Abstract
Eating disorders are debilitating diseases that have twin impacts on the body and mind and are associated with a number of physiological and psychological comorbidities (Blinder, Cumella, and Sanathara 2006; Casiero and Frishman 2006), including increased suicide risk (Arcelus et al. 2011; Lipson and Sonneville 2020). In addition, eating disorders are growing in prevalence (Gilmache et al. 2019) and impact women at much higher rates than men (Bearman, Martinez, and Stice 2006), especially in adolescence (Spriggs, Kettner, and Carhart-Harris 2021). Anorexia nervosa (AN) is a particularly devastating eating disorder, with one of the highest mortality rates of any psychiatric disorder (Sullivan 1995). Despite the severity of the condition, current treatments for AN are limited in their efficacy (Khalsa et al. 2017). Based on the growing body of evidence demonstrating the short-term and long-term efficacy of psychedelic-assisted psychotherapy for the treatment of other mental illnesses, I argue that research into psychedelic-assisted psychotherapy for AN should be funded.
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Introduction
Eating disorders are behavioural conditions that have twin impacts on the body and mind, characterized by “severe and persistent disturbance in eating behaviours and associated with distressing thoughts and emotions” (American Psychiatric Association 2021, ¶1). Eating disorders are growing in prevalence (Gilmache et al. 2019) and impact women at much higher rates than men (Bearman, Martinez, and Stice 2006), especially in adolescence (Spriggs, Kettner, and Carhart-Harris 2021). It is estimated that around 2 per cent of New Zealand’s population will have an eating disorder at some point in their lives (Ministry of Health 2008). The core psychopathology of eating disorders is thought to be the “attitudinal disturbance” that involves overevaluation of weight and shape and the disproportionately large impact thinness has on the individual’s feelings of self-worth (Fairburn and Harrison 2003).
In general, eating disorders have been linked to high rates of psychiatric comorbidities such as obsessive-compulsive disorder (OCD) (Blinder, Cumella, and Sanathara 2006) and post-traumatic stress disorder (PTSD) (Brady et al. 2000), as well as cardiovascular complications (Casiero and Frishman 2006) and increased suicide risk (Arcelus et al. 2011; Lipson and Sonneville 2020). One study reported that the suicide rate for women with an eating disorder was fifty-eight times greater than women without an eating disorder (Herzog et al. 2000). Anorexia nervosa (AN) has one of the highest mortality rates of any eating disorder, as well as any psychiatric disorder (Sullivan 1995), killing one out of every five sufferers (Lester 2019). Despite the clear severity of the condition, treatment for individuals with AN is limited in its efficacy. Individuals with AN are at an exceedingly high risk for relapse; upwards of 50 per cent of individuals relapse within the first year after successful hospital treatment (Khalsa et al. 2017). Due to the debilitating physical impacts of AN, conventional treatment tends to focus more on symptom management than treating the underlying psychological causes of the illness (Lester 2019; Spriggs, Kettner, and Carhart-Harris 2021).
While cognitive-behavioural therapy has emerged as the leading treatment for some eating disorders such as bulimia nervosa, there is no such consensus on a “first-line psychotherapeutic model” for AN (Spriggs, Kettner, and Carhart-Harris 2021, 1265). This state of clinical equipoise indicates the ethical imperative for additional research to be carried out on a variety of treatment methodologies in order to ascertain the most effective treatment clinicians can offer to patients with AN. A potentially promising path forward involves the integration of psychedelic substances into psychotherapy: psychedelic-assisted psychotherapy. Substances being considered for use include the “classic psychedelics” psilocybin (found in “magic” mushrooms), mescaline, or lysergic acid diethylamide (LSD) as well as empathogens such as 3,4-Methylenedioxymethamphetamine, better known as MDMA.
In this paper, I will argue that due to the severity and growing prevalence of AN, compounded with the shortfall of currently available treatments and state of clinical equipoise, research into psychedelic-assisted psychotherapy for AN should be funded. In the first part of the paper, I provide a brief history of western research into the use of psychedelics in psychotherapy. I will begin by outlining the sociocultural approach to eating disorders and will argue that psychedelic-assisted psychotherapy may be effective under this model due to the ability of psychedelic experiences to interrupt rigid thinking patterns and deeply ingrained images and notions of the self. I will then share evidence from studies using psychedelic-assisted psychotherapy to treat other mental illnesses and argue that the same mechanisms could have a positive impact for individuals with AN. I will couple this with narrative evidence of positive outcomes of non-clinical psychedelic experiences for individuals with eating disorders including AN. Having established that there is plausible evidence indicating the efficacy of psychedelic-assisted psychotherapy for AN, I will close by arguing why it is important and ethically responsible to fund research in this area.
