A study directed by Rafael Maldonado, director of the Neuropharmacology Laboratory of the Department of Experimental and Health Sciences (CEXS) of the UPF, with the collaboration of researchers at the Biotechnology and Genic Therapy Animal Center, led by Fátima Bosch, shows the crucial role the CB2 endocannabinoid receptor plays in the control of the glucidic metabolism.

The endocannabinoid system plays an important role in food intake and metabolism. Two cannabinoid receptors have been identified and characterized: the CB1 cannabinoid receptor, which is mainly located in the central nervous system and in several peripheral tissues, and the CB2 cannabinoid receptor, which is mainly located in peripheral tissues.

After the drugs developed from the CB1 cannabinoid receptor presented  unwanted secondary effects, the CB2 cannabinoid receptor was considered an alternative strategy of great interest for obtaining the therapeutic effects associated with a pharmacological intervention in the endocannabinoid system, avoiding any possible unwanted effects taking into account the mainly peripheral location of this receptor.

 Promising results in a study of deficient mice in CB2 receptors.

The recently published study in the journal Diabetología highlighted that as they grow old, knockout mice deficient in CB2 receptors increase their body weight and food intake. However, despite the appearance of this metabolic alteration, these knockout mice failed to develop either insulin resistance or inflammatory reaction of the adipose tissue, which are signs that are classically related to obesity. On the contrary, insulin sensitivity was better in these knockout mice.

According to Rafael Maldonado, the lead researcher in the project, "In this research, we have proved for the first time that the CB2 receptor plays a crucial role in controlling glucidic metabolism, by using knockout mice deficient in CB2 receptors and selective medicines that can activate or block these receptors. Furthermore, mice deficient in CB2 receptors have turned out to be protected from the harmful metabolic effects caused by chronic exposure to a high-fat diet.

These results have been confirmed using pharmacological techniques.Chronic administration of a selective antagonist of CB2 receptors has therefore contributed to significantly improving sensitivity to insulin.

A new path to treating obesity and associated insulin resistance

The modulation of CB2 receptor activity s is therefore a new area for the development of new drugs for the treatment of obesity and associated insulin resistance, while avoiding the unwanted effects that appeared when using CB1 antagonists.

Insulin is a hormone that is involved in the absorption of sugars from nutrition to provide energy. In some people, this process is inefficient and they become resistant. This dysfunction is frequently accompanied by other health problems such as diabetes, hypertension, obesity and cardiovascular problems. When some of these problems occur simultaneously, it is described as insulin resistance syndrome.

Protection against insulin resistance and the harmful metabolic effects of fat consumption observed in mice by blocking CB2 receptors shows the huge therapeutic interest of this new pharmacological target.

Reference works:

Agudo J, Martin M, Roca C, Molas M, Bura AS, Zimmer A, Bosch F, Maldonado R. (2010), " Deficiency of CB2 cannabinoid receptor in mice improves insulin sensitivity but increases food intake and obesity with age. " Diabetología, Sep 11.