Transcriptomic and Functional Responses of Human Airway Cells to Vaped ∆8-THC and its Oxidation Product ∆8-THCQ

Transcriptomic and Functional Responses of Human Airway Cells to Vaped ∆8-THC and its Oxidation Product ∆8-THCQ | 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 Article Transcriptomic and Functional Responses of Human Airway Cells to Vaped ∆8-THC and its Oxidation Product ∆8-THCQ Charlotte Love, Hye-Young Kim, Julia Rager, Keri Tallman, Kevin Schichlein, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8790511/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 12 You are reading this latest preprint version Abstract Δ8tetrahydrocannabinol (Δ8THC) products have expanded rapidly since the 2018 Farm Bill, yet they remain largely unregulated despite containing high cannabinoid levels, additives, and contaminants, and growing evidence of respiratory risks. We identify the reactive electrophile Δ8THC quinone (Δ8THCQ, HU336) as a major constituent of commercial Δ8THC distillates and disposable vape products, with concentrations increasing substantially after vaping. Across highpotency products, Δ8THCQ rose an average of 3.67fold, reaching millimolar levels. While Δ8THC alone elicited no detectable transcriptomic response in a bronchial epithelial cell line, Δ8THCQ caused marked geneexpression changes, activating ciliarelated, stressresponse, xenobioticmetabolism, and inflammatory pathways. Using primary differentiated human bronchial epithelial cells and the UNC Vaping Product Exposure System (VaPES), we found that aerosols from commercial Δ8THC mixtures rapidly induced immediateearly stress genes, suppressed ribosomal and mitochondrial programs, and activated fibrosislinked signaling. In contrast, Δ8THCcontaining “juice” products had milder effects, mainly upregulating cellcycle and proliferation pathways. Computational analyses linked the chemical composition of Δ8THC aerosols to distinct transcriptional responses, identifying clusters of compounds driving specific airway effects. Functionally, distillate and disposable aerosols impaired motilecilia activity. Collectively, these findings indicate that vaping generates substantial Δ8THCQ and suggest that repeated inhalation may disrupt mucociliary defense and promote chronic airway injury. Biological sciences/Cell biology Health sciences/Diseases Biological sciences/Molecular biology Full Text Additional Declarations No competing interests reported. Supplementary Files SupplementDelta8VapingSciRep1.docx SupplementalTablesDelta8VapingSciRep.xlsx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 13 Apr, 2026 Reviews received at journal 27 Mar, 2026 Reviews received at journal 20 Mar, 2026 Reviews received at journal 10 Mar, 2026 Reviewers agreed at journal 05 Mar, 2026 Reviewers agreed at journal 05 Mar, 2026 Reviewers agreed at journal 26 Feb, 2026 Reviewers invited by journal 24 Feb, 2026 Editor assigned by journal 24 Feb, 2026 Editor invited by journal 24 Feb, 2026 Submission checks completed at journal 22 Feb, 2026 First submitted to journal 22 Feb, 2026 You are reading this latest preprint version 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-8790511","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":596593480,"identity":"875d36db-d7aa-4328-8dbe-02dfc3500e57","order_by":0,"name":"Charlotte Love","email":"","orcid":"","institution":"University of North Carolina at Chapel Hill","correspondingAuthor":false,"prefix":"","firstName":"Charlotte","middleName":"","lastName":"Love","suffix":""},{"id":596593481,"identity":"cb19b7cc-1727-44aa-8529-86c3a5b039d0","order_by":1,"name":"Hye-Young Kim","email":"","orcid":"","institution":"Vanderbilt University","correspondingAuthor":false,"prefix":"","firstName":"Hye-Young","middleName":"","lastName":"Kim","suffix":""},{"id":596593482,"identity":"01152b67-e342-4b7e-85ed-229ef83ab268","order_by":2,"name":"Julia Rager","email":"","orcid":"","institution":"University of North Carolina at Chapel Hill","correspondingAuthor":false,"prefix":"","firstName":"Julia","middleName":"","lastName":"Rager","suffix":""},{"id":596593483,"identity":"18e2f48f-9040-498c-9d9a-9f4ef3d5c18c","order_by":3,"name":"Keri Tallman","email":"","orcid":"","institution":"Vanderbilt University","correspondingAuthor":false,"prefix":"","firstName":"Keri","middleName":"","lastName":"Tallman","suffix":""},{"id":596593484,"identity":"5bd29716-85a8-4be1-95e8-0f6ed622c7bd","order_by":4,"name":"Kevin Schichlein","email":"","orcid":"","institution":"University of North Carolina at Chapel Hill","correspondingAuthor":false,"prefix":"","firstName":"Kevin","middleName":"","lastName":"Schichlein","suffix":""},{"id":596593485,"identity":"eaefb275-c1f3-4270-b68a-6b08e51078a9","order_by":5,"name":"Ned Porter","email":"","orcid":"","institution":"Vanderbilt University","correspondingAuthor":false,"prefix":"","firstName":"Ned","middleName":"","lastName":"Porter","suffix":""},{"id":596593486,"identity":"3ecb5ac1-1f5f-4f08-ab7c-6748dc567edd","order_by":6,"name":"Ilona Jaspers","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABBElEQVRIiWNgGAWjYBACNnYIBeVWAPEBCJOxAZcWZhQtZ4jQwsCMzGFsI0ILHzPzsQc/GPjk5Wc3H/v4c942Ob4DPGZAERvZDQdwOYwt3bCHgc1ww51jybN5t902ljzAYw4USTPGrYXHTIKHgY1xg0SOMTPjttuJG4C2SDMwHE7Ep0XyDwOb/fwZ+Z8Zf865XQ/V8h+vFmmgLYkNN3KYGXgbbicYQLQcwKOFLU1ahoEtGegXY2aeY7cNZx5mK5PsMUg2nolDi3x78zHJNwzHbOfPbn7M+KPmtjzf8eZtEj8q7GT7cGgBA8Z/xxgYJGA8cEwZ4FEOATVIWkbBKBgFo2AUoAEA1MBUVWWKeW8AAAAASUVORK5CYII=","orcid":"","institution":"University of North Carolina at Chapel Hill","correspondingAuthor":true,"prefix":"","firstName":"Ilona","middleName":"","lastName":"Jaspers","suffix":""}],"badges":[],"createdAt":"2026-02-04 22:08:54","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8790511/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8790511/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104397936,"identity":"71c26135-dfce-46c6-a507-4cd524b24837","added_by":"auto","created_at":"2026-03-11 11:58:56","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1550815,"visible":true,"origin":"","legend":"","description":"","filename":"ManuscriptDelta8VapingSciRep02222026.