Novel Psychoactive Substances: Classification, Pharmacology and Toxicology

By David M. Wood

Novel Psychoactive Substances: Classification, Pharmacology and Toxicology, Second Edition provides readers with a comprehensive examination on the classification, detection, supply and availability of novel psychoactive substances, otherwise known as "legal highs." The book covers individual classes of novel psychoactive substances that have recently emerged onto the recreational drug scene and provides an overview of the pharmacology of the substance and a discussion of their associated acute and chronic harm and toxicity. This second edition addresses drugs new to the scene, with completely updated and revised chapters.

Written by international experts in the field, this multi-authored book is an essential reference for scientists, clinicians, academics, and regulatory and law enforcement professionals.

• Includes chapters written by international experts in the field
• Presents a comprehensive overview on the classification, detection, availability and supply of novel psychoactive substances, in addition to the pharmacology and toxicology associated with the substance
• Offers a single source for all interested parties working in this area, including scientists, academics, clinicians, law enforcement and regulatory agencies
• Provides a full treatment of novel psychoactive substances that have recently emerged onto the recreational drug scene, including amphetamines and the synthetic cannabinoid receptors in ‘spice’ and ‘K2’

• Language: English
• Publisher: Academic Press
• Release date: Sep 6, 2021
• ISBN: 9780128190302

Book preview

Part I

Background

1 Legal classification and international systems for monitoring and responding to novel psychoactive substances 3

2 Availability and supply of novel psychoactive substances 57

3 Prevalence of use of novel psychoactive substances 85

4 Pharmacological profiling of novel psychoactive substances 109

5 Novel detection methods and data triangulation for novel psychoactive substances (NPS) 131

6 Social issues in the use of new psychoactive substances: Differentiated demand, displacement and adulteration 157

7 General management of the patient with novel psychoactive substance toxicity 181

8 Addiction and treatment of novel psychoactive substance dependence 203

Chapter 1

Legal classification and international systems for monitoring and responding to novel psychoactive substances

Michael Evans-Brown, Brendan Hughes and Roumen Sedefov

European Monitoring Centre for Drugs and Drug Addiction, Lisbon, Portugal

Abstract

Novel psychoactive substances make up a broad range of drugs that are not controlled by the United Nations international drug laws. They include synthetic cannabinoids, stimulants, benzodiazepines, opioids, hallucinogens, and dissociatives. Many of these substances are intended to mimic the effects of controlled drugs and are traded as ‘legal’ replacements for them. While the emergence of novel psychoactive substances is not a new phenomenon, driven by globalisation there has been a large increase in the availability, and, subsequently, harms caused by these substances since around 2008. At least until relatively recently, as the list of substances controlled at national level were largely based on those substances controlled under the international drug control system, few novel psychoactive substances were subject to control measures in many countries. However, in response to the growth in the market, increasingly some novel substances have been controlled or otherwise regulated at national level, irrespective of whether or not they are controlled internationally. Invariably, despite this, novel substances continue to appear on the drug market, albeit at a slower pace. This chapter: examines the legal classification of novel psychoactive substances; provides an overview of some of the early warning systems for monitoring and responding to these substances; discusses the current situation in Europe; and highlights the possible future of these substances and how our responses made need to adapt to ever-changing globalized drug markets. This includes a discussion of the work of the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) as part of a unique regional three-step legal framework of early warning, risk assessment, and control measures that allows the European Union to rapidly detect, assess, and respond to public health and social threats caused by these substances.

Keywords

Early-warning systems; Globalisation; Health security; Public health policy; Risk assessment; New psychoactive substances; Preparedness; Outbreaks; Fentanils; Synthetic cannabinoid receptor agonists; Synthetic cathinones; Legal highs; Dietary supplements; Adulteration; Pandemic; COVID-19

Statement on the United Kingdom

The United Kingdom left the European Union on the 31 January 2020. However, during the transitional period, the United Kingdom continued to participate in the European Union Early Warning System on new psychoactive substances operated by the EMCDDA. Unless stated otherwise, for the purpose of this chapter, the term ‘Member States’ includes the United Kingdom.

Key methodological points

In this chapter, data regarding first identifications of a new psychoactive substance in Europe (formal notification data) relate to the period from 1 January 2005 to 31 December 2020.

The seizure data used in this chapter are from 1 January 2005 to 31 December 2019.

Law enforcement seizures of novel psychoactive substances reported to the EMCDDA should be understood as minimum values. This is because data are drawn from case reports rather than routine monitoring systems. Reports are influenced by a range of factors such as increasing awareness of new substances, their changing legal status, law enforcement capacities and priorities, the reporting practices of agencies and the structure of national early warning systems which differ widely across Europe. The seizure data are not directly comparable with the data on controlled drugs. Quantitative data on the amount of novel psychoactive substances present in a seizure (purity) are typically not available, as this type of analysis is not routinely performed by laboratories. As a result, seizures are not adjusted for purity. Seizures are also not adjusted for the potency of the substance. In addition, a novel psychoactive substance may be found in a mixture with one or more novel psychoactive substances and, in such cases, the first novel psychoactive substance reported by the laboratory is taken as the substance in the seizure.

