Research study · JAMA Internal Medicine · 2025
Cannabidiol and Liver Enzyme Level Elevations in Healthy Adults
Verified on PubMed Oxford CEBM Level 1B: Randomized Controlled Trial
A 2025 randomized controlled trial in JAMA Internal Medicine tested cannabidiol in liver safety. The extract caused elevated liver enzymes in a small number of healthy adults. This research demonstrates that a common daily amount of hemp extract can elevate liver enzymes in healthy people over a four-week period, even though the changes resolved after.
In plain language
Study overview
Researchers investigated whether taking a common daily amount of hemp extract oil affects liver health and hormone levels in healthy adults. Over two hundred participants took either the study liquid or an inactive liquid twice daily for four weeks while having their blood tested regularly.
Findings
The extract caused elevated liver enzymes in a small number of healthy adults. About five percent of the participants taking the extract experienced liver enzyme increases above the safety threshold, whereas none of the participants taking the inactive liquid had these elevations, and hormone levels showed no differences between the two groups.
Explore Dr. Caplan's interactive tool detailing cytochrome P450 pathways, clinical titration intervals, and physician surveillance rules.
The deeper readScientific analysis
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.
The paper
Citation
Florian J, Salcedo P, Burkhart K, Shah A, Chekka LMS, Keshishi D, et al. Cannabidiol and Liver Enzyme Level Elevations in Healthy Adults. JAMA Internal Medicine (2025). PubMed 40622698 · DOI
Limitations the authors noted
The study dose of 5 mg/kg/d was on the higher end of reported consumer use and administered twice daily. The population was limited to healthy adults aged 18 to 55 years without comorbidities or concomitant medications, which may underestimate risk in older or medically complex populations. The treatment duration was limited to 1 month, preventing assessment of longer-term health impacts. Laboratory monitoring was weekly, which may not have captured initial elevations in all cases as frequently as necessary.
In practice
Why this matters
This research demonstrates that a common daily amount of hemp extract can elevate liver enzymes in healthy people over a four-week period, even though the changes resolved after stopping the substance. It highlights the importance of keeping liver health in mind for people who regularly use these extracts, while leaving open whether lower amounts or longer periods of use carry similar risks.
Frequently asked questions
Clinical Questions & Answers
What were the primary clinical findings regarding Alanine transaminase and Adverse events?
The extract caused elevated liver enzymes in a small number of healthy adults. About five percent of the participants taking the extract experienced liver enzyme increases above the safety threshold, whereas none of the participants taking the inactive liquid had these elevations, and hormone levels showed no differences between the two groups.
What study limitations or clinical safeguards should patients keep in mind?
The study dose of 5 mg/kg/d was on the higher end of reported consumer use and administered twice daily. The population was limited to healthy adults aged 18 to 55 years without comorbidities or concomitant medications, which may underestimate risk in older or medically complex populations...
Browse related research
Condition: Adverse events Condition: Affect Condition: Liver safety Topic: Alanine transaminase Topic: Aspartate aminotransferases Topic: CBD
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Reviewed by Dr. Caplan on October 22, 2026.
This page is general education about a published study. It is not medical advice and does not create a doctor-patient relationship. For care specific to you, book a consultation.
