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However, previous studies have demonstrated that excessive iron during early postnatal life induces oxidative reactions, leading to mitochondrial dysfunction and synaptic failure. These alterations compromise energy metabolism and neuronal integrity, contributing to long-lasting cognitive dysfunction and increased brain vulnerability later in life. This study evaluated the effects of cannabidiol (CBD) and cannabigerol (CBG) on behavioral, neuroinflammatory, and blood-brain barrier (BBB) outcomes in rats exposed to early-life iron overload. Male Wistar rats received iron carbonyl (30\u00a0mg\/kg, intragastrically) from postnatal day 12 to 14. At three months of age, they were treated intraperitoneally with CBD, CBG (both at 10\u00a0mg\/kg), or vehicle for 21 days. Cognitive performance was assessed in the open field and object recognition tasks. We examined hippocampal levels of interleukin-1 beta (IL-1\u03b2), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-\u03b1), as proinflammatory markers, and occludin, a protein known to regulate BBB permeability. Iron-exposed animals showed impaired recognition memory, with elevated TNF-\u03b1 and IL-1\u03b2, while CBD reversed memory deficits and reduced IL-1\u03b2 in iron-treated animals, without affecting TNF-\u03b1. CBG restored memory, decreased IL-1\u03b2 in both iron-treated and controls, and increased TNF-\u03b1 in controls. Also, iron overload reduced occludin expression in vehicle-treated rats which was reversed by both CBD and CBG. These findings highlight inflammation and BBB disruption as mediators of iron-induced cognitive dysfunction and show that both phytocannabinoids act through distinct but complementary mechanisms, supporting their therapeutic potential in neuroinflammation linked to iron overload.<\/jats:p>","DOI":"10.1007\/s12640-026-00826-x","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T05:16:20Z","timestamp":1787894180000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Differential Effects of Cannabidiol and Cannabigerol on Cognition, Neuroinflammation, and Blood\u2013Brain Barrier Integrity in a Rat Model of Iron Overload"],"prefix":"10.1007","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1767-8972","authenticated-orcid":false,"given":"Layza","family":"Kowalski","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5859-4065","authenticated-orcid":false,"given":"Anna C. 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Front Aging Neurosci. https:\/\/doi.org\/10.3389\/fnagi.2024.1485530","journal-title":"Front Aging Neurosci"}],"container-title":["Neurotoxicity Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12640-026-00826-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12640-026-00826-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12640-026-00826-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T19:02:12Z","timestamp":1793300532000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12640-026-00826-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,28]]},"references-count":42,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["826"],"URL":"https:\/\/doi.org\/10.1007\/s12640-026-00826-x","relation":{},"ISSN":["1029-8428","1476-3524"],"issn-type":[{"value":"1029-8428","type":"print"},{"value":"1476-3524","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,28]]},"assertion":[{"value":"12 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 August 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 August 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 August 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"JAC is a member of the International Advisory Board of the Australian Centre for Cannabinoid Clinical and Research Excellence (ACRE) \u2013 National Health and Medical Research Council (NHMRC). JAC and JEH have received travel support to attend scientific meetings and personal consultation fees from BSPG-Pharm. JAC, JEH and AWZ are coinventors of the patent \u201cFluorinated CBD compounds, compositions and uses thereof. Pub. No.: WO\/2014\/108899. International Application No.: PCT\/IL2014\/050023; Def. US Reg. No. 62\/193,296; July 29, 2015; INPI No. BR1120150164927 (Mechoulam R, Zuardi AW, Kapczinski F, Hallak JEC, Guimaraes FS, Crippa JAS, Breuer A). The Universidade de S\u00e3o Paulo (USP) has licensed this patent to Phytecs Pharm (USP Resolution No. 15.1.130002.1.1) and has an agreement with Prati-Donaduzzi to develop a pharmaceutical product containing synthetic CBD for epilepsy, schizophrenia, Parkinson\u2019s disease and anxiety disorders. JAC, JEH and AWZ are also coinventors of the patent \u201cCannabinoid-containing oral pharmaceutical composition, method for preparing and using same\u201d, INPI filed Sept 16 2016 (BR 112018005423-2). JAC has received personal consultation fees from EaseLabs, BSPG-Pharm and PurMed Global. JAC has received speaking fees from Torrent, Ach\u00e9, Green Care Store, Janssen and consultation\/speaking fees from EaseLabs.All other authors declare that they have no relevant financial or non-financial interests to disclose.\u00a0All other authors declare that they have no relevant financial or non-financial interests to disclose.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"48"}}