Exposure to Ketamine and 2-Fluorodeschloroketamine Impairs Mitochondrial Oxidative Phosphorylation in Human Cerebral Organoids: Implications for Neurodevelopmental Toxicity.
Current neuropharmacology June 30, 2026 Jiaying Wang, Rui Zhang, Yuanyuan Ma et al.
Prenatal exposure to ketamine or its analog 2-fluorodeschloroketamine disrupts mitochondrial energy production in developing brain cells, increasing the risk of neurological damage. Using human cerebral organoids and single-cell RNA sequencing of 83,436 cells, the study found that both substances altered gene networks controlling mitochondrial oxidative phosphorylation in cortical cells. Experiments in fetal mouse neurons confirmed that exposure increased mitochondrial fragmentation and oxidative stress while reducing ATP production capacity. These energy disruptions during rapid brain development can make offspring more vulnerable to neurological issues. The results provide direct evidence of neurodevelopmental toxicity from these substances and identify mitochondrial dysfunction as a probable primary molecular mechanism.