Roumen Sedefov

Legal Highs on the Internet

This article describes the findings of a descriptive analysis of 27 online drug retailers selling legal alternatives to illegal drugs, commonly referred to as “herbal highs” and “legal highs” in . The study attempted to quantify the online availability of drug retailers, to describe common products and characteristics in EU-based retail sales. The findings highlight the concern about the lack of objective information about products offered, including potential risks to health. Systems should be developed to assess the contents of products and the accuracy of information provided on the Internet, alongside continued monitoring of this market for “legal high” substances.

The pharmacology and toxicology of the synthetic cathinone mephedrone (4‐methylmethcathinone)

Mephedrone (4-methylmethcathinone) is a synthetic cathinone that is used as a recreational drug. It has been available since 2007 but its availability and use increased significantly during 2009 and 2010. In this review article we will summarize the available literature on the sources, availability, and prevalence of the use of mephedrone. We will also discuss the pharmacology of mephedrone, the patterns of acute toxicity associated with its use, the reports of fatalities associated with its use, and the potential for mephedrone dependence.

Khat use and monitoring drug use in Europe: the current situation and issues for the future.

AIM OF THE STUDY To review the information available on the use of khat (Catha edulis) in the EU, and to assess the future use of this drug and related substances. MATERIAL AND METHODS Khat is not controlled by international law and it has not been systematically included in the list of illicit drugs monitored in the EU. The current principal source of information on khat use in Europe is the early-warning system set up to monitor new and emerging drugs. Further information was obtained from official national reports to the EMCDDA and from the scientific literature. RESULTS Across Europe, the use of khat is low. Khat use is limited to countries with immigrant communities from countries where khat use is common (such as Ethiopia, Somalia and Kenya). Information on the prevalence of khat use in the general population is scarce. Data on seizures provide an insight on the situation, though these may be difficult to interpret. The most recent estimates suggest that Europe accounts for about 40% of the khat seized worldwide. CONCLUSION The shortage of data on the use and patterns of use of khat in Europe does not allow an evaluation of the needs for health and social interventions in communities in which the drug is used. But seizures of the plant are increasing in the EU, and more synthetic derivatives of the pharmacologically active ingredients of the plant (cathine and cathinone) are appearing on the market. Some of these, like mephedrone, have significant potential for future diffusion, and are likely to play a greater role on the European drug scene of the future.

The drug situation in Europe: an overview of data available on illicit drugs and new psychoactive substances from European monitoring in 2015

AIM A central task for the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) is to produce an annual report of the latest data available on drug demand and drug supply in Europe. This paper is intended to facilitate a better understanding of, and easier access to, the main quantitative European level data sets available in 2015. METHODS The European reporting system formally covers all 28 European Union (EU) Member States, Norway and Turkey and incorporates multiple indicators alongside an early warning system (EWS) on uncontrolled new psychoactive substances (NPS). While epidemiological information is based largely on registries, surveys and other routine data reported annually, the EWS collects case-based data on an ongoing basis. The 2015 reporting exercise is centred primarily on a set of standardized reporting tools. RESULTS The most recent data provided by European countries are presented, including data on drug use, drug-related morbidity and mortality, treatment demand, drug markets and new psychoactive substances, with data tables provided and methodological information. A number of key results are highlighted for illustrative purposes. Drug prevalence estimates from national surveys since 2012 (last year prevalence of use among the 15-34 age band) range from 0.4% in Turkey to 22.1% in France for cannabis, from 0.2% in Greece and Romania to 4.2% in the United Kingdom for cocaine, from 0.1% in Italy and Turkey to 3% in the Czech Republic and the United Kingdom for ecstasy, and from 0.1% or less in Romania, Italy and Portugal to 2.5% in Estonia for amphetamine. Declining trends in new HIV detections among people who inject drugs are illustrated, in addition to presentation of a breakdown of NPS reported to the EU early warning system, which have risen exponentially from fewer than 20 a year between 2005 and 2008, to 101 reported in 2014. CONCLUSIONS Structured information is now available on patterns and trends in drug consumption in Europe, which permits triangulation of data from different sources and consideration of methodological limitations. Opioid drugs continue to place a burden on the drug treatment system, although both new heroin entrants and injecting show declines. More than 450 new psychoactive substances are now monitored by the European early warning system with 31 new synthetic cathinones and 30 new synthetic cannabinoid receptor agonists notified in 2014.

