Just like people, the simple nematode worm Caenorhabditis elegans is driven to consume high-calorie food when its cannabinoid receptors are activated, hinting at a common signalling pathway for preventing starvation

Nematode worms seek out high-calorie food after they consume a cannabis-like substance, much like people who get the “munchies” after smoking marijuana.

The finding suggests that cannabis hijacks an important mechanism that has been conserved across the animal kingdom to help regulate appetite.

In people, smoking or ingesting marijuana can lead to strong food cravings, particularly for high-calorie snacks like chocolate bars, a tendency known as the munchies.

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These cravings occur because chemicals in cannabis, including tetrahydrocannabinol (THC), bind to cannabinoid receptors in the brain that are involved in motivating us to eat. These receptors are also activated by naturally occurring chemicals in the body called endocannabinoids.

Shawn Lockery at the University of Oregon and his colleagues have now investigated whether a similar cannabinoid signalling pathway exists in Caenorhabditis elegans, a microscopic nematode worm that feeds on bacteria.

They soaked nematodes in an endocannabinoid called anandamide, which the organisms absorbed through their outer surfaces, boosting the natural levels of it in their bodies. Next, the researchers placed the nematodes in a T-shaped maze that allowed them the choice of heading towards either high-calorie bacteria or low-calorie bacteria.

Nematodes that weren’t exposed to extra anandamide showed no preference for either food, but those given it were 20 per cent more likely to migrate to the high-calorie bacteria in the first 30 minutes.

By also trying the experiment with nematodes genetically engineered to lack a key cannabinoid receptor or the neurons that detect odours of edible bacteria, the researchers showed that the behaviour was influenced by anandamide binding to cannabinoid receptors in the nematodes and stimulating neurons that are involved in differentiating odours of various bacteria.

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Lockery believes that exposing nematodes to actual cannabis would also make them favour high-calorie food by activating the same receptors, but his lab hasn’t yet got approval to study this.

C. elegans, one of the simplest animals on Earth, diverged from the evolutionary lineage that led to mammals more than 500 million years ago. The fact that the cannabinoid system has been conserved along this evolutionary path – despite the organism having a tiny brain and just 302 cells in its nervous system – suggests it must play a fundamental role, says Lockery.

Under natural conditions, endocannabinoids probably drive animals to find high-calorie food when they are running out of energy, he says. For example, they may signal to C. elegans that “we are about to die! No more grazing on whatever bacteria are out there! Seek and consume only those that are the best!”, he says.

Zhizhen Wang at the University of Sydney in Australia says that now that we know that C. elegans has a cannabinoid system similar to our own, the organism could be used for initial screening of drugs developed to target this; for example, to treat eating disorders.

Journal reference: Current BiologyDOI: 10.1016/j.cub.2023.03.013