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Weight Management is Not Enough for Cannabinoid Type 1 (CB1),Receptor Antagonists to Become a Commercial Success

North America study evidenced sustained effects on waist circumference, body weight and cardiometabolic risk factors. Mechanism-based adverse effects associated with CB1 receptor antagonists have not been reported. Results of the SERENADE trial published in December 2006 showed that patients with type 2 diabetes not currently treated with anti-diabetic medication experienced significant improvements in glucose control and weight as well as in HDL cholesterol and triglycerides. Importantly, about 57 % of the improvements in HbA1C were independent of the weight loss achieved.

The mechanism of action of CB1 antagonists still is not yet fully understood. Data indicate a loss of appetite as well as an increase in metabolic rate and a loss of fat mass. In addition, it has been shown that cannabinoid antagonists can prevent drug reinstatement with cocaine, alcohol and nicotine. Sanofi-Aventis had studied rimonabant as an aid to smoking cessation and submitted an NDA based on studies for up to one year in over 6,500 smokers. However, the FDA issued a non-approvable letter for this indication. Studies with other molecules are ongoing to explore the utility of CB1 antagonist in the neuroscience field.

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