Daily CBD Use at Consumer-Level Doses May Elevate Liver Enzymes, FDA-Led Trial Shows

Cannabidiol (CBD) is increasingly used by adults in the US, with nearly 21% reporting use in the past year; its popularity spans conditions such as anxiety, sleep disturbances, and chronic pain.¹ Cross-sectional data show that about 43% of users take CBD to self-manage anxiety or stress, while roughly 42% use it for sleep problems and over 30% for chronic pain relief.² Despite its widespread acceptance, an FDA-led clinical trial unexpectedly found that even a low-dose CBD regimen led to clinically meaningful liver enzyme elevations in 5.6% of healthy volunteers—effects that resolved after discontinuation. This evidence underscores the critical need for pharmacist-led liver function monitoring, patient education about asymptomatic enzyme changes, and proactive management of potential drug-drug interactions.³

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Insights From Controlled Clinical Trials

A randomized, double-blind, placebo-controlled trial evaluated oral CBD at consumer-relevant doses (5mg/kg/day) over 28 days in healthy adults aged 18 to 55. Participants underwent weekly liver function monitoring, including alanine transaminase (ALT), aspartate aminotransferase (AST), bilirubin, and alkaline phosphatase.²

In the CBD arm, 5.6% of participants had ALT or AST elevations greater than 3 times the upper limit of normal, compared with none in the placebo group. 7 participants met criteria for potential drug-induced liver injury, though none developed clinical symptoms. Enzyme levels returned to normal within a fortnight of stopping CBD.²

An analysis published in MedPage Today confirmed enzyme elevations in about 6% of typical CBD users—aligning closely with the clinical trial data.¹ Most of these cases remained asymptomatic and went undetected without routine testing.³

Animal Toxicology Reports

A comprehensive 90-day oral toxicity study in rodents evaluated repeated CBD exposure at escalating doses—30, 115, 230, and 460 mg/kg body weight daily with a 35-day post-treatment recovery period. Notably, male rats receiving 460 mg/kg and females at 230 mg/kg exhibited moderate increases in liver weight and liver-to-body weight ratio, indicative of hepatic stress even in the absence of overt clinical toxicity. Histological examination revealed signs of hepatocellular hypertrophy, particularly near central veins, which correlated with observed liver weight changes. Importantly, these structural alterations reversed fully during the recovery phase, suggesting the liver’s capacity to recover post-exposure.³

Although the CBD doses in the clinical trial were much lower, these preclinical findings lend biological plausibility to the enzyme elevations seen in humans. The rodent data reveal a dose-dependent hepatic response to CBD that mirrors transient enzyme increases in healthy adult volunteers, reinforcing the need for cautious hepatic monitoring even at consumer-relevant dosages.³

Strategies for Safe CBD Use

Given the 5% to 6% risk of enzyme elevations, pharmacists should recommend baseline liver tests before initiation, followed by follow-up labs every 4 weeks during the initial treatment month. Elevated readings above 3 times upper limit of normal warrant repeated testing and possible discontinuation. Patients should be educated that even low-dose CBD may affect liver enzymes and that elevations can be asymptomatic. They should be counseled to avoid alcohol, acetaminophen, and other hepatoxic substances, and the report any abnormal symptoms. CBD’s inhibition of CYP2C19 and CYP3A4 (enzyme proteins) may raise plasma levels of commonly used drugs such as statins, antidepressants, and antiepileptics. Pharmacists should review patient medication profiles, advise on appropriate dosage adjustments, and monitor for cumulative toxicity. Since product purity varies widely, pharmacists should recommend reputable, lab-tested CBD brands. This reduces the risk of unlabeled ingredients or contaminants that may exacerbate liver strain. Pharmacists should collaborate with prescribers for patients with pre-existing liver disease or those taking interacting drugs, ensuring a shared plan for monitoring and response to potential enzyme elevations.^1-3

Conclusion

Overall, the study indicates that CBD—at dosages commonly used by consumers—can cause mild, reversible elevations in liver enzymes in approximately 5% to 6% of healthy adults. These effects appear transient and asymptomatic when monitored properly. The lack of long-term safety data leaves room for caution, particularly in patients with risk factors or polypharmacy.

Pharmacy professionals are crucial in translating these findings into safe, informed CBD used: conducting risk assessments, guiding safe dosing practices, arranging liver monitoring, and liaising with prescribers. As CBD’s popularity surges, ensuring hepatic safety becomes a core component of patient care.

REFERENCES

1. Minnerd J. Even Low Doses of CBD May Elevate Liver Enzymes in Healthy Adults. MedPage Today. Published June 6, 2024. https://www.medpagetoday.com/gastroenterology/generalhepatology/116386

2. ClinicalTrials.gov. Clinical Study to Evaluate Cannabidiol Liver Enzyme Elevations and Drug Interactions (NCT06192589). Published April 10, 2024. https://clinicaltrials.gov/study/NCT06192589

3. Tallon MJ, Child R. Subchronic oral toxicity assessment of a cannabis extract. Regulatory Toxicology and Pharmacology. 2023;144:105496. doi:10.1016/j.yrtph.2023.105496