The data also include an increasing number of former novel psychoactive substances that are now controlled under the United Nations international drug laws. These include 2C-B, some synthetic cathinones (such as mephedrone), synthetic cannabinoids (such as 4F-MDMB-BINACA) and opioids (such as carfentanil).

The figures depicting trends in the quantity of material seized aggregate quantities for all forms reported in weight (kg) and exclude all material reported as tablets (units), volume (liters), and other forms. Trends are presented for the EU Member States (EU) and the EU Member States plus Norway and Turkey (EU+2).

Introduction

Humans have used psychoactive substances (drugs) for thousands of years. Throughout this time, they have been used for nutritional, medicinal, spiritual, and social reasons, for self-discovery and to enlighten, for relaxation, excitement, pleasure, and curiosity, as well as to enhance creativity and performance [1–7]. Initially, most of these substances were used by eating or drinking crude plant material, such as from the opium poppy, cannabis, ephedra, coca, and peyote [1,2].

Since those early days, a general trend has been towards an increase in the number and types of risks faced by people who use drugs, and, more generally, society. These risks are related to continuous social, economic, cultural, and technological changes [4,6]. They include the ability to isolate and purify psychoactive substances from crude plant material [5], the increased availability of drugs, new ways of using them (such as smoking, injecting, and, now vaping) [e.g. 8], increasing numbers of users, the invention of more potent synthetic substances [5], the emergence of new infectious diseases (such as HIV [9] and hepatitis C [10]), as well as from unintended consequences from some of the policy responses that societies have opted for in their attempts to reduce drug use [11,12]. These risks have become particularly acute in the last few decades [12,13].

The origins of novel psychoactive substances

As the field of organic chemistry developed during the nineteenth and twentieth centuries, scientists were able to isolate and purify the psychoactive substances from crude plant material [5]. This allowed doctors to provide more consistent and accurate doses of these medicines to their patients; but purified substances, such as morphine from opium and cocaine from coca leaves also meant more potent effects — effects that were even more accentuated by the invention of the hypodermic needle and syringe in the 1850s that allowed these drugs to be delivered directly into the bloodstream from where they quickly made their way to the brain to cause an even greater ‘high’ or ‘rush’ as well as a risk of overdose [8].

Organic chemistry also allowed scientists to determine the chemical structures of these active substances, manipulate them, and develop a range of new substances [5]. Crude opium from the poppy was purified to give morphine, whose structure was tweaked to give diacetylmorphine — a more potent opioid that was sold from the 1890s onwards under the trade name heroin, and marketed, incorrectly as it turned out, as a ‘non-addictive’ replacement to morphine [6]. Ephedra led to the isolation of ephedrine, which was subsequently used as a template to make amphetamine — a potent stimulant that was extensively over-prescribed in 1950s America for weight loss and mood disorders [14,15]. Other developments in the field of chemistry led to the discovery of additional sources that could be used as the building blocks for new types of chemicals, leading, overall, to the invention of a large range of psychoactive substances [5].

The goal of much of this work was to develop new and better medicines. While a relatively small number were successfully commercialized as such, many others fed into the research cycle, being used as pharmacological and clinical tools to study the body and provide insights into disease states, and as chemical templates for developing new types of substances. The results of this ongoing work are catalogued in the scientific and patent literature that provides the blueprints and recipes for making thousands of psychoactive substances [5]. For example, while only 30 or so benzodiazepines have been commercialized as medicines (one of the most important groups of medicines that produced sedation and sleep), hundreds more were synthesized by chemists but were never marketed [16].

Of the relative small number of substances that were used as medicines — such as the opioid morphine, stimulant amphetamine, and sedative–hypnotic benzodiazepines — most rapidly spread beyond the field of medicine — driven by consumer demand, weak regulation, and wider social and cultural changes [4,17–20]. As concerns grew during the 20th century over the health and social harms caused by the non-medical use of these substances (sometimes called ‘abuse’), control measures were increasingly introduced or tightened at international and national level in an attempt to reduce their availability and limit their harms [11,21,22].

As a result, in many cases illicit markets sprang up. Some of these were supplied by diverted medicines, in other cases from illicit (clandestine) laboratories. In addition to these markets, attempts were made to get round these controls by making novel substances that were not controlled by drug laws. For example, after morphine became a controlled drug in the 1920s, pharmaceutical companies produced vast quantities of the non-controlled morphine esters benzylmorphine and acetylpropionylmorphine to sell on the illicit opioid market [23]; in the 1960s, following the discovery and synthesis of THC, which is the main psychoactive constituent of cannabis, raids on illicit laboratories found the ingredients and recipes to make ‘synthetic marijuana’ [24]; while from the late 1970s onwards the fentanils — highly potent derivatives of the opioid analgesic fentanyl [25,26] — were made in illicit laboratories and sold as heroin or ‘synthetic heroin’ to unsuspecting users [27–29].

