NPSNPS--EuronetEuronet project: patterns of NPS use using wastewater ––basedbased epidemiology

Sara Castiglioni

Mario Negri Institute for Pharmacological Research

2018 Expert meeting on the indicator, EMCDDA, Lisbon, 16th May 2018 Identification and Assessment of New Psychoactive Substances: A European Network

Wastewater – Based Epidemiology (WBE)

Measurement of excretion residues (biomarker) in urban wastewater

Evaluation of consumption or exposure to substances

V Almost all substances we consume are excreted unchanged or as a mixture of metabolites in urine and/faeces

V Excreted substances entry in sewer network VEnter sewage treatment plants VSampling and analysis raw wastewater Identification and Assessment of New Psychoactive Substances: A European Network

Wastewater – Based Epidemiology (WBE)

Estimation of illicit drugs consumption in three European cities Zuccato et al., Environ. Health Perspect. 2008

Sewage analysis CORE group (SCORE) Activities (2010) EuropeEurope--widewide monitoring (2011(2011--2017)2017) Results available at: http://www.emcdda.europa.eu/topics/pods/waste-water-analysis Identification and Assessment of New Psychoactive Substances: A European Network Wastewater – Based Epidemiology (WBE)

http://www.emcdda.europa.eu/topics/pods/waste-water-analysis Identification and Assessment of New Psychoactive Substances: A European Network

Aim of the study

Identification and Assessment of New Psycoactive Substances in Europe using WBE

V Select substances (NPS) to be investigated

V Develop a method to screen the presence of NPS (qualitative analyses)

V Develop a method to measure NPS (quantitative analyses)

V Monitor wastewater samples from different countries Identification and Assessment of New Psychoactive Substances: A European Network

WBE Advantages and Challenges for NPS

Ability to provide: Challenges:

‹ Objective estimates ‹ Limited use ‹ Near realreal--timetime estimates ‹Lots of substances ‹Low levels in wastewater ‹ Updated information ‹ Human metabolism unknown ‹ Qualitative and quantitative Difficult identify biomarkers data ‹

Identification of NPS WBE needs to be Evaluation of use tested Identification and Assessment of New Psychoactive Substances: A European Network

Samples investigated

COST SCORE Monitoring campaign 2016 -2017

Raw Wastewater Samples

Ireland The Netherlands Poland 14 European countries Slovakia 21 cities Switzerland Hungary Romania Slovenia Italy Serbia Bosnia and Bulgaria Herzegovina Portugal Pooled samples Weekdays - Weekend Identification and Assessment of New Psychoactive Substances: A European Network

Qualitative screening - NPS Selection

Sources

Alerts Reports of new substances (December 2013-March 2016) DATABASE 195 substances Alerts (Europe and Italy) + Italy seizure list + Notifications in Italy (intoxications) , (October 2013-March 2016) arilcicloexilamine - analogues, piperidine, UNODC control list tryptamine, synthetic cathinones, synthetic , synthetic , Criteria aminorex derivates, natural psychoactive Frequency of reporting substances, Most recently reported benzodiazepines Identification and Assessment of New Psychoactive Substances: A European Network

Qualitative screening - NPS Identified

Classes of NPS NPS Country Synthetic cathinones 3,4-DMeO--PVP Poland, Romania, Portugal The Netherlands, Slovenia, Tryptamines AMT (alpha-methyltryptamine) Slovakia, Italy, Germany, Portugal, Spain N-methyaminorex Slovenia Aminorex derivates 4,4 DMAR Ukraine NPDPA Serbia, Romania Bosnia Herzegovina, Portugal, 2-methoxyamphetamine Spain, Italy Phenethylamines 25iP-NBoME Romania 25E - NBoMe Slovenia, Germany 25H - NBoMe Spain Identification and Assessment of New Psychoactive Substances: A European Network

