Methamphetamine (METH) dependence is a globally significant public health concern with no efficacious treatment. Trait impulsivity is associated with the initiation, maintenance, and recurrence of substance abuse. However, the presence of these associations in METH addiction, as well as the underlying neurobiological mechanisms, remains incompletely understood.

We scanned 110 individuals with METH use disorder (MUDs) and 55 matched healthy controls (HCs) using T1-weighted imaging and assessed their drug use characteristics and trait impulsivity. Surface-based morphometry and graph theoretical analysis were used to investigate group differences in brain morphometry and network attributes. Partial correlations were conducted to investigate the relationships between brain morphometric changes, drug use parameters, and trait impulsivity. Mediation analyses examined how trait impulsivity and drug craving influenced the link between brain morphometric change and MUD severity in patients.

MUDs exhibited thinner thickness in the left fusiform gyrus and right pars opercularis, as well as diminished small-world properties in their structural covariance networks (SCNs) compared to HCs. Furthermore, reduced cortical thickness in the right pars opercularis was linked to motor impulsivity (MI) and MUD severity, and the association between the right pars opercularis thickness and MUD severity was significantly mediated by both MI and cue-induced craving.

These findings suggest that MUDs exhibit distinct brain structural abnormalities in both the cortical thickness and SCNs and highlight the critical role of impulse control in METH addiction. This insight may offer a potential neurobiological target for developing therapeutic interventions to treat addiction and prevent relapse.