Evaluation of THC-induced neurotoxicity via oxidative stress in undifferentiated SH-SY5Y cells

Abstract

The increasing global consumption of cannabis, particularly high-THC products, has raised public health concerns due to potential neurotoxic effects, although its association with oxidative stress remains a subject of debated. Some studies link THC-rich cannabis to increased oxidative damage, while others highlight antioxidant properties of cannabinoids. This study aimed to evaluate whether THC concentrations observed in real-world scenarios, specifically in the blood of drivers involved in traffic accidents, can induce neuronal damage through oxidative stress in vitro. Human undifferentiated SH-SY5Y neuroblastoma cells were exposed to 0.66, 20, 73.75, and 150 ng/mL THC. High concentrations (73.75 and 150 ng/mL) significantly reduced cell viability (to 76.5 % and 64.6 % at 48 h) and caused morphological changes. THC exposure increased ROS, peaking at 116.5 % at 150 ng/mL, disrupted glutathione balance (GSH/GSSG ratio decreased by 69.2 %), and moderately increased lipid peroxidation (34.5 %). Activities of antioxidant enzymes (CAT, SOD, GR, GPx) declined concentration-dependently. Additionally, nuclear condensation and mitochondrial membrane depolarization indicated early apoptosis. These findings suggest that high THC levels can trigger neurotoxicity via oxidative stress and mitochondrial dysfunction.