2026-08-20T02:11:06Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/1286732025-12-11T00:54:42Zcom_20.500.14352_14col_20.500.14352_15

Evaluation of THC-induced neurotoxicity via oxidative stress in undifferentiated SH-SY5Y cells Sanz-Pérez, Amadeo Anaya, Brayan Javier Fraguas Sánchez, Ana Isabel Serrano López, Dolores Remedios Pérez Pérez, Teresa Basilicata, Pascale Pieri, María González Burgos, Elena María 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. 2025-12-10T09:18:48Z 2025-12-10T09:18:48Z 2026 journal article 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. 10.1016/j.etap.2025.104891 https://hdl.handle.net/20.500.14352/128673 https://doi.org/10.1016/j.etap.2025.104891 eng 2022I014 info:eu-repo/grantAgreement/MS//2022I014 http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 International Elsevier