The results suggested that the subjects with the C/C genotype in the rs2952768 SNP required more analgesics than the subjects with the other genotypes, attributable to the decreased effectiveness of opioid analgesics in both cohorts. Given the fact that the opioid system is involved in both rewarding and analgesic effects, one could assume that decreased opioid sensitivity may reflect the decreased rewarding effects of various drugs or behaviors and less liability to serious dependence. To test this hypothesis, we investigated the contribution of the rs2952768 SNP to the vulnerability to substance dependence in additional subjects with METH dependence, alcohol dependence and eating disorders (Supplementary Tables S6–8). In the initial case–control analyses, no associations in the genotypic and allelic distribution of this SNP were found between the subjects with psychiatric disorders and corresponding control subjects (Supplementary Table S9). However, a significant difference in the genotypic distribution was found between the absent and present subgroups of polydrug use among the patients with METH dependence (χ2=3.979, P=0.046). Indeed, fewer polydrug abusers carried the C/C genotype compared with monodrug users (Table 1). A similar
