University of Oregon research suggests humans aren’t the only ones who get the munchies

A new study out of the University of Oregon suggests that humans aren’t the only ones who get the munchies under the influence of cannabis.

Researchers soaked worms in an endocannabinoid – described as a THC-like substance produced in the brain – and observed a similar response to humans. The worms gravitated toward the types of bacteria they prefer to eat and consumed them at a faster rate than normal. The findings could provide insight into the human endocannabinoid system, which is surprisingly similar to the worms, and regulates bodily responses such as appetite, pain and inflammation.

Shawn Lockery is a professor at UO’s Institute of Neuroscience. He joins us with more details on the study.

Note: This transcript was computer generated and edited by a volunteer.

Dave Miller: This is Think Out Loud on OPB. I’m Dave Miller. A new study out of the University of Oregon suggests that humans might not be the only species that get the munchies from marijuana. Researchers soaked worms in an endocannabinoid - described as a THC-like substance produced in the brain - and they observed a similar response to humans who’ve taken marijuana. The worms ate more of their favorite bacterial food. Shawn Lockery is a professor in the U of O’s Institute of Neuroscience. He created this study and he joins us now with  more details. It’s great to have you on the show.

Shawn Lockery: Thank you for inviting me, David. Wonderful to be here.

Miller: What sparked this particular study?

Lockery: Well, my research group at the University of Oregon is a bunch of neurobiologists and geneticists who are interested in a very important question, which is that of how brains control behavior. And we’ve chosen to work on one of the smallest brains known to science so that we have some chance of figuring out how the whole thing works. And that is the brain of the nematode C. elegans. It’s a type of roundworm actually and just about the time marijuana got legalized in Oregon, we had been investigating a very special kind of behavior called ‘economic decision making,’ which involves challenging an animal with choices between things they like, but that have different prices.

In our case, as you mentioned, this nematode eats bacteria for a living but not all bacteria are created equal, from the nematode’s point of view. Some of them are sort of like pizza to the worm. They’re rich in nutrients and worms really like them. And some are more like oatmeal, they’ll eat them in a pinch. And so we’ve been asking worms, simultaneously giving them these two foods, which do you prefer? And as expected, they preferred this one, the pizza-like bacteria.

And then we soaked the worms in an endocannabinoid, as you mentioned. And what we found was that that experience amplified the worm’s normal preference for the pizza-like bacteria, but it did so in an interesting way. It not only increased the preference for pizza-like bacteria, but it decreased the preference for the oatmeal-like bacteria.

Miller: So, meaning they crawled along, so after you soaked them in this substance, they’re more likely to crawl to the place that had the tastier bacteria?

Lockery: Exactly right. We actually put them in a so-called T-maze, where one arm of the T has the high quality bacteria, the pizza bacteria, and the other has the oatmeal bacteria and we start them at the bottom of the T and then we watch them crawl around and count the number of worms in each little patch of food.

Miller: Can they smell?

Lockery: Oh, yes. And that’s another part of the story which I’m sure we’ll get to. But we also found, well, we can talk about it now. So after we found the behavioral effect, which exists actually at two levels, with the version I just told you where we watch where the worms go. But we also found that they feed more rapidly on the high quality food, when they’ve been exposed to the cannabinoid, and they feed less rapidly on the low quality food when exposed to the cannabinoid.

Miller: They actually eat faster?

Lockery: Correct. They chew faster, basically. And so once again, there’s this theme of, more in the good stuff and less in the not so good stuff. And what was really surprising about the study was we found the same pattern of reciprocity in the so-called olfactory neurons. These are the neurons that produce the perception of smell for the worm. We have them also. And these neurons respond after exposure to cannabinoid, they respond more strongly to the high quality food and less strongly to the medium quality food. And we know that this particular neuron we studied is absolutely essential for finding and staying in patches of food. So it all made beautiful sense.

