. 2018 Apr 24:10.1111/add.14252.

doi: 10.1111/add.14252. Online ahead of print.

Testing associations between cannabis use and subcortical volumes in two large population-based samples

Nathan A Gillespie^{1

2}, Michael C Neale¹, Timothy C Bates³, Lisa T Eyler^{4

5}, Christine Fennema-Notestine⁵, Jasmin Vassileva⁶, Michael J Lyons⁷, Elizabeth C Prom-Wormley⁸, Katie L McMahon⁹, Paul M Thompson⁹, Greig de Zubicaray^{10

11}, Ian B Hickie¹², John J McGrath^{13

14}, Lachlan T Strike^{2

9

10}, Miguel E Rentería², Matthew S Panizzon⁵, Nicholas G Martin², Carol E Franz⁵, William S Kremen^{5

14}, Margaret J Wright^{2

9}

Affiliations

¹ Virginia Institute for Psychiatric and Behavior Genetics, Virginia Commonwealth University, VA, USA.
² QIMR Berghofer Medical Research Institute, QLD, Australia.
³ Department of Psychology, University of Edinburgh, EH8 9JZ, UK.
⁴ Desert-Pacific Mental Illness Research, Education and Clinical Center, VA San Diego Healthcare System, CA, USA.
⁵ Department of Psychiatry, University of California San Diego, CA, USA.
⁶ Institute for Drug and Alcohol Studies, Virginia Commonwealth University, VA, USA.
⁷ Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA.
⁸ Department of Family Medicine and Population Health, Virginia Commonwealth University, VA, USA.
⁹ Centre for Advanced Imaging, The University of Queensland, QLD, Australia.
¹⁰ School of Psychology, The University of Queensland, QLD, Australia.
¹¹ Faculty of Health and Institute of Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.
¹² Brain and Mind Research Institute, University of Sydney, NSW, Australia.
¹³ Queensland Brain Institute, The University of Queensland, QLD, Australia.
¹⁴ VA San Diego Center of Excellence for Stress and Mental Health, CA, USA.

PMID: 29691937
PMCID: PMC6200645
DOI: 10.1111/add.14252

Testing associations between cannabis use and subcortical volumes in two large population-based samples

Nathan A Gillespie et al. Addiction. 2018.

. 2018 Apr 24:10.1111/add.14252.

doi: 10.1111/add.14252. Online ahead of print.

Authors

Affiliations

¹ Virginia Institute for Psychiatric and Behavior Genetics, Virginia Commonwealth University, VA, USA.
² QIMR Berghofer Medical Research Institute, QLD, Australia.
³ Department of Psychology, University of Edinburgh, EH8 9JZ, UK.
⁴ Desert-Pacific Mental Illness Research, Education and Clinical Center, VA San Diego Healthcare System, CA, USA.
⁵ Department of Psychiatry, University of California San Diego, CA, USA.
⁶ Institute for Drug and Alcohol Studies, Virginia Commonwealth University, VA, USA.
⁷ Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA.
⁸ Department of Family Medicine and Population Health, Virginia Commonwealth University, VA, USA.
⁹ Centre for Advanced Imaging, The University of Queensland, QLD, Australia.
¹⁰ School of Psychology, The University of Queensland, QLD, Australia.
¹¹ Faculty of Health and Institute of Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.
¹² Brain and Mind Research Institute, University of Sydney, NSW, Australia.
¹³ Queensland Brain Institute, The University of Queensland, QLD, Australia.
¹⁴ VA San Diego Center of Excellence for Stress and Mental Health, CA, USA.

PMID: 29691937
PMCID: PMC6200645
DOI: 10.1111/add.14252

Abstract

Background and aims: Disentangling the putative impact of cannabis on brain morphology from other comorbid substance use is critical. After controlling for the effects of nicotine, alcohol and multi-substance use, this study aimed to determine whether frequent cannabis use is associated with significantly smaller subcortical grey matter volumes.

Design: Exploratory analyses using mixed linear models, one per region of interest (ROI), were performed whereby individual differences in volume (outcome) at seven subcortical ROIs were regressed onto cannabis and comorbid substance use (predictors).

Setting: Two large population-based twin samples from the United States and Australia.

Participants: A total of 622 young Australian adults [66% female; μ_age = 25.9, standard deviation SD) = 3.6] and 474 middle-aged US males (μ_age = 56.1_{SD = 2.6} ) of predominately Anglo-Saxon ancestry with complete substance use and imaging data. Subjects with a history of stroke or traumatic brain injury were excluded.

Measurements: Magnetic resonance imaging (MRI) and volumetric segmentation methods were used to estimate volume in seven subcortical ROIs: thalamus, caudate nucleus, putamen, pallidum, hippocampus, amygdala and nucleus accumbens. Substance use measurements included maximum nicotine and alcohol use, total life-time multi-substance use, maximum cannabis use in the young adults and regular cannabis use in the middle-aged males.

Findings: After correcting for multiple testing (P = 0.007), cannabis use was unrelated to any subcortical ROI. However, maximum nicotine use was associated with significantly smaller thalamus volumes in middle-aged males.

Conclusions: In exploratory analyses based on young adult and middle-aged samples, normal variation in cannabis use is unrelated statistically to individual differences in brain morphology as measured by subcortical volume.

Keywords: Brain volume; cannabis use; grey matter; imaging; multi-substance use; subcortical.

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Conflict of interest statement

Competing interests

We declare no competing interests defined as those of a financial nature that, through their potential influence on behavior or content, or from perception of such potential influences, which could undermine the objectivity, integrity or perceived value of this publication.

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References

1. Substance Abuse and Mental Health Services Administration. Results from the 2012 National Survey on Drug Use and Health: Summary of National Findings, Rockville, MD: NSDUH; Series H-46, HHS Publication No. (SMA) 13–4795; 2012.
1. Bava S , Tapert SF Adolescent brain development and the risk for alcohol and other drug problems, Neuropsychol Rev 2010: 20: 398–413. - PMC - PubMed
1. Compton WM , Thomas YF , Stinson FS , Grant BF Prevalence, correlates, disability, and comorbidity of DSM-IV drug abuse and dependence in the United States: results from the national epidemiologic survey on alcohol and related conditions, Arch Gen Psychiatry 2007: 64: 566–576. - PubMed
1. Silins E , Horwood LJ , Patton GC , Fergusson DM , Olsson CA , Hutchinson DM et al. Young adult sequelae of adolescent cannabis use: an integrative analysis, Lancet Psychiatry 2014: 1: 286–293. - PubMed
1. Lyons MJ , Bar JL , Panizzon MS , Toomey R , Eisen S , Xian H et al. Neuropsychological consequences of regular marijuana use: a twin study, Psychol Med 2004: 34: 1239–1250. - PubMed

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Testing associations between cannabis use and subcortical volumes in two large population-based samples

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Testing associations between cannabis use and subcortical volumes in two large population-based samples

Authors

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Abstract

Conflict of interest statement

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