Until the 1960s, most of the substances that did appear on the illicit drug market were established medicines. After that, a handful of the other substances also began to appear as word of their effects escaped laboratory and clinical research studies and spread to small groups of people who were keen to experiment with them. Some failed to catch on further and remained ‘chemical curiosities’, usually because the pharmacological effects were of interest only to a small number of people or because of the unpleasant or harmful effects that they produced [30–32]. Others, such as LSD, ketamine, PCP, and MDMA (or ‘ecstasy’ as it is better known) spread more widely, being produced in hobbyist and illicit laboratories, and eventually became important substances for the drug market. These substances often have long and fascinating stories that tell of how they came to be discovered and used within society [33–40].

Until the mid-2000s, most of the novel substances that emerged in Europe were produced in hobbyist and illicit laboratories and often distributed through close social networks or through the established illicit drug market. These substances became known as ‘designer drugs’ — a reference to the fact that they appeared to have been ‘designed’ to circumvent drug laws, though, in reality, many had been previously described in the scientific and patent literature [27–29]. One of the best known examples of this phenomenon was the emergence of the phenethylamine MDMA, which rapidly established itself on the drug market in the United States [27], and, subsequently, Europe during the 1980s and 1990s [35,36]. It also included a number of other phenethylamines and tryptamines following the publication of the books PiHKAL (Phenethylamines I Have Known and Loved) and TiHKAL (Tryptamines I Have Known and Loved) during the 1990s by the chemist Alexander T. Shulgin and his wife Ann Shulgin that provided information on the self-experimentation with dozens of these substances as well the materials and methods used for their synthesis [41,42] — information which was then used by hobbyist and illicit chemists to make these substances.

So, the appearance and use of ‘novel’ substances is not a new chapter in the history of drug use [43,44]. While diverted medicines, such as pregabalin [45–48], and substances produced in illicit laboratories, such as 4-methylamphetamine [49] and 4F-amphetamine [50], continue to be important sources of novel substances, what is new is the dramatic increase in the number, type, and availability of novel substances appearing on the drug market since the mid-2000s onwards. The trickle of novel substances has turned into a flood, as driven by globalisation and new technologies such as the internet, entrepreneurs and crime groups have systematically exploited the scientific and patent literature and produced, sold, and supplied on an industrial scale a large range of new substances and branded products, leading to huge growth in the market [51–58].

Despite this growth, very few of the novel substances that have appeared in recent years have become popular substances in their own right. However, this is not the objective for the mass market. Most suppliers are not looking for a long-term replacement for cannabis, MDMA, cocaine, heroin, or diazepam; they are simply supplying substances that can mimic their effects and that can be produced, transported, and sold freely. The reality is that most novel substances that have appeared on the market in the last few years are seen as disposable, as manufacturers can have replacement substances ready for sale even before a substance is controlled; the recipes for many thousands more are in the scientific and patent literature ready to be exploited. In the past this simply was not possible as suppliers were constrained by a lack of capacity to produce and supply a large range of substances in sufficient quantities to fuel such a market. In addition, the market in novel substances has developed strong links with the market in established illicit drugs — with novel substances commonly being mis-sold as or used to adulterate established drugs usually without the knowledge of consumers. Overall, these factors have created a resilient and highly dynamic novel psychoactive substances market, making it difficult to disrupt.

Responding to novel psychoactive substances

Faced with the large growth in the market in recent years, the authoritative and timely information on novel psychoactive substances has become critical to informing effective and timely public health responses. Such information is essential to developing practical, actionable, evidence based preparedness and response measures — whether this be prevention, health protection, treatment and supply reduction measures, or policy development and implementation — including decision making on the need for control measures whether at international, regional, or national level.

This chapter examines these issues and how societies are responding to novel psychoactive substances through a specific focus on legal classification and monitoring and response systems. It is divided into several parts: The first provides an overview of legal classification of novel psychoactive substances at international, European, and national level, as well as an overview of the work of the United Nations in monitoring and responding to novel substances. The second part provides a detailed case study the three-step legal framework of early warning, risk assessment, and control measures that for more than 20 years has allowed the European Union and the Member States to rapidly detect, assess, and respond to public health and social threats caused by novel substances. While the third part provides an overview of the current situation in Europe with novel psychoactive substances up to the end of 2020. Finally, the fourth part examines what may be next for the market in novel psychoactive substances in the era of ‘global markets, glocal threats’, and what is required in order to strengthen preparedness and response measures in order to protect society from the public health and social threats caused by these substances over the next few years, including during and after the COVID-19 pandemic.

Legal classification of novel (new) psychoactive substances

Terms and definitions

Over the last 20 years, a variety of terms and definitions have been used for novel psychoactive substances that emerge on the market and are not controlled under the international or national drug control systems. Here we briefly review those relating to the experiences at international level and in the European Union, while recognizing that other terms and definitions are used in different settings.

While there is no legal definition of new psychoactive substances at international level, in order to promote clear and consistent terminology, the United Nations Organization on Drugs and Crime (UNODC) defines them as ‘substances of abuse, either in a pure form or a preparation, that are not controlled by the 1961 Single Convention on Narcotic Drugs or the 1971 Convention on Psychotropic Substances, but which may pose a public health threat’ [59].

