Therapeutic uses of psychedelics for eating disorders and body dysmorphic disorder

Body dysmorphic disorder (BDD) and eating disorders (EDs), particularly anorexia nervosa (AN), are psychiatric conditions marked by excessive preoccupation with appearance and disturbed eating behaviours, and they carry high morbidity, mortality and functional impairment. Ledwos and colleagues note overlap between BDD and EDs in phenomenology, sociodemographic features, and neurobiological findings such as altered visuospatial processing and serotonergic signalling; conventional treatments (psychotherapy and pharmacotherapy) produce limited and often unsustained responses, prompting calls for novel interventions. In response to this treatment gap, the study aimed to systematically review published evidence to the end of February 2022 on the therapeutic potential of classic serotonergic psychedelics (for example psilocybin, LSD, ayahuasca, DMT, mescaline) for patients with diagnosed EDs and/or BDD. The authors restricted the search to agents acting largely via 5-HT2A receptor agonism and excluded MDMA due to its differing pharmacology; the review set out to collect and critically evaluate all study designs reporting symptom change in these populations.

Ledwos and colleagues performed a systematic review following PRISMA guidelines. Searches were run across multiple databases (PsycInfo, PubMed, Embase, Web of Science, Google Scholar, Cochrane Library, CINAHL) and gray literature sources (WorldCat, Google Scholar) through the end of February 2022. Search terms combined a wide set of psychedelic-related terms (e.g. "psilocybin", "LSD", "ayahuasca", "DMT") with diagnostic and symptom terms for body image disorders and eating disorders (e.g. "Anorexia Nervosa", "Bulimia Nervosa", "Body Dysmorphic Disorder"). Registered clinical trial registries were also searched. All study designs were eligible if they involved patients with ED and/or BDD diagnoses (per ICD-10 or DSM) and reported descriptive or validated measures of symptom change following use of serotonergic psychedelics. MDMA studies were excluded. The review was limited to English-language publications. Screening and full-text review were conducted in Covidence: two independent reviewers screened titles/abstracts and full texts (NL and JR), with conflicts resolved by a third reviewer (DC). Due to the small number of eligible articles, one reviewer (NL) performed data extraction with team review. Extracted variables included study objectives, design, sample characteristics, diagnosis, psychedelic assessed, assessment measures and results.

The search identified 372 records; after automatic duplicate removal 92 duplicates were removed and 26 articles underwent full-text review. Twenty-one full texts were excluded for reasons such as wrong publication type, unsuitable outcomes or populations, leaving five articles that met the inclusion criteria. These comprised two retrospective exploratory qualitative studies (both from the same research group) involving participants who had taken ayahuasca, two case reports (one reporting a person with BDD who used psilocybin, and an English translation of a 1959 French clinical note describing psilocybin use), and one prospective survey study. Across the five included reports, four described reductions in ED or BDD symptoms following ingestion of ayahuasca or psilocybin. The two qualitative ayahuasca studies—retrospective interviews of predominantly female samples with AN or bulimia nervosa—identified themes in which participants reported being better able to identify root causes of their ED, experiencing shifts in self-perception towards greater self-love and self-forgiveness, and reporting improved insight and changes in body image. The BDD case report described three acute psilocybin experiences in which the patient perceived his mirror image as no longer deformed and subsequently engaged with pharmacotherapy (fluoxetine); the translated 1959 case reported short-term euphoria and weight gain after psilocybin injections but limited documentation and loss of effect at one-year follow-up. One included prospective study did not directly measure post-ingestion ED symptoms but documented improvements in well-being and reductions in depressive symptoms.

Ledwos and colleagues interpret the collected literature as sparse but tentatively promising, emphasising that current evidence is preliminary and largely descriptive. The authors describe two broad classes of plausible mechanisms by which classic psychedelics might benefit BDD and EDs. First, neurobiological mechanisms: serotonergic psychedelics agonise 5-HT2A receptors and may ameliorate dysfunctional serotonergic signalling and cognitive inflexibility—features implicated in AN, BN and OCD—potentially enhancing cognitive and neural flexibility. Changes in network dynamics are also discussed; psychedelics may downregulate the default mode network (DMN), increasing global integration and thereby enabling the disruption of rigid self-referential patterns. Agonism at 5-HT receptors in visual cortex could transiently alter visual perception, which might explain acute perceptual changes reported in a BDD case, and a predictive coding model is proposed whereby psychedelics reduce over-weighting of rigid top-down beliefs about the body, allowing bottom-up sensory inputs to recalibrate body-image representations. Second, psychological mechanisms are emphasised: acute psychedelic experiences may promote emotional processing, insight, and changes in body perception and self-identity. The qualitative ayahuasca reports describe confronting difficult emotions, enhanced emotion regulation and shifts toward greater self-acceptance—processes that could plausibly reduce disordered eating behaviours. The authors also consider related findings in other disorders (treatment-resistant depression, OCD, smoking cessation) to suggest shared therapeutic targets. Safety, ethics and implementation are discussed at length. Contemporary clinical trials report mostly transient and tolerable adverse events (for example increases in blood pressure, nausea, headaches, and vomiting with ayahuasca), but archival case material from the 1960s and early work documented longer-lasting harms such as flashbacks and hallucinogen-persisting perception disorder; the authors note such historical data are biased because they derive from harm-compensation records. Ledwos and colleagues stress the importance of rigorous, transparent protocols (including careful selection, preparation and aftercare), attention to set and setting, and involvement of people with lived experience when designing trials. The authors also present preliminary, indirect evidence for related serotonergic interventions: an exploratory analysis from an MDMA-assisted therapy trial for PTSD showed a statistically significant reduction in Eating Attitudes Test-26 scores (F(2,79) = 4.68, p = 0.0335; Hedge's g = 0.33) but Reliable Change Index values did not indicate reliable or clinically meaningful change, underscoring the need for disorder-specific trials. Finally, the authors acknowledge major limitations of the evidence base: the five included studies were small, largely uncontrolled and methodologically heterogeneous; the search was limited to English and no randomized controlled trials were identified. They note five registered clinical trials across North America and Europe, predominantly investigating psilocybin for AN and one for BDD, and call for larger, rigorous trials to determine safety and efficacy.

This systematic review identified only five eligible publications up to February 2022 examining classic psychedelics in patients with BDD or EDs. All included studies reported positive effects on core symptoms or related well-being measures, but evidence is preliminary and largely descriptive. Ledwos and colleagues conclude that existing basic-science and clinical findings from related disorders provide a rationale for further investigation, and they highlight ongoing registered trials of psilocybin in EDs and one in BDD as likely to generate more definitive safety and efficacy data in the near future.