Methylation Status of the DAT1 Dopamine Transporter Gene in Individuals With Cannabis Use Disorder: Associations With Personality Traits

Abstract

Cannabis use is a growing public health concern due to its neuropsychiatric consequences and potential epigenetic effects. This study investigated the methylation status of the DAT1 dopamine transporter gene in individuals with cannabis use disorder (CUD) and examined associations with personality traits. A total of 490 male participants (212 with CUD and 278 controls) were assessed using the NEO Five-Factor Inventory (NEO-FFI) and the State–Trait Anxiety Inventory (STAI). DNA methylation levels at 33 CpG sites within the DAT1 promoter region were quantified through methylation-specific PCR and sequencing. Although no significant group differences were found in overall methylation levels, logistic regression revealed significant associations between methylation status and personality dimensions. CUD was linked to higher neuroticism and openness, lower agreeableness and conscientiousness, and elevated anxiety scores. Importantly, reduced DAT1 methylation was a significant predictor of CUD. These findings underscore the interplay between personality, gene regulation, and addiction, supporting a role for epigenetic mechanisms in the development and maintenance of substance use disorders. Future research should explore site-specific CpG alterations and their longitudinal impact on neurobehavioral outcomes.