Scientists Give Worms the Munchies — and Uncover a Neurological Mystery

It’s one of the most well-known side effects of cannabis: the munchies. That insatiable hunger for fatty, sugary, calorically dense foods sneaks up on many people when they’re high.

But it turns out we’re not the only living things who get an urge to snack on something tasty when our bodies are flooded with cannabis compounds. The tiny worm Caenorhabditis elegans gets the munchies too, according to a new study.

Writing on 4/20 in the journal Current Biology, researchers explored how the eating habits of the worms changed when they were exposed to high levels of cannabinoids — compounds found in cannabis and the human body. Even though C. elegans’ anatomy and diet is vastly different from our own, the worms behaved similarly to a high human on the hunt to satisfy their cravings.

Giving worms the munchies

When the state of Oregon legalized recreational weed in 2015, University of Oregon neuroscientist Shawn Lockery was immersed in research on C. elegans. The nematode, which is only a fraction of the size of a human eyelash, has been a focus of Lockrey’s work for over 30 years.

Back then, Lockery’s lab was looking into how the worm makes decisions, specifically about what it wants to eat. But right around the time marijuana became legal, the drug’s new status “was kind of on everybody's mind,” Lockery tells Inverse.

That spawned a so-called Friday afternoon experiment; one where Lockery and his colleagues tried, mainly for fun, to mimic the effects of marijuana on nematodes to see if it would influence their food preferences.

Getting approval to use cannabis in scientific research is a notoriously time-consuming process, even in states where the drug is legal. But accessing endocannabinoids — the compounds made naturally by the human body that function identically to plant-based cannabinoids — is a lot easier.

“The worm actually has at least seven different endocannabinoids, only two of which are found at high levels in mammals,” Lockery says. “So we made sure we picked an endocannabinoid in the worm that was actually used in the mammalian brain also.”

The researcher’s compound of choice was anandamide (AEA), which binds to cannabinoid receptors in both C. elegans and humans. Because the worms are so tiny, soaking them in a highly concentrated solution of the compound was the best way to get it to saturate their bodies.

Road to deliciousness

Once the worms were full of cannabinoids, the researchers dropped them at the bottom of a T-shaped maze and offered them something to eat. Low-quality food, made of bacterial colonies with fewer nutrients, was placed on one side. On the other side were high-quality, calorically-dense bacteria – the food C. elegans typically prefers.

Even when the worms tried the low-quality food first, many realized they were missing out on a better option and swam over to the tastier bacteria. Not only was their preference clear, but the worms ate their favorite food faster.

Lockery points out that the worms’ sense of hunger wasn’t what changed, but rather their sensitivity to the pleasurable aspects of eating. The same thing happens in humans who’ve consumed cannabis — people with the munchies tend to prefer tastier, denser foods like pizza and cake, for example.

So that made the researchers curious about what, exactly, was happening in the worm’s brains to up that sensitivity to deliciousness. Because C. elegans is a simple animal with just 302 neurons (compared to 86 billion in the human body), the researchers were able to pinpoint which parts of the brain and body were activated in response to the influx of cannabinoids.

“You can stare down at an image [of] a live, behaving worm and know exactly what neuron you're looking at,” Lockery explains.

The cannabinoids seemed to influence an olfactory neuron, called AWC, by increasing its sensitivity to the foods that the worms naturally preferred, and influencing them to eat those foods. But this discovery sparked some questions, too, since AWC doesn’t have a cannabinoid receptor attached to it, meaning cannabinoids aren’t directly influencing it.

Lockery’s hypothesis is that cannabinoids make other neurons release some sort of neurotransmitter — a chemical messenger — that in turn activates AWC and changes its sensitivity.

“Which neurons release that stuff, and what it is, or what several things it is, we have no idea,” Lockery explains. “So that would be the next thing we need to figure out.”

Munchie Mysteries

Finding exactly how the munchies work in C. elegans is a surprisingly complex question, one that can help scientists glean how cannabinoids function in many species.

Lockery describes the research as playful, but meaningful. “We've shown that the worm’s endocannabinoid signaling system operates, at least at the level of food preferences, just like the human one,” he adds.

And it also shows that the endocannabinoid system, which influences sleep, emotional control, eating, and many other functions in humans, appears to have a deep evolutionary importance — even if it’s not fully understood yet.

“In an animal whose line diverged from the line leading to humans 500 million years ago, not only is there a functional cannabinoid system, but it has these high-level effects on preferences,” Lockery says.

While many questions remain about cannabinoids in C. elegans, Lockery says he plans to shift gears to do other experiments on the worm. Now that Oregon recently legalized psilocybin, psychedelic drugs are the new thing on everyone’s mind.

About a month ago, Lockery and colleagues began groundwork on new experiments to test if psychedelics might affect worms like they do humans. If C. elegans has the right receptors, the researchers could test similar compounds to the ones found in magic mushrooms and see how psychedelics interact with different neurons.

“Plus, I’m just curious, you know — what does a tripping worm look like?” Lockery says.