Psychedelic-Assisted Therapy for People with Eating Disorders

The extracted text does not provide a clear, reproducible methods section for the review (for example, there is no reported database search strategy, date range, or formal inclusion/exclusion criteria). Therefore, the paper should be treated as a narrative review synthesising diverse sources rather than a systematic review or meta-analysis with a published search protocol. Within that narrative framework, the authors examine multiple types of evidence relevant to PAT and eating disorders: pharmacology and historical clinical work, preclinical findings, contemporary functional imaging and mechanistic studies, qualitative reports and case series, secondary analyses of larger trials, and early-phase clinical studies and pilot trials. The review emphasises findings relevant to anorexia nervosa but also notes data concerning other eating-disorder diagnoses and common psychiatric comorbidities. Where specific trial identifiers or pilot studies are available, these are reported (for example, ongoing pilot trials registered on ClinicalTrials.gov and secondary analyses of randomized trials). Details on appraisal methods, risk-of-bias assessment, or formal data synthesis procedures are not provided in the extracted text.

Pharmacology and historical evidence: Classic psychedelics (psilocybin, LSD, DMT, mescaline) primarily act as serotonin 2A (5-HT2A) receptor agonists and have downstream glutamatergic effects; they may also promote neuroplasticity and exert anti-inflammatory actions. MDMA and ketamine are described as non-classic compounds with psychedelic-like subjective effects but distinct primary mechanisms: MDMA affects monoamine release and 5-HT receptors, while ketamine is an NMDA receptor antagonist with glutamatergic effects. Contemporary trials report low rates of serious adverse events with proper screening; common somatic effects include tachycardia, hypertension, nausea, dizziness and headache, and transient psychologically challenging experiences occur in 26-63% of dosing sessions depending on definitions. The authors note that classic psychedelics appear to have relatively low abuse potential based on existing data. Evidence of efficacy in other disorders and relevance to eating disorders: Psilocybin PAT has produced very large effect sizes for MDD in contemporary trials (reported Cohen d values of about 2.2–2.5; Cohen d is a standardised measure of effect size), with response rates up to 71% and remission rates up to 58% in some studies, and antidepressant effects appearing within days and sometimes lasting a year or more. MDMA-assisted therapy shows promising efficacy for PTSD in Phase I–II work. The authors use these findings to motivate exploration of PAT for eating disorders and outline several mechanistic pathways that could plausibly be relevant to eating-disorder pathology: 5-HT2A receptor modulation, changes in resting-state functional connectivity (notably in the default mode network, DMN), reductions in amygdala reactivity to emotional stimuli, promotion of neuroplasticity (e.g., via BDNF), anti-inflammatory effects (e.g., TNF-alpha modulation), and psychological shifts such as increased cognitive and behavioural flexibility, openness and occurrence of mystical or insightful experiences. Clinical and preclinical findings specific to eating disorders: First-wave (1940s–1970s) human data are sparse and of limited rigour, consisting mainly of case reports and superficial series. Contemporary empirical reports are limited but include: a qualitative study of 16 North American individuals with self-reported eating-disorder histories who used ayahuasca, where 11 participants (69%) reported reductions in disordered eating and about half reported decreased comorbid symptoms; a secondary analysis of a large online survey (Spriggs et al.) that found improvements in depression and well-being among 28 participants with self-reported lifetime eating disorders following planned psychedelic use; and a secondary analysis of an MDMA PTSD trial in which, among participants with elevated EAT-26 scores, those receiving MDMA showed a larger mean reduction in EAT-26 than placebo in the high-risk subgroup (scores ≥ 11): mean change -9.58 (SD 7.59) versus -5.58 for placebo, p = 0.0058. Pilot clinical trials and preclinical models: Since 2019, three pilot studies of psilocybin in people with AN have been registered, and one trial that used a single 25 mg dose in a supported setting has reported preliminary outcomes: 5 of 10 participants met criteria for remission at 1 month and 6 of 10 at 3 months according to the Eating Disorder Examination, though the sample had a mean baseline BMI of 19.7 kg/m2 and 50% were in partial remission at entry. Preclinical work using the activity-based anorexia rodent model reported that psilocybin improved reversal learning (a measure of cognitive flexibility), reduced compulsive running and increased food intake, suggesting potential mechanistic relevance. Methodological, safety and implementation challenges: The authors highlight several complications for rigorous trials in this population. Effective blinding is difficult because subjective drug effects are salient, and inactive placebos may lead to demoralisation and nocebo effects; active placebos (niacin, very low-dose psilocybin, or other psychoactive comparators) have been explored but remain imperfect. Distinguishing drug-specific effects from the psychotherapeutic container is challenging because PAT inherently includes substantial psychotherapeutic support. Participants with AN in a pilot study reported lower-than-expected subjective effects from comparable psilocybin doses; the authors suggest possible contributors including starvation-related physiology, illness-related traits, or high rates of recent serotonergic antidepressant use, which can blunt psychedelic effects. Although standard practice involves tapering antidepressants before dosing, secondary analyses suggest prior antidepressant exposure may reduce clinical efficacy even after a washout. Medical complications common in eating disorders—electrolyte disturbances, hypoglycaemia, arrhythmias, hepatic or renal impairment—raise safety concerns; contemporary pilots have used minimum BMI cutoffs (typically ≥ 15–16 kg/m2) and baseline medical screening to mitigate acute risks. Open questions remain about optimal timing of PAT relative to nutritional rehabilitation, the type and duration of post-dosing therapeutic supports needed to sustain behavioural change, and selection of patients most likely to benefit.

