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Yale Researchers Tackle Cannabis Use and Obesity in WHRY-Funded Studies

October 17, 2016

Cannabis Use

Dr. Kelly Cosgrove, Associate Professor of Psychiatry, Radiology and Biomedical Imaging, and Neuroscience, will receive the Wendy U. and Thomas C. Naratil Pioneer Award to examine how smoking cannabis affects the brain in women and men. As Cosgrove notes, there are differences in the ways males and females initiate use of cannabis, progress to dependence, and experience withdrawal symptoms. Her focus will be to determine the sex-specific mechanisms underlying the drug’s rewarding properties and the potential for addiction.

“Cannabis is generally thought of as a safe drug despite a substantial number of studies showing negative, potentially long-term effects on the brain, including cognitive dysfunction and a possible trigger for mental illness,” Cosgrove said. “Over the past 30 years, cannabis has become increasingly potent, with its major psychoactive ingredient, THC, increasing from an average of 1.5 percent before the 1980s to current strains that contain upwards of 25 percent.”

Over the last 20 years, 24 states and the District of Columbia passed laws making cannabis legal for medical or recreational use, even as it remains illegal under federal law. Moreover, cannabis is the most commonly used illicit drug in the United States, with about 22 million people reporting having used it in the previous month. While use of other drugs has declined in recent years, cannabis use has grown.

According to a 2014 national survey, 4.2 million Americans have a marijuana use disorder, defined as use that causes significant problems with health or the ability to meet responsibilities.

Cosgrove’s team has developed a way of using a type of brain scan to show sex differences in the neurochemical response to smoking a tobacco cigarette. They plan to adapt this method and scan men and women smoking cannabis, expecting to see a faster reward response in women at the brain’s suspected hub of drug reinforcement.

“Neurochemical sex differences have been documented for tobacco smoking and alcohol dependence, and we need to find out if there are sex differences in the neurochemistry of cannabis use in humans,” Cosgrove said. “We need to investigate these differences so people can understand what cannabis does to their brains and — for people who become addicted — allow for the development of gender-sensitive treatments.”

Obesity

More than one-third of adults in the country are considered obese. Combining obese adults (those excessively overweight for their height) with less severely overweight adults, 69 percent of the nation’s people are at an unhealthy weight.

While obesity can be found in about equal numbers of women and men, obese women suffer up to eight times greater rates of obesity-related conditions, such as heart disease, stroke, and type 2 diabetes. It’s not clear why.

We need to investigate these differences so people can understand what cannabis does to their brains and — for people who become addicted — allow for the development of gender-sensitive treatments.

Dr. Kelly Cosgrove

Dr. Matthew Rodeheffer, Associate Professor of Comparative Medicine and Molecular, Cellular and Developmental Biology, will also receive a Wendy U. and Thomas C. Naratil Pioneer Award to determine if the molecular pathways driving the growth of fat cells are fundamentally different in females. If so, this would identify a key mechanism that links increased fat mass to metabolic disease in women.

Rodeheffer plans to continue research he first advanced with a 2011 WHRY grant that focused on how women’s body fat increases in obesity.

In that previous research, Rodeheffer’s team showed that obese female mice generate more under-the-skin fat cells (which mostly accumulate around the butt and thighs) while obese male mice do not, suggesting mice could be used to model sex differences in fat distribution. In addition, they showed that removing estrogen from female mice causes them to gain weight in a male pattern (mostly in the stomach).

The new study aims to define how fat cell production is increased in female obesity and determine if the increase in under-the-skin fat cells affects the onset of obesity-associated diseases in females.

“We have learned that females develop fat in different patterns,” Rodeheffer said. “But there is still much to learn about the molecular mechanism driving this difference and how it relates to metabolic disease. We hope to reach a better understanding of this difference and find sex-specific diets and medicines to treat obesity-associated diseases that disproportionately affect women.”