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8790511/v1_covered_92af27f0-3bca-49c8-a4c5-426b313cab72.pdf"},{"id":103496608,"identity":"06b41818-9210-480b-bc93-cec6a2bf7e33","added_by":"auto","created_at":"2026-02-26 11:14:19","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":7715767,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementDelta8VapingSciRep1.docx","url":"https://assets-eu.researchsquare.com/files/rs-8790511/v1/1b0ea04d5b182bd9782edd1e.docx"},{"id":103496607,"identity":"ff28749e-a612-4bca-a44d-8fa4bd76d655","added_by":"auto","created_at":"2026-02-26 11:14:19","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":349079,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalTablesDelta8VapingSciRep.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-8790511/v1/4d16f6f51c7792840a1b4b38.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Transcriptomic and Functional Responses of Human Airway Cells to Vaped ∆8-THC and its Oxidation Product ∆8-THCQ","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8790511/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8790511/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Δ8tetrahydrocannabinol (Δ8THC) products have expanded rapidly since the 2018 Farm Bill, yet they remain largely unregulated despite containing high cannabinoid levels, additives, and contaminants, and growing evidence of respiratory risks. We identify the reactive electrophile Δ8THC quinone (Δ8THCQ, HU336) as a major constituent of commercial Δ8THC distillates and disposable vape products, with concentrations increasing substantially after vaping. Across highpotency products, Δ8THCQ rose an average of 3.67fold, reaching millimolar levels. While Δ8THC alone elicited no detectable transcriptomic response in a bronchial epithelial cell line, Δ8THCQ caused marked geneexpression changes, activating ciliarelated, stressresponse, xenobioticmetabolism, and inflammatory pathways. Using primary differentiated human bronchial epithelial cells and the UNC Vaping Product Exposure System (VaPES), we found that aerosols from commercial Δ8THC mixtures rapidly induced immediateearly stress genes, suppressed ribosomal and mitochondrial programs, and activated fibrosislinked signaling. In contrast, Δ8THCcontaining “juice” products had milder effects, mainly upregulating cellcycle and proliferation pathways. Computational analyses linked the chemical composition of Δ8THC aerosols to distinct transcriptional responses, identifying clusters of compounds driving specific airway effects. Functionally, distillate and disposable aerosols impaired motilecilia activity. Collectively, these findings indicate that vaping generates substantial Δ8THCQ and suggest that repeated inhalation may disrupt mucociliary defense and promote chronic airway injury.","manuscriptTitle":"Transcriptomic and Functional Responses of Human Airway Cells to Vaped ∆8-THC and its Oxidation Product ∆8-THCQ","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-26 11:14:14","doi":"10.21203/rs.3.rs-8790511/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-13T04:06:38+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-27T07:35:03+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-20T23:58:57+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-10T14:56:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"331530240077028357092364946503940479095","date":"2026-03-05T18:27:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"245511110349161203316031970483438287914","date":"2026-03-05T14:27:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"232498228688637824087207020929711668079","date":"2026-02-26T15:19:04+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-24T17:04:13+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-24T16:59:24+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-24T05:35:19+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-22T15:15:01+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2026-02-22T14:51:56+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6818c9f9-7005-45cd-ad05-a3d808a54a60","owner":[],"postedDate":"February 26th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":63480110,"name":"Biological sciences/Cell biology"},{"id":63480111,"name":"Health sciences/Diseases"},{"id":63480112,"name":"Biological sciences/Molecular biology"}],"tags":[],"updatedAt":"2026-05-12T05:24:14+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-26 11:14:14","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8790511","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8790511","identity":"rs-8790511","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}