DIETING
July 27, 2012

What the Munchies Tell Us About Weight Loss

A new drug desensitizes cannabinoid receptors and improves the appetite-reducing action of leptin.

A new drug that sensitizes the body to leptin, an appetite suppressant, could aid in losing weight and keeping it off. So far, the new drug has only been tested on mice, but the findings have implications for the development of new treatments for obesity in humans.

It's thought that one reason people overeat is as a result of desensitization to the hormone; leptin is still there, but our bodies can no longer respond to it. Cannabinoid receptors are believed to be behind this stifled response, though it is not yet clear exactly how they operate. Cannabinoids are responsible for the hunger –munchies -- produced by marijuana. They also occur naturally in the body.

'By sensitizing the body to naturally occurring leptin, the new drug could not only promote weight loss, but also help maintain it.'

Rather than providing more leptin to the body, researchers wondered if blocking these receptors wouldn't be a more effective long-term weight loss strategy.

The idea of enlisting the body's own appetite suppressant and blocking cannabinoid receptors is not new. In 2006, a cannabinoid receptor type 1 (CB1R) drug was developed in Europe, but because it caused serious psychological side effects such as anxiety, depression and thoughts of suicide, it was taken off the market a few years later.

A team led by George Kunos of the National Institute on Alcohol Abuse and Alcoholism sought to minimize these side effects by developing a compound that did not affect the brain. The group had already developed a CB1R-targeting drug, but though it did not penetrate the brain, it also was not as useful at reducing weight and improving metabolic health as hoped.

In a new study, the group tested JD5037, a new compound, that targets CB1R without penetrating the brain. JD5037 successfully suppressed the appetite of obese mice, caused weight loss, and even improved metabolic health. More importantly, the mice did not show signs of anxiety or other behavioral side effects. Because the it blocks cannabinoid receptors, JD5037 operates, in part by resensitizing mice to the appetite-suppressing hormone leptin. The belief is that as in any kind of dieting, reducing the desire for food, and therefore the intake of calories, is key to long-term weight-loss and keeping weight off.

"By sensitizing the body to naturally occurring leptin, the new drug could not only promote weight loss, but also help maintain it," said Kunos in a press release. "This finding bodes well for the development of a new class of compounds for the treatment of obesity and its metabolic consequences."

The study appears in the journal, Cell Metabolism.

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