Recently, we found hypermethylation of two CpG sites in the μ-opioid receptor (OPRM1) gene promoter in DNA from peripheral lymphocytes from Caucasian methadone maintained former heroin addicts (Nielsen et al. 2009). The OPRM1 gene codes for the μ-opioid receptor, the receptor to which morphine, methadone, and β-endorphin bind and exert their actions (Kreek et al. 2005). We hypothesized that this hypermethylation may alter the transcriptional regulation of the OPRM1 gene in these individuals. It is not known whether the hypermethylation of these two CpG sites was due to heroin use, methadone maintenance pharmacotherapy, imprinting, or major life events prior to using heroin. Other studies have shown that DNA methylation is higher in genomic DNA from lymphocytes of alcoholics than from those of controls (Bleich et al. 2006; Bonsch et al. 2004, 2006). Increased DNA methylation was found in the promoter regions of the α-synuclein SNCA gene (Bonsch et al. 2005), the homocysteine induced endoplasmic reticulum protein HERP gene (Bleich et al. 2006), and the vasopressin AVP gene (Hillemacher et al. 2009) and decreased methylation of the promoter region of the