Worms on cannabinoids also get the munchies

Yes, you read that correctly. In an experiment designed just “to see what happens”, US scientists dumped an endocannabinoid called anandamide on nematode worms.

Authors of the latest study concluded: “Cannabinoids make nematodes hungrier for their favoured foods and less hungry for their non-favoured foods,” says Shawn Lockery, Professor of Biology at the University of Oregon.

“The effects of cannabinoids in nematodes parallels the effects of marijuana on human appetites.”

One of the most well-known side effects of cannabis is that is gives people “the munchies” – a craving for the tastiest, sweet, or high fat content food – due to the presence of the cannabinoid tetrahydrocannabinol or THC.

The fact that an endocannabinoid has the same effect in a worm was surprising.

“Nematodes diverged from the lineage leading to mammals more than 500 million years ago,” explains Lockery.

“It is truly remarkable that the effects of cannabinoids on appetite are preserved through this length of evolutionary time.”

The study was initially inspired by the legalisation of cannabis in Oregon in 2015.

“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,” says Lockely.

“In almost literally a ‘Friday afternoon experiment’ – read: ‘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.”

Cannabinoids bind to cannabinoid receptors in the brain, nervous system, and other parts of the body. They mimic cannabinoid-like molecules that are naturally present in the body, called endocannabinoids, which the receptors would normally bind to.

Microscope image of tiny worms exposed to endocannabinoids next to an eyelash
A population of
C. elegans
with an author’s eyelash for scale. Credit: Shawn Lockery

The endocannabinoid system is known to play important roles in eating, anxiety, learning and memory, reproduction, metabolism, and more.

The team exposed worms to anandamide, an endocannabinoid common to nematodes and mammals, and found that the munchies were dependent on the presence of the worm’s cannabinoid receptors.

Then, when they genetically replaced the C. elegans cannabinoid receptor with the human cannabinoid receptor, they found that the animals still got the munchies. Apparently, these effects depend on the presence of specific neurons that play a role in food detection.

“We found that the sensitivity of one of the main food-detecting olfactory neurons in C. elegans is dramatically altered by cannabinoids,” Lockery says.

“Upon cannabinoid exposure, it becomes more sensitive to favoured food odours and less sensitive to non-favoured food odours. 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.”

So, why do we care about the fact that worms get the munchies?

“Cannabinoid signalling is present in the majority of tissues in our body. It therefore could be involved in the cause and treatment of a wide range of diseases,” explains Lockery.

“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 signalling and metabolism, with profound implications for human health.”

The studies won’t stop here, because the researchers say that there are still big questions remaining. For instance, how do cannabinoids change the sensitivity of C. elegans olfactory neurons, which don’t have cannabinoid receptors?

They also want 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,” Lockery says.

The research has been published in the journal Current Biology.

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