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

Binge Eating Disorder (BED) is the most prevalent eating disorder and is associated with psychiatric comorbidities, health impairments, and decreased quality of life. Emerging evidence suggests that psilocybin-assisted therapy may promote cognitive and emotional flexibility and disrupt maladaptive behavioral patterns, making it a promising candidate for BED treatment. This open-label pilot study evaluated the feasibility, safety, and preliminary therapeutic effects of a single 25 mg dose of psilocybin administered in the context of Acceptance and Commitment Therapy (ACT)-based psychotherapy in adults with BED (N = 5). Primary outcomes included safety measures, and exploratory outcomes included self-reported binge eating frequency, depression, anxiety, psychological flexibility, anthropometric indices, and neuroimaging biomarkers assessed over a 14-week follow-up. Psilocybin was well tolerated, with no serious adverse events. Reductions in self-reported binge eating frequency were observed across all participants and sustained through week 14. Improvements were also noted in depression, anxiety, and psychological inflexibility. Three participants showed reductions in body mass index and waist circumference. Given the open label design and small sample size, causality cannot be inferred. fMRI analyses generated preliminary signals of change-such as increased functional activation from pre- to post-intervention in the middle frontal gyrus, angular gyrus, and supramarginal gyrus in response to processed versus unprocessed food cues. Psilocybin-assisted therapy was feasible and well-tolerated in individuals with BED. The clinical and neurobiological observations provide directions for future adequately powered trials.