Miller: Well, that last part, it gets to the questions I have about what it means to call something an endocannabinoid because you weren’t going to a cannabis store and buying gummies and dissolving them in water, say, or grinding up flour and making some kind of slurry that you put the worms in. You were exposing them to a related, I guess, but a different chemical. So what is an endocannabinoid?

Lockery: Right. It’s a good question. So THC works on us because it mimics a type of natural neurotransmitter that we all have in our brains anyway. And these are these things that I’ve been talking about called endocannabinoids. The mammals, including humans, have two main endocannabinoids. They have technical names like 2AG and AEA or anandamide. And it turns out that the worm has seven endocannabinoids and favorably for us, two of those seven are exactly the same two that mammals, including humans, have. And so of course, because we wanted to understand, we wanted to apply our study ultimately to understanding the human brain. We used one of the human endocannabinoids. We used anandamide.

Miller: When and why do we make these endocannabinoids?

Lockery: That’s a very good question also. Well, it’s remarkable, but the endocannabinoids are part of a signaling mechanism between one cell and another. And endocannabinoid signaling occurs in almost every tissue in the human body, the brain of course, but other tissues where issues like inflammation and pain are relevant. And so the short answer to the question is that these substances are produced in order for one cell to be able to say something to another cell. So one cell will emit one of these endocannabinoids and certain other cells are studded or decorated on the outside with these little proteins called receptor proteins that have a little pocket on them that only, only a particular endocannabinoid can fit into. So, these are called, as I said, receptor proteins. And when they receive the endocannabinoid signal, it changes the shape of the protein and that changes its ability to interact with constituents inside the cell and cause the next step in the process to happen.

Miller: That’s the mechanism.

Lockery: Right.

Miller: But what’s the why, evolutionarily speaking, what purpose might it serve worms or humans to have these particular neurotransmitters, which in this case, can make us hungrier for particularly calorically intense food?

Lockery: Right. So let’s talk about the endocannabinoid signals that occur in the brain. There’s evidence from rodents that endocannabinoids are produced in larger amounts when the animal is very, very hungry. And they are produced in parts of the brain that are associated with appetite.

Miller: Oh, so it could be a message in case the creature, the human or the rat or whatever hasn’t gotten the message yet, that really for real, it’s time to eat some good food or some food that will give you energy?

Lockery: Exactly right. And so the field of endocannabinoid research has come around to the point of view, and it’s still a hypothesis that endocannabinoid signaling in the brain relative to appetite is kind of like a fast response emergency system for when the animal is facing death by starvation. And in that case, you really don’t want to waste your time eating grass or something that’s not so nutritious, you should really focus on something that will save you. And so what we’re seeing here, is that what we see in the nematode fits with that except that we don’t yet know why and when endocannabinoids are produced by the nematode. But as we talk about this short latency survival mechanism for when you’re starving, it’s probably worth pointing out something we mentioned in our study, which is that the line leading to humans and the evolutionary line leading to nematodes diverged about 500 million years ago. That’s a long period of time, in terms of evolution. But we both still have this emergency feeding mechanism and what it points to is that our last common ancestor probably also got the munchies. So this has been something that’s been around and essential for a long time.

Miller: Although, I guess both for the worms soaked in that bath or for humans today, not in emergency situations, not starving, the question isn’t, what do I want to eat: oatmeal or pizza. It’s our brains. In a sense, [they] trick us into thinking there’s an emergency and then we will eat whatever we want, as much as we want.

Lockery: I’m sorry, are you talking about if you’re under the influence of THC?

Miller: Well, I’m talking about the worms. I mean, the worms that you had, they weren’t starving, but their brains, still based on millions of years of evolution, told them to eat the thing that you should eat if you were starving. And I guess I’m saying that even in non-emergency situations, the neurotransmitters still work in the ways that they have been trained to work.

Lockery: Gotcha. Yes, yes, right. So we basically made the animals sort of hallucinate that they were starving by soaking them in the cannabinoid.

