Medicine
Cannabidiol CBD can elevate liver enzymes
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Ainhoa Pérez
Alumni
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MPH, MSc.
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Is cannabidiol safe? A new clinical trial reveals that CBD can cause elevated liver enzymes in healthy adults.
PATHOPHYSIOLOGY AND MECHANISMS
Cannabidiol (CBD) is a non-psychoactive phytocannabinoid derived from cannabis (Cannabis sativa L), chemically distinct from delta-9-tetrahydrocannabinol (THC), which is primarily responsible for the psychoactive effects. Different cannabinoids have varied effects on the cannabinoid receptors in the nervous system, producing anxiolytic, analgesic, anticonvulsant, anti-inflammatory, and immunomodulatory effects. Although its clinical use is approved for certain neurological conditions, its over-the-counter sale, given its lack of addictive potential, has led to its growing use to treat problems such as insomnia, chronic pain, anxiety, and various psychological symptoms. However, evidence on its safety is limited, and its ability to interfere with liver enzymes raises questions about its long-term effects in different clinical settings. CBD inhibits cytochrome P450 enzymes (e.g., CYP3A4, CYP2C19), which may explain drug interactions and cumulative toxicity. Previous studies have documented potential hepatotoxicity developed with CBD.STUDY
A randomized, double-blind, placebo-controlled clinical trial (Florian et al., 2025) evaluated the hepatic and endocrine safety of CBD in over 200 healthy adults aged 18 to 55 years with no baseline liver abnormalities. Participants received oral cannabidiol (5 mg/kg/day) or a placebo for 28 days. Follow-up included weekly clinical and laboratory checks and an additional visit after the end of treatment. Possible elevations in alanine aminotransferase or aspartate aminotransferase were studied, and drug-induced liver damage was considered when analytical (enzymes, bilirubin, alkaline phosphatase) and clinical (symptoms or eosinophilia) criteria were met. Various hormones were also measured. Plasma concentrations of CBD and its metabolites were determined by mass spectrometry.MAIN RESULTS
5.6% of participants who received CBD had enzyme elevations greater than three times the normal limit, compared to no cases in the placebo group. Seven people met the predefined criteria for possible drug-induced liver injury, mainly in weeks 3 and 4, leading to their withdrawal from the study. In several cases with enzyme elevation, associated eosinophilia was detected. None of these cases developed severe clinical symptoms or overt liver damage, indicating that the abnormalities were reversible after CBD discontinuation. Other liver enzymes such as GGT and alkaline phosphatase were measured as exploratory measures but did not show significant elevations in the treated group. No differences between groups were observed in the levels of other hormones.CONCLUSION AND CLINICAL RELEVANCE
Frequent use of cannabidiol in healthy adults may induce subclinical liver abnormalities in a relevant proportion of cases. These findings are consistent with previous studies in clinical populations and confirm that the risk of liver abnormalities is not limited to high doses or patients with pre-existing comorbidities, but that a percentage of individuals show liver toxicity to CBD. The enzyme elevation could be due to CBD interference with hepatic metabolic pathways and also to immunological effects, as suggested by the eosinophilia observed. Although enzyme abnormalities reversed with CBD discontinuation, continued use raises questions about the evolution of potential liver damage, underscoring the need for additional studies in regular cannabidiol users. The main limitations of the study include the short follow-up period and the exclusion of individuals with pre-existing liver disease. Expanding research to other populations and evaluating risks and benefits in real-world settings will be key to establishing solid clinical recommendations. Caution is recommended with continued use, including periodic monitoring of liver enzymes. We remind veterinarians and pet owners to exercise caution, given the growing use of CBD in animals. It should be monitored, and both veterinarians and pet owners should be informed of the potential elevation of liver enzymes associated with CBD to avoid a diagnostic spiral and poor clinical decisions in the animal.
#cbd #cannabidiol #cannabis #liverdiseases
References:
Florian, J et al, 2025. Cannabidiol and liver enzyme level elevations in healthy adults: A randomized clinical trial. JAMA Internal Medicine. https://doi.org/10.1001/jamainternmed.2025.2366
* The news published on studies do not represent an official position of ICNS, nor a clinical recommendation.
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