c14951b8720d36ecfd30be2533ec5956 pmc_33805054.pdf 95a060c97651c5f64b480c83a3146669d4814241 pmc_33805054.pdf eefae7d61dfbd7f875f0a64d011efde4a6e03e2441eb064acee5ab33d0855978 pmc_33805054.pdf Title: Acute Pharmacological Effects and Oral Fluid Biomarkers of the Synthetic Cannabinoid UR-144 and THC in Recreational Users Subject: Synthetic cannabinoids (SCs) are one of the most frequent classes of new psychoactive substances monitored by the EU Early Warning System and World Health Organization. UR-144 is a SC with a relative low affinity for the CB1 receptor with respect to that for the CB2 receptor. As with other cannabinoid receptor agonists, it has been monitored by the EU Early Warning System since 2012 for severe adverse effects on consumers. Since data for UR-144 human pharmacology are very limited, an observational study was carried out to evaluate its acute pharmacological effects following its administration using a cannabis joint as term of comparison. Disposition of UR-144 and delta-9-tetrahydrocannibinol (THC) was investigated in oral fluid. Sixteen volunteers smoked a joint prepared with tobacco and 1 or 1.5 mg dose of UR-144 (n = 8) or cannabis flowering tops containing 10 or 20 mg THC (n = 8). Physiological variables including systolic and diastolic blood pressure, heart rate and cutaneous temperature were measured. A set of Visual Analog Scales (VAS), the Addiction Research Centre Inventory (ARCI)-49-item short form version and the Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) were administered to evaluate subjective effects. Oral fluid was collected at baseline, 10, 20, 40 min and 1, 2, 3 and 4 h after smoking, for UR-144 or THC concentration monitoring. Results showed significant statistical increases in both systolic and diastolic blood pressure and heart rate after both UR-144 and cannabis smoking. Both substances produced an increase in VAS related to stimulant-like and high effects, but scores were significantly higher after cannabis administration. No hallucinogenic effects were observed. Maximal oral fluid UR-144 and THC concentrations appeared at 20 and 10 min after smoking, respectively. The presence of UR-144 in oral fluid constitutes a non-invasive biomarker of SC consumption. The results of this observational study provide valuable preliminary data of the pharmacological effects of UR-144, showing a similar profile of cardiovascular effects in comparison with THC but lower intensity of subjective effects. Our results have to be confirmed by research in a larger sample to extensively clarify pharmacological effects and the health risk profile of UR-144. Keywords: UR-144; synthetic cannabinoids (SCs); cannabis; THC; physiological effects; subjective effects; oral fluid concentration Author: Nunzia La Maida, Esther Papaseit, Lucia Martínez, Clara Pérez-Mañá, Lourdes Poyatos, Manuela Pellegrini, Simona Pichini, Roberta Pacifici, Mireia Ventura, Liliana Galindo, Francesco Paolo Busardò and Magí Farré Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Mar 25 03:22:36 2021 CET ModDate: Thu Mar 25 03:24:44 2021 CET Custom Metadata: no Metadata Stream: no 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: 1014947 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- MPDLZD+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 CMFVHJ+VnURWPalladioL Type 1 Custom yes yes no 15 0 DAMBGL+URWPalladioL-Ital Type 1 Custom yes yes no 19 0 GHRRWK+URWPalladioL-Bold Type 1 Custom yes yes no 24 0 DVUBSN+URWPalladioL-Roma Type 1 Custom yes yes no 28 0 GLCFZC+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 36 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 58 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 62 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 66 0 MPUDFL+PazoMath Type 1 Builtin yes yes no 78 0 LREJRV+CMSY10 Type 1 Builtin yes yes no 91 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes no 98 0 TMHVPV+MSAM10 Type 1 Builtin yes yes no 108 0 GMALOA+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 119 0 GMALOB+PalatinoLinotype CID TrueType Identity-H yes yes yes 122 0 GMALOC+PalatinoLinotype TrueType WinAnsi yes yes no 128 0 GMALOD+PalatinoLinotype,Italic CID TrueType Identity-H yes yes yes 131 0 GMALOE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 137 0 GMALOA+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 151 0 GMALOB+PalatinoLinotype CID TrueType Identity-H yes yes yes 154 0 GMALOC+PalatinoLinotype TrueType WinAnsi yes yes no 160 0 GMALOE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 163 0 GMALOA+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 178 0 GMALOB+PalatinoLinotype CID TrueType Identity-H yes yes yes 181 0 GMALOC+PalatinoLinotype TrueType WinAnsi yes yes no 187 0 GMALOE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 190 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-10-02 03:24:52 CEST RepresentationInformation: pmc_33805054.