{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T09:47:24Z","timestamp":1782380844625,"version":"3.54.5"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T00:00:00Z","timestamp":1780704000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T00:00:00Z","timestamp":1780704000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"Canopy Growth Corporation","award":["Canopy Growth Corporation"],"award-info":[{"award-number":["Canopy Growth Corporation"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Forensic Toxicol"],"published-print":{"date-parts":[[2026,7]]},"DOI":"10.1007\/s11419-026-00772-5","type":"journal-article","created":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T09:34:24Z","timestamp":1780738464000},"page":"437-444","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolite patterns in human urine after oral administration of highly purified \u03948-THCV"],"prefix":"10.1007","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8095-612X","authenticated-orcid":false,"given":"Cristina","family":"Sempio","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Campos-Palomino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Klawitter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica N.","family":"Peters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"MacNair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Haghdoost","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"Bonn-Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Harrison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanna","family":"Babalonis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilyn A.","family":"Huestis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Christians","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jost","family":"Klawitter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,6]]},"reference":[{"issue":"1","key":"772_CR1","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/s42238-020-0016-7","volume":"31","author":"A Abioye","year":"2020","unstructured":"Abioye A, Ayodele O, Marinkovic A, Patidar R, Akinwekomi A, Sanyaolu A (2020) \u22069-Tetrahydrocannabivarin (THCV): a commentary on potential therapeutic benefit for the management of obesity and diabetes. J Cannabis Res Jan 31(1):6. https:\/\/doi.org\/10.1186\/s42238-020-0016-7 PMID: 33526143; PMCID: PMC7819335","journal-title":"J Cannabis Res Jan"},{"issue":"8","key":"772_CR2","doi-asserted-by":"publisher","first-page":"2450","DOI":"10.1111\/j.1476-5381.2011.01410.x","volume":"165","author":"S B\u00e1tkai","year":"2012","unstructured":"B\u00e1tkai S, Mukhopadhyay P, Horv\u00e1th B, Rajesh M, Gao RY, Mahadevan A, Amere M, Battista N, Lichtman AH, Gauson LA, Maccarrone M, Pertwee RG, Pacher P (2012) \u22068-Tetrahydrocannabivarin prevents hepatic ischaemia\/reperfusion injury by decreasing oxidative stress and inflammatory responses through cannabinoid CB2 receptors. Br J Pharmacol Apr 165(8):2450\u20132461. https:\/\/doi.org\/10.1111\/j.1476-5381.2011.01410.x PMID: 21470208; PMCID: PMC3423240","journal-title":"Br J Pharmacol Apr"},{"key":"772_CR3","doi-asserted-by":"publisher","unstructured":"Peters EN, MacNair L, Harrison A, Feldner MT, Eglit GML, Babalonis S, Turcotte C, Bonn-Miller MO (2023) A Two-Phase, Dose-Ranging, Placebo-Controlled Study of the Safety and Preliminary Test of Acute Effects of Oral \u22068-Tetrahydrocannabivarin in Healthy Participants. Cannabis Cannabinoid Res. Sep;8(S1):S71-S82. https:\/\/doi.org\/10.1089\/can.2023.0038. PMID: 