Blocking the CB1 receptor reduced cholesterol problems and artery disease in mice, even without obesity

In lean mice with dyslipidemia, 20 weeks of rimonabant treatment reduced VLDL-TG production by 52%, lowered non-HDL-C by 19%, raised HDL-C by 57%, and decreased atherosclerotic lesion size by 64% with reduced severity (28% vs. 56% severe lesions).

Female APOE*3-Leiden.CETP transgenic mice (a humanized model of dyslipidemia) were fed a Western-type diet with or without rimonabant (20 mg/kg/day) for up to 20 weeks. Plasma lipids, bile acids, and atherosclerotic lesions in the aortic valve region were measured.

This study separated the cardiovascular benefits of endocannabinoid system inhibition from its anti-obesity effects, showing that CB1 blockade can protect against atherosclerosis through direct lipid metabolism improvements.

While rimonabant was withdrawn from human use due to psychiatric side effects, these results suggest the endocannabinoid system plays a direct role in lipid metabolism and atherosclerosis beyond its effects on body weight.

Animal study in a specialized transgenic mouse model. Rimonabant was pulled from the European market due to psychiatric adverse effects, limiting direct clinical translation. Sex-specific (only female mice).