Clinical Trial Tests Effects of CBD on Liver Enzyme Levels

A recently published clinical trial measured how cannabidiol (CBD) affected the levels of liver enzymes and endocrine hormones (1). Unregulated CBD use is growing, but information on the potential risks to consumers is lacking, the study explains. Stating that most research focuses on CBD doses taken by patients, researchers used doses of CBD that were on the higher end of the range reported by consumers for unregulated CBD products. “Cannabidiol and Liver Enzyme Level Elevations in Healthy Adults: A Randomized Clinical Trial,” was published in JAMA Internal Medicine in July 2025. The study was funded by the US Food and Drug Administration (FDA) as part of a continued effort to further understand the safety of CBD products and inform management of the potential risks of consumption.

The study involved 201 healthy adult participants ages 18-55 given 2.5 mg/kg of an oral solution of CBD twice daily – or a placebo – for four weeks, with weekly measurements taken in a laboratory and at a day 35 follow up. To avoid potential contaminants in unregulated products, the CBD used in the study was Epidiolex, which is FDA-approved to treat seizures associated with certain conditions, and has been shown by some studies to have an increased risk of increase liver enzyme levels at labeled doses up to 25 mg/kg/d.

Highlighted results of the study included:

• 8 out of the 151 participants (5.6%) in the CBD group had liver enzyme level elevation greater than three times the upper limit of normal
• In comparison, none of the 50 participants in the placebo group had liver enzyme level elevation greater than three times the upper limit of normal
• Seven participants withdrew due to meeting the criteria for possible drug-induced liver injury, which was detected at day 21 in two participants and day 28 in five participants
• No changes in total testosterone and inhibin B in male participants were seen from baseline in male participants in either group
• No changes in thyrotropin, total triiodothyronine, and free thyroxine were seen for all participants in either group

Adverse events were reported, but none were serious or life-threatening. Hepatic enzyme levels returned to normal one to two weeks after the trial.

Limitations of the study included the possibility of different doses or different frequency of use by consumers, the lack of data for older adult participants, and the shorter length of the study, which did not test long-term effects.

Overall, the researchers concluded that the results indicated that more research was needed for consumer safety. “In this study, the incidence of elevated alanine aminotransferase or aspartate aminotransferase coupled with the finding of increased eosinophilia, underscores the need for further investigation on the long-term effects of CBD use, its impact on various populations, and the safety of lower doses commonly used by consumers,” the researchers concluded.

Reference

1. Florian, J.; Salcedo, P.; Burkhart, K.; Shah, A.; Cheka, LMS.; Keshishi, D.; et al. Cannabidiol and Liver Enzyme Level Elevations in Healthy Adults: A Randomized Clinical Trial. JAMA Intern Med. 2025. DOI: 10.1001/jamainternmed.2025.2366.