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New Psychoactive Substances

glass tubes and drug

Department research section: Drug identification and analysis

What are New Psychoactive Substances (NPS)?

The term ‘new psychoactive substances’ (NPS) can be defined as substances of abuse, either in a pure form or in a preparation, that are not controlled by the 1961 United Nations Single Convention on Narcotic Drugs or the 1971 United Nations Single Convention on Psychotropic Substances, but which may post a public health threat comparable to that posed by substances listed in these conventions.In general terms,NPS, most commonly marketed as ‘legal highs’, ‘designer drugs’, and ‘research chemicals’, are forms of recreational drugs, which have been increasing in popularity at an unprecedented rate over the last decade. NPS can produce psychopharmacological effects similar or greater than those of illicit drugs, such as amphetamines, cocaine, heroin and cannabis. These substances are cleverly designed and marketed to avoid contravening existing national and international drug legislation. NPS are available from several sources, including the internet, specialised shops (in some countries), known as ‘head shops’, and on the illicit drug market. Unlike pharmaceuticals, which undergo extensive analytical and clinical testing in controlled studies, NPS are developed with non-existent quality control and clinical drug safety testing in place. These substances arrive onto the recreational drug market with little information available on their chemical or pharmacological properties. The absence of chemical information creates challenges for scientists who are posed with the unequivocal identification of NPS in forensic drug seizures or clinical samples. In addition, the unknown pharmacological properties of NPS, routes of administration and unknown potency can result in adverse effects in users.

What we do?

The NPS phenomenon has created challenges for scientists who are tasked with the unambiguous identification of NPS in drug seizures or clinical samples. In recent times, the identification and characterisation of newly emerging psychoactive drugs has become a continuous part of forensic drug chemistry. The investigations concerning NPS can be greatly affected by the absence of chemical reference standards for both parent drugs and their metabolites. In addition, further difficulties associated with the unique identification of NPS arise when positional isomers and stereoisomers exist, or when mixtures of NPS or difficult matrices are presented. From the medical viewpoint, knowledge of the pharmacological activity of NPS is vital for emergency medical professionals treating patients with drug intoxications.

The primary aim of this research is to provide chemical profiles of new psychoactive substances, through the development of syntheses protocols for reference materials, including positional isomers, followed by extensive analytical characterisation. Techniques used in the analytical characterisation include several chromatographic, spectroscopic, mass spectrometric platforms and x-ray crystal structure analysis. A secondary aim is to provide pharmacological information on these NPS. Pharmacological profiles of NPS are achieved through collaboration with the Designer Drug Research Unit (DDRU), Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, USA. The pharmacological profile of a selected NPS and its isomers are ascertained using monoamine transporter assays. This assay provides information on the reuptake and releasing properties of a selected drug at the dopamine, norepinephrine and serotonin transporters using in vitro transporter assays in rat brain synaptosomes. This technique can determine if the drugs under investigation are strong/weak transporter blockers or transporter substrates, thus providing information pertaining to the molecular mechanism of action of the drugs.

Overall, this research on NPS utilises a multidisciplinary approach to ascertain the chemical and pharmacological profiles of NPS following their detection on the recreational drug market. This strategy utilises the expertise of a collaborative multidisciplinary team of scientists and combines organic and analytical chemistry with pharmacological-based studies. The research ethos follows an in-house protocol developed to provide information on NPS in a timely manner:

  • Notification of the NPS
  • Synthesis and analytical characterisation of the reference material of the NPS, plus possible positional isomers.
  • Characterisation of the NPS original sample (vendor sample)
  • Pharmacological evaluation of the NPS, plus positional isomers.
  • Information disseminated via peer-reviewed scientific publication.
  • Application to forensic case studies

Researchers:

