Cannabis and THC May Explain Weight Loss in Mice

For decades, cannabis carried a heavy stigma, but researchers are now examining the plant and its compounds more closely than ever.

With rules and restrictions loosening across many regions, including the US, scientists can at last test this contentious plant and the health claims associated with it since ancient times.

For years, researchers have observed that some people who use cannabis are likely to have a lower body weight and a lower risk of developing type 2 diabetes than non-users.

This seems surprising because cannabis is widely known for causing the 'munchies' – an increased desire to eat among people using the drug.

Researchers at the University of California, Riverside (UCR) now believe they may have identified an explanation for this apparent contradiction.

Cannabis, THC and weight changes in mice

In laboratory tests, the team gave obese adult mice long-term exposure to either pure THC, cannabis's principal psychoactive compound, or a whole-plant extract containing an equivalent level of THC.

THC is psychoactive because it affects the central nervous system. It is considered the compound behind the 'munchies', apparently making the brain perceive hunger.

The mice ate a Western-style diet rich in fat and sugar for 60 days, with THC treatment starting 30 days after the diet began.

When cannabis was introduced, mice in both THC-treated groups lost weight. Untreated mice, meanwhile, continued to put on weight.

By the end of the experiment, the cannabis-treated mice also had a lower proportion of body fat than mice fed the Western diet without cannabis, even though their food intake was similar.

However, significant metabolic changes, including improved glucose tolerance, were seen only in mice that received the whole-plant extract.

THC by itself did not produce that result.

"This suggests that THC alone is not responsible for the metabolic benefits associated with cannabis use," says biomedical scientist Nicholas DiPatrizio, who directs the UCR Center for Cannabinoid Research.

"Other compounds in the plant appear to play a critical role."

Put another way, although THC may make someone feel more hungry, the mouse findings suggest that other plant compounds could have a particular effect on glucose metabolism.

DiPatrizio is not, however, advising people to use cannabis for weight management or diabetes. There is simply no clinical evidence to justify this.

Nevertheless, "clinicians, researchers, and policymakers should stay tuned and pay attention to this space," DiPatrizio says.

Much remains to be understood, with thousands of new studies published every year.

Expanding cannabis research beyond THC and CBD

Research into cannabis has grown rapidly in recent years. One peer-reviewed analysis reported that PubMed-listed cannabis publications rose 4.5-fold between 2000 and 2017, while publications on medical cannabis increased by almost 9-fold.

The full cannabis plant contains hundreds of cannabinoids, terpenes, flavonoids and other phytochemicals that may possess medicinal properties.

It is also possible that these compounds work together to produce certain effects, although they are frequently researched separately.

So far, most studies have concentrated on two principal compounds: THC and CBD. Yet other compounds, including CBG, have shown considerable promise and are moving towards clinical trials.

This research area is still comparatively new, so emerging findings should be treated with caution.

"Dissecting the relative contribution of individual phytocannabinoids will be an important direction for future studies," argue UCR researchers.

"The chemical composition of different cannabis strains could have differential effects on metabolic parameters."

For example, some recent studies in obese mice indicate that CBG (cannabigerol), sometimes called the 'mother of all cannabinoids', may improve blood sugar regulation, decrease liver fat and reduce blood lipid levels.

Furthermore, CBG appears to produce these metabolic effects almost entirely beyond the classical cannabinoid receptors found in the liver and gut.

Potential risks and unanswered mechanisms

In other words, these compounds may influence mammalian health through an entirely different mechanism that researchers have not yet discovered.

Nor will the effects necessarily be beneficial in every situation. Cannabis exposure very early in life, for example, could potentially interfere with the body's natural fat storage in harmful ways.

This may explain why rodent pups exposed to THC have lower birth weights.

"We need evidence-based approaches to fully understand both the risks and potential benefits of cannabis and its components," DiPatrizio says.

The study was published in The Journal of Physiology.