New Study: Cannabidiol Use Linked to Liver Enzyme Elevations in Healthy Adults

A randomized, double-blind clinical trial examined the effects of twice-daily use of cannabidiol (CBD) on liver enzyme levels and endocrine hormones in healthy adults. Conducted at a clinical pharmacology unit in Wisconsin and published in JAMA Internal Medicine in July 2025, the four-week study found that CBD doses like those used in unregulated CBD consumer products were associated with increased liver enzyme levels and, in several cases, potential drug-induced liver injury. The study findings highlight concerns about the long-term liver safety of widely used CBD products and alert clinicians to the need to screen patients with elevated liver enzyme levels for CBD use.[1]

CBD use and liver health

CBD is one of the most prevalent bioactive compounds in the cannabis plant. Unlike the psychoactive cannabinoid delta-9-tetrahydrocannabinol (Δ9-THC), CBD does not produce intoxicating effects. After Congress passed the Agriculture Improvement Act of 2018, which removed hemp-derived cannabinoids with low Δ9-THC concentrations from the definition of marijuana in the Controlled Substances Act, the market for CBD products rapidly expanded in the United States.

CBD products, which are neither regulated nor approved by the Food and Drug Administration (FDA), are marketed for various purported benefits such as reducing pain, relieving anxiety or obsessive-compulsive disorder symptoms, and improving sleep.[2] The products are marketed in many forms — gummies, creams, oils, beverages, and even pet treats. According to the 2022 National Survey on Drug Use and Health, 21% of adults in the United States reported using CBD in the past year.[3]

At present, the only FDA-approved CBD product is EPIDIOLEX, which is prescribed for seizures associated with Lennox-Gastaut syndrome, Dravet syndrome and tuberous sclerosis complex.[4] In clinical trials, liver toxicity is a common adverse effect, especially at higher doses or when combined with other medications, such as antiepileptic drugs.[5] However, little is known about how the lower doses of CBD in unregulated consumer products may affect liver health.

Recent public endorsements of CBD have also created mixed messages, particularly for older adults. In September 2025 President Donald Trump shared a video that promoted CBD as a beneficial treatment for seniors; the video also suggested that Medicare should cover CBD.[6] Trump’s post was met with skepticism; researchers emphasized that evidence supporting CBD for common age-related health conditions was inconclusive. Moreover, older adults, especially those taking multiple medications, may be at increased risk of liver injury from these unregulated products.[7]

The new study[8]

This randomized, double-blind, placebo-controlled trial evaluated the effects of CBD on liver enzyme levels and endocrine hormones at a dose within the range of consumer use. A total of 201 healthy adults were recruited and randomly assigned to receive either CBD at 5 mg/kg/day (approximately 400 mg/day) taken in twice-daily doses of half the total amount or placebo. Both groups underwent weekly laboratory monitoring for 28 days.

The researchers measured alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels as the primary endpoints. The proportion of participants in each group that had ALT or AST elevations greater than three times the upper limit of normal during the study period was assessed. In the CBD group, eight of 151 participants (5.6%) had ALT or AST elevations greater than three times the upper limit of normal, whereas zero of 50 participants in the placebo group had such elevated liver enzyme levels. These elevations developed within three to four weeks of starting CBD, peaked one to two days after discontinuation of treatment, and returned to baseline within one to two weeks.

Additionally, seven participants in the CBD group (4.9%) had to stop taking CBD because they met prespecified criteria for potential drug-induced liver injury.[9] No serious or life-threatening adverse events occurred. For endocrine hormones, the researchers observed no substantial differences in the changes from baseline between the CBD and placebo groups.[10]

Although the study did not assess longer-term effects of CBD use on liver health, the enzyme level elevations without noticeable symptoms suggest that CBD-related liver injury may go undetected without routine clinical monitoring. The findings raise concerns for consumers who use CBD products for long periods of time without medical supervision.

The results of the new study align with a prior randomized, open-label study using 300 mg/day of CBD for four weeks, where four participants (6.8%) experienced liver enzyme elevations greater than three times the upper limit of normal; one case was classified as “critical.” No liver enzyme elevation was observed in the placebo group.

What You Can Do

If you use an unregulated over-the-counter CBD product, particularly if you have used this product regularly for a long period of time, let your clinician know during your medical visits. Discuss with your clinician whether you need blood tests to monitor your liver enzyme levels. Avoid over-the-counter CBD products if you already have liver disease, drink alcohol frequently, have a history of alcoholism or drug/substance misuse, or take prescription drugs that may harm the liver.
 

References

[1] Florian J, Salcedo P, Burkhart K, et al. Cannabidiol and liver enzyme level elevations in healthy adults: a randomized clinical trial. JAMA Intern Med. 2025;185(9):1070–1078. doi:10.1001/jamainternmed.2025.2366

[2] Santos I, Oliveira MBPP, Casas A, et al. Understanding the potential of CBD for health benefits: An overview. Curr Drug Discov Technol. 2025;22(3):e060624230799.

[3] Choi NG, Marti CN, Choi BY. Prevalence of cannabidiol use and correlates in U.S. adults. Drug Alcohol Depend Rep. 2024 Oct 9;13:100289.

[4] Jazz Pharmaceuticals. Label: cannabidiol (EPIDIOLEX). June 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210365lbl.pdf. Accessed November 7, 2025.

[5] Lo LA, Christiansen A, Eadie L, et al. Cannabidiol-associated hepatotoxicity: A systematic review and meta-analysis. J Intern Med. 2023;293(6):724-752.

[6] Ovalle D. Trump posts video endorsing CBD for seniors. Researchers urge caution. The Washington Post. September 30, 2025. https://www.washingtonpost.com/health/2025/09/30/trump-cbd-endorsement-hemp/. Accessed November 7, 2025.

[7] Ibid.

[8] Florian J, Salcedo P, Burkhart K, et al. Cannabidiol and liver enzyme level elevations in healthy adults: A randomized clinical trial. JAMA Intern Med. 2025;185(9):1070–1078. doi:10.1001/jamainternmed.2025.2366

[9] Food and Drug Administration. Guidance for industry: drug-induced liver injury: premarketing clinical evaluation. July 2009. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/drug-induced-liver-injury-premarketing-clinical-evaluation. Accessed November 7, 2025.

[10] Crippa JAS, Zuardi AW, Guimarães FS, et al. Efficacy and safety of cannabidiol plus standard care vs standard care alone for the treatment of emotional exhaustion and burnout among frontline health care workers during the COVID-19 pandemic: A randomized clinical trial. JAMA Netw Open. 2021;4(8):e2120603.