Introduction: Drug addiction is one of the most devastating brain disorders, involving the impairment of brain reward pathway. The enzyme catechol-O-methyltransferase (COMT) metabolizes dopamine and influences the reward pathway functioning. COMT activity is influenced by genetic variations, particularly the p.Val158Met (rs4680); the Met/ Met genotype has been associated with a 40% reduction in enzyme activity. The aim of this study was to determine p.Val158Met COMT polymorphism in a Portuguese population of drugs addicts seeking treatment and its association with paranoid ideation.