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γ-Oryzanol, a unique component of rice bran, has been shown to exert anti-anxiety and anti-depressive effects. Evidence suggests that γ-oryzanol may affect sleep; however, sedative-hypnotic effects have not been reported. In this study, a pentobarbital-induced sleep test and sleep-wake profile assessment using recorded electroencephalography are used. Also, the molecular mechanism of γ-oryzanol’s sleep effects is evaluated in histamine H₁ receptor (H₁R)-knockout (KO) mice. γ-Oryzanol gave a dose-dependent reduction in sleep latency and increased the amount of non-rapid eye movement sleep (NREMS). The hypnotic effects of γ-oryzanol were comparable to those of the positive control doxepin, an H₁R antagonist. In an in vivo mechanistic study, its hypnotic effects were completely blocked by the H₁R agonist 2-pyridylethylamine. Additionally, neither γ-oryzanol nor doxepin increased NREMS or …