Worm model strips new insights into endocannabinoid system – Neuroscience News

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Summary: A new study on worms brings new insights into how the endocannabinoid system works and helps answer the question why cannabis use improves mood and gives people the “munchies”. Researchers have found that cannabis consumption activates the endocannabinoid system and evokes cravings for high-calorie foods.

Source: University of Oregon

If you feed a grass worm, it may just need a snack.

Worms exposed to a cannabinoid become even more interested in the type of food they would already prefer, new research from the OU shows. The effect is similar to a craving for chips and ice cream after a few hits of marijuana, a phenomenon known scientifically as “hedonic eating,” but colloquially called “the munchies.”

The study, led by neuroscientist Shawn Lockery of the College of Arts and Sciences, points to worms as a useful tool to better understand the many roles cannabinoids play naturally in the body. And it could help researchers develop better drugs that target this system.

He and his team released their findings on April 20Current biology.

The endocannabinoid system is a far-reaching signaling network that helps regulate key body systems such as appetite, mood, and pain sensation. Molecules called endocannabinoids send chemical messages by interacting with cannabinoid receptors, special proteins that are disseminated throughout the body and brain.

Normally, these messages help keep different bodily systems in balance. But the marijuana-like THC molecules also interact with cannabinoid receptors, making you feel high after drinking it and causing other effects as well.

When Lockery and his team began this research, marijuana had just been legalized recreationally in Oregon, “so we thought, well heck, let’s give it a try!” said Lockery. “We thought it would be fun if it worked.”

The idea wasn’t entirely off the field. Research in the Lockery lab focuses on the neurobiology of decision making, using a species of tiny, bacteria-eating worms called C. elegans that eat bacteria as a simple way to test hypotheses. He often uses food choice experiments, testing animals with bacterial mixtures to see which they prefer under different conditions.

To see how marijuana-like substances might affect the food preferences of the worms, Lockery’s team soaked them in anandamide. Anandamide is an endocannabinoid, a molecule produced by the body that activates the body’s cannabinoid receptors.

Then, they placed the worms in a T-shaped maze. On one side of the maze was high-quality food; on the other, inferior quality food. Previous research has shown that on high-quality food sources, worms grow rapidly; on those of lower quality, they grow more slowly. Worms also find high-quality food more desirable and preferentially seek it out.

In the T-maze experiment, under normal conditions, the worms actually preferred the higher quality food. But when they were doused in anandamide, that preference became even stronger, they flocked to the high-quality food and stayed there longer than usual.

“We suggest that this increase in existing preferences is analogous to eating more foods that you would crave anyway,” Lockery said. “It’s like choosing pizza versus oatmeal.”

Higher-quality food might call to mind a nutritious spread of fruits, vegetables, and whole grains. But evolutionarily, “higher grade” food is the kind high in calories to ensure survival. So, in this case, “higher grade” worm food is more like human junk food – it quickly packs in a lot of calories.

Image of worm genetically modified so that some neurons and muscles are fluorescent. The green dots are neurons that respond to cannabinoids. Credit: Stacy Levichev

“The endocannabinoid system helps ensure that a starving animal chooses foods high in fat and sugar,” Lockery said. It’s one of the reasons why, after consuming cannabis, you’re more likely to crave chocolate pudding, but not necessarily a salad.

In follow-up experiments, Lockery’s team was able to identify some of the neurons affected by anandamide. Under the influence, these neurons became more sensitive to the smell of higher quality food and less sensitive to the smell of lower quality food.

The results indicate how old the endocannabinoid system is, evolutionarily speaking. Worms and humans last shared a common ancestor more than 600 million years ago, yet cannabinoids influence our food preferences in similar ways. “It’s a really nice example of what the endocannabinoid system probably served in the beginning,” Lockery said.

The similarity in response between worms and humans also suggests that worms may be a useful model for studying the endocannabinoid system.

In particular, a current limitation in tapping into the medicinal properties of cannabinoids is their wide-ranging effects. Cannabinoid receptors are found throughout the body, so a drug targeting these receptors could help the problem at hand, but it could also come with many unwanted side effects. For example, smoking weed might ease pain, but it might also make it difficult to focus on work.

But the other nearby proteins, which are also involved in the chemical message cascade, vary according to the bodily system at play. So better drugs could target these other proteins, narrowing the drug’s effects.

Because scientists know so much about the genetics of worms, they’re a good study system to separate these kinds of paths, Lockery suggests. “The ability to quickly find signaling pathways in the worm could help identify better drug targets, with fewer side effects.”

About this neuroscience research news

Author: Press office
Source: University of Oregon
Contact: Press Office – University of Oregon
Image: The picture is attributed to Stacy Levichev

Original research: Free access.
“The conserved endocannabinoid anandamide modulates olfactory sensitivity to induce hedonic feeding in C. elegans” by Shawn R. Lockery et al. Current biology


The conserved endocannabinoid anandamide modulates olfactory sensitivity to induce hedonic feeding in C. elegans


  • The EEA mutually alters the consumption of high and low quality food inC. elegans
  • Reciprocity is evident in both feeding speed and preference for chemotaxis
  • Deletion of the native cannabinoid receptornpr-19it is rescued by the human gene CNR1
  • AEA mutually alters the sensitivity of olfactory neurons to high- and low-quality foods


Cannabis’ ability to increase food consumption has been known for centuries. In addition to producing hyperphagia, cannabinoids can amplify existing preferences for calorically dense and palatable food sources, a phenomenon called hedonic amplification of nutrition.

These effects result from the action of plant-derived cannabinoids that mimic endogenous ligands called endocannabinoids. The high degree of conservation of cannabinoid signaling at the molecular level throughout the animal kingdom suggests that hedonic feeding may also be largely conserved.

Here, we show that exposure ofCaenorhabditis elegansto anandamide, an endocannabinoid common to nematodes and mammals, shifts both appetitive and consuming responses to a nutritionally superior food, an effect analogous to hedonic feeding.

We find that the effect of anandamides on nutrition requires theC. eleganscannabinoid receptor NPR-19 but may also be mediated by the human CB1 cannabinoid receptor, indicating functional conservation between the nematode and mammalian endocannabinoid systems for the regulation of food preferences.

Furthermore, anandamide has reciprocal effects on appetitive and consumptive responses to food, increasing and decreasing responses to inferior and superior foods, respectively. The behavioral effects of anandamide require AWC chemosensory neurons, and anandamide makes these neurons more sensitive to higher foods and less sensitive to inferior foods, mirroring the reciprocal effects observed behaviorally.

Our results reveal a striking degree of functional conservation in the effects of endocannabinoids on hedonic nutrition across species and establish a new system for studying the cellular and molecular basis of endocannabinoid system function in regulating food choice.

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