Prevalence rates of OUD and responses to opioids are dependent on sex98–100. Between unaffected individuals and individuals with OUD, we found a significant effect of sex on DEGs in neurons and glia. Overall, the impact of sex on DEGs in OUD was magnified in neurons (Fig. 3a) relative to glia (Fig. 5a). Therefore, we conducted complementary, secondary analyses to identify sex-specific transcriptional alterations in neurons and glia associated with OUD (Supplementary Data 1–S12). First, we identified DEGs within either female or male individuals with OUD (Fig. 6a, FDR < 0.05), revealing more sex-specific DEGs in glial cells relative to neurons. Additionally, we found a higher number of DEGs in females than males, (360 ± 60 versus 212 ± 67, respectively), in glial cells, and similarly in neurons (females: 91 ± 9.1; and males: 66 ± 7.9. Second, we explored the interaction between sex and OUD across genes and cell types to identify cell type-specific gene expression changes occurring in only males or females of individuals with OUD. Consistent with our analysis on the main effect of sex in OUD, we
