New Psychoactive Substances Seminar – Monitoring Trends, Tackling Challenges Clarion Hotel & Congress, Trondheim, Norway 27 May 2014 Monitoring new psychoactive substances – The UK experience and beyond Presenter: John M. Corkery, BA Hons, MSc, MPhil, PGC in L&T in HE Research Co-ordinator, Department of Pharmacy, & Lead for Drug Misuse, Centre for Clinical Practice, Safe Medicines and Drug Misuse Research University of Hertfordshire Co-founder & former Programme Manager, National Programme on Substance Abuse Deaths St George’s University of London UK Focal Point Drug-Related Deaths expert since 2000 1 Overview This presentation provides information on: (a) the European Early Warning System and current developments; (b) monitoring adverse health consequences from NPS use; (c) an example of contributions to monitoring by the UK National Programme on Substance Abuse Deaths; and (d) an outline of the EC-funded project “EU- MADNESS”. 2 Scope of the EWS o New psychoactive substances ‘New’ to the drug market or newly misused o Changes in purity of established (controlled) drugs o Established (controlled) drugs adulterated with unusual and/or harmful cutting agents Anthrax outbreak among heroin injecting drug users, cocaine adulterated with levamisole, etc. o Substances sold as others Heroin sold as cocaine o New patterns (forms) of use Recreational use of methamphetamine injected o Fatal and non-fatal intoxications o Large seizures, seizures that show evidence of international trafficking and/or involvement of organised crime 3 4 Council Decision 2005/387/JHA EMCDDA – Europol annual implementation reports EWS guidelines Risk assessment guidelines More than 15 years of regional monitoring (30 reporting countries) I. Information exchange II. Risk assessment III. Decision-making Early warning system (EWS) Joint Report Council Decisions on control Biannual EWS reports Reporting forms (ad hoc) Risk assessment reports European Database on New Drugs (EDND) http://www.emcdda.europa.eu/drug-situation/new-drugs EWS institutional partners EMCDDA Reitox Focal Points Europol National Units Pharmacovigilance system EWS Europol EMA 6 The EWS – triangulation of multi-source information Multidisciplinary stakeholders • Forensic science and toxicology networks Reporting • Heath and care system forensic analysis • Law enforcement agencies toxicology, law enforcement, • Relevant national agencies surveys, health & • ‘Street’ level key informants care • Other Targeted research test purchase, wastewater analysis, Open source information computational modelling, Internet, media, users, pharmacotoxicological scientific/grey literature profiling the EWS information sources 7 The EWS – increase of the number and diversity of new drugs 444 421 208 169 90 61 43 41 44 ↑ Quantity and quality of information provided 8 Many substances classified in the ‘Others’ group 3 R 5-APB 5-APDB N 2 1 R R 2 1 R 1 MDAI ODT 3 R Fentanyl derivatives 2 R NH 1 R Ketamine Methoxetamine 1 2 Dimethocaine R R D2PM pFBT 2-DPMP Reclassification of drug families NH 2 N H 10 Reclassification of drug families – based on chemistry Chemical Family Examples substructure Arylcyclohexylamines ketamine tramadol N phencyclidine/PCP methoxetamine Aminoindanes 1-aminoindane 2-aminoindane MDAI NH2 Arylalkylamines bromo-dragonfly thienoamphetamine 6-APB C=0,1,3,… Benzodiazepines Diazepam Phenazepam Flubromazepam Pyrazolam Piperidines & or ethylphenidate desoxypipradrol/2-DPMP pyrrolidines diphenylprolinol/D2PM 11 Reclassification of drug families º 12 EMCDDA-Europol Joint Reports 2014: 4,4′-DMAR MT-45 • Derivative of aminorex and 4- • Substituted piperazine. methylaminorex (both synthetic • Synthetic opioid (a ctivity stimulants) similar tomorphine), patented in 1970s • EWS: first reported Dec 2012 (the Netherlands) • EWS: first reported Dec 2013 (Sweden) • (±)-cis-4,4′-DMAR is a potent, efficacious substrate-type releaser • EWS: 2 non-fatal intoxications at transporters for dopamine, in one Member State norepinephrine and serotonin. • EWS: 27 deaths associated with • EWS:12 deaths associated with 4,4′-DMAR in 2 Member States MT-45 in one Member State (Northern Ireland) Epidemiological sources on adverse health consequences Presentations for treatment: General Practitioners, Drug Services, Specialist treatment services e.g. Club Drug Clinics. Those realising they have an issue of dependence, psychiatric issues (psychoses, paranoia), or risky behaviours (injecting mephedrone) Acute health issues – overdoses/intoxications/poisoning: Call-outs to paramedic/emergency services, admissions to Emergency Departments, Intensive Care Units, in-patient wards. These can lead to calls to National Poisons Information Units, and toxicological databases (Toxbase) by health professionals, forensic