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A 4-week regimen of cannabidiol at a consumer-relevant dose of 5 mg/kg/d causes significant liver enzyme elevations indicative of potential drug-induced liver injury in a subset of healthy adults. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

July 7, 2025JAMA Internal Medicine21 citationsOpen Access

Cannabidiol and Liver Enzyme Level Elevations in Healthy Adults

JFJeffry FlorianUnited States Food and Drug Administration PSPablo A. SalcedoCenter for Drug Evaluation and Research KBKeith BurkhartUnited States Food and Drug Administration

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Abstract

Importance: The wide use of unregulated cannabidiol (CBD) products among consumers raises safety concerns. Most research on CBD has studied the relatively high doses used by patients taking prescription CBD. However, limited safety data are available at lower doses. Objective: To study the effects of 4-weeks of twice-daily CBD use on the liver and endocrine hormones using a dose within the range consumers are taking with unregulated CBD products. Design, Setting, and Participants: This randomized double-blinded placebo-controlled trial from January to August 2024, using per protocol analysis, included healthy adults recruited from a clinical pharmacology unit (Spaulding Clinical Research in West Bend, Wisconsin). Interventions: Healthy participants were randomized to CBD, 5 mg/kg/d (2.5 mg/kg/d twice daily), or placebo for 28 days with weekly laboratory assessments. Main Outcomes and Measures: The primary end point was the percentage of participants with an alanine aminotransferase or aspartate aminotransferase level elevation greater than 3 times the upper limit of normal during the study. Results: In 201 healthy participants (median age, 36 years IQR, 30-43 years; 89 women 44%), 8 participants (5.6%; 95% CI, 1.8%-9.3%) in the CBD group and 0 participants (0%; 95% CI, 0%-7.6%) in the placebo group had liver enzyme level elevation greater than 3 times the upper limit of normal. Seven participants met withdrawal criteria for potential drug-induced liver injury, detected at day 21 in 2 participants and day 28 in 5 participants. No differences in change from baseline were observed between the CBD and placebo groups for total testosterone and inhibin B in male participants or thyrotropin, total triiodothyronine, and free thyroxine in all participants. Conclusions and Relevance: In this study, the incidence of elevated alanine aminotransferase or aspartate aminotransferase 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. Trial Registration: ClinicalTrials.gov Identifier: NCT06192589.

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