The worldwide epidemic of obesity has generated great interest in the neural mechanisms that control appetite and energy metabolism. Marijuana smoking is known to increase appetite, causing the "munchies." The discovery of marijuana’s endogenous counterparts, the endocannabinoids, in the 1990s, raised the question whether these lipid mediators are involved in the physiological regulation of appetite.

“The worldwide epidemic of obesity has generated great interest in the neural mechanisms that control appetite and energy metabolism.”

Our paper shows that mice lacking the brain-type or CB1 receptor for cannabinoids eat less when exposed to hunger than normal mice, and a drug that blocks CB1 receptors reduces food intake in normal mice to the same levels seen in CB1-deficient mice. We further show that genetically obese mice lacking the appetite-suppressing hormone leptin or having a defective leptin receptor have elevated levels of endocannabinoids in the hypothalamus, a brain area involved in appetite control.

These results showed for the first time that endocannabinoids are involved in the neural regulation of appetite, that they are negatively regulated by leptin, and that they contribute to the overeating and obesity in leptin-deficient states.

One important implication of this work is related to the treatment of obesity. Once the role of an endogenous substance in the control of appetite becomes clear, drugs that interfere with the action of this substance can be considered for the treatment of obesity and various eating disorders.

A selective antagonist of the CB1 receptor has recently been introduced in Europe for the treatment of obesity. Interestingly, treatment of obese individuals with this CB1 receptor-blocking drug resulted not only in weight reduction, but also in improvements in their plasma lipids and in the control of their blood sugar levels. This is important because changes in plasma lipids and an inadequate control of blood sugar in many obese individuals expose them to greater risk for cardiovascular disease.

My interest in this field was triggered by the discovery of the first endogenous cannabinoid by Professor Raphael Mechoulam’s group at the Hebrew University of Jerusalem in 1992.

I soon realized that many of the well-known effects of smoking marijuana may reflect the similar effects of its endogenous counterparts, and that exploring these effects will not only help us understand how they are regulated in the body, but could also offer novel approaches for treatment of various disorders.

For example, other experiments in my laboratory have indicated that endocannabinoids are also involved in the control of alcohol-drinking behavior, as well as in the regulation of blood pressure and cardiac contractility, and also in various liver functions, each with possible therapeutic implications.