clinicians, clinical toxicologists, etc. Direct drug-induced deaths: overdoses (accidental or intentional); suicides (induced by psychiatric conditions including depression, anxiety, psychoses, caused/triggered by NPS); accidents resulting from impaired judgement – traffic accidents, falls from heights, drowning, etc. 14 Methodological issues & what is needed Regular data and information are needed from all of these types of sources to understand the characteristics of those using and suffering adverse health consequences, as well as trends in NPS used and how they are used. We need to understand what are the effects of NPS and how they are brought about, and the characteristics of those suffering them. Problems: little if any research or literature (including animal studies) on physiological, pharmacological, and toxicological properties/effects of NPS. Case-studies and anecdotal reports help a little, but do not provide all the information needed to assess their potential health impacts, and to develop appropriate responses, interventions, treatments, etc. Where information might be generated, it is often not collected. If it is collected, this is often not done in a standardised way. Furthermore, often is not possible to collate this even at regional (sub-national) level. 15 Methodological issues & what is needed Inadequate resources at local level to identify opportunities to collect data and to conduct collection on a regular and systematic basis. Lack of agreed protocols/instruments for data collection. Legal/ethical problems about sharing data between agencies – patient condidentiality, data protection legislation. This has been overcome in some local areas with memoranda of understanding; but then issue of sharing these data at higher levels. Mainly a problem with ‘health’ data, but also problem sharing names etc between those investigating drug deaths (coroners, pathologists, toxicologists) and those monitoring them, thereby not helping the latter with case identification and follow-up. Insufficient resources (including financial) for those investigating NPS characteristics – neurobiologists, pharmacologists, toxicologists, etc.; and those monitoring adverse health consequences – locally & nationally. Often based on ‘good will’; perhaps need statutory or mandatory authority to collect and report data to nominated specialist centres. 16 National Programme on Substance Abuse Deaths (np- SAD) The Programme’s objectives include: Collect and collate drug-related mortality data Monitor and examine patterns and trends, e.g. geographic, demographic, substances implicated in death, method of death Act as part of an early warning system (e.g. UK EWS, EMCDDA) Inform and facilitate discussion on the prevention of drug-related deaths Provide data for local and national drug abuse policy formulation and programme planning (e.g. UK Advisory Council on the Misuse of Drugs) Disseminate information on drug-related mortality to the scientific community, clinicians, policy makers and other interested parties 17 Methods and source(s) of data The National Programme on Substance Abuse Deaths (np-SAD) regularly receives information from coroners on a voluntary basis on deaths related to drugs in both addicts and non-addicts in England and Wales, Northern Ireland, the Channel Islands and the Isle of Man. Since 2004, information has also been received from the Scottish Crime and Drug Enforcement Agency and the General Register Office for Northern Ireland. Since 1997 details of about 30,000 deaths have been received (Corkery et al., 2014). The average annual response rate from coroners in England and Wales to np-SAD has been between 89% and 95% (Ghodse et al., 2010). 18 To be recorded in the np-SAD database as a drug-related death, at least one of the following criteria must be met: (a) presence of one or more psychoactive substances directly implicated in death; (b) history of dependence or abuse of drugs; and (c) presence of controlled drugs at post-mortem. Ethical approval is not required in the UK for studies whose subjects are deceased, and solely involves retrospective reviews of death records. However, confidentiality arrangements are in place with each of the respective data providers. 19 np-SAD np-SAD often receives autopsy & PM toxicology reports A range of documents are contained in coronial inquest files, although the variety differs from case to case. Typically, the coroner has access to: statements from witnesses, family & friends; General Practitioner records; reports from ambulance, police or other emergency services; hospital Emergency Department & clinical ward reports; psychiatric & substance abuse team reports; autopsy & PM toxicology reports. 20 np-SAD Case identification and verification A range