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Home , Acetylfentanyl, Acrylfentanyl, Alfentanil, Butyrfentanyl, Furanylfentanyl, Methoxyacetylfentanyl

17 GLOBAL March S MART UPDATE VOLUME VOLUME

Fentanyl and its analogues - 50 years on

Research 2017 GLOBAL SMART UPDATE About the SMART Update Content

Synthetic drugs constitute one of the most significant SPECIAL SEGMENT 3 drug problems worldwide. After , amphet- amine-type stimulants (ATS) are the second most widely used drugs across the globe, with use levels SHORT SEGMENTS 8 often exceeding those of and/or . Along BEIJING, China – September 2015 with ATS, the continued growth of thenew psychoactive 8 substances (NPS) market over the last years has become BEIJING, China – May 2015 8 a policy challenge and a major international concern. A growing interplay between these new drugs and tra- TOKYO, Japan – August 2016 8 ditional illicit drug markets is being observed. By July 2016, the emergence of NPS had been reported from HELSINKI, Finland – June 2015 8 102 countries and territories. Trends on the synthetic drug market evolve quickly each year. STOCKHOLM, Sweden – August 2016 9 The UNODC Global Synthetics Monitoring: Analyses, Reporting and Trends (SMART) Programme enhances TALLINN, Estonia – July 2016 9 the capacity of Member States in priority regions to VIENNA, Austria – May 2016 generate, manage, analyse, report and use synthetic 9 drug information to design effective policy and pro- VIENNA, Austria – November 2016 9 gramme interventions. Launched in September 2008, the Global SMART Programme provides capacity building GENEVA, Switzerland – November 2016 10 to laboratory personnel, law enforcement and research officers in the Pacific, East and South-East Asia, South BRUSSELS, Belgium – 2015 10 Asia, the Near and Middle East, Africa and Latin America; and regularly reviews the global -type DUBLIN, Ireland – 2016 10 stimulants andnew psychoactive substances situation. Its main products include online drug data collection, SÃO PAULO, Brazil – September 2016 10 situation reports, regional assessments and the UNODC Early Warning Advisory (EWA) on new psychoactive OTTAWA, Canada – September 2016 11 substances. The EWA is a webportal that offers regu- lar updates on new psychoactive substances, including LOS ANGELES, California – March 2016 11 trend data on emergence and persistence, chemical data, supporting documentation on laboratory analysis BRITISH COLUMBIA, Canada – June 2016 11 and national legislative responses (available at: www. WASHINGTON D.C., United States – 2016 11 unodc.org/NPS). The Global SMART Update (GSU) series is published twice a year in English, Spanish and Russian and provides information on emerging patterns and trends of the global synthetic drug situation in a concise format. Each issue of the Global SMART Update contains a special segment and short segments on the topic of interest.* Electronic copies of the Global SMART Updates and other publications are available at: www.unodc.org/ unodc/en/scientists/publications-smart.html. Past issues have covered topics such as UNGASS 2016 recommenda- tions, injecting use of synthetic drugs, legal responses to NPS, key facts about synthetic and regional patterns of manufacture.

* The information and data contained within this report are from official Government reports, press releases, scientific journals or incidents confirmed by UNODC Field Offices. An asterisk (*) indicates that information is preliminary as it stems from ‘open sources’ where UNODC is waiting for official confir- mation. This report has not been formally edited. The contents of this publication do not necessarily reflect the views or policies of UNODC or contributory organizations and neither do they imply any endorsement. Suggested citation: UNODC, Global SMART Update Volume 17, March 2017.

