with advanced cancer, and in individuals with alcohol use disorder. Studies of psychedelics have shown positive results across a wide range of diagnoses, but there is a lack of placebo-controlled conditions and a general attitude toward psychedelics in the West that suggests a dangerous potential for abuse with little to no clinical benefit.
Set and setting theory posits that psychological, environmental, and social factors can affect the psychedelic experience. This theory has been cited as an explanation for varied and contradictory reports of drug effects in early psychedelic research. In typical drug studies, factors known to boost placebo response are actively minimized. However, standard practices in psychedelic assisted treatment are at odds with the goal of minimizing placebo response. A number of similarities exist between psychotherapy and psychedelic-assisted treatment, including a substantial reliance on contextual factors. Both seem to provide benefit for a wide range of mental health conditions.
Psychotherapy can be attributed to placebo effects, and the same claim has been made of psychedelics. Common factors theory can be used to explain the role of contextual or “common” factors in psychotherapy, and can inform future research and understanding across cultures.
Psychotherapy is a form of healing that has existed from the earliest days of human history and likely prehistory. It was developed in 18th and 19th century Europe by Sigmund Freud and his contemporaries and intellectual heirs. Although conflicting theories exist about why any given model of psychotherapy should work, it is rare that one form has been demonstrated to be significantly more effective than another.
Frank described psychotherapy as a salve for demoralization, and suggested that successful psychotherapies exert their effects via four broad features: 1) an emotionally charged, confiding relationship with a helping person, 2) a healing setting, 3) a rationale, conceptual scheme, or myth, and 4) a ritual.
Decades of research have shown that the therapeutic relationship is more important than a therapist’s adherence to any specialized technique. The most researched component of the therapeutic relationship is the therapeutic alliance, which is highly correlated with outcomes.
The interpersonal affective bond with the patient is distinct from the alliance and is characterized by empathy, congruence, and positive regard.
Researchers found that perceived therapist empathy was highly predictive of therapeutic benefit. Similarly, perceived positive regard was positively correlated with outcomes. Individual characteristics of therapist and patient can affect outcomes. For example, patients with lower neuroticism and higher agreeableness have better outcomes following CBT for depression, but this relationship may actually be mediated via therapeutic alliance. Participants in psychedelic-assisted treatment typically have the support of two clinicians during preparatory, dosing, and follow-up sessions. This may boost expectancy and introduce a novel complicating factor, the rapport and dynamic between the two therapists themselves.
Patients with depressed or anxious moods were more likely to report negative experiences during drug administration, and higher levels of trait neuroticism were associated with higher likelihood of challenging experiences.
Frank highlighted the importance of a specialized environment for healing. Studies have shown that certain factors such as décor, furniture, lighting, amount of space, olfactory and sound cues can affect patient expectation and credibility.
The environment used in clinical psychedelic research is rather idiosyncratic, and often includes relics from various cultures and faith traditions. These cues may have substantial effects on expectancy, signaling to patients that the procedure that takes place in this setting is particularly powerful or special. Contemporary research on setting in psychedelics has included a prospective analysis of contextual factors in naturalistic use of psychedelics. The authors reported that wellbeing was positively associated with “setting” two weeks after drug ingestion.
According to Frank, the conceptual scheme behind a given psychotherapy inspires expectations of help, arouses strong emotional responses, and enhances a sense of mastery or self-efficacy. The actual contents or scientific validity of the myth seem to be less important to producing positive outcomes. Frank advises that therapeutic procedures should not be confused with their functions, which are to establish the therapeutic relationship and demonstrate expertise.
Scientists are uncovering information about the objective neurobiological effects of psychedelics, and are attempting to explain these effects with images like the one produced by Petri et al. (2014). However, whether functional connectivity adequately explains the acute or enduring effects of psychedelics is yet to be determined. Psychedelics produce subjective experiences that some people interpret as deeply meaningful, emotionally rich, or even “mystical”. These experiences may have a dose-dependent relationship with measures of “mystical” qualities of the experience, with greater mystical qualities being correlated with better outcomes.
The ritual is a symbolic extension of the myth or rationale that is usually undertaken together by healer and patient. The ritual provides a key opportunity for practice and may strengthen self-confidence and mastery.
Therapy can enhance morale by providing new experiences that show patients new ways of looking at themselves and their problems. A 63-year-old woman was treated for espanto in a village in Guatemala. After a 12-hour ritual, the healer broke eggs into a bowl of water and declared his efforts successful; the woman fell into a deep sleep and showed marked improvement. The drug dosing day ritual in psychedelic treatment involves the patient being greeted by her session guides and being given a capsule to take with water.
