Ettore Zuccato Plenary meeting 4, Milan 1-2 February 2018 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 4, Milan 1-2 February 2018 Milan 1-2 February 2018

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 Outputs of the Work Streams Committee activities (steering committee for publication; progress monitoring committee , coordinating groups for the WS) News, Information Milan 1-2 February 2018

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) Milan 1-2 February 2018 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 25 26 27 Feb Jul Jan Apr 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 Final revision Milan 1-2 February 2018

Identification and Assessment of New Psychoactive Substances: A European Network WS1 /1 NPS List List of 195 NPS; sub-list of 37 priority NPS (yellow list) Done /2a NPS identif. WW, urine List of 15 NPS confirmed in WW/Urine /2b - Urine collection - Epidemiology - Urine analysed (3 music festivals NO, 1 PT) - Epidemiology study (SIRUS) Ongoing (Norway Portugal) /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) ?? ?? /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 /2 RA – in vivo FFUL/EMCES Ongoing /3 RA - ex vivo WS3 /1 Synthesis standards and metabolites (UJI, FFULISBOA, MN) List of standards available Purchasing from the market Synthesis of unavailable molecules Done Ongoing (4MM-Fenidate, buphed.) /2 Anal. methods set up All the Partners /3 Analysis of Wastewater (EU cities) -Quantitative MN, UJI Ongoing /4 NPS use in Europe - Estimation

Identification and Assessment of New Psychoactive Substances: A European Network WS1 /1 NPS List List of 194 NPS; sub-list of 37 priority NPS (yellow list) Done - website /2a NPS identif. WW, urine List of 15 NPS confirmed - /2b - Urine collection - Epidemiology - Urine collected and analysed (3 music festivals NO, PT) - Epidemiology study. Protocol on best practice of prevention (SIRUS) Ongoing (paper ongoing) Ongoing Norway. PT SICAD Record /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) Ongoing FFUL Paulo (update of the method including metabolism) FFUL Rui, Maria, Cristina /3b Degradation exp. In vivo metabolism (UJI) Done (study of 5-MeO-MiPT; paper published) /3c Phisico-Chemical and PK studies By QSAR/in silico – prediction of NPS characteristics and pharmacokinetic (FFUL) Ongoing (software validation, buphedrone study) FFUL (Nuno Silva and Paulo) WS2 /1 RA - in vitro Neurodegeneration/neurotoxicity + neuro inflammation (FFUL) Yeast model impact (EMCES) Ongoing (effect of methedrone…) Ongoing (all NPS, Yellow list ?) FFUL (Dora Brites ) EMCES (Alexandre Quintas) /2 RA – in vivo in vivo studies (FFUL/EMCES) Ongoing ? Cristina, Alvaro L.. /3 RA - ex vivo ex vivo studies (FFUL) Ongoing? FFUL Cristina S., Dora 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 (+ Mario List) Done Ongoing (4MM-Fenidate, buphedrone ….) - (incl. Mario list) - UJI, FFUL (Maria Bronze, Rui) /2 Analytical methods set up All the Partners /3 Analysis of Wastewater (EU cities) IRFMN, UJI INMLCF (urine) Ongoing /4 NPS in Europe All the Partners (common paper) IRFMN, UJI, INMLCF..

