An open-label pilot study of psilocybin-assisted therapy for binge eating disorder

Binge eating disorder (BED) is described as the most prevalent eating disorder and is associated with obesity, impaired quality of life, and psychiatric comorbidity, including depression, anxiety, and impulsivity. The authors note that although existing treatments such as cognitive behavioural therapy and pharmacotherapy can produce moderate to large short-term effects, relapse, treatment resistance, attrition, and limited impact on weight remain common, and long-term effectiveness is still uncertain. They also argue that BED involves rigid, maladaptive behavioural and emotional patterns, along with altered reward processing, inhibitory control, and emotion regulation, which may make it relevant to emerging psychedelic approaches. Against this background, the study set out to examine whether psilocybin-assisted therapy could be feasible, safe, and potentially therapeutically useful for adults with BED. The researchers framed the work as an open-label pilot study of a single 25 mg dose of psilocybin given alongside Acceptance and Commitment Therapy (ACT)-based psychotherapy, with exploratory assessment of binge eating, mood, psychological flexibility, body measures, metabolic biomarkers, and neuroimaging over 14 weeks. The study is presented as an early feasibility and signal-detection trial rather than a definitive efficacy study. The authors state that it was intended to generate preliminary clinical and neurobiological data to guide larger, adequately powered trials.

Dallery and colleagues conducted an open-label pilot study in adults aged 18 to 64 years who met DSM-5 criteria for binge eating disorder. Participants were self-referred via ClinicalTrials.gov and underwent informed consent, screening medical evaluation, physical examination, ECG, and laboratory tests. Exclusions included significant suicide risk, psychotic disorders, bipolar disorder, family history of psychosis, moderate to severe alcohol or substance use disorder, positive drug or alcohol screening, use of several interacting medications or serotonergic supplements, and MRI contraindications where relevant. An unplanned interim review of the first five dosed participants led the researchers to close the study early, before the originally planned enrolment of 10 was reached. The intervention consisted of ACT-based psilocybin-assisted therapy delivered by two trained therapists. Participants attended two preparatory psychotherapy sessions before dosing, then received a single oral dose of synthetic psilocybin 25 mg at approximately 8:00 am in a prepared session room with eyeshades, music, and supportive monitoring. Medical staff and rescue benzodiazepines were available. After the dosing session, therapists conducted integration sessions focused on cognitive defusion, acceptance, mindfulness, and translating insights into values-based action, with an additional follow-up therapy session at week 4. Safety monitoring included adverse events, vital signs, ECGs, laboratory measures, physical examinations, and Columbia-Suicide Severity Rating Scale assessments across the study. Behavioural and subjective psychedelic effects were assessed using the Monitor Rating Scale during dosing and the Mystical Experience Questionnaire, Emotional Breakthrough Inventory, and Challenging Experiences Questionnaire the next day. Binge eating was tracked using daily smartphone reports around the dosing period, the Binge-Eating Scale at multiple follow-ups, and additional self-report measures of anxiety, depression, psychological flexibility, and global improvement. Body mass index and waist circumference were measured serially, and blood biomarkers included leptin, ghrelin, insulin, and glucose. Functional MRI was performed once before dosing and again at week 6, including resting-state and food cue reactivity tasks in fasted and fed states. The imaging analysis used standard preprocessing in CONN, and the food cue task was analysed in SPM12 with whole-brain general linear modelling and cluster-level false discovery rate correction. Because the sample was very small and the study was primarily feasibility-focused, no inferential statistical tests were planned for the behavioural outcome measures; the paper emphasises graphed individual change over time and descriptive reporting.

