Opioid Pharmacology and Toxicology

Photo: Shutterstock

Opioids are responsible for almost 80% of all drug-related deaths worldwide. During the past 10–15 years, there has been a shift in the type of opioids causing the majority of deaths, from heroin to prescription painkillers and highly potent synthetic opioids. Misuse of opioids has become a global public health problem, commonly referred to as the opioid epidemic.

Our project aims to study the pharmacokinetics, pharmacodynamics, mechanism of action, potency, and toxicology of various opioids. We study different medications used in the treatment of opioid dependence, from traditional pharmacological treatment with methadone or buprenorphine to innovative immunotherapy.

Increased use of opioids in the population has led to a corresponding increase in opioid use among pregnant women. We study the long-term effects on offspring after exposure to opioids in fetal life using animal models. We also develop new analytical methods to monitor the prevalence of new synthetic and highly potent opioids on the Norwegian drug market. Additionally, we have evaluated the ability of harm reduction tools such as drug self-testing to detect fentanyls in street drugs.

For more information about our research on opioids, see

• Prenatal Opioid Exposure
• Heroin - from Injection to Treatment
• New Psychoactive Substances (NPS)

If you have questions about the project or suggestions for research collaboration, please contact: Jannike Mørch Andersen (jannike.morch.andersen@ous-hf.no) or Inger Lise Bogen (inger.lise.bogen@ous-hf.no), Department of Forensic Sciences, Oslo University Hospital, Norway.

Publications

Bogen IL, Boix F, Andersen JM, Steinsland S, Nerem E, Mørland J (2023)
Heroin metabolism in human blood and its impact for the design of an immunotherapeutic approach against heroin effects
Basic Clin Pharmacol Toxicol, 133 (4), 418-427
DOI 10.1111/bcpt.13926, PubMed 37452619

Rajalingam D, Boix F, Khoder A, Andersen JM, Paulsen RE (2023)
Distribution of morphine and methadone to the brain in a developmental chicken embryo model
Toxicol Appl Pharmacol, 479, 116731
DOI 10.1016/j.taap.2023.116731, PubMed 37866706

D'Ottavio G, Reverte I, Ragozzino D, Meringolo M, Milella MS, Boix F, Venniro M, Badiani A, Caprioli D (2022)
Increased heroin intake and relapse vulnerability in intermittent relative to continuous self-administration: Sex differences in rats
Br J Pharmacol, 180 (7), 910-926
DOI 10.1111/bph.15791, PubMed 34986504

Kogler S, Aizenshtadt A, Harrison S, Skottvoll FS, Berg HE, Abadpour S, Scholz H, Sullivan G, Thiede B, Lundanes E, Bogen IL, Krauss S, Røberg-Larsen H, Wilson SR (2022)
"Organ-in-a-Column" Coupled On-line with Liquid Chromatography-Mass Spectrometry
Anal Chem, 94 (50), 17677-17684
DOI 10.1021/acs.analchem.2c04530, PubMed 36484723

Andersen JM, Bogen IL, Karinen R, Brochmann GW, Mørland J, Vindenes V, Boix F (2021)
Does the preparation for intravenous administration affect the composition of heroin injections? A controlled laboratory study
Addiction, 116 (11), 3104-3112
DOI 10.1111/add.15492, PubMed 33739552

Bergh MS, Bogen IL, Garibay N, Baumann MH (2021)
Pharmacokinetics and pharmacodynamics of cyclopropylfentanyl in male rats
Psychopharmacology (Berl), 238 (12), 3629-3641
DOI 10.1007/s00213-021-05981-x, PubMed 34613431

Bergh MSS, Bogen IL, Nerem E, Wohlfarth A, Wilson SR, Oiestad AML (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
DOI 10.1007/s11419-020-00560-9

Skottvoll FS, Hansen FA, Harrison S, Boger IS, Mrsa A, Restan MS, Stein M, Lundanes E, Pedersen-Bjergaard S, Aizenshtadt A, Krauss S, Sullivan G, Bogen IL, Wilson SR (2021)
Electromembrane Extraction and Mass Spectrometry for Liver Organoid Drug Metabolism Studies
Anal Chem, 93 (7), 3576-3585
DOI 10.1021/acs.analchem.0c05082, PubMed 33534551

