2026 ECNP Congress

PS03-3064

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

Rachael Taylor — H. Simmons, Z. Alashe, S.T. Aaronson, J. Farrington, H. Himmerich, W. Kaye, J.R. Kelly, Z. Sidney, E. Williams, C. Sisa, M. Croal, G.M. Goodwin · Compass Pathways, Research and Development, London, United Kingdom

2026 ECNP Congress

Introduction

Anorexia nervosa (AN) has the highest mortality rate of all psychiatric conditions and has no approved pharmacological treatments1. Psychological therapies show limited efficacy, with relapse rates reported up to 52% and poor long‑term outcomes2-4, highlighting a substantial unmet clinical need for novel treatment approaches. This study evaluated the efficacy and safety of a single dose of COMP360 (a proprietary, pharmaceutical-grade synthetic psilocybin formulation, developed by Compass Pathfinder Ltd.), administered with support and monitoring in participants with AN.

Methods

This was a phase II, randomised, fixed-dose, double-blind, multi-centre study conducted in the United Kingdom, Ireland, and the United States. The target sample was up to 60 participants, randomised 2:1 to a single 25 mg or 1 mg dose of COMP360. Following a 3–6-week screening period, participants completed a baseline assessment one day before dosing, and were followed up for 12-weeks. The primary endpoint was change from Baseline in EDE scores at Week 4 (25 mg vs 1 mg). Secondary endpoints included change from Baseline in Y-BOCS scores at Week 4 and weight at Week 12. Efficacy outcomes were analysed using mixed effects models for repeated measures, with treatment and visit as fixed effects, treatment-by-visit interaction, and Baseline EDE global score as a covariate.

Safety assessments included adverse events (AEs), vital signs, clinical laboratory tests, suicidality assessments, and ECG.

Results

Thirty-two female outpatients aged between 20-54 years (Mean [M]=33.4, standard deviation [SD]=9.15) participated. All met the DSM-5 criteria for mild to severe AN, with a mean illness duration of 14.8 years (SD=9.58). Mean baseline EDE global score was 3.27 (SD=1.04).

Rapid improvements in EDE scores were observed for the COMP360 25 mg arm vs the 1 mg arm at Week 2 (least squares mean (LSM) difference (standard error [SE]) [95% confidence interval {CI}] = -1.05 (0.42) [-1.92, -0.18]). Improvement in the 25 mg group was maintained at Weeks 4 to 12, but the between-group difference and sample size was reduced (Week 4 LSM difference (SE) [95% CI] = -0.27 (0.44) [-1.16, 0.62], d=-0.28; Week 12 LSM difference (SE) [95% CI] = -0.38 (0.44) [-1.28, 0.52], d=-0.78).

For Y-BOCS, a moderate treatment effect was observed at Day 2 (LSM difference from 1 mg (SE) [95%CI] = -3.1 (2.15) [-7.5, 1.3], d=-0.53), but the treatment difference reduced over time (-0.5 at Week 4, and -0.4 at Week 12). There were no discernible differences in weight change between groups.

There were no new safety signals. The most common TEAEs were headache (71.4 % (25 mg) and 36.4% (1 mg)) and nausea (61.9% (25 mg) and 27.3% (1 mg)). Most events were mild and resolved within 24 hours. Four TESAEs occurred in 2 participants in the 25 mg group, all resolved.

Conclusions

A single administration of COMP360 demonstrated initial promise in rapidly improving symptoms associated with AN and was generally safe and well tolerated. However, recruitment challenges, control‑arm dropout, and potential limitations of current outcome measures should be addressed in future studies.

References

  1. Arcelus J, Mitchell AJ, Wales J, Nielsen S. Mortality Rates in Patients With Anorexia Nervosa and Other Eating Disorders: A Meta-analysis of 36 Studies. Arch Gen Psychiatry. 2011 July 1;68(7):724–31.
  2. Keel PK, Herzog DB, Eddy KT, Thomas JJ, Keshaviah A, Tabri N, et al. Recovery From Anorexia Nervosa and Bulimia Nervosa at 22-Year Follow-Up. 2017 Feb 22 [cited 2026 Jan 23]; Available from: https://www.psychiatrist.com/jcp/recovery-from-anorexia-and-bulimia-at-year-follow-up/
  3. Eddy KT, Keel PK, Dorer DJ, Delinsky SS, Franko DL, Herzog DB. Longitudinal comparison of anorexia nervosa subtypes. International Journal of Eating Disorders. 2002;31(2):191–201.
  4. Khalsa SS, Portnoff LC, McCurdy-McKinnon D, Feusner JD. What happens after treatment? A systematic review of relapse, remission, and recovery in anorexia nervosa. J Eat Disord. 2017 June 14;5(1):20.