Cannabidiol-Induced Recovery of Social Behaviour in Mouse Models of Syndromic Autism

Cannabidiol-Induced Recovery of Social Behaviour in Mouse Models of Syndromic Autism | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Cannabidiol-Induced Recovery of Social Behaviour in Mouse Models of Syndromic Autism Michael Parkhill, Samantha L. Baglot, Vern Lewis, Brandon Rodrigue, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6683632/v2 This work is licensed under a CC BY 4.0 License Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Abstract Despite the growing prevalence of autism, no pharmacological interventions have been approved for core symptoms. The endocannabinoid system (ECS) has recently gained interest as a potential target for treating autism. Cannabidiol (CBD), a compound found in Cannabis sativa , is a potential treatment due to its tolerability and promising early results in fragile X syndrome patients. Here, we aimed to evaluate CBD’s efficacy in treating social deficits and restrictive/repetitive behaviours in Shank3 and Fmr1 knockout (KO) mice. Male and female mice were tested in the 3-chamber social apparatus or for self-grooming and in the open field (baseline), followed by five daily treatments with vehicle or CBD (s.c., 5 mg/kg for males, 50 mg/kg for females), and retested post-treatment. At baseline and following vehicle treatment, male and female Shank3 and Fmr1 KO mice exhibited deficits in social novelty, which were restored to control levels following CBD administration. Meanwhile, self-grooming (increased in Shank3 KO mice) and open-field exploration (decreased locomotion in Shank3 KO mice) were not affected by CBD. Females had hippocampal CBD levels ~ 11.6 times higher than males (consistent with dosing) and exhibited elevated anandamide (AEA) levels in CBD-treated groups. Transcriptomic analysis of the hippocampus revealed few sex- and strain-specific differentially expressed genes (DEGs) and only three mRNAs regulated by CBD ( Vwf and Lcn2 in females and Grm2 in Shank3 KO mice). These findings highlight the potential for CBD as a treatment for social deficits in syndromic autism and indicate that the therapeutic effect may be driven by dose-, sex-, or strain-specific mechanisms. Full Text Additional Declarations The authors declare potential competing interests as follows: Mr. Keith Woefel is the Director of Research Development at Caliper Foods, who supplied the CBD preparation for this study. Dr. Gabriella Gobbi is the inventor of patents on selective melatonin compounds and the Founder of Cosmas Therapeutics. She is also the inventor of a patent on the use of LSD, which was licensed out to Diamond Therapeutics. Her lab received research grants from Diamond Therapeutics. Dr. Argel Aguilar-Valles is a scientific advisor for BetterLife Pharma, and his lab had a research contract with Gilgamesh Pharma. The remaining authors declare that they have no conflicts of interest to disclose. Cite Share Download PDF Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6683632","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":554276503,"identity":"4fa12712-bdaa-4d85-9ff2-a4057c11bb4e","order_by":0,"name":"Michael Parkhill","email":"","orcid":"","institution":"Carleton University","correspondingAuthor":false,"prefix":"","firstName":"Michael","middleName":"","lastName":"Parkhill","suffix":""},{"id":554276505,"identity":"3832c057-9304-4c53-ab72-1f0c920cb4d9","order_by":1,"name":"Samantha L. 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Dr. Gabriella Gobbi is the inventor of patents on selective melatonin compounds and the Founder of Cosmas Therapeutics. She is also the inventor of a patent on the use of LSD, which was licensed out to Diamond Therapeutics. Her lab received research grants from Diamond Therapeutics. Dr. Argel Aguilar-Valles is a scientific advisor for BetterLife Pharma, and his lab had a research contract with Gilgamesh Pharma. The remaining authors declare that they have no conflicts of interest to disclose.","formattedTitle":"Cannabidiol-Induced Recovery of Social Behaviour in Mouse Models of Syndromic Autism","fulltext":[],"fulltextSource":"","fullText":"","funders":[{"identity":"37f91020-d3c5-491e-8465-470f773939dc","identifier":"10.13039/501100000024","name":"Canadian Institutes of Health Research","awardNumber":"N/A","order_by":0}],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Carleton University","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6683632/v2","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6683632/v2","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eDespite the growing prevalence of autism, no pharmacological interventions have been approved for core symptoms. The endocannabinoid system (ECS) has recently gained interest as a potential target for treating autism. Cannabidiol (CBD), a compound found in \u003cem\u003eCannabis sativa\u003c/em\u003e, is a potential treatment due to its tolerability and promising early results in fragile X syndrome patients. Here, we aimed to evaluate CBD\u0026rsquo;s efficacy in treating social deficits and restrictive/repetitive behaviours in \u003cem\u003eShank3\u003c/em\u003e and \u003cem\u003eFmr1\u003c/em\u003e knockout (KO) mice. Male and female mice were tested in the 3-chamber social apparatus or for self-grooming and in the open field (baseline), followed by five daily treatments with vehicle or CBD (s.c., 5 mg/kg for males, 50 mg/kg for females), and retested post-treatment. At baseline and following vehicle treatment, male and female \u003cem\u003eShank3\u003c/em\u003e and \u003cem\u003eFmr1\u003c/em\u003e KO mice exhibited deficits in social novelty, which were restored to control levels following CBD administration. Meanwhile, self-grooming (increased in \u003cem\u003eShank3\u003c/em\u003e KO mice) and open-field exploration (decreased locomotion in Shank3 KO mice) were not affected by CBD. Females had hippocampal CBD levels\u0026thinsp;~\u0026thinsp;11.6 times higher than males (consistent with dosing) and exhibited elevated anandamide (AEA) levels in CBD-treated groups. Transcriptomic analysis of the hippocampus revealed few sex- and strain-specific differentially expressed genes (DEGs) and only three mRNAs regulated by CBD (\u003cem\u003eVwf\u003c/em\u003e and \u003cem\u003eLcn2\u003c/em\u003e in females and \u003cem\u003eGrm2\u003c/em\u003e in Shank3 KO mice). These findings highlight the potential for CBD as a treatment for social deficits in syndromic autism and indicate that the therapeutic effect may be driven by dose-, sex-, or strain-specific mechanisms.\u003c/p\u003e","manuscriptTitle":"Cannabidiol-Induced Recovery of Social Behaviour in Mouse Models of Syndromic Autism","msid":"","msnumber":"","nonDraftVersions":[{"code":2,"date":"2025-12-17 14:32:06","doi":"10.21203/rs.3.rs-6683632/v2","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2025-05-22 13:15:50","doi":"10.21203/rs.3.rs-6683632/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0f46a179-86bb-44f4-8ca5-66bcdbd2f908","owner":[],"postedDate":"December 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-05-22T13:15:51+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-17 14:32:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v2","identity":"rs-6683632","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6683632","identity":"rs-6683632","version":["v2"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}