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TOPLINE:

Cannabidiol use at 5 mg/kg/day in healthy adults resulted in liver enzyme levels exceeding three times the upper limit of normal in 5.6%, with no significant changes in endocrine hormone levels compared with placebo.

METHODOLOGY:

• A randomized controlled trial was conducted in Wisconsin from January to August 2024 to evaluate the effects of daily use of cannabidiol on liver enzyme levels at a dose similar to that reported for consumer use with unregulated products.
• A total of 201 healthy adults (median age, 36 years; 44% women; 49% White individuals) who were nonsmokers, weighed at least 50 kg, and had normal health records were randomly assigned to receive either a 2.5 mg/kg oral solution of cannabidiol twice a day (n = 151) or an inactive placebo solution (n = 50) for 28 days.
• Levels of liver enzymes and endocrine hormones were assessed at multiple timepoints from baseline until day 35.
• The primary outcome was the percentage of participants with serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels exceeding three times the upper limit of normal.
• The secondary outcomes included the percentage of participants meeting the withdrawal criteria for potential drug-induced liver injury (characterized by elevations in ALT, AST, alkaline phosphatase, or bilirubin levels accompanied by symptoms or eosinophilia) and changes in endocrine hormone levels.

TAKEAWAY:

• In the cannabidiol group, eight participants (5.6%) had elevated levels of the liver enzyme ALT that exceeded three times the upper limit of normal, while no such cases occurred in the placebo group.
• Seven participants (4.9%) in the cannabidiol group met the withdrawal criteria for potential drug-induced liver injury; two stopped taking cannabidiol on day 21 and five on day 28. These participants had elevated ALT levels with accompanying eosinophilia.
• No substantial differences in the levels of endocrine hormones, including testosterone (in men) and thyroid-stimulating hormone, were observed between the groups.
• No serious or life-threatening adverse events were reported. Adverse events, including increased hepatic enzyme levels and eosinophilia, occurred in 29% of participants in the cannabidiol group, while 18% of the placebo group experienced events such as insomnia and upper respiratory tract infections.

IN PRACTICE:

“The findings suggest that CBD [cannabidiol] use at doses representative of currently available unregulated consumer products can lead to liver enzyme level elevations in healthy adults. As CBD users may not notice these changes on their own, this study highlights the need for caution and potentially routine monitoring in CBD users,” the authors of the study wrote.

“Overall, results of the trial by Florian et al underscore that clinicians should be aware of CBD-associated hepatoxic effects and screen patients with elevated liver enzyme levels for CBD use,” experts wrote in an accompanying editorial.

SOURCE:

The study was led by Jeffry Florian, PhD, of the Center for Drug Evaluation and Research, US FDA in Silver Spring, Maryland. It was published online on July 7, 2025, in JAMA Internal Medicine.

LIMITATIONS:

The cannabidiol dosage was on the higher end of what consumers typically used. The age range of 18-55 years excluded older adults who often used cannabidiol. The monitoring frequency was insufficient to determine if liver enzyme elevations would return to normal without discontinuing the treatment.

DISCLOSURES:

This study was funded by the US FDA. One author reported that Spaulding Clinical received payment from the FDA to carry out the clinical study.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.