Review: The endocannabinoid system: a new therapeutic target for cardiovascular risk factor management

uropean guidelines on cardiovascular disease prevention in clinical practice have identified obesity and smoking as primary risk factors for cardiovascular disease, the increased prevalence of which underlines the need for new therapeutic targets. The endocannabinoid (EC) system is a physiological system, comprising the cannabinoid receptors, cannabinoid type 1 (CB1) and type 2 (CB2), and their natural ligands, such as anandamide and 2-arachidonyl-glycerol (2-AG). The system plays a key role in energy balance regulation, both centrally and peripherally impacting on food intake, lipid and glucose metabolism, and fat accumulation. The EC system is also involved in nicotine dependence. Over activity of the EC system, associated with obesity or chronic tobacco use, leads to increased levels of endogenous ligands (endocannabinoids) and disrupts the feedback mechanism related to steady state homeostasis. Rimonabant, the first selective CB1 receptor blocker, normalises the EC system, reduces food intake and body weight, improves lipid and glucose metabolism and insulin sensitivity and reduces nicotine self-administration. Clinical trials are ongoing to support the therapeutic potential of rimonabant in reducing these multiple cardiovascular risk factors.