Effect of dronabinol therapy on physical activity in anorexia nervosa: a randomised, controlled trial.

Purpose: The level of physical activity is inappropriately high in up to 80% of the patients suffering of anorexia nervosa (AN), as a result of conscious efforts to lose weight, affect regulation and biological adaptive changes to starvation induced by hypothermia and neuroendocrine mechanisms. The purposes of this paper were to (1) assess the effect of dronabinol-a synthetic cannabinoid agonist-on physical activity in patients with chronic and stable AN, and to (2) unravel the role of leptin and cortisol in this process. Methods: This prospective, randomised, double-blind, crossover study was conducted at a specialised care centre for eating disorders. Twenty-four adult women with AN of at least 5-year duration received either the dronabinol-placebo or placebo-dronabinol sequence. Physical activity was monitored during the fourth week of each intervention. Body weight, leptin and urinary free cortisol excretion were measured repeatedly during the trial. Changes in behavioural dimensions related to AN were assessed by Eating Disorder Inventory-2. Results: The total duration of physical activity did not change, while its average intensity increased by 20% (P = 0.01) during dronabinol therapy, resulting in an increased energy expenditure with 68.2 kcal/day (P = 0.01) above placebo. Conclusions: This randomised, double-blind study revealed that cannabinoid agonist treatment was associated with a modest increase in physical activity in adult women with severe and longstanding AN. Additionally, we detected a strong relationship between the circulating levels of leptin and physical activity in these chronically undernourished patients.