Andersen JM, Høiseth G, Nygaard E (2020)
Prenatal exposure to methadone or buprenorphine and long-term outcomes: A meta-analysis
Early Hum Dev, 143, 104997
DOI 10.1016/j.earlhumdev.2020.104997, PubMed 32146140

Andersen JM, Opdal SH, Müller CP, Boix F (2020)
CaMKII is activated in opioid induced conditioned place preference, but αCaMKII Thr286 autophosphorylation is not necessary for its establishment
Behav Brain Res, 390, 112676
DOI 10.1016/j.bbr.2020.112676, PubMed 32407818

Bergh MS, Øiestad ÅML, Baumann MH, Bogen IL (2020)
Selectivity and sensitivity of urine fentanyl test strips to detect fentanyl analogues in illicit drugs
Int J Drug Policy, 90, 103065
DOI 10.1016/j.drugpo.2020.103065, PubMed 33333419

Kongstorp M, Bogen IL, Steinsland S, Nerem E, Salih TW, Stiris T, Andersen JM (2020)
Prenatal exposure to methadone or buprenorphine alters µ-opioid receptor binding and downstream signaling in the rat brain
Int J Dev Neurosci, 80 (5), 443-453
DOI 10.1002/jdn.10043, PubMed 32484968

Kongstorp M, Bogen IL, Stiris T, Andersen JM (2020)
Prenatal exposure to methadone or buprenorphine impairs cognitive performance in young adult rats
Drug Alcohol Depend, 212, 108008
DOI 10.1016/j.drugalcdep.2020.108008, PubMed 32402939

Rhein C, Mühle C, Lenz B, Richter-Schmidinger T, Kogias G, Boix F, Lourdusamy A, Dörfler A, Peters O, Ramirez, Gjerde H, Bretteville-Jensen AL, Furuhaugen H, Bache-Andreassen L, Bergh MS, Vindenes V (2020)
Determination of drug residues in used syringe needles
Drug Test Anal, 12 (3), 410-416
DOI 10.1002/dta.2759, PubMed 31899604

Bergh MS, Bogen IL, Garibay N, Baumann MH (2019)
Evidence for nonlinear accumulation of the ultrapotent fentanyl analog, carfentanil, after systemic administration to male rats
Neuropharmacology, 158, 107596
DOI 10.1016/j.neuropharm.2019.04.002, PubMed 30965021

Bergh MS, Bogen IL, Wohlfarth A, Wilson SR, Øiestad ÅML (2019)
Distinguishing Between Cyclopropylfentanyl and Crotonylfentanyl by Methods Commonly Available in the Forensic Laboratory
Ther Drug Monit, 41 (4), 519-527
DOI 10.1097/FTD.0000000000000617, PubMed 30807539

Fjelldal MF, Hadera MG, Kongstorp M, Austdal LPE, Šulović A, Andersen JM, Paulsen RE (2019)
Opioid receptor-mediated changes in the NMDA receptor in developing rat and chicken
Int J Dev Neurosci, 78, 19-27
DOI 10.1016/j.ijdevneu.2019.07.009, PubMed 31351113

Kongstorp M, Bogen IL, Stiris T, Andersen JM (2019)
High Accumulation of Methadone Compared with Buprenorphine in Fetal Rat Brain after Maternal Exposure
J Pharmacol Exp Ther, 371 (1), 130-137
DOI 10.1124/jpet.119.259531, PubMed 31358559

Kvello AMS, Andersen JM, Boix F, Mørland J, Bogen IL (2019)
The role of 6-acetylmorphine in heroin-induced reward and locomotor sensitization in mice
Addict Biol, 25 (2), e12727
DOI 10.1111/adb.12727, PubMed 30788879

Avvisati R, Bogen IL, Andersen JM, Vindenes V, Mørland J, Badiani A, Boix F (2018)
The active heroin metabolite 6-acetylmorphine has robust reinforcing effects as assessed by self-administration in the rat
Neuropharmacology, 150, 192-199
DOI 10.1016/j.neuropharm.2018.12.023, PubMed 30578794

Bergh MS, Bogen IL, Wilson SR, Øiestad ÅML (2018)
Addressing the Fentanyl Analogue Epidemic by Multiplex UHPLC-MS/MS Analysis of Whole Blood
Ther Drug Monit, 40 (6), 738-748
DOI 10.1097/FTD.0000000000000564, PubMed 30157097

