(Fig. S5). Preferential expression of OPRD1 and PENK in D2 MSNs in human striatum is consistent with rodent striatum44. Across MSNs, we detected OPRK1 expression at many folds lower than OPRM1, OPRD1, PENK, or PDYN, suggesting that targets of the dynorphin-kappa opioid receptor signaling by D1-striosome MSNs may primarily be outside of dorsal striatum45,46. Between unaffected individuals and individuals with OUD, we found no significant differences in opioid receptor and/or endogenous ligand expression within specific cell types. Other mechanisms involved in the post-transcriptional and/or post-translational regulation of opioid receptor and ligand expression, along with receptor binding activity, may be altered in OUD.