Today, the European Union has decided to subject two new synthetic opioids to control measures across the 28 Member States. The implementing decision of the Council of the EU (1), based on a proposal from the European Commission, was adopted in the final stage of the three-step legal procedure designed to respond to new psychoactive substances (NPS) that may pose public health and social threats (2)(3). The substances, which have been raising health concerns in Europe, are cyclopropylfentanyl and methoxyacetylfentanyl (4). Both are chemically related to fentanyl, the controlled drug widely used in medicine in pain management and anaesthesia.

Harmful effects linked to the use of the two substances have been reported by the Member States through the EU Early Warning System (EWS), operated by the EMCDDA and Europol. Similar to other opioid analgesics, the most serious acute risk arising from their use is likely to be from respiratory depression (which can lead to apnoea, respiratory arrest and death). Naloxone is expected to work as an antidote to poisoning (5).

Today’s decision is based on the findings of formal risk assessments of the substances, conducted by the extended EMCDDA Scientific Committee in March 2018, with participation of additional experts from the EU Member States, European Commission, Europol and the European Medicines Agency. The risk assessments explored the health and social risks of the drugs, as well as international trafficking and the involvement of organised crime (6). The decision states that the evidence available provides ‘sufficient ground for subjecting cyclopropylfentanyl and methoxyacetylfentanyl to control measures across the Union’. Reasons for the conclusion include: the similarity of the substances to fentanyl and the risks they pose.

Available in the EU since at least June 2017, cyclopropylfentanyl has been detected in six EU Member States and Norway. At the time of the risk assessment, 78 deaths with confirmed exposure to the substance had been reported by two EU Member States (Sweden and the UK). Methoxyacetylfentanyl has been available on the EU drug market since at least November 2016 and has been detected in 11 EU Member States and Norway. At the time of the risk assessment, 13 deaths with confirmed exposure to the substance had been reported by four EU Member States (Belgium, Czech Republic, Sweden and the UK).

The two substances, sold online in powder form, are also available as ready-to-use nasal sprays. These new dosage forms are both easier to obtain and to consume and have the potential to make use of fentanils more socially acceptable (7). Cyclopropylfentanyl has been detected in tablets, among these falsified benzodiazepines (e.g. fake Xanax®) and opioid painkillers (e.g. fake OxyContin®). This increases the risk of poisoning in unsuspecting users.

A small number of fentanils (e.g. fentanyl, alfentanil, sufentanil and remifentanil) are used legitimately in human and veterinary medicine. But fentanils also have a long history of illicit use as replacements for heroin and other controlled opioids. Over the past few years, there has been a large increase in the availability of fentanils in the United States, Canada and Europe. The EMCDDA is currently monitoring 32 fentanils through the EU EWS on new psychoactive substances (8); all of these have been detected on the EU drug market since 2012.

Of the nine risk assessments carried out by the EMCDDA in 2017, five were related to synthetic opioids (acryloylfentanyl, furanylfentanyl, 4-fluoroisobutyrylfentanyl (4F-iBF), tetrahydrofuranylfentanyl (THF-F) and carfentanil) (9). All five substances are now controlled internationally under the United Nations 1961 Single Convention on Narcotic Drugs.

Following publication of today’s decision on cyclopropylfentanyl and methoxyacetylfentanyl in the Official Journal of the European Union, the EU Member States will have one year to introduce the controls into their national legislation.