Study Finds CBD Shields Primary Neurons From Rotenone-Induced Toxicity Through TRPV1 Pathways

The study, published in Chemistry: An Asian Journal, examined primary hippocampal neurons exposed to rotenone, a well-established mitochondrial complex I inhibitor that triggers structural deterioration, oxidative stress, and sharp declines in cell viability. In the experiment, rotenone caused a concentration-dependent drop in viability, with an LC50 of 189.1 nM. At 200 nM, viability fell to 45.6% and neurons displayed pronounced neurite degeneration. When CBD was introduced at 2.5 µM, viability rose to 69.9% under pre-treatment and 64.7% when applied at the same time as rotenone. Confocal imaging confirmed that CBD helped preserve axonal branching and overall neuronal structure, even under mitochondrial stress.

Follow-up testing showed that this protection depended heavily on TRPV1. Blocking TRPV1 sharply reduced CBD’s benefit, while inhibition of 5-HT1A receptors produced only a small change. Additional imaging with mitochondrial markers showed that CBD partially maintained mitochondrial activity compared with rotenone-only conditions.

The authors note that CBD’s role as a mechanistically distinct antioxidant, combined with its influence on receptor-mediated survival pathways, may explain its performance in this model. Overall, the findings indicate that CBD can blunt rotenone-induced damage in primary hippocampal neurons, with TRPV1 signaling acting as a central driver of its protective effect.