Acute recreational drug and new psychoactive substance toxicity in Europe: 12 months data collection from the European Drug Emergencies Network (Euro-DEN).

Context. Despite the potential for recreational drugs and new psychoactive substances (NPSs) to cause significant morbidity and mortality, there is limited collection of systematic data on acute drug/NPS toxicity in Europe. Objective. To report data on acute drug/NPS toxicity collected by a network of sentinel centres across Europe with a specialist clinical and research interest in the acute toxicity of recreational drugs and NPS to address this knowledge gap. Methods. Sixteen sentinel centres in 10 European countries (Denmark, Estonia, France, Germany, Ireland, Norway, Poland, Spain, Switzerland and the UK) collected data on all acute drug toxicity presentations to their Emergency Rooms (ERs) for 12 months (October 2013–September 2014); information on the drug(s) involved in the presentations was on the basis of patient self-reporting. Results. Data were collected on a total of 5529 presentations involving 8709 drugs (median (interquartile range [IQR]): 1 (1–2) drugs per presentation), a median of 0.3% of all ER attendances. Classical recreational drugs were most common (64.6%) followed by prescription drugs (26.5%) and NPS (5.6%). The ‘top five’ drugs recorded were heroin (1345 reports), cocaine (957), cannabis (904), GHB/GBL (711) and amphetamine (593). 69.5% of individuals went to hospital by ambulance (peak time between 19:00 and 02:00 at weekends); the median (IQR) age was 31 (24–39) years and 75.4% were male. Although serious clinical features were not seen in most presentations and 56.9% were medically discharged from the ER (median length of stay: 4.6 hours), a significant number (26.5%) was agitated, in 10.5% the GCS was 8 or less and 35 presented in cardiac arrest. There were 27 fatalities with opioids implicated in 13. Conclusion. The Euro-DEN dataset provides a unique insight into the drugs involved in and clinical pattern of toxicity/outcome of acute recreational drug toxicity presentations to hospitals around Europe. This is complimentary to other indicators of drug-related harm and helps to build a fuller picture of the public health implications of drug use in Europe.

