{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T21:10:20Z","timestamp":1793913020896,"version":"4.8.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,10,29]],"date-time":"2022-10-29T00:00:00Z","timestamp":1667001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2022,10,29]],"date-time":"2022-10-29T00:00:00Z","timestamp":1667001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Adv Ther"],"published-print":{"date-parts":[[2023,1]]},"DOI":"10.1007\/s12325-022-02345-5","type":"journal-article","created":{"date-parts":[[2022,10,29]],"date-time":"2022-10-29T11:03:05Z","timestamp":1667041385000},"page":"282-293","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Examining the Systemic Bioavailability of Cannabidiol and Tetrahydrocannabinol from a Novel Transdermal Delivery System in Healthy Adults: A Single-Arm, Open-Label, Exploratory Study"],"prefix":"10.1007","volume":"40","clinical-trial-number":[{"clinical-trial-number":"nct05121506","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2975-2049","authenticated-orcid":false,"given":"Gyula","family":"Varadi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry D.","family":"Crowley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Moulin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajib","family":"Dey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin D.","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malkanthi","family":"Evans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,10,29]]},"reference":[{"issue":"3\u20134","key":"2345_CR1","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1300\/J175v01n03_09","volume":"1","author":"F Grotenhermen","year":"2001","unstructured":"Grotenhermen F. Harm reduction associated with inhalation and oral administration of cannabis and THC. J Cannabis Ther. 2001;1(3\u20134):133\u201352.","journal-title":"J Cannabis Ther"},{"key":"2345_CR2","first-page":"1","volume":"62","author":"K Light","year":"2021","unstructured":"Light K, Karboune S. Emulsion, hydrogel and emulgel systems and novel applications in cannabinoid delivery: a review. Crit Rev Food Sci Nutr. 2021;62:1\u201331.","journal-title":"Crit Rev Food Sci Nutr"},{"issue":"2","key":"2345_CR3","doi-asserted-by":"publisher","first-page":"438","DOI":"10.3390\/pharmaceutics14020438","volume":"14","author":"H Mahmoudinoodezh","year":"2022","unstructured":"Mahmoudinoodezh H, Telukutla SR, Bhangu SK, Bachari A, Cavalieri F, Mantri N. The transdermal delivery of therapeutic cannabinoids. Pharmaceutics. 2022;14(2):438.","journal-title":"Pharmaceutics"},{"issue":"10","key":"2345_CR4","doi-asserted-by":"publisher","first-page":"2478","DOI":"10.3390\/molecules23102478","volume":"23","author":"N Bruni","year":"2018","unstructured":"Bruni N, Della Pepa C, Oliaro-Bosso S, Pessione E, Gastaldi D, Dosio F. Cannabinoid delivery systems for pain and inflammation treatment. Molecules. 2018;23(10):2478.","journal-title":"Molecules"},{"issue":"8","key":"2345_CR5","doi-asserted-by":"publisher","first-page":"1770","DOI":"10.1002\/cbdv.200790152","volume":"4","author":"MA Huestis","year":"2007","unstructured":"Huestis MA. Human cannabinoid pharmacokinetics. Chem Biodivers. 2007;4(8):1770\u2013804.","journal-title":"Chem Biodivers"},{"key":"2345_CR6","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.forsciint.2017.01.008","volume":"272","author":"C Hess","year":"2017","unstructured":"Hess C, Kr\u00e4mer M, Madea B. Topical application of THC containing products is not able to cause positive cannabinoid finding in blood or urine. Forensic Sci Int. 2017;272:68\u201371.","journal-title":"Forensic Sci Int"},{"key":"2345_CR7","unstructured":"Gefion Canada. Technology Platform. 2020. https:\/\/www.gefioncanada.com\/technology-platform\/. Accessed April 2021."