The therapeutic potential and mechanisms of action of psilocybin-assisted therapy in anorexia nervosa treatment

Anorexia nervosa (AN) is a serious eating disorder (ED) with high rates of mortality and chronicity. Given the ambivalence towards engaging in treatment and recovery that is characteristic of this condition, the identification of novel treatment avenues that can target motivation and demonstrate superior efficacy to existing treatment options is desperately needed. Psilocybin-therapy has demonstrated efficacy in safely alleviating symptoms of multiple psychiatric conditions, primarily depressive disorders. Although indicated by psychological and neurobiological mechanisms of action, the efficacy of psilocybin-therapy in AN had not been investigated at the commencement of this PhD project. The study detailed in this thesis was a single-blind and within-subject feasibility study in which 21 adult female participants diagnosed with AN were administered with 1mg, 25mg, and 25mg psilocybin in a fixed-order design over a 6-week period, with a subsequent remote 12-month follow-up period. The first aim of this thesis was to investigate the feasibility, safety, and efficacy of this psilocybin-therapy protocol. The feasibility and safety of this treatment protocol was demonstrated. Efficacy in improving ED psychopathology and readiness and motivation to change up to the 12-month follow-up was also reported. The second aim of this thesis was to elucidate causal mechanisms of action of psilocybin-therapy in AN, specifically neuroplasticity and interoception. An electroencephalography (EEG) paradigm reported ED severity-dependent deficits in neuroplasticity at baseline and demonstrated trend-level enhancements in neuroplasticity after high-dose psilocybin. Increases in interoceptive sensibility (IS) were demonstrated via a self-report questionnaire, with trend-level improvements in interoceptive accuracy (iACC) reported via a cardioceptive behavioural task. Enhanced interoception was found to correlate with positive clinical outcomes. This thesis demonstrates the feasibility, safety, and efficacy of this psilocybin-therapy protocol to treat this cohort of adult females with AN. Using multimodal methodologies, potential causal mechanisms of enhanced neuroplasticity and interoception were indicated, warranting their further investigation.