A Brief History of Western Research into Therapeutic Uses of Psychedelic Substances
Indigenous peoples have been using naturally occurring psychedelic substances including psilocybin mushrooms, ayahuasca, and peyote for ceremonial healing for centuries, long before the laboratory discovery of LSD (Sessa 2016). What follows is a brief overview of the history of western research into therapeutic uses of psychedelic substances. I chose to take this focus because, rightly or not, it is largely this white, male, Western-driven history that forms the basis for the contemporary reintegration of psychedelic substances into psychotherapy.Footnote 1 However, it is critical to note and uplift the important work being done to highlight the contributions of indigenous populations in this realm (George et al. 2020). For example, researchers from the University of Waikato are developing a framework to ensure than indigenous peoples are involved in—and benefit from—the development of psychoactive molecules for the treatment of mental health issues (Head and Hudson 2022).
Albert Hofmann first synthesized LSD in his lab in Switzerland in 1938. Following its subsequent arrival in the United States in the late ’40s, by the early-1950s research into potential therapeutic uses of psychedelic drugs was booming. Many of the studies published in the following fifteen years supported claims that LSD could “expedite the psychotherapeutic process” for the treatment of a variety of “emotional disorders” (Grof 1980, ¶3 under “Therapeutic Experimentation with LSD”). Over 1,000 scientific papers were published reporting potential therapeutic uses of psychedelics. All of this progress ground to a halt in 1962 when the U.S. government instituted new drug safety restrictions that designated LSD as an experimental drug. This, of course, did not stop LSD from seeping into the public. Recreational use of LSD became widespread among certain cultural milieu in the mid-to-late-’60s. This was especially true in the anti-government “hippie counterculture.” Following a long campaign framing LSD as a drug of abuse, the compound was outlawed by the U.S. government as part of the infamous war on drugs in 1968 (Costandi 2014). Recently in the second decade of the twenty-first century, after this “legally mandated, decades-long global arrest of research on psychedelic drugs” (Nutt, Erritzoe, and Carhart-Harris 2020, 24), regulatory barriers have begun to loosen.
The last few years have seen a resurgence of research into psychedelic-assisted psychotherapy that is building a strong evidence base for its efficacy in treating a variety of mental illnesses including treatment-resistant depression (Carhart-Harris et al. 2018), post-traumatic stress disorder (Krediet et al. 2020), and substance use disorder (Bogenschultz et al. 2015). For example, four separate studies conducted between 2011 and 2016 reported improvements in depressive symptoms after psilocybin-assisted psychotherapy (Grob et al. 2011; Griffiths et al. 2016; Ross et al. 2016). In particular, one study conducted by Carhart-Harris et al. found that patients with severe, unipolar, treatment-resistant depression showed significant reduction in depressive symptoms after two oral doses of psilocybin taken seven days apart (Carhart-Harris et al. 2018). Perhaps even more impressive is that these improvements lasted from a few weeks to several months; no patient sought conventional antidepressant treatment within five weeks of their psilocybin use (Carhart-Harris et al. 2018, 400). Researchers suggest that this wide array of successful applications is indicative of the “transdiagnostic action” of psychedelics (Spriggs, Kettner, and Carhart-Harris 2021, 1269). Since 2020, there have been a small number of phase 1 and 2 studies in the United States and United Kingdom aiming to assess the safety and efficacy of psilocybin in participants with anorexia nervosa (Spriggs el al. 2021).Footnote 2 As of writing, no results have been published.
