Cardiovascular Risk Management by Blocking the Endocannabinoid System

Abstract

The specific blockade of endocannabinoids at the level of the cannabinoid receptor 1 (CB₁ receptor) is a new therapeutic option to reduce body weight and manage cardiovascular risk. Although clinical trials are underway to document the safety and efficacy of this approach, much is still unknown about this endogenous system. Endocannabinoids and their receptors are expressed in the central nervous system as well as in the periphery and regulate the central neural circuits for food uptake and peripheral metabolic circuits. Within the context of food uptake, the stimulation of the CB₁ receptor with Δ⁹-tetrahydrocannabiol (Δ⁹-THC) enhances food consumption, while its blockade with receptor antagonists is an emerging relevant therapeutic means to reduce body weight. Rimonabant is the first of a new class of drugs that interferes with the endocannabinoid system by blocking the CB₁ receptor. In recent clinical studies, a substantial reduction in body weight and waist circumference was associated with an improvement of the cardiovascular risk profile. In particular, increased HDL cholesterol, decreased serum triglycerides and improved insulin sensivity were observed. Further research will serve to establish the role of these compounds in cardiovascular risk management.

Key words

Overweight - rimonabant - endocannabinoid system - cardiovascular risk - metabolic syndrome

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