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Marijuana: The next diabetes drug?

2:37 PM, Oct 5, 2013   |    comments
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(TIME.com) -- Toking up may help marijuana users to stay slim and lower their risk of developing diabetes, according to the latest study, which suggests that cannabis compounds may help in controlling blood sugar.

Although marijuana has a well-deserved reputation for increasing appetite via what stoners call "the munchies," the new research, which was published in the American Journal of Medicine, is not the first to find that the drug has a two-faced relationship to weight.

Three prior studies have shown that marijuana users are less likely to be obese, have a lower risk for diabetes and have lower body-mass-index measurements. And these trends occurred despite the fact that they seemed to take in more calories.

Why? "The most important finding is that current users of marijuana appeared to have better carbohydrate metabolism than nonusers," says Murray Mittleman, an associate professor of medicine at Harvard Medical School and the lead author of the study. "Their fasting insulin levels were lower, and they appeared to be less resistant to the insulin produced by their body to maintain a normal blood-sugar level."

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The research included over 4,600 men and women participating in the National Health and Nutrition Examination Survey between 2005 and 2010. 

Among them, 48% had smoked marijuana at least once in their lives, and 12% were current cannabis smokers. The authors controlled for other factors like age, sex, income, alcohol use, cigarette smoking and physical activity that could also affect diabetes risk.

Even after these adjustments, the current marijuana users showed fasting insulin levels that were 16% lower than those of former or never users, along with a 17% reduction in another measure of insulin resistance as well. Higher levels on both tests are associated with Type II diabetes, which is linked with obesity.

Marijuana users also had higher levels of high-density lipoprotein, the so-called good cholesterol, which can protect against heart disease. 

And the regular smokers also boasted smaller waistlines: on average, they were 1.5 inches (3.8 cm) slimmer than the former users and those who had never smoked cannabis.

Researchers don't yet know how to explain these correlations -- and since the study was not a controlled trial, it's not clear whether marijuana or some other factor in marijuana users' lifestyles actually accounted for the beneficial effects.

Studies showed, however, that the cannabinoid brain receptors affected by marijuana are deeply involved in appetite and metabolism. But the exact details of how the compound alters the relationship between appetite, caloric intake and insulin response isn't obvious yet.

One clue, however, may lie in the effects of a diet drug that was developed to have the opposite effect that marijuana has on the brain. That drug, rimonabant, produced significant weight loss and a drop in fasting insulin levels by affecting certain cannabinoid receptors in the exact opposite way that THC, marijuana's main psychoactive ingredient, does.

This action is complex: rimonabant doesn't simply block the receptor and keep the natural cannabinoids from activating it. Instead, while the natural cannabinoids elevate the normal level of activity already going on in the system, rimonabant lowers it so the result is precisely the reverse of activating the receptor naturally.

However, because of psychiatric side effects like increasing suicide risk, rimonabant was pulled from the European market and never approved in the United States.

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How could both marijuana and a compound that has the opposite effect of pot act on the same brain receptors and lead to weight loss?

Natural marijuana includes many different potentially active compounds, and one of them -- rather than THC -- could be responsible for this effect. One potential candidate is a substance called cannabidiol, which also affects cannabinoid receptors, but in a different way from the way THC or rimonabant does.

Another possibility involves tolerance: repeated use of a drug can make receptors less sensitive over time. "The most likely explanation is that prolonged cannabis use causes the (receptors) to lose sensitivity and become inactive," says Daniele Piomelli, a professor of pharmacology at the University of California, Irvine, who was not associated with the new research.

"This has been shown to happen in people who smoke marijuana. This weakening of (these receptors) translates into a lower risk for obesity and diabetes because the inactive receptor would be unable to respond to our own cannabis-like molecules, which we know are important in keeping us chubby."

While marijuana may initially promote appetite and overeating, in the long run it has the opposite effect because it desensitizes cannabinoid receptors and may even protect against obesity.

So don't skip the gym and break out the bong just yet: there's still not enough data to tell whether marijuana, like alcohol, could have health benefits in moderation. Mittleman says the study relied on self-reported use of marijuana, which can be unreliable. However, he points out that since people are more likely to hide drug use than they are to falsely claim it, the findings could even underestimate marijuana's effects.

But whether that's true, and whether marijuana might be a window into understanding how to best control glucose and insulin to prevent diabetes, isn't known yet.

"It is much too early to say," says Mittleman. "We need much more research to better understand the biologic responses to marijuana use. We really need more research to allow physicians and patients to make decisions based on solid evidence." An editorial that accompanied the study also urged government action to reduce barriers to such research.

Even with 18 states now approving marijuana for medical uses, the politics of pot will always overshadow research efforts to understand how cannabinoids work in the brain -- or affect disease. But, as Piomelli says, "the (new) study suggests that smoking marijuana (may) protect people against obesity and diabetes." And following up on that finding could yield new insights into how to tackle one of our biggest public-health issues.
This story was initially published on TIME.com.

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