New research from a randomised clinical trial indicates that daily cannabidiol (CBD) use, even at doses commonly reported by consumers, may be associated with significant elevations in liver enzymes among healthy adults. These findings underscore the importance of clinical vigilance and routine medical screening for individuals using CBD products, particularly those with pre-existing liver conditions or who are taking other medications.
Key Findings from the Clinical Trial
The study, conducted by a team of FDA scientists led by Jeffry Florian, PhD, of the FDA’s Center for Drug Evaluation and Research, involved 201 healthy adult participants over 28 days. The results, published in JAMA Internal Medicine, as reported by MedPage Today, revealed notable increases in liver enzyme levels in the CBD group compared to the placebo group.
- Eight participants (5.6%) in the CBD group experienced liver enzyme levels greater than three times the upper limit of normal (ULN).
- Five individuals (3.3%) had peak aminotransferase levels exceeding five times the ULN.
- Two participants (1.3%) showed aminotransferase levels greater than 10 times the ULN, with one reaching more than 18 times higher.
Florian’s team reported that seven of these participants met the criteria for drug-induced liver injury. While eosinophilia was also observed in seven of the eight individuals with elevated liver enzymes, no participants developed jaundice or experienced other clinical symptoms related to impaired liver function. Importantly, the researchers noted that liver enzymes normalised within one to two weeks after discontinuing CBD use.
Implications for Patient Care and Regulatory Oversight
These findings carry significant implications for consumers and healthcare providers. Florian and colleagues emphasised that this clinical trial is part of broader FDA efforts to understand the safety profile of CBD products and to inform discussions about necessary safeguards and oversight. “These findings may have important implications for consumers who may otherwise be unaware of potential safety risks,” they wrote.
Given the increasing availability of unregulated CBD-containing products, the researchers suggested that “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 also noted that for patients presenting with elevated liver enzymes, CBD use could be a factor 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, highlighted the widespread use of CBD, with over 20% of U.S. adults reporting use in the past year, according to 2022 National Survey on Drug Use and Health data. Stall and Covinsky stated that the study “underscores that clinicians should be aware of CBD-associated hepatoxic effects and screen patients with elevated liver enzyme levels for CBD use.” They also called for regulators to balance the proliferation of CBD products with increased public awareness and clinical vigilance.
Understanding the Study’s Design and Limitations
The randomised, double-blinded, placebo-controlled trial was conducted from January to August 2024. Participants were healthy adults, aged 18-55 years, recruited from a clinical pharmacology unit. They were randomised to receive either CBD at 5 mg/kg/d (2.5 mg/kg/d twice daily) or a placebo for 28 days, with weekly laboratory assessments.
The study’s primary endpoint was the percentage of participants with an alanine aminotransferase or aspartate aminotransferase level elevation greater than three times the ULN. However, the researchers acknowledged several limitations:
- The study enrolled only healthy participants without other medications or comorbidities that might increase susceptibility to liver enzyme elevations, meaning the impacts on other populations are not yet clear.
- The short duration of the study (28 days) prevents conclusions about potential longer-term health effects.
- Dosing was discontinued when elevated liver enzymes were observed, so it is unknown if these levels would have resolved naturally or escalated further without intervention.
- While the CBD dosing was within the range of reported consumer use, it was on the higher end and administered twice daily. The researchers also noted the potential for inaccurate labelling of over-the-counter CBD products, which could mean individuals self-dosing may consume different amounts than expected.
These findings serve as an important reminder for both consumers and healthcare professionals to approach CBD use with caution and to consider potential interactions and individual health profiles, particularly concerning liver health.
Disclaimer: This article is for informational purposes only and does not constitute medical advice. Hemp Gazette does not provide medical recommendations, diagnoses, or treatment plans. Always consult a qualified healthcare practitioner before making any decisions regarding your health or any medical condition. Statements concerning the therapeutic uses of hemp, cannabis, or cannabinoid-derived products have not been evaluated by Australia’s Therapeutic Goods Administration (TGA). Medicinal cannabis products in Australia are accessed via prescription pathways under TGA regulation.