In the European Union, a new psychoactive substance is defined in law as ‘a substance in pure form or in a preparation that is not covered by the 1961 United Nations Single Convention on Narcotic Drugs, as amended by the 1972 Protocol, or by the 1971 United Nations Convention on Psychotropic Substances but may pose health or social risks similar to those posed by the substances covered by those Conventions’ [60,61]. This definition is used by the legal framework that establishes a three-step system of early warning system, risk-assessment, and control measures for new psychoactive substances within Europe. This system is discussed in greater detail in the second part of this chapter.

The UNODC and European Union definitions of a new psychoactive substance are very similar, with both defining such substances by way of analogy to substances controlled under the international drug control system. Essentially, a substance is defined as new psychoactive substances because it is not controlled under either of the 1961 or 1971 United Nations conventions but may pose health or social risks similar to those substances covered by those Conventions. In some countries these definitions, or derivations thereof, have also been used for operational, administrative, and regulatory purposes.

In addition to these definitions, a large number of terms are used in the mass media and in society in general to describe non-controlled, novel, psychoactive substances and products containing them. For example, in English-speaking countries the term ‘legal highs’ has been used as an umbrella term for novel psychoactive substances, or products claiming to contain them, which are intended to mimic the effects of controlled drugs. While the term has been used since the 1950s, it has only been in common use since around 2008 or so, when the term was increasingly used to describe a wide range of synthetic and plant derived substances and products that started to appear on the market in Europe. These were marketed as ‘legal highs’ (emphasizing ‘legality’), ‘herbal highs’ (stressing the natural/plant origin), as well as ‘research chemicals’ and ‘party pills’. These products were often deliberately mislabeled with regard to their intended use (e.g. labeled as ‘not for human consumption’, ‘plant food’, ‘bath salts’, ‘room odourisers’) and to hide the identify of the active substances that they contained. So-called ‘legal highs’ were usually sold via the Internet or in bricks and mortar shops (often known as ‘head shops’ or ‘smart shops’). Recent response measures in Europe have restricted the open sale of ‘legal highs’, particularly on the high street and surface websites in many countries, as well as novel substances more broadly [62–66], which appears to have led to the term ‘legal highs’ falling somewhat out of common use.

International drug control system

To a great extent, the current drug legislation of most countries originates from their obligations under the international drug control system, namely the United Nations Single Convention on Narcotic Drugs, 1961, the Convention on Psychotropic Substances, 1971, and the United Nations Convention against Illicit Traffic in Narcotic Drugs and Psychotropic Substances of 1988 [67–69].

The 1961 and 1971 Conventions codify internationally applicable control measures in order to ensure the availability of narcotic drugs and psychotropic substances for medical and scientific purposes, and to prevent their diversion into illicit channels. They also include general provisions on drug trafficking and drug abuse [67,68]. The 1988 United Nations Convention against Illicit Traffic in Narcotic Drugs and Psychotropic Substances extends the control regime to precursors, and focuses on establishing measures to combat illicit drug trafficking and related money-laundering, as well as strengthening the framework of international cooperation in criminal matters, including extradition and mutual legal assistance [69]. The 1988 Convention will not be discussed further in this chapter.

World health organization

The World Health Organization (WHO) is a specialized agency of the United Nations. Through its Expert Committee on Drug Dependence (ECDD), it conducts the medical, scientific and public health evaluation of psychoactive substances in order to inform the decisions made by the United Nations Commission on Narcotic Drugs (CND) on whether to control a substance under the international drug control system [70].

In 2010, the World Health Organization adopted a revision of their guidelines for the review of psychoactive substances for international control [71]. The guidelines ensure that the review process is of clear methodology, transparent, and based on scientific and public health related principles. The guidelines detail the procedure for preparing a critical review, including how it is decided if a pre-review or critical review will be held, how to prepare the review reports and the criteria on which the ECDD should base their judgement. The ECDD is to first consider the applicability of the 1961 Convention — that is, whether the substance shows similar abuse liability profile and dependence-producing properties to drugs already controlled under this convention — and if not, whether the 1971 Convention is applicable. For all substances that are reviewed, a summary assessment giving a description of the ECDD’s findings should include the extent or likelihood of abuse, the degree of seriousness of the public health and social problem, the degree of usefulness of the substance in medical therapy, and advice on the control measures that would be appropriate. The guidelines also cover the meeting, membership and functions of the ECDD and its collaboration with other organizations and experts for the decision-making process.

Following international concern over the growth in the availability of novel psychoactive substances over the past few years, an increasing number of novel substances have been reviewed by the ECDD, and, based on their recommendations, controlled under the international drug control system [72–74]. Information for the prioritization of novel psychoactive substances for review by the ECDD is provided by, among other sources, data collected by the World Health Organization, data provided by the UNODC through Early Warning Advisory on New Psychoactive Substances which is part of the Global SMART Programme, and data provided by the EMCDDA from its early warning and risk assessment activities in Europe.

United nations office on drugs and crime

The Global Synthetics Monitoring: Analyses, Reporting and Trends (SMART) Programme operated by the United Nations Office on Drugs and Crime (UNODC) aims is to improve the capacity of specific Member States to generate, manage, analyze, report and use information on illicit synthetic drugs. In addition, since 2011, the SMART Programme has also played an increasing role in responding to new psychoactive substances [75]. In 2013, the first global situation assessment of the challenge posed by new psychoactive substances [76] was conducted in accordance with CND Resolution 55/1 (2012) on ‘Promoting international cooperation in responding to the challenges posed by new psychoactive substances’ [77]. This provided a- consolidated upto-date analysis of the situation across the world, based on information provided by United Nations Member States and the network of drug analysis laboratories participating in the UNODC International Collaborative Exercises (ICE) [78].

