4f792c7fd03688e5b28694ac4279f86b pmc_33322849.pdf 64a86a6dc1d1278139c43052314c27adb738cd22 pmc_33322849.pdf 48f4d208ce881ed43d3d829b711a22b2918f0d2c92bc7002312f30c1b65ed708 pmc_33322849.pdf Title: Disposition of Cannabidiol Metabolites in Serum and Urine from Healthy Individuals Treated with Pharmaceutical Preparations of Medical Cannabis Subject: The use of cannabis flowering tops with standardized amounts of active phytocannabinoids was recently authorized in several countries to treat several painful pathological conditions. The acute pharmacological effects and disposition of -9-tetrahydrocannabinol (THC), cannabidiol (CBD), their acidic precursors and THC metabolites after oil and decoction administration have been already described. In this study, the disposition of CBD metabolites: 7-carboxy-cannabidiol (7-COOH-CBD), 7-hydroxycannabidiol (7-OH-CBD), 6–hydroxycannabidiol (6–OH-CBD), and 6–hydroxycannabidiol (6–OH-CBD) in the serum and urine of healthy volunteers was presented. Thirteen healthy volunteers were administered 100 mL of cannabis decoction in the first experimental session and, after 15 days of washout, 0.45 mL of oil. Serum and urine samples were collected at different time points, and the CBD metabolites were quantified by ultra-high-performance liquid chromatography–tandem mass spectrometry. The most abundant serum metabolite was 7-COOH-CBD, followed by 7-OH-CBD, 6–OH-CBD, and6–OH-CBD, after decoction and oil. Both 7-OH-CBD and the 6–OH-CBD showed similar pharmacokinetic properties following administration of both cannabis preparations, whereas 7-COOH and 6–OH-CBD displayed a significant higher bioavailability after decoction consumption. All CBD metabolites were similarly excreted after oil and decoction intake apart from 6–OH-CBD, which had a significantly lower excretion after oil administration. The pharmacokinetic characterization of CBD metabolites is crucial for clinical practice since the cannabis herbal preparations are increasingly used for several pathological conditions. Keywords: cannabis; cannabidiol; cannabidiol metabolism; medical cannabis Author: Ana Pilar Pérez-Acevedo, Francesco Paolo Busardò, Roberta Pacifici, Giulio Mannocchi, Massimo Gottardi, Lourdes Poyatos, Esther Papaseit, Clara Pérez-Mañá, Soraya Martin, Annagiulia Di Trana, Simona Pichini and Magí Farré Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Mon Dec 14 11:25:54 2020 CET ModDate: Mon Dec 14 11:31:35 2020 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 9 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1301424 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- XNRVWF+Pxsy Type 1 Builtin yes yes no 10 0 KORLVE+VnURWPalladioL Type 1 Custom yes yes no 14 0 LRWZOI+URWPalladioL-Ital Type 1 Custom yes yes no 19 0 LNRLJT+URWPalladioL-Bold Type 1 Custom yes yes no 24 0 JYZCFF+URWPalladioL-Roma Type 1 Custom yes yes no 28 0 FATHTC+Rpxr Type 1 Builtin yes yes no 32 0 MPUDFL+PazoMath Type 1 Builtin yes yes no 36 0 VVSYYB+EURM10 Type 1 Builtin yes yes no 40 0 MPDLZD+VnURWPalladioL-Bold Type 1 Custom yes yes no 44 0 CUAJJQ+Pxbsy Type 1 Builtin yes yes no 48 0 VWRBXB+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 56 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 78 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 82 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 86 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes no 102 0 TGMEOR+Rpcxr Type 1 Builtin yes yes no 118 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-10-03 02:33:15 CEST RepresentationInformation: pmc_33322849.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2020-12-28 03:45:59 CET Size: 1301424 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 221 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Children: Item: Title: Subjects and Study Design Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Concentration Time Profiles and Pharmacokinetics of CBD Metabolites in Serum after Decoction and Oil Administration Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Urinary Excretion of CBD Metabolites after Decoction and Oil Administration Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Materials and Method Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Children: Item: Title: Subjects’ Enrolment Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Cannabis Decoction and Oil Preparation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Study Design Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Biological Samples’ Collection Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Determination of Cannabinoids in Herbal Preparations and CDB Metabolites in Serum and Urine Samples Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Info: Title: Disposition of Cannabidiol Metabolites in Serum and Urine from Healthy Individuals Treated with Pharmaceutical Preparations of Medical Cannabis Author: Ana Pilar Pérez-Acevedo, Francesco Paolo Busardò, Roberta Pacifici, Giulio Mannocchi, Massimo Gottardi, Lourdes Poyatos, Esther Papaseit, Clara Pérez-Mañá, Soraya Martin, Annagiulia Di Trana, Simona Pichini and Magí Farré Subject: The use of cannabis flowering tops with standardized amounts of active phytocannabinoids was recently authorized in several countries to treat several painful pathological conditions. The acute pharmacological effects and disposition of -9-tetrahydrocannabinol (THC), cannabidiol (CBD), their acidic precursors and THC metabolites after oil and decoction administration have been already described. In this study, the disposition of CBD metabolites: 7-carboxy-cannabidiol (7-COOH-CBD), 7-hydroxycannabidiol (7-OH-CBD), 6 hydroxycannabidiol (6 OH-CBD), and 6 hydroxycannabidiol (6 OH-CBD) in the serum and urine of healthy volunteers was presented. Thirteen healthy volunteers were administered 100 mL of cannabis decoction in the first experimental session and, after 15 days of washout, 0.45 mL of oil. Serum and urine samples were collected at different time points, and the CBD metabolites were quantified by ultra-high-performance liquid chromatography tandem mass spectrometry. The most abundant serum metabolite was 7-COOH-CBD, followed by 7-OH-CBD, 6 OH-CBD, and6 OH-CBD, after decoction and oil. Both 7-OH-CBD and the 6 OH-CBD showed similar pharmacokinetic properties following administration of both cannabis preparations, whereas 7-COOH and 6 OH-CBD displayed a significant higher bioavailability after decoction consumption. All CBD metabolites were similarly excreted after oil and decoction intake apart from 6 OH-CBD, which had a significantly lower excretion after oil administration. The pharmacokinetic characterization of CBD metabolites is crucial for clinical practice since the cannabis herbal preparations are increasingly used for several pathological conditions. 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