Those who celebrate an apparently unofficial holiday 4/20 a phenomenon known to occur on Thursday scientists and non-professionals – “snacks”. Cannabis’ appetite-stimulating ability is one of its many medically beneficial properties, but it can also lead cannabis drinkers to gulp down pints of ice cream, gobble up mountains of Cheetos, or nibble a log of raw cookie dough to a stump.

According to University of Oregon neuroscientist Sean Lockery, these feats of gluttony demonstrate one of the hallmarks of gluttony, which is not only an almost insatiable hunger, but an increased desire to inhale the most delicious and high-calorie foods within reach.

But it turns out that beetles aren’t limited to humans or even mammals. Lockery and colleagues show in a study published Thursday in Current biologythat even a millimeter nematode worm Caenorhabditis elegans chews his favorite foods with great pleasure while under the influence of cannabis molecules called cannabinoids.

These reactions to cannabinoids are unexpected because the evolutionary lines that produced humans and nematode worms diverged in different directions over 500 million years ago, and because S. elegans has only 302 neurons compared to about 86 billion of our neurons.

“Surprisingly, in 500 million years of evolution, the cannabinoid signaling system of the worm and humans hasn’t diverged that much,” Lockery says. This similarity could allow studies of nematode worms like this one to eventually provide insights into how more complex brains like ours work at a fundamental level.

Scientists have long known that both humans and nematode worms have receptors throughout their bodies that respond to cannabinoids. These cannabinoid receptors have evolved to bind to molecules naturally produced within the body called endocannabinoids, compounds structurally similar to the cannabinoids found in the cannabis plant.

Together, endocannabinoids and cannabinoid receptors form the endocannabinoid system, which in humans is involved in the regulation of a vast range of biological functions, including learning and memory, sleep, pain, inflammatory and immune responses, and, of course, food intake.

Inspiration to learn how WITH elegant the reaction to cannabinoids is partly due to the legalization of recreational marijuana in Oregon in 2015. That same year, Lockery and his team studied decision making using food selection in nematodes. Lockery says someone once asked out loud, almost as a joke, “What happens if you soak worms in cannabinoids?”

Previous studies have shown that S. elegans prefers food that will help it grow faster, and that these nematodes can track food, primarily bacteria, with chemical signals that approximate smell and taste.

From the very first experiment with cannabinoids, the effect was clear, says Lockery: dose nematodes with endocannabinoid anandamide and it will make them eat faster, increase their preference for their favorite foods, reduce their consumption of their least favorite foods, and not affect their health. their diet is neutral food.

The researchers showed an increase in a worm’s feeding rate using a device that can electrically measure how many times an individual worm swallows a tiny tube, and they recorded how much each test subject ate in one minute. To see how S. elegans responded to different foods, the team presented individual worms with a menu of five different types of bacteria. The bacteria in the experiments contained two species known to be delicacy nematodes, one neutral species and two undesirable species.

In further testing, the researchers placed a group of worms in a T-shaped maze with patches of different bacteria at each end. The researchers then counted the number of worms in each spot of bacteria at 15-minute intervals over one hour and found that endocannabinoids also made worms more likely to seek out their favorite food, less likely to hunt down foods they didn’t need, and no more or less inspired to sit on a patch of neutral bacteria.

The team then added a paralytic agent to the bacterial buffet to keep the worms from switching between pieces of food after they made their initial choice. The results didn’t change: more anandamide-injected worms clustered around areas with preferred bacteria, and fewer worms turned their attention to the least preferred bacteria.

“This tells us that a worm odor detection system was involved,” Lockery says.

To test this further, the team used a strain of mutant worms that lacked olfactory neurons, known as AWC neurons. Lockery and colleagues found that for these mutant worms, the effects of endocannabinoids vanished—dosed subjects showed normal nutritional levels for all five bacterial species. The results showed that endocannabinoid-induced changes in eating behavior were associated with heightened sensitivity to food odors.

Expanding yet another layer of complexity, the team also used mutant worms that lack a cannabinoid receptor called NPR-19 to show that behavioral shifts require that receptor. The team then manipulated these mutant worms by restoring the NPR-19 receptor, and the nematodes were fed again. Surprisingly, the researchers got the same result when they replaced the worm’s NPR-19 cannabinoid receptor with a version found in humans called CB1.

“The same functional pathway in the endocannabinoid system is present in this simple animal, which has only 302 neurons,” says Shrikant Chalasani, a neuroscientist at the Salk Institute for Biological Research who was not involved in the study. “It shows commonality over a huge biological and evolutionary distance. When nature finds something good, it often uses the same thing over and over again, which I find beautiful and fascinating.”

Lockery and co-authors looked for the NPR-19 cannabinoid receptor on AWC olfactory neurons but did not find it there, suggesting that the true mechanism is more complex.

“That gives us a whole bushel of hypotheses to test,” Lockery says. The NPR-19 cannabinoid receptor is present on 28 different neurons in the worm’s head, and Lockery says future experiments could simply remove them one by one to find out where the cannabinoids trigger their behavioral effects.

In humans, this list of potential neurons to test would be much longer than 28, but Lockery’s research shows a striking similarity in how the endocannabinoid system functions, despite the relative simplicity of the worm.

“The more similar we are, the better we can learn about the human endocannabinoid system from studying these worms,” says Martin Skumlien, a psychopharmacologist at the University of Bath who was not involved in the study. “The endocannabinoid system regulates the amount of other neurotransmitters in the human brain.”

Skumlien says she has studied the role of the endocannabinoid system in reward processing during activities such as eating or using recreational drugs. “If we really deepened our understanding of how it all fits together,” she says, “you could imagine drugs that act on the endocannabinoid system to make drugs less attractive.”