Cannabidiol (CBD) is the nonpsychoactive component of cannabis and is available as an FDA–approved prescription medication (Epidiolex; Greenwich Biosciences) for the management of epilepsy. In doses up to 25 mg/kg/d, this drug has been associated with increased liver enzyme levels but not with serious liver disease with jaundice.
CBD is also available in unregulated over-the-counter (OTC) products such as oils, gummies, creams, and vaping solutions. The lower doses of CBD in OTC products has not been consistently associated with elevation of liver enzymes.
A randomized double-blinded placebo-controlled trial was undertaken to determine the effect of CBD on liver enzymes at doses at or near the upper end of OTC CBD products. The study randomly assigned 201 healthy participants aged 18 to 55 years to receive either CBD or placebo for 28 days. A total of 151 people received CBD at a dose of 5 mg/kg/d and 50 received placebo for 28 days.
Eight participants receiving CBD (5.6%) had markedly elevated liver enzymes; one had peak alanine aminotransferase levels (ALT) greater than 3 times the upper limit of normal (ULN), five had peak ALT levels greater than 5 times the ULN, and two had ALT levels greater than 10 times the ULN. The ULN for ALT was 33 U/L for males and 25 U/L for females. Five of the eight patients with elevated ALT were females. Seven of the eight patients also developed eosinophilia. None of them exhibited jaundice clinical symptoms of impaired liver function. Liver enzymes returned to the reference range in all participants within 1 to 2 weeks of discontinuing CBD administration.
The 2022 National Survey on Drug Use and Health reported that 20.6% of adults in the US used CBD in the prior year. Older adults are the fastest growing population of cannabis users. Many CBD users are probably not as healthy or as young as the participants in this study and consume higher doses of CBD for much longer than 28 days. Some may concurrently consume hepatotoxic medications, drugs, or alcohol. Therefore, the number of CBD users with elevated liver enzymes in the general population may be significantly higher than reported in this study. Clinicians need to include CBD use in their differential diagnosis when working up patients with elevated liver enzymes.
Reference
Florian J et al. Cannabidiol and Liver Enzyme Level Elevations in Healthy Adults: A Randomized Clinical Trial, JAMA Intern Med, published online July 7, 2025, doi:10.1001/jamainternmed.2025.2366
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