  • Prof. Michael Barry – Pharmacology and Therapeutics, TCD.
  • Dr. Pierce Kavanagh – Pharmacology and Therapeutics, TCD.
  • Dr. Gavin McLaughlin – Forensic Science Ireland (FSI).
  • Dr. Geraldine Dowling – Institute of Technology Sligo and Pharmacology and Therapeutics, TCD.
  • Dr. John Power – Forensic Science Ireland (FSI).
  • Dr. Brendan Twamley – School of Chemistry, TCD.
  • Dr. John O’Brien – School of Chemistry, TCD.
  • Mr Brian Talbot – School of Pharmacy, TCD.
  • Dr. Gary Hessman, School of Chemistry, TCD

Main external collaborators

  • Dr. Simon D. Brandt – Liverpool John Moores University, Liverpool, UK.
  • Dr. Michael H. Baumann – Designer Drug Research Unit, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, USA.
  • Dr. Rachel Christie – European Monitoring Centre for Drug and Drug Addiction, Lisbon, Portugal.
  • Prof. Elizabeth Gardner – University of Alabama at Birmingham, Birmingham, Alabama, USA.

Selection of Publications

Gavin McLaughlin, Noreen Morris, Pierce V. Kavanagh, John D. Power, Geraldine Dowling, Brendan Twamley, John O’Brien, Gary Hessman, Brian Murphy, Donna Walther, John S. Partilla, Michael H. Baumann, Simon D. Brandt. Analytical characterization and pharmacological evaluation of the new psychoactive substance 4-fluoromethylphenidate (4F-MPH) and differentiation between the (±)-threo and (±)-erythro diastereomers. Drug Testing and Analysis. 2017, 9, 347-357. DOI: 10.1002/dta.2167

John D. Power, Pierce V. Kavanagh, Gavin McLaughlin, Michael Barry, Geraldine Dowling, Simon D. Brandt. ‘APAAN in the neck’ – A reflection on some novel impurities found in seized materials containing amphetamine in Ireland during forensic analysis. Drug Testing and Analysis. 2017. DOI: 10.1002/dta.2194

Geraldine Dowling, Pierce V. Kavanagh, Brian Talbot, John O’Brien, Gary Hessman, Gavin McLaughlin, Brendan Twamley, Simon D. Brandt. Outsmarted by nootropics? An investigation into the thermal degradation of modafinil, modafinic acid, adrafinil, CRL-40,940 and CRL-40,941 in the GC injector: formation of 1,1,2,2-tetraphenylethane and its tetra fluoro analog. Drug Testing and Analysis. 2017, 9, 446-452. DOI: 10.1002/dta.2142

Gavin McLaughlin, Noreen Morris, Pierce V. Kavanagh, John D. Power, Geraldine Dowling, Brendan Twamley, John O’Brien, Brian Talbot, Donna Walther, John S. Partilla, Michael H. Baumann, Simon D. Brandt. Synthesis, characterization and monoamine transporter activity of the new psychoactive substance mexedrone and its N-methoxy positional isomer, N-methoxymephedrone. Drug Testing and Analysis. 2017, 9, 358-368. DOI: 10.1002/dta.2053

Simon D. Brandt, Pierce V. Kavanagh. Addressing the challenges in forensic drug chemistry. Drug Testing and Analysis, 2017, 9, 342–346. DOI: 10.1002/dta.2169

Florian Franz, Verena Angerer, Simon D. Brandt, Gavin McLaughlin, Pierce V. Kavanagh, Bjoern Moosmann, Volker Auwarter. In vitro metabolism of the synthetic cannabinoid 3,5-AB-CHMFUPPYCA and its 5,3-regioisomer and investigation of their thermal stability. Drug Testing and Analysis. 2017, 9, 311-316. DOI: 10.1002/dta.1950.

Gavin McLaughlin, Noreen Morris, Pierce V. Kavanagh, Geraldine Dowling, John D. Power, Brendan Twamley, John O'Brien, Brian Talbot, Harald H. Sitte, Simon D. Brandt. Test purchase, synthesis and characterization of 3-fluorophenmetrazine (3-FPM) and differentiation from its ortho- and para-substituted isomers. Drug Testing and Analysis. 2017, 9, 369-377. DOI: 10.1002/dta.1945.

