White matter signatures of addiction diverge across opioids, cannabis and nicotine and predict impulsive choice in cannabis dependence
Abstract
White matter (WM) microstructure is implicated in the neurobiology of substance use disorders (SUDs), yet direct comparisons across substance-dependence syndromes remain scarce. It is also unclear whether WM abnormalities relate to impulsive decision-making and substance use severity. We performed a cross-sectional, dual-centre diffusion MRI study and quantified WM microstructure using diffusion tensor imaging and neurite orientation dispersion and density imaging in 87 individuals with SUDs (48 with cannabis dependence (CUD), 16 with opioid dependence (OUD), and 23 with nicotine dependence (NUD)) and 53 nonsmoking healthy controls. Whole-brain tract-based spatial statistics and tract-specific analyses of the middle longitudinal fasciculus (MLF), a temporo-parietal tract implicated in cognitive control and valuation, were performed. OUD and CUD exhibited convergent, widespread WM abnormalities characterised by reduced fractional anisotropy and increased mean diffusivity and orientation dispersion across fronto-temporo-parietal and limbic pathways, including the superior longitudinal fasciculus, arcuate fasciculus, cingulum, and MLF. In contrast, NUD showed more circumscribed alterations observed primarily in MD and localised mainly to anterior and callosal white matter regions. In CUD, higher MLF orientation dispersion was associated with steeper delay discounting (r = 0.41, p = 0.011). Moderated mediation analyses indicated that this association was indirectly driven by cannabis consumption, with asignificant conditional indirect effects observed only among daily users. No significant MLF-discounting associations were observed in OUD. Our findings reveal both shared and distinct WM alterations across SUDs and identify a link between MLF microstructure and impulsive choice in cannabis dependence.
Related
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- Nicotine and Cannabis Co-Use are Associated with Higher Symptom Burden than Use of Either Drug Alone in Early Psychosis: Results from a Multisite Study
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- Effects of Intensive Electroacupuncture on Nicotine Withdrawal and Withdrawal-Related Sleep Symptoms in Patients with Nicotine Dependence: A Three-Arm Randomized Controlled Trial.
BibTeX
@article{nkrumah2026white,
title = {{White matter signatures of addiction diverge across opioids, cannabis and nicotine and predict impulsive choice in cannabis dependence}},
author = {Richard O. Nkrumah and Lea Wetzel and Justin Böhmer and Katharina Eidenmueller and Patrick Bach and Silvia De Santis and Henrik Walter and Wolfgang H. Sommer and Gabriele Ende},
journal = {Translational Psychiatry},
year = {2026},
month = oct,
doi = {10.1038/s41398-026-04491-8},
url = {https://www.nature.com/articles/s41398-026-04491-8},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - White matter signatures of addiction diverge across opioids, cannabis and nicotine and predict impulsive choice in cannabis dependence
AU - Richard O. Nkrumah
AU - Lea Wetzel
AU - Justin Böhmer
AU - Katharina Eidenmueller
AU - Patrick Bach
AU - Silvia De Santis
AU - Henrik Walter
AU - Wolfgang H. Sommer
AU - Gabriele Ende
PY - 2026
DA - 2026/10/09
JO - Translational Psychiatry
DO - 10.1038/s41398-026-04491-8
UR - https://www.nature.com/articles/s41398-026-04491-8
AB - White matter (WM) microstructure is implicated in the neurobiology of substance use disorders (SUDs), yet direct comparisons across substance-dependence syndromes remain scarce. It is also unclear whether WM abnormalities relate to impulsive decision-making and substance use severity. We performed a cross-sectional, dual-centre diffusion MRI study and quantified WM microstructure using diffusion tensor imaging and neurite orientation dispersion and density imaging in 87 individuals with SUDs (48 with cannabis dependence (CUD), 16 with opioid dependence (OUD), and 23 with nicotine dependence (NUD)) and 53 nonsmoking healthy controls. Whole-brain tract-based spatial statistics and tract-specific analyses of the middle longitudinal fasciculus (MLF), a temporo-parietal tract implicated in cognitive control and valuation, were performed. OUD and CUD exhibited convergent, widespread WM abnormalities characterised by reduced fractional anisotropy and increased mean diffusivity and orientation dispersion across fronto-temporo-parietal and limbic pathways, including the superior longitudinal fasciculus, arcuate fasciculus, cingulum, and MLF. In contrast, NUD showed more circumscribed alterations observed primarily in MD and localised mainly to anterior and callosal white matter regions. In CUD, higher MLF orientation dispersion was associated with steeper delay discounting (r = 0.41, p = 0.011). Moderated mediation analyses indicated that this association was indirectly driven by cannabis consumption, with asignificant conditional indirect effects observed only among daily users. No significant MLF-discounting associations were observed in OUD. Our findings reveal both shared and distinct WM alterations across SUDs and identify a link between MLF microstructure and impulsive choice in cannabis dependence.
SN - 2158-3188
ER -