CBD and Liver Enzymes: What New Research Reveals

A new study published in JAMA Internal Medicine is making waves in the wellness and cannabinoid science communities by reporting that daily use of cannabidiol (CBD) may lead to elevated liver enzymes, a potential indicator of liver stress or damage. Conducted by researchers at Spaulding Clinical Research, the randomized, double-blind, placebo-controlled trial aimed to provide the FDA with data on the safety of consumer-level CBD doses.

While the study has sparked concerns, especially among cautious regulators and physicians, the full picture reveals inconsistencies and limitations that should temper any rush to judgment.

What the Study Investigated

With the explosion of CBD products on the market, from gummies and tinctures to lotions and seltzers, many consumers assume it’s safe because it’s widely available. However, unlike pharmaceutical CBD formulations such as Epidiolex, most over-the-counter CBD products are not regulated for dosage or purity by the FDA.

To help inform federal oversight, researchers studied 201 healthy adults between January and August 2024, giving 151 of them a daily oral dose of CBD (5 mg/day split into two doses) for 28 days. The remaining 50 participants received a placebo. Weekly bloodwork tracked liver enzyme levels and endocrine hormone changes.

The Main Finding: 5.6% Had Elevated Liver Enzymes

According to the study¹, 8 out of 151 participants (5.6%) in the CBD group experienced elevations in liver enzymes, specifically alanine aminotransferase (ALT) or aspartate aminotransferase (AST), that were more than three times the upper limit of normal. None of the participants in the placebo group exhibited such elevations.

The study authors noted these results were consistent with possible drug-induced liver injury (DILI), leading to the withdrawal of seven participants due to safety criteria. The majority of these enzyme spikes occurred around days 21 to 28 of the trial.

While this may seem concerning on the surface, a deeper look into the data introduces complexity that can’t be ignored.

Dissecting the Data: Viral Links, Immunity, and Side Effects

Prior Viral Infections in Affected Participants

Of the eight participants who experienced elevated liver enzymes, six had evidence of prior viral infections known to affect the liver. These included:

• Epstein-Barr Virus (EBV): Present in 63% (5 out of 8)
• Cytomegalovirus (CMV): Present in 50% (4 out of 8)
• Herpes Simplex Virus 2 (HSV-2): Present in 25% (2 out of 8)

Although these infections were not active at the time of testing and were dismissed by researchers as unrelated, it’s scientifically difficult to fully rule out latent viral effects on liver function, especially when examining subtle biomarker changes like enzyme levels. The study didn’t include a virology-specific subgroup analysis to account for these confounding variables.

Eosinophilia Adds Complexity

Another layer of nuance: 7 out of 8 participants with liver enzyme elevations also showed increased eosinophil levels, a type of white blood cell typically associated with allergic reactions or immune responses. This raises the possibility that the enzyme changes were immune-mediated, not hepatotoxic in the classic sense.

Yet the study did not perform follow-up immunological testing or allergic reactivity assessments that might have clarified this mechanism.

Placebo Group Also Had Side Effects

While the placebo group showed no elevated liver enzymes, they were not without side effects. In fact, 27% reported insomnia and 18% reported upper respiratory infections, both higher than some of the adverse effects in the CBD group, such as somnolence (8%) and diarrhea (8%).

This opens questions about environmental or psychosomatic influences, such as participant expectations (nocebo effect) or seasonal illnesses, that were not fully controlled for.

Endocrine System: No Observed Differences

An important finding often overshadowed by the liver concerns was that CBD had no significant effect on hormone levels, including testosterone, inhibin B, thyrotropin, triiodothyronine, or thyroxine. This is notable because some early studies speculated that cannabinoids might disrupt hormonal balance. This study suggests that, at least over a four-week period and at common doses, CBD does not appear to alter endocrine function in healthy adults.

What This Study Tells Us and What It Doesn’t

From a research perspective, this study highlights the urgent need for further clinical trials exploring CBD’s safety, especially in different populations, dosage levels, and durations of use. However, it’s important not to take these findings as conclusive proof that consumer-level CBD use poses a liver risk for everyone.

Some key limitations include:

• Short trial duration (28 days): CBD is often used for months or years. The long-term effects remain unknown.
• Limited diversity in product form: Only one delivery method (oral CBD oil) was tested.
• Small placebo group (n=50): The control arm was significantly smaller than the CBD group, which can skew comparative data.
• Confounding variables not fully explored: Prior viral infections, eosinophilia, and lifestyle and environmental factors were not deeply controlled for.

Final Thoughts: Caution, Not Condemnation

The rise in CBD use among the general public makes studies like this one critically important, especially in the absence of robust oversight. But science must be interpreted with nuance.

This trial suggests a possible correlation between CBD use and transient liver enzyme elevations, but not causation. The relatively low incidence (5.6%), lack of serious health events, and the presence of pre-existing viral factors all point to the need for larger, longer-term studies before drawing hard conclusions.

CBD users, especially those with liver conditions or who are taking medications metabolized by the liver, should always consult a healthcare provider. But for the average healthy consumer, this study should be seen as a call for better data, not immediate alarm.

Studies Referenced:

^{1. Florian, J., Salcedo, P., Burkhart, K., Shah, A., Chekka, L. M. S., Keshishi, D., Patel, V., Yang, S., Fein, M., DePalma, R., Matta, M., Strauss, D. G., & Rouse, R. (2025). Cannabidiol and liver enzyme level elevations in healthy adults: A randomized clinical trial. JAMA Internal Medicine. Advance online publication. https://doi.org/10.1001/jamainternmed.2025.2366}