Why so impulsive? White matter alterations are associated with impulsivity in chronic marijuana smokers.

Abstract

Difficulty monitoring and inhibiting impulsive behaviors has been reported in marijuana (MJ) smokers; neuroimaging studies, which examined frontal systems in chronic MJ smokers, have reported alterations during inhibitory tasks. Diffusion tensor imaging (DTI) provides a quantitative estimate of white matter integrity at the microstructural level. We applied DTI, clinical ratings, and impulsivity measures to explore the hypotheses that chronic, heavy MJ smokers would demonstrate alterations in white matter microstructure and a different association between white matter measures and impulsivity relative to nonsmoking control subjects (NS). Fractional anisotropy (FA), a measure of directional coherence, and trace, a measure of overall diffusivity, were calculated for 6 locations including bilateral frontal regions in 15 chronic MJ smokers and 15 NS. Subjects completed clinical rating scales, including the Barratt Impulsivity Scale (BIS). Analyses revealed significant reductions in left frontal FA in MJ smokers relative to NS and significantly higher levels of trace in the right genu. MJ smokers also had significantly higher BIS total and motor subscale scores relative to NS, which were positively correlated with left frontal FA values. Finally, age of onset of MJ use was positively correlated with frontal FA values and inversely related to trace. These data represent the first report of significant alterations in frontal white matter tracts associated with measures of impulsivity in chronic MJ smokers. Early MJ use may result in reduced FA and increased diffusivity, which may be associated with increased impulsivity, and ultimately contribute to the initiation of MJ use or the inability to discontinue use.

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

“…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.…”

“…Alternatively, these increases in white matter may arise as a reactive response to reduced gray matter (Yücel et al 2008;Lorenzetti et al 2010) or be an imaging artefact due to smaller axons leading to falsely elevated axon density (Beaulieu 2002). Additionally, differentially altered white matter integrity across age groups, which to our knowledge has not been previously examined, may explain the seemingly disparate reports of both increases (DeLisi et al 2006;Jacobus et al 2009;Bava et al 2010;Filbey et al 2014) and decreases (Gruber and Yurgelun-Todd 2005;Arnone et al 2008;Ashtari et al 2009;Gruber et al 2011;Gruber et al 2014) in white matter integrity in cannabis users. Lastly, cannabinoid neurotoxicity may be mediated by immune processes (Molina-Holgado et al 2003), or be compounded by direct toxicity from hydrocarbons and carbon monoxide produced by combustion during cannabis smoking (Prockop and Naidu 1999;Abrams et al 2007).…”

“…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.…”

“…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).…”

1301 – Structural and functional imaging studies in chronic cannabis users: a systematic review of adolescent and adult findings

“…Structural differences were obtained in seven of them in terms of global brain measures [143] or gray/white matter changes [144][145][146][147][148][149]. Four studies did not find any significant structural alterations when comparing chronic cannabis users with healthy controls [150][151][152][153].…”