2 Volume 17

Fentanyl and its analogues - 50 years on

ABSTRACT Fentanyl is the strongest Fentanyl and its analogues are potent synthetic , which are available for medical use in humans, with about 100 times the potency of liable to abuse. They are often sold under the guise of heroin or morphine2. It is highly valued for its prescription medicines, such as , and this exacerbates and effects and the risk of overdose and associated fatalities. An increasing num- widely used in the management of ber of deaths have been associated with the use of fentanyl and severe pain and in anaesthesia. The its analogues, particularly in North America. The facile synthesis of three fentanyl analogues approved a number of these substances, coupled with the ease in obtaining for pharmaceutical use, , and , have the required precursor chemicals and equipment, has led to an very short onset and duration of SEGMENT SPECIAL increase in clandestine manufacture. action, and their medical use is lim- ited to intravenous anaesthesia3. Introduction , estimated to be about 10,000 times more potent than Recent years have seen a sharp rise and fentanyl analogues. Evidence on morphine4, is intended only for vet- in opioid-related overdose deaths fatalities associated with emerging erinary use on large animals, and not mainly in North America, and to a fentanyl analogues is accumulating, approved for medical use in humans. certain extent, in Europe. While the also, in other regions of the world. challenge posed by these fatalities The pills and powders containing The liability of fentanyl and its is complex, more evidence is emerg- such substances sold on the illicit analogues to abuse and the depen- ing about the role fentanyl and its market pose a threat to public health dence-potential are reflected in the analogues play in the current crisis. because of the variable quantity and international legislative responses. Fentanyl itself is a powerful opioid potency of the active components, Fentanyl was first synthesized in analgesic, with an established place which in extreme cases, such as with 1959, and was placed under inter- national control as a Schedule 1 in medicine. Yet, there has always carfentanil, may be 10,000 times substance in 1964 under the Single been concern about its potential for more potent than . Such Convention on Drugs of abuse and dependence, and it was products can prove particularly dan- 1961. During the ensuing decades, therefore placed under international gerous when sold as street heroin, together with heroin or as counter- the list of scheduled substances control as far back as 1964. In the has grown to include all fentanyl 1970s and 1980s, products con- feit prescription drugs, without the user’s knowledge. analogues approved for human taining fentanyl and its analogues medical use (sufentanil in 1980, appeared on the illicit drug market, This publication aims to inform alfentanil in 1984, and remifentanil and became notorious for accidental about the growing complexity of the 1 in 1999), and several analogues overdoses. The problem seems to opioid market, in particular the fen- which have not been developed have resurfaced and the clandes- tanyl group, international controls, into pharmaceutical products tine manufacturing of fentanyl has evolving patterns of use and associ- (acetyl-alpha- methylfentanyl, alpha- risen to unprecedented levels. The ated risks, global developments in methylfentanyl and 3-methylfentanyl required materials and equipment manufacture and trafficking of fen- were placed under international for manufacture are readily available tanyl analogues and their precursors. control in 1988, and alpha-methyl- online, at low cost. This situation is , beta-hydroxyfentanyl, aggravated by the rapid emergence Good medicines, beta-hydroxy-3-methylfentanyl, of novel fentanyl analogues which bad drugs? 3-methylthiofentanyl, para-fluoro- have not been approved for medi- Fentanyl belongs to a class of potent fentanyl and thiofentanyl in 1990). cal use. opioid , the 4-anilidopi- North America is particularly affected peridines. These synthetic opioids by an crisis. While have a high affinity for theµ -opioid originally, the sharp rise in over- receptor, which presents both bene- doses was attributed to heroin, the fits and drawbacks. On the one hand, current crisis is mainly attributed to strong µ- 2 Chodoff P, Domino EF. Comparative phar- macology of drugs used in neuroleptanalge- clandestinely manufactured fentanyl from the fentanyl family have excel- sia. and Analgesia, 44 (5) (1965), lent pain-relieving properties. On the pp. 558–563 other hand, such drugs are liable to 3 Lemmens H. Pharmacokinetic-pharmaco- abuse and have high dependence- dynamic relationships for opioids in bal- producing properties. anced anaesthesia. Clin Pharmacokinet. 1 Henderson GL. Fentanyl-related deaths: 1995;29:231–242. demographics, circumstances, and toxicology 4 Janssen PA. Potent, new analgesics, tailor- of 112 cases. Journal of Forensic Science. made for different purposes. Acta Anaesthe- 1991 Mar 1;36(2):422-33. siol Scand. 1982 Jun;26(3):262-8.

3 GLOBAL SMART UPDATE Figure 1: International control of fentanyl and its analogues, 1964-2016

the UNODC Early Warning Advisory

lel para-fluoroisobutyrfentanyl , elel

elel oel emel

alphameloel betaoel betaomelel meloel para-fluorofentanyl, thiofentanyl lel elalphamelel alphamelel melel

uel

el 1961 Single Convention on Narcotic Drugs

Acetylfentanyl was placed under These substances were described in Nonmedical use of fentanyl and its international control in 2016, while scientific literature but never devel- analogues can have severe health butyrfentanyl has been recom- oped into pharmaceutical products. consequences. Tolerance and depen- mended for control by the WHO5. Examples include , dence develop very fast, and may Carfentanil, which was first synthe- butyrfentanyl, furanylfentanyl, reach extreme levels. Above all, each sized in 1974 and remains the most and . Other substances episode of nonmedical use carries a potent commercially available opioid currently present in the illicit opioid high risk of overdose and death as in the world, is not under interna- market are newly designed fentanyl a result of respiratory depression tional control. analogues, such as – a common side-effect of opioids. Within the last five years, more than and para-fluoroisobutyrfentanyl. A report from a drug consumption The countless possibilities to create a dozen additional fentanyl ana- room in Sydney found that under new compounds by small changes in logues have entered the illicit opioid medical surveillance, the risk of chemical structures pose a growing market. Some of these analogues overdose upon injecting fentanyl have been re-discovered by traffick- challenge to international control of the opioid trade. Between 2012 and was two times higher than upon ers from research work carried out injecting heroin, and eight times between the 1960s and 1990s. 2016, seventeen fentanyl analogues were reported to the UNODC EWA higher than upon injecting other 6 from countries in East Asia, Europe prescription opioids . 5 Commission on Narcotic Drugs, Recon- and North America (see Table 1). So Overdoses can be effectively vened fifty-ninth session. Extract from the far, only one of them, acetylfentanyl, reversed by , a µ-opioid Report of the 38th Expert Committee on Drug Dependence, convened from 14 to has been placed under international 18 November 2016, at WHO headquarters control. 6 Latimer J, Ling S, Flaherty I, Jauncey M, in Geneva. 30 November 2016. https:// Salmon AM. Risk of fentanyl overdose www.unodc.org/documents/commissions/ among clients of the Sydney Medically CND/CND_Sessions/CND_59Reconvened/ Supervised Injecting Centre. Int J Drug ECN72016_CRP13_V1610192.pdf Policy. 2016 Oct 14;37:111-114