},{"issue":"15","key":"2345_CR8","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1186\/2050-6511-15-58","volume":"16","author":"N Solowij","year":"2014","unstructured":"Solowij N, Broyd SJ, van Hell HH, Hazekamp A. A protocol for the delivery of cannabidiol (CBD) and combined CBD and 9-tetrahydrocannabinol (THC) by vaporisation. BMC Pharmacol Toxicol. 2014;16(15):58.","journal-title":"BMC Pharmacol Toxicol"},{"issue":"6","key":"2345_CR9","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1111\/epi.12631","volume":"55","author":"O Devinsky","year":"2014","unstructured":"Devinsky O, Cilio MR, Cross H, Fernandez-Ruiz J, French J, Hill C, et\u00a0al. Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia. 2014;55(6):791\u2013802.","journal-title":"Epilepsia"},{"issue":"2","key":"2345_CR10","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1007\/s40262-014-0195-5","volume":"54","author":"JA Heuberger","year":"2015","unstructured":"Heuberger JA, Guan Z, Oyetayo O-O, Klumpers L, Morrison PD, Beumer TL, et\u00a0al. Population pharmacokinetic model of THC integrates oral, intravenous, and pulmonary dosing and characterizes short-and long-term pharmacokinetics. Clin Pharmacokinet. 2015;54(2):209\u201319.","journal-title":"Clin Pharmacokinet"},{"issue":"2","key":"2345_CR11","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1002\/bms.1200130206","volume":"13","author":"A Ohlsson","year":"1986","unstructured":"Ohlsson A, Lindgren JE, Andersson S, Agurell S, Gillespie H, Hollister LE. Single-dose kinetics of deuterium-labelled cannabidiol in man after smoking and intravenous administration. Biomed Environ Mass Spectrom. 1986;13(2):77\u201383.","journal-title":"Biomed Environ Mass Spectrom"},{"key":"2345_CR12","doi-asserted-by":"crossref","unstructured":"Barrus DG, Capogrossi KL, Cates SC, Gourdet CK, Peiper NC, Novak SP, et\u00a0al. Tasty THC: promises and challenges of cannabis edibles. Methods Rep RTI Press. 2016.","DOI":"10.3768\/rtipress.2016.op.0035.1611"},{"issue":"8","key":"2345_CR13","first-page":"49","volume":"14","author":"PM Patel","year":"2021","unstructured":"Patel PM, Lio PA. Safety and sourcing of topical cannabinoids: many questions, few answers. J Clin Aesthet Dermatol. 2021;14(8):49.","journal-title":"J Clin Aesthet Dermatol"},{"issue":"2","key":"2345_CR14","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/S0378-5173(02)00262-4","volume":"241","author":"PV Challapalli","year":"2002","unstructured":"Challapalli PV, Stinchcomb AL. In vitro experiment optimization for measuring tetrahydrocannabinol skin permeation. Int J Pharm. 2002;241(2):329\u201339.","journal-title":"Int J Pharm"},{"issue":"3","key":"2345_CR15","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1211\/0022357022791","volume":"56","author":"AL Stinchcomb","year":"2004","unstructured":"Stinchcomb AL, Valiveti S, Hammell DC, Ramsey DR. Human skin permeation of \u03948-tetrahydrocannabinol, cannabidiol and cannabinol. J Pharm Pharmacol. 2004;56(3):291\u20137.","journal-title":"J Pharm Pharmacol"},{"key":"2345_CR16","doi-asserted-by":"publisher","first-page":"1365","DOI":"10.3389\/fphar.2018.01365","volume":"9","author":"SA Millar","year":"2018","unstructured":"Millar SA, Stone NL, Yates AS, O\u2019Sullivan SE. A systematic review on the pharmacokinetics of cannabidiol in humans. Front Pharmacol. 2018;9:1365.","journal-title":"Front Pharmacol"},{"issue":"5","key":"2345_CR17","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1007\/s00228-012-1441-0","volume":"69","author":"CG Stott","year":"2013","unstructured":"Stott CG, White L, Wright S, Wilbraham D, Guy GW. A phase I study to assess the single and multiple dose pharmacokinetics of THC\/CBD oromucosal spray. Eur J Clin Pharmacol. 