This study investigates the relationship between cannabinoid use disorder (CUD) or synthetic cannabinoid use disorder (SCUD) and the global methylation, methylation of NR3C1 gene promotor, and NR3C1 BclI poly-morphism, considering clinical parameters. Based on the DSM-5 criteria, 172 SCUD patients? and 44 CUD pa-tients? diagnoses were confirmed with a positive urine test; 88 healthy volunteers were also included in the study. Global DNA methylation was measured using a 5-methylcytosine (5-mC) DNA ELISA Kit. Methylation-specific PCR was used to identify the methylation of the NR3C1 gene. The analysis of the BclI polymorphism of the NR3C1 gene was evaluated by using the PCR-RFLP. Our results demonstrated that the mean of 5-mC percentages of SCUD patients differed significantly from those of the control group. When comparing NR3C1 gene methyl-ation and clinical parameters due to NR3C1 genotype distribution in patients, the genotype distribution was significantly different between the groups, due to the former polysubstance abuse. Additionally, there was a significantly positive correlation between the 5-mC percentages of SCUD patients and the reported durations of their disorders. In summary, whereas global DNA methylation may be associated with SCUD, the methylation of the NR3C1 gene and NR3C1 BclI polymorphism were not related to CUD or SCUD.