The identification of DNA methylation in heroin addiction could lead to novel pharmacotherapies for the treatment of opiate addiction. There are several pharmacological agents, such as azacitidine and valproic acid, that could be explored in future preclinical studies on heroin and methadone effects. Azacitidine, a pyrimidine nucleoside analog of cytidine, when metabolized and incorporated into DNA, acts as an irreversible inhibitor of DNA methyltransferases, preventing DNA methylation, with antineoplastic activity and is thought to activate tumor suppressor genes silenced by hypermethylation. Azacitidine is approved for the treatment of several subtypes of myelodysplastic syndrome, a group of diseases characterized by a disruption in the production of blood cells (Issa and Kantarjian, 2005). Valproic acid, an anticonvulsant, is a histone deacetylase inhibitor (Phiel et al, 2001), and histone acetylation and DNA methylation have been shown to be coupled. Valproic acid is used in the treatment of bipolar disorder and the prevention of migraine headaches. Both azacitidine and valproic acid are currently in clinical trials of the National Cancer Institute.
