Psilocybin as a Transdiagnostic Treatment for Eating Disorders and Comorbid Psychopathology: Implications for Clinical Nosology and Research Directions

Objective: Eating disorders (EDs) are characterized by high rates of psychiatric comorbidity and suboptimal treatment outcomes. There remain critical gaps in research, including the exploration of effective transdiagnostic interventions. This forum article examines the potential of psilocybin treatment (PT) as a transdiagnostic intervention for EDs and common comorbidities, including the implications for alternative nosological frameworks, trial design, and clinical care.

Method: A narrative review was conducted synthesizing clinical, mechanistic, and conceptual literature on PT for EDs and common psychiatric comorbidities. Searches of academic databases were supplemented by hand-searching and clinical trial registries. Thematic synthesis focused on transdiagnostic clinical evidence, mechanistic theories, and implications for the Hierarchical Taxonomy of Psychopathology (HiTOP), Research Domain Criteria (RDoC), treatment development, and clinical trial design.

Results: Preliminary clinical evidence supports the feasibility, safety, and therapeutic effects of PT for EDs, with robust transdiagnostic effects observed across comorbid conditions. Proposed mechanisms (i.e., serotonergic receptor agonism, psychoplastogenic effects, neural network desynchronization) target shared vulnerabilities that map onto dimensional constructs in HiTOP (Emotional Dysfunction superspectrum, Internalizing spectrum) and RDoC (negative/positive valence, cognitive, and social process domains) nosologies. Future research should explore pragmatic trial designs and dimensional outcome measures to capture the real-world complexities of PT for EDs.

Discussion: PT demonstrates transdiagnostic therapeutic potential for EDs, and the advancement of dimensional nosologies, complex intervention frameworks, and personalized treatment protocols may address existing gaps in research and clinical care.