John D. Power, Pierce V. Kavanagh, Gavin McLaughlin, Geraldine Dowling, Michael Barry, John O'Brien, Brian Talbot, Brendan Twamley, Simon D. Brandt. Forensic analysis of P2P derived amphetamine synthesis impurities: identification and characterization of indene by-products. Drug Testing and Analysis. 2017, 9, 446-452. DOI: 10.1002/dta.1944.

Simon D. Brandt, Pierce V. Kavanagh, Geraldine Dowling, Brian Talbot, Folker Westphal, Markus R. Meyer, Hans H. Maurer, Adam L. Halberstadt. Analytical characterization of N,N-diallyltryptamine (DALT) and 16 ring-substituted derivatives. Drug Testing and Analysis. 2017, 9, 115–126. DOI: 10.1002/dta.1974

Kelly B. Texter, Rachel Waymach, Pierce V. Kavanagh, John O'Brien, Brian Talbot, Simon D. Brandt, Elizabeth A. Gardner. Identification of pyrolysis products of the new psychoactive substance 2-amino-1-(4-bromo-2,5-dimethoxyphenyl)ethanone hydrochloride (bk-2C-B) and its iodo analogue bk-2C-I. Drug Testing and Analysis, 2017. DOI: 10.1002/dta.2200

Simon D. Brandt, Pierce V. Kavanagh, Folker Westphal, Simon P. Elliott, Jason Wallach, Alexander Stratford, David E. Nichols, Adam L. Halberstadt. Return of the lysergamides. Part III: Analytical characterization of N6-ethyl-6-norlysergic acid diethylamide (ETH-LAD) and 1-propionyl ETH-LAD (1P–ETH-LAD). Drug Testing and Analysis. 2017, DOI: 10.1002/dta.2196

Simon D. Brandt, Pierce V. Kavanagh, Folker Westphal, Simon P. Elliott, Jason Wallach, Tristan Colestock, Timothy E. Burrow, Stephen J. Chapman, Alexander Stratford, David E. Nichols, Adam L. Halberstadt. Return of the lysergamides. Part II: Analytical and behavioural characterization of N6-allyl-6-norlysergic acid diethylamide (AL-LAD) and (2’S,4’S)-lysergic acid 2,4-dimethylazetidide (LSZ). Drug Testing and Analysis. 2017, 9, 38–50. DOI: 10.1002/dta.1985

Simon D. Brandt, Pierce V. Kavanagh, Brendan Twamley, Simon P. Elliott, Jason Wallach, Alexander Stratford, Landon M. Klein, John D. McCorvy, David E. Nichlos. Return of the lysergamides. Part IV: Analytical and pharmacological characterization of lysergic acid morpholide (LSM-775). Drug Testing and Analysis. 2017, DOI: 10.1002/dta.2222

2016

Gavin McLaughlin, Noreen Morris, Pierce V. Kavanagh, John D. Power, Brendan Twamley, John O’Brien, Brian Talbot, Geraldine Dowling, Simon D. Brandt. The synthesis and characterisation of the ‘research chemical’ N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(cyclohexylmethyl)-3-(4-fluorophenyl)-1H-pyrazole-5-carboxamide (3,5-AB-CHMFUPPYCA) and differentiation from its 5,3-regioisomer. Drug Testing and Analysis. 2016, 8, 920-929. DOI: 10.1002/dta.1864.

Jason Wallach, Tristan Colestock, Brian Cicali, Simon P. Elliott, Pierce V. Kavanagh, Adeboye Adejare, Nicola M. Dempster, Simon D. Brandt  Syntheses and analytical characterizations of N-alkyl-arylcyclohexylamines. Drug Testing and Analysis. 2016, 8, 801–815. DOI: 10.1002/dta.1861.

