Oxidative stress and mitochondrial dysfunction in neuronal cells induced by commercial CBD products

The global cannabis market is rapidly expanding, but safety concerns are rising due to inconsistent CBD product labelling and contamination, driven by rapid commercialization and weak regulation. Studies show significant discrepancies in CBD concentrations, with many products either over- or under-labelled, and some contaminated with THC, pesticides, or heavy metals. This study investigates the neurotoxic effects of commercial CBD formulations, focusing on oxidative stress and redox imbalance in neurons. The analysis of two commercially available CBD samples (white and pink powder) revealed the presence of cannabidiol (CBD) in a content of 51.8 % and 51.4 %, respectively. Elemental analysis revealed notable contamination, with predominant metals including boron, lead, silicon, and zinc in the white sample, and boron, iron, silicon, and chromium in the pink sample. Treatment of SH-SY5Y neuroblastoma cells with these samples for 48 h resulted in a concentration-dependent reduction in cell viability, particularly at 10 and 50 μg/mL, accompanied by morphological changes. Both samples significantly increased reactive oxygen species (ROS) production and induced oxidative stress, evidenced by a reduced GSH/GSSG ratio and elevated lipid peroxidation at 50 μg/mL. Additionally, the activity of key antioxidant enzymes including catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR), was markedly inhibited. Mitochondrial function was also impaired, as indicated by decreased mitochondrial content and signal intensity. These findings underscore the potential neurotoxic effects of commercially available CBD products, particularly due to heavy metal contamination, and highlight the urgent need for comprehensive regulatory measures to ensure consumer safety amidst growing market availability.