Diffusion abnormalities in adolescents and young adults with a history of heavy cannabis use

Abstract

Background There is growing evidence that adolescence is a key period for neuronal maturation. Despite the high prevalence of marijuana use among adolescents and young adults in the United States and internationally, very little is known about its impact on the developing brain. Based on neuroimaging literature on normal brain developmental during adolescence, we hypothesized that individuals with heavy cannabis use (HCU) would have brain structure abnormalities in similar brain regions that undergo development during late adolescence, particularly the fronto-temporal connection. Method Fourteen young adult males in residential treatment for cannabis dependence and 14 age-matched healthy male control subjects were recruited. Patients had a history of HCU throughout adolescence; 5 had concurrent alcohol abuse. Subjects underwent structural and diffusion tensor magnetic resonance imaging. White matter integrity was compared between subject groups using voxelwise and fiber tractography analysis. Results Voxelwise and tractography analyses revealed that adolescents with HCU had reduced fractional anisotropy, increased radial diffusivity, and increased trace in the homologous areas known to be involved in ongoing development during late adolescence, particularly in the fronto-temporal connection via arcuate fasciculus. Conclusions Our results support the hypothesis that heavy cannabis use during adolescence may affect the trajectory of normal brain maturation. Due to concurrent alcohol consumption in five HCU subjects, conclusions from this study should be considered preliminary, as the DTI findings reported here may be reflective of the combination of alcohol and marijuana use. Further research in larger samples, longitudinal in nature, and controlling for alcohol consumption is needed to better understand the pathophysiology of the effect of cannabis on the developing brain.

An MRI study of white matter tract integrity in regular cannabis users: effects of cannabis use and age

“…Our finding of lower FA in the forceps minor tract has been demonstrated in the literature for younger users (Ashtari et al 2009;Filbey et al 2014), although Becker et al (2015) did note higher FA in cannabis users than non-users. This effect on the forceps minor is congruent with the known increased density of cannabinoid type 1 receptors (which are activated by the main psychoactive constituent of cannabis, delta-9-tetrahydrocannabinol (THC)) in frontal brain regions (Svíženská et al 2008).…”

“…These differences were significant from approximately age 32 onwards, highlighting the limitations of past research that typically assessed samples with a mean age below 25 (DeLisi et al 2006;Arnone et al 2008;Ashtari et al 2009;Jacobus et al 2009;Bava et al 2010;Gruber et al 2011;Gruber et al 2014;Becker et al 2015;Shollenbarger et al 2015). Our findings provide a preliminary extension for longitudinal studies in younger users which noted altered FA in the frontal regions (Becker et al 2015) and the left inferior longitudinal fasciculus (Epstein and Kumra 2015) to additional tracts within the brain.…”

“…Lower FA has been demonstrated in cannabis users in the anterior corpus callosum (Gruber and Yurgelun-Todd 2005;Arnone et al 2008;Gruber et al 2011;Gruber et al 2014;Epstein and Kumra 2015), fronto-thalamic connections (Ashtari et al 2009), uncinate fasciculus (Shollenbarger et al 2015), as well as temporal and parietal brain regions, including the left superior longitudinal fasciculus and inferior longitudinal fasciculus (Bava et al 2010;Epstein and Kumra 2015). Additionally, using newer whole-brain network analysis methods, we have previously reported that cannabis users had fewer streamlines in the right fimbria of the hippocampus and in hippocampal commissural fibres connecting the splenium of the corpus callosum and the right precuneus (Zalesky et al 2012), with lower FA in the hippocampal commissural fibre bundle (Solowij et al in press).…”

“…This inconsistency has been attributed to low sample sizes (Gruber and Yurgelun-Todd 2005;DeLisi et al 2006) or less detailed scanning parameters in earlier studies (as described by Ashtari et al 2009) which may have overlooked smaller, more subtle, or regionally-specific changes. Additionally, some studies have been confounded by samples with concomitant cannabis and alcohol abuse, preventing the detection of cannabis specific effects (Jacobus et al 2009;Bava et al 2010).…”

“…The current literature on white matter in cannabis users has generally focused on adolescents and young adults, utilising samples with a mean age less than 25 (DeLisi et al 2006;Arnone et al 2008;Gruber et al 2011;Gruber et al 2014;Shollenbarger et al 2015) or 20 (Ashtari et al 2009;Jacobus et al 2009;Bava et al 2010;Becker et al 2015), with only two studies utilising slightly older participants (mean 27 years of age, Rigucci et al 2015, and mean 28 years of age, Filbey et al 2014). While this focus may be justified by concerns regarding the critical brain development occurring during this period (Bossong and Niesink 2010), restriction to young samples may impose major limitations to understanding the impact of cannabis exposure on white matter given its prolonged developmental trajectory.…”