Brain structural changes in cannabis dependence: association with MAGL

Abstract

Cannabis use is rising, yet there is poor understanding of biological processes that might link chronic cannabis use to brain structural abnormalities. To lend insight into this topic, we examined white matter microstructural integrity and gray matter cortical thickness/density differences between 89 individuals with cannabis dependence (CD) and 89 matched controls (64 males, 25 females in each group) from the Human Connectome Project. We tested whether cortical patterns for expression of genes relevant for cannabinoid signaling (from Allen Human Brain Atlas postmortem tissue) were associated with spatial patterns of cortical thickness/density differences in CD. CD had lower fractional anisotropy than controls in white matter bundles innervating posterior cingulate and parietal cortex, basal ganglia, and temporal cortex. The CD group also had significantly less gray matter thickness and density in precuneus, relative to controls. Sibling-pair analysis found support for causal and graded liability effects of cannabis on precuneus structure. Spatial patterns of gray matter differences in CD were significantly associated with regional differences in monoacylglycerol lipase (MAGL) expression in postmortem brain tissue, such that regions with higher MAGL expression (but not fatty-acid amide hydrolase or FAAH) were more vulnerable to cortical thinning. In sum, chronic cannabis use is associated with structural differences in white and gray matter, which was most prominent in precuneus and associated white matter tracts. Regions with high MAGL expression, and therefore with potentially physiologically restricted endogenous cannabinoid signaling, may be more vulnerable to the effects of chronic cannabis use on cortical thickness.

Associations of cannabis use disorder with cognition, brain structure, and brain function inAfrican Americans

“…However, a few recent large studies did find morphometric differences in association with cannabis use. ; Although the literature is consistent in reporting lower structural connectivity in participants with CUD (Arnone et al, 2008;Ashtari et al, 2009;Becker et al, 2015;Epstein & Kumra, 2015;Gruber et al, 2014;Jacobus et al, 2009;Jakabek et al, 2016;Manza et al, 2019;Murray et al, 2017;Orr et al, 2016;Shollenbarger et al, 2015;Zalesky et al, 2012), we did not find conclusive evidence for lower FA in the CUD group (0.3 < BF < 3). Functional connectivity studies, however, are more inconsistent.…”

“…Nevertheless, a smaller hippocampal volume has been associated with current cannabis dependence (Chye et al, 2019), and tetrahydrocannabinol (THC, a psychoactive component of cannabis) positive urine but not lifetime use (Owens, Sweet, & MacKillop, 2020). In contrast, white matter integrity, as inferred from fractional anisotropy (FA) derived from diffusion tensor imaging (DTI) may be reduced in cannabis users (Arnone et al, 2008; Becker, Collins, Lim, Muetzel, & Luciana, 2015; Epstein & Kumra, 2015; Gruber, Dahlgren, Sagar, Gönenç, & Lukas, 2014; Jacobus, Squeglia, Bava, & Tapert, 2013; Jakabek, Yücel, Lorenzetti, & Solowij, 2016; Manza, Yuan, Shokri‐Kojori, Tomasi, & Volkow, 2019; Murray et al, 2017; J. M. Orr et al, 2016; Shollenbarger, Price, Wieser, & Lisdahl, 2015), even after months of abstinence (Ashtari, Cervellione, Cottone, Ardekani, & Kumra, 2009). Although many studies have looked at functional connectivity and cannabis use, most studies involve activation tasks and/or region of interest approach (Blest‐Hopley, Giampietro, & Bhattacharyya, 2018).…”

Cannabis Affects Cerebellar Volume and Sleep Differently in Men and Women

“…Findings have been inconsistent, with some studies finding substantially smaller subcortical volumes in chronic cannabis users compared to controls ( 16 – 18 ), whereas others have reported that after controlling for key confounding variables like tobacco usage, these differences are virtually non-existent ( 19 , 20 ). We and others have argued that these discrepant findings are due to generally small sample sizes and inadequate matching on control groups ( 21 ). Nevertheless, several recent reviews have been devoted to the topic ( 22 – 24 ) and some consensus seems to have emerged that cerebellum, amygdala, and hippocampus volumes appear to be most consistently affected by chronic cannabis use across studies ( 8 ).…”

Δ9‐Tetrahydrocannabinol promotes oligodendrocyte development and CNS myelination in vivo

“…An extensive number of studies have pointed out some similarities in the mode of action of the molecules that modulate oligodendrogenesis during postnatal development and in the adult CNS (Itoh, Maki, Lok, & Arai, 2015;Patel & Klein, 2011). Indeed, chronic cannabis use has been associated with structural differences in the gray matter, but more prominently in white matter tracts (Manza, Yuan, Shokri-Kojori, Tomasi, & Volkow, 2019;Orr, Paschall, & Banich, 2016), with greater functional connectivity in orbitofrontal cortex network and increased structural connectivity of the forceps minor of cannabis users, which in turn has been suggested to reflect better myelination and/or intact axons (Filbey et al, 2014;Song et al, 2002). Therefore, the identification in this study of THC as a potent inductor of OPC differentiation in vivo opens the possibility that this molecule could potentially modulate CNS myelination in the adult human brain.…”