The endogenous cardiac cannabinoid system: a new protective mechanism against myocardial ischemia

The pharmacological (and recreational) effects of cannabis have been known for centuries. However, it is only recently that one has identified two subtypes of G-protein-coupled receptors, namely CB1 and CB2-receptors, which mediate the numerous effects of delta9-tetrahydrocannabinol and other cannabinoids. Logically, the existence of cannabinoid-receptors implies that endogenous ligands for these receptors (endocannabinoids) exist and exert a physiological role. Hence, arachidonoylethanolamide (anandamide) and sn-2 arachidonoylglycerol, the first two endocannabinoids identified, are formed from plasma membrane phospholipids and act as CB1 and/or CB2 agonists. The presence of both CB1 and CB2-receptors in the rat heart is noteworthy. This endogenous cardiac cannabinoid system is involved in several phenomena associated with cardioprotective effects. The reduction in infarct size following myocardial ischemia, observed in rats exposed to either LPS or heat stress 24 hours before, is abolished in the presence of a CB2-receptor antagonist. Endocannabinoids and synthetic cannabinoids, the latter through either CB1 or CB2-receptors, exert direct cardioprotective effects in rat isolated hearts. The ability of cannabinoids to reduce infarct size has been confirmed in vivo in anesthetized mice and rats. This latter effect appears to be mediated through CB2-receptors. Thus, the endogenous cardiac cannabinoid system, through activation of CB2-receptors, appears to be an important mechanism of protection against myocardial ischemia.