COMMENTARY

Lose Weight With Marijuana?

Kate Johnson

Disclosures

August 28, 2019

Thomas Clark, PhD, has always specialized in mosquitoes, but now he's being distracted by marijuana. Outside of his regular job as professor and chief of biological sciences at Indiana University, South Bend, he is increasingly called upon to lecture about the benefits of cannabis in humans — especially the potential for weed as a weight loss aid.

"I'm becoming more of a believer all the time, the more data I see," says Clark, who has recently digressed from insects and published several reviews and commentaries on his new topic of interest. "There are some inconsistencies in the data, but I really have decided that the positive effects of at least moderate use strongly outweigh the negative effects, and the negative effects can be avoided by controlling dose and using other delivery methods."

Clark's latest commentary, published in the Journal of Drug Abuse, extolls "the beneficial effects of moderate, adult use" and claims the current discussion of the public health impact of cannabis use results in "a misleading perception of harm."

"Cannabis use counteracts two serious public health crises," he writes, "the obesity epidemic and the drug overdose epidemic, thereby providing a net improvement in public health."

He is quick to point out that he doesn't think cannabis is a "miracle drug," but if there's evidence that weed might boost weight loss, it could catapult the herb into a whole new stratosphere — and your patients will be clamoring for answers.

Delving further into Clark's theory turns up a lot of question marks. While there's definitely curiosity in the scientific community, there's also pushback.

"I am inherently skeptical of these ideas," says Steven Heymsfield, MD, president of The Obesity Society, who has been involved in developing other weight loss drugs that never made it to market.

But colleagues of Heymsfield at the Pennington Biomedical Research Center, which lists obesity at the forefront of its mission, believe otherwise.

"There is a promise that medical marijuana may be part of the solution to the obesity and diabetes epidemic," write the center's executive director, John Kirwan, PhD, and chief medical officer, Frank Greenway, MD, in a recent editorial published in the International Journal of Obesity.

"I have a certain degree of reticence about marijuana because it hasn't been well studied," says Greenway, an endocrinologist. "But rather than just writing it off entirely I do think it's an appropriate subject to study."

As cannabis legally powers into mainstream culture across state and international borders, more scientists are starting to take notice. Canada is a new breeding ground. With cannabis federally legalized there last October, there's a flurry of scientific investigation — and excitement.

"Initially I had a student who started working on this; we did epidemiologic work but then he brought me the results," says Terence Bukong, PhD, a hepatology and infectious disease researcher at Montreal's Institut Armand-Frappier Research Centre, part of the University of Quebec's National Institute of Scientific Research. "I was amazed and said there might be something here."

After publishing studies about cannabis users who appear to be protected from various forms of liver disease, Bukong has now moved from observation to investigation in the lab. "What we're seeing in the context of epidemiologic reports we are also mirroring in the context of in vitro cell lines and mouse models," he says. "Our preliminary results show that specific formulations [of cannabis] actually enhance fat-burning while others enhance fat buildup."

But getting high and getting the munchies are the signature effects of marijuana, so wouldn't that make weed an unlikely diet aid? No, says Indiana scientist Clark; even with the accompanying snacks, pot users still shed pounds, based on data from his recent meta-analysis.

With the help of three medical students, Clark crunched the data on 17 studies of body weight and marijuana use, and found consistently that among almost 156,000 study participants, those who used marijuana were skinnier than non-users, despite eating an average of about 800 extra calories per day. On average, while non-users were overweight, users stayed in the normal weight range. That translated to an average 7% spread in body mass index (BMI).

Despite increasing appetite in the short term, the long-term impact of a single dose of weed "more than offsets" this, he says, with a 3- to 4-week period of decreased appetite and faster metabolism.

While the weed–weight loss association has been extensively documented in epidemiologic studies, legal limitations have hampered the pursuit of reliable, placebo-controlled, randomized trials. To explain healthier weights in marijuana users, many experts have assumed that they use less alcohol and more cigarettes. However, Clark's work adjusted for these and many other variables.

That's why even skeptic Heymsfield described Clark's study as "an incredibly well-documented manuscript with a very large number of references." He went on: "Given the extent to which the authors documented their hypotheses, we should pay attention."

Keith Sharkey, PhD, needs no convincing. His studies in mice also link weed with weight, although his caveat is that users are "somehow protected from weight gain," which is not the same as weight loss.

"What we've shown is that animals on a high-calorie diet equivalent to a Western diet, that would normally gain weight quite substantively, were protected from that weight gain when they were given THC, which is the major ingredient of cannabis," says Sharkey, professor of physiology and pharmacology and medicine at the University of Calgary in Canada.

The same thing is showing up in Bukong's mice on marijuana. "They eat the same amount of food, they lose the weight, and they don't have the inflammation and all of the associated metabolic dysfunction that you get in the context of the control group," he says.

Bukong's mice are also proving some other buzz: that not all cannabis is equal.

"The cannabis plant has over 400 active ingredients. Certain strains give beneficial effects and others do not. We have formulations with high THC, or high CBD, or equal parts; they have different mechanisms of action," he explained. "When you use a certain cannabis formulation, you see weight loss in mouse models that we put on a Western diet of high fat, high cholesterol, high sugar."

For researchers familiar with the endocannabinoid system, the glaring question about weed and weight loss hinges on the CB1 and CB2 receptors. Cannabis stimulates those receptors, but research also shows that blocking them with inverse agonists can induce weight loss. In fact, Heymsfield led clinical development of the now-abandoned drug taranabant, which did exactly this, resulting in large amounts of weight loss in humans for up to 2 years.

"I find it hard to imagine that activating the CB1 receptor with THC would cause the same effects as blocking it," he says. "How could that be reconciled?" (Development of both taranabant and rimonabant, another CB1 inverse agonist, was halted because the drugs were linked with severe anxiety, depression, and suicide, along with weight loss.)

"There is a well-known explanation for the fact that both stimulating and blocking the CB receptors has the same effect," answers Clark. When the receptor is stimulated, there is a fast response and a slow response, he explains. Fast activation of the CB1 receptor promotes weight gain and is responsible for the "high" of cannabis that lasts a couple of hours or so. However, receptors also show a slow response that adjusts the sensitivity of the pathways.

For Bukong, much of the mystery of marijuana and appetite likely lies with the dose and formulation. "Striking the precise therapeutic timing, dose, and balance between CB1 and CB2 receptor activation or inhibition seems to be crucial," he wrote in a recent paper.

As pressure builds in the bottleneck of scientific inquiry and patient curiosity, resolving those questions may take time.

"We need more funding for something that is counter to most mainstream scientific thinking," says Bukong, whose research is funded by the Canadian Institutes of Health Research. "Eventually the answers will become obvious, but for now we just have to keep working."

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