Aberrant structural-functional coupling in adult cannabis users.

Cellular studies indicate that endocannabinoid type-1 retrograde signaling plays a major role in synaptic plasticity. Disruption of these processes by delta-9-tetrahydrocannabinol (THC) could produce alterations either in structural and functional brain connectivity or in their association in cannabis (CB) users. Graph theoretic structural and functional networks were generated with diffusion tensor imaging and resting-state functional imaging in 37 current CB users and 31 healthy non-users. The primary outcome measures were coupling between structural and functional connectivity, global network characteristics, association between the coupling and network properties, and measures of rich-club organization. Structural-functional (SC-FC) coupling was globally preserved showing a positive association in current CB users. However, the 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 revealed impaired SC-FC coupling in the hippocampus and caudate of users. This study provides evidence of the abnormal SC-FC association in CB users. The effect was predominant in shorter connections of the brain network, suggesting that the impact of CB use or predispositional factors may be most apparent in local interconnections. Notably, the hippocampus and caudate specifically showed aberrant structural and functional coupling. These structures have high CB1 receptor density and may also be associated with changes in learning and habit formation that occur with chronic cannabis use.