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Detection and activity profiling of synthetic cannabinoids and their metabolites with a newly developed bioassay

(2016) ANALYTICAL CHEMISTRY. 88(23). p.11476-11485
Author
Organization
Abstract
Synthetic cannabinoids (SCs) are the largest group of compounds currently monitored in Europe by the EU Early Warning System on new psychoactive substances. Emerging recreational use of these products has led to multiple cases of adverse health effects and even death. In contrast to marijuana, where Delta(9)-tetrahydrocannabinol (Delta(THC)-T-9) is metabolized to only one major active metabolite, it has been reported that several major phase I metabolites of SCs remain biologically active, exerting cannabinoid (CB) receptor affinity, potency, and efficacy greater than those of Delta(THC)-T-9. It is therefore reasonable that more SCs can also be biotransformed into molecules with various levels of CB activity. Here, we developed and applied a new G-protein coupled receptor (GPCR) activation assay based on NanoLuc binary technology (Promega). More specifically, by demonstrating CB1 and CB2 receptor activation by JWH-018 and a selection of its metabolites, we are the first to show the suitability of the newly developed bioassay for monitoring GPCR-mediated activity. We also successfully applied this reporter system to evaluate the in vitro activity of JWH-122, JWH-210, and PB-22, their S-fluoro analogues (MAM-2201, EAM-2201, and SF-PB-22, respectively), and their main phase I metabolites. By doing so, we demonstrate that several major metabolites of these SCs retain their activity at cannabinoid receptors. All of these active metabolites may prolong the parent compound's psychotropic and physiological effects and may contribute to its toxicity profile. We also demonstrate a proof of concept of the applicability of the newly developed bioassay for screening urine for CB receptor activity exerted by SCs.
Keywords
PERFORMANCE LIQUID-CHROMATOGRAPHY, FLIGHT MASS-SPECTROMETRY, RECEPTOR AGONIST, QUANTITATIVE MEASUREMENT, NEUTRAL ANTAGONIST, BETA-ARRESTIN, HERBAL BLENDS, ADB-FUBINACA, AB-FUBINACA, HUMAN URINE

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Citation

Please use this url to cite or link to this publication:

MLA
Cannaert, Annelies et al. “Detection and Activity Profiling of Synthetic Cannabinoids and Their Metabolites with a Newly Developed Bioassay.” ANALYTICAL CHEMISTRY 88.23 (2016): 11476–11485. Print.
APA
Cannaert, A., Storme, J., Franz, F., Auwärter, V., & Stove, C. (2016). Detection and activity profiling of synthetic cannabinoids and their metabolites with a newly developed bioassay. ANALYTICAL CHEMISTRY, 88(23), 11476–11485.
Chicago author-date
Cannaert, Annelies, Jolien Storme, Florian Franz, Volker Auwärter, and Christophe Stove. 2016. “Detection and Activity Profiling of Synthetic Cannabinoids and Their Metabolites with a Newly Developed Bioassay.” Analytical Chemistry 88 (23): 11476–11485.
Chicago author-date (all authors)
Cannaert, Annelies, Jolien Storme, Florian Franz, Volker Auwärter, and Christophe Stove. 2016. “Detection and Activity Profiling of Synthetic Cannabinoids and Their Metabolites with a Newly Developed Bioassay.” Analytical Chemistry 88 (23): 11476–11485.
Vancouver
1.
Cannaert A, Storme J, Franz F, Auwärter V, Stove C. Detection and activity profiling of synthetic cannabinoids and their metabolites with a newly developed bioassay. ANALYTICAL CHEMISTRY. 2016;88(23):11476–85.
IEEE
[1]
A. Cannaert, J. Storme, F. Franz, V. Auwärter, and C. Stove, “Detection and activity profiling of synthetic cannabinoids and their metabolites with a newly developed bioassay,” ANALYTICAL CHEMISTRY, vol. 88, no. 23, pp. 11476–11485, 2016.
@article{8506703,
  abstract     = {Synthetic cannabinoids (SCs) are the largest group of compounds currently monitored in Europe by the EU Early Warning System on new psychoactive substances. Emerging recreational use of these products has led to multiple cases of adverse health effects and even death. In contrast to marijuana, where Delta(9)-tetrahydrocannabinol (Delta(THC)-T-9) is metabolized to only one major active metabolite, it has been reported that several major phase I metabolites of SCs remain biologically active, exerting cannabinoid (CB) receptor affinity, potency, and efficacy greater than those of Delta(THC)-T-9. It is therefore reasonable that more SCs can also be biotransformed into molecules with various levels of CB activity. Here, we developed and applied a new G-protein coupled receptor (GPCR) activation assay based on NanoLuc binary technology (Promega). More specifically, by demonstrating CB1 and CB2 receptor activation by JWH-018 and a selection of its metabolites, we are the first to show the suitability of the newly developed bioassay for monitoring GPCR-mediated activity. We also successfully applied this reporter system to evaluate the in vitro activity of JWH-122, JWH-210, and PB-22, their S-fluoro analogues (MAM-2201, EAM-2201, and SF-PB-22, respectively), and their main phase I metabolites. By doing so, we demonstrate that several major metabolites of these SCs retain their activity at cannabinoid receptors. All of these active metabolites may prolong the parent compound's psychotropic and physiological effects and may contribute to its toxicity profile. We also demonstrate a proof of concept of the applicability of the newly developed bioassay for screening urine for CB receptor activity exerted by SCs.},
  author       = {Cannaert, Annelies and Storme, Jolien and Franz, Florian and Auwärter, Volker and Stove, Christophe},
  issn         = {0003-2700},
  journal      = {ANALYTICAL CHEMISTRY},
  keywords     = {PERFORMANCE LIQUID-CHROMATOGRAPHY,FLIGHT MASS-SPECTROMETRY,RECEPTOR AGONIST,QUANTITATIVE MEASUREMENT,NEUTRAL ANTAGONIST,BETA-ARRESTIN,HERBAL BLENDS,ADB-FUBINACA,AB-FUBINACA,HUMAN URINE},
  language     = {eng},
  number       = {23},
  pages        = {11476--11485},
  title        = {Detection and activity profiling of synthetic cannabinoids and their metabolites with a newly developed bioassay},
  url          = {http://dx.doi.org/10.1021/acs.analchem.6b02600},
  volume       = {88},
  year         = {2016},
}

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