Abstract
Cannabis Use Disorder (CUD) affects ~ 50 million individuals globally. CUD has been associated with adverse psychosocial outcomes, including affective flattening, apathy, and anhedonia, which prominent neuroscientific theories ascribe (in part) to altered integrity in brain reward pathways. Yet, emerging evidence from functional neuroimaging (fMRI) is mixed. We examined the activity in key regions-of-interest (ROIs) of the reward neurocircuitry in moderate-to-severe CUD vs. controls, and associations with cannabis use patterns in addition to Apathy Evaluation Scale scores. Brain reward function was examined in 57 people with moderate-to-severe CUD and 35 age and sex-matched controls using the Monetary Incentive Delay fMRI task. We compared brain function between groups, adjusting for age and sex, using exploratory whole-brain and hypothesis-driven ROI analyses in the ventral striatum, dorsal caudate, putamen, insula, cingulate, and orbitofrontal cortices. ROI analyses showed greater activity in the CUD vs. control group in bilateral insula and right putamen when receiving monetary wins vs. receiving neutral wins (i.e., outcomes with no monetary gain). The ROI analysis also showed greater activity in the CUD vs. controls in the right putamen when receiving monetary wins vs. receiving missed monetary wins. There were no other significant effects for the other ROIs, the whole-brain analyses, or brain-behaviour correlations. Overall, people with CUD showed altered activity in key brain reward regions during the receipt phase of rewards, compared to controls.
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Acknowledgements
We thank all participants for their contribution of data and time to the project. We acknowledge Ms Natalie DeBono, Dr Lisa-Marie Greenwood, Dr Leonie Duehlmeyer, and Dr Penny Hartman for their contribution to the management of the setting up of the project. We acknowledge Matthijs Vink for creating the Monetary Incentive Delay fMRI Task scripts for this study. We acknowledge Dr Alexandra Gaillard, Ms Marianna Quinones, Ms Stephanie Antopolous, Ms Claire Chua, Dr Leonie Duehlmeyer, Mr Lachlan Grant, Ms Kirsty Kearney, Dr Magdalena Kowalczyk, Ms Emily Robinson, Ms Elizabeth Sharp, and Ms Danielle Tichelaar, for their contribution to data collection. We acknowledge Professor Shanlin Fu and the team at the Drugs and Toxicology Group, Centre for Forensic Science, University of Technology Sydney, for conducting urine toxicology analyses.
Funding
Valentina 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 Addiction and Mental Health Program, Healthy Brain and Mind Research Centre, was supported via an ACU competitive scheme. Emillie Beyer, Hannah Thomson, and Hannah Sehl were funded by Australian Government Research Training Program (RTP) Stipend scholarships doi.org/10.82133/C42F-K220. 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.
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Ms Emillie Beyer reports no financial relationships with commercial interests. Dr Martine Skumlien reports no financial relationships with commercial interests. Dr Govinda Poudel is the founder, director and CTO of BrainCast Pty Ltd, which has developed novel brain imaging markers for monitoring brain injury. Arush Honnedevasthana Arun reports no financial relationships with commercial interests. Dr Eugene McTavish reports no financial relationships with commercial interests. Dr Hannah Thomson contracts for Syneos Health Learning Solutions, with the Insights and Evidence Generation Team in Patient Insights and Assessment Research (Implementation Science). Dr Hannah Sehl reports no financial relationships with commercial interests. Dr Rebecca Segrave reports no financial relationships with commercial interests. Dr Adam Clemente reports no financial relationships with commercial interests. Dr Izelle Labuschagne is the founder and director of Complete Thesis Support, which provides developmental programs for research students. Professor Peter Rendell reports no financial relationships with commercial interests. Associate Professor Gill Terrett reports no financial relationships with commercial interests. 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 Chao Suo reports no financial relationships with commercial interests. Professor Valentina Lorenzetti reports no financial relationships with commercial interests.
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Beyer, E., Skumlien, M., Poudel, G. et al. Brain reward function in people with moderate-to-severe cannabis use disorder who tried to cut down or quit: an fMRI study. Sci Rep (2026). https://doi.org/10.1038/s41598-026-50870-y
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DOI: https://doi.org/10.1038/s41598-026-50870-y