Simon D. Brandt, Pierce V. Kavanagh, Folker Westphal, Alexander Stratford, Simon P. Elliott, Khoa Hoang, Jason Wallach, Adam L. Halberstadt. Return of the lysergamides. Part I: Analytical and behavioural characterization of 1-propionyl-d-lysergic acid diethylamide (1P-LSD). Drug Testing and Analysis. 2016, 8, 891–902. DOI: 10.1002/dta.1884.

Gavin McLaughlin, Noreen Morris, Pierce V. Kavanagh, John D. Power, John O’Brien, Brian Talbot, Simon P. Elliott, Jason Wallach, K. Hoang, Hamilton Morris, Simon D. Brandt. Test purchase, synthesis and characterization of 2-methoxydiphenidine (MXP) and differentiation from its meta- and para-substituted isomers. Drug Testing and Analysis. 2015, 8, 98-109. DOI: 10.1002/dta.1800.

John D. Power, Pierce Kavanagh, Gavin McLaughlin, John O’Brien, Brian Talbot, Michael Barry, Brendan Twamley, Geraldine Dowling, Simon D. Brandt. Identification and characterization of an imidazolium by-product formed during the synthesis of 4-methylmethcathinone (mephedrone). Drug Testing and Analysis. 2015, 7, 894-902. DOI: 10.1002/dta.1789.

John D. Power, Pierce V. Kavanagh, John O'Brien, Michael Barry, Brendan Twamley, Brian Talbot, Geraldine Dowling, Simon D. Brandt. Test purchase, identification and synthesis of 2-amino-1-(4-bromo-2, 5-dimethoxyphenyl)ethan-1-one (bk-2C-B). Drug Testing and Analysis. 2015, 7, 512–518. DOI: 10.1002/dta.1699

Gavin McLaughlin, Noreen Morris, Pierce V. Kavanagh, John D. Power, Brendan Twamley, John O’Brien, Brian Talbot, Geraldine Dowling, Olivia Mahony, Simon D. Brandt, Julian Patrick, Roland P. Archer, John S. Partilla, Michael H. Baumann. Synthesis, characterization and monoamine transporter activity of the new psychoactive substance 3’,4’-methylenedioxy-4-methylaminorex (MDMAR). Drug Testing and Analysis. 2014, 7, 555-564. DOI: 10.1002/dta.1732.

Jason Wallach, Pierce V. Kavanagh, Gavin McLaughlin, Noreen Morris, John D. Power, Simon P. Elliott, Marion S. Mercier, David Lodge, Hamilton Morris, Nicola M. Dempster, Simon D. Brandt. Preparation and characterization of the ‘research chemical’ diphenidine, its pyrrolidine analogue, and their 2,2-diphenylethyl isomers.  Drug Testing and Analysis. 2014, 7, 358-367. DOI: 10.1002/dta.1689

Pierce V. Kavanagh, John D. Power. New psychoactive substances legislation in Ireland – Perspectives from academia. Drug Testing and Analysis. 2014, 6, 884-891. DOI: 10.1002/dta.1598

Emily D. Bouso, Elizabeth A. Gardner, John O’Brien, Brian Talbot, Pierce V. Kavanagh. Characterization of the pyrolysis products of methiopropamine. Drug Testing and Analysis. 2014, 4, 676-683. DOI: 10.1002/dta.1571
Kenneth R. Scott, John D. Power, Sean D. McDermott, John E. O'Brien, Brian N. Talbot, Michael G. Barry, Pierce V. Kavanagh. Identification of (2-aminopropyl)indole positional isomers in forensic samples. Drug Testing and Analysis. 2014, 6, 598–606. DOI:10.1002/dta.1508

John D. Power, Kenneth R. Scott, Elizabeth A. Gardner, Bronagh M. Curran McAteer, John E. O'Brien, Margaret Brehon, Brian Talbot, Pierce V. Kavanagh. The syntheses, characterization and in vitro metabolism of nitracaine, methoxypiperamide and mephtetramine. Drug Testing and Analysis. 2014, 6, 668–675. DOI:10.1002/dta.1616

