Corpus callosum damage in heavy marijuana use: Preliminary evidence from diffusion tensor tractography and tract-based spatial statistics

Arnone, Danilo; Barrick, Thomas R.; Chengappa, Sanjoo; Mackay, Clare E.; Clark, Chris A.; Abou‐Saleh, Mohammed T.

doi:10.1016/j.neuroimage.2008.02.064

Cited by 154 publications

(127 citation statements)

References 51 publications

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“…Although decreased FA was observed in the forceps minor when considering the tract as a whole, we did not replicate previous findings of reduced FA values in this tract in cannabis users using TBSS (Arnone et al 2008). Notably, previous research only examined younger cannabis users.…”

Section: Discussioncontrasting

confidence: 99%

“…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.…”

Section: Discussionmentioning

confidence: 53%

“…Additionally, the general paucity of significant voxel-based differences observed using TBSS suggests that the effect of cannabis is evident only when considering the tract as a whole. Notably, recent research has generally moved away from voxel-based comparisons (DeLisi et al 2006;Arnone et al 2008) to considering tracts as a whole (Filbey et al 2014;Epstein and Kumra 2015;Shollenbarger et al 2015). We have demonstrated somewhat consistent effects on RD utilising both approaches, however we note that different methods have isolated different tracts of interest.…”

Section: Discussionmentioning

confidence: 58%

“…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.…”

Section: Introductionmentioning

confidence: 99%

“…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).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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Rationale Conflicting evidence exists on the effects of cannabis use on brain white matter integrity. The extant literature has exclusively focused on younger cannabis users, with no studies sampling older cannabis users. Objectives We recruited a sample with a broad age range to examine the integrity of major white matter tracts in association with cannabis use parameters and neurodevelopmental stage. Methods Regular cannabis users (n = 56) and non-users (n = 20) with a mean age of 32 (range 18-55 years) underwent structural and diffusion MRI scans. White matter was examined using voxel-based statistics and via probabilistic tract reconstruction. The integrity of tracts was assessed using average fractional anisotropy, axial diffusivity and radial diffusivity. Diffusion measures were compared between users and non-users and as group-by-age interactions. Correlations between diffusion measures and age of onset, duration, frequency and dose of current cannabis use were examined. Results Cannabis users overall had lower fractional anisotropy than healthy non-users in the forceps minor tract only (p = .015, partial eta = 0.07), with no voxel-wise differences observed. Younger users showed predominantly reduced axial diffusivity, whereas older users had higher radial diffusivity in widespread tracts. Higher axial diffusivity was associated with duration of cannabis use in the cingulum angular bundle (beta = 5.00 x 10−5, p = .003). Isolated higher AD in older cannabis users was also observed. Conclusions The findings suggest that exogenous cannabinoids alter normal brain maturation, with differing effects at various neurodevelopmental stages of life. These age-related differences are posited to account for the disparate results described in the literature.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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Structural and Functional Neuroimaging Methods: Applications to Substance Abuse and Addiction

Yang

Chefer

Geng

et al. 2011

Neuroimaging in Addiction

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Cannabidiol induces intracellular calcium elevation and cytotoxicity in oligodendrocytes

Mato

Sánchez‐Gómez

Matute

2010

Glia

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Heavy marijuana use has been linked to white matter histological alterations. However, the impact of cannabis constituents on oligodendroglial pathophysiology remains poorly understood. Here, we investigated the in vitro effects of cannabidiol, the main nonpsychoactive marijuana component, on oligodendrocytes. Exposure to cannabidiol induced an intracellular Ca(2+) rise in optic nerve oligodendrocytes that was not primarily mediated by entry from the extracellular space, nor by interactions with ryanodine or IP(3) receptors. Application of the mitochondrial protonophore carbonylcyanide-p-trifluoromethoxyphenylhydrazone (FCCP; 1 μM) completely prevented subsequent cannabidiol-induced Ca(2+) responses. Conversely, the increase in cytosolic Ca(2+) levels elicited by FCCP was reduced after previous exposure to cannabidiol, further suggesting that the mitochondria acts as the source of cannabidiol-evoked Ca(2+) rise in oligodendrocytes. n addition, brief exposure to cannabidiol (100 nM-10 μM) led to a concentration-dependent decrease of oligodendroglial viability that was not prevented by antagonists of CB(1), CB(2), vanilloid, A(2A) or PPARγ receptors, but was instead reduced in the absence of extracellular Ca(2+). The oligodendrotoxic effect of cannabidiol was partially blocked by inhibitors of caspase-3, -8 and -9, PARP-1 and calpains, suggesting the activation of caspase-dependent and -independent death pathways. Cannabidiol also elicited a concentration-dependent alteration of mitochondrial membrane potential, and an increase in reactive oxygen species (ROS) that was reduced in the absence of extracellular Ca(2+). Finally, cannabidiol-induced cytotoxicity was partially prevented by the ROS scavenger trolox. Together, these results suggest that cannabidiol causes intracellular Ca(2+) dysregulation which can lead to oligodendrocytes demise.

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Corpus callosum damage in heavy marijuana use: Preliminary evidence from diffusion tensor tractography and tract-based spatial statistics

Cited by 154 publications

References 51 publications

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

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

Structural and Functional Neuroimaging Methods: Applications to Substance Abuse and Addiction

Cannabidiol induces intracellular calcium elevation and cytotoxicity in oligodendrocytes

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