Brains from people with heroin use disorder have an increased number of hypocretin (Hcrt, orexin) neurons, which in turn are significantly smaller than in healthy controls. Meanwhile, human narcolepsy is known to present an average 90% loss of Hcrt neurons and no risk for drug abuse or overdose, even under methamphetamine or methylphenidate prescription, because of a greatly reduced reward activation of the ventral tegmental area (VTA).