Therefore, in the current study, we continued studying the cardiometabolic benefits of CB1R modulation and aimed to investigate whether CB1R inverse agonism attenuates atherosclerosis development through reversal of dyslipidemia using APOE∗3-Leiden.CETP (E3L.CETP) mice, a well-established mouse model for human-like atherosclerosis development with an intact ApoE-LDLr pathway. This evidence concerns the gene APOE and metabolic syndrome.