Subchronic Exposure to Low-Dose Cannabidiol (CBD) and Δ9-Tetrahydrocannabinol (Δ9-THC) Nanoemulsions Suggests Low Renal Toxicity: A Preliminary Study.

Abstract

Background/Objectives: The increasing therapeutic use of cannabinoid-based formulations highlights the need to better characterize their safety profile, particularly in organs involved in xenobiotic elimination, such as the kidneys. This study evaluated the renal effects of cannabidiol (CBD) and Δ⁹-tetrahydrocannabinol (Δ⁹-THC) nanoemulsions following subchronic oral administration in male Wistar rats. Methods: Forty animals (n = 8/group) were randomly allocated into five groups: vehicle control (Licuri oil + Pluronic^® F127), CBD 2.5 mg/kg, CBD 5 mg/kg, CBD+THC 2.5 mg/kg, and CBD+THC 5 mg/kg. Treatments were administered daily by oral gavage for 21 consecutive days. Kidney samples were analyzed by histopathology and immunohistochemistry (Ki-67, GST-P, and cleaved caspase-3). Results: High-dose groups (5 mg/kg) exhibited marked histopathological alterations, including tubular and glomerular damage, hemorrhagic areas, inflammatory infiltration, and necrosis. These groups also showed increased Ki-67 and cleaved caspase-3 immunoexpression compared to controls. GST-P expression was significantly increased only in the CBD 5 mg/kg group. No significant changes were observed in the low-dose groups. Conclusions: These findings suggest dose-dependent morphological and molecular alterations in renal tissue associated with cannabinoid nanoemulsion exposure under experimental conditions.