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          <jats:p>\n                    Cannabis was previously associated with worse memory function in men but not in women. As the hippocampus is crucial in the formation and retrieval of memory, we studied if cumulative exposure to cannabis is associated with differences in the hippocampal tissue volume, fractional anisotropy (FA) and cerebral brain perfusion (CBF) by MRI, overall and by sex, stratified by ever tobacco smoking, in multivariable adjusted linear regression models in both sexes. We included participants of the CARDIA cohort, followed since 1985, with cannabis assessed during each follow up. Categories of self-reported cumulative exposure were never, &lt;0.5, 0.5\u2013&lt;2, and &gt;2 cannabis-years, where 1 cannabis-year=365 days of use. We included 648 participants: 52% were women; mean age was 55 years, 86% reported ever using cannabis and 48% ever smoking tobacco. There was no difference in mean hippocampal volume according to greater cumulative use of cannabis. The coefficient of hippocampal volume in participants never smoking tobacco reporting &gt;2 cannabis-years was \u221237.99mm\n                    <jats:sup>3<\/jats:sup>\n                    (95% CI \u2212201.08\u2013125.09) compared to never users. There was no significant difference when stratifying by sex or ever tobacco exposure, or for FA or CBF. Cumulative cannabis exposure over 30 years was not associated with hippocampal volume, integrity or blood flow in middle age. The differences in memory function in cannabis users are likely not attributable to the hippocampus only. Future studies should assess further neuronal mechanisms and social determinants associated with cognition in cannabis users.\n                  <\/jats:p>","DOI":"10.1038\/s41398-026-04096-1","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T04:55:55Z","timestamp":1779166555000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cumulative exposure to cannabis and hippocampus MRI in middle age: results from the coronary artery risk development in young adults (CARDIA) study"],"prefix":"10.1038","volume":"16","author":[{"given":"Barbara","family":"Schilling","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baptiste","family":"Pasquier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5035-0370","authenticated-orcid":false,"given":"Martine","family":"Elbejjani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared","family":"Reis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamal S.","family":"Rana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2454-2560","authenticated-orcid":false,"given":"Kali","family":"Tal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3238-7612","authenticated-orcid":false,"given":"Lenore J.","family":"Launer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Baggio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Sidney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"Bryan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristine","family":"Yaffe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reto","family":"Auer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8429-3231","authenticated-orcid":false,"given":"Julian","family":"Jakob","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"4096_CR1","unstructured":"UNODC. 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The CARDIA study obtained the approval of institutional review boards at each study center (Oakland, Chicago, Minneapolis, and Birmingham). Informed consent was obtained from all participants. There are no identifiable images from human research participants in this manuscript.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services. We used no AI in this study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclaimer"}}],"article-number":"354"}}