Date of Award

August 2017

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Psychology

First Advisor

Krista M. Lisdahl

Committee Members

Christine Larson, Han Joo Lee, Deborah Hannula, Raymond Fleming

Keywords

Brain, Cannabis, Development, fMRI, Frontolimbic, Mood

Abstract

Introduction: Recent legislation changes regarding cannabis in the United States highlights the importance of investigating the impact of regular cannabis use on populations, such as emerging adults, that will likely drive the market given their greater daily use (see Johnston et al., 2014). The endocannbinoid system plays a role in neurodevelopment (see Bossong & Niesink, 2010) and has been implicated in behavioral and emotional processing (see Moreira & Lutz, 2008; see Solinas et al., 2008; see Covey et al., 2014). The current study utilized a multisite functional magnetic resonance imaging (fMRI) dataset of intrinsic (a.k.a. no task/resting state) frontolimbic connectivity among healthy emerging adults. A secondary aim examined the relationship between cannabis group connectivity differences and self-reported mood and affect symptoms.

Methods: Participants included consortium data totaling 79 cannabis users (average of 58 past month joints) and 80 controls (0 past month joints & no history of regular use) emerging adults (ages of 18-30), balanced for gender, reading ability, and age. Exclusion criteria included history of medical/neurological illness or injury, independent DSM-IV-TR axis I disorders, and inability to maintain monitored abstinence. Structural and functional neuroimages were preprocessed and analyzed using CPAC software. Regions of interest included: anterior cingulate (rostral and caudal subdivisions), amygdala, insula, and ventral medial prefrontal cortex. Behavioral measurements included the Beck Depression Inventory-II, Beck Anxiety Scale, and the State Trait Anxiety Inventory-Y1. Standard multiple regressions were used to predict if cannabis group status was associated with frontolimbic connectivity after controlling for site, past month alcohol and nicotine use, and days of abstinence from cannabis. Pearson r correlations were run to examine the relationship between group differences in connectivity and self-reported depression and anxiety total scores.

Results: On self-reported measures, cannabis users reported significantly more total depression (p=.02) and anxiety (p=.04) symptoms. After controlling for site, past month alcohol and nicotine use, and days of abstinence from cannabis, cannabis users demonstrated significantly greater connectivity between left rACC and the following: left amygdala (p=.03; corrected p=.47; ƒ2 = .17), left insula (p=.03; corrected p=.47; ƒ2 = .16), and right rACC (p=.001; corrected p=.05; ƒ2 =.55). Among cannabis users, greater bilateral rACC connectivity was associated with significantly greater total depressive scores (p=.02).

Discussion: Cannabis using young adults demonstrated greater connectivity within frontolimbic regions compared to controls with no recent or regular cannabis use. In cannabis users, greater bilateral rACC intrinsic connectivity was associated with higher levels of depression symptoms. Current findings suggest that regular cannabis use during neurodevelopmental periods may alter intrinsic brain characteristics involved in cognitive control and emotion regulation, and this finding should be considered when designing clinical interventions for this population. Future research may investigate the mechanisms underlying altered rACC connectivity, such as GABA and GLUT signaling, and the impact on mood in young cannabis users.

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