Healing, Harms, and Humility: Expanding the Scope of Psychedelic-Assisted Psychotherapy Research
Publication: American Journal of Psychiatry
“No research without therapy; no therapy without research”—John Bowlby (1)
Research into the mechanisms and therapeutic utility of psychedelic substances has increased dramatically in recent years. In clinical studies of psychiatric populations, “psychedelic medicine” has primarily been investigated as psychedelic-assisted psychotherapy (PAP), a combination treatment that comprises one or more supervised or facilitated psychedelic experiences, as well as multiple drug-free psychotherapy sessions, the content of which has varied across studies (2–4). Results of recent and future randomized controlled trials (RCTs) are likely to inform policy and practice. Hence, great care is warranted when considering and communicating the content, promises, and pitfalls of this emerging discipline, and when designing and conducting new psychedelic research (5–8). We propose that such care be rooted in a stance of epistemic humility, and a recognition that this field is still taking shape.
In critical theory, the concept of epistemic humility (from the Greek episteme, knowledge) refers to a stance in which a person—or a professional field—recognizes the limits of knowledge obtained through a particular methodology (9, 10). Epistemic humility is not merely an acknowledgement that one’s knowledge base is constrained by the evidence that is presently available (e.g., “Mechanistic research hasn’t told us everything about how PAP works—yet”). It also recognizes that any given theory of what it means to “know” something (i.e., any specific epistemology) filters what’s considered to be “evidence” in the first place. An investigator rooted in epistemic humility brings these filters into awareness and considers their cost (referred to as epistemic harm, or epistemic injustice) (6, 10). As such, deeply understood, an orientation of epistemic humility does not merely acknowledge the uncertainties, biases, and assumptions inherent in one’s heuristic; it also carries an ethical obligation to both identify and work to correct epistemic injustice. From that vantage point, in the service of rigorous and ethical PAP research, we propose that a broader range of methodologies and voices be brought to bear in the study of these compounds and treatments.
Expanding Psychotherapy Research
Therapist Factors
Trials designed to assess clinical outcomes have formed the backbone of PAP research to date. Comparative efficacy research (e.g., investigating the optimal: “type” and “dose” of psychotherapy; training and skills of session facilitators; and number and content of psychedelic experiences) will be an important area of future study. However, many other important aspects of PAP are also crucial areas to explore. For example, although PAP is delivered by one or more therapists, how therapist-specific factors contribute to clinical outcomes has not been an area of scientific inquiry. It is possible—even likely (11)—that certain practitioners are more effective than others, notwithstanding rigorous trial design and manualized treatments. Many factors might implicitly or explicitly, subtly or crudely, shape a therapist’s expectancy and practice, which may in turn affect the content, process, and outcomes of the intervention in question (11, 12). Such therapist-specific factors might include their theoretical framework and worldview, intersectional identities (and potential for matches and mismatches with those of their patients), psychospiritual orientations, personal (distant or recent) psychedelic experiences, professional credentials, and/or training lineage (including any influences from outside conventional mental health settings). Although these and related factors are also relevant to non-psychedelic (and even non-pharmacologic) therapies, they may be particularly important in PAP, given 1) the rich history of psychedelic use outside medical and research settings; and 2) the amplified relevance of suggestibility and expectancy in therapeutic outcomes (12–14).
Process Research
In addition to studying therapist-specific factors, another complement to PAP outcomes research is psychotherapy process research, which studies “what takes place between, and within, the patient and therapist during the course of their interaction” (15). What are psychedelic therapists doing—verbally and nonverbally, before, during, and after the psychedelic experience itself—to occasion these clinical outcomes? For example, diverse healing modalities converge on an aim to reshape a patient’s own attitudes and beliefs, either directly or indirectly, by way of what Frank (16) calls the “therapeutic myth,” i.e., a shared belief regarding mechanism(s) of change. What is the therapeutic myth in different models of psychedelic use, including nonmedical use? How do different contextual factors strengthen that myth, prime patients to have particular kinds of psychedelic experiences, and/or shape clinical outcomes (17, 18)? Particular attention should be paid to how the therapist frames the role of the psychedelic experience itself, e.g., is it a vehicle for spiritual insight, or a substance that enhances psychological flexibility—and are either or both of these associated with clinical improvement? This framing is a contextual factor that likely plays a crucial role in the expectancy of patients and therapists alike (19, 20).
Similar questions are relevant to the drug-free integration therapy visits that take place after the dosing session. These integration therapy sessions likely help the participant retain and/or make sense of certain details of the psychedelic experience (21, 22). Which details are highlighted, and which are forgotten or ignored? These choices could be essential for the patient’s short- and long-term gains, as the psychedelic experience itself may increase neuroplasticity (23, 24) and increase psychological flexibility (25, 26) even after the drug has been metabolized. What therapeutic processes during that time optimize outcomes while minimizing risk?
The consequences of amplified suggestibility also have both clinical and ethical implications (27–29). Indeed, the very factors making psychedelic-assisted therapies potentially powerful agents of change may render them equally powerful mediators of harm (28). Psychotherapy process research can be used to investigate how interventions with a potential for harm as well as benefit (e.g., the use of touch, or self-disclosure) are utilized safely and effectively, and how the principle of active, ongoing informed consent, central to ethical treatment in PAP, is put into practice (30–32).