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Figure 2: Development of new fentanyl analogues by small changes in chemical structures. (A) fentanyl, (B) acetylfentanyl, (C) butyrfentanyl

N N N

N N N

O O O

A BC

Table 1: NPS fentanyl analogues reported to the UNODC EWA, 2012-2016

COMMON NAME REPORTED IN 3-fluorofentanyl Europe 4-fluorobutyrfentanyl Europe 4-methoxybutyrfentanyl Europe acetylfentanyl Asia, Europe, North America acrylfentanyl Asia, Europe beta-hydroxy-thiofentanyl North America butyrfentanyl Asia, Europe, North America despropionylfentanyl Latin America, North America despropionyl-2-fluorofentanyl Europe furanylfentanyl Asia, Europe, North America isobutyrfentanyl Africa, Europe (iso)butyr-F-fentanyl N-benzyl analogue Europe Europe ocfentanil Europe para-fluoroisobutyrfentanyl North America tetrahydrofuranylfentanyl Europe Asia, Europe, North America . setting, the recreational use of prod- Use of illicitly manufactured fen- Importantly, reversing overdoses ucts containing fentanyl may easily tanyl and its analogues amplifies of fentanyl or its analogues often prove fatal with increase in the the hazards because such products requires very high doses of naloxone. administered dose, or a change in lack quality control, are typically not In response to the growing need for the route of administration (e.g. portioned in precise doses, and can overdose treatment, some countries extracting the drug from a trans- be deadly in minuscule amounts due have introduced or expanded nalox- dermal patch into liquid to prepare to the extreme potencies. Attempts one distribution programs. Canada an injection or nasal spray, inhal- to prepare a single dose by weigh- authorised sale of naloxone with- ing volatilized fentanyl, or placing a ing without precision equipment are out prescription, including the nasal highly risky. Another approach is to 7 transdermal patch on oral mucous spray version, in 2016 . membranes). A study conducted in bring a larger amount of the drug Risky practices rural Australia concluded that users into solution, which is then appor- typically did not revert to less potent tioned into single doses; however, Although fentanyl is safe under errors in calculations can be lethal. opioids after becoming dependent clinical supervision, e.g. in a hospital Users experimenting with new fen- on fentanyl, practiced unsafe prepa- tanyl analogues, whose potency is ration and administration methods, not well-defined, increase the odds 7 Health Canada. Notice - Availability of and their risk of overdose was of making a fatal mistake. Naloxone Hydrochloride Nasal Spray exacerbated by misinformation cir- (NARCAN®) in Canada. July 6, 2016. culating amongst peers8. (http://www.hc-sc.gc.ca/dhp-mps/prodp- Clarke I, and Campbell, M. Illicit Fentanyl harma/activit/announce-annonce/notice-avis- use in Rural Australia – An Exploratory nasal-eng.php) 8 Allan J, Herridge N, Griffiths P, Fisher A, Study. 2015 J Drug Depend 3:196.

