Representative differential impact of gene variants on opioid metabolism in European and African Americans. (A) -2044C/A haplotypes modulate the reward pathway to have a net negative effect on OUD, where European Americans with this allele are more susceptible to OUD than African Americans (Luo et al., 2003 [119]). By contrast, (B) a higher frequency of the *1B allele is present in African Americans, and this allele confers the extended metabolizer phenotype (Chapman et al. 2018 [81]; Wandel et al., 2000 [83]; Fernandez-Santander et al., 2016. [82], thus increasing chances of relapse in African Americans undergoing opioid replacement therapy with Buprenorphine/Suboxone. CYP3A4, Cytochrome P450 3A4; GABA, gamma-aminobutyric acid; NAc, Nucleus accumbens; OPRM1, mu opioid receptor; VTA, ventral tegmental area. (A higher resolution / colour version of this figure is available in the electronic copy of the article).