Breakthrough Findings from Hebrew University Research
Researchers at the Hebrew University of Jerusalem have uncovered promising evidence that non-psychoactive compounds from cannabis, specifically cannabidiol (CBD) and cannabigerol (CBG), can significantly reduce liver fat accumulation and improve metabolic health in models of metabolic dysfunction-associated steatotic liver disease (MASLD). This condition, previously known as non-alcoholic fatty liver disease (NAFLD), affects roughly one-third of adults worldwide and is a leading cause of chronic liver issues linked to obesity, insulin resistance, and type 2 diabetes. The study, published in the British Journal of Pharmacology, highlights a novel mechanism involving enhanced energy buffering and lysosomal restoration in the liver, opening new avenues for therapeutic development.
Led by Prof. Joseph Tam, director of the Multidisciplinary Center for Cannabinoid Research at Hebrew University's School of Pharmacy, the team including Dr. Liad Hinden and PhD student Radka Kočvarová, demonstrated these effects in preclinical mouse models. Their work builds on Israel's pioneering role in cannabis science, tracing back to Prof. Raphael Mechoulam's discoveries of the endocannabinoid system.
Understanding MASLD: The Silent Epidemic in the US
MASLD occurs when excess fat builds up in the liver without significant alcohol consumption, often progressing silently to inflammation (MASH), fibrosis, cirrhosis, or liver cancer if unchecked. In the United States, prevalence among adults stands at approximately 33.7%, impacting over 86 million people as of recent estimates, with projections reaching 41.4% or 121.9 million by 2050. Risk factors include metabolic syndrome components like central obesity, hypertension, and dyslipidemia, disproportionately affecting Hispanic Americans and those with type 2 diabetes, where rates exceed 69%.
Current management relies on lifestyle interventions—weight loss of 7-10% can reduce liver fat—but adherence is low, and no FDA-approved drugs exist specifically for MASLD. This gap underscores the urgency of innovative therapies like those explored in cannabinoid research.
Detailed Methods and Quantitative Results from the Study
The Hebrew University team employed male C57Bl/6 mice fed a high-fat diet (HFD) for 14 weeks to induce obesity and MASLD, mimicking human metabolic stress. Mice then received daily intraperitoneal injections of CBD, CBG, or vehicle for 4 weeks. Assessments encompassed body composition, glucose tolerance tests, serum biochemistry, VLDL-triglyceride profiling, hepatic metabolomics, lipidomics, creatine kinase (CK) activity, and cathepsin probes.
- Hepatic triglycerides (TGs) and lipid droplet area significantly reduced, with TGs comprising nearly half of all diminished lipids.
- Ceramides (Cer), drivers of insulin resistance and inflammation, markedly lowered.
- Glycaemic control improved, with normalized blood glucose and enhanced insulin sensitivity (CBG superior).
- Serum lipids normalized: total cholesterol and LDL reduced.
- Hepatic creatine elevated 1.38-fold (CBD) and 2.27-fold (CBG); phosphocreatine surged fourfold (CBD) and 3.4-fold (CBG); CK activity doubled.
- Total cathepsin activity restored to standard diet levels; cathepsins B, S, L rescued or exceeded controls.
CBG proved more potent in reducing body fat mass, while both compounds spared energy expenditure.
The Novel Mechanisms: Phosphocreatine Buffering and Lysosomal Restoration
Under HFD stress, livers deplete primary energy sources (fatty acid oxidation, glycolysis), impairing function. CBD and CBG innovatively boost phosphocreatine—a high-energy phosphate typically prominent in muscle—as a 'backup battery,' enabling rapid ATP regeneration independent of fatty acid changes. This endocannabinoid system-independent pathway enhances resilience.
Simultaneously, they reactivate lysosomal cathepsins, the liver's 'cleaning crew,' restoring lipid degradation. Lipidomics revealed upregulated phospholipids (PA, PS, PE, PC, PI) and lysobisphosphatidic acids (LBPAs), aiding waste clearance. In choline-deficient models, CBG's benefits vanished, pinpointing phospholipid dependence.
Prof. Tam notes: "Our findings identify a new mechanism by which CBD and CBG enhance hepatic energy and lysosomal function. This dual metabolic remodeling contributes to improved liver lipid handling."
Comparing CBD and CBG: Which Shows Greater Promise?
While both cannabinoids ameliorated MASLD hallmarks, CBG outperformed in body fat reduction, cholesterol lowering, and insulin sensitivity. CBD excelled in phosphocreatine elevation. Their synergy—first tested together—suggests combination therapies. Non-psychoactive nature makes them ideal, avoiding THC's intoxicating effects.
The team has patented this CBD/CBG duo for metabolic disorders, eyeing human trials.
Photo by Richard Bell on Unsplash
Building on Prior Cannabinoid-Liver Research
Observational data links cannabis use to lower NAFLD odds (e.g., 54% reduced prevalence in users). Mouse studies show THC/CBD mitigating high-fat diet steatosis via microbiome modulation. CBD attenuates alcohol-induced steatosis. A VCU-led study found cannabis lowers alcohol-related liver disease risk. Meta-analyses confirm liver fat index drops in users.
Yet, human trials lag; a UK pilot (NCT02948647) tests CBD on liver fat in high-risk groups.
Read the full Hebrew University studyUS Research Landscape Amid Cannabis Legalization
With 24 states legalizing recreational cannabis and CBD federally approved since 2018, US universities ramp up studies. Institutions like University of Florida and UT Health San Antonio offer NIDA-funded postdocs in cannabis research. VCU explores cannabinoids for liver protection. For aspiring researchers, opportunities abound in pharmacology and hepatology at higher-ed research jobs.
NIH and CDC highlight MASLD's rise, urging innovation amid 100M+ affected Americans.
Path to Clinical Trials: Challenges and Opportunities
Preclinical success paves for phase I/II trials testing safety/dosing in humans. Challenges: optimal formulations, long-term effects, interactions. Benefits: plant-derived, low side effects. Pharma interest grows; resmetirom (FDA-approved for MASH) sets precedent.
US sites like Mayo Clinic or UCSF could lead trials. Explore clinical research jobs in metabolic disorders.
Implications for Higher Education and Research Careers
This study exemplifies interdisciplinary cannabinoid research at universities, blending pharmacology, metabolomics, and lipidomics. US programs at Johns Hopkins, UCLA expand, creating roles for PhDs/postdocs. Aspiring academics: hone skills in academic CV writing for cannabinoid labs. Institutions seek experts in MASLD amid funding surges.
Ongoing CBD liver fat trial (NCT02948647)Future Outlook: Toward Cannabinoid-Based MASLD Therapies
With patents filed, human trials could yield first cannabis-derived MASLD drug. Combined with lifestyle, it promises reversal for millions. Broader impacts: obesity epidemic combat. Researchers like Tam envision: "a cannabinoid-based drug to help the human population suffering from fatty liver disease."
Stay informed via higher education news. For careers, check university jobs in pharmacology.
Conclusion: A New Era in Liver Health Research
The Hebrew University breakthrough spotlights cannabis compounds' potential against MASLD, a US public health crisis. As research accelerates, universities drive innovation. Explore opportunities at Rate My Professor, higher ed jobs, career advice, university jobs, or recruitment. Engage in comments below.