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