Eleven people were screened, six were excluded, and five participants completed the trial; these were four women and one man. One participant was enrolled despite a relatively low body mass index because BMI was not an exclusion criterion. Another participant was initially excluded for hypertension but was later rescreened and enrolled after blood pressure stabilised. The paper indicates that a table contains baseline characteristics, but the extracted text does not provide the full numerical detail. Safety findings were favourable. All adverse events were mild and resolved without intervention except for mild sweating in one participant and increased hypoglycaemic events in another. Two participants experienced mild headache attributed to psilocybin. No serious adverse events, suicidal ideation, clinically significant ECG abnormalities, or clinically significant laboratory abnormalities were reported. Subjective effects during dosing varied across participants. Monitor ratings suggested a range from low to more substantial drug effects. On the post-session questionnaires, challenging experiences were generally low in three participants but higher in two, while mystical-type experiences were relatively high in two participants; one participant met criteria for a complete mystical experience. Emotional breakthrough scores were meaningfully high in all but one participant. For binge eating and psychological outcomes, all participants showed reductions in self-reported episodes of eating a large amount of food and loss-of-control eating relative to baseline. The reductions began during the preparation period for some participants and appeared to deepen after dosing, with effects described as sustained through the 14-week follow-up. The Binge-Eating Scale also generally decreased over time, although there was individual variability; one participant did not show a decrease at week 6 and tended to have higher scores later than the others. Anxiety, depression, and psychological inflexibility also declined from screening values in nearly all participants, with one exception for anxiety in a single participant. Global improvement ratings by participants and clinicians were usually in the “very much improved”, “much improved”, or “minimally improved” range, although one participant was rated as showing no change at several time points. Anthropometric changes were mixed. By week 14, three participants showed reductions in both BMI and waist circumference, whereas two showed increases. The researchers report no consistent or meaningful change in the measured metabolic biomarkers. In the fMRI analyses, presentation of processed versus unprocessed food cues showed significant pre-to post-treatment changes in several left-hemisphere regions, including the middle frontal gyrus, supramarginal gyrus, and angular gyrus. Before treatment, processed food cues were associated with lower activation than unprocessed cues in these regions, whereas the pattern reversed after treatment. The extracted text cuts off before the end of the fMRI results, so it does not clearly report whether there were additional significant findings beyond these clusters.

The authors interpret the study as showing that psilocybin-assisted therapy was feasible and well tolerated in people with binge eating disorder, with no serious safety concerns and only mild adverse events. They argue that the observed reductions in binge eating, alongside improvements in anxiety, depression, psychological inflexibility, and some anthropometric measures, suggest the intervention may have promise for BED, although they emphasise that the findings are preliminary. They place these observations in the context of earlier psilocybin research in other psychiatric conditions, including substance use disorders, obsessive-compulsive disorder, anorexia nervosa, and Parkinson's disease. On this basis, they suggest that psilocybin may have transdiagnostic value for disorders characterised by rigid thinking, compulsive behaviours, emotional dysregulation, and maladaptive behavioural patterns. They also note that the imaging findings, particularly the post-treatment increase in activation in regions involved in reward processing, salience, memory, and inhibitory control, could reflect a normalisation of responses to highly appetitive food cues, but they stress that this remains speculative. The authors discuss subjective psychedelic effects as variable, ranging from minimal effects to profound mystical-type experiences. They report no clear relationship between the intensity of these subjective effects and clinical change in this small sample, and they frame this as broadly consistent with earlier metacorrelation work suggesting that subjective effects may contribute to, but do not fully determine, therapeutic response. They also highlight psychological flexibility as a plausible mechanism of change, noting that self-reported inflexibility generally decreased after treatment. Several limitations are acknowledged. The study was open-label, so expectancy effects and lack of causal inference are major concerns. The sample was very small, follow-up was short, and no inferential statistics were planned for the behavioural outcomes, limiting generalisability. They also note substantial heterogeneity in participant responses, which means moderators of treatment response remain unknown. A further limitation was the timing of the post-dose fMRI assessment at week 6, which may have missed acute or sub-acute neural effects; the authors suggest earlier imaging in future studies. Overall, they call for larger randomised controlled trials to test efficacy more rigorously and to clarify clinical and neural mechanisms.