Endocannabinoid system shows promise in combating obesity

May 3 2006

As the obesity epidemic grows in the United States, the medical community is faced with the significant challenge of properly treating patients before complications such as heart disease arise.

But, as obesity expert Louis Aronne, MD, explained, ongoing research into the endocannabinoid (EC) system shows promise in combating obesity and the associated cardiometabolic risks.

"The picture that is emerging is that there's a cascade of events that occur as a result of an overactivated EC system," said Dr. Aronne, who is director of the Comprehensive Weight Control Program at NewYork-Presbyterian Hospital/Weill Cornell Medical Center and clinical professor of medicine at Weill Medical College of Cornell University, in New York. "As we learn more about this system, I believe we'll see a shift in the treatment of obesity, which will effectively reduce cardiovascular disease in the population."

Dr. Aronne spoke at an American Medical Association media briefing, Cardiovascular Disease, in New York City.

According to Dr. Aronne, researchers believe that the EC system acts as a modulator and coordinator of a variety processes in the body that regulate body weight, energy balance, and glucose homeostasis, as well as the the production and accumulation of triglycerides in adipose tissue and liver, all of which appear to play important roles in the pathophysiology of insulin resistance and diabetes. The term cardiometabolic risk describes the interaction of each of these elements as they relate to the development of cardiovascular disease.

"It seems as though the EC system receptors are overactivated when 'fattening foods' are consumed and weight is gained. This overactivation leads to an increase in food intake and more fat production in the liver," explained Dr. Aronne. "Eventually, what starts out as just eating the wrong foods will lead to the development of obesity, cardiometabolic risks, and heart disease."

By blocking these receptors, Dr. Aronne and his colleagues hope to reduce cardiometabolic risk. "It's not purely about helping obese patients lose weight," he said. "We've seen that blocking these receptors results in not only reduction of food intake and body weight but also a reduction in triglycerides and glucose, and an increase in good cholesterol. The results to date are above and beyond what we can see with weight loss alone."

Dr. Aronne stresses that the discovery of the EC system is not a "miracle" for those struggling with obesity, and that there are still a lot of questions that must be answered before a treatment approach can be effectively used in the clinical setting. "We're not sure if blocking receptors to combat obesity will work in all people or just in certain populations. We also don't know if we must pair the treatment with other medications or lifestyle changes."

Clinical trials on receptor-blocking drugs, some already in Phase 3 and 4, are currently underway to answer some of these questions. "I think we'll see something similar to what evolved out of the statin trials," explained Dr. Aronne. "Some of these drugs may be better than others and some of them may be remarkably similar."

"In the future, we'll see a paradigm shift, or a change in the treatment of cardiometabolic risk," said Dr. Aronne. "Instead of waiting for risk factors and disease to emerge, we'll be treating those who are obese earlier and earlier to prevent disease and offset complications. It will be a more cost efficient and better approach to healthcare."