Quantitative analysis Results 2016 Results 2017

Synthetic Cathinones Synthetic Cathinones Mephedrone Phenethylamines Phenethylamines Mephedrone Methcathinone PMA PMA Methcathinone N,N-Dimethylcathinone PMMA PMMA N,N-Dimethylcathinone Ethcathinone 25-B-NBoMe Ethcathinone 25-B-NBoMe Methedrone 25-C-NBoMe Methedrone 25-C-NBoMe 4-FMC 25-I-NBoMe 4-FMC 25-I-NBoMe 3,4-DMMC 25-iP-NBoMe 3,4-DMMC Ketamine analogues 4-MEC NEDPA 4-MEC Methoxethamine Buphedrone Ketamine analogues Buphedrone Tryptamines Pentedrone Methoxethamine Pentedrone 5-MeO-MIPT Methylone Tryptamines Methylone Ethylone 5-MeO-MIPT Ethylone Butylone Butylone Pentylone 5-Fluoropentyl-3- Pentylone 1-Naphyrone pyridinoylindole 1-Naphyrone 26 substances searched Naphyrone Aminorex derivates Naphyrone MDPV 4-4'-DMAR (4-4'- MDPV 10 substances found in α -PVP dimethylaminorex) α -PVP 4-Cl- α -PPP 4-Cl- α -PPP wastewater (21 cities)

30 substances searched 5 substances found in wastewater (7 cities) Identification and Assessment of New Psychoactive Substances: A European Network

Results 2017 – Weekly Profile NPS

14 Mephedrone 2.0 Methcathinone Pool Week Pool Week 1.8 12 Pool Weekend 1.6 Pool Weekend 10 1.4

8 1.2 1.0 6 0.8 4 0.6 0.4 2

Mass loads mg/day/1000 inh Slovakia Center Italy Pool Week Pool Weekend Pool Week Pool Weekend Buphedrone 0.26 0.17

Zuccato et al., (2008), Environmental Health Perspectives 116, 1027-1032

Thomas et al., (2012), STOTEN, 432:432-9 Identification and Assessment of New Psychoactive Substances: A European Network

Comparison NPS - Classical Drugs

Classical Drugs NPS Mass Loads (mg/day/ 1000 inhabitants) Mass Loads (mg/day/ 1000 inhabitants) 3.8-120 0.3 -177 0.2 -21 MDMA 2.9-60 47-476

NPS levels in wastewater are at least 5 times lower than classical drugs

This reflects a lower use of NPS Identification and Assessment of New Psychoactive Substances: A European Network

Conclusions

V WBE was applied successfully to monitor the use of NPS

VA quantitative analysis was done for > 30 substances

V The levels of NPS were lower than those of the “classical” drugs – lower use ? V Different s patial and temporal patterns of use were found among countries V WBE is a good complementary tool to evaluate the use of NPS Identification and Assessment of New Psychoactive Substances: A European Network Acknowledgements Project Partners

1. Mario Negri Institute (coordinator) 2. University Jaume I 3. Faculdade de Farmacia Universidade de Lisboa 4. Instituto Nacional de Medicina Legal EMCDDA e Ciencias Forenses Paul Griffith, Liesbeth 5. Institute of Health Sciences “Egas Monitz” Vandam, Ana Gallegos, 6. (Norwegian Institute of Water Research) João Matias

Project Collaborators (who kindly provided samples)

Igor Bodik (Slovakia); Ester Heath (Slovenia); Katarzyna Styszko (Poland); Erik Emke (The Netherlands); Barbara Kasprzyk-Hordern (UK); Lisa Jones (Ireland); Mariya Skobley and Tanya Bodnarchuk (Ucraine); Maja Turk Sekulic and Jelena Radonic (Serbia); Andjelka Petkovic (Serbia); Simone Milanolo (Bosnia Herzegovina); Simion Beldean (Romania); Jelyaz Rangelov and Teodora Todorova (Bulgary); Francesca Pizza (Italy); Francesco Poretti (Switzerland); Miguel Santos (Portugal). Thanks for your attention!