Date of Award

August 2021

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Psychology

First Advisor

Krista M Lisdahl

Committee Members

Christine L Larson, Cecilia J Hillard, Hanjoo Lee, Ryan C Shorey

Keywords

Adolescence, Cannabis, Cognition, Default Mode Network, Gender, Resting State Functional Connectivity

Abstract

Introduction: Cannabis is the most commonly used illicit substance in the United States, and nearly 1 in 4 young adults are current cannabis users. The psychoactive component of cannabis, THC, is active at cannabinoid receptors, type 1, or CB1 receptors. CB1 receptors play a critical role in neural development, and chronic cannabis use causes desensitization and downregulation of these receptors. Chronic cannabis use is associated with changes in resting state functional connectivity (RSFC) in the default mode network (DMN) in adolescents and young adults, although results are somewhat inconsistent across studies, likely due to differing methodologies. Additionally, cannabis effects appear to be moderated by gender; while females appear to be more susceptible to receptor-level adverse effects of chronic THC exposure, effects of chronic cannabis use on cognition are inconsistent between males and females. Notably, no study to date has examined gender differences in the effects of cannabis on RSFC in the DMN in adolescents and young adults. Methods: Seventy-seven adolescent and young adult subjects underwent an MRI scan (including resting state scan), neuropsychological battery, toxicology screening, and drug use interview. Differences in DMN connectivity were examined between groups and with a group by gender interaction, using a left posterior cingulate cortex seed-based analysis conducted in AFNI. Results: Cannabis users demonstrated weaker connectivity than controls between the left PCC seed and various DMN nodes, including the left PCC/precuneus, right lingual gyrus/precuneus, and right parahippocampal gyrus. Weaker connectivity was also seen in cannabis users between the left PCC and the right Rolandic operculum/Heschl’s gyrus. Stronger connectivity was seen in cannabis users between the left PCC and the left and right cerebellum, and the left supramarginal gyrus. The group by gender interaction was not significantly associated with any differences in connectivity between the left PCC and the rest of the brain. Stronger left PCC—cerebellum connectivity was associated with poorer performance on cognitive measures in cannabis users. In controls, intra-DMN connectivity was positively correlated with performance on a speeded selective/sustained attention measure. Discussion: Consistent with our hypotheses and other studies, cannabis users demonstrated weaker connectivity between the left PCC and other DMN nodes. Cannabis users had stronger connectivity with the cerebellum, inconsistent with other studies. In the present study, this was related to poorer performance on cognitive measures. One possible mechanism for these findings may be that chronic THC exposure may alter GABA and glutamate concentrations, which relate to altered communication between brain regions. Future studies should be conducted with a larger sample size, examining gender differences, using a longitudinal design, and examining the neurochemical mechanism by which these differences may arise.

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