Cannabinoids also give worms munchies

“Cannabinoids make the nematodes more hungry for their favorite foods and less hungry for their non-favorite foods,” says Shawn Lockery of the University of Oregon in Eugene. “Therefore, the effects of cannabinoids on nematodes parallel the effects of marijuana on human appetite.

“Nematodes diverged from the lineage that led to mammals more than 500 million years ago,” he added. “It’s really remarkable that the effects of cannabinoids on appetite are conserved through this evolutionary time.”

Lockery explained that the new study was inspired by 2015, when cannabis became legal in Oregon. “At the time, our laboratory at the University of Oregon was deeply involved in assessing nematode food preferences as part of our investigation into the neural basis of economic decision making,” she said. “In almost literally a ‘Friday afternoon experiment’, read: ‘let’s throw this to see what happens’, we decided to see if dipping worms in cannabinoids alters existing food preferences. It does, and the paper is the result of many years of follow-up research”.

Cannabinoids are known to work by binding to cannabinoid-sensing proteins called cannabinoid receptors in the brain, nervous system, and other parts of the body. Those receptors in the body normally respond to related molecules that are naturally present in the body, known as endocannabinoids. The endocannabinoid system plays an important role in eating, anxiety, learning and memory, reproduction, metabolism, and more.

On a molecular level, the cannabinoid system of nematodes closely resembles that of people and other animals. He raised the question of whether the so-called hedonic feeding effects of cannabinoids would also be conserved across species.

In the new study, the researchers first showed that the worms react to the endocannabinoid anandamide by eating more. They also ate more of their favorite food. The researchers found that these endocannabinoid effects depended on the presence of the worms’ cannabinoid receptors.

In later studies, they genetically replaced the C. elegans cannabinoid receptor with the human cannabinoid receptor to see what happened, and found that the animals responded normally to cannabinoids. The discovery emphasizes the similarity of the effects of cannabinoids on nematodes and humans, the researchers say. They report that the effects of anandamide also depend on neurons that play a role in sensing food.

“We found that the sensitivity of one of the main olfactory neurons that detect food in C. elegans it is dramatically altered by cannabinoids,” Lockery said. “Upon exposure to cannabinoids, you become more sensitive to favored food odors and less sensitive to unfavorable food odors. This effect helps explain the changes in food consumption by the worm, and is reminiscent of how THC makes tasty food even tastier in humans.”

The worm findings are not only entertaining, Lockery says, but also have important practical implications.

“Cannabinoid signaling is present in most tissues in our bodies,” he said. “Therefore, it could be involved in the cause and treatment of a wide range of diseases. The fact that the human cannabinoid receptor gene is functional in C. elegans Food choice experiments set the stage for rapid and inexpensive screening of drugs that target a wide variety of proteins involved in cannabinoid signaling and metabolism, with profound implications for human health.”

The researchers note that big questions remain, including how cannabinoids change the sensitivity of C. elegans olfactory neurons, which do not have cannabinoid receptors. They are also curious to study the effects of psychedelics on nematodes.

“Perhaps we can find a new set of similarities between humans and worms, now in the case of drugs that alter perception and psychological well-being,” says Lockery.