5 GLOBAL SMART UPDATE Figure 3: Variable dose of active substance in clandestinely manufactured pills

Active for tableting

tableting

Tablets with variable contents

Risk of exposure to for the current overdose epidemic trend in deaths resulting from use fentanyl and its analogues in the region. In the USA, fentanyl of diverted pharmaceutical fentanyl, and its analogues have contributed with at least 123 fentanyl-associated Overdose may also result from to more than 5000 overdose deaths deaths reported between 2000 and handling strong synthetic opioids since fall 201311. In Canada, fentanyl 201215. Death cases resulting from without the precautions that pre- was determined to be the cause, or self-administration of multiple fen- vent the substance from being a contributing factor, in at least 655 tanyl patches were also reported in inhaled or absorbed through the death cases that occurred between Algeria16 and Morocco17. skin or mucous membranes. Con- 2009 and 201412. In the European tact with fentanyl or its analogues Union, death cases involving sub- In recent years, several emerging is so hazardous that both Canada stances from the fentanyl group synthetic opioids have been docu- and the USA recorded incidents of were first documented in the 1990s mented to cause serious adverse 18 hospitalization of law enforcement in Italy and Sweden, resurged in events and deaths . In 2016, a record officers that carried out seizures the early 2000s in Estonia (where spike in drug overdoses in Midwest of such chemicals. The USA Drug most recorded overdose deaths are USA was attributed to carfentanil, Enforcement Administration (DEA) related to fentanyl and 3-methyl- and at least two carfentanil fatali- has recently released safety alerts fentanyl use13), and have also been ties in Canada were reported by the on fentanyl and carfentanil, advis- reported more recently in several press. ing on steps to follow in situations other EU Member States, includ- where such drugs might be present, ing Finland, Germany, Greece, and Markets for specific including immediate application of the United Kingdom14. Australia products naloxone in case of exposure 9,10. has been experiencing a growing Products sold on the illicit synthetic Overdose deaths opioid market are highly diversified, 11 Green TC1, Gilbert M2. Counterfeit Medi- and often region-specific. Injecting The nonmedical use of fentanyl and cations and Fentanyl. JAMA Intern Med. 2016 Oct 1;176(10):1555-1557. its analogues has resulted in thou- 12 Canadian Centre on Substance Abuse. 15 NCIS. Deaths related to fentanyl misuse - An sands of fatalities worldwide. In Deaths involving fentanyl in Canada, 2009– update: Fact Sheet. Retrieved 10 November North America, illicitly manufactured 2014. CCENDU Bulletin, Ottawa, ON 2016. fentanyl or fentanyl analogues have (2015) 16 Salmi A. Fentanyl Patch... The Bad Use. 13 Uusküla A, Raag M, Vorobjov S, Rüütel K, Journal of Clinical Toxicology. 2015 Nov caused several epidemics of over- Lyubimova A, Levina OS, Heimer R. Non- 9;2015. dose deaths since the 1970s, and fatal overdoses and related risk factors among 17 Serghini I. Fentanyl intoxication: case report. are to a large extent responsible people who inject drugs in St. Petersburg, Reactions. 2015 Feb;1539:148-21. Russia and Kohtla-Järve, Estonia. BMC 18 UNODC EWA. Deaths associated with Public Health. 2015 Dec 18;15:1255. use of emerging synthetic opioids. [news 9 https://ndews.umd.edu/sites/ndews.umd.edu/ 14 Mounteney J, Giraudon I, Denissov G, Grif- announcement]. 2016 Nov. https:// files/DEA%20Fentanyl.pdf fiths P. : Are we missing the signs? www.unodc.org/LSS/Announcement/ 10 https://www.dea.gov/divisions/hq/2016/ Highly potent and on the rise in Europe. Int Details/466aa396-492d-4129-a1bc- hq092216.shtml J Drug Policy. 2015 Jul;26(7):626-31. f519ecb5d443#_ftn10