Prevalence of use and acute toxicity associated with the use of NBOMe drugs

Abstract Introduction. The 25X-NBOMe series are N-2-methoxybenzyl analogues of the respective 2C-X substituted phenethylamine and include 25B-N(BOMe)2, 25B-NBOMe, 25C-NBOMe, 25D-NBOMe, 25E-NBOMe, 25G-NBOMe, 25H-NBOMe, 25I-NBOMe, 25N-NBOMe and 25iP-NBOMe. There are reports of their use as novel psychoactive substances and associated acute toxicity from Europe, the United States and elsewhere over the last five years. This review will discuss the epidemiology of use and pattern of acute toxicity associated with use of these compounds. Methods. A PubMed search was performed using the search terms ‘NBOMe’, ‘25B-N(BOMe)2’, ‘25B-NBOMe’, ‘25C-NBOMe’, ‘25D-NBOMe’, ‘25E-NBOMe’, ‘25G-NBOMe’, ‘25H-NBOMe’, ‘25I-NBOMe’, ‘25N-NBOMe’ and ‘25iP-NBOMe’ covering the years 1966–2014. In addition, abstracts from the 2010–2014 congresses of the European Association of Poisons Centres and Clinical Toxicologists and the 2010–2013 North American Congress of Clinical Toxicology were reviewed using these search terms. Further information was obtained from the European Information System and Database on New Drugs co-ordinated by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Prevalence of use. There are no national or international surveys collecting data on the prevalence of use of NBOMe drugs. The only information on prevalence of use is from two sub-population surveys of individuals who frequent nightclubs. Of 22,289 respondents of the 2013 Global Drugs Survey, 582 (2.6%) had previously used an NBOMe; the most commonly used NBOMe was 25I-NBOMe (442 respondents, 2.0% of whole cohort and 75.9% of those who had used an NBOMe). In a survey of 397 clubbers in London nightclubs in 2013, 11.8% had heard of the NBOMe drugs (compared with 96.0% for mephedrone), and 4.8% had ever used an NBOMe (compared with 76.6% for mephedrone). Acute toxicity. There were 29 published cases in the literature of acute toxicity associated with the use of an NBOMe: 25I-NBOMe – 23 cases; 25B-NBOMe – 3 cases; 25C-NBOMe – 3 cases. Commonly reported features include tachycardia (96.6%), hypertension (62.0%), agitation/aggression (48.2%), seizures (37.9%) and hyperthermia (27.6%). Five patients were reported to have developed acute kidney injury. There were an additional 25 reports of acute toxicity related to the use of 25I-NBOMe reported to the EMCDDA. The pattern of toxicity in these cases is similar to that seen in the published cases. NBOMe-related deaths. 25I-NBOMe has been detected in eight fatalities; in one of these, 25C-NBOMe was also detected. The role of the NBOMe drugs in these deaths has not been determined in all cases. Conclusions. Currently, there is evidence suggesting limited use of the NBOMe class of drugs as novel psychoactive substances compared with that of classical recreational drugs and other novel psychoactive substances such as mephedrone.

Getting up to speed with the public health and regulatory challenges posed by new psychoactive substances in the information age.

Until about a decade ago, most new psychoactive substances that emerged were typically sold on the illicit market. They were usually produced in clandestine laboratories and called ‘designer drugs’, or were sourced from diverted medicines. This continues to be the case, with some of these drugs simply acting as temporary substitutes—often unknown to users—for established controlled drugs that are in short supply, such as 3,4methylenedioxy-N-methylamphetamine (MDMA). The sale of new drugs on an open market, beginning with 1-benzylpiperazine (BZP) and methylone, followed by mephedrone, marked the start of what is now called the ‘legal highs’ market. We now know that many new drugs that are destined for the ‘legal highs’ market are produced in bulk in China and India and imported into Europe and elsewhere, where they are processed, packaged and sold. The marketing and distribution of these drugs has reached a new level of sophistication, including advertisement and sale on the open market, such as through the internet (with delivery via courier and postal services), as well as ‘head shops’ in towns and cities. They may also sold by streetlevel drug dealers [1]. Addiction has drawn together a collection of papers that have been published over the last few years, as a virtual issue which considers the challenges presented by these new psychoactive substances. Only a few years ago the issue of the ‘legal highs’ market was regarded as an area of limited significance. Things change rapidly, however, and today the question of how to respond to the challenges posed by the emergence of new drugs has become one of major international concern [2]. The papers begin the task of elaborating the policy challenges we now face, particularly in relation to public health and regulatory responses. Before introducing them, however, it is worth taking a brief moment to reflect upon why these things have come to pass, and in so doing ground this virtual issue within the wider social and contextual factors that not only help to shape contemporary patterns of substance consumption but also impact upon almost all other aspects of our modern life. Posting on an internet discussion forum on 26 September 2006, Mexican Seafood noted that some of his, or possibly her, friends had been smoking a herbal mixture called ‘Spice’ that was, by all accounts, surprisingly impressive. The post contained a list of the 14 herbal constitutes it was claimed to contain and sought advice on their provenance. This was swift in coming, with MadScientist claiming early the next day that none of these substances contained CB1 agonists and that laboratory testing had not revealed any cannabinoids to be present. It was further speculated that the product might contain ‘additional active compounds as there were many legal and structurally distinct CB1 agonist available’. This post was followed within hours by claims from Shamantra that ‘Spice’ contained the synthetic cannabinoid HU-210 and speculating that none of the herbal substances claimed on the labelling were likely to be present. It was also noted that the effects were similar to, but longer-lasting than, hashish [3]. While not the first online discussion relating to ‘Spice’, the excerpts above are examples of how modern communication has impacted upon drug use trends [1]. It also serves to highlight the speed at which developments can now occur in the drugs field and by contrast how lumbering remain our efforts to track them.To put these posts into historical perspective, it was only in December 2008 that three synthetic cannabinoids, JWH-018, CP-47 497 and its active homologue, were identified in ‘Spice’ products [4]. Addiction was among the first journals to open the scientific debate on this topic, and by the time the editorial on ‘Spice’ products was published in 2010 nine synthetic cannabinoids had been reported to the European Union Early warning system on new psychoactive substances [4]. By June 2013, more than 80 synthetic cannabinoids

