Measuring white matter microstructure in 1,457 cannabis users and 1,441 controls: A systematic review of diffusion-weighted MRI studies

Abstract

IntroductionCannabis is the most widely used regulated substance by youth and adults. Cannabis use has been associated with psychosocial problems, which have been partly ascribed to neurobiological changes. Emerging evidence to date from diffusion-MRI studies shows that cannabis users compared to controls show poorer integrity of white matter fibre tracts, which structurally connect distinct brain regions to facilitate neural communication. However, the most recent evidence from diffusion-MRI studies thus far has yet to be integrated. Therefore, it is unclear if white matter differences in cannabis users are evident consistently in selected locations, in specific diffusion-MRI metrics, and whether these differences in metrics are associated with cannabis exposure levels.MethodsWe systematically reviewed the results from diffusion-MRI imaging studies that compared white matter differences between cannabis users and controls. We also examined the associations between cannabis exposure and other behavioral variables due to changes in white matter. Our review was pre-registered in PROSPERO (ID: 258250; https://www.crd.york.ac.uk/prospero/).ResultsWe identified 30 diffusion-MRI studies including 1,457 cannabis users and 1,441 controls aged 16-to-45 years. All but 6 studies reported group differences in white matter integrity. The most consistent differences between cannabis users and controls were lower fractional anisotropy within the arcuate/superior longitudinal fasciculus (7 studies), and lower fractional anisotropy of the corpus callosum (6 studies) as well as higher mean diffusivity and trace (4 studies). Differences in fractional anisotropy were associated with cannabis use onset (4 studies), especially in the corpus callosum (3 studies).DiscussionThe mechanisms underscoring white matter differences are unclear, and they may include effects of cannabis use onset during youth, neurotoxic effects or neuro adaptations from regular exposure to tetrahydrocannabinol (THC), which exerts its effects by binding to brain receptors, or a neurobiological vulnerability predating the onset of cannabis use. Future multimodal neuroimaging studies, including recently developed advanced diffusion-MRI metrics, can be used to track cannabis users over time and to define with precision when and which region of the brain the white matter changes commence in youth cannabis users, and whether cessation of use recovers white matter differences.Systematic review registrationwww.crd.york.ac.uk/prospero/, identifier: 258250.

White matter alterations associated with chronic cannabis use disorder: a structural network and fixel-based analysis

“…This is a vital neural junction that supports both fundamental and complex mental processes from attention to memory and social cognition (52), highlighting the signi cance of related WM pathways for neural communication to this region. We did not observe evidence of associations between WM metrics and any cognitive or mental health outcomes, which is in line with the recent systemic review by Robinson et al (53). However, we observed a signi cant association between total cannabis consumption (the last month prior to study) and the strength of connectivity between left lateral orbitofrontal cortex and right inferior parietal lobe.…”

Multi‐level prediction of substance use: Interaction of white matter integrity, resting‐state connectivity and inhibitory control measured repeatedly in every‐day life

“…Our study is the first to integrate white matter microstructural integrity into the multiple levels of impairment that SUD patients exhibit in Low FA values typically reflect low coherence of the linear microstructure of white matter tracts. 42 As presumed outcomes of the toxic effect of substance use, studies demonstrated that FA values decrease with heavy 43 or long-term drinking, 44 continued smoking 45 and cannabis use 46 generally with lower scores being linked to poorer clinical outcomes. In our study, lower FA values in clusters encompassing the callosal genu and body and the bilateral anterior corona radiata were linked to poorer mean inhibition performance assessed via mobile Stroop testing in the SUD sample.…”

Tract-based analyses of white matter in schizophrenia, bipolar disorder, aging, and dementia using high spatial and directional resolution diffusion imaging: a pilot study

“…Antipsychotic use, for example, has been reported to increase tract FA ( 81 , 82 ), while others have reported a subtle loss of white matter integrity ( 83 ). Diffusion studies have also found poorer integrity of white matter in cannabis users compared to non-users ( 84 , 85 ). In addition, potential protective factors for white matter abnormalities including psychotherapy ( 86 , 87 ) or cognitive training ( 88 ) may have been a confounder in our study, and such data were unavailable from our participants for analyses.…”