Synthetic cannabinoids abuse is a serious social problem worldwide. It can cause severe toxicity, including seizures and even death. This study aims to examine the role of sub-chronic administration of AMB-FUBINACA SC in the induction of brain injury. 32 Male adult rats divided into four groups (8 rats per cage) were used, Control group: IP injected with 0.5 ml of the vehicle, and the others each IP injected with 0.5 ml of the three different doses of AMB-FUBINACA as following: Group1: 1mg/kg, Group 2: 3mg/kg and Group 3: 4mg/kg. The drug was injected once a day for 6 consecutive days. Tremors were observed 30 minutes following drug injection especially with 3 and 4 mg/kg doses followed with depressant effect. Then rats became hyperactive and aggressive. The drug administration induced a significant disturbance in the redox status of brain and significantly increased TNF-α, IL-6 and S100B serum levels. In addition, the mRNA expression levels of NF-𝜅B, MAPK p38 and Caspase-3 were significantly up-regulated. Meanwhile, the mRNA expression levels of Cannabinoid receptors (CB1R, CB2R) and BDNF were significantly down-regulated. The obtained results demonstrated that, AMB-FUBINACA harmful effects increase with the dose, which was supported by the brain histopathological examination. We concluded that, AMB-FUBINACA has a functional and structural deleterious CNS effects with sub chronic exposure in adult male rats. The induced brain injury and seizures that accompanied with the synthetic cannabinoids abuse might be mediated through the generation of oxidative stress, activating inflammatory cellular signaling mechanism and neural cell death via apoptosis.