Endocannabinoids and cannabinoid CB1 receptors are known to play a generalized role in energy homeostasis. However, clinical trials with the first generation of CB1 blockers, now discontinued due to psychiatric side effects, were originally designed to reduce food intake and body weight rather than the metabolic risk factors associated with obesity. In this review, we discuss how, in addition to promoting energy intake, endocannabinoids control lipid and glucose metabolism in several peripheral organs, particularly the liver and adipose tissue. Direct actions in skeletal muscle and pancreas are also emerging. This knowledge may help in the design of future therapies for the metabolic syndrome.

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