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

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...

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Detalles Bibliográficos
Autores: 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
Tipo de recurso: artículo
Fecha de publicación:2026
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/128673
Acceso en línea:https://hdl.handle.net/20.500.14352/128673
Access Level:acceso abierto
Palabra clave:615.9
615.01/.03
Cannabis
THC
Oxidative stress
Neurotoxicity
Mitochondrial dysfunction
Ciencias Biomédicas
Toxicología (Farmacia)
Farmacología (Farmacia)
3214 Toxicología
3209 Farmacología
Descripción
Sumario: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.