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) Milan 1-2 February 2018

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 confirmed NPS CONFIRMED NPS LIST (January 2018) IUPAC name CAS number   Mephedrone (4-MMC) (RS)-2-methylamino-1-(4-methylphenyl)propan-1-one 1189805-46-6 4-MEC (4-Methylethcathinone) (RS)-2-ethylamino-1-(4-methylphenyl)propan-1-one 1225617-18-4 MDPV (3,4-Methylenedioxypyrovalerone) 1-(Benzo[d] [1,3]dioxol-5-yl)-2-(pyrrolidin-1-yl)pentan-1-one 687603-66-3 3,4-dimethylmethcathinone (3,4-DMMC) 1-(3,4-dimethylphenyl)-2-(methylamino)propan-1-one 1082110-00-6 α-PVP (α-pyrrolidinopentiophenone) NEW (RS)-1-Phenyl-2-(1-pyrrolidinyl)-1-pentanone 14530-33-7 PMA NEW para-Methoxyamphetamine (PMA) ; 4-methoxyamphetamine (4-MA) 23239-32-9 4-fluoromethcathinone (4-FMC ; Flephedrone) 1-(4-Fluorophenyl)-2-(methylamino)propan-1-one 447-40-5 4’-chloro-α-PPP 1-(4-chlorophenyl)-2-(1-pyrrolidinyl)-1-propanone 93307-24-5 (HCl) 3-MMC (3-methylmethcathinone) 2-(Methylamino)-1-(3-methylphenyl)propan-1-one 1246816-62-5 Methylone 1-(1,3-Benzodioxol-5-yl)-2-(methylamino)propan-1-one 186028-79-5 Penthylone 1-(1,3-benzodioxol-5-yl)-2-(methylamino)1-pentanone 17763-01-8 Butylone 1-(1,3-benzodioxol-5-yl)-2-(methylamino)butan-1-one 805875-11-7 Methcathinone α-methylamino-propiophenone ; ephedrone 5650-44-2 (R form); 112117-24-5 (S form) N,N dimethylcathinone (metamfepramone) (RS)-2-dimethylamino-1-phenylpropan-1-one 10105-90-5 (HCl) Ethylone (3,4-methylenedioxy-N-ethylcathinone) (RS)-1-(1,3-benzodioxol-5-yl)-2-(ethylamino)propan-1-one 1112937-64-0 Milan 1-2 February 2018

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 15 NPS confirmed Wastewater analysis should be focalized on confirmed NPS Risk Assessment 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 (for confirmation or not) synthetic cannabinoid metabolites (to investigate synthetic cannabinoids in WW) Milan 1-2 February 2018

1 (best practice of prevention) Identification and Assessment of New Psychoactive Substances: A European Network Outputs of the Work Streams (grant agreement) WS Research papers Chapter books Master thesis Protocols Training School events Post graduate courses WS1 2 1 (best practice of prevention) 1 WS2 WS3 Fulfilled Open/ongoing Milan 1-2 February 2018

Identification and Assessment of New Psychoactive Substances: A European Network Dissemination Dissemination (from the mid-term progress report): 5 scientific papers in high-ranked peer-reviewed international scientific journals (covering WS1 and WS3) 1 article in a newspaper (WS2) 2 oral presentations at international conferences (WS1) 8 educational activities involving a total of 200 students (WS2) and 2 “open laboratories” activities for students (WS2). 22/11/17 Jornada de formacion sobre nuevas substancias psicoactivas (training event/meeting-post graduate course) 1 paper ongoing in Norway (best practice on prevention) 5 papers planned for WS1 or WS3 What else ? (please, remember the acknowledgement to the EC !!) 3 further papers published by UJI Missing 1 post-graduate course for WS1 and WS2, 1 training event and 2 post-graduate course for WS3 Missing 2 research paper for WS2 (will be prepared) Milan 1-2 February 2018

Steering committee for publication/outputs/final report : Identification and Assessment of New Psychoactive Substances: A European Network Committee activities Steering committee for publication/outputs/final report : 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 meeting tomorrow, or a skype, for monitoring publications/outputs, Project progress, and for coordination among WSs (minutes !!) Milan 1-2 February 2018

Final Project Meeting, Lisbon, EMCDDA venue, April 2018 ? Identification and Assessment of New Psychoactive Substances: A European Network Problems discussion : Final Project Meeting, Lisbon, EMCDDA venue, April 2018 ? Meeting/Post graduate course (in Lisbon ?) Final Report Other Milan 1-2 February 2018