Network Topology and Cannabis Use following Two Weeks of Monitored Abstinence: Moderation of sex and patterns of use findings

Kyle A. Baacke ^1* Ryan M. Sullivan ^1,2 Chase A. Shankula ¹ Krista M. Lisdahl ^1*

• ¹ University of Wisconsin–Milwaukee, Milwaukee, United States
• ² University of California, San Diego, La Jolla, California, United States

Background: Chronic cannabis use (CU) can result in subtle deficits in cognitive performance that may be linked with alterations in underlying neural functioning. However, these network alterations are not well-characterized following monitored abstinence. Here, we evaluate differences in functional brain network activity associated with CU patterns in adolescents/young adults.Methods: Functional connectomes were generated using resting-state fMRI data collected from 83 healthy young adults (44 male) following two weeks of monitored cannabis abstinence. Network topology metrics were calculated for each of the 7 Yeo 2011 intrinsic connectivity networks (ICNs) and on the whole-brain level. Multiple linear regressions were used to evaluate whether CU (regularusers, n=35 vs non-using controls, n=40) was associated with network topology metric differences after controlling for past-year alcohol use, age, sex, and cotinine levels; moderation by sex was also investigated. Regressions were run within CU group to test for associations between cannabis use patterns (lifetime CU, age of CU initiation, and past-year CU) and network topology. Finally, a network-based statistic (NBS) approach was used to search for connectome subcomponents associated with CU group, CU*sex, and patterns of CU.Results: No significant association between CU groups and ICN topology was observed. Sex moderation was observed; within male cannabis users, higher past-year CU was associated with significantly higher frontoparietal and ventral attention network (VAN) efficiency. Within female cannabis users, higher past-year CU was associated with significantly lower Default Mode Network assortativity. Within individuals who initiated CU before the age of 17, males had lower assortativity in the VAN and Somatomotor network. NBS analyses indicated that connectivity strength within a primarily right-lateralized subnetwork distributed throughout the connectome was significantly and reliably associated with past-year CU).The present findings suggest that subtle differences in resting-state network topology associated with CU may persist after an extended period of abstinence in young adults, particularly males, especially those with heavier past-year use and those who initiated CU earlier in life. While further replication is required in larger samples, these findings suggest potential neuroimaging correlates underlying long-term changes in brain network topology associated with CU.