Few studies have analyzed the pharmacogenetic effects of OPRM1 variants on the standard treatments for opioid dependence and an even smaller number directly measure patient outcome or treatment efficacy (Table 2). A118G and the intronic SNP rs1074287 were both not associated with opioid positive urine drug screens during methadone maintenance therapy [64, 65]. A group of SNPs from multiple genes, including A118G, were associated with optimal methadone dose, although A118G was not significantly associated by itself [66]. While other research has not examined treatment outcome, several studies suggest differences in response to opioid dependence treatments based on OPRM1 genotype. Buprenorphine patients with the A/G genotype at the A118G locus have suppressed activation of the hypothalamic-pituitary-adrenal axis, which may indicate decreased craving, while those on methadone have higher plasma levels of the medication compared to homozygous A/A patients [67, 68]. Individuals with the A/G and G/G genotypes also have decreased pupillary constriction compared to A/A individuals in response to treatment with levomethadone, a methadone-like agonist [69]. This differential response is consistent with the hypothesis that the G allele of A118G may