Simon D. Brandt, Michael H. Baumann, John S. Partilla, Pierce V. Kavanagh, John D. Power, Brian Talbot, Brendan Twamley, Olivia Mahony, John O'Brien, Simon P. Elliott, Roland P. Archer, Julian Patrick, Kuldip Singh, Nicola M. Dempster, Simon H. Cosbey. Characterization of a novel and potentially lethal designer drug (±)-cis-para-methyl-4-methylaminorex (4,4'-DMAR, or ‘Serotoni’). Drug Testing and Analysis. 2014, 6, 684–695. DOI:10.1002/dta.1668

Daniel Angelov, John O'Brien, Pierce V. Kavanagh. The syntheses of 1-(2-thienyl)-2-(methylamino) propane (methiopropamine) and its 3-thienyl isomer for use as reference standards. Drug Testing and Analysis. 2013, 5, 145–149. DOI:10.1002/dta.298

Pierce V. Kavanagh, John O'Brien, John D. Power, Brian Talbot, Sean D. McDermott. ‘Smoking’ mephedrone: The identification of the pyrolysis products of 4-methylmethcathinone hydrochloride. Drug Testing and Analysis. 2013, 5, 291–305. DOI:10.1002/dta.1373

Andrzej Stanczuk, Noreen Morris, Elizabeth A. Gardner, Pierce V. Kavanagh. Identification of (2-aminopropyl)benzofuran (APB) phenyl ring positional isomers in Internet purchased products. Drug Testing and Analysis. 2013, 5, 270–276. DOI:10.1002/dta.1451

Pierce V. Kavanagh, Daniel Angelov, John O'Brien, John D. Power, Sean D. McDermott, Brian Talbot, John Fox, Cora O'Donnell, Rachel Christie. The synthesis and characterization N-methyl-3-phenyl-norbornan-2-amine (Camfetamine™). Drug Testing and Analysis. 2013, 5, 247–253. DOI:10.1002/dta.411

Andrej Grigoryev, Pierce V. Kavanagh, Aleksandra Melnik. The detection of the urinary metabolites of 1-[(5-fluoropentyl)-1H-indol-3-yl]-(2-iodophenyl)methanone (AM-694), a high affinity cannabimimetic, by gas chromatography – mass spectrometry. Drug Testing and Analysis. 2013, 5, 110–115. DOI:10.1002/dta.1336

Pierce V. Kavanagh, Andrej Grigoryev, Sergey Savchuk, IrinaMikhura, Andrew Formanovsky. UR-144 in products sold via the Internet: Identification of related compounds and characterization of pyrolysis products. Drug Testing and Analysis. 2013, 5, 683–692. DOI:10.1002/dta.1456

Pierce V. Kavanagh, Daniel Angelov, John O'Brien, John Fox, Cora O'Donnell, Rachel Christie, John D. Power, Sean D. McDermott. The syntheses and characterization 3β-(4-fluorobenzoyloxy)tropane (fluorotropacocaine) and its 3α isomer. Drug Testing and Analysis. 2012, 4, 33–38. DOI:10.1002/dta.362

Andrej Grigoryev, Pierce V. Kavanagh, Aleksandra Melnik. The detection of the urinary metabolites of 3-[(adamantan-1-yl)carbonyl]-1-pentylindole (AB-001), a novel cannabimimetic, by gas chromatography-mass spectrometry. Drug Testing and Analysis. 2012, 4, 519–524. DOI:10.1002/dta.350

Pierce V. Kavanagh, John O’Brien, John Fox, Cora O’Donnell, Rachel Christie, John D. Power, Sean D. McDermott. The analysis of substituted cathinones. part 3. synthesis and characterization of 2,3-methylenedioxy substituted cathinones. Forensic Science International. 2012, 216, 19-28. DOI: 10.1016/j.forsciint.2011.08.011