New Psychoactive Substances (NPS): the EU Early Warning System (EWS) perspective

Rachel Christie, PhD – Action on new drugs, Risks to public safety and security unit, EMCDDA CADAP Regional Conference on new psychoactive substances, 6 February 2019, Bishkek, Kyrgyzstan Historical perspective: the future of drugs of abuse?

In 1988 Henderson made some predictions about the future drugs of abuse…..

• Future drugs of abuse will be synthetics  • Synthesised from readily available precursors  • Derivatives of pharmaceuticals  • Very potent  • Often very selective  • Marketed very cleverly  Henderson GL. Designer drugs: past history and future prospects. Journal of Forensic Science. 1988 Mar 2 1;33(2):569-75 The future of drugs of abuse?

3 The future of drugs of abuse?

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NPS: from imitation to innovation

‘Designer drugs’ Party Herbal Research Legal pills highs chemicals highs

‘Legal highs’

Phenethylamines Tryptamines Piperazines Cathinones Synthetic CBs 1980s 1990s 2000s 2005 2008

Quest for new ‘ecstasy’ BZP Mephedrone Spice Who we are, what we do

Factual, Objective, Reliable, Comparable Substances monitored by the EU EWS

2018: 55

>700 substances monitored in 13 categories (2005–2018): • >190 synthetic cannabinoids • >130 synthetic cathinones • ~50

• >20 benzodiazepines 8 NPS detections in the EU

More than 300,000 seizures of NPS reported by Synthetic cannabinoids and cathinones law enforcement from 2005–2016 account for almost 80% of all seizure cases reported in 2016 Almost 71,000 seizures of NPS in 2016

9 NPS quantities in the EU

More than 24 tonnes of NPS seized by law enforcement from 2005–2016 Synthetic cannabinoids and cathinones accounted for 80% of all seizure cases and Just over 4 tonnes of NPS seized in quantities seized in 2016 2016

10 What caused the flood?

11 What caused the flood?

China ▪ In 2015 almost 1.2 tonnes of the total quantity of NPS substances seized in the EU originated in China.

▪ 11 single seizures at airports in Spain, almost 1.1 tonnes of cathinones.

▪ October 2015: the People’s Republic of China subjected 116 NPS to control

▪ In 2016, just over 300 kg of NPS seized in the EU had originated in China. ▪ Almost 90% of those seizures occurred at airports in Spain and consisted of cathinones, cannabinoids and other NPS.

In 2016, China, Spain, the Netherlands and the UK were the most frequently reported NPS origin countries based on seizures reported to the EWS

12 Responding to harms

Public health alerts issued in 2016 and 2017 included:

• Serious adverse events associated with the use of cannabinoids • Deaths associated with the use of potent opioids and fentanils • Superman logo ecstasy tablets containing PMMA • Deaths associated with CUMYL-4CN-BINACA Responding to harms: risk assessments completed 1998 - 2018

1998 1999 2000 2001 2002 2003 2004 2005 2006

MBDB 4-MTA PMMA 2-CI GHB 2-C-T-2 2-C-T-7 TMA-2

2007 2008 2009 2010 2011 2012 2013 2014 2015

BZP mephedrone 4-MA 5-IT Methoxetamine α-PVP MDPV 25I-NBOMe AH-7921 4,4’-DMAR MT-45 2016 …. 2017 …. 2018 …. Acryloylfentanyl MDMB-CHMICA Cyclopropylfentanyl Methoxyacetylfentanyl AB-CHMINACA ADB-CHMINACA 5F-MDMB-PINACA CUMYL-4CN-BINACA 4F-iBF THF-F Fentanils Fentanils: 1979-2010

16 Notifications of fentanils, 2012–2018 7 risk assessments

2017–2018 (Iso)butyryl-F- N-benzyl analogue Acryloylfentanyl (47 deaths), Furanylfentanyl (23), Isobutyrylfentanyl Tetrahydrofuranylfentanyl (14), 4-Fluoroisobutyrylfentanyl (20), Carfentanil (61), Cyclopropylfentanyl (78), Methoxyacetylfentanyl (13)

