Could cannabis promote weight loss?

The ‘munchies’ is one of the most common side effects of cannabis consumption, but a growing body of research suggests that THC could actually promote weight loss, despite it triggering increased appetite and cravings for unhealthy foods.

Cannabis is well-known for inducing an urge to snack, often on high-fat, nutritionally poor foods (AKA the munchies). But surprisingly, most epidemiological studies have found that chronic cannabis use may in fact reduce body weight and decrease the risk of type two diabetes.

To get to the bottom of this strange paradox, Cannabis Health sat in for a lecture from Dr Kenneth Mackie of Indiana University at a virtual conference hosted by the New York Academy of Sciences.

Mackie and his team are investigating this strange phenomenon by studying mice and their response to the psychoactive chemical found in cannabis, THC.

The research explores the endocannabinoid system, a network of receptors and enzymes that keeps the body in a state of equilibrium. Named after the cannabis plant, the system was discovered in the 1990s by scientists who were studying the effects of THC on the brain.

The endocannabinoid system is centred around two main receptors, referred to as CB1 and CB2. The former is found primarily in the brain and is associated with the intoxicating effects of THC, including the ‘munchies’. CB2 on the other hand is commonly linked to the anti-inflammatory properties of cannabis.

It is generally accepted by the academic community that the activation of CB1 receptors by THC leads to increased appetite in both humans and rats. Interestingly, these effects are usually maintained even in the case of long-term chronic cannabis users who report that their urge to snack has not decreased over time.

If the activation of CB1 receptors increases appetite, it was logical for researchers to begin studying possible treatments for obesity by blocking the receptor. This research was successful, with a study of 25,000 subjects finding that inhibiting CB1 receptors consistently led to weight loss.

The question is, why do chronic cannabis users generally lose weight over time despite the regular activation of their CB1 receptors? Dr Mackie believes the answer lies in THC’s “protective” effects on the metabolic system.

“If you look at chronic cannabis users and their medical risks, despite well documented increased calorie consumption by these individuals, most studies suggest that chronic cannabis consumption may have beneficial metabolic effects that are fairly broad,” says Dr Mackie, Professor and chair of Neuroscience in the Department of Psychological and Brain Sciences at Indiana University.

The effects seen amongst chronic cannabis users include decreased body mass index, decreased waist circumference, decreased risk of metabolic syndrome, decreased insulin resistance and decreased risk of type two diabetes.

As the majority of published research shows relatively little association between the body’s CB receptors and metabolism, Mackie and his team explored what he calls the “extended” endocannabinoid system to search for an answer.

“The role of CB1 in metabolism has been extensively explored, so this is unlikely to be caused by CB1 receptors,” Dr Mackie continued. “The role of CB2 and metabolism is less clear but appears modest at best.

“One thing to keep in mind is that and the endocannabinoid system is very broad. CB1 and CB2 can be thought of as being in the centre of the endocannabinoid system. But then on the periphery, there are a number of different compounds, mostly lipids, that can interact with receptors.”

The scientists at Indiana University took a sample of mice, both male and female, and subjected them to a high-fat diet over the course of three months.

After three months, the obese mice were given various doses of THC by injection to see how they would react. Over the course of two weeks, the mice treated with THC lost weight, confirming the hypothesis.

Dr Mackie and his team theorise that the effects of THC on weight loss and glucose tolerance are due to a protein and found in the pancreas and the gut called GPR119; a member of the ‘extended’ endocannabinoid system.

Rather than being activated by THC itself, he speculates that GPR119 is activated by the end-products after THC has been metabolised by the body; also known as THC metabolites. This process, Dr Mackie believes, leads to the favouring of incretin secretion (the hormone responsible for decreasing blood sugar levels) over insulin secretion.

“This is metabolically protective,” Dr Mackie explains. “These results suggest that sustained use of cannabis might activate GPR119, leading to weight loss or attenuated weight gain, increased incretin secretion and an overall improvement in metabolic health.”

As the GPR119 is found in the digestive system, it made sense to Dr Mackie that THC would have a greater impact on metabolism if it were ingested orally rather than injected into the bloodstream.

“If our theory is correct, then we’d expect that oral THC to be more effective,” he says.

The mice that were administered THC orally lost weight as predicted and also displayed improved glucose tolerance, indicating that the mice were at a lower risk of type two diabetes.

“One of the striking findings from human epidemiology is that THC decreases risk of type two diabetes and decrease insulin levels,” Dr Mackie continues. “So, we wanted to see what happens in these high-fat diet mice when fed THC.

“What we see in oral treatment at 30 mg per kilogramme is a substantially improved glucose tolerance in both males and female mice.”

According to Dr Mackie, more studies are needed before reaching any concrete conclusions. One notable area of research that he says needs more extensive work is the differing response to THC between sexes.

He adds: “There’s some data that suggests that males may receive more benefit from using cannabis chronically under metabolic status than females.

“When you do this experiment, initially, the mice gain weight normally, but with time the THC mice start to gain weight slower than the [non-THC mice].

“If you break this out by sex, it looks like the males are affected by this transition more quickly than the females are.”