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Addict Biol. 2019 Jul;24(4):822-834. doi: 10.1111/adb.12652. Epub 2018 Jul 18.

Alteration to hippocampal volume and shape confined to cannabis dependence: a multi-site study.

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Brain and Mental Health Laboratory, Monash Institute of Cognitive and Clinical Neurosciences, School of Psychological Sciences, Monash University, Australia.
Melbourne Neuropsychiatry Centre with School of Psychology, Faculty of Health, Australian Catholic University, Australia.
Department of Psychological Sciences, Institute of Psychology, Health and Society, The University of Liverpool, UK.
Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, The Netherlands.
Department of Psychiatry and Psychology, Hospital Clinic, IDIBAPS, CIBERSAM and Institute of Neuroscience, University of Barcelona, Spain.
Department of Developmental Psychology, University of Amsterdam, The Netherlands.
Department of Psychiatry, Amsterdam Institute for Addiction Research, Academic Medical Centre, University of Amsterdam, The Netherlands.
Arkin Mental Health Care, The Netherlands.
FMRIB Centre, John Radcliffe Hospital, University of Oxford, UK.
Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne, Australia.
School of Psychology and Illawarra Health and Medical Research Institute, University of Wollongong, Australia.
The Australian Centre for Cannabinoid Clinical and Research Excellence (ACRE), Australia.


Cannabis use is highly prevalent and often considered to be relatively harmless. Nonetheless, a subset of regular cannabis users may develop dependence, experiencing poorer quality of life and greater mental health problems relative to non-dependent users. The neuroanatomy characterizing cannabis use versus dependence is poorly understood. We aimed to delineate the contributing role of cannabis use and dependence on morphology of the hippocampus, one of the most consistently altered brain regions in cannabis users, in a large multi-site dataset aggregated across four research sites. We compared hippocampal volume and vertex-level hippocampal shape differences (1) between 121 non-using controls and 140 cannabis users; (2) between 106 controls, 50 non-dependent users and 70 dependent users; and (3) between a subset of 41 controls, 41 non-dependent users and 41 dependent users, matched on sample characteristics and cannabis use pattern (onset age and dosage). Cannabis users did not differ from controls in hippocampal volume or shape. However, cannabis-dependent users had significantly smaller right and left hippocampi relative to controls and non-dependent users, irrespective of cannabis dosage. Shape analysis indicated localized deflations in the superior-medial body of the hippocampus. Our findings support neuroscientific theories postulating dependence-specific neuroadaptations in cannabis users. Future efforts should uncover the neurobiological risk and liabilities separating dependent and non-dependent use of cannabis.


MRI; brain; cannabis; dependence; hippocampus; neuroimaging; substance use


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