COVER ILLUSTRATION Disruption of endocannabinoid type-1 signaling could produce alterations in synaptic plasticity. In cannabis (CB) users, it might lead to alterations either in structural (SC) and functional connectivity (FC) or in their association (i.e., SC-FC coupling). Structural (top left) and functional networks (top right) were generated based on the whole brain parcellation (bottom left) using diffusion tensor MRI and resting-state functional MRI in 37 current CB users and 31 healthy non-users. CB users had disrupted associations between SC-FC coupling and network topological characteristics, most perturbed for shorter connections implying region-specific disruption by CB use. Rich-club analysis (bottom right) revealed impaired SC-FC coupling in the hippocampus and caudate of users, suggesting that the impact of CB use may be most apparent in the local interconnections. This study provides evidence of the abnormal SC-FC association in CB users.