Effective treatments for methamphetamine (MA)-use disorder (MUD) are critically needed. Treatment outcomes, however, are variable, especially for women, as sex differences in treatment efficacy have not been adequately studied. With rates of MUD recently tripling in women, it's critical to identify sex-specific mechanisms and targets for tailored medications. Women exhibit higher levels of inflammation and greater activation in emotional centers of the brain. These differences may explain why women resort to MA more frequently to alleviate negative emotions. Despite evidence of sex differences in biological mechanisms, there is a lack of studies extending these results in MUD. This proposal therefore aims to address the knowledge gap in sex differences in MUD, focusing on inflammation and brain function.