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Sex and dependence related neuroanatomical differences in regular cannabis users: findings from the ENIGMA Addiction Working Group.

ABSTRACT: Males and females show different patterns of cannabis use and related psychosocial outcomes. However, the neuroanatomical substrates underlying such differences are poorly understood. The aim of this study was to map sex differences in the neurobiology (as indexed by brain volumes) of dependent and recreational cannabis use. We compared the volume of a priori regions of interest (i.e., amygdala, hippocampus, nucleus accumbens, insula, orbitofrontal cortex (OFC), anterior cingulate cortex and cerebellum) between 129 regular cannabis users (of whom 70 were recreational users and 59 cannabis dependent) and 114 controls recruited from the ENIGMA Addiction Working Group, accounting for intracranial volume, age, IQ, and alcohol and tobacco use. Dependent cannabis users, particularly females, had (marginally significant) smaller volumes of the lateral OFC and cerebellar white matter than recreational users and controls. In dependent (but not recreational) cannabis users, there was a significant association between female sex and smaller volumes of the cerebellar white matter and OFC. Volume of the OFC was also predicted by monthly standard drinks. No significant effects emerged the other brain regions of interest. Our findings warrant future multimodal studies that examine if sex and cannabis dependence are specific key drivers of neurobiological alterations in cannabis users. This, in turn, could help to identify neural pathways specifically involved in vulnerable cannabis users (e.g., females with cannabis dependence) and inform individually tailored neurobiological targets for treatment.

SUBMITTER: Rossetti MG

PROVIDER: S-EPMC8102553 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectivesStudies examining the impact of adolescent and young adult cannabis use on structural outcomes have been heterogeneous. One already-identified moderator is sex, while a novel potential moderator is extent of aerobic fitness. Here, we sought to investigate the associations of cannabis use, sex, and aerobic fitness levels on brain volume. Second, we explored brain-behavior relationships to interpret these findings.MethodsSeventy-four adolescents and young adults (36 cannabis users and 38 controls) underwent 3 weeks of monitored cannabis abstinence, aerobic fitness testing, structural neuroimaging, and neuropsychological testing. Linear regressions examined cannabis use and its interaction with sex and aerobic fitness on whole-brain cortical volume and subcortical regions of interests.ResultsNo main-effect differences between cannabis users and nonusers were observed; however, cannabis-by-sex interactions identified differences in frontal, temporal, and paracentral volumes. Female cannabis users generally exhibited greater volume while male users exhibited less volume compared to same-sex controls. Positive associations between aerobic fitness and frontal, parietal, cerebellum, and caudate volumes were observed. Cannabis-by-fitness interaction was linked with left superior temporal volume. Preliminary brain-behavior correlations revealed that abnormal volumes were not advantageous in either male or female cannabis users.ConclusionsAerobic fitness was linked with greater brain volume and sex moderated the effect of cannabis use on volume; preliminary brain-behavior correlations revealed that differences in cannabis users were not linked with advantageous cognitive performance. Implications of sex-specific subtleties and mechanisms of aerobic fitness require large-scale investigation. Furthermore, present findings and prior literature on aerobic exercise warrant examinations of aerobic fitness interventions that aimed at improving neurocognitive health in substance-using youth.

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Sex and dependence related neuroanatomical differences in regular cannabis users: findings from the ENIGMA Addiction Working Group.

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