Hypoxanthine and xanthine, intermediates in purine degradation that generate ROS through xanthine oxidase activity [81], were elevated in methamphetamine dependence [45], consistent with chronic upregulation of ROS-generating pathways, yet reduced in acute ischemic stroke [47], highlighting a contrast between chronic oxidative upregulation and acute purine depletion due to energy failure. The gene discussed is XDH; the disease is substance dependence.