• 2018-07
  • 2018-10
  • 2018-11
  • br Methods br Results br Discussion This study looked


    Discussion This study looked at cortical thickness estimates at three independent time points (ages 18, 19, and 21, respectively) in adolescent marijuana and alcohol users compared to controls with limited substance use histories. We found significant between-group differences in cortical thickness cox 2 inhibitor estimates after controlling for lifetime alcohol use. MJ+ALC demonstrated increased cortical thickness estimates in all four lobes of the brain, bilaterally. Notably, 18 of 23 regions in which differences were observed were in the frontal and parietal cortex. Positive dose-dependent associations were identified in temporal cox 2 inhibitor regions, as cumulative marijuana use from ages 16 to 22 was associated with thicker cortices in inferior temporal and entorhinal cortex. Several negative associations were observed with lifetime alcohol use, as more alcohol use reported was associated with thinner cortical estimates in all four lobes. It is important to detail how these findings compare to our previous work with a similar sample, as we found both similarities and differences from our cortical thickness study in which adolescent marijuana users were observed pre- and post 28-days of monitored abstinence (Jacobus et al., 2014). In Jacobus et al. (2014), increased thickness estimates in our marijuana users (controlling for alcohol use) was found in the entorhinal cortex compared to matched controls. Similarly, the present study found increased thickness estimates in our user group compared to our controls, and findings were more widespread and noted in all four lobes of the brain. The present study also found more lifetime marijuana use was associated with increased thickness in the entorhinal cortex, a region rich in cannabinoid 1 (CB1) receptors and important for learning and memory (Battistella et al., 2014; Iversen, 2003; Tsou et al., 1998). However, dose-dependent bivariate correlations were different in that previously (Jacobus et al., 2014) we saw increased marijuana use associated with thinner cortices and increased alcohol use associated with thicker cortical estimates at age 17, pre- and post monitored abstinence. Our dose-dependent associations in the present study suggest otherwise. We found increased lifetime marijuana use reported associated with thicker cortical estimates and increased lifetime alcohol use reported associated with thinner cortices (at age ∼21). This may reflect several points recently discussed by Filbey and colleagues (2014) in the literature, including (1) methodological issues, the present study assessed substance independently over the course of three years compared to 28-days at age 17; (2) age and maturational bias, correlations in the present study reflect associations following many years of substance use and potential for interference with complex neurodevelopmental processes; (3) changes in marijuana and alcohol use patterns, as individuals in the present study remain relatively chronic in their marijuana use over time but subtly increase in their alcohol use; and (4) possible interactions with pre-existing vulnerabilities that are present at age 17 (near initiation), but likely changes as the individual continues to chronically use substances and increase in age (Cheetham et al., 2012; Filbey et al., 2014; Jacobus et al., 2013a; Squeglia et al., 2014) Lopez-Larson and colleagues (2011) cross-sectionally investigated cortical thickness in adolescents ages 16–19 years, with heavy marijuana use histories. They found decreased thickness in frontal regions and the insula, along with increased thickness in lingual, temporal, and parietal regions. The present study found increases in thickness in parietal, temporal, and occipital cortices, consistent with work by this team. The mechanism by which marijuana may alter the neural architecture and plasticity of the brain is undetermined. The endocannabinoid system plays a role in neuromaturational processes (e.g., pruning) and modulates neurotransmission for several neurotransmitter systems (Berghuis et al., 2007; Iversen, 2003; Rubino and Parolaro, 2008; Stella, 2013). Interference with this system due to marijuana, or tetrahydrocannabinol (THC) administration, likely causes a cascade of neuronal events (Kim and Thayer, 2001; Kim et al., 2008) that changes brain structure and function (Batalla et al., 2013), and thereby neurocognitive processing (Meier et al., 2012), emotional regulation and reward processing (Cousijn et al., 2011), and propensity for psychiatric comorbidities and addiction (Hall, 2014).