Whose Voices are Included?
Epistemic harm is done when important stakeholders’ voices are left out of clinical research. Practitioners with significant PAP experience within (or even outside) the research setting may have important information about PAP that is not adequately conveyed in efficacy outcomes research, formal adverse event reporting, and/or qualitative studies that focus on the participant’s internal experience. As such, research into clinicians’ experiences, and clinical research that builds upon them, could be a crucial supplement to the current literature, and might lead to improvements in safety, therapeutic efficacy, and therapist education.
Patients, too, have critical knowledge to share. What has been helpful, and what has been harmful in their experience of PAP? Psychotherapy itself is not without risk (33), and the addition of a psychedelic may increase those risks, including but not limited to the possibility of worsening psychological distress (27, 34, 35) and/or exposure to boundary violations (27) by unethical practitioners exploiting a patient’s enhanced trust (36) and/or suggestibility (37, 38) during and after a psychedelic experience. Amplifying the voices of patients who have been harmed by PAP, within or outside the research setting, may impact the risk-benefit assessment for a particular intervention; the informed consent process; therapist training and technique; and PAP policy and regulation more broadly, including the development and reinforcement of best practices.
In addition to patients and clinicians operating in a Western mental health treatment paradigm, other silent stakeholders may include wisdom-keepers of cultural and faith traditions that have long used psychedelics outside the biomedical setting (29, 39). Indeed, the secular model of psychedelic-AT that dominates the contemporary medical literature has thoroughly separated the substances in question from their Indigenous roots and ceremonial uses. A stance of epistemic humility asks what has been lost in that disconnection, who has been harmed by it (39), and whether there may be therapeutic and/or ethical value to a rapprochement (6, 40–42). Public dialogues with practitioners and communities whose work with psychedelic substances is embedded in different cultural contexts could inform and potentially improve research design, clinical practice, and public policy. Moreover, amplifying within the research community the people(s) and practices that have silently shaped the very intervention we study might be a small but meaningful step toward reciprocity (43).
Cultural and Diversity Considerations
When considering the limits and epistemic harms of PAP research to date, it is essential to consider the individuals and populations that have and have not been studied. The limited diversity among recent psychedelic research participants (44) is therefore relevant to more than the external validity of contemporary clinical trials. As in any psychotherapeutic intervention, prior experience shapes what a practitioner believes “works” with a given treatment and patient population (45). It therefore also influences how that treatment is conceptualized, studied, developed, and taught. Greater diversity is therefore required in order to develop and optimize treatment protocols in a way that is genuinely patient-centered. Actively recruiting participants from underrepresented communities is essential (46) but insufficient, particularly given the tendency to reduce “diversity” to a few (often marginalized) identities (47), without considering the many other patient- and therapist-specific aspects of social location influencing the therapeutic process. Epistemic humility invites serious consideration of the complexities of intersectionality, and the consideration of intersectional identities of patients and therapists in outcomes and process research alike. It also invites the input of diverse communities in research design, recognizing the contribution of culture and community to genuinely patient-centered care (48, 49).
Conclusions
From a position of epistemic humility, we call for research not only into the basic science of psychedelics, but also the implicit and explicit content and process of psychotherapy in PAP; the use of psychedelics in Indigenous and other non-medical communities; and the ways in which intrapersonal, interpersonal, social, and other contextual factors shape psychedelic experiences and therapeutic efficacy. Given the increased physical and psychological vulnerability of patients in non-ordinary states of consciousness, additional research into the attendant risks of PAP is called for, to support the development of educational materials and clear behavioral and ethical guidelines for psychedelic therapists.
Though many of the foregoing recommendations apply equally to non-psychedelic psychotherapy research, the stakes may be especially high with PAP (28). Indeed, the probability of a replication crisis in psychedelic research is not negligible, and may be amplified by the role of expectancy and functional unblinding in clinical outcomes. In PAP outcomes research, standardizing the therapeutic intervention is essential if others are to learn from, study, and replicate positive findings. Such standardization generally begins with a therapy manual and therapist training materials, which despite being essential “methods” used to conduct PAP research are nevertheless not always published alongside trial outcomes (4). We urge PAP researchers to hold themselves to a higher standard—not only to develop and study standardized interventions, but to describe the conceptual framework, content, and effort required to train therapists to perform that intervention with a high degree of fidelity. Adequate communication of those factors is essential for replication purposes. No less importantly, it may also inform decision-making regarding the financial resources and infrastructure needed for safe and efficacious implementation of PAP in the future, outside the research context. If research, clinical practice, and policy inform one another, and if all are informed by an awareness of and responsiveness to the broader social and environmental context in which these interventions are embedded, the outcomes will be more meaningful, the practices more ethical, and the conclusions more accurate.
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Information & Authors
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Received: 30 September 2023
Revision received: 24 May 2024
Revision received: 16 June 2024
Accepted: 18 July 2024
Published online: 1 January 2025
Published in print: January 01, 2025
Keywords
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Competing Interests
Dr. O’Donnell has received payments from Lykos Therapeutics for consultation and the education and supervision of research therapists. The other authors report no financial relationships with commercial interests.
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