Ten Weeks of Daily CBD Oil Did Not Damage Rat Liver Structure | Research

The takeaway

Ten weeks of daily oral CBD oil (10 mg/kg) in rats caused no structural liver damage, though the number of Kupffer cells (immune cells in the liver) increased significantly, especially near portal zones.

Toxicologists, hepatologists, and CBD product safety researchers.

What the researchers found

No pathohistological changes were observed in rat liver sinusoids after 10 weeks of daily CBD oil. However, Kupffer cell numbers increased significantly in all zones of the liver lobule (p<0.001), with a 1.58-fold increase near the portal zone. Perisinusoidal (stellate) cells remained the least abundant cell type. The study concluded CBD oil was safe for long-term liver exposure.

Why it matters

Liver safety is a key concern for CBD, given Epidiolex's liver enzyme warning. This study provides histological evidence that long-term oral CBD at a moderate dose does not cause structural liver damage, though the Kupffer cell increase suggests the liver's immune cells are responding to chronic CBD exposure.

The numbers in context

14 treated rats, 6 controls. 10 mg/kg/day for 10 weeks. No pathological liver changes. Kupffer cells increased 1.58-fold in portal zone (p<0.001). Significant increase in all lobule zones. Perisinusoidal cells remained lowest count.

How the study worked

20 male rats: 14 received daily oral CBD oil (10 mg/kg) for 10 weeks, 6 controls received hemp seed oil. Histological, immunohistochemical, and morphometric analyses of liver sinusoidal cell composition with statistical analysis (p<0.05 threshold).

What this study cannot tell us

Small sample (14 treated, 6 controls). Single dose tested (10 mg/kg). Male rats only. 10-week duration may not capture very long-term effects. CBD oil composition not fully characterized. Histological assessment may miss functional changes detectable only by blood tests or metabolomics.

How to read the evidence

Appropriate histological and immunohistochemical methods with statistical analysis, but small sample, single dose, and single species limit the conclusions.

When this study was published

Published 2025.

The bigger picture

The Kupffer cell increase without structural damage suggests CBD activates hepatic immune surveillance without causing harm. This could be either a benign adaptive response or an early signal of immune-mediated liver changes that might manifest with longer exposure or higher doses.

Questions still open

Whether the Kupffer cell increase has functional consequences at longer time points or higher doses
Whether this Kupffer cell activation relates to the liver enzyme elevations seen with high-dose CBD in clinical settings

Common questions

Is long-term CBD safe for the liver?

This study found no structural liver damage after 10 weeks of daily CBD at a moderate dose, which is reassuring. However, the increase in immune cells suggests the liver is responding to chronic CBD exposure, and whether this matters over months or years of human use is unknown.

What are Kupffer cells?

Kupffer cells are specialized immune cells that reside in the liver's blood channels (sinusoids). They detect and clear toxins, pathogens, and damaged cells. Their increase in response to CBD suggests the liver is recognizing and processing CBD as a foreign substance, activating its surveillance system.

Read the original research

Qualitative and quantitative analysis of rat liver sinusoids under condition of a long-term experimental exposure to cannabidiol oil.

Wiadomosci lekarskie (Warsaw, Poland : 1960), 78(12), 2611-2619

View on PubMed ↗Publisher’s paper ↗

Citation

Shevchuk, Mykola M; Volos, Liliya I; Kovalska, Oksana R. (2025). Qualitative and quantitative analysis of rat liver sinusoids under condition of a long-term experimental exposure to cannabidiol oil.. Wiadomosci lekarskie (Warsaw, Poland : 1960), 78(12), 2611-2619. https://doi.org/10.36740/WLek/215799