, Volume 234, Issue 13, pp 1985–1995 | Cite as

Orbitofrontal and caudate volumes in cannabis users: a multi-site mega-analysis comparing dependent versus non-dependent users

  • Yann Chye
  • Nadia Solowij
  • Chao Suo
  • Albert Batalla
  • Janna Cousijn
  • Anna E. Goudriaan
  • Rocio Martin-Santos
  • Sarah Whittle
  • Valentina LorenzettiEmail author
  • Murat YücelEmail author
Original Investigation



Cannabis (CB) use and dependence are associated with regionally specific alterations to brain circuitry and substantial psychosocial impairment.


The objective of this study was to investigate the association between CB use and dependence, and the volumes of brain regions critically involved in goal-directed learning and behaviour—the orbitofrontal cortex (OFC) and caudate.


In the largest multi-site structural imaging study of CB users vs healthy controls (HC), 140 CB users and 121 HC were recruited from four research sites. Group differences in OFC and caudate volumes were investigated between HC and CB users and between 70 dependent (CB-dep) and 50 non-dependent (CB-nondep) users. The relationship between quantity of CB use and age of onset of use and caudate and OFC volumes was explored.


CB users (consisting of CB-dep and CB-nondep) did not significantly differ from HC in OFC or caudate volume. CB-dep compared to CB-nondep users exhibited significantly smaller volume in the medial and the lateral OFC. Lateral OFC volume was particularly smaller in CB-dep females, and reduced volume in the CB-dep group was associated with higher monthly cannabis dosage.


Smaller medial OFC volume may be driven by CB dependence-related mechanisms, while smaller lateral OFC volume may be due to ongoing exposure to cannabinoid compounds. The results highlight a distinction between cannabis use and dependence and warrant examination of gender-specific effects in studies of CB dependence.


Cannabis MRI Brain structure Orbitofrontal cortex Caudate Dependence Gender 



The Amsterdam sample was obtained with the support of grants from the Netherlands Organisation for Scientific Research–Health Research and Development, ZON-Mw grant #31180002 and an Amsterdam Brain Imaging Platform grant. The Barcelona sample was obtained with the support of grant PNSD:2011/050, Plan Nacional sobre Drogas. Ministerio de Sanidad y Política Social and grant SGR2014/1114, Generalitat de Catalunya, Spain. The Wollongong sample was obtained with the support of grants from the Clive and Vera Ramaciotti Foundation for Biomedical Research, and the Schizophrenia Research Institute with infrastructure funding from NSW Health. The Melbourne sample was obtained with the support of the National Health and Medical Research Council (NHMRC) of Australia Project Grant (#459111).

Compliance with ethical standards

This study was approved by the Monash University Human Research Ethics Committee. All participants provided written informed consent.

Conflict of interests

M.Y. was supported by a National Health and Medical Research Council of Australia Fellowship (App#1117188) and the David Winston Turner Endowment Fund. The authors declare that they have no conflict of interest.

Supplementary material

213_2017_4606_MOESM1_ESM.pdf (553 kb)
ESM 1 (PDF 553 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Yann Chye
    • 1
  • Nadia Solowij
    • 2
  • Chao Suo
    • 1
  • Albert Batalla
    • 3
    • 4
  • Janna Cousijn
    • 5
  • Anna E. Goudriaan
    • 6
    • 7
  • Rocio Martin-Santos
    • 4
  • Sarah Whittle
    • 8
  • Valentina Lorenzetti
    • 1
    • 8
    • 9
    Email author
  • Murat Yücel
    • 1
    Email author
  1. 1.Brain and Mental Health Laboratory, Monash Institute of Cognitive and Clinical Neurosciences, School of Psychological SciencesMonash UniversityMelbourneAustralia
  2. 2.School of Psychology and Illawarra Health and Medical Research InstituteUniversity of WollongongWollongongAustralia
  3. 3.Department of Psychiatry, Donders Institute for Brain, Cognition and BehaviourRadboud University Medical CentreNijmegenThe Netherlands
  4. 4.Department of Psychiatry and PsychologyHospital Clinic, IDIBAPS, CIBERSAM and Institute of Neuroscience, University of BarcelonaBarcelonaSpain
  5. 5.Department of Developmental PsychologyUniversity of AmsterdamAmsterdamThe Netherlands
  6. 6.Department of Psychiatry, Amsterdam Institute for Addiction Research, Academic Medical CentreUniversity of AmsterdamAmsterdamThe Netherlands
  7. 7.Arkin Mental Health CareAmsterdamThe Netherlands
  8. 8.Melbourne Neuropsychiatry Centre, Department of PsychiatryThe University of Melbourne and Melbourne HealthMelbourneAustralia
  9. 9.School of Psychological Sciences, Institute of Psychology, Health and SocietyThe University of LiverpoolLiverpoolUK

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