6 Volume 17 fentanyl diverted from pharmaceu- as /acetaminophen, furanylfentanyl, can be synthesized tical products (mostly extracted the content of fentanyl in analysed from NPP or ANPP via the Siegfried from transdermal patches), seems pills varied between 600-6,900 μg/ route. However, the majority of fen- to be the major form of nonmedical pill24. New types of counterfeit pre- tanyl analogues that were put under fentanyl use in Australia19 and Ger- scription pills containing synthetic international control between the many20, and was also reported in opioids continue to appear25. Cases sixties and the nineties and which do New Zealand21. Clandestinely man- of fentanyl and analogues sold under not appear to be linked to the cur- ufactured fentanyl or its analogues the guise of heroin have also been rent opioid crisis in the USA, cannot may be sold in solid or liquid form observed in Europe. For example, readily be produced from NPP or as the consumer’s drug of choice, ocfentanil has been sold on the ANPP. such as is the case in Estonia, where hidden web as heroin, as revealed Data reported to the UNODC on fentanyl and 3-methylfentanyl are by analysis of samples collected in dismantled laboratories manufactur- the most widely used opioids, and Spain and France26. ing fentanyl include: three cases in the primary injected drugs22. Manufacturing and Canada (one kitchen laboratory and In North America, heroin containing, one industrial-scale facility in 2011, or substituted with, drugs from the trafficking and one medium- to large-scale facil- fentanyl group appeared already in According to the DEA27, the current ity in 2012), one kitchen laboratory the 1970s on the illicit drug market fentanyl crisis in the USA is largely in Slovakia (2011), three kitchen under names like “China White”, fuelled by illicitly manufactured laboratories in the USA (one in 2013 “Tango and Cash” or “Synthetic fentanyl and its analogues, which and two in 2015), one kitchen labo- Heroin”. This trend is now making a are either illegally imported as ratory in Germany (2015), and one comeback. Illicitly manufactured fen- such or synthesized from imported case of manufacturing 3-methylfen- tanyl is most commonly mixed with precursors. The materials and appa- tanyl in Russia (2014).29 or sold as white powder heroin, but ratus used in fentanyl synthesis and 23 Due to their extreme potencies, also as cocaine products or black tableting are inexpensive and easy fentanyl and its analogues are often tar heroin. The most recent develop- to obtain from online vendors, present in trace amounts in the ment is the emergence of counterfeit and the synthesis does not require products available, be it has phar- pharmaceutical preparations sophisticated laboratory skills. This maceuticals, illicitly-manufactured containing illicitly manufactured facilitates the entry into small-scale material or in admixture with for fentanyl and its analogues. The sale manufacturing for minor drug-traf- example, heroin. This makes detec- of counterfeit products to unwitting ficking organizations. Most fentanyl tion of these substances extremely customers increases the danger of recently seized in the USA was of challenging in the forensic laboratory overdose, as they do not know which non-pharmaceutical origin and syn- and could lead to under-reporting substance they are consuming, and thesized via the so-called Siegfried of the extent to which these prod- cannot determine the safe amount. method, which was first described ucts appear on the illicitly-used drug Importantly, clandestine manufac- in the 1980s, and is relatively easy market. turers often lack the ability to ensure 28 to perform. Precursor chemicals uniform distribution of such highly used in this route are N-phenethyl- potent substances in marketed prep- 4-piperidone (NPP) or its derivative, arations, such as pills or powders. As 4-anilino-N-phenethylpiperidine a result, some pills or powders may (ANPP). The majority of fentanyl contain a lethal dose. In a Californian analogues reported to the UNODC study on an outbreak of poisonings EWA in recent years, including caused by fentanyl-adulterated acetylfentanyl, butyrfentanyl and tablets purchased on the street 24 Sutter ME, Gerona RR, Davis MT, Roche 19 Roxburgh A, Burns L, Drummer OH, Pil- BM, Colby DK, Chenoweth JA, Adams AJ, grim J, Farrell M, Degenhardt L. Trends in Owen KP, Ford JB, Black HB, Albertson fentanyl prescriptions and fentanyl-related TE. Fatal Fentanyl: One Pill Can Kill. Acad mortality in Australia. Drug Alcohol Rev. Emerg Med. 2016 Jun 20. 2013 May;32(3):269-75. 25 Canadian Centre on Substance Abuse. Novel 20 Erbas B, Arnold M. [Death from fentanyl: Synthetic Opioids in Counterfeit Pharma- Causative and preventive approaches in ceuticals and Other Illicit Street Drugs. Bavaria]. German. MMW Fortschr Med. CCENDU Bulletin, Ottawa, ON, June 2016 2016 Feb 18;158(3):54-6. 26 Quintana P, Ventura M, Grifell M, Palma 21 Schauer CK, Shand JA, Reynolds TM. The A, Galindo L, Fornís I, Gil C, Carbón X, Fentanyl Patch Boil-Up - A Novel Method of Caudevilla F, Farré M, Torrens M. The Opioid Abuse. Basic Clin Pharmacol Toxicol. hidden web and the fentanyl problem: Detec- 2015 Nov;117(5):358-9. tion of ocfentanil as an adulterant in heroin. 22 Abel-Ollo K, Salekešin M, Vorobjov S, Vals International Journal of Drug Policy. 2016 K, Rüütel K. 2014 national report (2013 Nov 23. data) to the EMCDDA by the Reitox 27 DEA. Counterfeit prescription pills contain- National Focal Point. ing fentanyls: A global threat. DEA Intel- 23 Lucyk SN, Nelson LS. Novel Synthetic Opi- ligence Brief. 2016 DEA-DCT-DIB-021-16. oids: An Opioid Epidemic Within an Opioid 28 DEA. Counterfeit prescription pills contain- Epidemic. Annals of emergency medicine. ing fentanyls: A global threat. DEA Intel- 29 UNODC Annual Reports Questionnaires, 2017 Jan 1;69(1):91-3. ligence Brief. 2016 DEA-DCT-DIB-021-16. 2011-2015.

7 GLOBAL SMART UPDATE Japan: “Bath salt” containing acetylfen- SHORT SEGMENTS tanyl and 4-methoxy PV8 linked to a case of acute poisoning TOKYO, Japan – August 2016. In Japan, a forensic autopsy report on a man in his 30s has attributed Source: UNODC this case of acute poisoning to a “bath salt” prod- uct containing acetylfentanyl and 4-methoxy PV8 China: Six fentanyl analogues are placed (4-methoxy PHPP). It is suspected that the substances under national control had been self-administered by an intravenous injec- tion. The deceased had been a habitual user of “bath BEIJING, China – September 2015. On 29 Septem- salts” and, for many years, had a history of metham- ber, 2015 the Chinese Drug and Food Administration phetamine use. A small plastic bag containing a pale announced “Administrative Measures on brown white powder and a filled syringe were also and Psychotropic Substances without Medical Use” found at the scene. by which 116 psychoactive substances, including six fentanyl analogues, were placed under national Yonemitsu, K. et al. (2016) “A fatal poisoning case by intravenous injection of “bath salts” containing acetylfentanyl and 4-methoxy control. This decision came into effect on 1st Octo- PV8.” Forensic Science International267: e6–e9. ber, 2015. The six fentanyl analogues that have been placed under national control are acetylfentanyl, butyrfentanyl, β-hydroxythiofentanyl, 4-fluorobu-

tyrfentanyl, isobutyrfentanyl and ocfentanil. Various H3C O other NPS, have also been included to the list of con- trolled substances. N

