2a47482a4a62ed6b798e0cd9b924dd44 pmc_33451073.pdf e07702e058c923ba3ae66c4eced8646536d6ab78 pmc_33451073.pdf aaa164d7e479f80380d9c961a962192db1912e91e7b268ee4ee55c131c006f68 pmc_33451073.pdf Title: Disposition of Phytocannabinoids, Their Acidic Precursors and Their Metabolites in Biological Matrices of Healthy Individuals Treated with Vaporized Medical Cannabis Subject: Inhalation by vaporization is a useful application mode for medical cannabis. In this study, we present the disposition of 9-tetrahydrocannabinol (THC), cannabidiol (CBD), their acidic precursors, and their metabolites in serum, oral fluid, and urine together with the acute pharmacological effects in 14 healthy individuals treated with vaporized medical cannabis. THC and CBD peaked firstly in serum and then in oral fluid, with higher concentrations in the first biological matrices and consequent higher area under the curve AUCs. Acidic precursors -9-tetrahydrocannabinolic acid A (THCA) and cannabidiolic acid (CBDA) showed a similar time course profile but lower concentrations due to the fact that vaporization partly decarboxylated these compounds. All THC and CBD metabolites showed a later onset with respect to the parent compounds in the absorption phase and a slower decrease to baseline. In agreement with serum kinetics, THC-COOH-GLUC and 7-COOH-CBD were the significantly most excreted THC and CBD metabolites. The administration of vaporized medical cannabis induced prototypical effects associated with the administration of cannabis or THC in humans, with a kinetic trend overlapping that of parent compounds and metabolites in serum. The pharmacokinetics of cannabinoids, their precursors, and their metabolites in biological fluids of individuals treated with vaporized medical cannabis preparations showed a high interindividual variability as in the case of oral medical cannabis decoction and oil. Inhaled medical cannabis was absorbed into the organism earlier than decoction and oil. Cannabinoids reached higher systemic concentrations, also due to the fact that the acid precursors decarboxylated to parent cannabinoids at high temperatures, and consequently, the physiological and subjective effects occurred earlier and resulted with higher intensity. No serious adverse effects were observed. Keywords: cannabis; cannabidiol; cannabidiol metabolism; medical cannabis Author: Francesco Paolo Busardò, Ana Pilar Pérez-Acevedo, Roberta Pacifici, Giulio Mannocchi, Massimo Gottardi, Esther Papaseit, Clara Pérez-Mañá, Soraya Martin, Lourdes Poyatos, Simona Pichini and Magí Farré Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Jan 14 11:04:23 2021 CET ModDate: Thu Jan 14 11:13:46 2021 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 14 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1592418 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- YHLBEF+VnURWPalladioL Type 1 Custom yes yes no 10 0 KHRHQY+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 BMZLAE+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 EJQDTE+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 MPUDFL+PazoMath Type 1 Builtin 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IEDHBC+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 242 0 IEDHBD+PalatinoLinotype CID TrueType Identity-H yes yes yes 245 0 IEDHBE+PalatinoLinotype TrueType WinAnsi yes yes no 251 0 IEDHBG+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 254 0 IEDJEK+Arial CID TrueType Identity-H yes yes yes 257 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2021-03-06 02:23:17 CET RepresentationInformation: pmc_33451073.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2021-02-01 03:46:48 CET Size: 1592418 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 422 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Children: Item: Title: Subjects and Study Design Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Concentration-Time Profiles and Pharmacokinetics of THC, CBD, and Their Acidic Precursors in Serum and Oral Fluid after Vaporized Cannabis Administration Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Concentration-Time Profiles and Pharmacokinetics of THC Metabolites in Seum after Vaporized Cannabis Administration Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Concentration-Time Profiles and Pharmacokinetics of CBD Metabolites in Serum after Vaporized Cannabis Administration Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Urinary Excretion of THC and CBD Metabolites after Vaporized Cannabis Administration Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Physiological Measures and Subjective Effects Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Materials and Method Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Children: Item: Title: Subjects Enrolment Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Preparation and Inhalation Procedure for Vaporized Cannabis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Study Design Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Physiological and Subjective Effects Measurement Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: Biological Samples Collection Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: Title: Determination of Cannabinoids, Acidic Precursors, and Metabolites in Biological Samples Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4eb7f003 Info: Title: Disposition of Phytocannabinoids, Their Acidic Precursors and Their Metabolites in Biological Matrices of Healthy Individuals Treated with Vaporized Medical Cannabis Author: Francesco Paolo Busardò, Ana Pilar Pérez-Acevedo, Roberta Pacifici, Giulio Mannocchi, Massimo Gottardi, Esther Papaseit, Clara Pérez-Mañá, Soraya Martin, Lourdes Poyatos, Simona Pichini and Magí Farré Subject: Inhalation by vaporization is a useful application mode for medical cannabis. In this study, we present the disposition of 9-tetrahydrocannabinol (THC), cannabidiol (CBD), their acidic precursors, and their metabolites in serum, oral fluid, and urine together with the acute pharmacological effects in 14 healthy individuals treated with vaporized medical cannabis. THC and CBD peaked firstly in serum and then in oral fluid, with higher concentrations in the first biological matrices and consequent higher area under the curve AUCs. Acidic precursors -9-tetrahydrocannabinolic acid A (THCA) and cannabidiolic acid (CBDA) showed a similar time course profile but lower concentrations due to the fact that vaporization partly decarboxylated these compounds. All THC and CBD metabolites showed a later onset with respect to the parent compounds in the absorption phase and a slower decrease to baseline. In agreement with serum kinetics, THC-COOH-GLUC and 7-COOH-CBD were the significantly most excreted THC and CBD metabolites. The administration of vaporized medical cannabis induced prototypical effects associated with the administration of cannabis or THC in humans, with a kinetic trend overlapping that of parent compounds and metabolites in serum. The pharmacokinetics of cannabinoids, their precursors, and their metabolites in biological fluids of individuals treated with vaporized medical cannabis preparations showed a high interindividual variability as in the case of oral medical cannabis decoction and oil. Inhaled medical cannabis was absorbed into the organism earlier than decoction and oil. Cannabinoids reached higher systemic concentrations, also due to the fact that the acid precursors decarboxylated to parent cannabinoids at high temperatures, and consequently, the physiological and subjective effects occurred earlier and resulted with higher intensity. No serious adverse effects were observed. 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