cannabidiol and Metabolic-Syndrome

Cannabidiol, a cannabinoid and serotonin receptor antagonist, may alleviate hyperphagia without the side effects of rimonabant (for example depression and reduced insulin sensitivity). Similar to the peroxisome proliferator-activated receptor-gamma agonists, it may also help the differentation of adipocytes. Cannabidiol has an immunomodulating effect, as well, that helps lessen the progression of atherosclerosis induced by high glucose level. It may also be effective in fighting ischaemic diseases, the most harmful complications of metabolic syndrome. However, it can only be administered as an adjuvant therapy because of its low binding potency, and its inhibiting effect of cytochrome P450 enzymes should also be considered. Nevertheless, it may be beneficially used in adjuvant therapy because of its few side effects.

Topics: Adipocytes; Appetite Depressants; Atherosclerosis; Cannabidiol; Cannabinoid Receptor Antagonists; Disease Progression; Humans; Hyperphagia; Ischemia; Metabolic Syndrome; Obesity; Piperidines; PPAR gamma; Pyrazoles; Rimonabant

Endocannabinoids are lipid mediators of the same cannabinoid (CB) receptors that mediate the effects of marijuana. The endocannabinoid system (ECS) consists of CB receptors, endocannabinoids, and the enzymes involved in their biosynthesis and degradation, and it is present in both brain and peripheral tissues, including the liver. The hepatic ECS is activated in various liver diseases and contributes to the underlying pathologies. In patients with cirrhosis of various etiologies, the activation of vascular and cardiac CB(1) receptors by macrophage-derived and platelet-derived endocannabinoids contributes to the vasodilated state and cardiomyopathy, which can be reversed by CB(1) blockade. In mouse models of liver fibrosis, the activation of CB(1) receptors on hepatic stellate cells is fibrogenic, and CB(1) blockade slows the progression of fibrosis. Fatty liver induced by a high-fat diet or chronic alcohol feeding depends on the activation of peripheral receptors, including hepatic CB(1) receptors, which also contribute to insulin resistance and dyslipidemias. Although the documented therapeutic potential of CB(1) blockade is limited by neuropsychiatric side effects, these may be mitigated by using novel, peripherally restricted CB(1) antagonists.

Topics: Animals; Cannabidiol; Cannabinoid Receptor Antagonists; Cannabinoid Receptor Modulators; Endocannabinoids; Fatty Liver; Fatty Liver, Alcoholic; Hepatic Encephalopathy; Hepatitis, Autoimmune; Humans; Liver Cirrhosis; Liver Diseases; Metabolic Syndrome; Mice; Receptor, Cannabinoid, CB1; Receptors, Cannabinoid; Reperfusion Injury