In accordance with CND Resolution 56/4 (2013) ‘Enhancing international cooperation in the identification and reporting of new psychoactive substances’ [79], the UNODC further developed the electronic portal of ICE, providing a global reference point and early warning advisory on new psychoactive substances.

The Early Warning Advisory (EWA), launched in June 2013, aims to monitor, analyze, and report trends on the patterns of distribution and use of NPS, in order to support effective evidence-based policy responses. It also serves as a repository for information on these substances and a platform for providing technical assistance to countries [80,81]. Recently, the EWA has also developed an online information system that allows the collection, analysis and sharing of data on toxicology and harm related to the use of NPS [82].

The EWA provides access to basic information on new psychoactive substances intended for the public. Specific information on NPS which is only available to registered users is aimed at three main user groups: forensic drug laboratories, law enforcement authorities, and policy makers/organizations [79].

According to the UNODC, the EWA [80,81,83]:

• acts as a reference point and platform for collating and coordinating existing information on NPS at the global level;

• provides knowledge to the international community in facilitating the understanding of NPS;

• shows a real-time picture on the global emergence of NPS;

• offers listings of new NPS, their emergence, and recent trends;

• provides information on the different types of legislation in place including country specific information;

• releases an EWA newsletter.

Information on NPS are collected from a range of sources, including [80,81]:

• The global survey on NPS conducted by the Global SMART programme (2012, 2014, 2016 and 2019);

• The UNODC International Collaborative Exercises (ICE) programme with over 280 national forensic science laboratories in 84 countries (2018);

• Law enforcement data collected through the UNODC Individual Drug Seizure (IDS) Database;

• The Annual Report Questionnaire (ARQ) submitted by all United Nations Member States;

• Implementation of the statement of intent of the G-8 plus group under the UK presidency;

• Proactive collection of data by the Global SMART teams in Asia using the Drug Abuse Information Network for Asia and the Pacific (DAINAP);

• The Drug Abuse Information Network in Latin America and the Caribbean in collaboration with the Organization of American States;

• Reports of regional networks of forensic science institutions;

• Interagency meetings designed to facilitate sharing of data and information (EMCDDA, United States Drug Enforcement Administration (DEA), International Narcotics Control Board (INCB), Organization of American States (OAS), World Anti-Doping Agency (WADA), World Customs Organization (WCO), and WHO).

National drug control laws

Until relatively recently, the list of drugs controlled at national level largely reflected those that countries were required to control under the international drug control system. However, countries are also free to control other substances as they see fit. Despite this, for many years there was rarely need to control other substances not controlled internationally because their appearance on the drug market were few and far between, and, where necessary, they were usually eventually controlled by the international drug control system. Because of this, the simplest method of control was to name them as individual chemical entities or plant products, known as ‘specific listing’. Here we briefly review some of the legal responses taken within Europe, based on a study published by the EMCDDA in 2018, in order to respond to novel psychoactive substances while recognizing that other approaches have been used in different settings [83,84].

European countries take measures to prevent the supply of drugs under three United Nations Conventions, which provide a framework for control of production, trade and possession of over 280 psychoactive substances. The rapid emergence of novel psychoactive substances and the diversity of available products has proved challenging for the Conventions and for European policymakers and lawmakers. The administrative procedures involved in adding a substance to national drug laws show considerable variation.

At the national level in Europe, increased supply drove the relatively sudden appearance of a large range of innovative legal responses designed towards controlling the open sale of these substances. These include rapid interventions that have been put in place to allow countries time to develop other responses or as a temporary solution before drug control law can be enacted. Broadly speaking, three types of response have been used, differentiated largely by the speed with which they can be implemented. These responses are not necessarily mutually exclusive, as some countries have initiated more than one response, either simultaneously or consecutively. Many countries in Europe first responded by using consumer safety legislation, and subsequently extended or adapted existing drug laws to incorporate new psychoactive substances. Increasingly, countries have designed specific new legislation to address this phenomenon.

For many years, most European countries only listed controlled substances individually. However, as the number of new substances detected in Europe increased, more countries have sought to control groups of substances. Most of the countries have defined the groups by chemical structure (‘generic’ groups), though a few have defined the groups by the effects. Most of the countries that have taken the generic approach have added the group definitions to existing drug laws, but some have only included such groups in specific new psychoactive substance legislation.

Controls using consumer safety or medicines legislation

Using existing legislation to restrict the open distribution of a new psychoactive substance requires little or no time to implement changes. A number of European countries have successfully used consumer safety or medicines laws, which, as they are based on harmonized European Union (EU) definitions, were operational (and available for use) in all Member States. In practice, different types of consumer safety laws have been enforced, some targeting psychoactive products in general (as happened in Poland, resulting in large-scale closure of bricks and mortar shops selling such substances), others directed towards individual substances. In Italy, for example, regulations requiring that goods or food on sale be clearly and accurately labeled in relation to their expected use were used to confiscate products containing synthetic cannabinoids that were not labeled in the national language. A similar approach was used in the United Kingdom to stop the sale of mephedrone labeled as ‘bath salts’ and ‘plant food’. Having first used consumer safety laws, Poland subsequently modified its legal definition of a ‘substitute drug’ (a substance used instead of a drug or for the same purposes) and updated the health protection law, so that it could be used when there was suspicion that a substitute drug posed a health threat.

