Both CBD and THC Cannabis Improved Insulin Resistance and Liver Disease in Obese Mice | Research

The takeaway

In obese mice, both high-CBD and high-THC cannabis significantly reduced insulin resistance and liver disease severity while shifting inflammatory macrophages toward a less harmful profile.

Metabolic disease researchers, endocrinologists, and anyone interested in cannabis and obesity/diabetes connections.

What the researchers found

Both high-CBD and high-THC cannabis significantly mitigated obesity-induced increases in insulin resistance (HOMA-IR) and metabolic dysfunction-associated steatohepatitis (MASH), while reducing proinflammatory M1-like macrophages in the liver.

Why it matters

Obesity-related insulin resistance and fatty liver disease affect hundreds of millions of people worldwide. If cannabis-derived treatments can improve metabolic dysfunction and shift immune responses, they could offer a novel therapeutic approach to these conditions.

The numbers in context

High CBD cannabis: ~4.2 mg/kg, 10.5% CBD content. High THC cannabis: ~7.3 mg/kg, 18.16% THC content. Both significantly reduced HOMA-IR and MASH scores compared to obese placebo (p values significant). Treatment was 3 times/week for 4 weeks.

How the study worked

Female C57BL/6 mice were randomized into four groups (n=15 each): lean, obese placebo, obese receiving high-CBD cannabis (~4.2 mg/kg), and obese receiving high-THC cannabis (~7.3 mg/kg) three times per week for 4 weeks after 16 weeks of high-fat diet.

What this study cannot tell us

Mouse study using female mice only — results may not translate to humans or male subjects. Cannabis was administered as whole plant (not isolated compounds). Short 4-week intervention after 16 weeks of established obesity.

How to read the evidence

Well-designed preclinical study with appropriate controls and randomization, but limited to female mice with a short intervention period.

When this study was published

Published 2025.

The bigger picture

The finding that both CBD and THC improved metabolic markers challenges the assumption that only CBD has therapeutic metabolic effects. The immune-modulating mechanism — shifting macrophage profiles — suggests cannabis may address the inflammatory root of metabolic disease, not just symptoms.

Questions still open

Would similar metabolic improvements occur in humans? Are the effects driven by specific cannabinoids or the entourage effect? Would longer treatment duration produce greater benefits? How do male mice respond?

Common questions

Does cannabis help with weight loss or diabetes?

This mouse study showed improvements in insulin resistance and liver disease markers, but not necessarily weight loss. Human clinical trials are needed before any metabolic health claims can be made.

Was CBD or THC more effective?

Both high-CBD and high-THC cannabis showed significant improvements. The study did not report one being clearly superior to the other for metabolic outcomes.

Read the original research

Cannabis improves metabolic dysfunction and macrophage signatures in obese mice.

American journal of physiology. Cell physiology, 329(4), C1316-C1331

View on PubMed ↗Publisher’s paper ↗

Citation

VanderVeen, Brandon N; Cardaci, Thomas D; Unger, Christian A; NeSmith, Mitchell M; Freeman, Jeffrey C; Bastian, Arianna V; Roark, Kasie; Upadhyay, Mansi; Levy, Andrew G; Bullard, Brooke M; McDonald, Sierra J; Velázquez, Kandy T; Enos, Reilly T; Kubinak, Jason L; Hofseth, Lorne J; Hebert, James R; Fan, Daping; Murphy, E Angela. (2025). Cannabis improves metabolic dysfunction and macrophage signatures in obese mice.. American journal of physiology. Cell physiology, 329(4), C1316-C1331. https://doi.org/10.1152/ajpcell.00503.2025