Family-based, adoption, and twin studies have indicated that there is a strong (50%) heritable component to vulnerability to substance abuse addiction.
Especially among genetically vulnerable individuals, repeated exposure to a drug of abuse in adolescence or adulthood causes addiction by inducing stable downregulation or upregulation in expression of specific genes and microRNAs through epigenetic alterations.  Such downregulation or upregulation has been shown to occur in the brain's reward regions, such as the nucleus accumbens.  (See, for example, Epigenetics of cocaine addiction.)