Worm model eliminates new insight into the endocannabinoid system

Summary: A new worm study provides new insights into how the endocannabinoid system works and helps answer the question of why cannabis use improves mood and gives people “the cravings”. Researchers found that consuming cannabis activated the endocannabinoid system and evoked cravings for high-calorie foods.

Source: University of Oregon

If you give a worm grass, it may just need a snack to go with it.

Worms exposed to a cannabinoid become even more interested in the type of food they already prefer, according to new UO research. The effect is similar to craving potato chips and ice cream after a few puffs of marijuana – a phenomenon known scientifically as “hedonic eating”, but colloquially referred to as “food cravings”.

The study, led by neuroscientist Shawn Lockery of the College of Arts and Sciences, points to worms as a useful tool for better understanding 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 published their findings on April 20 in Current biology.

The endocannabinoid system is a wide-ranging signaling network that helps regulate key bodily systems like appetite, mood, and pain sensation. Molecules called endocannabinoids send chemical messages by interacting with cannabinoid receptors, special proteins that are scattered throughout the body and brain.

Normally, these messages help maintain the balance of the various bodily systems. But molecules in marijuana, like THC, also interact with cannabinoid receptors, making you feel good after consuming and causing other effects as well.

When Lockery and his team began this research, marijuana had just been legalized for recreational use in Oregon, “so we thought, damn it, let’s just try this!” said Lockery. “We thought it would be fun if it worked.”

The idea wasn’t totally out of left 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 eats bacteria as a simple system for testing hypotheses. He often uses food choice experiments, tempting animals with bacterial mixtures to see which they prefer under different conditions.

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

Then they put the worms in a T-shaped maze. On one side of the maze was high-quality food; on the other hand, lower 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 foods more desirable and seek them out preferentially.

In the T-maze experiment, under normal conditions, the worms did indeed prefer the higher quality food. But once soaked in the anandamide, this preference became even stronger – they flocked to the high-quality food and stayed there longer than usual.

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

Higher quality foods can recall a nutritious variety of fruits, vegetables, and whole grains. But from an evolutionary perspective, the “best quality” foods are those that contain calories to ensure survival. So in this case, “premium” worm food is more like human junk food – it packs a lot of calories fast.

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

“The endocannabinoid system works to ensure that a hungry animal opts for foods high in fat and sugar,” Lockery said. This is one of the reasons why after consuming cannabis you are more likely to get chocolate pudding, but not necessarily hungry for 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 foods and less sensitive to the smell of lower quality foods.

The results show how ancient the endocannabinoid system is, from an evolutionary perspective. Worms and humans last shared a common ancestor over 600 million years ago, but cannabinoids affect our food preferences in the same way. “It’s a really nice example of what the early endocannabinoid system was probably for,” 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 to exploiting the medicinal properties of cannabinoids is their large-scale effects. Cannabinoid receptors are found throughout the body, so a drug targeting these receptors could solve the problem in question, but could also have many unwanted side effects. For example, smoking weed can relieve your pain, but can also make it difficult for you to concentrate on your work.

But the other nearby proteins that are also involved in the chemical message cascade vary depending on the body system involved. So better drugs might target these other proteins, thereby reducing the effects of the drug.

Because scientists know so much about the genetics of worms, they provide a good study system for distinguishing between these types of pathways, 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
Picture: Image is credited 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


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

Strong points

  • EAA reciprocally alters the consumption of high and low quality foods in C.elegans
  • Reciprocity is evident in both feeding rate and chemotaxis preference
  • Suppression of the native cannabinoid receptor npr-19 is rescued by the human CNR1 gene
  • AEA reciprocally alters the sensitivity of olfactory neurons to high- and low-quality foods


The ability of cannabis to increase food consumption has been known for centuries. In addition to producing binge eating, cannabinoids can amplify existing preferences for high-calorie, palatable food sources, a phenomenon called hedonic eating amplification.

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 the exposure of Caenorhabditis elegans to anandamide, an endocannabinoid common to nematodes and mammals, shifts appetitive and consumptive responses to nutritionally superior foods, an effect analogous to hedonic eating.

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

Additionally, anandamide has reciprocal effects on appetitive and consumptive responses to food, increasing and decreasing lower and higher food responses, respectively. The behavioral effects of anandamide necessitate the AWC chemosensory neurons, and anandamide makes these neurons more sensitive to higher foods and less sensitive to lower foods, mirroring the reciprocal effects observed at the behavioral level.

Our findings reveal a surprising degree of functional conservation of the effects of endocannabinoids on hedonic eating across species and establish a novel system for investigating the cellular and molecular basis of the function of the endocannabinoid system in regulating food choice.

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