Cannabinoids might be valuable for treating cardiovascular disease, according to recent research published in Nature. Steffens and colleagues show that oral treatment with a low dose of Δ-9-tetrahydrocannabinol (THC) — the major constituent of marijuana — inhibits disease progression in a mouse model of atherosclerosis.

Atherosclerosis, the main cause of cardiovascular disease and stroke in Western countries, is generally recognized as a chronic inflammatory disorder. Given the growing evidence that cannabinoids such as THC have anti-inflammatory and immunomodulatory effects, Steffens et al. set out to investigate whether cannabinoid treatment would alter inflammatory processes pivotal for the development of atherosclerosis in the well-established apolipoprotein-E -knockout (ApoE−/−) mouse model.

A daily oral dose of THC that was sufficient to produce anti-inflammatory effects, but lower than that associated with psychotropic effects, was given to ApoE−/− mice that had established atherosclerotic lesions as a result of being fed a high-cholesterol diet for 5 weeks. After 6 further weeks on the same high-cholesterol diet, mice that received daily THC during this period showed significantly reduced progression of atherosclerotic lesions compared with control mice.

So, what underlies this effect? It has been suggested that the immunomodulatory effects of cannabinoids are mediated by the CB2 receptor, which is primarily expressed on immune cells (the CB1 receptor that is thought to mediate their psychotropic effects is expressed primarily in the brain). Indeed, the authors found that CB2 receptors were present in atherosclerotic plaques of human and mouse diseased arteries, but not in non-diseased arteries. Moreover, the inhibitory effect of THC on atherosclerotic lesion progression was completely abolished in the presence of a specific CB2 receptor antagonist.

Further experiments provided evidence that THC suppresses the TH1 response, which is thought to be important during early atherosclerosis development, and that it inhibits the migration of inflammatory cells into atherosclerotic lesions; this inhibitory effect was also blocked by the CB2 receptor antagonist. Overall, the findings indicate that developing compounds with activity at the CB2 receptor could be a promising novel therapeutic strategy for atherosclerosis.