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Cannabinoids Give Worms the Munchies Too, Study Finds

By Alexander Beadle

Published: Apr 21, 2023   
A nematode worm, highlighted in green and pink on a black background.

Image credit: Stacy Levichev.

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Getting “the munchies” after smoking cannabis is more than just a pop culture joke – numerous studies have found that cannabis use does indeed increase reported cravings for high-calorie foods.

But now researchers at the University of Oregon’s Institute of Neuroscience have found that humans aren’t the only animals to have a changed appetite following cannabis exposure.

Published in the journal Current Biology, the researchers describe how Caenorhabditis elegans nematode worms also tend to gravitate towards more nutritionally complete foods after being exposed to the endocannabinoid anandamide (AEA).

Despite humans and nematodes diverging from each other in the course of evolution hundreds of millions of years ago, the study authors believe that this commonality between the human and nematode cannabinoid systems may suggest a new path for faster and cheaper drug screening approaches.

Nematode worms prefer high-quality food when exposed to cannabinoids

C. elegans nematodes feed on bacteria, so, for these experiments, the researchers exposed the worms to five different bacteria strains in the presence of AEA. Some of these strains were a good source of nutrition for the worms, while others were of worse or neutral nutritional content.

The researchers found that exposure to the cannabinoid caused a clear preference for these high-quality foods, with the nematodes increasing their feeding rates on these foods and decreasing their feeding rate on the less-preferable options.

“Cannabinoids make nematodes hungrier for their favored foods and less hungry for their non-favored foods,” study author Shawn Lockery, a professor of biology and neuroscience at the University of Oregon in Eugene, said in a statement. “Thus, the effects of cannabinoids in nematodes parallels the effects of marijuana on human appetites.”

“Nematodes diverged from the lineage leading to mammals more than 500 million years ago,” he added. “It is truly remarkable that the effects of cannabinoids on appetite are preserved through this length of evolutionary time.”

Why do cannabinoids change eating habits?

To better understand why the nematode worms were affected by AEA in this way, the researchers began to examine the function of specific olfactory neurons when the worms were exposed to different foods both with and without AEA.

Working with a certain mutant species of C. elegans that had an impairment of its AWC olfactory neuron – which deals with food-related odors – the researchers identified key differences in behavior that suggest that this neuron could play a role in this “hedonic feeding” behavior.

“We found that the sensitivity of one of the main food-detecting olfactory neurons in C. elegans is dramatically altered by cannabinoids,” Lockery reported. “Upon cannabinoid exposure, it becomes more sensitive to favored food odors and less sensitive to non-favored food odors. This effect helps explain changes in the worm’s consumption of food, and it is reminiscent of how THC makes tasty food even tastier in humans.”

In a further experiment, the researchers also genetically altered the nematodes so that the C. elegans cannabinoid receptor was replaced with human cannabinoid receptors. Even in this case, the animals continued to respond as expected to the cannabinoid exposure. This, the researchers say, underscores the similarities in the human and nematode cannabinoid systems.

Towards rapid cannabinoid drug screening

This study is important as it established for the first time that endocannabinoids play a role in inducing hedonic feeding behaviors – “the munchies” – in nematodes.

“At the time, our laboratory at the University of Oregon was deeply involved in assessing nematode food preferences as part of our research on the neuronal basis of economic decision-making,” Lockery said.

“In almost literally a ‘Friday afternoon experiment’ – ‘let’s dump this stuff on to see what happens’- we decided to see if soaking worms in cannabinoids alters existing food preferences. It does, and the paper is the result of many years of follow-up research.”

But as the researchers explain, the impact of this research is also likely to go far beyond simply expanding what we know about nematodes. The similarity in how these animals and humans react to cannabinoids across species could have lasting practical implications on how cannabinoid drugs are studied.

“Cannabinoid signaling is present in the majority of tissues in our body,” Lockery said. “It therefore 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 sets the stage for rapid and inexpensive screening for drugs that target a wide variety of proteins involved in cannabinoid signaling and metabolism, with profound implications for human health.”

Several important questions still remain, such as unraveling exactly how cannabinoids alter the sensitivity of olfactory neurons, which themselves don’t have cannabinoid receptors. More novel questions, such as whether there are any commonalities in the human and nematode response to psychedelics, is another point that the study authors say they are eager to investigate.

“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,” Lockery said.


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