701. Efficacy and safety of COMP360 psilocybin therapy in anorexia nervosa: a proof-of-concept study

Abstract Background There are no approved medications for treating anorexia nervosa (AN) despite having the highest mortality rate of all psychiatric conditions. Talk therapies have limited efficacy, with relapse rates as high as 52% and poor long-term outcomes. Aims & Objectives This study evaluated the effects and safety of COMP360 psilocybin, a novel treatment, in individuals with anorexia nervosa (AN).

Method: Participants were assigned to either of two arms, receiving a single dose of 25 mg or 1 mg psilocybin.

Results: Rapid improvements in Eating Disorder Examination (EDE) global scores were noted in the 25 mg group compared to the 1 mg group as early as Week 2, with benefits maintained up to Week 12, though the difference between groups and the sample size diminished over time. At Week 2, the least squares mean (LSM) difference between groups was statistically significant, but by Weeks 4 and 12, the difference was smaller and less certain. The effect size also decreased, indicating a waning treatment impact over time. For the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), which measures obsessive-compulsive symptoms, a moderate treatment effect was observed in the 25 mg group at Day 2, but this effect lessened by Week 4 and Week 12. This suggests that while COMP360 may offer rapid symptom relief, the longer-term benefits are less clear and may require further investigation. Importantly, there were no significant differences in weight change between the two groups, indicating that the treatment did not affect this key clinical outcome for AN patients during the study period. Safety was a central focus, and the findings were reassuring. No new safety signals emerged for the AN population. The most frequent treatment-emergent adverse events (TEAEs) were headache and nausea, with a higher incidence observed in the 25 mg group compared to the 1 mg group. Most adverse events were mild and resolved within 24 hours. Four treatment-emergent serious adverse events (TESAEs) occurred in two participants in the 25 mg group, but all were resolved without lasting consequences. Discussion & Conclusions Despite the promising rapid symptomatic improvement and favourable safety profile, the trial encountered several challenges. Recruitment proved difficult, resulting in the target sample size not being achieved. Furthermore, dropout rates were high in the control arm, which may have affected the robustness and generalisability of the findings. Existing measures of AN symptoms, such as the EDE, may also lack sensitivity to detect meaningful change in this population, highlighting a need for more appropriate outcome assessments in future research. In summary, COMP360 appears to show potential for quickly improving symptoms and behaviours associated with anorexia nervosa and demonstrates a generally safe and well-tolerated profile. However, the diminishing effect over time, recruitment issues, and limitations in current symptom measurement tools suggest that future studies should carefully consider the study population and methods of outcome assessment. Further research is necessary to confirm these findings and optimise the evaluation of new treatments for patients with AN.