The principle has been demonstrated in very different systems that allow orexin to enter the CSF: intranasal orexin, alleviating cognitive deficits produced by loss of sleep in nonhuman primates [171] and human narcolepsy [172]; i.c.v. administration in an experimental model to treat the severe fatigue that can persist for months or years after chemotherapy [116], and, by the same route, administration to produce arousal effects on acute alcohol intoxication-induced coma in rats [170]. Here, HCRT is linked to narcolepsy.