Cannabis chemicals from gut cells induce eating

Intestinal cells manufacture their own marijuana-like chemicals to trigger the "munchies" for fatty foods, new research has shown.

Cannabis use has been linked previously to sensations of hunger, an effect which has been attributed to actions of the drug within the brain and targeted by the (since withdrawn) weight-loss agent Rimonabant. But now it looks like the intestines might also be another site of marijuana action and a ripe target for weight-loss drugs.

Working with rats and publishing in PNAS, University of California Irvine scientist Nicholas DiPatrizio has found that, when the animals are fed a greasy meal, the levels of two cannabis-like chemicals, called 2-AG and anadamide, increase dramatically in the small intestine where they appear to reinforce the drive to consume further fatty food.

The effect is not linked to the presence of the food directly, because the scientists used an implanted cannula to drain the contents of the stomach before anything entered the intestine, proving that the effect is a neurological one. Instead, the scientists suspect that the oral sensations associated with the consumption of fatty food are fed to the brain, which in turn signals to cells in the intestine via the Vagus nerve that runs from the brainstem down into the abdomen.

To understand the role of these endogenous cannabis-like intestinal chemicals, the researchers administered to the rats a drug called URB447, which blocks the action of cannabinoids around the body but does not get into the brain. The result was that the treated rats consumed significantly less of a fatty meal when the drug was administered, but normal (non-fatty) food intake was much less affected.

This suggests that the cannabis-like chemicals in the gut give eaters a taste for more fat, possibly by modifying the release of other appetite-affecting satiety signals including the hormone ghrelin, which is known to promote food intake. Targeting this intestinal signalling system could therefore be a very effective way to reduce fat intake but without resorting to brain-acting drugs that could have behavioural consequences.