Role of the Endocannabinoid System in Management of Patients with Type 2 Diabetes Mellitus and Cardiovascular Risk Factors

Abstract

To review the role of the endogenous cannabinoid system (ECS) in the peripheral and central regulation of food intake, appetite, and energy storage and discuss the potential for the ECS to be an important target for lowering cardiovascular risk. Materials used for this article were identified through a MEDLINE search of the pertinent literature (1975 to present), including English-language randomized controlled, prospective, cohort, review, and observational studies. We summarize the available experimental and clinical data. The ECS is composed of two 7-transmembrane G protein-coupled cannabinoid receptor subtypes, CB1 and CB2, endogenous cannabinoid ligands (anandamide and 2-arachidonoylglycerol), and the enzymes that synthesize and break down the ligands. Understanding the role of the ECS in central and peripheral metabolic processes related to the regulation of food intake and energy balance as well as the endocrine role of excess adipose tissue, particularly visceral adipose tissue, and its promotion of global cardiometabolic risk has led to the development of pharmacologic agents with potential for blockade of CB1 receptors. In several studies, rimonabant (20 mg daily) demonstrated a favorable effect on various risk factors for cardiovascular disease, including dyslipidemia, abdominal obesity, insulin resistance, blood pressure, and measures of inflammation. The ECS has been shown to have a key role in the regulation of energy balance, and modulation of this system may affect multiple cardiometabolic risk factors. Clinical studies involving pharmacologic blockade of CB1 receptors in overweight patients with and without type 2 diabetes have demonstrated effective weight loss and improvements in several risk factors for cardiovascular disease.