Regular CBD use linked with liver enzyme elevations, FDA trial finds

Healthy adults exposed to twice-daily cannabidiol (CBD) for 28 days had elevations in hepatic aminotransferase levels and eosinophilia, a randomized trial carried out by the FDA found.

To determine the effects of CBD use on the liver and endocrine hormones, investigators randomized 201 participants (median age, 36 years; 44% women) to CBD, 2.5 mg/kg/d twice daily, or placebo for 28 days, with weekly laboratory assessments between January and August 2024. The dose was within the range consumers are taking with unregulated CBD products, the authors wrote. The primary end point was the percentage of participants with an elevation in alanine aminotransferase or aspartate aminotransferase level that was greater than three times the upper limit of normal. Findings were published by JAMA Internal Medicine on July 7.

Eight participants (5.6%; 95% CI, 1.8% to 9.3%) in the CBD group and 0 participants (0%; 95% CI, 0% to 7.6%) in the placebo group had liver enzyme level elevations greater than three times the upper limit of normal. A total of seven participants met withdrawal criteria for potential drug-induced liver injury, detected at day 21 in two participants and at day 28 in five participants. Five of the eight aminotransferase elevations occurred in females, as did the highest observed elevations. There were no differences between groups in change from baseline for total testosterone and inhibin B in male participants or thyrotropin, total triiodothyronine, and free thyroxine in all participants. Hepatic enzymes returned to normal within one to two weeks of CBD discontinuation.

Forty-three (29%) participants in the CBD group and nine (18%) in the placebo group experienced adverse events, none of which were serious or life-threatening. The most commonly reported adverse events in the CBD group were hepatic enzyme increase (11%), eosinophilia (9%), somnolence (8%), and diarrhea (8%).

Limitations include that the dose tested was on the higher end of the range of reported consumer use and that CBD was administered twice daily. The age range of the study's population was also 18 to 55 years, so extrapolation to other age groups is uncertain.

The incidence of elevated alanine aminotransferase or aspartate aminotransferase, with a notably higher prevalence among female participants, 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 authors wrote.

An accompanying editorial noted that the trial does not provide information about the effects of CBD on users at the highest risk for toxicity, such as patients also taking hepatoxic medications or drinking alcohol or those with abnormal liver enzyme levels and underlying liver disease at baseline. The results “underscore that clinicians should be aware of CBD-associated hepatoxic effects and screen patients with elevated liver enzyme levels for CBD use,” the editorialists concluded.