As the harmonized EU definition of a medicinal product (medicine) appeared not to require such a product to have therapeutic properties, there has been room for countries to use this legislation to respond to new psychoactive substances. When a national medicines agency classifies a novel psychoactive substance as a medicinal product, it can then require a license for any importation, marketing, or distribution. In this way, at least eight countries used medicines laws to control supply of novel substances. However, in July 2014 the European Court of Justice ruled that this was not a correct interpretation of the harmonized EU definition, and so this method is no longer available as a systematic form of control of new psychoactive substances in the EU [85].

Extending and adapting existing laws and processes

An alternative response to responding to the availability of novel substances has been for countries to manage them under existing drug legislation, through either modification or extension of these laws. There is often limited information on novel substances when they first appear on the market, especially the harms, and scientific risk assessment panels were created in Hungary (2010) and Finland (2011) to provide the evidence base for decisions to control new substances.

In order to accelerate legal processes, some countries have introduced temporary control systems, allowing time for investigation of the need for permanent control. For example, temporary control procedures were enacted in Latvia and Slovakia in 2013, implemented respectively by the Centre for Disease Prevention and Control and the Minister of Health. In 2011 the United Kingdom enacted a procedure allowing temporary class drug orders, under which named substances could be rapidly controlled under drug laws for up to one year. A similar system was enacted in Hungary in 2012, revising the risk assessment and allowing the addition of non- therapeutic drugs to the list of controlled substances on the basis that they can pose as serious a threat to public health as substances already listed in the drug schedules. While personal possession of new psychoactive substances has often been excluded from punishment, in 2014 it was made an administrative offence in Latvia, and possession of more than 10 g of active substance was criminalized in Hungary.

In the Czech Republic controlled drugs had been listed in a parliamentary law; their transfer to a new government decree in 2014 should reduce the time required to add new substances in future. At the end of 2014 Finland extended its Narcotics Act to cover also ‘psychoactive substances banned from the consumer market’, listed in a new Government Decree following the above risk assessment, with unauthorized supply punishable by up to a year in prison as an offence endangering health and safety.

Some countries have chosen to extend the coverage of existing drug laws by listing defined groups of substances, rather than individual drugs as had been done previously. Tight ‘generic’ group definitions have been used for years in Ireland and the United Kingdom, while broader ‘analogue’ groups, or derivatives, are controlled in Bulgaria, Latvia and Malta (see ‘Terms and definitions’).

However, group definitions have been introduced into the drug laws of other countries (Fig. 1.1), including Luxembourg, Italy, Cyprus, Lithuania, Denmark, France, Norway, Croatia, Germany, Belgium, and Turkey. Latvia has supplemented its ‘derivatives’ with generic definitions, and the definition of ‘drugs’ in Finland now includes ‘positional isomers for such a substance’. The Netherlands rejected the group definitions approach in 2012 because of the complexity of targeting some substances that may have valid uses, while not restricting other substances. (Other countries have also introduced group definitions but only in their separate new psychoactive substances lists.)

Fig. 1.1 Appearance of new psychoactive substances and introduction of generic-group controls in Europe, 2005–2017.

Terms and definitions

Generic system: legislation includes a precise definition of a family of substances (such as by describing substitution patterns in a parent molecule). Examples are Ireland and the United Kingdom.

Analogue system: legislation includes a more general definition of ‘similarity in pharmacological activity’, as well as ‘similarity in chemical structure’. Examples are Latvia and Bulgaria.

Developing new legislation to respond to novel substances

The most comprehensive response undertaken by European countries has been the introduction of new laws to manage unauthorized distribution of novel psychoactive substances, as has occurred in Ireland, Austria, Portugal, Romania, Sweden, and the United Kingdom. In spite of many similarities in the ways in which the new legislation has been developed in all these countries except Sweden, a number of differences exist. Regarding the substance, all five countries define a psychoactive substance as one that stimulates or depresses the central nervous system, which in Ireland, Austria, Portugal and Romania is associated with dependency, hallucinations or disturbances in motor function or behavior; in the United Kingdom it is one that ‘affects’ the person’s mental functioning or emotional state. In Ireland and Portugal these disturbances should be ‘significant’; in Austria substances can be listed only if they are likely to be ‘abused’ by certain sections of society and pose a possible threat to consumer health. In Romanian and UK law there is no specified requirement for harmfulness.