Kvello AMS, Andersen JM, Øiestad EL, Steinsland S, Aase A, Mørland J, Bogen IL (2018)
A Monoclonal Antibody against 6-Acetylmorphine Protects Female Mice Offspring from Adverse Behavioral Effects Induced by Prenatal Heroin Exposure
J Pharmacol Exp Ther, 368 (1), 106-115
DOI 10.1124/jpet.118.251504, PubMed 30361238

Thaulow CH, Øiestad ÅML, Rogde S, Andersen JM, Høiseth G, Handal M, Mørland J, Vindenes V (2018)
Can measurements of heroin metabolites in post-mortem matrices other than peripheral blood indicate if death was rapid or delayed?
Forensic Sci Int, 290, 121-128
DOI 10.1016/j.forsciint.2018.06.041, PubMed 30015276

Thaulow CH, Øiestad ÅML, Rogde S, Karinen R, Brochmann GW, Andersen JM, Høiseth G, Handal M, Mørland J, Arnestad M, Øiestad EL, Strand DH, Vindenes V (2018)
Metabolites of Heroin in Several Different Post-mortem Matrices
J Anal Toxicol, 42 (5), 311-320
DOI 10.1093/jat/bky002, PubMed 29409037

Eriksen GS, Andersen JM, Boix F, Bergh MS, Vindenes V, Rice KC, Huestis MA, Mørland J (2016)
Comparison of (+)- and (-)-Naloxone on the Acute Psychomotor-Stimulating Effects of Heroin, 6-Acetylmorphine, and Morphine in Mice
J Pharmacol Exp Ther, 358 (2), 209-15
DOI 10.1124/jpet.116.233544, PubMed 27278234

Kvello AM, Andersen JM, Øiestad EL, Mørland J, Bogen IL (2016)
Pharmacological Effects of a Monoclonal Antibody against 6-Monoacetylmorphine upon Heroin-Induced Locomotor Activity and Pharmacokinetics in Mice
J Pharmacol Exp Ther, 358 (2), 181-9
DOI 10.1124/jpet.116.233510, PubMed 27217591

Gottås A, Ripel Å, Boix F, Vindenes V, Mørland J, Øiestad EL (2015)
Determination of dopamine concentrations in brain extracellular fluid using microdialysis with short sampling intervals, analyzed by ultra high performance liquid chromatography tandem mass spectrometry
J Pharmacol Toxicol Methods, 74, 75-9
DOI 10.1016/j.vascn.2015.06.002, PubMed 26123500

Bogen IL, Boix F, Nerem E, Mørland J, Andersen JM (2014)
A monoclonal antibody specific for 6-monoacetylmorphine reduces acute heroin effects in mice
J Pharmacol Exp Ther, 349 (3), 568-76
DOI 10.1124/jpet.113.212035, PubMed 24700886

Eriksen GS, Andersen JM, Boix F, Mørland J (2014)
3-Methoxynaltrexone is not a selective antagonist for the acute psychomotor stimulating effects of heroin and 6-monoacetylmorphine in mice
Pharmacol Biochem Behav, 122, 82-8
DOI 10.1016/j.pbb.2014.03.018, PubMed 24699386

Gottås A, Boix F, Øiestad EL, Vindenes V, Mørland J (2014)
Role of 6-monoacetylmorphine in the acute release of striatal dopamine induced by intravenous heroin
Int J Neuropsychopharmacol, 17 (9), 1357-65
DOI 10.1017/S1461145714000169, PubMed 24576415

Thaulow CH, Høiseth G, Andersen JM, Handal M, Mørland J (2014)
Pharmacokinetic interactions between ethanol and heroin: a study on post-mortem cases
Forensic Sci Int, 242, 127-134
DOI 10.1016/j.forsciint.2014.06.032, PubMed 25050840

Andersen JM, Haugen KS, Ripel A, Mørland J (2013)
The interference of ethanol with heroin-stimulated psychomotor activation in mice is not related to changed brain concentrations of the active metabolites 6MAM or morphine
Basic Clin Pharmacol Toxicol, 114 (2), 197-201
DOI 10.1111/bcpt.12133, PubMed 24102968

