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

Stephen N. Davis, MD, FRCP; Jennifer M. Perkins, MD


Endocr Pract. 2007;13(7):790-804. 

In This Article

Abstract and Introduction


Objective: 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.Methods: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.
Results: 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 CB1receptors. 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.
Conclusion: 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 CB1receptors in overweight patients with and without type 2 diabetes have demonstrated effective weight loss and improvements in several risk factors for cardiovascular disease.


The endogenous cannabinoid system (ECS) is a physiologic system whose modulation or blockade may pro-vide an approach to lower the risk of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM). The ECS has an important role in the central and peripheral promotion of food intake and energy storage and also influences feeding behavior and appetite.[1] Recent advancements in the characterization of the ECS have identified its blockade as a new therapeutic option in the management of global cardiometabolic risk.[2] In this article, we will discuss the function of the ECS in modulating central and peripheral metabolic processes related to the regulation of food intake and energy balance. The endocrine role of excess adipose tissue, particularly visceral adipose tissue, in the promotion of global cardiometabolic risk, especially in patients with T2DM or prediabetes, will be examined. Lastly, the blockade of the ECS as a pharmacologic approach to reduction of global cardiometabolic risk will be addressed. Materials for this review were identified by conducting a MEDLINE search of the related literature published between 1975 and the present.


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