Endocannabinoids and cardiovascular prevention: real progress?

Abstract

The prevalence of obesity continues to increase and represents one of the principal causes of cardiovascular morbidity and mortality. After the discovery of a specific receptor of the psychoactive principle of marijuana, the cannabinoid receptors and their endogenous ligands, several studies have demonstrated the role of this system in the control of food intake and energy balance and its overactivity in obesity. Recent studies with the CB1 receptor antagonist rimonabant have demonstrated favorable effects such as a reduction in body weight and waist circumference and an improvement in metabolic factors (cholesterol, triglycerides, glycemia etc). Therefore, the antagonism of the endocannabinoid (EC) system, if recent data can be confirmed, could be a new treatment target for high risk overweight or obese patients. Obesity is a growing problem that has epidemic proportions worldwide and is associated with an increased risk of premature death (1-3). Individuals with a central deposition of fats have elevated cardiovascular morbidity and mortality (including stroke, heart failure and myocardial infarction) and, because of a growing prevalence not only in adults but also in adolescents, it was reclassified in AHA guidelines as a "major modifiable risk factor" for coronary heart disease (4, 5). Although first choice therapy in obesity is based on correcting lifestyle (diet and physical activity) in patients with abdominal obesity and high cardiovascular risk and diabetes, often it is necessary to use drugs which reduce the risks. The EC system represents a new target for weight control and the improvement of lipid and glycemic metabolism (6, 7).

Keywords: CB1 antagonists; Endocannabinoid system; Obesity.

Fig. 1

Endocannabinoids.

Fig. 2

Effects of rimonobant on adiponectin mRNA levels in lean and obese rats and in CB1 knockout mice.

Fig. 3

Association between obesity and overactivity of the EC system.

Fig. 4

Possible action mechanisms of CB1 receptor blockers and rimonabant effects.

Fig. 5

Study design of RIO (rimonabant in obesity).

Fig. 6

Results of RIO: reduction in body-weight in rimonabant vs. placebo group.