Sex and dependence related neuroanatomical differences in regular cannabis users: Findings from the ENIGMA Addiction Working Group

Maria Gloria Rossetti, Scott Mackey, Praveetha Patalay, Nicholas B Allen, Albert Batalla, Marcella Bellani, Yann Chye, Patricia Conrod, Janna Cousijn, Hugh Garavan, Anna E Goudriaan, Robert Hester, Rocio Martin-Santos, Nadia Solowij, Chao Suo, Paul M Thompson, Murat Yücel, Paolo Brambilla, Valentina Lorenzetti

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Males and females show different patterns of cannabis use and related psychosocial outcomes. However, the neuroanatomical substrates underlying such differences are poorly understood. The aim of this study was to map sex differences in the neurobiology (as indexed by brain volumes) of dependent and recreational cannabis use. We compared the volume of a priori regions of interest (i.e., amygdala, hippocampus, nucleus accumbens, insula, orbitofrontal cortex (OFC), anterior cingulate cortex and cerebellum) between 129 regular cannabis users (of whom 70 were recreational users and 59 cannabis dependent) and 114 controls recruited from the ENIGMA Addiction Working Group, accounting for intracranial volume, age, IQ, and alcohol and tobacco use. Dependent cannabis users, particularly females, had (marginally significant) smaller volumes of the lateral OFC and cerebellar white matter than recreational users and controls. In dependent (but not recreational) cannabis users, there was a significant association between female sex and smaller volumes of the cerebellar white matter and OFC. Volume of the OFC was also predicted by monthly standard drinks. No significant effects emerged the other brain regions of interest. Our findings warrant future multimodal studies that examine if sex and cannabis dependence are specific key drivers of neurobiological alterations in cannabis users. This, in turn, could help to identify neural pathways specifically involved in vulnerable cannabis users (e.g., females with cannabis dependence) and inform individually tailored neurobiological targets for treatment.

Original languageEnglish
Article number272
JournalTranslational Psychiatry
Issue number1
Publication statusPublished - 6 May 2021

Bibliographical note

Funding Information:
P.M.T. received partial grant support from Biogen, Inc. (Boston, USA) for research unrelated to this manuscript. M.Y. has received funding from several law firms in relation to expert witness reports. The other authors declare no conflicts of interest.

Funding Information:
P.M.T. was funded in part by NIH grants U54 EB020403, R01MH116147, and R56 AG058854. Data collection: A.E.G. received funding from ZonMW grant 91676084 from NWO. A.E.G. and J.C. received funding for the Cannabis Prospective study from ZonMW grant 31180002 from NWO. N.S. received funding from the Clive and Vera Ramaciotti Foundation for Biomedical Research National and Health and Medical Research Council Project grant 459111 and was supported by Australian Research Council Future Fellowship FT110100752. M.Y. was supported by National Health and Medical Research Council Fellowship 1117188 and the David Winston Turner Endowment Fund. V.L. was supported by The Australian Catholic University through a competitive scheme.

Publisher Copyright:
© 2021, The Author(s).


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