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It’s a cannabis paradox. The drug famously triggers the munchies, yet regular users have lower rates of obesity and type 2 diabetes.

New research in mice, published in The Journal of Physiology, points to a potential explanation: Cannabis compounds may help regulate metabolism by enhancing “cross talk” between fat cells and the pancreas.

While delta-9-tetrahydrocannabinol (THC) is often touted for medicinal benefits, this study suggests that other, nonpsychoactive compounds might drive the plant’s metabolic perks.

“Compared to THC alone, whole plant cannabis extracts reversed type 2 diabetes and more effectively and more potently enabled the communication between fat cells and the pancreas,” said study author Nicholas V. DiPatrizio, a professor of biomedical sciences at the UC Riverside School of Medicine.

DiPatrizio believes these findings could eventually lead to new, cannabis-derived treatments for metabolic disorders — without the complication of getting high. A few research groups around the world are exploring this possibility. DiPatrizio’s team is following up on their findings with more studies to better understand the mechanisms at play — and how to deliver them for therapeutic benefit.

“We’re identifying places in the body outside the brain that can be targeted therapeutically without psychiatric side effects,” said DiPatrizio.

How Cannabis Compounds Might Influence Metabolism

Researchers gave mice with obesity and elevated blood sugar one of two treatments: pure THC or a whole plant cannabis extract. Both treatments contained the same dose of THC: 5 mg/kg of body weight, chosen to mimic the blood concentration in humans after smoking a standard joint, DiPatrizio said.

While both groups lost weight and body fat, the mice given the whole plant extract showed significantly greater metabolic improvements. These included:

• Improved blood sugar regulation
• Faster glucose clearance (reaching rates similar to those found in lean mice)
• Normalized the activity of adipokines

In obese mice, cross talk between the pancreas and adipose tissue gets dysregulated, causing blood sugar to rise, DiPatrizio said. By enhancing cross talk between fat cells and the pancreas, cannabis compounds may help correct this dysregulation — possibly explaining why users tend to have better metabolic health. 

Fixing the ‘Adipoinsular Axis’

Compounds in cannabis might help restore the function of the adipoinsular axis — the communication line between fat cells and the pancreas that modulates blood sugar.

While scientists are still mapping out exactly how cannabis opens these lines of communication, DiPatrizio suspects that cannabinoid 1 (CB1) receptors — found in the central nervous system, fatty tissue, liver, and pancreas — play a major role.

The Two-Phase Effect: Why the Munchies Fade

THC binds to and activates CB1 receptors, causing the munchies and impairing short-term glucose tolerance. But repeated exposure and chronic activation may desensitize these receptors.

“[CB1] belong to a family of receptors that has this specific mechanism,” said Omayma Alshaarawy, MBBS, PhD, an associate professor of family medicine at Michigan State University in East Lansing, Michigan, who studies cannabis use and cardiometabolic health. “The more you activate them, you actually see downregulation, and sometimes you see reversal of those effects.”

As a result, many cannabis effects come in two phases. “You give one dose, you see greater food intake,” Alshaarawy said. “But then you give repeated doses, you see a reduction in food intake.”

At the extreme end, this can lead to cannabis hyperemesis syndrome — a phenomenon that sends some frequent cannabis users to the emergency department with uncontrollable vomiting.

The Future of Metabolic Medicine

More rodent research is needed to map the precise mechanics before moving on to human clinical trials to prove safety and efficacy. Despite the promising data, scientists strongly advise against using recreational cannabis for weight loss or metabolic health. The goal is to leverage the body’s internal cannabinoid system to develop targeted medications, not to encourage people to pick up a cannabis habit, Alshaarawy noted.

“The dialogue between clinicians and their patients who are inquiring about the potential for cannabis-based medication needs to be pretty clear that we have those receptors available in our body, and it’s not about cannabis,” said Alshaarawy.

More research is still needed to understand how chronic use of cannabis influences the long-term risk for cardiovascular disease, diabetes, obesity, and stroke as people age, Alshaarawy added.

The experts cited in this article had no relevant disclosures.