Many drugs of abuse increase orexin production in both animal and human brains. Blocking the orexin system reverses addiction in animals. Orexin levels normally cycle in a circadian rhythm, with additional activation when under stress. Opioids, cocaine, alcohol, and other substances activate the cells that produce orexin, but don’t deactivate them. They stay on constantly, producing high levels of orexin that drive the desire for another hit. Anti-orexin insomnia medications might be of benefit in treating addiction.