The role of sex in the association between cannabis use disorder and resting-state functional connectivity.

While Cannabis use disorder (CUD) is twice as prevalent in males, females transition more quickly from heavy use to CUD and experience more severe withdrawal. These clinically relevant sex differences contrast the lack of knowledge about the underlying brain mechanisms. This study investigated the relationship between CUD and resting-state functional brain connectivity (RSFC), assessing potential sex differences herein. RSFC of the Salience Network (SN), Basal Ganglia Network (BGN), Executive Control Network (ECN), and Default Mode Network (DMN) was compared between 152 individuals (76 males) with CUD and 114 matched controls (47 males). Within the CUD group, relationships between RSFC and heaviness of cannabis use, age of onset, and CUD symptom severity, along with their associations with sex, were investigated. CUD and control groups showed similar RSFC across all networks, regardless of sex. In the CUD group, heavier cannabis use correlated with higher RSFC across all networks and earlier age of onset was related to higher RSFC in the anterior SN, BGN, left ECN, and dorsal DMN. These associations were similar for males and females. CUD severity was related to higher RSFC in the anterior SN, which was moderated by sex, with a positive association seen only in males. In conclusion, CUD may not necessarily be associated with altered RSFC. Individual use characteristics such age of onset and severity of use may determine the potential impact of cannabis use on RSFC in a largely similar way in males and females.