UNODC Early Warning Advisory on New Psychoactive Sub- N stances. “Drug Laws/Individual Listing for CHINA.”

Source: UNODC

China: Chinese Customs seizes fentanyl Finland: International cooperation and acetylfentanyl destined for Mexico disrupts acetylfentanyl trafficking BEIJING, China – May 2015. In May 2015, Chinese HELSINKI, Finland – June 2015. After being notified Customs officials seized 46 kg of fentanyl and 26 kg by Belgium Customs, 2.36 grams of acetylfentanyl of acetylfentanyl that had been concealed in a cargo that had been sourced in China were seized in Fin- container destined for Mexico. The substances had land. The substance was in powder form and had been transferred via five freight forwarders before been declared as acrylic paint phenolic resin for an arriving at customs where six customs officials individual in Finland. Previously, in 2014, Finland also became ill and one fell into a coma as a result of reported three acetylfentanyl seizures in small quan- handling the drugs. Later, in March 2016, the Drug tities that had been discovered in the post and had Enforcement Administration (DEA) and Homeland originated from China and Belgium. Security Investigations offices in the south-eastern United States also reported to have seized multiple European Monitoring Centre for Drugs and Drug Addiction shipments that had come from China containing (EMCDDA); Europol. Acetylfentanyl. Luxembourg: Publications mislabeled pill presses, as well as fentanyl, acetylfen- Office of the European Union, 2016. tanyl, and butyrfentanyl.

Drug Enforcement Administration (DEA). DEA Intelligence Brief: Counterfeit Prescription Pills Containing Fentanyls: A Global Threat. July 2016.

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Sweden: Fentanyl analogues linked to several deaths and intoxications STOCKHOLM, Sweden – August 2016. According to the National Board of Forensic Medicine, acrylfen- tanyl has been linked to 20 deaths that occurred in Sweden between April and August 2016. Results from Source: UNODC the Swedish early warning system called the STRIDA project also showed that among patients with sus- UNODC: International control of pected NPS exposure at emergency departments in acetylfentanyl and MT-45 enters into Sweden between April and November 2015, nine force had analytically confirmed intoxications involving acetylfentanyl, three involving 4-methoxybutyrfen- VIENNA, Austria – May 2016. On 17 May 2016, the tanyl, one involving furanylfentanyl, and another decision adopted by the Commission on Narcotic involving a combination of 4-methoxybutyrfentanyl Drugs (CND) during its 59th Session in March 2016 to and furanylfentanyl. All of these patients were aged add the synthetic opioids acetylfentanyl to Schedule I 20-40 and mostly male. In 12 of the cases, patients and IV and MT-45 to Schedule I of the Single Conven- were admitted to intensive care, where two required tion on Narcotic Drugs of 1961 entered into force. intubation and mechanical ventilation. UNODC Early Warning Advisory on New Psychoactive Sub- Helander A., Bäckberg M., and Beck O. (February 2016) stances. “June 2016 – UNODC: Commission on Narcotic Drugs “Intoxications involving the fentanyl analogs acetylfentanyl, decision on international control of acetylfentanyl and MT-45 4-methoxybutyrfentanyl and furanylfentanyl: results from the enters into force.” June 2016. Available at: https://www.unodc. Swedish STRIDA project.” Clinical Toxicology 54 (4): 324-332. org/LSS/Announcement/Details/3ec66e50-249f-438e-8a79- 470d5e269b8d