Under the new legislation, naming of a substance is not required in Ireland, Romania or the UK, as supply of any substance that possesses the properties defined in the law is implicitly covered. In Austria, however, the minister for health must name the substances in a regulation; in Portugal the substances are listed in an Administrative Rule, but the authorities also have the power to confiscate and test any other substances if they suspect a serious threat to health, temporarily prohibiting distribution. In addition, the supply of new psychoactive substances is a crime in Austria if the supplier has the intention to benefit and intends that the product will be used for its psychoactive effects; in the United Kingdom the supplier must know that (or be reckless as to whether) the substance is likely to be consumed for its psychoactive effects, while in Ireland only knowledge of likely human consumption is necessary; in Romania neither is required. Maximum penalties for supply in Austria, Ireland, Romania and the United Kingdom are two, five, three and seven years’ imprisonment, respectively, rising significantly in Austria if supply causes serious injury or death. The Portuguese law is different in this respect, defining immediate administrative (not criminal) sanctions and giving to health protection authorities the power to remove substances from sale and close shops.

Distinct from the above punitive approaches, Sweden passed a law in 2011 that gives administrative power to police and customs to confiscate certain intoxicating harmful substances, with no other penalty. Prosecutors may then order their destruction.

European Union

Joint action on new synthetic drugs 97/396/JHA, 1997–2005

For more than 20 years, a legal framework has been in place in the European Union that allows it to rapidly detect, assess, and respond to the appearance of novel psychoactive substances on the drug market. The origins of this legislation lie in the surprise appearance and popularity of MDMA and other similar synthetic drugs in Europe during the late 1980s and early 1990s where they were part of the acid house, electronic dance music and rave scenes [35,36]. These substances were commonly referred to as ‘designer drugs’ — a reference to the fact that they had been ‘designed’ to circumvent drug laws, though, in reality, many had been previously described in the scientific and patent literature [44]. As demand rose, some of these drugs were produced on a relatively large scale in illicit laboratories typically operated by organized crime groups. Their appearance raised questions about possible health risks and the problems that could arise in law enforcement and judicial cooperation between countries if such substances were controlled in some Member States but not others. As a result, governments agreed on the need to share information on these types of substances as well as to strengthen law enforcement and judicial cooperation [86].

In 1997, this led to the introduction of the first piece of EU legislation known as the Joint Action on New Synthetic Drugs [87]. The legislation defined a three-step process of information exchange (which commonly became known as ‘early warning’), risk assessment and control measures. The scope of the Joint Action was limited to ‘new synthetic drugs’ which were defined as drugs not listed in any of the Schedules to the United Nations 1971 Convention on Psychotropic Substances, and which posed a comparable serious threat to public health as the substances listed in Schedules I or II thereto and which have a limited therapeutic value. More than 30 new synthetic drugs were notified under the Joint Action. Most were phenethylamines and tryptamines described in PHiKAL and TiHKAL [41,42]; less common were cathinones and piperazines. Few were seized in large amounts or were widespread. Most had a limited life on the drug market. Risk assessments were carried out on nine of them: MDMB, 4-MTA, GHB, ketamine, PMMA, TMA-2, 2C-T-2, 2C-T-7, and 2C-I. Although neither ketamine nor GHB strictly qualified as ‘new synthetic drugs’, it was considered appropriate to carry out risk assessments because at that time there was information of non-medical use and they were not under international control. A common feature of the remaining seven drugs was that they were often found as tablets marked with logos similar to those seen on MDMA ‘ecstasy’ tablets. By contrast, the reported tryptamines, none of which has so far been risk assessed, were more commonly seen as powders. Of the nine substances, 4-MTA, PMMA, TMA-2, 2C- T-2, 2C-T-7 and 2C-I were brought under control throughout the EU. Subsequently, 4-MTA and GHB were controlled in 2001 under the 1971 UN Convention, while PMMA was controlled in 2016.

Council Decision 2005/387/JHA, 2005–2018

Following a review of the effectiveness of the Joint Action by the European Commission, it was replaced by Council Decision 2005/387/JHA on the information exchange, risk-assessment and control of new psychoactive substances in May 2005 [88]. The Council Decision kept the three-step approach of the Joint Action but extended the scope and strengthened the overall system. The term ‘new psychoactive substances’ was also used for the first time and given legal meaning, being defined as substances not currently listed in any of the schedules to the United Nations 1961 Single Convention on Narcotic Drugs, as amended by the 1972 Protocol, that may pose a comparable threat to the substances listed in Schedules I or II or IV thereof; and the United Nations 1971 Convention on Psychotropic Substances that may pose a comparable threat to public health as the substances listed in Schedule I or II or III or IV thereof. From the mid-2000s there was a large increase in new psychoactive substances in Europe. This was driven by globalisation and new technologies, such as the internet, that allowed them to be produced, sold, and supplied on an industrial scale [44,51,89].