Psychedelic-assisted psychotherapy, as commonly structured in the contemporary era, proceeds in three stages (Pollan 2018). The first stage consists of preparatory sessions during which the clinician discusses with the patient the type of sensations and experiences to expect to have during the “trip,” helps the patient to set an intention, and may discuss strategies to deal with uncomfortable or challenging experiences. The second step is the dosing, or “trip”, itself. The psychedelic substance is administered to the patient, who is often blindfolded and may listen to music in order to facilitate an inwardly directed experience (Schenberg 2018). One or two clinicians remain present throughout the trip in order to ensure the patient is kept physically comfortable and to provide empathetic support, if needed. The length of the trip varies by psychedelic drug. For example, a psilocybin trip tends to last between four to six hours while an LSD trip can last up to eight to twelve hours. The final step is integration. During this session, the clinician aims to help the patient make sense of her experiences, which often elude verbal reasoning. This session is critical for distilling findings and charting a path to continue to work towards whatever goal the patient has identified.Footnote 3
The Sociocultural Approach to Eating Disorders and Theoretical Link to Psychedelic-Assisted Psychotherapy
Current research and treatment of eating disorders is split into two dominant paradigms (Levine and Smolak 2014). While there is little disagreement that the neurochemical functions of individuals with active eating disorders differs from that of control groups, the biopsychiatric and sociocultural models locate the cause of the illness in different places. The biopsychiatric approach emphasizes the neurochemical and genetic causes of eating disorders and sees them as primarily biologically based. On the other side is the sociocultural perspective that focuses on social messages about gender, eating, and body shape that play a primary role in an individual’s development of an eating disorder. Since being female is the highest risk factor for developing an eating disorder (Wacker and Doblin-MacNab 2020), a number of researchers have asked whether there may be a relationship between holding a feminist identity and having greater resistance to developing an eating disorder (Borowsky et al. 2016). The connection here is that women who identify as feminist may be more likely to be critically aware of the misogynistic cultural representations of women that can fuel disordered eating and thus more able to consciously reject those influences. In addition, there is evidence that “feminist-informed protective factors” such as having support people who challenge disordered eating behaviours, being active in one’s community, and a strong sense of personal agency separate from physical appearance can be instrumental in preventing sub-threshold eating disorders from further developing into more severe, clinically diagnosable disorders (Wacker and Doblin-MacNab 2020).
It is this sense of personal agency and self-identity that can be accessed, interrogated, and altered in psychedelic experiences. The Handbook for the Therapeutic Use of Lysergic Acid Diethylamide-25 Individual and Group Procedures (Blewett and Chwelos 1959), written in 1959, was one of the earliest handbooks written on the potential therapeutic uses of LSD for a wide variety of mental illnesses. The aim of psychedelic-assisted therapy professed by this handbook is “to help the patient overcome his reluctance to face himself as he really is” (3). A central source of anguish that fuels eating disorders under the sociocultural approach is an overidentification of self-worth with thinness. This is emblematic of a lack of self-acceptance and an attempt to construe meaning and build a personal identity around an external rather than internal characteristic. Even back in 1959, Blewett and Chewlos noted that psychedelic use appears to disrupt perception of body image and tends to shift attitudes and beliefs toward greater self-acceptance and self-understanding. This heightened ability for perceptual and attitudinal shifts could be harnessed to encourage a healthier basis of identity for individuals struggling with eating disorders like AN.
Although they remain illegal for recreational use in most countries, psychedelic substances can be accessed outside the clinical setting with relative ease. One study estimated that 13.6 per cent of the U.S. adult population have used psychedelics at least once in their lifetime (Sexton et al. 2019). While the majority of these were likely recreational, self-administered experiences, a small portion would have been more structured experiences facilitated by a shaman or ceremonial healer. In one truly fascinating study, researchers interviewed sixteen individuals with eating disorders who had participated in ayahuasca ceremonies (Lafrance et al. 2017). The majority of participants (81 per cent) had engaged in specific treatment for their eating disorder prior to the ayahuasca experience. Sixty-nine per cent of participants reported a reduction of eating disorder thoughts and symptoms, with one participant reporting, “I felt like I had more distance between my behaviors and, you know the thought patterns and the triggers… it was like my brain was reprogrammed” (Lafrance et al. 2017, 429). In addition, half of the participants reported reductions in anxiety, depression, self-harm, suicidality, and problematic substance use. Most interestingly, from my perspective, is that the majority of participants indicated that their ayahuasca experiences helped them to identify what they perceived as the root psychological causes of their eating disorders. This was coupled with frequent reports of shifts in self-perception in positive, healing directions leading to greater self-love, self-esteem, and self-compassion.
