June 1, 2018

Why does pot make you so hungry? How cannabis affects our bodies and brains

UCalgary researchers explore the biology behind cannabis, and how it acts upon various systems in our bodies.

Dr. Keith Sharkey, PhD, loves food. This isn't unusual. But unlike most people, he can also tell you exactly what happens to your food before, during and after eating it – where your hunger impulses come from, how your body breaks down food, and how you get energy and nutrients from your food while it's in your gut. And he knows why cannabis makes you want more of it.

"I loved food so much that my first degree was in nutrition," says Sharkey, a professor in the Department of Physiology and Pharmacology in UCalgary's Cumming School of Medicine, and interim director of the Hotchkiss Brain Institute. "From there, I moved into gastrointestinal physiology and from there, into neuroscience. So I'm a hybrid researcher."

Sharkey's lab studies the nervous system in the gastrointestinal tract, and how the gut communicates with the brain to regulate things like energy levels and digestion. Part of that research involves understanding the endocannabinoid system. Endocannabinoids, chemical compounds the body produces, play a role in everything from stress to pain to appetite to digestion.

In the gut, endocannabinoids regulate how quickly food moves through the intestines. They also help to digest food. And they help to protect our bodies from outside contaminants in our food, as well as from our own stomach acid, which is highly corrosive.

"The process of digestion and absorption of nutrients in the gut is quite complicated," says Sharkey. "It's a fantastic thing to think through and to study. We've been studying how the endocannabinoid system is involved."

The endocannabinoid system wasn't discovered until the 1990s, so how exactly it works isn't yet fully understood. "It wasn't really until the 2000s that major research was started," says Sharkey. "We still have a lot to learn, and we make major discoveries fairly regularly."

Sharkey says as more research is done, it's becoming clear how important the endocannabinoid system is to the way our bodies work. "We used to think the nervous system and the immune system were the two big ones," he says. "Now we know it's involved in metabolism, in the heart, the skin, the liver. It's remarkably widespread."

Your brain (and body) on drugs

The endocannabinoid system works by releasing compounds that bind to cannabinoid receptors and activate processes in cells throughout the body. Each cannabinoid has a specific message for the cells to which it binds. If you think of a cell in the body like a room in a house, and a receptor like a lock with many combinations, then each cannabinoid has a different combination that allows you to do a different thing once you get into the room. Each cell can have dozens of different receptors.

The body produces cannabinoids on its own, but the cannabis plant also contains many different types of cannabinoids that bind to the receptors in our bodies. Tetrahydrocannabinol, or THC, is the main psychoactive ingredient in cannabis. It's what gets you high.

Cannabidiol is another major cannabinoid. It's non-psychoactive and is thought to have some medical benefits, like being a sleep aid and an anti-inflammatory.

When you take cannabis, it floods the cannabinoid receptors in your body and brain with THC and other cannabinoids. These have various effects depending on the dose, the potency and the person.

For example, in the case of what we call "the munchies" – the tendency of people who have taken cannabis to crave high-fat, high-carbohydrate snack foods – THC stimulates the appetite centres in the brain. We usually associate hunger with the gut, but Sharkey says the impulse is driven by the endocannabinoid system, which controls behavioural triggers in the brain related to eating.

"You eat because your body determines that your energy stores are reduced," says Sharkey.  "That's called homeostatic feeding, or feeding that you need in order to maintain your typical lifestyle." Our bodies measure our energy and fat levels carefully, and communicate to our brains when it's time to replenish the supply.

"There's another type of eating called hedonic or pleasurable eating," says Sharkey. "When you see a buffet, for example. And you eat your normal meal, say one plateful of food. But there's so much food, and you're so excited by the way it looks and the way it tastes, that you eat two platefuls of food. That's hedonic. You don't need to eat that much, but you do."

Cannabinoids work on both the homeostatic and the hedonic systems. "It makes food more rewarding to eat," says Sharkey.

An anti-obesity drug?

You might expect a group of people who regularly eat large amounts of high-carb, high-fat foods to have issues with weight. But, says Sharkey, paradoxically, population-level studies show regular users of cannabis tend to be thinner.

Sharkey's lab investigated the phenomenon in a month-long study where mice were given THC. Some were fed a high-fat "Western" diet, and some were fed regular mouse food. To his surprise, not only did the mice who ate the high-fat diet lose weight, but their gut bacteria were altered.

"People who are obese have different gut bacteria than people who are lean," says Sharkey. "We see the same in mice. We can reproduce this readily. The surprising thing we discovered is that the animals who were treated with THC, who lost weight, ended up with normal, healthy gut bacteria. That was a big surprise. That's the first time that's ever been seen."

Sharkey says that it would take human studies to confirm the findings, but he theorizes that THC somehow normalizes gut bacteria. How this happens is not yet understood. "Cannabis is not a weight-loss agent," he says. "But what it does to metabolism is fascinating. It may explain why cannabis users are not as obese or why they're thinner than the regular population."

Barriers to research falling

Because cannabis has been illegal until now, it's been difficult to study in controlled, scientific settings. "It's hard to get funding, you won't get government support, and it's hard to access to the product," says Dr. Matthew Hill, PhD, an associate professor in the departments of Cell Biology and Anatomy and Psychiatry in the Cumming School of Medicine, and a member of the Hotchkiss Brain Institute and the Mathison Centre for Mental Health Research & Education.

