{"paper_id":"1d63ccd0-e376-4da9-8ff0-b975a13c1db6","body_text":"ABSTRACT\nCannabis use disorder (CUD) affects ∼22M people globally and is characterised by difficulties in cutting down and quitting use, but the underlying neurobiology remains unclear. We examined resting-state functional connectivity (rsFC) between regions-of-interest (ROIs) of the addiction neurocircuitry and the rest of the brain in 65 individuals with moderate-to-severe CUD who reported attempts to cut down or quit, compared to 42 controls, and explored the association between rsFC and cannabis exposure and related problems, to elucidate potential drivers of rsFC alterations. The CUD group showed greater rsFC than controls between ROIs implicated in reward processing and habitual substance use (i.e., nucleus accumbens, putamen, pallidum) and occipito/parietal areas implicated in salience processing and disinhibition. Putamen-occipital rsFC correlated with levels of problematic cannabis use and depression symptoms. CUD appears to show neuroadaptations of the addiction neurocircuitry, previously demonstrated in other substance use disorders.\nCompeting Interest Statement\nDr Izelle Labuschagne is the founder and director of Complete Thesis Support, which provides developmental programs for research students. Dr Victoria Manning was the Founder, CEO, Director and a shareholder of Cognitive Training Solutions Pty Ltd between March 2021 and Aug 2023, which commercialised the SWiPE app which delivers Cognitive Bias Modification to reduce alcohol use. Dr Govinda Poudel is the founder, director and CTO of BrainCast Pty Ltd which has developed novel brain imaging markers for monitoring brain injury. Dr Hannah Thomson contracts for Syneos Health Learning Solutions, with the Insights and Evidence Generation Team in Patient Insights and Assessment Research (Implementation Science).\nClinical Trial\nISRCTN ID: 76056942\nFunding Statement\nValentina Lorenzetti was supported by an Al and Val Rosenstrauss Research Fellowship (2022-2026), and by a National Health & Medical Research Council (NHMRC) Investigator Grant (2023-2027, ID 2016833) and an Australian Catholic University competitive scheme. The work within the Neuroscience of Addition and Mental Health Program, Healthy Brain and Mind Research Centre was supported via an ACU competitive scheme. Hannah Thomson and Hannah Sehl were funded by Australian Government Research Training Program (RTP) Stipend scholarships. Victoria Manning has received funding from the National Health and Medical Research Council (NHMRC), VicHealth, Department of Health Victoria, the Victorian Responsible Gambling Foundation, the National Centre for Clinical Research on Emerging Drugs (NCCRED), HCF, and philanthropic organisations.\nAuthor Declarations\nI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.\nYes\nThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:\nThis cross-sectional, case-control study was nested within a larger, pre-registered project (ISRCTN ID: 76056942) and was approved by the Australian Catholic University Human Research and Ethics Committee (HREC:2019-71H).\nI confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.\nYes\nI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).\nYes\nI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.\nYes\nData Availability\nThe datasets generated during the current study will be available upon reasonable request from Dr Valentina Lorenzetti (Valentina.Lorenzetti{at}acu.edu.au), Principal Investigator. Data will include relevant group allocations and outcome variables and will be anonymised. Data will be available either as it is published, or on request (following completion of the data collection process, estimated end of 2021). A time limit will not be set on the duration of availability. Data will be shared with anyone who wishes to access it, for meta-analyses or other pre-approved purposes, via email. All participants provided informed consent. All data is de-identified.","source_license":"CC-BY-4.0","license_restricted":false}