Background/Aim: One of the risk factors for increasing psychotic disorders is the use of cannabis. It has been shown that the inactivation of dopamine and other catecholamines causes a common polymorphism generating substantial variations in COMT enzyme activity. We aimed to understand the role of cannabis in the etiology of schizophrenia with and without pre-morbid usage. Patients and Methods: The study group consisted of 80 male patients and genotyping of COMT enzyme Val158Met gene polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: It was found that the Val/Val genotype is significantly higher in patients with premorbid cannabis use (88.9%) compared to patients without pre-morbid cannabis use (68.4%). Also, the mean total positive and negative syndrome scale (PANSS) score seen in the Val/Val genotype group is significantly higher than the scores of the patients with the Met allele. Conclusion: The findings from this study confirm the association between COMT Val158 Met polymorphism and pre-morbid cannabis use in causing schizophrenia.