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

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

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

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

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

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.

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

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

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.

Increasing seizures of synthetic cannabinoids and cathinones

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

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.

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

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-47700 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)

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

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

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

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

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

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

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

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

Acknowledgment and thanks to the Reitox network and the national early warning system correspondents Email: Rachel.Christie@emcdda.europa.eu Email: EMCDDA-AND@emcdda.europa.eu