Miller: Were you surprised by the robustness of your finding? You had a hypothesis or a question, and then it turned out that indeed these worms did behave in the way that you had maybe hoped they would. Was it a surprise?

Lockery: Yeah, it’s always a surprise in science when you get the result you were hoping for, because so often you don’t, so there’s that level of surprise. And then I was pleasantly surprised to see there’s a strong similarity between humans and these animals that are, you could say, so primitive and diverged from us so long ago. What a surprise.

Miller: Was this experiment fun to come up with the idea for, and then to put into practice?

Lockery: Yes, it was. And, it was the first time in my scientific career that I did anything with drugs of abuse. It’s never been high on my list of scientific issues to tackle, but I just thought that if the result worked out, it would be so amusing to everyone.

There’s this thing that they give out at MIT called The Ignoble Award. I don’t know if you’ve heard about this thing but it’s sort of like a takeoff on the Nobel Prizes. And the byline here is pretty good. The award is given for science that first makes you laugh and then makes you think. And so I would put my desire to do this study in that sort of category. It was amusing but actually meaningful.

Miller: What are the big questions that you - I mean, you’ve been working, I should say, with this particular kind of nematode, this particular kind of roundworm for 33 years now. What has kept you interested?

Lockery: Thank you for asking. So I was actually a philosophy major in college and I got really, really interested in what thinking is or maybe I could say I started off being really interested in what thinking is and that turn took me to philosophy, but I became dissatisfied with that in the later part of my undergraduate career. And I wanted to understand thinking at the level of chemistry and physics and biology. So I started taking courses in neuroscience and then I did a PhD in Neuroscience. And that issue has been the prime driver for my whole career, to try to understand what thinking is, you could say, understand what consciousness is. And many of us in the field of neuroscience are compelled by that problem.

And in our other work, we are using economic theory to demonstrate that the worm actually makes decisions based on subjective value as opposed to other causes. So they have their own preferences and we’re trying to figure out how those preferences are represented in the brain in such a way that they generate the appropriate behavioral response in various different situations. So the short answer to your question is, I want to understand what my subjective experience is, but to understand it at the level of, as I said, chemistry, physics and biology.

Miller: I understand that one of your most recent experiments is to give these worms, your beloved worms, psychedelics. What are you doing?

Lockery: Well, we were spurred on by the success with the endocannabinoids. And there’s a lot of parallels here, just as cannabinoids are being legalized in Oregon, now psychedelics are legalized for certain purposes. And it’s been on our minds. There are a number of people at the Institute of Neuroscience at the University of Oregon who are studying the effects of psychedelics on certain organisms. And we’re motivated by curiosity.

What we have been doing is very similar to what you and I have been talking about. We soak the worms in a particular psychedelic. You wouldn’t find it on the street. It’s called DOI. It’s one of the few that are not regulated by the drug enforcement agency. So we’re able to use them without further approval. And we just soaked them and we looked at their behavior in the two simplest ways we know how to do, which is to look at the rate at which they feed. And also we looked at the rate at which they crawl.

Remarkably, we find that the rate of feeding goes down when the animals are exposed to DOI and the rate of locomotion goes up. And I was discussing these very preliminary findings last week with one of the world’s experts on the neurophysiology of psychedelics. And he said, “oh, that’s exactly what happens in rats.” They become hypophagic, which means they eat less. So that’s similar to eating at a lower rate, you could say, and they also become hyperactive, which is a lot like speeding up your locomotion. So we’re very excited to follow this up.

And the next step for us is to try to discover, using genetics, which of these psychedelic receptor proteins, similar to the endocannabinoid receptors I told you about, are the ones that are required to mediate the effect of this psychedelic.

Miller: Shawn Lockery, thanks very much for joining us.

Lockery: Thank you for having me. It’s been a pleasure.

Miller: Likewise. Shawn Lockery is a professor in the University of Oregon’s Institute of Neuroscience.

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