The endocannabinoid system functions as a potent regulator of feeding behavior and energy balance through complex central and peripheral mechanisms. Recent findings have demonstrated the existence of cooperation between peripheral cannabinoid CB1 receptors and the satiety hormone cholecystokinin (CCK). The two systems have opposing actions in the modulation of feeding: while endocannabinoids such as anandamide promote feeding, CCK controls gastrointestinal motility and appetite suppression. In this review, we examine the individual contribution of endocannabinoids and CCK in the modulation of appetite and explore the interaction between the two systems. We also highlight the potential benefits of simultaneously targeting peripheral CB1 and CCK1 receptors to design new therapies to fight obesity.
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