Gukasyan and colleagues interpret the current literature as suggestive but insufficient: PAT has theoretical and preliminary empirical reasons to be of interest for eating disorders, particularly AN, yet high-quality clinical evidence specific to these conditions remains limited. They situate the existing findings against stronger evidence in other indications (for example, MDD and PTSD), noting that mechanistic plausibility—serotonergic modulation, network-level changes, neuroplasticity and psychological flexibility—provides a biological and psychological rationale for further investigation. The authors explicitly acknowledge important limitations and uncertainties. Historical human data are sparse and methodologically weak; contemporary human data specific to eating disorders are limited to small uncontrolled studies, qualitative reports, secondary analyses and preliminary pilot trials with small sample sizes and participant heterogeneity. They also flag methodological difficulties that could bias estimates of effect, including impaired blinding, confounding by psychotherapeutic elements of PAT, and potential attenuation of drug effects by recent antidepressant exposure or starvation-related neurobiology. Safety concerns are emphasised because of common medical complications in this population; the paper notes that ongoing trials have used conservative BMI cutoffs and screening but that more safety data are needed. In terms of implications, the authors advise clinicians to be prepared to discuss what is known and unknown about psychedelics with patients and families. For researchers, they recommend prioritising carefully controlled clinical trials to delineate risks, dosing, timing, patient selection, concomitant supports and longer-term outcomes. Regulatory and access issues are also discussed: even if rescheduling occurs for some indications, access for eating-disorder patients may be constrained by risk-management strategies, reimbursement questions, and non-medical routes of access such as decriminalisation initiatives or private retreat centres, which carry variable screening and safety protections.

Eating disorders are complex, high-burden illnesses with substantial medical and psychiatric comorbidity. While PAT shows promise for conditions that commonly co-occur with eating disorders and preliminary preclinical and early human data indicate potential benefits, robust evidence for efficacy and safety in people with eating disorders is currently lacking. The authors conclude that numerous unanswered questions remain—about which patients might benefit, appropriate dosing, timing relative to nutritional status, and safety monitoring—and they call for rigorous, well-controlled clinical trials to establish the therapeutic role of PAT in this population. Clinicians should be ready to discuss the current state of knowledge and uncertainty with patients, and researchers must focus on resolving the outstanding methodological and safety issues.