A diet drug that selectively targets peripheral CB1 receptors such as those in the liver, instead of targeting all the body's CB1 receptors including those in the brain like Acomplia (rimonabant), may help patients lose weight and lower cardiometabolic risk factors without side effects like anxiety and depression.

That was the conclusion of National Institutes of Health researchers who said that in a study which targeted only CB1 receptors in the livers of mice, the mice still gained weight but had reduced insulin resistance, leptin resistance, and dyslipidemia -- changes that increase the risk of type 2 diabetes.

The mice in which researchers targeted only CB1 receptors in the liver also exhibited less severe diet–induced fatty liver, which often leads to liver cirrhosis, they reported.

Acomplia, which blocks both peripheral CB1 receptors and those in the brain, is sold in Europe and a variety of other countries, but has been kept from the U.S. market because of FDA concern over central nervous system side effects that include suicidality.

The NIH researchers, reporting in the Journal of Clinical Investigation, said their study indicted that obesity is influenced by CB1 receptors found in tissues other than the liver, but said their findings did not "identify the specific site or sites" of these CB1 receptors.

The researchers suggested that further studies selectively targeting CB1 receptors at other body locations are needed.

"The therapeutic potential of CB1 antagonists in obesity/metabolic syndrome appears to be limited by the side effects" of targeting CB1 in the brain, the researchers said. Targeting CB1 in peripheral organs, minimizing central nervous system side-effects, may ultimately provide an effective way to treat obesity-related medical conditions, they concluded.