O O

N

N

Source: UNODC

Source: UNODC Estonia: Furanylfentanyl is placed under national control UNODC: Increasing number of non- controlled fentanyl analogues reported TALLINN, Estonia – July 2016. In July 2016, fura- nylfentanyl was added to Schedule I of the narcotic to the Early Warning Advisory and psychotropic substances regulation. According VIENNA, Austria – November 2016. Of the 13 to the Chemical Department of the Estonian Forensic non-controlled fentanyl analogues that have been Science Institute, furanylfentanyl had been submit- reported by Member States to the UNODC Early ted for analysis five times by June 2016 totaling a Warning Advisory (EWA) by November 2016, eight quantity of 14.185 grams. Although it has not yet have been reported within the last year. These been officially confirmed, the Estonian Forensic Sci- substances include 4-methoxybutyrfentanyl, ence Institute also suspects that the deaths of three butyrfentanyl, despropionylfentanyl, despropionyl- people in Estonia might have been linked to the use 2-fluorofentanyl, furanylfentanyl, acrylfentanyl, of furanylfentanyl. para-fluoroisobutyrfentanyl, and valerylfentanyl. Europäische Kommission. “Notifizierungsangaben: Entwurf zur Additionally, (Iso)butyrfentanyl, (iso)butyr-F-fentanyl Änderung der Verordnung Nr. 73 des Sozialministers.” Available N-benzyl analogue, acetylfentanyl (controlled under at: http://ec.europa.eu/growth/tools-databases/tris/de/index. Schedule I of the Single Convention on Narcotic Drugs cfm/search/?trisaction=search.detail&year=2016&num=33 of 1961), ocfentanil, and beta-hydroxy-thiofentanyl 1&mLang=EN have also been reported to the EWA.

UNODC Early Warning Advisory on New Psychoactive Sub- stances. “Search NPS Data” November 2016.

9 GLOBAL SMART UPDATE

Source: Ioulia Kondratovitch

Ireland: Authorities in Dublin and Cork World Health Organization: WHO Expert investigate deaths involving fentanyl Committee on Drug Dependence reviews analogues twelve psychoactive substances DUBLIN, Ireland – 2016. Between April and July GENEVA, Switzerland – November 2016. At the 2016, five deaths have been linked to the use of flu- 38th meeting of the WHO Expert Committee on Drug orofentanyl (isomer not specified) and ocfentanil in Dependence (ECDD) from 14 to 18 November 2016, Dublin and Cork. As a result of these fentanyl-related twelve psychoactive substances have been consid- deaths, the Health Service Executive (HSE) of Ireland ered for review, among them two synthetic opioids: issued an alert in July 2016 highlighting the dangers U-47700 and butyrfentanyl. The other substances of fentanyl and its analogues. According to the HSE, reviewed are: 4-MEC; 3-MMC; ethylone; pentedrone; fentanyl analogues might be sold to drug users as ethylphenidate; methiopropamine; MDMB-CHMICA; heroin in powder form possibly mixed with heroin 5F-APINACA; JWH-073; and XLR-11. Recommenda- or mixed with caffeine and to mimic tions from the WHO on whether or not to place the effect of heroin. specific substances under international control are Health Service Executive. “Fentanyl Implicated in Overdose addressed to the Secretary-General of the United Deaths.” 28 July, 2016. Available at: http://www.hse.ie/eng/ Nations, and are subject to a vote by the United services/news/media/pressrel/Fentanlydeaths.html Nations Commission on Narcotic Drugs (CND).

UNODC Early Warning Advisory on New Psychoactive Substances. “August 2016 - World Health Organization: NPS to be reviewed for potential scheduling under the International Drug Control Conventions.” August 2016.

Belgium: Belgian Customs Service

reports seizures of acetylfentanyl en Source: UNODC route to France and Germany Brazil: Fentanyl and butylone implicated Brussels, Belgium – 2015. Since June 2015, the Bel- gian Customs Service has reported of three seizure in acute poisonings cases of acetylfentanyl that were perceived to have SÃO PAULO, Brazil – September 2016. In September been sourced in China. In the first case, 103.57 g of 2016, the Laboratory of the Toxicology Faculty of packaged acetylfentanyl that was seized in the post Medicine (FCM) of Unicamp reported that fentanyl and intended for onward trafficking to an individual in and butylone were suspected to have been linked to France, while the second seizure case involved 11.30 six cases of acute poisoning in August 2016 in Campi- g of packaged acetylfentanyl that was also discovered nas, Sumaré, and Indaiatuba, in Brazil. According to in the post and intended for onward trafficking to toxicologists at the Center of Intoxication of Unicamp an individual in Germany. In the third seizure case, (JRC), drug users might not have been aware that three plastic sachets were discovered in the postal they were using fentanyl and butylone because of stream in a plastic package containing 2.42 grams the similarities in appearance to LSD and other drugs. of propylfentanyl, 2.41 grams of acetylfentanyl and The JRC has issued alerts to all emergency rooms in 2.40 grams of flubromazepam. According to the Bel- São Paulo to notify them of the symptoms and effects gian Customs Service, the substances were sourced that these substances can have on drug users. in China and intended for onward trafficking to an individual in Germany. ProMED-mail International Society for Infectious Diseases. “Fen- tanil e butilona - Brasil (SP), uso recreacional, intoxicação, alerta.” European Monitoring Centre for Drugs and Drug Addiction 10 September, 2016. Available at: http://www.promedmail. (EMCDDA); Europol. Acetylfentanyl. Luxembourg: Publica- org/direct.php?id=20160910.4479040 tions Office of the European Union, 2016.

