Peripheral endocannabinoid system activity in patients treated with sibutramine


  • S. Engeli
  • K. Heusser
  • J. Janke
  • K. Gorzelniak
  • S. Batkai
  • P. Pacher
  • J. Harvey-White
  • F.C. Luft
  • J. Jordan


  • Obesity


  • Obesity (Silver Spring) 16 (5): 1135-1137


  • Objective:The endocannabinoid system (ECS) promotes weight gain and obesity-associated metabolic changes. Weight loss interventions may influence obesity-associated risk indirectly through modulation of the peripheral ECS. We investigated the effect of acute and chronic treatment with sibutramine on components of the peripheral ECS.Methods and Procedures:Twenty obese otherwise healthy patients received randomized, double-blind, crossover treatment with placebo and 15 mg/day sibutramine for 5 days each, followed by 12 weeks open-label sibutramine treatment. We determined circulating anandamide and 2-arachidonoylglycerol and expression levels of endocannabinoid genes in subcutaneous abdominal adipose tissue biopsies.Results:Body weight was stable during the acute treatment period and decreased by 6.0 +/- 0.8 kg in those patients completing 3 months of sibutramine treatment (P < 0.05). Circulating endocannabinoids and the expression of ECS genes did not change with acute or chronic sibutramine treatment.Discussion:The ECS is activated in obesity. We did not find any influence of 5% body weight loss induced by sibutramine on circulating levels of endocannabinoids and adipose-tissue expression of endocannabinoid genes in obese subjects. These data confirm our previous findings on dietary weight loss and suggest that the dysregulation of the ECS may be a cause rather than a consequence of obesity.