37721990","DOI":"10.1089\/can.2023.0038"},{"key":"772_CR4","doi-asserted-by":"publisher","unstructured":"Mehmedic Z, Chandra S, Slade D, Denham H, Foster S, Patel AS, Ross SA, Khan IA, ElSohly MA (2010) Potency trends of \u22069-THC and other cannabinoids in confiscated cannabis preparations from 1993 to 2008. J Forensic Sci. Sep;55(5):1209-17. https:\/\/doi.org\/10.1111\/j.1556-4029.2010.01441.x. PMID: 20487147","DOI":"10.1111\/j.1556-4029.2010.01441.x"},{"key":"772_CR5","doi-asserted-by":"publisher","unstructured":"Haghdoost M, L\u00f3pez de Los Santos Y, Brunstetter M, Ferretti ML, Roberts M, Bonn-Miller MO (2024) Using In Silico Molecular Docking to Explain Differences in Receptor Binding Behavior of HHC and THCV Isomers: Revealing New Binding Modes. Pharmaceuticals (Basel). May 15;17(5):637. https:\/\/doi.org\/10.3390\/ph17050637. PMID: 38794207; PMCID: PMC11125018","DOI":"10.3390\/ph17050637"},{"issue":"8","key":"772_CR6","doi-asserted-by":"publisher","first-page":"1770","DOI":"10.1002\/cbdv.200790152","volume":"4","author":"MA Huestis","year":"2007","unstructured":"Huestis MA (2007) Human cannabinoid pharmacokinetics. Chem Biodivers 4(8):1770\u20131804. https:\/\/doi.org\/10.1002\/cbdv.200790152","journal-title":"Chem Biodivers"},{"key":"772_CR7","doi-asserted-by":"publisher","unstructured":"Muir LS, Doumit SE, Seither JZ, Knittel JL, Walterscheid JP, Karschner EL (2025) Comprehensive LC-MS-MS analysis of THC isomers, analogs, homologs, and metabolites in blood and urine. J Anal Toxicol. May 16;49(5):322\u2013331. https:\/\/doi.org\/10.1093\/jat\/bkaf023. PMID: 40098275","DOI":"10.1093\/jat\/bkaf023"},{"key":"772_CR8","doi-asserted-by":"publisher","unstructured":"Rosano TG, Cooper JA, Scholz KL, Wood M (2023) Confirmation of cannabinoids in forensic toxicology casework by isomer-selective UPLC-MS-MS analysis in urine. J Anal Toxicol. Nov 1;47(8):709\u2013718. https:\/\/doi.org\/10.1093\/jat\/bkad048. PMID: 37540526","DOI":"10.1093\/jat\/bkad048"},{"key":"772_CR9","doi-asserted-by":"publisher","first-page":"123568","DOI":"10.1016\/j.jchromb.2022.123568","volume":"1","author":"YE Sim","year":"2023","unstructured":"Sim YE, Kim JW, Ko BJ, Kim JY, Cheong JC, Pyo J (2023) Determination of urinary metabolites of cannabidiol, \u22068-tetrahydrocannabinol, and \u22069-tetrahydrocannabinol by automated online \u00b5SPE-LC-MS\/MS method. J Chromatogr B Analyt Technol Biomed Life Sci Jan 1:1214:123568 Epub 2022 Dec 9. PMID: 36527808","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci Jan"},{"key":"772_CR10","doi-asserted-by":"publisher","unstructured":"Sempio C, Campos-Palomino J, Klawitter J, Harrison A, Peters EN, MacNair L, Haghdoost M, Bonn-Miller M, Babalonis S, Huestis MA, Christians U, Klawitter J (2024) LC-MS-MS quantification of \u22068-THC, \u22069-THC, THCV isomers and their main metabolites in human plasma. J Anal Toxicol. Aug 21;48(7):499\u2013506. https:\/\/doi.org\/10.1093\/jat\/bkae048. PMID: 38836589","DOI":"10.1093\/jat\/bkae048"},{"key":"772_CR11","doi-asserted-by":"publisher","unstructured":"ElSohly MA, Feng S, Murphy TP, Warrington AW, Ross S, Nimrod A, Mehmedic Z, Fortner N (2001) Identification and quantitation of 11-nor-delta9-tetrahydrocannabivarin-9-carboxylic acid, a major metabolite of delta9-tetrahydrocannabivarin. J Anal Toxicol. Sep;25(6):476\u2009\u2013\u200980. https:\/\/doi.org\/10.1093\/jat\/25.6.476. PMID: 11550824","DOI":"10.1093\/jat\/25.6.476"},{"issue":"23","key":"772_CR12","doi-asserted-by":"publisher","first-page":"6461","DOI":"10.1007\/s00216-016-9765-8","volume":"408","author":"M