10 Volume 17

Canada: Health Canada proposes national control of fentanyl precursor chemicals OTTAWA, Canada – September 2016. On 3 Septem- ber 2016, Health Canada issued a notice proposing to add six precursor chemicals used in the production of fentanyl to Part 1 of Schedule VI of the Controlled Drugs and Substances Act and to the schedule of the Source: RCMP Precursor Control Regulations as Class A precursor chemicals: propionyl chloride; 1-phenethyl-4-piper- idone (NPP) and its salts; 4-piperidone and its salts; Canada: Promoting safe handling of norfentanyl (N-phenyl-N-piperidin-4-ylpropanamide) fentanyl by first responders and its salts; 1-phenethylpiperidin-4-ylidenephenyl- BRITISH COLUMBIA, Canada – June 2016. Spon- amine and its salts; and N-phenyl-4-piperidinamine sored by the Justice Institute of British Columbia and and its salts. These regulatory amendments came the British Columbia Association of Chiefs of Police, into force on 30 November 2016. the Royal Canadian Mounted Police (RCMP) has Government of Canada. “Canada Gazette.” Vol. 150, No. 36, Sep- provided two-day workshops to train police, para- tember 3, 2016. Available at: http://www.gazette.gc.ca/rp-pr/ medics, firefighters, correctional officers, Canada p1/2016/2016-09-03/html/notice-avis-eng.php Border Services agents and Transport Canada staff in safe handling of fentanyl in British Columbia. The RCMP also raised awareness of the dangers of fen- tanyl to first responders and the general public by releasing a video in September 2016 that featured two British Columbia RCMP officers who became sick immediately after inhaling or touching fentanyl that belonged to people they had come across during a car inspection.

Source: DEA British Columbia Government News. “Workshops safeguard first responders from deadly fentanyl.” 14 June 2016. Available at: United States: Counterfeit oxycodone https://news.gov.bc.ca/releases/2016PSSG0118-001025 Royal Canadian Mounted Police (RCMP). “Video on the dangers and Xanax tablets contain fentanyl and of fentanyl.” Available at: http://www.rcmp.gc.ca/en/fentanyl- analogues video?nr LOS ANGELES, California – March 2016. In Los Angeles, the Drug Enforcement Administration (DEA) seized a counterfeit prescription pill manufactur- United States: Fentanyl analogues are ing site in March 2016 that had employed the use placed under national control of fentanyl and other synthetic . Previously, in January 2016, the DEA of New Jersey arrested WASHINGTON D.C., United States – 2016. Based a counterfeit prescription pill producer who had on the recent surge of fentanyl-related deaths, manufactured tablets in New York to look like 30 the DEA issued a nationwide alert on fentanyl and milligram oxycodone tablets, but in fact contained its analogues in March 2015. Since 17 July 2015, either fentanyl citrate or acetylfentanyl. According to acetylfentanyl is a controlled substance in the United the DEA, nine people died of the use of counterfeit States under Schedule I of the Controlled Substances Xanax® tablets containing fentanyl in Pinellas County, Act. In September 2016, the DEA issued a notice of in Florida between January and March 2016. In March intent to temporarily schedule the synthetic opioid and April 2016, another 52 overdoses and 10 deaths furanylfentanyl. occurred in Sacramento, California, through the use UNODC Early Warning Advisory on New Psychoactive Substances. of counterfeit Norco® pills containing fentanyl. “July 2015 – United States of America: Acetylfentanyl placed under temporary control.” July 2015. Available at: https://www.unodc. Drug Enforcement Administration (DEA). DEA Intelligence Brief: org/LSS/Announcement/Details/a9a23075-6d57-4cc2-9a49- Counterfeit Prescription Pills Containing Fentanyls: A Global 0bcce189e776 Threat. July 2016.

11 Recent Global SMART Publications

Afghanistan Synthetic Drugs Situation Assessment

Goba M roramme

anar 201

Global SMART Global SMART Global SMART Afghanistan Synthetic Drugs Update Volume 16 Update Volume 15 Update Volume 13 Situation Assessment (English and Spanish) (English and Spanish) (now Russian) 2017

World Drug Report Information Bulletin on Early Warning Advisory Updated New Psychoactive 2016 synthetic drugs in Latin America Newsletter Volume 9, Substance leaflet and poster and the Caribbean 10 and 11 (English and Spanish) Volume 1 and 2 (English and Spanish)

Global SMART UNODC Early Warning Publications Advisory on NPS

Contact details Global SMART Programme Vienna International Centre www.unodc.org/unodc/en/scientists/smart-new.html P.O. Box 500 www.unodc.org/nps A-1400, Vienna www.apaic.org Austria [email protected]

UNODC would like to thank the following Governments for their financial contributions to the Global SMART Programme.

Australia Canada China Japan New Zealand Republic of Korea

Russian Federation Thailand United Arab Emirates United Kingdom United States