Introduction: Voodoo is a mixture of herbs and spices that are sprayed with a synthetic compound that mimics the effects of Cannabis. The widespread over-the-counter availability of these products made these compounds the 2nd most common frequently used recreational drug after marijuana in teenagers and young adults. This study aimed to investigate the sub chronic toxic effects of Voodoo (Voodoo abuse) on the central nervous system (CNS) in adult male albino rats. Methodology: thirty adult male albino rats were divided into three equal groups; negative control group, positive control group, and Voodoo extract treated group. Behavioral tests, neurotransmitter concentration in brain tissues and histopathological examination of brain tissues were performed. Results: general activity changes, significant decrease in food intake, feces formation and weight gain were reported between control and Voodoo treated group. The behavioral Y maze test revealed significant inhibition of the spontaneous alternation while, locomotor activity and rotarod test revealed significant inhibition of the neuromuscular coordinative function. The neurotransmitters (serotonin, dopamine, adrenaline and noradrenaline) assaying in the brain tissues of Voodoo treated group revealed significant decrease. These neurological changes were supported by the histopathological findings in the form of shrunken cells with dense nuclei and vacuolated cytoplasm in addition to the positive cytoplasmic immunoreaction for caspase -3 in the brain tissues. Conclusion: Voodoo extract was found to have a functional and structural deleterious CNS effect with sub chronic exposure in adult male albino rats.