[Comment] Peripheral CB1 receptor blockade for treatment of obesity

The endocannabinoid system—comprising cannabinoid receptors (CB1 and CB2), lipid-derived ligands, and metabolic enzymes—plays a major role in regulating energy homoeostasis.1 CB1 receptors are abundant in the brain, where they influence emotionality, cognition, and social behaviour, but are also found in peripheral metabolic organs such as adipose tissue, liver, and pancreas. In these organs, CB1 activation promotes lipogenesis, reduces insulin sensitivity, and impairs leptin action, contributing to obesity-related metabolic dysfunction.