Opioids use cause thousands of deaths per year in United States. Lately, several studies have been focused on ibogaine (IBO), a psychoactive alkaloid with the ability to treat drug dependence and reduce withdrawal syndrome. The mechanism by which IBO exerts its anti-addictive effects is unknown. This study aims to identify changes in the gene expression after a single oral dose of IBO in different brain areas. Male and female C57BL/6 mice were treated with 60 mg/kg of IBO by gavage. Four hours post-administration frontal cortex samples of three males and three females were obtained to perform transcriptomic analysis. In parallel, four and eight hours after IBO administration, six males and six females were euthanized to obtain frontal cortex, striatum and hypothalamus to perform the qPCR. Transcriptomic analysis revealed that IBO increased oxytocin and vasopressin, as well as genes involved in synaptogenesis, while genes associated with apoptosis and endosomal transport were decreased. Gender differences were observed with up to 28 genes affected in females beside eight in males. Gene expression at four and eight hours showed IBO effects in all the brain areas evaluated while sex differences in hormonal and synaptogenesis pathways was also observed in hypothalamus and striatum. Our result indicates that after the IBO peak at four hours its effects on gene expression persist or increase. This study expands our knowledge of IBO molecular action. Further research is needed to study the contribution IBO and its metabolite Noribogaine in the reported changes and to evaluate long-term effects of IBO.