Cannabis Compounds May Combat Fatty Liver Disease

The Hebrew University of Jerusalem

Researchers have discovered that non-psychoactive cannabis compounds, CBD and CBG, can significantly reduce liver fat and improve metabolic health. The study reveals that these compounds work by creating a backup energy reserve in the liver and restoring the activity of cellular "cleaning crews" to break down harmful waste. These findings highlight a new, plant-based path for treating the world's most common chronic liver disorder.

A study led by Prof. Joseph (Yossi) Tam, Dr. Liad Hinden, the PhD student Radka Kočvarová, and the Tam's team at the School of Pharmacy at the Faculty of Medicine of the Hebrew University of Jerusalem has found that two compounds from the cannabis plant could help treat fatty liver disease. The research suggests that Cannabidiol (CBD) and Cannabigerol (CBG), which are non-psychoactive and do not cause a high, can improve liver health by changing how the organ manages energy and cleans itself.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently the most common chronic liver disorder in the world. It affects approximately one-third of the adult population and is closely linked to obesity, high blood pressure, and insulin resistance. While lifestyle changes like diet and exercise are important, they can be hard to maintain, and there are very few approved medicines available for this condition. This makes the search for new treatments a high priority for scientists.

The researchers used advanced tools to show that CBD and CBG do more than just reduce fat. They actually help the liver function better internally through a unique process of "metabolic remodeling". One of the most important findings was the impact on the liver's energy reserves. These compounds increase levels of phosphocreatine, which acts like a backup battery to help the liver stay healthy under the stress caused by a high-fat diet. This is a new discovery, as the liver does not usually rely heavily on this specific energy system.

Additionally, the study showed that CBD and CBG restore the activity of cathepsins. These are enzymes that act like a cleaning crew within the cell's recycling centers, known as lysosomes. By getting this cleaning crew back to work, the liver is better able to break down and clear out harmful fats and waste. The researchers also found that both treatments 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.

The study observed that while both compounds were effective, they each provided slightly different benefits for metabolic health. Both CBD and CBG were able to normalize blood sugar levels and improve how the body clears glucose. However, CBG appeared to have a more pronounced effect on certain metrics. It significantly reduced body fat mass and improved insulin sensitivity more robustly than CBD. CBG was also particularly effective at lowering total cholesterol and "bad" LDL cholesterol levels.

"Our findings identify a new mechanism by which CBD and CBG enhance hepatic energy and lysosomal function," says Prof. Joseph Tam. "This dual metabolic remodeling contributes to improved liver lipid handling and highlights these compounds as promising therapeutic agents for MASLD".

While these results are very encouraging, the team notes that more research is needed to understand how these findings can best be applied to human patients. This study opens a new path for using plant-based compounds to treat metabolic diseases by focusing on how cells manage energy and waste.

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