Psilocybin therapy for females with anorexia nervosa: a phase 1, open-label feasibility study

Introduction

Anorexia nervosa (AN) is a severe, often chronic and deadly psychiatric disorder with substantial morbidity and mortality, including an estimated 18-fold increase in mortality and elevated suicide risk. Despite these consequences, adult AN lacks proven treatments that reliably reverse core psychopathology and has no approved pharmacological therapies; fewer than half of patients recover, relapse rates approach 50% and about 20% develop a chronic course. Previous research indicates altered serotonergic function in AN and altered 5-HT2A receptor activity, and contemporary studies of psilocybin suggest that a single administration can produce rapid and enduring neural and psychological changes via serotonergic (and downstream dopaminergic and glutamatergic) mechanisms. This raises the possibility that psilocybin therapy, when paired with psychological support, might disrupt rigid, ego-syntonic patterns and improve emotional processing and cognitive flexibility relevant to AN symptoms. Peck and colleagues report a Phase I, open-label feasibility study that aimed to evaluate the safety, tolerability and acceptability of a single 25 mg dose of pharmaceutical-grade synthetic psilocybin (COMP360) administered with psychological support to adult females meeting DSM-5 criteria for AN or partial remission (pAN). In addition to primary safety endpoints, the investigators explored preliminary signals of efficacy on eating-disorder-specific psychopathology and related measures over a 3-month follow-up, to inform the design of future controlled trials.