Poorer frontolimbic white matter integrity is associated with chronic cannabis use, FAAH genotype, and increased depressive and apathy symptoms in adolescents and young adults

Shollenbarger, Skyler G.; Price, J. Waide; Wieser, Jon; Medina, Krista Lisdahl

doi:10.1016/j.nicl.2015.03.024

Cited by 56 publications

(65 citation statements)

References 89 publications

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“…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%

“…In combining automated methodologies, we utilised the exploratory voxel-based comparison of TBSS together with the overall tract integrity assessment of TRACULA. Moreover, we sought to expand our search beyond just anterior tracts (Shollenbarger et al 2015) to all major defined tracts in the brain.…”

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: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 58%

Section: Introductionmentioning

confidence: 99%

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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Fatty acid amide hydrolase C385A polymorphism affects susceptibility to various diseases

Anvar

Ahmadalipour

2022

BioFactors

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The endocannabinoid (eCB) system is an important neuromodulatory system with its extensive network of receptors throughout the human body that has complex actions in the nervous system, immune system, and all of the body's other organs. Fatty acid amide hydrolase (FAAH) is an important membranebound homodimeric degrading enzyme that controls the biological activity of N-arachidonoylethanolamide (AEA) in the eCB system and other relevant bioactive lipids. It has been shown that several single nucleotide polymorphisms (SNPs) of FAAH are associated with various phenotypes and diseases including cardiovascular, endocrine, drug abuse, and neuropsychiatric disorders. A common functional and most studied polymorphism of this gene is C385A (rs324420), which results in the replacement of a conserved proline to threonine in the FAAH enzyme structure, leads to a reduction of the activity and expression of FAAH, compromises the inactivation of AEA and causes higher synaptic concentrations of AEA that can be associated with several various phenotypes. The focus of this review is on evidence-based studies on the associations of the FAAH C385A polymorphism and the various diseases or traits.Although there was variability in the results of these reports, the overall consensus is that the FAAH C385A genotype can affect susceptibility to some multifactorial disorders and can be considered a potential therapeutic target.

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

Koenis

Durnez

Rodrigue

et al. 2020

Human Brain Mapping

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Although previous studies have highlighted associations of cannabis use with cognition and brain morphometry, critical questions remain with regard to the association between cannabis use and brain structural and functional connectivity. In a cross‐sectional community sample of 205 African Americans (age 18–70) we tested for associations of cannabis use disorder (CUD, n = 57) with multi‐domain cognitive measures and structural, diffusion, and resting state brain‐imaging phenotypes. Post hoc model evidence was computed with Bayes factors (BF) and posterior probabilities of association (PPA) to account for multiple testing. General cognitive functioning, verbal intelligence, verbal memory, working memory, and motor speed were lower in the CUD group compared with non‐users (p < .011; 1.9 < BF < 3,217). CUD was associated with altered functional connectivity in a network comprising the motor‐hand region in the superior parietal gyri and the anterior insula (p < .04). These differences were not explained by alcohol, other drug use, or education. No associations with CUD were observed in cortical thickness, cortical surface area, subcortical or cerebellar volumes (0.12 < BF < 1.5), or graph‐theoretical metrics of resting state connectivity (PPA < 0.01). In a large sample collected irrespective of cannabis used to minimize recruitment bias, we confirm the literature on poorer cognitive functioning in CUD, and an absence of volumetric brain differences between CUD and non‐CUD. We did not find evidence for or against a disruption of structural connectivity, whereas we did find localized resting state functional dysconnectivity in CUD. There was sufficient proof, however, that organization of functional connectivity as determined via graph metrics does not differ between CUD and non‐user group.

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Poorer frontolimbic white matter integrity is associated with chronic cannabis use, FAAH genotype, and increased depressive and apathy symptoms in adolescents and young adults

Cited by 56 publications

References 89 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

Fatty acid amide hydrolase C385A polymorphism affects susceptibility to various diseases

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

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