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The endocannabinoid system is a critical regulator of energy homeostasis and food intake. Through cannabinoid (CB)1 receptors in the brain and periphery, endocannabinoids exert powerful effects on the systems of the body that coordinate the balance between food intake, metabolism, and energy expenditure. These integrative systems control food intake both by modulating the inputs to various brain areas that monitor energy balance and by increasing the hedonic or reward value of the food consumed. Cannabinoids also alter metabolism, acting through both centrally located CB1 receptors that drive neuronal pathways controlling metabolism and peripheral CB1 receptors located in tissues throughout the body.