Ettore Zuccato Plenary meeting 3, Castellon 29th March 2017 Identification and Assessment of New Psychoactive Substances: A European Network Overview of the Project NPS-Euronet “present situation and future perspectives” Ettore Zuccato Plenary meeting 3, Castellon 29th March 2017 Castellon, 29th March 2017

Discussion topics Present situation and future activities Identification and Assessment of New Psychoactive Substances: A European Network Discussion topics Present situation and future activities Tasks not (yet) fulfilled (who and when) NPS selection for Risk Assessment and further studies Outputs of the Work Streams Committee activities (steering committee for publication; progress monitoring committee , coordinating groups for the WS) Castellon, 29th March 2017

Original Revised (Lisbon meeting) Identification and Assessment of New Psychoactive Substances: A European Network   Months Activities 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 WS0 WS1 - activity 1 WS1 - activity 2a WS1 - activity 2b WS1 - activity 3a WS1 - activity 3b WS1 - activity 3c WS2 WS3 - activity 1 WS3 - activity 2 WS3 - activity 3 Original   Months Activities 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Feb Jul  Sep Jan  16 WS0 WS1 - activity 1 WS1 - activity 2a WS1 - activity 2b WS1 - activity 3a WS1 - activity 3b WS1 - activity 3c WS2 WS3 - activity 1 WS3 - activity 2 WS3 - activity 3 Revised (Lisbon meeting) Castellon, 29th March 2017

Identification and Assessment of New Psychoactive Substances: A European Network   Months Activities 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Feb Jul  Sep Jan  16 WS0 WS1 - activity 1 WS1 - activity 2a WS1 - activity 2b WS1 - activity 3a WS1 - activity 3b WS1 - activity 3c WS2 WS3 - activity 1 WS3 - activity 2 WS3 - activity 3 + 4 Castellon, 29th March 2017

Identification and Assessment of New Psychoactive Substances: A European Network WS1 /1 NPS List List of 190 NPS; sub-list of 30 priority NPS (yellow list) Done /2a NPS identif. WW, urine List of 13 NPS confirmed + 12 NPS suspected Done/ongoing /2b - Urine collection - Epidemiology - Urine collected and analysed (3 music festivals) - Epidemiology study (SIRUS) Data GAP /3a Identif. metabolites, transf. products (TPs) in silico modelling for prediction of metabolism (NIVA) In vitro studies (microsomes, hepatocytes) (FFUL) Covered by FFUL (mid-term PR) Starting now /3b Degradation exp. In vivo metabolism (UJI) Ongoing (study of 5-MeO-MiPT) /3c Phisico-Chemical and PK studies By QSAR/in silico – prediction of NPS characteristics and pharmacokinetic (FFUL) Ongoing (software validation, buphedrone study) WS2 /1 RA - in vitro Neurodegeneration + neuro inflammation (FFUL) Yeast model impact (EMCES) Ongoing -effect of methedrone Ongoing -effect buphedrone (no ef.) /2 RA – in vivo FFUL/EMCES /3 RA - ex vivo

Identification and Assessment of New Psychoactive Substances: A European Network WS3 /1 Synthesis standards and metabolites (UJI, FFULISBOA, MN) List of standards available (inter laboratory exch.) Purchasing from the market Synthesis of unavailable molecules Done Ongoing Ongoing (4MM-Fenidate, buphedrone) /2 Analytical methods set up All the Partners /3 Analysis of Wastewater (EU cities) -Quantitative MN, UJI Future/starting now /4 NPS use in Europe - Estimation Future