2013;69(5):1135\u201347.","journal-title":"Eur J Clin Pharmacol"},{"issue":"2","key":"2345_CR18","doi-asserted-by":"publisher","first-page":"102","DOI":"10.2174\/1872312811206020102","volume":"6","author":"M Joerger","year":"2012","unstructured":"Joerger M, Wilkins J, Fagagnini S, Baldinger R, Brenneisen R, Schneider U, et\u00a0al. Single-dose pharmacokinetics and tolerability of oral delta-9-tetrahydrocannabinol in patients with amyotrophic lateral sclerosis. Drug Metab Lett. 2012;6(2):102\u20138.","journal-title":"Drug Metab Lett"},{"issue":"12","key":"2345_CR19","doi-asserted-by":"publisher","first-page":"1579","DOI":"10.1373\/clinchem.2016.263475","volume":"62","author":"MN Newmeyer","year":"2016","unstructured":"Newmeyer MN, Swortwood MJ, Barnes AJ, Abulseoud OA, Scheidweiler KB, Huestis MA. Free and glucuronide whole blood cannabinoids\u2019 pharmacokinetics after controlled smoked, vaporized, and oral cannabis administration in frequent and occasional cannabis users: identification of recent cannabis intake. Clin Chem. 2016;62(12):1579\u201392.","journal-title":"Clin Chem"},{"issue":"9","key":"2345_CR20","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.3109\/03639041003657295","volume":"36","author":"KS Paudel","year":"2010","unstructured":"Paudel KS, Hammell DC, Agu RU, Valiveti S, Stinchcomb AL. Cannabidiol bioavailability after nasal and transdermal application: effect of permeation enhancers. Drug Dev Ind Pharm. 2010;36(9):1088\u201397.","journal-title":"Drug Dev Ind Pharm"},{"issue":"6","key":"2345_CR21","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1097\/01.ftd.0000177223.19294.5c","volume":"27","author":"T Nadulski","year":"2005","unstructured":"Nadulski T, Pragst F, Weinberg G, Roser P, Schnelle M, Fronk E-M, et\u00a0al. Randomized, double-blind, placebo-controlled study about the effects of cannabidiol (CBD) on the pharmacokinetics of \u03949-tetrahydrocannabinol (THC) after oral application of THC verses standardized cannabis extract. Ther Drug Monit. 2005;27(6):799\u2013810.","journal-title":"Ther Drug Monit"},{"issue":"2","key":"2345_CR22","doi-asserted-by":"publisher","first-page":"107","DOI":"10.2165\/00003088-200342020-00001","volume":"42","author":"JB Schwartz","year":"2003","unstructured":"Schwartz JB. The influence of sex on pharmacokinetics. Clin Pharmacokinet. 2003;42(2):107\u201321.","journal-title":"Clin Pharmacokinet"},{"issue":"1","key":"2345_CR23","doi-asserted-by":"publisher","first-page":"4","DOI":"10.4103\/2230-973X.76721","volume":"1","author":"I Singh","year":"2011","unstructured":"Singh I, Morris AP. Performance of transdermal therapeutic systems: effects of biological factors. Int J Pharm Investig. 2011;1(1):4.","journal-title":"Int J Pharm Investig"},{"issue":"4","key":"2345_CR24","doi-asserted-by":"publisher","first-page":"1062","DOI":"10.1016\/j.tiv.2008.01.009","volume":"22","author":"VM Meidan","year":"2008","unstructured":"Meidan VM, Roper CS. Inter-and intra-individual variability in human skin barrier function: a large scale retrospective study. Toxicol In Vitro. 2008;22(4):1062\u20139.","journal-title":"Toxicol In Vitro"},{"issue":"1\u20132","key":"2345_CR25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ijpharm.2008.11.020","volume":"367","author":"S Farahmand","year":"2009","unstructured":"Farahmand S, Maibach HI. Transdermal drug pharmacokinetics in man: interindividual variability and partial prediction. Int J Pharm. 2009;367(1\u20132):1\u201315.","journal-title":"Int J Pharm"},{"issue":"9","key":"2345_CR26","first-page":"24","volume":"52","author":"J Fore","year":"2006","unstructured":"Fore J. A review of skin and the effects of aging on skin structure and function. Ostomy Wound Manag. 2006;52(9):24\u201335 (quiz 6).","journal-title":"Ostomy Wound Manag"},{"issue":"6","key":"2345_CR27","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1007\/BF01062121","volume":"17","author":"KV Roskos","year":"1989","unstructured":"Roskos KV, Maibach HI, Guy RH. The effect of aging on percutaneous absorption in man. J Pharmacokinet Biopharm. 