‘New’ synthetic opioids in Europe: perspective from the EU EWS Rita Jorge, PhD Lisboa, 25 October 2017 Lisbon Addictions 2017

Treatment entrants citing opioids as primary drug Quick overview Treatment entrants citing opioids as primary drug

NPS identified for the first time: 2005-2017

Opioids identified for the first time: 2005-2017 4 4 4 3 9 8 1

‘New’ synthetic opioid seizures 2009-2016 number of detections (cases) amount detected (g, mL, tablets)

Characteristics of the ‘new’ opioids market Manufacture: chemical/pharma companies in China; limited evidence of production in Europe processing can occur in Europe (e.g. nasal sprays) Sale: openly on the surface web (‘research chemicals’) but also on the darknet; in business-to-business or business-to-consumer websites; in novel dosage forms (nasal sprays, liquids for e-cigarettes) cost varies, but 1 kg of powder ≈ 50,000 bottles ≈ € 1 million in sales Distribution: typically using legitimate express mail companies from manufacturer to consumer in as little as 2 days often misdeclared (‘hot melt powder’) frequently mis-sold, especially at street level but also online Nasal spray bottles w/ furanylfentanyl Found in a postal shipment, Norway, 2017

Misseling of ‘new’ synthetic opioids as benzodiazepines as/in heroin, amphetamine, cocaine and other fentanils ocfentanil sold as heroin (WEDINOS, 2016) ocfentanil sold as ‘speed’ (WEDINOS, 2015) U-47,700 sold as diazepam (Police Scotland, 2016)

Exposure to ‘new’ opioids Who uses ‘new’ synthetic opioids and why? Those who experiment (‘psychonauts’) Those looking for substitutes for opioids may actively seek out new synthetic opioids those who use heroin (including high risk opioid users) those who self medicate with other opioids (pain, opioid withdrawal) those avoiding drug testing Some use the substance unknowingly Use of ‘new’ synthetic opioids happens frequently at home, alone Accidental exposure!

Acetylfentanyl Less potent than fentanyl; but MORE toxic (animal studies) Detected in 9 countries 32 deaths (COD/contributing in 19, even when other substances present) 40% deaths in 1 month

Acryloylfentanyl Less potent than fentanyl; toxicity data not known detected in 6 countries, nasal spray findings common 47 deaths (COD/contributing in 40, even when other substances present) 70% deaths in 3 months (June – August 2016)

Since then R = −CH2CH3 fentanyl −CH3 acetylfentanyl −CH=CH2 acryloylfentanyl − furanyl furanylfentanyl − furanyl-H2 tetrahydrofuranylfentanyl … carfentanil … 4F-isobutyrfentanyl Out of 33 new opioids under monitoring: 24 are fentanils (73%), of which 6 were the target of detailed investigations From the 6 finished investigations: At least 180 deaths identified in Europe with confirmed exposure to 1/more Large majority of those: 2015 - 2017

Joint Reports launched Oct 2017 What’s next? Joint Reports launched Oct 2017 detected in 4 countries 22 deaths (June – August 2017); COD/contributing in at least 6 USA: found in fake Percocet tablets detected in 5 countries 6 deaths (December 2016 – June 2017); COD/contributing in at least 5 What about chronic harms? Helander et al.,(2017) Br J Dermatol,176:1021

What’s next? Reducing harms, preventing overdoses EU Early Warning System notifications, alerts, advisories, briefings opioid substitution treatment — good evidence naloxone: take-home programmes in 8 countries drug consumption rooms in 6 countries stocks and availability of the naloxone, as well as adequacy of training in how to resuscitate poisoned patients both in clinical and community settings may need to be assessed availability of naloxone to users through community and take-home naloxone programmes? use in a safe environment; don't use alone; don't mix with other drugs (esp., CNS depressants; take home naloxone? skin contact, inhalation, or ingestion of fentanils poses a serious risk of poisoning to those who may come into contact with them family and friends of users, law enforcement, emergency personnel, as well as medical and forensic laboratory personnel extreme caution when handling materials suspected to contain fentanils working environments and personnel should be equipped with appropriate protective equipment antidote naloxone should be readily available to personnel in sufficient quantities; training in naloxone administration and resuscitation should also be available

Obrigada rita.jorge@emcdda.europa.eu

EU Early Warning System Backbone of the system: analytical identification of a ‘new’ substance in a confiscation or in a biological sample but it is not merely a repository of analytical data Core function: to identify signals of serious harms and react as necessary Push information (informs and helps prepare at national level) Pull information (solicits information, investigates) Formal notifications Alerts, Advisories, Briefings Joint Reports Risk Assessments The backbone of the information collected by the EU EWS is the analytical identification of a new substance in a confiscation (by police or customs, for example) and/or in a biological sample (in an acute intoxication or a death). But rather than being a repository of analytical data the main function of the EU EWS is to identify signals of serious harms associated with NPS and to react accordingly.