Soon after, the patient is guided to lay down on the couch with eyeshades and headphones playing a program of music, and encouraged to draw her focus inward. During the psychedelic experience, blood pressure and heart rate are monitored intermittently, and guides are available to provide reassurance and physical forms of support as needed. Some participants have dysphoric or “challenging” experiences, but ultimately even a challenging experience can be associated with overall positive outcomes.
In psychotherapy, common factors such as the healing relationship and various other cues that affect patient expectation are central to the problem of designing gold-standard randomized, placebo-controlled double-blind clinical research.
Psychotherapy is a form of alternative medicine, and the placebo effect is produced by factors other than the physical properties of the treatment. Therefore, the effect of psychotherapy is ipso facto a placebo effect, and psychotherapy is ipso facto a placebo.
Blinding and allegiance pose additional problems with respect to working in the placebo-controlled framework in psychotherapy. Allegiance may be a substantial problem for disentangling the true effects of psychedelics from those of contextual factors.
We identified several candidate factors that may explain a significant portion of “set and setting” effects in psychedelic-assisted treatment. These factors include expectancy and credibility effects, the working alliance, and various other factors of the therapeutic relationship.
The Working Alliance Inventory (WAI) and Barrett-Lennard Relationship Inventory (BLRI) are validated scales that could be readily applied to psychedelic clinical trials. The Credibility and Expectancy Questionnaire (CEQ) is another widely used and applicable measure that could be used for expectancy. Common factors theory suggests that psychedelic trials could be improved by manipulating expectancy effects, plausible treatment rationales, and ritual surrounding drug administration. However, given the dependence of psychedelic drugs on context, some manipulations may be unethical.
Researchers should be vigilant about the effects of media attention on psychedelics, and should measure common factors in psychedelic trials.
The current psychedelic treatment research model involves running one study participant at a time, and so group factors such as cohesion are not relevant. However, alternative models involving group preparation, dosing or integration sessions may begin to look more attractive. Psychedelic treatment has much in common with established forms of mental healthcare, and may help us understand how to harness the “active psychological ingredients” of psychotherapy, set and setting, and placebo effects.
Funding
A meta-analysis of component studies in counseling and psychotherapy found that personality and differential treatment response in major depression were associated with personality traits, psilocybin use, and therapist sex pairing. A proof-of-concept study of psilocybin-assisted psychotherapy for alcohol dependence was published in 2015, and clinical interpretations of patient experience were published in 2018 in Frontiers in pharmacology.
Psychedelics, context, and the alliance in adult psychotherapy: A meta-analytic synthesis. Cuijpers, P., Driessen, E., Hollon, S. D., van Oppen, P., Barth, J., & Andersson, G. (2012).
Positive regard and affirmation are important in psychotherapy. Frost, N. D., Laska, K. M., & Wampold, B. E. (2014) reviewed the evidence for present-centered therapy as a treatment for posttraumatic stress disorder.
Psilocybin decreases depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial.
A prospective study of psychedelic responses found that set and setting were important factors in predicting responses.
Hartogsohn, I., Heinonen, E., Lindfors, O., Laaksonen, M. A., & Knekt, P. (2017). Constructing drug effects: a history of set and setting.
LSD enhances the emotional response to music via changes in parahippocampal connectivity, according to Kaelen, Barrett, Roseman, Lorenz, Family, N., Bolstridge, M., Carhart-Harris, R. L., and others. Kolden, G., et al. (2019), Congruence/Genuineness, Kirsch, I., Wampold, B., & Kelley, J. M. (2016). Controlling for the placebo effect in psychotherapy: Noble quest or tilting at windmills?, Lambert, M. J., & Barley, D. E. (2001), and Leary, T. (1961). MacLean, Johnson, Griffiths, & Metzner (2011) found that people who experienced mystical experiences with psilocybin had higher openness in their personality.
Orlinsky, D. E., Howard, K. I., Petri, G., Expert, P., Turkheimer, F., Carhart-Harris, R., Nutt, D., Hellyer, P. J., & Vaccarino, F. (2014) reviewed the theory of psychotherapy and the research on psychedelics and religious experiences.
Author biographical notes
Natalie Gukasyan, M.D. is a post-doctoral fellow at Johns Hopkins University, and is currently working on a study of psilocybin-assisted treatment for anorexia nervosa.
Sandeep M. Nayak, M.D. is a physician interested in addiction, behavior change, mood disorders and clinical applications of psychedelic-facilitated treatment.
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