Altered functional connectivity and oscillatory dynamics in polysubstance and cannabis only users during visuospatial processing

Rationale and objectives Cannabis use is often associated with the use of other psychoactive substances, which is subsequently linked to an increased risk for addiction. While there is a growing body of neuroimaging literature investigating the cognitive effect of long-term cannabis use, very little is known about the potential additive effects of cannabis polysubstance use. Methods Fifty-six adults composed of 18 polysubstance users (i.e., cannabis plus at least one other illicit substance), 19 cannabis-only users, and 19 nonusers completed a visuospatial attention task while undergoing magnetoencephalography. A data-driven approach was used to identify oscillatory neural responses, which were imaged using a beamforming approach. The resulting cortical regions were probed for group differences and used as seeds for whole-brain connectivity analysis. Results Participants exhibited robust theta, alpha, beta, and gamma responses during visuospatial processing. Statistical analyses indicated that the cannabis-only group had weaker occipital theta relative to the nonusers, and that both polysubstance and cannabis-only users had reduced spontaneous gamma in the occipital cortices during the pre-stimulus baseline period relative to nonusers. Finally, functional connectivity analyses revealed that polysubstance users had sharply reduced beta connectivity between occipital and prefrontal, as well as occipital and left temporal cortices. Conclusions Cannabis use should be considered in a polysubstance context, as our correlational design suggests differences in functional connectivity among those who reported cannabis-only versus polysubstance use in occipital to prefrontal pathways critical to visuospatial processing and attention function. Future work should distinguish the effect of different polysubstance combinations and use more causal designs.