CYP2C19 and heroin dependence: Methadone has been studied most intensively in heroin addiction pharmacogenetics research.[12] Several ABCB1, CYP2B6, and OPRD1 variants have been associated with methadone plasma levels in candidate gene studies.[12,13] In addition, 2 genome wide association studies (GWAS) identified significant associations of CYP2B6 and OPRM1 with methadone dose.[14,15] Because of the chemical structure of methadone, the isozymes CYP2C19 and CYP2B6 metabolize the R-enantiomer[16] and S-enantiomer[17,18] of methadone in the liver, respectively.