Carfentanil Valerylfentanyl Ocfentanil Acryloylfentanyl 2-Fluorofentanyl 4-Chloroisobutyrylfentanyl 4-Fluoroisobutyrylfentanyl 3-Methylcrotonylfentanyl 3-Fluorofentanyl 4-Hydroxybutyrfentanyl Methoxyacetylfentanyl 4-Fluoro- Tetrahydrofuranylfentanyl cyclopropylbenzylfentanyl Furanylbenzylfentanyl 2-Methylacetylfentanyl

Despropionyl-2-fluorofentanyl 4-Methoxybutyrfentanyl Furanylfentanyl 3-Phenylpropanoylfentanyl Tetramethylcyclopropanefentanyl Cyclopropylfentanyl Thiophenefentanyl Benzoyloylbenzylfentanyl Acetylbenzylfentanyl

2012 2013 2014 2015 2016 2017 2018 Fentanils: easier to get hold of, easier to use

• More than 30 detected since 2012 • Surface web, darknet, street-level • Sold as ‘legal’ replacements to illicit opioids • Sold as , fake medicines, cocaine • Novel dosage forms (nasal sprays and e-liquids) • Rapid onset of life-threatening respiratory depression • Increase in poisonings (inc outbreaks)

Seizure of nasal sprays containing , 2016. © Swedish Police Seizure of carfentanil, 2017. © Norwegian National Criminal Investigation Service Fentanils: availability in the EU Fentanils: forms detected

Methoxyacetylfentanyl sold as ‘ching’ Acryloylfentanyl detected in (Slovenia, 2017) capsule (Denmark, 2016)

Carfentanil detected in blotters Ocfentanil detected in hashish- (Canada, 2018) like substance (Sweden, 2016)

20 Fentanils: sold as medicines Fentanils: associated death cases Synthetic Cannabinoids Synthetic cannabinoids: 2006 - present

24 Synthetic cannabinoids: potent, disposable, cheap

• Sold as legal replacements to cannabis • Highly potent & efficacious (often full agonists at CB1 & CB2; other targets?) • Disposable (appear, controlled, replaced) • 178 detected in Europe since 2005 • Increase in severe poisonings and deaths • Outbreaks of mass poisonings (overwhelm emergency responders/ hospital emergencies) • A reputation as a cheap and powerful intoxicant with vulnerable groups • Sold as other drugs Synthetic cannabinoids: availability in the EU

Formal notifications 35

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25

20

15

10

5

0 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018

Seizures by law enforcement of synthetic cannabinoids reported to the EU Early Warning System. Trends in number and quantity seized, 2005–16. Synthetic cannabinoids: smoking mixtures Synthetic cannabinoids: expect the unexpected

• Poisonings reported in Oldham & Rochdale, United Kingdom, June 2017

• Crystals sold as MDMA (ecstasy)

• Analysis identifies ADB-FUBICA & ADB-FUBINACA (high purity, >99% by GC-MS)

• ADB-FUBINACA sold as ecstasy caused 15 poisonings in Hungary in May 2015

• Patients took 1 tablet, 20% had mild, 73.3% moderate and 6.7% severe intoxication

© Dr Oliver Sutcliffe & Matthew Hulme © Hungarian National Focal Point Synthetic cannabinoids: associated death cases 20 years of monitoring – overall trends

• Decrease in the number of new substances identified for the first time in 2016 and 2017 • However, a large increase observed in: • Availability of NPS in Europe • Detections reported by law enforcement agencies • Serious adverse events i.e. non-fatal intoxications, deaths and other harms

• Consumer groups of NPS have broadened • Trend towards highly potent substances • Growing interactions between the NPS and the established illicit drug market

30 Acknowledgment and thanks to the Reitox network and the national early warning system correspondents

Email: [email protected] http://www.emcdda.europa.eu/activities/action-on-new-drugs

http://www.emcdda.europa.eu /system/files/publications/8870 emcdda.europa.eu /2018-2489-td0118414enn.pdf twitter.com/emcdda facebook.com/emcdda youtube.com/emcddatube flickr.com/photos/emcdda