Studies of New Psychoactive Substances

The complexity of the illicit drug market is increasing with the continuously growing number of new psychoactive substances (NPS), also known as legal highs, designer drugs, bath salts or research chemicals. NPS are synthesized with the main purpose of evading existing drug laws, and are usually generated by altering the structures of already existing pharmaceuticals and illicit drugs. NPS are often sold as other common drugs of abuse or mixed in with other drugs, which can result in accidental overdoses in users being unaware of the high drug potency. Analysis methods are needed to monitor the prevalence of NPS on the illicit drug market and to enable the acceleration of preventive measures. In forensic case work, the parent compound can be absent or undetectable in biological samples, making metabolite identification essential to confirm NPS intake. Furthermore, knowledge of the pharmacokinetic and pharmacodynamic properties of NPS is needed to assess drug potency and the impact of a drug in clinical and forensic toxicology cases.

The primary aim of our research is to develop sensitive and selective analysis methods for the determination of NPS, as well as expand on the knowledge on their metabolism, pharmacodynamic effects and mechanisms of action.

Ongoing projects

Studies of Fentanyl analogues
In this project, sensitive and selective analytical methods were developed and validated for determination of fentanyl analogs inhuman whole blood, rat plasma, as well as used syringe needles. The metabolism of selected fentanyl analogs was studied employing human liver in vitro models. The pharmacodynamic effects of the fentanyl analogs carfentanil and cyclopropylfentanyl were also examined in vivo in a rat model. Finally, we have examined the selectivity and sensitivity of different commercially available urine fentanyl test strips to detect fentanyl analogs in drug solutions.

Studies of Synthetic Tryptamines
In this project, bioanalytical methods will be developed and validated for the detection of synthetic tryptamines. The metabolism of a selection of synthetic tryptamines will be examined by the use of a human in vitro model.

Studies of Amphetamine-type NPS
This includes studies of the pharmacokinetics and pharmacodynamic effects of the methamphetamine analogue methiopropamine, as well as studies of the metabolism of para-methoxymethamphetamine (PMMA) and the influence of CYP2D6 genetics.

Project members
Marianne Skov-Skov Bergh (Postdoctoral researcher, PhD)
Inger Lise Bogen (Senior Scientist, PhD)
Åse-Marit Leere Øiestad (Senior Scientist, PhD)
Jannike Mørch Andersen (Senior Scientist, PhD)
Elisabeth Nerem (Laboratory engineer, BSc)
Synne Steinsland (Laboratory engineer, MSc)

Collaboration
Michael H. Baumann, National Institute on Drug Abuse, Baltimore, USA
Ariane Wohlfarth, Forensic Toxicological Centre, Munich, Germany
Steven Ray Wilson, Department of Chemistry, University of Oslo and Hybrid Technology-Hub, Centre of Excellence, Oslo, Norway
Merete Vevelstad, Department of Forensic Sciences, Oslo University Hospital, Oslo, Norway

News and Media Reports
Håret ditt kan avsløre rusbruk i årevis etter inntak
Forsker på nye ekstremt potente opioider på rusmiddelmarkedet
Kommer opioidepidemien til Norge?

If you have questions about the project or suggestions for research collaboration, please contact: Marianne Skov-Skov Bergh (rmmabe@ous-hf.no) or Inger Lise Bogen (inger.lise.bogen@ous-hf.no) at the Section for Drug Abuse Research, Department of Forensic Sciences, Oslo University Hospital, Oslo, Norway.

Publications
Bergh, M. S. et al. (2021). Discovering the major metabolites of the three novel fentanyl analogues 3-methylcrotonylfentanyl, furanylbenzylfentanyl, and 4-fluorocyclopropylbenzylfentanyl for forensic case work. Forensic Toxicol, 39(1), 167-178. https://doi.org/10.1007/s11419-020-00560-9    

Bergh, M. S. et al. (2021). Selectivity and sensitivity of urine fentanyl test strips to detect fentanyl analogues in illicit drugs. Int. J. Drug Policy, 90, 103065.https://doi.org/10.1016/j.drugpo.2020.103065

Gjerde, H. et al. (2020). Determination of drug residues in used syringe needles. Drug Test Anal, https://doi.org/10.1002/dta.2759 

Bergh, M. S. et al. (2019). Evidence for nonlinear accumulation of the ultrapotent fentanyl analog, carfentanil, after systemic administration to male rats. Neuropharmacology, 158, 107596. https://doi.org/10.1016/j.neuropharm.2019.04.002

Bergh, M. S. et al. (2019). Distinguishing Between Cyclopropylfentanyl and Crotonylfentanyl by Methods Commonly Available in the Forensic Laboratory. Ther Drug Monit, 41(4), 519-527. https://doi.org/10.1097/ftd.0000000000000617  

Bergh, M. S. et al. (2018). Addressing the Fentanyl Analogue Epidemic by Multiplex UHPLC-MS/MS Analysis of Whole Blood. Ther Drug Monit, 40(6), 738-748. https://doi.org/10.1097/ftd.0000000000000564   

Vevelstad M, Øiestad EL, Nerem E, Arnestad M, Bogen IL (2017). Studies on Para-Methoxymethamphetamine (PMMA) Metabolite Pattern and Influence of CYP2D6 Genetics in Human Liver Microsomes and Authentic Samples from Fatal PMMA Intoxications. Drug Metab Dispos, 45 (12), 1326-1335. https://doi.org/10.1124/dmd.117.077263

 
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