Andersson","year":"2016","unstructured":"Andersson M, Scheidweiler KB, Sempio C, Barnes AJ, Huestis MA (2016) Simultaneous quantification of 11 cannabinoids and metabolites in human urine by liquid chromatography tandem mass spectrometry using WAX-S tips. Anal Bioanal Chem Sep 408(23):6461\u20136471. https:\/\/doi.org\/10.1007\/s00216-016-9765-8 Epub 2016 Jul 15. PMID: 27422645; PMCID: PMC5010516","journal-title":"Anal Bioanal Chem Sep"},{"key":"772_CR13","doi-asserted-by":"publisher","unstructured":"Huestis MA, Sempio C, Newmeyer MN, Andersson M, Barnes AJ, Abulseoud OA, Blount BC, Schroeder J, Smith ML (2020) Free and Glucuronide Urine Cannabinoids after Controlled Smoked, Vaporized and Oral Cannabis Administration in Frequent and Occasional Cannabis Users. J Anal Toxicol. Oct 12;44(7):651\u2013660. https:\/\/doi.org\/10.1093\/jat\/bkaa046. PMID: 32369162; PMCID: PMC7673603","DOI":"10.1093\/jat\/bkaa046"},{"issue":"5","key":"772_CR14","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1097\/FTD.0000000000000427","volume":"39","author":"J Klawitter","year":"2017","unstructured":"Klawitter J, Sempio C, M\u00f6rlein S, De Bloois E, Klepacki J, Henthorn T, Leehey MA, Hoffenberg EJ, Knupp K, Wang GS, Hopfer C, Kinney G, Bowler R, Foreman N, Galinkin J, Christians U, Klawitter J (2017) An Atmospheric Pressure Chemical Ionization MS\/MS Assay Using Online Extraction for the Analysis of 11 Cannabinoids and Metabolites in Human Plasma and Urine. Ther Drug Monit Oct 39(5):556\u2013564. https:\/\/doi.org\/10.1097\/FTD.0000000000000427 PMID: 28640062; PMCID: PMC5600652","journal-title":"Ther Drug Monit Oct"},{"key":"772_CR15","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.clinbiochem.2021.09.005","volume":"98","author":"JD Reber","year":"2021","unstructured":"Reber JD, Karschner EL, Seither JZ, Knittel JL, Walterscheid JP (2021) Screening and confirmation methods for the qualitative identification of nine phytocannabinoids in urine by LC-MS\/MS. Clin Biochem Dec 98:54\u201362 Epub 2021 Sep 13. PMID: 34529995","journal-title":"Clin Biochem Dec"},{"key":"772_CR16","doi-asserted-by":"publisher","unstructured":"Sholler DJ, Zamarripa CA, Spindle TR, Martin EL, Kuntz D, Vandrey R, Grabenauer M (2022) Urinary Excretion Profile of Cannabinoid Analytes Following Acute Administration of Oral and Vaporized Cannabis in Infrequent Cannabis Users. J Anal Toxicol. Oct 14;46(8):882\u2013890. https:\/\/doi.org\/10.1093\/jat\/bkac042. Erratum in: J Anal Toxicol. 2022;46(8):e196. doi: 10.1093\/jat\/bkac052. PMID: 35770374; PMCID: PMC9995664","DOI":"10.1093\/jat\/bkac042"},{"key":"772_CR17","doi-asserted-by":"publisher","unstructured":"Vikingsson S, Winecker RE, Cone EJ, Kuntz DJ, Dorsey B, Jacques M, Senter M, Flegel RR, Hayes ED (2022) Prevalence of Cannabidiol, \u22069- and \u22068-Tetrahydrocannabinol and Metabolites in Workplace Drug Testing Urine Specimens. J Anal Toxicol. Oct 14;46(8):866\u2013874. https:\/\/doi.org\/10.1093\/jat\/bkac013. PMID: 35260906","DOI":"10.1093\/jat\/bkac013"},{"key":"772_CR18","doi-asserted-by":"publisher","unstructured":"Baird SN, Frazee CC, Garg U (2023) Evaluation of a Delta-9-Tetrahydrocannabinol Carboxylic Acid (\u22069-THC-COOH) Immunoassay and a Gas Chromatography-Mass Spectrometry (GC-MS) Method for the Detection of Delta-8-Tetrahydrocannabinol Carboxylic Acid (\u22068-THC-COOH). J Appl Lab Med. Jul 5;8(4):665\u2013673. https:\/\/doi.org\/10.1093\/jalm\/jfad017. PMID: 