It is known to be largely related to behavioural changes and neuropsychiatric disorders, and studies demonstrating the influence of eNOS gene variants in the development of depressive, aggressive and suicidal behaviours exist in the literature. Here, we investigate two polymorphisms in the eNOS gene, namely, G894T (Glu298Asp) and intron 4 VNTR, as possible genetic contributing factors to cannabis addiction. DNA samples used in this work were purified from the peripheral blood of 94 unrelated Turkish cannabis-dependent subjects and 100 Turkish control subjects from the southeastern region of Turkey. The eNOS polymorphisms were characterised by the PCR and/or PCR-RFLP (Polymerase Chain Reaction-restriction fragment length polymorphism) method. The De-finetti programme, chi-square, Fisher's exact test, odds ratio and 95% confidence intervals (CI) were used for statistical analysis. The incidence of aa and TT genotypes and the frequency of the alleles a and T were found to be significantly higher in the cannabis addicts group than in the control subjects (p<0.05). The results indicate that G894T and intron 4 VNTR eNOS gene polymorphisms are statistically-significant contributing factors to susceptibility to cannabis addiction, while the same polymorphism alleles associated with high NO levels are a protective factor in Turkish subjects. To the best of our knowledge, this is the first study on eNOS gene polymorphisms involving the Turkish population.