Identification and Assessment of New Psychoactive Substances: A European Network WS1 /1 NPS List List of 190 NPS; sub-list of 31 priority NPS (yellow list) Done - /2a NPS identif. WW, urine List of 13 NPS confirmed + 12 NPS suspected Done/ongoing UJI, IRFMN, INMLCF /2b - Urine collection - Epidemiology - Urine collected and analysed (3 music festivals) - Epidemiology study. Protocol on best practice of prevention (SIRUS) Data GAP What to do ? /3a Identif. metabolites, transf. products (TPs) in silico modelling for prediction of metabolism (NIVA) In vitro studies (microsomes, hepatocytes) (FFUL) Covered by FFUL? (according to mid-term Progress Report) Start now ? Who in charge ? FFUL (Alvaro) /3b Degradation exp. In vivo metabolism (UJI) Ongoing (study of 5-MeO-MiPT) UJI /3c Phisico-Chemical and PK studies By QSAR/in silico – prediction of NPS characteristics and pharmacokinetic (FFUL) Ongoing (software validation, buphedrone study) FFUL (Nuno Elvas Silva) WS2 /1 RA - in vitro Neurodegeneration/neurotoxicity + neuro inflammation (FFUL) Yeast model impact (EMCES) Ongoing -effect of methedrone Ongoing -effect of buphedrone FFUL (Dora Brites ) EMCES (Alexandre Quintas) /2 RA – in vivo in vivo studies (FFUL/EMCES) /3 RA - ex vivo ex vivo studies (FFUL/EMCES) WS3 /1 Synthesis standards and metabolites (UJI, FFULISBOA, MN) List of standards available (inter laboratory exch.) Purchasing from the market (also INMLCF) Synthesis of unavailable molecules Done Done/Ongoing Ongoing (4MM-Fenidate, buphedrone) - IRFMN, UJI, INMLCF UJI, FFUL (Maria Bronze) /2 Analytical methods set up All the Partners Ongoing IRFMN /3 Analysis of Wastewater (EU cities) IRFMN, UJI Future/starting now /4 NPS in Europe Future

NPS selection for Risk Assessment and further studies Identification and Assessment of New Psychoactive Substances: A European Network NPS selection for Risk Assessment and further studies List of 13 NPS confirmed (+ 12 NPS suspected) Confirmed NPS Suspected NPS In Yellow List In List (to be included in the yellow list) Not included in List or Yellow List (to be included in the yellow list) Castellon, 29th March 2017

NPS selection for Risk Assessment and further studies Identification and Assessment of New Psychoactive Substances: A European Network NPS selection for Risk Assessment and further studies List of 13 NPS confirmed (+ 12 NPS suspected) Wastewater analysis should be focalized on confirmed NPS RA should be focalized on confirmed NPS Metabolism studies should be focalized on “confirmed” NPS synthetic cannabinoids on the yellow list Synthesis of substances/metabolites should be focalized on “suspected” NPS synthetic cannabinoid metabolites Castellon, 29th March 2017

In List (to be included in the yellow list) Identification and Assessment of New Psychoactive Substances: A European Network Confirmed NPS Suspected NPS 4-MEC (4-Methylethcathinone) MDPV (3,4-Methylenedioxypyrovalerone) 3,4-dimethylmethcathinone (3,4-DMMC) 4-fluoromethcathinone (4-FMC ; Flephedrone) 4’-chloro-α-PPP 3-MMC (3-methylmethcathinone) Methylone Penthylone Butylone Methcathinone N,N dimethylcathinone (metamfepramone) Ethylone (3,4-methylenedioxy-N-ethylcathinone) 2-phenethylamine 3,4-DMeO-α-PVP 3-methoxymethcathinone 4'-chloro-α-PPP (confirmed) 4-methylmethylphenidate or methoxethamine bk-DMDBP (Dipentylone) PMMA (p-methoxymethamphetamine) α-methyltryptamine α-PVP (α-pyrrolidinopentiophenone) 5-fluoropentyl-3-pyridinoylindole PMA DB-MDBP* In Yellow List In List (to be included in the yellow list) Not included in List or Yellow List (to be included in the yellow list) Castellon, 29th March 2017

1 (best practice of prevention) Identification and Assessment of New Psychoactive Substances: A European Network Outputs of the Work Streams (expected) WS Research papers Chapter books Master thesis Protocols Training School events Meeting/Post graduate courses WS1 2 1 (best practice of prevention) 1 WS2 WS3 Castellon, 29th March 2017

Steering committee for publication/outputs : Identification and Assessment of New Psychoactive Substances: A European Network Committee activities Steering committee for publication/outputs : Alvaro Lopez, Juan Vincente Sancho, Ettore Zuccato Progress monitoring committee : Alvaro Lopez, Lubertus Bijlsma, Ettore Zuccato Coordinating groups for the WS : WS1 : Felix Hernandez WS2 : Dora Brites WS3 : Sara Castiglioni Suggested a skype each 2-3 months for monitoring publications/outputs, Project progress, and for coordination among WSs Castellon, 29th March 2017

Problem discussion and solving (discussion at 4 pm) Identification and Assessment of New Psychoactive Substances: A European Network Problem discussion and solving (discussion at 4 pm) Next meeting (where ?) Extension of the project (2-3 months more ?) Norwegian issue (wish to pay for the protocol ?) Others Castellon, 29th March 2017

Identification and Assessment of New Psychoactive Substances: A European Network Castellon, 29th March 2017