Catechol-O-methyl transferase (COMT) enzyme has a role in the inactivation of catecholamine neurotransmitters. Functional polymorphism in the COMT gene has been reported to play an important role in schizophrenia, bipolar affective disorder, aggressive and antisocial behavior, suicide attempts and the pathogenesis of Parkinson's disease. In this study, we aimed to investigate the effect of the Val158Met polymorphism of the COMT gene on substance use, and treatment history in patients with synthetic cannabinoid (SC) intoxication. The COMT enzyme Val158Met polymorphisms from DNA of 49 patients who were evaluated in the Emergency Department after SC use and 50 healthy control groups aged 18-45 years, were identified by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analyses as reported in the literature. Information regarding recurrent intake or hospitalization due to substance use was obtained from hospital records. Wild-type (WT) genotypes in 14 (28.6%) patients, heterozygous genotypes in 25 (51.0%) and homozygous genotypes in 10 (20.4%) patients were detected. Wild-type genotypes The homozygous genotype was found to be significantly higher in patients hospitalized due to drug addiction and substance use (p 0.008). The Val158 Met polymorphism of the COMT gene was not found to be significant in the first use after substance intake, while a significant relationship was found in terms of this polymorphism in patients with substance addiction diagnosis and treatment history.