The above study does have its shortcomings, namely that selection bias was likely to yield participants who had positive overall experiences with ayahuasca. However, this anecdotal evidence strongly supports the claim that psychedelic-assisted psychotherapy in a clinical setting could be beneficial to patients with AN due to the increased capacity for self-understanding and compassion, and the uprooting of ingrained mental patterns provided by a well-supported psychedelic experience. One external factor that was stressed as critical by participants was the importance of having their psychedelic experiences in a safe environment where they felt comfortable to ask for and receive help in moments of vulnerability. All participants likewise stressed the importance of aftercare and integration, either with the ceremonial healer or with a psychotherapist, which enabled them to translate their experiences into actionable next steps for their healing.
Ethical Concerns of Psychedelic-Assisted Psychotherapy for AN
In the sections above, I have outlined how the severity and growing prevalence of AN, coupled with the shortfalls of currently available treatments, warrants research into novel treatment. One such novel treatment I have focused on is psychedelic-assisted psychotherapy, a treatment which is supported by a growing evidence base in the context of other mental illnesses. Evidence suggests that psychedelics have transdiagnostic impact and can be beneficial to individuals with a wide range of mental illnesses. I proposed that part of this transdiagnostic action stems from heightened self-awareness, self-understanding, compassion, and a disruption of ingrained mental patterns. Moreover, there is strong evidence that the clinical use of psychedelic substances is safe, with very few adverse events reported throughout the literature (Smith and Sisti 2021). In sum, up to this point I have focused on the potential benefits of psychedelic-assisted psychotherapy for AN treatment; this is critical because a core ethical obligation that clinicians have to their patients is to try to provide the greatest benefit possible. As with any treatment, however, there are also potential harms that should be identified and mediated. Below, I will focus on three factors that contribute to the vulnerability of an individual with AN undergoing psychedelic-assisted psychotherapy and how the research setting only amplifies these vulnerabilities. I will then move to address the concern of whether any patient is able to give authentic informed consent for psychedelic-assisted psychotherapy, let alone adolescents with AN.
Patient Vulnerability
Patient vulnerability in psychedelic-assisted psychotherapy for AN is compounded by three individual sources of vulnerability. Any person under the influence of a psychedelic drug is vulnerable. Psychedelic drugs commonly produce a dramatic change in perception of space and time; it is also common to experience intense emotions, enhanced sensitivity to the feelings of others and sometimes a feeling of egolessness or oneness with the universe (Blewett and Chwelos 1959). These experiences can be uncomfortable and unsettling and do not lead themselves easily to verbalization. As such, it may be difficult for someone under the influence of a psychedelic drug to communicate how or why they are in distress as a result of internal emotional experiences or perceptual changes. Absent the use of sedation by another medication, there is no “off switch” for psychedelic experiences and delving into the roots of a mental illness, such as reliving a childhood trauma (Smith and Sisti 2021), may cause significant distress that cannot easily be avoided. In addition, the temporary but substantial altered state makes individuals vulnerable to psychological, emotional, or sexual abuse. Current research protocols attempt to mitigate this by requiring the administration of psychedelic-assisted psychotherapy to be done in pairs to increase accountability (Smith and Sisti 2021).
The second source of vulnerability stems from the clinician−patient relationship itself. Any patient participating in psychotherapy treatment is vulnerable. Emotional vulnerability may even be seen as a prerequisite for any patient seeking psychotherapeutic treatment but discouraged for clinicians, leading to an asymmetry of trust and disclosure (Palmer 2014). Such openness, coupled with the power dynamic inherent in the clinician−patient relationship leaves patients again vulnerable to abuse (Steinberg, Albert, and Courtois 2021).
