90-day CBD-rich hemp extract study in rats found no major toxicity but flagged kidney and liver signals | Research

The takeaway

A 90-day toxicity study of CBD-rich hemp extract in male and female rats found no adverse effects on organs, behavior, or survival, but detected sex-dependent changes in kidney and liver biomarkers and mapped CBD accumulation across tissues.

CBD users and healthcare professionals interested in safety data for long-term CBD supplementation.

CBD accumulated most in muscle and skin, least in brain, after 90 days of oral dosing

What the researchers found

No adverse effects on organ weight, body weight, behavior, locomotion, food intake, or mortality were observed at any dose (0.5-35 mg/kg/day). However, blood analysis showed significant decreases in calcium, sodium, potassium, chloride, alkaline phosphatase, and creatinine. Males showed decreased alanine transaminase; females showed hyperalbuminemia. CBD accumulated in tissues in the order: brain < serum < liver < heart < kidney < muscle and skin.

Why it matters

As CBD products proliferate, rigorous safety data remain limited. This 90-day study provides one of the more thorough safety profiles available, including tissue distribution mapping that shows CBD concentrates heavily in muscle, skin, and kidneys rather than the brain.

The numbers in context

Doses: 0.5, 5, 10, 35 mg CBD/kg/day for 90 days. Extract was 77% CBD. Tissue accumulation order: brain < serum < liver < heart << kidney <<< muscle and skin. CBD detected in dose-dependent manner (p values from <0.05 to <0.0001).

How the study worked

Male and female rats received CBD-rich (77% CBD) full-spectrum hemp extract at 0.5, 5, 10, or 35 mg/kg/day orally for 90 days. Researchers assessed organ and body weight, behavior, locomotion, food intake, mortality, pathomorphology, blood cells, serum biochemistry, electrolytes, and CBD tissue distribution.

What this study cannot tell us

Rat metabolism differs significantly from human metabolism. The extract was full-spectrum (not pure CBD), so other cannabinoids and compounds may contribute to effects. No recovery period was included to confirm reversibility of biomarker changes. The highest dose (35 mg/kg) is relatively modest compared to some human CBD dosing.

How to read the evidence

Well-designed 90-day sub-chronic toxicity study in both sexes with comprehensive tissue analysis, though limited to rats.

When this study was published

Published in 2025.

The bigger picture

The tissue distribution data are particularly interesting: CBD concentrated most heavily in muscle and skin, with relatively low brain levels. This suggests oral CBD may have limited central nervous system bioavailability while potentially accumulating in peripheral tissues. The sex-dependent kidney and liver biomarker changes, while likely reversible, warrant monitoring in long-term human CBD users.

Questions still open

Are the kidney and liver biomarker changes reversible after stopping CBD? Does the high CBD accumulation in skin and muscle have functional significance? Would higher doses or longer exposure produce more concerning effects? Do these tissue distribution patterns hold in humans?

Common questions

Was CBD toxic at any dose?

No organ damage, behavioral changes, or deaths were attributed to CBD at any of the four doses tested (0.5 to 35 mg/kg/day) over 90 days. The changes detected were subclinical biomarker shifts considered likely reversible.

Why did CBD accumulate in muscle and skin?

CBD is highly fat-soluble, so it tends to distribute into tissues with high lipid content. Muscle mass is large, and skin has significant lipid stores, which may explain the high accumulation in these tissues.

Were there sex differences?

Yes. Males showed decreased alanine transaminase (a liver enzyme), while females showed elevated albumin levels. Both findings suggest sex-dependent latent effects on liver and kidney function.

Read the original research

Safety assessment on CBD-rich hemp extract in sub-chronic cross-sex study with rats.

Toxicology and applied pharmacology, 495, 117218

View on PubMed ↗Publisher’s paper ↗

Citation

Dehner, Jan; Polanska, Hana Holcova; Petrlakova, Katerina; Zeljkovic, Sanja Cavar; Beres, Tibor; Hendrych, Michal; Storch, Jan; Tarkowski, Petr; Masarik, Michal; Babula, Petr; Vacek, Jan. (2025). Safety assessment on CBD-rich hemp extract in sub-chronic cross-sex study with rats.. Toxicology and applied pharmacology, 495, 117218. https://doi.org/10.1016/j.taap.2024.117218