BACKGROUND: Little is known about the physiological role of the endocannabinoid system in the regulation of the motility and the sensitivity of the stomach. Endocannabinoid system dysfunction has been hypothesized to contribute to the control of food intake and the pathogenesis of functional dyspepsia. AIM: To study the influence of rimonabant, the endocannabinoid 1 (CB1) receptor antagonist, on gastric sensorimotor function in healthy controls. METHODS: After 4 days of pre-treatment with rimonabant 20 mg/day or placebo, 12 healthy volunteers (mean age 34 +/- 12 years, six men) participated in a placebo-controlled, double-blind, randomized, crossover study with a gastric barostat assessment of gastric sensitivity to distension, gastric compliance, gastric accommodation and phasic motility on day 3 and a liquid nutrient challenge test on day 4. RESULTS: Rimonabant did not influence gastric compliance and sensitivity to distension. The meal-induced gastric accommodation reflex was significantly inhibited by rimonabant (154.3 +/- 30.9 vs. 64.3 +/- 32.4 mL, P = 0.02). Rimonabant did not affect maximal nutrient tolerance or meal-related symptoms during the satiety drinking test. CONCLUSION: Endocannabinoids acting on the CB1 receptor are involved in the control of gastric accommodation in man.