Finally, individuals with AN are highly vulnerable both mentally and physically due to the severe physical and psychological comorbidities commonly associated with AN. Sufferers of AN often present with liver or kidney failure, osteoporosis, low heart rate, dehydration, and electrolyte imbalance which make them very physically weak (Lester 2019). Individuals with AN may also have a wide range of psychiatric comorbidities including obsessive-compulsive disorder, mood, anxiety, and substance use disorders (Blinder, Cumella, and Sanathara 2006). One meta-analysis found that 97 per cent of female inpatients with eating disorders had at least one psychiatric comorbid diagnosis (Blinder, Cumella, and Sanathara 2006). These may manifest in deep self-loathing, relentless perfectionism, and difficulty forming intimate relationships and maintaining interpersonal boundaries (Lester 2019). Furthermore, individuals with AN and other eating disorders may feel deeply misunderstood and alienated by their encounters with a medical system that myopically focuses on biomedical indicators of success, for instance calorie intake and weight. While there is understandable urgency to treat the physiological symptoms of an eating disorder, this approach may prevent clinicians from attempts to understand the root psychological causes and patients’ continued motivation to partake in such harmful behaviour (Lester 2019). Finally and relatedly, in Western countries, individuals receiving treatment for AN are most frequently young and female (Martínez-González et al. 2020, 3834). Unfortunately, there have been reports of older male clinicians sexually abusing their patients (Palmer 2014), capitalizing on a range of vulnerabilities noted above, as well as the power disparity between clinician and patient. Therefore, individuals with AN, as a direct result of their eating disorder, are both physically and mentally vulnerable to abuse.
These three treatment vulnerability factors would be amplified in a research setting, where harms and benefits, as well as interactions with other psychiatric medications for the specific patient population have yet to be identified and empirically evaluated. Any research into this treatment modality must take into careful account these sources of vulnerability. One potential way to do this would be a rigorous screening which may exclude participants with certain physical or psychiatric comorbidities, such as low blood pressure or a history of substance use disorder, which may increase the risk of adverse side effects. Of course, this does raise the possibility of excluding those most at risk who could benefit most from the treatment. However, it would be prudent for researchers to proceed with the utmost caution in order to mitigate the known risk factors and identify any other unanticipated side effects. The participant pool could then be widened once a satisfactory risk profile is established.
Informed Consent
Psychedelic experiences can have profound effects on individuals on both a psychological and spiritual level. In one study, 67 per cent of participants reported fourteen months after a psilocybin trip that it was among the five most spiritually significant experiences of their life (Griffiths et al. 2008). Such intense and deeply affecting spiritual experiences such as ego dissolution or feelings of unity with the universe often elude verbal explanation. Because of the unique nature of psychedelic experiences, it is difficult for psychedelic-naïve patients to appreciate beforehand the full extent of the experience they are signing up for. How could an informed consent process be structured so that patient autonomy is respected by ensuring they are adequately informed when a written account of the expected experience is likely to fall far short of the experience itself?
Even if an experience could be sufficiently described in words, the nature of the psychedelic experience can vary significantly between individuals depending, among other factors, on their mindset, mental preparation and intentions for the experience (the “set”) and their level of comfort with their surroundings and clinician (the “setting”). Furthermore, due to differences in set or setting, the same individual may likely have two radically different experiences with the same dosage at two different points in time.
One of the prized functions of psychedelic-assisted psychotherapy is that it can allow patients to move past internal barriers that have prevented them from facing the deep-rooted causes of their illness (Grof 1980). Sometimes these deep causes may be hidden even from the patient herself as a type of coping mechanism to avoid encountering a painful memory. The potential harms from such a traumatic re-exposure must be acknowledged and made explicit in any informed consent document. Again, though, even after careful screening of patients and extensive pre-trip psychotherapy, the likelihood of such an event may be hard to predict. Reports also suggest that the therapeutic value of the experience comes partly through encountering such psychologically challenging experiences. The points raised above highlight just a few concerns about how to obtain authentic informed consent to psychedelic-assisted psychotherapy in both the research and clinical settings.
Another important factor pertains to the additional ethical issues raised by the significant subpopulation of adolescent individuals with AN. Could, say, a fifteen-year-old girl being treated for AN be considered competent to provide consent to psychedelic-assisted psychotherapy given her mental illness and the complex and unknown elements of the treatment? Would it be ethically permissible for parents to provide proxy consent? Could a court issue an order for this treatment?