37071885","DOI":"10.1093\/jalm\/jfad017"},{"key":"772_CR19","doi-asserted-by":"publisher","unstructured":"Grafinger KE, Weinmann W (2021) Determination of the Cross-Reactivity of the Biological Metabolite (-)-trans-\u22069-Tetrahydrocannabinol-Carboxylic Acid-Glucuronide (THC-COOH-Gluc) for Cannabinoid Immunoassays. J Anal Toxicol. Mar 12;45(3):291\u2013296. https:\/\/doi.org\/10.1093\/jat\/bkaa063. PMID: 32518954","DOI":"10.1093\/jat\/bkaa063"},{"issue":"2","key":"772_CR20","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1002\/dta.3190","volume":"14","author":"A Helander","year":"2022","unstructured":"Helander A, Johansson M, Andersson A, Vill\u00e9n T (2022) Analytical and medico-legal problems linked to the presence of delta-8-tetrahydrocannabinol (delta-8-THC): Results from urine drug testing in Sweden. Drug Test Anal Feb; 14(2):371\u2013376. https:\/\/doi.org\/10.1002\/dta.3190 Epub 2021 Nov 10. PMID: 34734479","journal-title":"Drug Test Anal"},{"key":"772_CR21","doi-asserted-by":"publisher","unstructured":"Mullen LD, Hart ED, Vikingsson S, Winecker RE, Hayes E, Flegel R (2023) \u22068-THC-COOH cross-reactivity with cannabinoid immunoassay kits and interference in chromatographic testing methods. J Anal Toxicol. Sep 15;47(7):557\u2013562. https:\/\/doi.org\/10.1093\/jat\/bkad042. PMID: 37405696","DOI":"10.1093\/jat\/bkad042"},{"issue":"10","key":"772_CR22","doi-asserted-by":"publisher","first-page":"1122","DOI":"10.1002\/dta.3631","volume":"16","author":"VS Nair","year":"2024","unstructured":"Nair VS, Heybroek M, Boyle E, Rogers M, Campbell T, Eichner D, Hill K (2024) Prevalence of carboxy-\u22068-tetrahydrocannabiniol in antidoping samples. Drug Test Anal Oct 16(10):1122\u20131126. https:\/\/doi.org\/10.1002\/dta.3631 Epub 2024 Jan 4. PMID: 38176407","journal-title":"Drug Test Anal Oct"},{"key":"772_CR23","doi-asserted-by":"publisher","unstructured":"Wolf CE, Pokhai AA, Poklis JL, Williams GR (2023) The cross-reactivity of cannabinoid analogs (delta-8-THC, delta-10-THC and CBD), their metabolites and chiral carboxy HHC metabolites in urine of six commercially available homogeneous immunoassays. J Anal Toxicol. Nov 1;47(8):732\u2013736. https:\/\/doi.org\/10.1093\/jat\/bkad059. PMID: 37602947","DOI":"10.1093\/jat\/bkad059"},{"key":"772_CR24","doi-asserted-by":"publisher","unstructured":"Kroner GM, Johnson-Davis KL, Doyle K, McMillin GA (2020) Cannabinol (CBN) Cross-Reacts with Two Urine Immunoassays Designed to Detect Tetrahydrocannabinol (THC) Metabolite. J Appl Lab Med. May 1;5(3):569\u2013574. https:\/\/doi.org\/10.1093\/jalm\/jfaa020. PMID: 32445358","DOI":"10.1093\/jalm\/jfaa020"},{"key":"772_CR25","unstructured":"CLSI (2014) Liquid-chromatography- mass spectrometry methods. Approved guideline In: C62-A Cd, editor. Clinical and Laboratory Standards Institute. Wayne, PA"},{"key":"772_CR26","doi-asserted-by":"publisher","unstructured":"Matuszewski BK, Constanzer ML, Chavez-Eng CM (2003) Strategies for the assessment of matrix effect in quantitative bioanalytical methods based on HPLC-MS\/MS. Anal Chem. Jul 1;75(13):3019-30. https:\/\/doi.org\/10.1021\/ac020361s. PMID: 12964746","DOI":"10.1021\/ac020361s"},{"key":"772_CR27","unstructured":"U.S. Department of Health and Human, Services FDA, Center for Drug Evaluation and Research and Center for Veterinary Medicine (2020) Cannabis and Cannabis-Derived Compounds: Quality Considerations for Clinical Research - Guidance for Industry. 