Cannabinoids for Therapeutic Use in Atherosclerosis ^†

Atherosclerosis remains the primary cause of heart disease and stroke that causes about 50% of all deaths in Western countries. The identification of promising novel anti-atherosclerotic therapeutics is therefore of great interest and represents a continued challenge to the medical community. Cannabinoids, such as D9-tetrahydrocannabinol (THC), the major psychoactive compound of marijuana, their synthetic analogs and endogenous cannabinoid ligands, produce their biological effects by interacting with specific receptors. In a mouse model of atherosclerosis, we have recently shown that THC inhibits disease progression through pleiotropic effects on inflammatory cells. Blocking of cannabinoid receptor CB2, the main cannabinoid receptor expressed on immune cells, abolished the observed effects. The potential therapeutic benefit is in conflict with the known health risks of marijuana use, as THC also binds to and activates neuronal CB1 cannabinoid receptors. Besides its well known neurobehavioral effects, THC also mediates cardiovascular effects such as vasodilation and hypotension. The development of novel cannabinoid receptor ligands that selectively target CB2 receptors and are devoid of adverse effects might overcome this problem. In addition, pharmacological modulation of the endocannabinoid system might also offer a new therapeutic strategy in the treatment of atherosclerosis. Several reports demonstrating an implication of the endocannabinoid system in different inflammatory conditions support this hypothesis.