We can look to case law for an indication of how a minor’s capacity to consent to a novel therapy with significant unknown future effects may be treated by the courts. The U.K. case Bell v Tavistock ([2020] EWHC 3274) centred around the question of whether, in general, teenagers with gender dysphoria have the capacity to consent to gender affirmation treatment. The Court ruled that due to the irreversible and complex impacts of the treatment, it is “doubtful” whether a child aged fourteen or fifteen could “understand and weigh the long-term risks and consequences” of the treatment sufficiently to give informed consent ([151]). The aim of the original litigation was to require the involvement of the court before anyone under the age of eighteen was prescribed puberty blockers. This decision has recently been overturned in the Court of Appeal, which looked back on Gillick (Gillick v West Norfolk and Wisbech Area Health Authority [1986] AC 112) to stress that it is for clinicians and not courts to determine the competence of a minor to consent to medical treatment (Bell v Tavistock [2021] EWCA Civ 1363, [87]). This latest judgment stresses that there is no one-size-fits-all approach to judging competence of a minor; the nature of a given treatment as controversial, novel, or complex does not in itself preclude a young person’s ability to give consent. The final decision, therefore, lies with the individual clinician who, ideally, has comprehensive knowledge of the risks and benefits of the treatment being proposed and factors about the individual patient that may prevent her from having capacity to consent to psychedelic-assisted psychotherapy.
Conclusion: Why Funding Matters
The current state of treatment for AN is inadequate and warrants swift attention. Simply put, innovation and improvements in treatment cannot happen without research. Research cannot happen without funding. Despite the severity, prevalence, and high mortality rate of eating disorders, research into treatments remains underfunded worldwide. It is reported that in 2017, the U.S. National Institute of Mental Health spent an estimated US$69 per affected individual on schizophrenia research, US$82 for autism, but only US$1.07 for eating disorders (as cited in Lester 2019).
Between 2009 and 2016, 3,835 individuals with a diagnosed eating disorder had contact with specialist mental health services in New Zealand (Lacey et al. 2020), and demand for eating disorder services has dramatically increased in the wake of the COVID-19 pandemic and lockdowns (Strongman 2021). The New Zealand government invests about NZ$120 million in health research annually through the Health Research Council (HRC) (Little 2021). From 2014−2019, the HRC invested NZ$27.2 million in research to improve mental health and well-being (Health Research Council of New Zealand 2019). However, none of the HRC research contracts current as of June 30, 2019 focus on eating disorders. In 2019−2020, the HRC invested NZ$13.5 million in mental health research Health Research Council of New Zealand 2020). But again, there is no record of any research being carried out that is focused on treatment for eating disorders, let alone research into the potential application of psychedelic-assisted psychotherapy in this area. I suggest that research into novel treatments for eating disorders, especially AN, should be made a funding priority. However, a recent Health Research Council-funded study using psychedelic-assisted therapy in advanced-stage cancer patients may indicate that attitudes and funding priorities are shifting to embrace these novel therapies in limited situations (Health Research Council of New Zealand 2022; National Institutes of Health 2022).
There is an emerging wave of evidence demonstrating the safety and efficacy of psychedelic-assisted psychotherapy for a wide range of mental illnesses. I have argued with researchers that psychedelic drugs’ facilitation of openness and self-compassion can have transdiagnostic impact and that it could be applied to the treatment of eating disorders like AN. There are a number of considerable ethical concerns related to the use of psychedelic drugs in psychotherapy with patients with AN, namely, how to obtain valid informed consent and how to mitigate the significant vulnerability of this patient population. Other concerns include the potential psychological harms of psychedelic experiences, possible interactions with other psychiatric medications, and the competency of clinicians to provide this specialized treatment modality. While funding for research does not necessarily translate into increased efficacy or availability of treatment, it would enable researchers to undertake careful investigation of these and other important questions to ensure that individuals with AN have the opportunity to benefit from what could be a ground-breaking treatment.
Notes
For an overview of the historic exclusion of indigenous voices and practice related to psychedelic use, see Ens, A. 2021. Silencing indigenous pasts: critical Indigenous theory and the history of psychedelics. International Journal of Qualitative Studies in Education https://doi.org/10.1080/09518398.2021.1942297.
For details on these two studies, see “Evaluation of Psilocybin in Anorexia Nervosa: Safety and Efficacy” <https://clinicaltrials.gov/ct2/show/NCT04661514> and “Psilocybin as a Treatment for Anorexia Nervosa: A Pilot Study” <https://clinicaltrials.gov/ct2/show/NCT04505189>.
For a detailed sample study protocol, including a timeline of study visits and dosing, see Spriggs et al. 2021.
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Otterman, L.S. Research into Psychedelic-Assisted Psychotherapy for Anorexia Nervosa Should be Funded. Bioethical Inquiry 20, 31–39 (2023). https://doi.org/10.1007/s11673-022-10220-9
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DOI: https://doi.org/10.1007/s11673-022-10220-9