CYP4F3 and substance withdrawal syndrome: Our study confirms the results of previous studies; in which pretreatment with melatonin significantly reduces the anxiolytic effects of rats experiencing withdrawal from repeated cocaine administration and that it can be used as a novel treatment for cocaine dependency.14,19,26,27 The physical withdrawal syndromes in morphine and cocaine dependent mice are inhibited by melatonin.14,27 Since ramelteon is metabolized by the cytochrome P-450 system, differences are seemed in the administration by the central method versus the systemic method.