Gottås A, Øiestad EL, Boix F, Vindenes V, Ripel Å, Thaulow CH, Mørland J (2013)
Levels of heroin and its metabolites in blood and brain extracellular fluid after i.v. heroin administration to freely moving rats
Br J Pharmacol, 170 (3), 546-56
DOI 10.1111/bph.12305, PubMed 23865556

Høiseth G, Andersen JM, Mørland J (2013)
Less glucuronidation of morphine in the presence of ethanol in vivo
Eur J Clin Pharmacol, 69 (9), 1683-7
DOI 10.1007/s00228-013-1533-5, PubMed 23739999

Andersen JM, Klykken C, Mørland J (2012)
Long-term methadone treatment reduces phosphorylation of CaMKII in rat brain
J Pharm Pharmacol, 64 (6), 843-7
DOI 10.1111/j.2042-7158.2012.01469.x, PubMed 22571262

Gottas A, Oiestad EL, Boix F, Ripel A, Thaulow CH, Pettersen BS, Vindenes V, Morland J (2012)
Simultaneous measurement of heroin and its metabolites in brain extracellular fluid by microdialysis and ultra performance liquid chromatography tandem mass spectrometry
J Pharmacol Toxicol Methods, 66 (1), 14-21
DOI 10.1016/j.vascn.2012.04.009, PubMed 22561414

Sankararaman A, Masiulis I, Richardson DR, Andersen JM, Mørland J, Eisch AJ (2012)
Methadone does not alter key parameters of adult hippocampal neurogenesis in the heroin-naïve rat
Neurosci Lett, 516 (1), 99-104
DOI 10.1016/j.neulet.2012.03.066, PubMed 22487733

Andersen JM, Olaussen CF, Ripel A, Mørland J (2011)
Long-term methadone treatment impairs novelty preference in rats both when present and absent in brain tissue
Pharmacol Biochem Behav, 98 (3), 412-6
DOI 10.1016/j.pbb.2011.02.017, PubMed 21352846

Boix F, Andersen JM, Mørland J (2011)
Pharmacokinetic modeling of subcutaneous heroin and its metabolites in blood and brain of mice
Addict Biol, 18 (1), 1-7
DOI 10.1111/j.1369-1600.2010.00298.x, PubMed 21481103

Andersen JM, Ripel A, Boix F, Normann PT, Mørland J (2009)
Increased locomotor activity induced by heroin in mice: pharmacokinetic demonstration of heroin acting as a prodrug for the mediator 6-monoacetylmorphine in vivo
J Pharmacol Exp Ther, 331 (1), 153-61
DOI 10.1124/jpet.109.152462, PubMed 19541908

Karinen R, Andersen JM, Ripel A, Hasvold I, Hopen AB, Mørland J, Christophersen AS (2009)
Determination of heroin and its main metabolites in small sample volumes of whole blood and brain tissue by reversed-phase liquid chromatography-tandem mass spectrometry
J Anal Toxicol, 33 (7), 345-50
DOI 10.1093/jat/33.7.345, PubMed 19796503

Vindenes V, Pettersen BS, Gottås A, Christiansen NL, Boix F, Mørland J (2009)
Different effects on dopamine release in nucleus accumbens in mice by the morphine metabolites morphine-6-glucuronide and morphine-3-glucuronide
Basic Clin Pharmacol Toxicol, 105 (5), 357-60
DOI 10.1111/j.1742-7843.2009.00451.x, PubMed 19663818

Vindenes V, Ripel A, Handal M, Boix F, Mørland J (2009)
Interactions between morphine and the morphine-glucuronides measured by conditioned place preference and locomotor activity
Pharmacol Biochem Behav, 93 (1), 1-9
DOI 10.1016/j.pbb.2009.03.013, PubMed 19351545

Vindenes V, Handal M, Ripel A, Thaulow CH, Vindenes HB, Boix F, Mørland J (2008)
Different time schedules affect conditioned place preference after morphine and morphine-6-glucuronide administration
Pharmacol Biochem Behav, 89 (3), 374-83
DOI 10.1016/j.pbb.2008.01.012, PubMed 18308383

Vindenes V, Handal M, Ripel A, Boix F, Mørland J (2006)
Conditioned place preference induced by morphine and morphine-6-glucuronide in mice
Pharmacol Biochem Behav, 85 (2), 292-7
DOI 10.1016/j.pbb.2006.08.010, PubMed 17011617