Worm Model Weeds Out New Insight Into Endocannabinoid System

Summary: A new study of worms brings new insight into the workings of the endocannabinoid system and helps answer the question of why cannabis consumption enhances mood and gives people “the munchies”. Researchers found cannabis consumption activates the endocannabinoid system and evokes cravings for higher-calorie foods.

Source: University of Oregon

If you give a worm some weed, he might just need a snack to go with it.

Worms exposed to a cannabinoid become even more interested in the kind of food that they’d already prefer, new UO research shows. The effect is similar to craving potato chips and ice cream after a few puffs of marijuana—a phenomenon known scientifically as “hedonic feeding,” but colloquially called “the munchies.”

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

He and his team published their findings April 20 in Current Biology.

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

Normally, these messages help keep different body systems in balance. But molecules in marijuana—like THC—also interact with cannabinoid receptors, making you feel high after partaking and causing other effects, too.

When Lockery and his team started this research, marijuana had just been legalized recreationally in Oregon, “so we thought, well heck, let’s just try this!” said Lockery. “We thought it would be amusing 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 to test hypotheses. He often uses food choice experiments, tempting the animals with bacterial blends 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 the body’s cannabinoid receptors.

Then, they put the worms into a T-shaped maze. On one side of the maze was high quality food; on the other side, lower quality food. Previous research has shown that on high quality food sources, the worms grow quickly; on lower-quality ones, 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 indeed prefered the higher-quality food. But when soaked in anandamide, that preference became even stronger—they flocked to the high quality food and stayed there longer than they usually did.

“We suggest that this increase in existing preference is analogous to eating more of the foods 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, veggies, and whole grains. But evolutionarily, “higher quality” food is the kind packed with calories to ensure survival. So in this case, “higher quality” worm food is more like human junk food—it packs in a lot of calories quickly.

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

“The endocannabinoid system helps make sure that an animal that’s starving goes for high fat and sugar content food,” Lockery said. It’s one reason why, after consuming cannabis, you’re more likely to reach for 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 food, and less sensitive to the smell of lower quality food.

The results drive home just how old the endocannabinoid system is, evolutionarily speaking. Worms and humans last shared a common ancestor more than 600 million years ago, yet cannabinoids affect our food preferences in a similar way. “It’s a really beautiful example of what the endocannabinoid system was probably for at the beginning,” Lockery said.

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

In particular, one current limitation with tapping into the medicinal properties of cannabinoids is their broad-ranging effects. Cannabinoid receptors are found throughout the body, so a drug targeting these receptors could help the problem at hand, but might also have lots of undesired side effects. For instance, smoking weed might relieve your pain, but could also make it hard to focus on work.

But the other nearby proteins that are also involved in the cascade of chemical messages varies depending on the body system at play. So better drugs could aim at these other proteins, narrowing the effects of the drug.

Because scientists know so much about worm genetics, they’re are a good study system for picking apart these kinds of pathways, Lockery suggests. “The ability to rapidly 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 image is credited to Stacy Levichev

Original Research: Open access.
The conserved endocannabinoid anandamide modulates olfactory sensitivity to induce hedonic feeding in C. elegans” by Shawn R. Lockery et al. Current Biology


Abstract

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

Highlights

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

Summary

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

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 across the animal kingdom suggests hedonic feeding may also be widely conserved.

Here, we show that exposure of Caenorhabditis elegans to anandamide, an endocannabinoid common to nematodes and mammals, shifts both appetitive and consummatory responses toward nutritionally superior food, an effect analogous to hedonic feeding.

We find that anandamide’s effect on feeding requires the C. elegans cannabinoid receptor NPR-19 but can 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 consummatory responses to food, increasing and decreasing responses to inferior and superior foods, respectively. Anandamide’s behavioral effects require the AWC chemosensory neurons, and anandamide renders these neurons more sensitive to superior foods and less sensitive to inferior foods, mirroring the reciprocal effects seen at the behavioral level.

Our findings reveal a surprising degree of functional conservation in the effects of endocannabinoids on hedonic feeding across species and establish a new system to investigate the cellular and molecular basis of endocannabinoid system function in the regulation of food choice.

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