, Volume 1, Issue 4, pp 216-228
Date: 02 Sep 2012

Obesity and the Endocannabinoid System: Is There Still a Future for CB1 Antagonists in Obesity?


The current epidemic of obesity in western countries is being worsened by the lack of effective pharmacotherapies. The apparent success of a central nervous system-acting cannabinoid CB1 receptor antagonist-based treatment for obesity was hampered by the appearance of psychiatric side effects in certain patients. These adverse effects forced its withdrawal from the market. However, the discovery that the main beneficial metabolic effects of cannabinoid CB1 receptor antagonists were derived of its activity in peripheral tissues, including the adipose tissue, opened the possibility of rescuing this type of therapy. This goal might be achieved by differential medicinal chemistry approaches. The present review examines these options that include peripheral-restricted cannabinoid CB1 receptor antagonists, dual ligands and combinatorial therapies using sub-effective doses of CB1 receptor antagonists that might be devoid of side effects.