2020"},{"key":"772_CR28","unstructured":"U.S. Department of Health and Human Services FDA (2022) M10 Bioanalytical Method Validation and Study Sample Analysis. Guidance for Industry. November 7, 2022 Available from: https:\/\/www.fda.gov\/media\/162903\/download"},{"key":"772_CR29","doi-asserted-by":"crossref","unstructured":"Assanangkornchai S, Kalayasiri R, Ratta-Apha W, Tanaree A (2023) Effects of cannabis legalization on the use of cannabis and other substances. Curr Opin Psychiatry. Jul 1;36(4):283\u2013289. doi: 10.1097\/YCO.0000000000000868. Epub 2023 Mar 28. PMID: 37185310","DOI":"10.1097\/YCO.0000000000000868"},{"issue":"5","key":"772_CR30","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1089\/can.2021.0097","volume":"6","author":"S Babalonis","year":"2021","unstructured":"Babalonis S, Raup-Konsavage WM, Akpunonu PD, Balla A, Vrana KE (2021) \u22068-THC: Legal Status, Widespread Availability, and Safety Concerns. Cannabis Cannabinoid Res Oct 6(5):362\u2013365. https:\/\/doi.org\/10.1089\/can.2021.0097 PMID: 34662224; PMCID: PMC8664123","journal-title":"Cannabis Cannabinoid Res Oct"},{"key":"772_CR31","doi-asserted-by":"publisher","unstructured":"Gon\u00e7alves J, Rosado T, Soares S, Sim\u00e3o AY, Caramelo D, Lu\u00eds \u00c2, Fern\u00e1ndez N, Barroso M, Gallardo E, Duarte AP (2019) Cannabis and Its Secondary Metabolites: Their Use as Therapeutic Drugs, Toxicological Aspects, and Analytical Determination. Medicines (Basel). Feb 23;6(1):31. https:\/\/doi.org\/10.3390\/medicines6010031. PMID: 30813390; PMCID: PMC6473697","DOI":"10.3390\/medicines6010031"}],"container-title":["Forensic Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11419-026-00772-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11419-026-00772-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11419-026-00772-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T09:07:34Z","timestamp":1782378454000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11419-026-00772-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,6]]},"references-count":31,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["772"],"URL":"https:\/\/doi.org\/10.1007\/s11419-026-00772-5","relation":{},"ISSN":["1860-8965","1860-8973"],"issn-type":[{"value":"1860-8965","type":"print"},{"value":"1860-8973","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,6]]},"assertion":[{"value":"9 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"C.S., J.CP., Je.K., U.C. and Jo.K. are employees of the University of Colorado. At the time of the clinical study, E.N.P., L.MN., A.H., M.H. and M.BM. were employed by Canopy Growth Corporation and received stock options during employment. M.A.H. has no conflicts. E.N.P. has served as a consultant to Battelle and Charlotte\u2019s Web. M.BM. is an employee of Charlotte\u2019s Web and board member of DeFloria, LLC. M.H. is now an employee of Nalu Bio Inc. and a consultant to Charlotte\u2019s Web.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This clinical study was conducted in accordance with consensus ethics principles, International.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"This work was presented at the following professional meetings. 2023 SOFT annual meeting, 29 October \u2013 3 November, Denver, Colorado, USA. 60th Annual Meeting of the TIAFT, 27 August \u2013 1 September 2023, Rome, Italy.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Presentation"}},{"value":"No AI was used for the clinical study or the manuscript preparation.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"AI"}}]}}