Background and objectives: Clozapine (CLZ) is a successful medication for treating resistant, incurable schizophrenia. However, due to its cardio toxic effect, worries regarding its safety had grown. The current study examines how the CB1 receptor antagonist rimonabant influences the cardio toxicity brought on by CLZ and the control of schizophrenia that CLZ provides. Methods: 48 adult male Wistar rats were used in the study, which lasted 5 weeks, and were separated into 6 groups: negative control, rimonabant solvent, and rimonabant control (3 mg/kg/d). The ketamine schizophrenia model (30 mg/kg), CLZ treatment (25 mg/kg/day) and rimonabant and CLZ treated. At the end of the study, cardiac functions were recorded. Morris maze test and forced swimming test were conducted to assess schizophrenia control and after sacrifice sera and hearts were examined for CLZ-induced toxic effects and brains were examined for dopamine and serotonin. Results: CLZ caused a significant increase in serum and cardiac inflammatory markers, marked electrophysiological disturbances and myocardial inflammation and fibrosis scores p value <0.001. Rimonabant significantly attenuated the histopathological and biochemical manifestations of myocarditis. Rimonabant also significantly improve Morris maze test and forced swimming test results beyond those obtained with CLZ alone. Dopamine and serotonin levels were raised with co-administration of both drugs. Conclusion Rimonabant has protective actions against CLZ-induced myocarditis with positive additive effect on schizophrenia contro

CLZ, schizophrenia, cannabinoid antagonist, myocarditis, rimonabant, cardiac toxicity