Prospects for the Use of Cannabinoid Receptor Ligands for the Treatment of Metabolic Syndrome and Atherosclerosis: Analysis of Experimental and Clinical Data

Abstract

An antagonist of central cannabinoid CB1 receptors rimonabant causes weight loss in patients with obesity and metabolic syndrome, improves blood lipid parameters, increases the adiponectin level, decreases the rate of glucose and glycosylated hemoglobin in patients with diabetes mellitus type-2. However, rimonabant adverse effects include depression, anxiety, nausea, and dizziness which are apparently due to the blockade of central CB1 receptors. In mice with a high-calorie diet, we defined that the blockade of peripheral CB1 receptors prevents obesity, steatosis of the liver, improves lipid and carbohydrate metabolism. Experimental studies suggest that peripheral CB2 receptor agonists have antiatherogenic effect. To validate the expediency of clinical research of CB2 receptor agonists in patients with atherosclerosis the comparative analysis of antiatherogenic properties of cannabinoids should be performed. In addition, experiments are needed on the combination use of cannabinoids with well-known antiatherogenic agents, such as statins.

Activating Cannabinoid Receptor 2 Protects Against Diabetic Cardiomyopathy Through Autophagy Induction

“…In the cardiovascular system, activating CB 2 shows an attenuative effect on the pathogenesis of myocardial ischemia through the protection of cardiomyocytes and maintenance of cardiac function ( Wang et al, 2014 ; Pacher et al, 2018 ). In other cardiovascular disorders such as atherosclerosis, activating CB 2 was also reported to be protective through the inhibition of inflammatory reaction and lipid metabolism in plaque macrophages ( Jiang et al, 2016 ; Maslov and Karpov, 2017 ). In addition, in diabetes, it was also demonstrated that deficiency of CB 2 worsened the severity of diabetes as well as renal functional abnormalities in STZ-induced diabetic mice ( Barutta et al, 2014 ).…”

“…Unlike CB 1 which is mainly distributed in the central nervous system, CB 2 is widely spread in peripheral tissues and cells in the immune system like macrophages and T cells as well as other peripheral tissues like the heart tissue ( Li et al, 2016 ; Han et al, 2017 ). Activating CB 2 has been reported to produce a cardio-protective effect in myocardial ischemia as well as other cardiovascular diseases like atherosclerosis ( Moris et al, 2015 ; Maslov et al, 2016 ; Maslov and Karpov, 2017 ). However, whether activating CB 2 protects against DCM has not been elucidated.…”

Role of Cannabinoids in Obesity

“…Therefore, the focal point is the possibility to use antagonists at CB1 in anti-obesity treatments. Rimonabant, antagonist at CB1, has long been used as an anti-obesity drug able to induce weight loss, improve blood lipid parameters and increase the adiponectin level in obese patients [ 67 ], but it had severe side effects including depression, anxiety, nausea and dizziness probably due to the blockade of central CB1. Because of these complications Rimonabant has been withdrawn from the market.…”

ZnO Nanoparticles Induce Dyslipidemia and Atherosclerotic Lesions Leading to Changes in Vascular Contractility and Cannabinoid Receptors Expression as Well as Increased Blood Pressure

“…Activation of the CB 1 receptor, with agonists such as anandamide, induces vasorelaxation [ 33 , 34 ] and a decrease in the blood pressure in normotensive and hypertension models [ 35 , 36 ]. Blockade of the CB 1 receptor decreases the atherosclerosis risk while activation of the CB 2 receptor decreases the progression of the atherosclerosis acting as a cardioprotective agent [ 37 , 38 , 39 , 40 , 41 ]. Furthermore, increased CB 1 receptor expression has been associated with vascular smooth muscle cell proliferation and atherosclerosis [ 42 , 43 ].…”