Cannabidiol in Anorexia Nervosa: A Double-Blind Randomized Placebo Controlled Pilot Study to Test Safety, Pharmacokinetics, and Symptom Change.

Objective: Anorexia nervosa (AN) is a severe psychiatric disorder marked by an intense fear of gaining weight and persistent body dissatisfaction, both during periods of underweight and after weight restoration. The endocannabinoid system may offer therapeutic benefits, particularly in reducing anxiety. This randomized controlled trial of cannabidiol (CBD) investigated safety, tolerability, pharmacokinetics, and symptomatic improvement in An. Method: In a double-blind design, women with AN or Atypical AN were randomized to receive CBD (n = 16) or placebo (n = 16) over 21 days. The dose was up-titrated weekly from 1.25 mg/kg twice daily to a maximum of 6.25 mg/kg twice daily, while assessing CBD and metabolite levels, liver function, and severity of eating disorder, depression, and anxiety symptoms. Results: Age at baseline was similar between the CBD and placebo group (22.9 +/- 2.8 years vs. 22.5 +/- 3.5 years), as was body mass index (BMI, kg/m (2) , 20.1 +/- 2.5 vs. 19.4 +/- 1.8). CBD demonstrated the expected pharmacokinetics with limited and nonserious adverse events. Repeated measures MANCOVA indicated a small but significant group-by-time interaction for BMI increase in favor of CBD (F = 3.039, p = 0.046, partial eta (2) = 0.252). Effect sizes for improvements in shape concern and perception of lack of control over eating were also large (partial eta (2) > 0.14), favoring CBD but nonsignificant. Discussion: This study suggests that CBD is well tolerated in individuals with AN. Furthermore, indication of better weight recovery and improvement of eating disorder specific symptoms in the CBD group suggest treatment effects of CBD in AN. The study was, however, constrained by its small sample size and limited duration and requires replication in a larger sample. Trial Registration: ClinicalTrials.gov identifier NCT04878627.