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- Blackwell, Simon E., et al.
(författare)
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Optimism and mental imagery : A possible cognitive marker to promote well-being?
- 2013
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Ingår i: Psychiatry Research. - : ELSEVIER IRELAND LTD. - 0165-1781 .- 1872-7123. ; 206:1, s. 56-61
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Tidskriftsartikel (refereegranskat)abstract
- Optimism is associated with a range of benefits not only for general well-being, but also for mental and physical health. The development of psychological interventions to boost optimism derived from cognitive science would have the potential to provide significant public health benefits, yet cognitive markers of optimism are little understood. The current study aimed to take a first step in this direction by identifying a cognitive marker for optimism that could provide a modifiable target for innovative interventions. In particular we predicted that the ability to generate vivid positive mental imagery of the future would be associated with dispositional optimism. A community sample of 237 participants completed a survey comprising measures of mental imagery and optimism, and socio-demographic information. Vividness of positive future imagery was significantly associated with optimism, even when adjusting for socio-demographic factors and everyday imagery use. The ability to generate vivid mental imagery of positive future events may provide a modifiable cognitive marker of optimism. Boosting positive future imagery could provide a cognitive target for treatment innovations to promote optimism, with implications for mental health and even physical well-being. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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- Carlier, Jeremy, et al.
(författare)
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In Vitro Metabolite Profiling of ADB-FUBINACA, A New Synthetic Cannabinoid
- 2017
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Ingår i: Current Neuropharmacology. - : BENTHAM SCIENCE PUBL LTD. - 1570-159X .- 1875-6190. ; 15:5, s. 682-691
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Tidskriftsartikel (refereegranskat)abstract
- Background: Metabolite profiling of novel psychoactive substances (NPS) is critical for documenting drug consumption. N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1-Hindazole-3-carboxamide (ADB-FUBINACA) is an emerging synthetic cannabinoid whose toxicological and metabolic data are currently unavailable. Methods: We aimed to determine optimal markers for identifying ADB-FUBINACA intake. Metabolic stability was evaluated with human liver microsome incubations. Metabolites were identified after 1 and 3 h incubation with pooled human hepatocytes, liquid chromatography-high resolution mass spectrometry in positive-ion mode (5600(+) TripleTOF (R), Sciex) and several data mining approaches (MetabolitePilot (TM), Sciex). Results: Metabolite separation was achieved on an Ultra Biphenyl column (Restek (R)); full-scan TOF-MS and information-dependent acquisition MS/MS data were acquired. ADB-FUBINACA microsomal half-life was 39.7 min, with a predicted hepatic clearance of 9.0 mL/min/kg and a 0.5 extraction ratio (intermediate-clearance drug). Twenty-three metabolites were identified. Major metabolic pathways were alkyl and indazole hydroxylation, terminal amide hydrolysis, subsequent glucuronide conjugations, and dehydrogenation. Conclusion: We recommend ADB-FUBINACA hydroxyalkyl, hydroxydehydroalkyl and hydroxylindazole metabolites as ADB-FUBINACA intake markers. N-dealkylated metabolites are not specific ADB-FUBINACA metabolites and should not be used as definitive markers of consumption. This is the first ADB-FUBINACA in vitro metabolism study; in vivo experiments enabling pharmacokinetic and pharmacodynamics studies or urine from authentic clinical/forensic cases are needed to confirm our results.
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- Diao, Xingxing, et al.
(författare)
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In vitro and in vivo human metabolism of a new synthetic cannabinoid NM-2201 (CBL-2201)
- 2017
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Ingår i: Forensic Toxicology. - : SPRINGER. - 1860-8965 .- 1860-8973. ; 35:1, s. 20-32
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Tidskriftsartikel (refereegranskat)abstract
- In 2014, NM-2201 (CBL-2201), a novel synthetic cannabinoid (SC), was detected by scientists at Russian and US laboratories. It has been already added to the list of scheduled drugs in Japan, Sweden and Germany. Unfortunately, no human metabolism data are currently available, which makes it challenging to confirm its intake, especially given that all SCs investigated thus far have been found to be extensively metabolized. The present study aims to recommend appropriate marker metabolites by investigating NM-2201 metabolism in human hepatocytes, and to confirm the results in authentic human urine specimens. For the metabolic stability assay, 1 A mu M NM-2201 was incubated in human liver microsomes (HLMs) for up to 1 h; for metabolite profiling, 10 A mu M of NM-2201 was incubated in human hepatocytes for 3 h. Two authentic urine specimens from NM-2201-positive cases were subjected to beta-glucuronidase hydrolysis prior to analysis. The identification of metabolites in hepatocyte samples and urine specimens was achieved with high-resolution mass spectrometry via information-dependent acquisition. NM-2201 was quickly metabolized in HLMs, with an 8.0-min half-life. In human hepatocyte incubation samples, a total of 13 NM-2201 metabolites were identified, generated mainly from ester hydrolysis and further hydroxylation, oxidative defluorination and subsequent glucuronidation. M13 (5-fluoro PB-22 3-carboxyindole) was found to be the major metabolite. In the urine specimens, the parent drug NM-2201 was not detected; M13 was the predominant metabolite after beta-glucuronidase hydrolysis. Therefore, based on the results of our study, we recommend M13 as a suitable urinary marker metabolite for confirming NM-2201 and/or 5F-PB-22 intake.
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