Anorexia nervosa carries one of the highest mortality rates of any psychiatric condition, yet no pharmacological treatment has demonstrated reliable efficacy in decades of research. That gap makes any signal of therapeutic benefit — however preliminary — worth scrutiny, particularly when it involves a mechanism as novel as psychedelic-assisted therapy.
This single-blind within-individual pilot enrolled 21 adult females diagnosed with anorexia nervosa, administering oral psilocybin (COMP360) across three sessions over six weeks in a fixed ascending dose sequence of 1 mg, 25 mg, and 25 mg, integrated with talk therapy alongside standard care. Primary outcomes centered on the Eating Disorder Examination global score and a precontemplation subscale of the Readiness and Motivation Questionnaire, assessed at six weeks, three months, and six months. All 21 participants tolerated the compound without treatment discontinuation; the most frequently reported adverse events were headache, nausea, and dizziness. Notably, two serious adverse events — suicide attempts — were recorded during the study period, a finding that demands careful contextual interpretation given this population's elevated baseline psychiatric risk.
This trial adds to a small but accumulating body of evidence suggesting psilocybin may modulate rigid cognitive patterns and body-image distortion via serotonin 5-HT2A receptor agonism, mechanisms theoretically relevant to the psychological core of anorexia. Prior work in depression and OCD, conditions with overlapping ruminative features, has shown comparable neuroplasticity effects. However, the limitations here are substantial: 21 participants with no parallel control arm makes causal inference impossible; the single-sex, within-individual design cannot separate drug effects from therapeutic alliance, expectancy, or natural illness fluctuation. The two serious adverse events also raise legitimate safety questions that a larger randomized controlled trial must address. As an incremental signal from a high-need area, this work justifies expanded controlled investigation, but clinical translation remains distant.