Marijuana--or more specifically its active ingredient, tetrahydrocannabinol--has a well-documented tendency to stimulate hunger. And while scientists have traced this property to cannabinoid receptors in the brain, they have had little understanding of the neural circuitry underlying this effect.
Understanding this circuitry has important practical implications because blocking the cannabinoid receptor, CB1, offers a promising approach to treating obesity. One such compound, rimonabant (trade name AcompliaTM) is already undergoing clinical testing.
In an article in the December 22, 2005, issue of Neuron, Young-Hwan Jo and colleagues report how the circuitry of CB1 is integrated with signaling by the appetite-suppressing hormone leptin. The CB1 receptor is normally triggered by natural regulatory molecules, called endocannabinoids.
In their studies, the researchers concentrated on the lateral hypothalamus (LH) of the brain, known to be a center of control of food intake. Their studies involved detailed electrophysiological measurements of the effects of specific neurons that they had identified in previous studies as being important in endocannabinoid signaling.
Their studies revealed that activation of CB1 receptors, as by endocannabinoid molecules, induced these neurons to be rendered more excitable by a mechanism called "depolarization-induced suppression of inhibition" (DSI).
What's more, they found that leptin inhibits DSI. However, they found that leptin did not interfere with the CB1 receptors themselves. Rather, leptin "short-circuits" the endocannabinoid effects by inhibiting pore-like channels in the neurons that regulate the flow of calcium into the neurons. Such calcium is necessary for the synthesis of endocannabinoids.