Cannabis compounds may improve metabolism and reduce diabetes risk

A University of California, Riverside preclinical study is shedding light on a long-observed but poorly understood phenomenon: chronic cannabis users tend to have lower body weight and a reduced risk of developing type 2 diabetes, despite the drug's well-known tendency to increase appetite.

A team led by Nicholas V. DiPatrizio, a professor of biomedical sciences at the UCR School of Medicine, set out to investigate this apparent paradox. While cannabis is commonly associated with increased food intake - often referred to as the "munchies" - population studies consistently show that regular users exhibit improved metabolic profiles compared to non-users. 

The new findings, published in The Journal of Physiology, suggest that specific compounds within cannabis may play a key role in regulating metabolism.

Using a mouse model designed to mimic human dietary patterns, DiPatrizio and his team compared the effects of pure delta-9 tetrahydrocannabinol (THC) - the primary psychoactive component of cannabis - with a whole-plant cannabis extract containing the same level of THC alongside other naturally occurring compounds.

Both treatments led to significant weight loss in obese mice. However, the metabolic outcomes differed dramatically.

Mice treated with THC alone showed no improvement in glucose regulation, a key indicator of type 2 diabetes. Despite losing weight, these animals continued to exhibit impaired glucose homeostasis, a hallmark of diabetes.

In contrast, mice treated with the whole cannabis extract not only lost weight but also experienced a reversal of these metabolic impairments.

"This suggests that THC alone is not responsible for the metabolic benefits associated with cannabis use," said DiPatrizio, who directs the UCR Center for Cannabinoid Research. "Other compounds in the plant appear to play a critical role."

The researchers' analysis points to a potential mechanism involving communication between fat tissue and the pancreas. In healthy systems, fat cells release signaling molecules that help regulate insulin secretion from the pancreas. In obesity and type 2 diabetes, this signaling becomes disrupted.

The study found that treatment with the full cannabis extract restored this communication pathway better than THC alone, allowing fat tissue to signal the pancreas and regulate blood glucose levels more effectively.

While the findings are promising, the researchers emphasize they do not necessarily support the use of cannabis as a treatment for metabolic disease given that further research is needed in preclinical and human studies.

"We're not suggesting people should use cannabis to manage weight or diabetes," DiPatrizio said.

DiPatrizio aims to identify non-psychoactive cannabis compounds for targeted therapies that deliver metabolic benefits without THC's intoxicating effects. Future studies will isolate and test individual compounds to pinpoint those responsible.

The research also underscores the importance of continued scientific investigation as cannabis use becomes more widespread and policies evolve.

"Clinicians, researchers, and policymakers should stay tuned and pay attention to this space," DiPatrizio said. "We need evidence-based approaches to fully understand both the risks and potential benefits of cannabis and its components."

DiPatrizio was joined in the study by Bryant Avalos, Martin Olmos, Courtney P. Wood, Camila Alvarez, Haley M. Read, Parima Udompholkul, and Theodore Garland Jr.

The research was funded by grants from the National Institutes of Health and the Tobacco-Related Disease Research Program managed by the University of California Office of the President.