Clinical Trial Sheds Light on Daily CBD Use and Liver Enzymes

https://www.medpagetoday.com/gastroenterology/generalhepatology/116386

Some trial participants had peak levels ten times higher than normal upper limit

Daily use of cannabidiol (CBD) at doses commonly reported by consumers was associated with potentially dangerous increases in liver enzymes, a randomized clinical trial found.

Among 201 healthy adult participants followed for 28 days, eight (5.6%) of those randomized to CBD had liver enzyme levels greater than three times the upper limit of normal (ULN) compared with none in the placebo group, said a team of FDA scientists led by Jeffry Florian, PhD, of the FDA’s Center for Drug Evaluation and Research in Silver Spring, Maryland.

Five individuals (3.3%) experienced peak aminotransferase levels greater than five times the ULN, and two (1.3%) had aminotransferase levels greater than 10 times the ULN, with the highest more than 18 times higher. These seven participants met criteria for drug-induced liver injury, Florian’s team reported online in JAMA Internal Medicine

Eosinophilia was also observed in seven of the eight individuals with elevated liver enzymes. However, no participants experienced jaundice or clinical symptoms related to impaired liver function, and liver enzymes normalized within 1 to 2 weeks of discontinuing CBD, the researchers said.

“This clinical trial is part of the FDA efforts to understand the safety of CBD products and inform discussions about safeguards and oversight to manage and minimize risks with CBD products. These findings may have important implications for consumers who may otherwise be unaware of potential safety risks,” Florian and colleagues wrote.

“Given the growing popularity of unregulated CBD-containing products in the market and the ability of CBD to cause liver enzyme level elevations, inclusion of CBD use as part of routine medical screening could be considered, particularly in patients with existing liver conditions or those taking medications metabolized by the liver,” they added. “For patients presenting with elevated liver enzymes, CBD use could be considered in the differential diagnosis.”

In an accompanying editorial, Nathan Stall, MD, PhD, of the University of Toronto, and Kenneth Covinsky, MD, MPH, of the University of California San Francisco, noted that data from the 2022 National Survey on Drug Use and Health indicated that more than 20% of U.S. adults reported using CBD in the past year. “Given the high use and increasing access to CBD without a prescription, the study by Florian et al raises several important concerns,” they wrote.

The results “underscore that clinicians should be aware of CBD-associated hepatoxic effects and screen patients with elevated liver enzyme levels for CBD use. Finally, regulators should balance the free market proliferation of CBD with the need for increased public awareness and clinical vigilance,” Stall and Covinsky said.

The randomized, double-blinded, placebo-controlled trial was conducted from January to August 2024 using per protocol analysis. It included healthy adults recruited from a clinical pharmacology unit. Participants were randomized to CBD 5 mg/kg/d (2.5 mg/kg/d twice daily), or placebo for 28 days. Laboratory assessments were done weekly. The primary endpoint was the percentage of participants with an alanine aminotransferase or aspartate aminotransferase level elevation greater than three times the ULN during the study.

Limitations included that the study enrolled healthy participants between 18-55 years of age who were not taking other medications and who had no comorbidities that could have increased their susceptibility to hepatic enzyme level elevations, so impacts on populations outside these conditions were not captured. In addition, the study’s short duration could not determine potential longer-term health effects. Because dosing was discontinued when elevated liver enzymes were observed, it is not known whether they would have resolved on their own or escalated further.

Finally, the researchers noted, the CBD dosing in the study was within the range of reported consumer use, but it was on the higher end and administered twice daily. “While many consumers report taking unregulated CBD more than once daily, most consume it less frequently. In addition, given the reports of inaccurate labeling of some over-the-counter CBD products, it is possible that individuals self-dosing CBD are consuming different doses than expected,” they said.

 

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