Current European data collection on emergency department presentations with acute recreational drug toxicity: Gaps and national variations

Abstract Background. The number of new (novel) psychoactive substances (NPS) available in the illegal market is increasing; however, current monitoring of the drug situation in Europe focuses mainly on classical drugs of abuse, with limited emphasis on clinical presentation in the emergency department (ED). The European Drug Emergencies Network (Euro-DEN) is a European Commission-funded project that aims to improve the knowledge of acute drug toxicity of both classical recreational drugs and NPS. As a baseline for this project, we performed a study to establish which data are currently being collected and reported in Europe on ED presentations with acute toxicity related to NPS and classical drugs of abuse. Methods. We used a three-pronged approach to identify any systematic collection of data on NPS toxicity in Europe by i) performing a literature search, ii) utilising an online survey of the European Monitoring Centre for Drugs and Drug Addiction Re seau Europe en d’Information sur les Drogues et les Toxicomanies national focal points and iii) exploiting the knowledge and resources of the Euro-DEN network members. Results. The literature search revealed 21 papers appropriate for assessment, but only one described a systematic collection of clinical data on NPS. Twenty-seven of thirty countries responded to the online survey. More than half of all the countries (52%) did not perform any registration at all of such data, 37% collected systematic clinical data on NPS at a national level, while 44% collected data on classical drugs. A few examples for good practice of systematic collection of clinical data on ED presentations due to acute toxicity were identified. Conclusion. The systematic collection of data on ED presentation of toxicity related to NPS and classical drugs in Europe is scarce; the existing collection is limited to single centres, single countries, groups of patients or not focused on novel drugs; the collection of data is highly variable between the different countries. Euro-DEN, a European Commission funded project, aims at closing some of these gaps.

New psychoactive substances: driving greater complexity into the drug problem

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Acryloylfentanyl, a recently emerged new psychoactive substance: a comprehensive review

N-(1-Phenethylpiperidin-4-yl)-N-phenylacrylamide, or acryloylfentanyl (acrylfentanyl), is a synthetic opioid and a close structural analogue of fentanyl, which is widely used in medicine as an adjunct to general anaesthesia during surgery and for pain management. Until recently, acryloylfentanyl was known only from the scientific literature, but in 2016 this non-controlled substance became available on the illicit drug market as a powder and nasal spray in Europe and the USA. By the end of 2016, detection of acryloylfentanyl in six European countries, including 47 deaths associated with the drug, had been reported to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) through the European Union Early Warning System, which is a part of the system designed to identify and respond to the appearance of new psychoactive substances that may pose potential public health risks similar to drugs controlled under the United Nations drug control conventions. Herein we review what is known about this potent narcotic opioid. In addition to describing its chemical properties and the synthetic routes, analytical methodologies for the identification of the substance, as well as the limited information on the biological properties, including in vitro and in vivo pharmacological studies with the substance, are summarised. Analytically confirmed acute intoxications show that the signs and symptoms of acryloylfentanyl poisoning correspond to the opioid overdose triad of decreased consciousness, miosis and respiratory depression. Importantly, naloxone works as an antidote in life-threatening poisoning. The major human urinary metabolites identified in fatal overdose cases were nor-acryloylfentanyl, as well as mono- and dihydroxylated derivatives and their conjugates.