Reframing psychedelic regulation: Tools,not treatments

Psychedelic-like substances, such as psilocybin or 3,4-methylenedioxymethamphetamine (MDMA), are associated with “a number of unique challenges” (US Food and Drug Administration (FDA), 2023) for drug regulators that are difficult to accommodate with existing regulatory frameworks. Chief among them are the extra-pharmacological elements of this class of treatment. In research (Garcia-Romeu and Richards, 2018; Horton et al., 2021) and clinical practice (Aicher and Gasser, 2024; Australian Therapeutic Goods Administration (TGA), 2023), the use of psychedelics in the treatment of mental disorders occurs alongside psychotherapy. Although survey studies suggest that, under favorable circumstances, psychedelic use can have beneficial effects outside of clinical settings (Haijen et al., 2018; Wolff et al., 2022, 2024), it is widely assumed that co-administration with psychotherapy (sometimes referred to as “psychological support”) is necessary to ensure both the safety and the efficacy of these treatments (Aday et al., 2024; Gründer et al., 2024; Schenberg et al., 2024). This view acknowledges the marked context-dependence of psychedelic drug effects (Aday et al., 2021; Carhart-Harris et al., 2018)—including effects that correspond to general change mechanisms of psychotherapy (Wolff et al., 2024). For example, recent clinical studies have shown that the therapeutic alliance (i.e. the emotional bond between participant and therapist, as well as mutual agreement on goals and tasks) predicts psychedelic therapy outcomes (Levin et al., 2024; Murphy et al., 2022; Zeifman et al., 2024). Furthermore, Levin et al. (2024) and Murphy et al. (2022) presented evidence for a reciprocal longitudinal relationship between the therapeutic alliance and participants’ therapeutic experiences in dosing sessions, which in turn mediate clinical outcomes. These results exemplify the close interweaving of pharmacological and extrapharmacological elements, from which it follows that drug effects on treatment outcomes cannot be meaningfully separated from the psychotherapeutic effects.

Do current regulatory pathways disincentivize psychotherapy?

However, regulatory bodies such as the FDA, EMA, and TGA are tasked with evaluating the safety and efficacy of drugs, not drug-assisted psychotherapy. While drug approval can be accompanied by conditions, for example, the FDA's Risk Evaluation and Mitigation Strategy (REMS), protocols and training for accompanying psychotherapy fall outside the remit. Considering the oft-repeated fact that regulators such as the FDA do not regulate psychotherapy, it seems opportune that some drug developers prefer not to name the psychotherapy conducted in approval studies as such. For example, in the largest published study to date testing psilocybin for depression (Goodwin et al., 2022), the treatment is referred to as psilocybin administered with “psychological support”. However, the same study's published therapist training program clearly describes the “psychological support” to be applied throughout preparatory, dosing, and integration sessions as a form of psychotherapy—including process-directive psychotherapeutic interventions delivered by extensively trained mental health professionals (Tai et al., 2021). The publication even explicitly states that the “psychological support” model is based on an integration of various models of psychotherapy, including cognitive behavioral therapy, mindfulness-based therapy, and acceptance and commitment therapy. Although psychotherapy was thus quite clearly part of the treatment, Goodwin et al. (2023) cited this study to support the claim that psilocybin can be effective and safe without psychotherapy, and that “psychological support” is merely a safety measure that does not contribute to efficacy. This strategy and other attempts to minimize psychotherapy, linguistically and in practice, have been criticized as scientifically unfounded and detrimental to both safety and efficacy (e.g. Alpert et al., 2024; Gründer et al., 2024; O’Donnell et al., 2024; Schenberg et al., 2024). In this light, the question must be asked whether current regulatory frameworks really require the minimization or mislabeling of psychotherapy as a “necessary evil” that must be accepted to get psychedelics approved. Langlitz (2024) summarized the prevailing incentives for drug developers as follows: “Neither the FDA nor EMA are responsible for the assessment of new psychotherapies and the psychedelic organizations applying for their approval have no interest in further complicating the process by emphasizing that they do not believe that psychedelics are therapeutic in their own right but that they function as catalysts of psychotherapies.”

Minimizing psychotherapy is unnecessary, and regulators can maintain their drug-specific focus, if psychedelics are viewed as therapeutic tools, not treatments

Given the central role of psychotherapy (sometimes referred to as “psychological support”) in the practice and outcomes associated with psychedelic therapy, we propose one of two regulatory changes need to be made: either drug regulators should expand their remit, include psychotherapy experts, and evaluate the psychotherapy in detail as a co-dependent technology; or alternatively, regulators should maintain their drug-specific focus, and acknowledge that a psychedelic substance used alongside psychotherapy can be assessed as a therapeutic adjunct, and not a traditional therapeutic. In other words, we propose that a more appropriate regulatory framework for psychedelic substances—when used alongside psychotherapy that is not subject to regulatory approval itself—may be to regard them as supportive tools for therapy rather than as treatments in their own right.

