An impressive midnight snack (Image: Dwight Eschliman/Getty)

Midnight fridge raids are part and parcel of a late-night marijuana smoking session. A study in mice has provided the most complete explanation yet for why a spliff triggers intense hunger pangs. The findings, which elucidate the role of smell, also suggest that we might eventually be able to treat common disorders such as obesity and loss of appetite with a simple nasal spray.

We know that the active ingredient in cannabis, THC, binds to cannabinoid receptors in the brain called CB1s. This binding inhibits chemical signals that tell us not to eat, and so make us feel hungry.

But this isn’t the end of the story. Since smell plays such a central role in making us feel hungry, it must be part of the explanation – but no one knew exactly how it fit.


To find out, Giovanni Marsicano of the French research agency INSERM in Bordeaux and his colleagues genetically modified mice to make it possible to turn on and off the CB1 receptor in particular nerve cells within the smell, or olfactory, system.

The key proved to be a group of nerve cells that carry signals from the cerebral cortex down to the olfactory bulb, the primary smell centre of the brain. When the team switched off CB1 on these cells, they found that hungry mice no longer ate more than their well-fed counterparts.

Conversely, activating CB1 in the same cells by injecting THC caused hungry mice to eat even more. THC-treated mice also responded to less-concentrated food smells than untreated mice, a sign that the chemical had enhanced their sense of smell.

This suggests the natural cannabinoids released during hunger do the same thing that THC does for pot smokers, effectively cranking up the volume on the olfactory system, which stimulates feeding.

Olfactory overdrive

Marsicano’s study is “a technical tour de force”, says Jaideep Bains, a neuroscientist at the Hotchkiss Brain Institute at the University of Calgary, Canada. The brain is teeming with cannabinoid receptors, he notes, and only precisely targeted experiments like Marsicano’s could have pinpointed the crucial cells.

If the findings hold true for humans, they may open the door to ways of treating appetite disorders by modifying the link between smell and appetite, says Bains. “If you are eating a lot, perhaps that olfactory system is in overdrive,” he says. If so, drugs that interfere with cannabinoid signalling might reduce hunger. Conversely, loss of appetite – often seen, for example, in people who have cancer – could be treated by enhancing that signalling. Many people with cancer already do this by “self-medicating” with marijuana.

In 2006, the drug company Sanofi-Aventis introduced a CB1 blocker drug, rimonabant, as an appetite suppressant for obese people. However, the drug – which blocked CB1 throughout the body – was withdrawn a few years later because it sometimes also produced severe anxiety and depression.

Marsicano’s discovery means that pharmaceutical companies may someday be able to avoid these side effects by developing a nasal spray that delivers the therapy direct to the olfactory bulb without affecting cannabinoid receptors elsewhere, Bains says.

Journal reference: Nature Neuroscience, DOI: 10.1038/nn.3647