1. The EU Early Warning System: 20 years of monitoring New Psychoactive Substances in Europe
Rachel Christie, PhD
24 October 2017, Lisbon
Lisbon Addictions 2017

2. variety of information sources triangulation of information
20 years of monitoring NPS
+660 NPS monitored
~150 public health alerts
23 risk assessments
holistic approach
variety of information sources
triangulation of information
…..since 2014
Europol and EMA
~300 NPS newly detected
+ 50 public health alerts
12 risk assessments

3. The EU EWS: who we are
1997: “New” drugs monitored under Joint Action 97/396/JHA
Until 2005: EMCDDA mainly collects data on a small number of drugs most of which controlled by the UN drug conventions
formal notification
risk communication
alerts
advisories
briefings
Future: new legislation – shorter deadlines

4. What we monitor…… 2 types of drugs…
What's important from Public health perspective is that both controlled drugs and NPS are essentially drugs and when it comes to NPS our knowledge is very limited as there is no prior use experience with those substances and the data on pharmacology and toxicity and safety profile are very limited
Drugs controlled under the UN Conventions
about 250
heroin, morphine, cocaine, amphetamine, benzodiazepines, MDMA, LSD, fentanyl…
years of human exposure
Drugs not controlled under the UN Conventions
we call these drugs 'new psychoactive substances'
620 detected on the drug market; 65% detected since 2012
1000s more are possible
no history

5. The EU EWS: definition and scope
‘New narcotic or psychotropic drug, in pure form or in preparation, that is not controlled by the 1961 or the 1971 UN Conventions, but which may pose a public health threat comparable to that posed by substances listed in Schedule I or II or IV of the former and in Schedule I or II or III or IV of the latter convention’ (CD 2005/387/JHA)
New psychoactive substances i.e. ‘New’ to the drug market or newly misused
Scope of the EU-EWS:
Changes in purity of established (controlled) drugs
Established (controlled) drugs adulterated with unusual and/or harmful cutting agents
Substances sold as others e.g. heroin sold as cocaine
New patterns (forms) of use e.g. injection of cathinones
Fatal and non-fatal intoxications
Large seizures, seizures that show evidence of international trafficking and/or involvement of organised crime

6. Reporting of seizures
Case-level data: EMCDDA-Europol Reporting Forms (RFs) Aggregated (routine) data: EWS Progress Reports (January – June) EWS Final Reports (July – December) Increase in the number and quality (level of detail) of case-level and aggregated data reported.

7. First detections of NPS in Europe
Case-level data
CLASSIFICATIONS
Increasing range of NPS
In 2016, a total of 66 NPS were detected for the first time in the EU
Overall, over 600 NPS monitored by the EU EWS

8. NPS available on the market is on the rise
1st detections of NPS in the EU
Number of NPS detected on the EU drug market each year:
2013: 299
2014: 365
2015: 423

9. Seizures of new psychoactive substances in Europe
Case-level data is reported through:
EMCDDA-Europol Reporting Forms (RFs)
Aggregated (routine) data is reported through:
EWS Progress Reports (January – June)
EWS Final Reports (July – December)
Increase in the number and quality (level of detail) of case-level and aggregated data reported.

10. Increasing seizures of synthetic cannabinoids and cathinones

11. Responding to NPS causing concerns
Toxicovigilance system
Signal Management system
Risk Communication system
Risk Assessments

12. Prioritisation: which substances should we react to?
Toxicovigilance
The active process of detecting, reporting, evaluating, understanding, monitoring and responding to adverse events associated with new psychoactive substances
In the context of early warning it focuses on serious adverse events…
Prioritisation: which substances should we react to?
We needed to do that As the market has grown in recent years, the EMCDDA has also had to deal with a growing number of reports of serious harms, often related to acute toxicity leading to hospitalisation and deaths.
The EMCDDA has responded to this challenge by working to strengthen the ability of the EU Early Warning System and its network to identify, report, understand and respond to such harms.
One of the core activities in this respect is issuing public health alerts, which serve to alert the network on serious and urgent issues. Since 2005 the EMCDDA has issued 117 public health alerts, with more than 70 % of these issued in the last five years. During 2014 some 16 alerts were issued. These included alerts on 4,4′-DMAR and MT-45 after deaths within Europe were reported (both of these substances were risk assessed during 2014), and on synthetic cannabinoids such as 5F-PB-22, ADB-PINACA and MDMB-FUBINACA after media monitoring by the EMCDDA identified serious harms in countries outside Europe.