Anesthetics as a useful analogy

The rationale for this claim can be illustrated by drawing parallels between psychedelics and another class of medical technology: anesthetics. There are various striking parallels between the surgical use of anesthetics and the psychotherapeutic use of psychedelics (for a recent historical analysis, see Stauffer, 2025). Relevant to our proposal here, anesthetic drugs are not treatments, but instead are used to induce a loss of sensation or consciousness that enables or facilitates safe and tolerable surgical or other medical procedures for a wide range of conditions. Consequently, regulatory approval of new anesthetic drugs does not require evaluation of the clinical outcome of the medical procedures for which the anesthetic is used (e.g. appendectomy, osteosynthesis, or organ transplantation). Instead, what is evaluated under regulatory approval is whether the anesthetic can safely and effectively induce an acute anesthetic effect required to perform such procedures. While regulatory approval of anesthetics requires assessment of the anesthetic endpoints (e.g. depth of anesthesia), the efficacy of the facilitated medical procedures is not assessed. In line with this, medical procedures involving anesthesia (e.g. surgeries) are not regulated by drug authorities such as the FDA, but by the respective medical bodies that define medical treatment guidelines.

Using context-independent acute effects as endpoints, instead of long-term clinical benefit

Like anesthetics, psychedelics can be considered as treatment tools rather than treatments in their own right. Based on this, regulatory approval of new psychedelic drugs might not necessarily require an evaluation of the clinical outcome of the psychotherapy for which the psychedelic is used (e.g. reduced depression symptoms). Instead, it may only be necessary to test whether a drug can safely and effectively induce specific transient altered states of awareness that are considered conducive to psychotherapy.

A key step in such a reframing of psychedelic regulation would be to define appropriate endpoints (outcome measures) for approval studies. To allow for a drug-focused evaluation that does not require taking into account interactions with psychotherapeutic interventions, such endpoints should not implicate complex associations between drug and non-drug factors. Rather, endpoints should be defined as acute psychological or neurophysiological states that can be pharmacologically induced in a relatively context-independent manner. Possible endpoints for entactogens such as MDMA could relate to enhanced emotional openness, empathy, or distress tolerance (Holze et al., 2020; Kangaslampi and Zijlmans, 2023). For classical psychedelics such as psilocybin, relatively context-independent acute effects of broad psychotherapeutic relevance may include “belief relaxation” (Carhart-Harris and Friston, 2019), “ego-dissolution” (Nour et al., 2016), and “noetic quality” (MacLean et al., 2012). To this end, further research is needed to clarify the link between therapeutic elements—acute effects of psychedelics, psychotherapeutic interventions, psychotherapeutic processes (Aday et al., 2024; Wolff et al., 2024)—and clinical outcomes (Cristea et al., 2024).

If drug regulators are only tasked with evaluating whether psychedelics can safely and effectively induce certain relevant features of a “psychedelic state”, other authorities such as those regulating psychiatry and psychotherapy must step in and take responsibility to define guidelines for the safe and effective use of these drugs within psychotherapeutic treatment contexts. The example of anesthetics shows that key challenges associated with the regulation of psychedelic drugs could be addressed through regulatory approaches that are already in place. From this, it may follow that in questions of regulation, too, we must avoid the pitfall of “psychedelic exceptionalism” (Johnson, 2021); that is, the notion that psychedelics are somehow too special to be accommodated by existing concepts and frameworks. While the regulatory challenges posed by psychedelics are certainly complex, the most appropriate regulatory approach may be one that treats psychedelics not as treatments in themselves, but as tools that facilitate or enable effective treatment using psychotherapeutic methods. This could avoid the need for product regulators to choose between regulating or relegating the extrapharmacological factors central to psychedelic-assisted psychotherapy, and permit more appropriate governing bodies to do so.

Conclusion

Several affordances may stem from our proposal here, which would critically depend on a shift in regulatory strategy from psychedelic drug sponsors, and in regulatory evaluation from regulators. Perhaps the most salient implication of this reframing may be to avert the current “race to the bottom” that has commenced within pharmaceutical development companies that have psychedelic candidates, many of whom appear to have identified psychotherapy as a regulatory liability within their psychedelic drug-development pipeline (Aday et al., 2023; Langlitz, 2024). Pharmaceutical development strategy appears to now be responding to medicine regulation and commercial incentives by whittling down psychedelic therapies into yet another set of psychotropic agents that may in the end produce moderate clinical benefit at best, and require ongoing use. That is, treating psychedelics as a class of psychiatric drugs may lead to the same underwhelming outcomes seen across psychiatry research over the last few decades. Our proposal here does not preclude or oppose current efforts to regulate psychedelics as treatments for specific mental disorders, but instead complements them. Indeed, we should consider the varieties of psychedelic regulation as this new class of treatments are developed and evaluated. This includes keeping an open mind to the theoretical possibility that psychedelics could have safe and effective psychiatric applications independent of psychotherapy. On the other hand, reframing the regulation of psychedelics as tools or technologies that can facilitate psychotherapy, as we propose here, could help balance the current trend of minimizing psychotherapy with complementary efforts that, instead, acknowledge and emphasize psychotherapy more strongly. The resulting more diverse range of approaches could significantly advance the emerging field of psychedelic therapies.