This study investigates the impact of methadone maintenance treatment (MMT) on the brain glymphatic system (GS) in opioid addiction in China. A total of 51 male MMT patients, 48 demographically matched healthy controls (HCs), and 20 heroin dependents (HDs) were recruited for this study. The GS functioning was assessed using diffusion-tensor-imaging analysis along perivascular spaces (DTI-ALPS index) and the bilateral ALPS divergency (DivALPS). Group differences were analyzed utilizing ANOVA and two-sample -tests. The relationship between DivALPS and relapse rate was explored using regression analysis. The DTI-ALPS index was significantly higher for the left-side brain than the right side in all three groups. There was a significant difference for the right side ( = 0.0098) between the groups. The MMT and HD groups showed significantly higher DTI-ALPS than the HC group ( = 0.018 and 0.016, respectively). The DivALPS varied significantly among the three groups ( = 0.04), with the HD group showing the lowest and the HC group the highest values. Significant negative relationships were found between relapse count, DivALPS ( < 0.0001, Exp(B) = 0.6047), and age ( < 0.0001, Exp(B) = 0.9142). The findings suggest that MMT may contribute to promoting brain GS recovery in heroin addicts, and modulation of the GS may serve as a potential biomarker for relapse risk, providing insights into novel therapeutic strategies.
