Two compounds from a cannabis plant could help what’s commonly known as “fatty liver disease,” Israeli researchers say.

Metabolic dysfunction-associated steatotic liver disease, known as MASLD, is the most common liver problem in the world, affecting about one out of every three adults.

However, “this disease does not have a current drug available whatsoever,” Prof. Yossi Tam of the Hebrew University of Jerusalem’s School of Pharmacy told the Times of Israel by phone.

Tam, 51, who is also director of the university’s Multidisciplinary Center for Cannabinoid Research, led the groundbreaking study that shows that Cannabidiol (CBD) and Cannabigerol (CBG), which are non-psychoactive and do not cause a high, can improve the health of the liver by changing how the organ manages energy and cleans itself.

The peer-reviewed research in mice, appearing Friday in The British Journal of Pharmacology, came across what Tam called the mechanism that the liver used for energy and cleaning that was previously unknown.

Lead author PhD student Radka Kočvarová, Dr. Liad Hinden of Tam’s lab, and researchers at Technion-Israel Institute of Technology also contributed to the study.

“Given that one third or more of adults in Western societies are at risk for this disorder accompanying the obesity epidemic, [the study] portends enormous public health significance,” said Dr. Ethan Russo, founder and CEO of CReDO Science, a research, development and educational company focusing on cannabis. Russo was not involved in the study.

Tam said the novel aspect of the research was its testing of both CBD and CBG. The lab has patented the use of the combination of CBD and CBG for metabolic disorders, and this step could pave the way for clinical trials of the treatment on humans.

According to a 2024 Knesset Health Committee report, nearly 60% of Israel’s adult population is overweight or obese, and one in five children suffers from obesity.

“This is a growing problem in Israel,” Tam said.

The uptick in obesity increases the risk of liver disease because the liver is forced to store extra fat. This buildup triggers a cycle of irritation and inflammation that may lead to permanent liver scarring and functional failure, including MASLD.

Some symptoms of the disease include feeling tired and unwell, and pain in the liver, primarily in the abdomen under the right side of the ribs.

MASLD can usually be treated with healthy lifestyle changes such as exercise and healthier eating, but only if the disease is caught in time.

Tam, who has a PhD in cannabinoid pharmacology, said his lab focuses on solutions for metabolic disorders using the body’s endocannabinoid system. That is the inner apparatus that helps regulate appetite, manage pain and operate the immune system.

The body manufactures chemicals similar to THC

The discovery of the endocannabinoid system was pioneered by Prof. Raphael Mechoulam, considered the father of cannabis research and founder of the Multidisciplinary Center.

Mechoulam’s discovery that the body produces chemicals similar to THC paved the way for groundbreaking studies about cannabis and the endocannabinoid system.

“Scientific literature already shows that CBD has some metabolic benefit by inhibiting your food consumption and reducing weight in clinical trials in humans,” Tam said. “We were really intrigued by this. What is the exact mechanism?”

He set up an experiment, hoping to find the answer.

‘High-fat diet’ experiment

There is a common model for diet-induced obesity in lab animals, Tam explained.

“You basically put the mice on high-fat diet for 14 weeks,” Tam said. “They become obese, they develop fatty liver disease, diabetes, all the features of the metabolic syndrome. And then we treat the animals for 28 days with the drug, and monitor their metabolism.”

Using advanced tools, the researchers showed that CBD and CBG do more than just reduce fat.

“The two compounds actually help the liver function better internally through a unique process of ‘metabolic remodeling,'” Tam said.

One of the most surprising findings was the impact on the liver’s energy reserves, he said.

The liver usually prefers slower, more sustained energy production from fats and sugars. But a high-fat diet depletes its normal energy reserves and leads to cell damage.

Both CBD and CBG offset the damage by increasing the levels of phosphocreatine, an energy molecule in the liver, whose job is to recharge the liver like a “backup battery,” Tam explained.

The study also showed that CBD and CBG restore the activity of enzymes called cathepsins that act like a “cleaning crew,” enabling the liver to clear out harmful fats and waste.

In addition, the researchers found that the cannabinoid treatment significantly reduced harmful lipids, such as triglycerides and ceramides. Ceramides are particularly dangerous because they are known to contribute to insulin resistance and liver inflammation.

Tam said he was surprised that CBG significantly reduced body fat mass and lowered total cholesterol levels.

“The study elucidates the benefits” of CBD and CBG to counteract MASLD, said Russo. The method could provide “an apparently safe and effective treatment option” based on two cannabis plant compounds.

Tam said the lab’s goal is to take the findings from the lab and begin clinical trials.

“My hope is to bring a cannabinoid-based drug to help the human population suffering from fatty liver disease and metabolic disorder,” he said.

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