13. Signal management system
Signal management is a stepwise process covering six steps; it begins with the detection of a signal and ends with a recommendation for action that details how we should react to the signal.
detection
validation
analysis
Prioritisation – which substances should we react to?
assessment
recommendation for action
We are developing our signal management system to allow us to ensure a systematic, reproducible, and transparent approach is used so that potential signals can be detected, validated, understood, prioritised, and, reacted to, according to the:
type of risk that they pose
seriousness of the risk
urgency of the risk
Impact analysis is used to assess the impact of the signal through an analysis of the strength of the data and the implications for public health within Europe
We look at things like:
intrinsic properties of the substance (is it an opioid?)
the impact on users (frequency, seriousness, duration, and outcome of the harm)
strength and consistency of the data supporting an association
the extent of utilisation of the substance and the patterns of use
the availability of the substance on the drug market
whether exposure to the substance is intentional or unknown to users
number of countries affected or that may be affected

14. Everything begins with a signal
A signal is the information arising from one or more sources which suggests either a new association or a new aspect of a known association between a substance, and an event or set of related events that is judged to be of sufficient likelihood to justify verificatory action, and, where necessary remedial action.
Any type of information could be a signal
first appearance of a substance
intrinsic nature of a substance (fentanils)
serious adverse events (individual, cluster, outbreak, infectious agents, etc)
circumstances of detection (U sold as diazepam; SCRAs in prison)
prior experience with the substance or analogous substance or analogous situation (e.g. PMMA in ecstasy tablets; fentanyl in heroin)
contamination with a substance of concern or potential substance of concern (scopolamine in fake flunitrazepam)

15. Recommendations for action
Awareness
Intensive monitoring (solicited reporting)
Risk communication (push and pull of information)
Formal notifications
Alerts
Advisories
Briefings
Joint Report

16. Substances of Concern – monitoring and responding to harms
Public health alerts issued by the EMCDDA in 2015:
Deaths associated with the use of potent opioids
Clusters and outbreaks of intoxications associated with cannabinoids
Seizures of ecstasy tablets containing 4-CMA
Deaths associated with PMMA sold as ecstasy and heroin sold as cocaine
Public health alerts issued in 2016 included:
Serious adverse events associated with the use of cannabinoids
Superman logo ecstasy tablets containing PMMA
Public health-related advisories were also issued in 2016:
Fatty acid amide hydrolase (FAAH) inhibitors;
Ocfentanil sold as heroin
Cocaine containing scopolamine and associated intoxications

17. Joint Report — the next stage of early warning
Evidence of intoxication or fatalities = serious adverse events
Toxicopharmacological properties of the new psychoactive substance or analogy with better-studied compounds
Amount of seized material
Evidence of the potential for further (rapid) spread
Evidence of international trafficking
Evidence of organised crime involvement
Based on the Joint Report the Council may request a risk assessment of the health and social risks

18. Risk assessment domains
A) Physical, chemical, pharmaceutical
and pharmacological information
B) Dependence and abuse potential
D) Health risks
E) Social risks
F) Involvement of organised crime
C) Prevalence level

19. Risk assessments 4-MTA PMMA Mephedrone 5-IT α-PVP MDMB- CHMICA MBDB
1998
1999
2000
2001
2003
2007
2010
2012
2013
2014
2015
2016
4-MTA
PMMA
Mephedrone
5-IT
α-PVP
MDMB-
CHMICA
MBDB
Ketamine
GHB
2C-I
2C-T-2
2C-T-7
TMA-2
BZP
4-MA
Methoxetamine
MDPV
25I-NBOMe
AH-7921
4,4’-DMAR
MT-45
Timeline – 3,5% as of 2016… 19

20. Risk assessments 2017 Completed in 2017: Acryloylfentanyl 2017
Furanylfentanyl (May) 2017
November 2017:
AB-CHMINACA
ADB-CHMINACA
5F-MDMB-PINACA
CUMYL-4CN-BINACA
4-Fluoro-isobutyrylfentanyl (4F-IBF)
Tetrohydrofuranylfentanyl (THF-F)
Carfentanil

21. Joint Report Questionnaire
MDMB-CHMICA timeline
Hungary
Police seizure
˂1 g herbal material
Austria
‘Bonzai’
7 NFIs
Sweden
4 deaths
6 NFIs
Germany
2 deaths
3 NFIs UK
1 NFI
Poland
‘Mocarz’
EU wide
13 deaths
23 NFIs
August
2014
15 Dec
2014
19 Dec
2014
25 Apr
2015
July
2015
08 Feb
2016
Reported to EMCDDA
EWS alert
EWS alert
External alerts
EWS alert
Formal request
Joint Report Questionnaire
EWS alert
Sept
2014
31 Aug
2016
22 July
2016
18 April
2016
N-cyclohexylmethyl indole-3-carboxamide
Synthetic cannabinoid receptor agonist
Potent full agonist at the CB1 receptor
Expected to undergo extensive metabolism
Pharmacology & toxicology largely unknown
No information on psychological and behavioural effects in humans
No legitimate uses or medical value
Data suggests bulk quantities in Europe mainly imported from China
Offered via the Internet either as powder (‘research chemical’) or in the form of ‘herbal mixtures’, where the product composition is usually not stated
MDMB-CHMICA may not be directly sought by users, who may purchase it unknowingly
Formal notification
to EWS
Proposal for
EU control
Risk Assessment
meeting
Joint Report
submission

22. Challenges Number, diversity and availability of NPS
In law enforcement seizures  NPS data
 Complexity of NPS market
 Serious adverse events
Outbreaks of infections and mass poisonings
- Lack of data on pharmacology, toxicology and epidemiology

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