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2023-03-31 12:09:30 CEST Size: 1014947 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 345 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Participants Destination: subsection.2.1 Item: Title: Study Design and Treatments Destination: subsection.2.2 Item: Title: Procedures Destination: subsection.2.3 Item: Title: Physiological Effects Destination: subsection.2.4 Item: Title: Subjective Effects Destination: subsection.2.5 Item: Title: Drugs Disposition in Oral Fluid Destination: subsection.2.6 Item: Title: Statistical Analysis Destination: subsection.2.7 Item: Title: Results Destination: section.3 Children: Item: Title: Participants Destination: subsection.3.1 Item: Title: Physiological Effects Destination: subsection.3.2 Item: Title: Subjective Effects Destination: subsection.3.3 Item: Title: UR-144 and THC of Concentrations Destination: subsection.3.4 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.5 Info: Title: Acute Pharmacological Effects and Oral Fluid Biomarkers of the Synthetic Cannabinoid UR-144 and THC in Recreational Users Author: Nunzia La Maida, Esther Papaseit, Lucia Martínez, Clara Pérez-Mañá, Lourdes Poyatos, Manuela Pellegrini, Simona Pichini, Roberta Pacifici, Mireia Ventura, Liliana Galindo, Francesco Paolo Busardò and Magí Farré Subject: Synthetic cannabinoids (SCs) are one of the most frequent classes of new psychoactive substances monitored by the EU Early Warning System and World Health Organization. UR-144 is a SC with a relative low affinity for the CB1 receptor with respect to that for the CB2 receptor. As with other cannabinoid receptor agonists, it has been monitored by the EU Early Warning System since 2012 for severe adverse effects on consumers. Since data for UR-144 human pharmacology are very limited, an observational study was carried out to evaluate its acute pharmacological effects following its administration using a cannabis joint as term of comparison. Disposition of UR-144 and delta-9-tetrahydrocannibinol (THC) was investigated in oral fluid. Sixteen volunteers smoked a joint prepared with tobacco and 1 or 1.5 mg dose of UR-144 (n = 8) or cannabis flowering tops containing 10 or 20 mg THC (n = 8). Physiological variables including systolic and diastolic blood pressure, heart rate and cutaneous temperature were measured. A set of Visual Analog Scales (VAS), the Addiction Research Centre Inventory (ARCI)-49-item short form version and the Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) were administered to evaluate subjective effects. Oral fluid was collected at baseline, 10, 20, 40 min and 1, 2, 3 and 4 h after smoking, for UR-144 or THC concentration monitoring. Results showed significant statistical increases in both systolic and diastolic blood pressure and heart rate after both UR-144 and cannabis smoking. Both substances produced an increase in VAS related to stimulant-like and high effects, but scores were significantly higher after cannabis administration. No hallucinogenic effects were observed. Maximal oral fluid UR-144 and THC concentrations appeared at 20 and 10 min after smoking, respectively. The presence of UR-144 in oral fluid constitutes a non-invasive biomarker of SC consumption. The results of this observational study provide valuable preliminary data of the pharmacological effects of UR-144, showing a similar profile of cardiovascular effects in comparison with THC but lower intensity of subjective effects. Our results have to be confirmed by research in a larger sample to extensively clarify pharmacological effects and the health risk profile of UR-144. 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