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

Nathan A Gillespie, Michael C Neale, Timothy C Bates, Lisa T Eyler, Christine Fennema-Notestine, Jasmin Vassileva, Michael J Lyons, Elizabeth C Prom-Wormley, Katie L McMahon, Paul M Thompson, Greig de Zubicaray, Ian B Hickie, John J McGrath, Lachlan T Strike, Miguel E Rentería, Matthew S Panizzon, Nicholas G. Martin, Carol E Franz, William S Kremen, Margaret J Wright

Research output: Contribution to journalArticlepeer-review


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: 622 young Australian adults (66% female; μage = 25.9, SD=3.6), and 474 middle-age U.S. males (μage = 56.1SD=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 lifetime multi-substance use, maximum cannabis use in the young adults, and regular cannabis use in the middle-age 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-age males.

CONCLUSIONS: In exploratory analyses based on young adult and middle age samples, normal variation in cannabis use is statistically unrelated to individual differences in brain morphology as measured by subcortical volume.
Original languageEnglish
Pages (from-to)1-12
Early online date24 Apr 2018
Publication statusPublished - Aug 2018


  • cannabis use
  • multi‐substance use
  • imaging
  • gray matter
  • subcortical
  • brain volume

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