The consumption of cannabidiol (CBD) has been growing and raising concerns about safety. Although there are reports of risk of elevation of liver enzymes at high doses, there is still a lack of data on the effects of intermediate doses, similar to those used by consumers.

A randomized, double-blind, placebo-controlled clinical trial, published in July 2025 in JAMA Internal Medicine, sought to fill part of this gap. 201 healthy adults, aged 18 to 55, were included, of which 151 received oral CBD at a dose of 5 mg/kg/day (approximately 400 mg daily) and 50 received placebo, for 28 days. The primary outcome was the proportion of participants who showed an increase in liver enzymes (ALT/AST) greater than three times the upper limit of normal.

The results revealed that eight participants in the CBD group (5.6%) developed significant elevations in transaminases, compared to no cases in the placebo group. In seven of these individuals, the criteria for possible drug-induced liver injury were met. The changes appeared only after the third week of exposure, reached maximum values even after drug discontinuation, and returned to normal within two weeks. The severity varied, with some cases reaching levels over ten times the normal limit, although none progressed to clinical liver impairment.

Regarding the endocrine axis, no relevant differences were detected between the groups in relation to total testosterone, inhibin B, TSH, total T3, and free T4, suggesting an absence of detectable effect in this follow-up period.

Although robust, the study has important limitations. The duration of only four weeks prevents conclusions about cumulative or long-term effects, and the exclusive inclusion of young and middle-aged adults, without comorbidities or polypharmacy, restricts the applicability of the results to more vulnerable groups, such as the elderly, people with previous liver diseases, or users of multiple medications. A noteworthy point was the predominance of females among the cases of enzyme elevation.

In light of these findings, it is clear that cannabidiol may pose risks to the liver even at doses used daily. This does not mean discarding its therapeutic potential, but reinforces the importance of clinical monitoring. More than ever, there is room for long-term investigations, involving different age groups, populations with comorbidities, and polypharmacy regimens. Only then will it be possible to fully understand the safety profile of CBD and ensure responsible use, balancing benefits and risks.

Reference
Florian J, Salcedo P, Burkhart K, Shah A, Chekka LMS, Keshishi D, Patel V, Yang S, Fein M, DePalma R, Matta M, Strauss DG, Rouse R. Cannabidiol and Liver Enzyme Level Elevations in Healthy Adults: A Randomized Clinical Trial. JAMA Intern Med. Published online July 7, 2025; doi:10.1001/jamainternmed.2025.2366