Yann Chye1, Nadia Solowij2, Chao Suo1, Albert Batalla3,4, Janna Cousijn5, Anna E Goudriaan6,7, Rocio Martin-Santos4, Sarah Whittle8, Valentina Lorenzetti9,10,11, Murat Yücel12. 1. Brain and Mental Health Laboratory, Monash Institute of Cognitive and Clinical Neurosciences, School of Psychological Sciences, Monash University, Melbourne, Australia. 2. School of Psychology and Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, Australia. 3. Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands. 4. Department of Psychiatry and Psychology, Hospital Clinic, IDIBAPS, CIBERSAM and Institute of Neuroscience, University of Barcelona, Barcelona, Spain. 5. Department of Developmental Psychology, University of Amsterdam, Amsterdam, The Netherlands. 6. Department of Psychiatry, Amsterdam Institute for Addiction Research, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. 7. Arkin Mental Health Care, Amsterdam, The Netherlands. 8. Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Melbourne, Australia. 9. Brain and Mental Health Laboratory, Monash Institute of Cognitive and Clinical Neurosciences, School of Psychological Sciences, Monash University, Melbourne, Australia. vlor@liv.ac.uk. 10. Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Melbourne, Australia. vlor@liv.ac.uk. 11. School of Psychological Sciences, Institute of Psychology, Health and Society, The University of Liverpool, Liverpool, UK. vlor@liv.ac.uk. 12. Brain and Mental Health Laboratory, Monash Institute of Cognitive and Clinical Neurosciences, School of Psychological Sciences, Monash University, Melbourne, Australia. murat.yucel@monash.edu.
Abstract
RATIONALE: Cannabis (CB) use and dependence are associated with regionally specific alterations to brain circuitry and substantial psychosocial impairment. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
RATIONALE: Cannabis (CB) use and dependence are associated with regionally specific alterations to brain circuitry and substantial psychosocial impairment. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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