RT Journal Article T1 Evaluation of THC-induced neurotoxicity via oxidative stress in undifferentiated SH-SY5Y cells A1 Sanz-Pérez, Amadeo A1 Anaya, Brayan Javier A1 Fraguas Sánchez, Ana Isabel A1 Serrano López, Dolores Remedios A1 Pérez Pérez, Teresa A1 Basilicata, Pascale A1 Pieri, María A1 González Burgos, Elena María AB 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. PB Elsevier YR 2026 FD 2026 LK https://hdl.handle.net/20.500.14352/128673 UL https://hdl.handle.net/20.500.14352/128673 LA eng NO Sanz-Pérez A, Anaya BJ, Fraguas-Sánchez AI, et al. Evaluation of THC-induced neurotoxicity via oxidative stress in undifferentiated SH-SY5Y cells. Environmental Toxicology and Pharmacology 2026;121:104891. https://doi.org/10.1016/j.etap.2025.104891. NO Ministerio de Sanidad (España) DS Docta Complutense RD 30 dic 2025