Towards a therapeutic use of selective CB2 cannabinoid receptor ligands for atherosclerosis

Atherosclerosis remains the primary cause of heart disease and stroke, causing approximately 50% of all deaths in Western countries. The identification of promising novel anti-atherosclerotic therapies is therefore of great interest and represents a continued challenge to the medical community. Cannabinoids, such as Delta9-tetrahydrocannabinol (THC), which is the major psychoactive compound of marijuana, modulate immune functions and might therefore be of therapeutic use for the treatment of inflammatory diseases. The authors have demonstrated recently that oral treatment with low dose THC inhibits atherosclerosis progression in mice through pleiotropic immunomodulatory effects on inflammatory cells. All these effects were mediated via the cannabinoid receptor CB(2), the main cannabinoid receptor expressed on immune cells. However, these promising results are in conflict with the known health risks of smoking marijuana, as THC binds to and activates both cannabinoid receptors, CB(1) and CB(2). The identification and characterization of cannabinoid derivative that selectively activate CB(2) receptors and are devoid of adverse effects might offer a novel therapeutic strategy for the treatment of atherosclerosis.