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Although cannabis and tobacco have distinct neurobiological actions, their associations with brain volumes are unclear. We aimed to review studies investigating cannabis use, tobacco use, their co\u2010use and brain volume and triangulate evidence across different study designs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic review and meta\u2010analysis preregistered on PROSPERO (CRD42022356982) and reported according to PRISMA 2020 guidelines. We searched SCOPUS, PubMed and PsycINFO up to 5 September 2024 for studies investigating cannabis use, tobacco use, co\u2010use and brain volume. Cross\u2010sectional, longitudinal and Mendelian randomisation studies were included. The outcome was brain volume of global, cortical and subcortical regions. We extracted adjusted and unadjusted estimates. Random effects meta\u2010analyses were stratified by exposure and study design across 33 brain regions. Risk of bias was assessed using a modified version of the Newcastle\u2010Ottawa scale.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Searches yielded 103 studies: 57 investigated cannabis use, 45 investigated tobacco use and one investigated tobacco and cannabis co\u2010use. Seventy\u2010seven studies were included in meta\u2010analysis (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200972\u2009798), 44 (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200918\u2009247) in the cross\u2010sectional cannabis analysis, 30 (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200951\u2009194) for tobacco cross\u2010sectional and four (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20093357) in the tobacco longitudinal analysis. Meta\u2010analysis of adjusted estimates from cross\u2010sectional studies (k denotes the number of independent studies) indicated smaller amygdala volumes [k\u2009=\u200917, g\u2009=\u20090.13, 95% confidence interval (CI) = 0.03, 0.23)] in people who use cannabis compared with controls. Relative to controls, people who smoked tobacco had smaller volumes in the amygdala (k\u2009=\u20095, g\u2009=\u20090.17, 95% CI = 0.04, 0.31), insula (k\u2009=\u20095, g\u2009=\u20090.17, 95% CI = 0.06, 0.27), pallidum (k\u2009=\u20095, g\u2009=\u20090.17, 95% CI = 0.13, 0.21) and total grey matter volume (TGMV) (k\u2009=\u20097, g\u2009=\u20090.17, 95% CI = 0.04, 0.30). Longitudinal studies indicated a larger decrease in TGMV in people who smoke tobacco (k\u2009=\u20095, g\u2009=\u20090.05, 95% CI = 0.01, 0.10) relative to controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Cannabis use appears to be associated with smaller volume in the amygdala. Tobacco use appears to be associated with smaller amygdala, insula, pallidum and total grey matter volume.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/add.70361","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T07:39:37Z","timestamp":1773905977000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Associations of cannabis use, tobacco use and co\u2010use with brain volume: A systematic review and meta\u2010analysis"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5194-0068","authenticated-orcid":false,"given":"Katherine","family":"Sawyer","sequence":"first","affiliation":[{"name":"Addiction and Mental Health Group University of Bath  Bath UK"},{"name":"Department of Addictions King's College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom P.","family":"Freeman","sequence":"additional","affiliation":[{"name":"Addiction and Mental Health Group University of Bath  Bath UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martine","family":"Skumlien","sequence":"additional","affiliation":[{"name":"Addiction and Mental Health Group University of Bath  Bath UK"},{"name":"Department of Addictions King's College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esther","family":"Walton","sequence":"additional","affiliation":[{"name":"Department of Psychology University of Bath  Bath UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Lancaster","sequence":"additional","affiliation":[{"name":"Department of Psychology University of Bath  Bath UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorien L.","family":"Treur","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Amsterdam University Medical Centre (UMC), Academic Medical Center (AMC)  Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5917-7068","authenticated-orcid":false,"given":"Valentina","family":"Lorenzetti","sequence":"additional","affiliation":[{"name":"Neuroscience of Addiction and Mental Health Program, Healthy Brain and Mind Research Centre Australian Catholic University  Fitzroy Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna K. 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