1989;17(6):617\u201330.","journal-title":"J Pharmacokinet Biopharm"},{"issue":"1","key":"2345_CR28","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1080\/15602210410001682551","volume":"4","author":"S Murdan","year":"2004","unstructured":"Murdan S. Transdermal and topical drug delivery. From theory to clinical practice. Pharm Educ. 2004;4(1):49\u201350.","journal-title":"Pharm Educ"},{"issue":"3","key":"2345_CR29","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.jdermsci.2009.06.001","volume":"55","author":"PU Giacomoni","year":"2009","unstructured":"Giacomoni PU, Mammone T, Teri M. Gender-linked differences in human skin. J Dermatol Sci. 2009;55(3):144\u20139.","journal-title":"J Dermatol Sci"},{"issue":"4","key":"2345_CR30","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1159\/000088499","volume":"211","author":"U Jacobi","year":"2005","unstructured":"Jacobi U, Gautier J, Sterry W, Lademann J. Gender-related differences in the physiology of the stratum corneum. Dermatology. 2005;211(4):312\u20137.","journal-title":"Dermatology"},{"key":"2345_CR31","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2020.119201","volume":"580","author":"D Izgelov","year":"2020","unstructured":"Izgelov D, Shmoeli E, Domb AJ, Hoffman A. The effect of medium chain and long chain triglycerides incorporated in self-nano emulsifying drug delivery systems on oral absorption of cannabinoids in rats. Int J Pharm. 2020;580: 119201.","journal-title":"Int J Pharm"},{"issue":"5","key":"2345_CR32","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1079\/BJN20041273","volume":"92","author":"M Arroyo","year":"2004","unstructured":"Arroyo M, Rocandio AM, Ansotegui L, Herrera H, Salces I, Rebato E. Comparison of predicted body fat percentage from anthropometric methods and from impedance in university students. Br J Nutr. 2004;92(5):827\u201332.","journal-title":"Br J Nutr"},{"key":"2345_CR33","unstructured":"Health Canada. Guidance document\u2014Conduct and analysis of comparative bioavailability studies. In: Health Canada, editor. Ottawa; 2018."},{"key":"2345_CR34","doi-asserted-by":"crossref","unstructured":"Berl V, Hurd YL, Lipshutz BH, Roggen M, Mathur EJ, Evans M. A randomized, triple-blind, comparator-controlled parallel study investigating the pharmacokinetics of cannabidiol and tetrahydrocannabinol in a novel delivery system, solutech, in association with cannabis use history. Cannabis Cannabinoid Res. 2022. Ahead of print.","DOI":"10.1089\/can.2021.0176"},{"issue":"20","key":"2345_CR35","doi-asserted-by":"publisher","first-page":"4790","DOI":"10.1111\/bph.13250","volume":"172","author":"R Laprairie","year":"2015","unstructured":"Laprairie R, Bagher A, Kelly M, Denovan-Wright E. Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor. Br J Pharmacol. 2015;172(20):4790\u2013805.","journal-title":"Br J Pharmacol"}],"container-title":["Advances in Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12325-022-02345-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12325-022-02345-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12325-022-02345-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T22:43:35Z","timestamp":1674254615000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12325-022-02345-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,29]]},"references-count":35,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,1]]}},"alternative-id":["2345"],"URL":"https:\/\/doi.org\/10.1007\/s12325-022-02345-5","relation":{},"ISSN":["0741-238X","1865-8652"],"issn-type":[{"value":"0741-238X","type":"print"},{"value":"1865-8652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,29]]},"assertion":[{"value":"1 September 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 September 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 October 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}