Hill, who researches the effects of stress on the endocannabinoid system, says the difficulty in conducting studies related to cannabis make the research scant and inconclusive. While small-scale studies have been done, Hill says it's tough to draw conclusions on a larger scale. "It's very hard to make causal assumptions unless we do controlled studies," he says.  

Hill says Canada's legalization of cannabis will provide researchers with more opportunities to study the drug and its effects on the body. "This will make Canada an international leader in this field," he says. "We're the first country that's going through legalization that has enough resources to promote research in this capacity. We are going to be the baseline that a lot of other countries use for their decisions."

Cannabis and PTSD

As an example of an area that warrants further study, Hill says there's a relationship between cannabis use and post-traumatic stress disorder (PTSD), where THC appears to help PTSD sufferers sleep and helps them unlearn some of the triggers around their stress, something called "extinction learning."

"If you had a traumatic event in a forest, you may develop symptoms every time you see trees or that forest," says Hill. "That's a learned response. Extinction learning involves teaching you that situation doesn't necessarily mean danger. Endocannabinoids seem to help that kind of learning. And when you do exposure training with THC, that learning seems to be improved."

As far as cannabis as a sleep aid goes, Hill points to studies done by the Canadian military, where war veterans were given THC pills before bed and asked to report on their symptoms. The findings show THC helps veterans sleep and makes their nightmares less troubling. "People with PTSD often have violent nightmares," says Hill. "There's a lot of re-experiencing of trauma during sleep, which exacerbates the symptoms. There is some emerging evidence that THC makes them sleep better and not have these nightmares, or at least not remember them."

While Hill doesn't directly research cannabis, his work shines a light on the biology behind its effects. "When someone uses cannabis, they flood their brain and body with THC, which activates cannabinoid receptors everywhere," he says. "Most people feel a reduction of stress and anxiety, and relaxation. The work we do helps us understand why cannabis modulates emotional behaviour and stress responses, and the potential of cannabinoids as therapeutic options for things like PTSD and social anxiety."

Not your grandparents' cannabis

Cannabis has changed drastically over the past decades, making what little research has been done even less valuable, says Sharkey. "The cannabis of today is ten times stronger than it was in the hippie era," he says. "So the old literature is really worthless because people are just not consuming that type of cannabis anymore. We need to do a lot of research to really understand what these newer products are doing."

Medicinal cannabis has been legal in Canada since 2001, taken to treat a wide variety of conditions. But the same restrictions have prevented much research from being done on how effective it actually is. "I would say medicinal cannabis is just as poorly understood as recreational cannabis," says Sharkey. "There's no question cannabis is a painkiller. Possibly it's an anti-inflammatory. There was a recent study showing that cannabidiol may have some benefits in epilepsy. There's a whole range of other things it may do. I say 'may' cautiously, because the literature just isn't that compelling."

In spite of his scientist's caution, Sharkey isn't ready to discount centuries of traditional belief in cannabis as a medicinal herb, and says he thinks further research is likely to bear out some of what medical cannabis users already know intuitively. "Enough people have talked about its benefits for long enough, and in enough different contexts, to believe there's something there," he says. "I don't think it's a purely psychological construct where people tell themselves they feel better just because they use it."

Learning from other jurisdictions

Both Hill and Sharkey say other jurisdictions that have legalized cannabis can teach us about what we can expect in the coming years. "You can look at Colorado and Washington as small-scale pilot studies," says Hill. "One of the short-term negative effects we saw was an uptick in acute ER visits where people have consumed too much, either through eating it or not knowing its potency, and have a panic attack or an adverse biological response. But I view that as a lack of proper educational campaigns."

A rise in hospital emergency visits is more than offset by a drop in drunk driving fatalities, as well as fewer opioid overdoses and deaths. This suggests users are taking cannabis instead of other substances. "Opioids are a huge public health problem in North America," says Hill. "So any benefit that comes from that, I would view as a positive."

"There's an enormous overuse of narcotics," says Sharkey. "People take a lot of painkillers, which leads to many problems, including addiction. Cannabis is also addictive, but it's far less addictive than opioids, and the harms we see because of cannabis rarely, if ever, include death."

The last substance-related social shift on this scale was the repeal of alcohol prohibition. In the decades since then, research has made it possible for us to gain a much better understanding of alcohol and its effects. Hill hopes with legalization of cannabis, we'll eventually have the same level of knowledge.

"We've learned a lot about the effects of alcohol on the brain, and risks associated with addiction, because of the fact we can study alcohol," says Hill. "That has helped us make very strong educational platforms about safe alcohol use, and understanding limitations. We don't have a baseline like that for cannabis.

"From a scientist's perspective, the most exciting part of this is the fact that the doors are going to open and allow us to study it properly."

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Keith Sharkey, PhD, is a professor in the Department of Physiology and Pharmacology in UCalgary's Cumming School of Medicine, and interim director of the Hotchkiss Brain Institute. Keith's research focuses on the role of nerves in the gastrointestinal (GI) tract, and brain-gut communication in relation to studies of energy balance and the control of GI functions. Read more about Keith

Matthew Hill, PhD, is an associate professor in the Departments of Cell Biology and Anatomy and Psychiatry in the Cumming School of Medicine and a member of the Hotchkiss Brain Institute and the Mathison Centre for Mental Health Research & Education. Matt's research seeks to understand the mechanisms by which exposure to stress causes changes in neural functioning and behaviour, with a particular emphasis on anxiety. Read more about Matt

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