At least initially, much of the growth in the market in novel psychoactive substances was driven by their open sale in shops on the high street as well as online stores. They were available as a range of slickly packaged products advertised as ‘legal highs’ (emphasizing ‘legality’), ‘research chemicals’ (implying legitimate research use), and ‘dietary supplements’ (suggesting they were foods and natural products). In the case of ‘legal highs’, the marketing would often allude to them having similar psychoactive effects to controlled drugs or even use common street (slang) names of drugs such as MDMA (ecstasy) or cocaine. They were also marketed in such a way as to appear to side-step consumer protection legislation, such as medicine legislation, that, at the time, was sometimes used to restrict sales — although in Europe an opinion from the Court of Justice of the European Union suggests that this legal approach can no longer be used [85]. Such strategies included labeling products as ‘not for human consumption’ as well as advertising them as ‘incense’, ‘plant food’, or ‘novelty items’. In addition to these innovative products, new psychoactive substances were also sold on the illicit drug market either under their own name or passed off as established controlled drugs to unsuspecting users. Some new substances, such as those from the benzodiazepines and synthetic opioid families, were also used to make falsified (fake) tablets of commonly prescribed benzodiazepine and opioid analgesic medicines which are also sold on the illicit market. Sales were through existing street-level drug markets as well as online markets, including on the darknet [89].

Initially, much of the use of novel substances was concentrated in people who explored them for novel experiences and effects (often called ‘psychonauts’) as well as other groups of ‘early adopters’ (such as electronic dance music fans). However, during the mid-2000s, the consumer base also grew in parallel with the range of substances and products that were offered. It included people who use them recreationally, those with problematic drug use, those who self-medicate, as well as people wanting to look better, get fitter, or enhance their performance at school or work. These developments were also linked to the growing interactions between the market in novel substances and established illicit drugs. As use began to grow an increase in the number of severe and fatal poisonings was also reported [89]. Changes in the patterns of drug injection have also been driven by novel substances [90,91]. In some places this has caused an increase in HIV, hepatitis C, as well as bacterial infections which have sometimes manifested as outbreaks [92–94].

This growth in the market led to a range of challenges for public health policy and practice. At least initially, national drug control laws struggled to keep up with the rapid flow of new substances appearing — their open sale in shops on the high street and internet often adding to this problem [44,51,89]. Nonetheless, the number of new substances reported for the first time each year has dropped from a high of around 100 in 2014 and 2015 to around 50 from 2016–2019. This is thought to partly reflect recent policy responses in Europe, including efforts to control new psychoactive substances and their open sale. It may also reflect control measures and law enforcement activity in countries where bulk quantities of novel psychoactive substances are produced, such as China.

Major new challenges have also emerged in the past few years. This includes what appears to be a general upward trend in more potent new psychoactive substances appearing on the market, especially substances such as the synthetic cannabinoids, opioids, and benzodiazepines. These types of substances pose a greater risk of life-threatening poisoning to users because their high potency makes it is easier to unintentionally overdose. This risk may be especially high when a substance first appears on the market because of a lack of experience with the substance, but also because, unknown to users, such substances may be passed off as highly sought after established drugs such as fake medicines. As a result, these types of substances can also cause explosive outbreaks of mass poisonings that can overwhelm local healthcare systems. Although the picture differs greatly across Europe, outbreaks involving a range of different types of new psychoactive substances have grown in recent years. In some circumstances there may also be a risk of occupational exposure to law enforcement personnel from such substances, who intercept large quantities of these substances either at the border or at illicit laboratories and processing sites [95,96].

Potent substances are also easier to conceal and smuggle, making them an attractive option for traffickers. A few grams of substances, easily hidden in an envelope, can be sufficient to make many thousands of doses for the drug market. It is also concerning that synthetic cannabinoids (known as ‘Spice’) are now sought after by some vulnerable groups, including people experiencing homelessness and prisoners, because they are cheap, easily available, and powerful, capable of causing ‘mind-numbing’ effects [89].

A total of 676 new psychoactive substances were notified under the Council Decision. Reflecting the growth of the ‘legal highs’ market, around half of these were synthetic cannabinoids (190) and synthetic cathinones (130). Reflecting changes in the market in the last few years an increasing number of new opioids and benzodiazepines have been notified.

Under the Council Decision, risk assessments were carried out on 23 new psychoactive substances: BZP, mephedrone, 4-MA, 5-IT, AH-7921, methoxetamine, 25I-NBOMe, MDPV, MT-45, 4,4′-DMAR, α-PVP, MDMB-CHMICA, acryloylfentanyl, furanylfentanyl, AB-CHMINACA, ADB-CHMINACA, 5F-MDMB-CHMINACA, CUMYL-4CN-BINACA, 4F-iBF, THF-F, carfentanil, cyclopropylfentanyl, and methoxyacetylfentanyl. Eighteen of these substances were brought under control throughout the EU: BZP, mephedrone, 4-MA, 5-IT, AH-7921, methoxetamine, 25I-NBOMe, MDPV, MT-45, 4,4′-DMAR, α-PVP, MDMB-CHMICA, acryloylfentanyl, furanylfentanyl, ADB-CHMINACA, CUMYL-4CN-BINACA, cyclopropylfentanyl, and methoxyacetylfentanyl. Four of the remaining substances, acetylfentanyl, 4-fluoroisobutyrylfentanyl, tetrahydrofuranylfentanyl, and carfentanil, were controlled under the United Nations 1961 Single Convention on Narcotic Drugs, as amended by the 1972 Protocol; while AB-CHMINACA was controlled under the 1971 Convention on Psychotropic Substances. This was because these substances were also assessed around the same time by the United Nations system.

Regulation (EU) 2017/2101 and Directive (EU) 2017/2103, 2018–onwards

In response to the large growth in the market in new psychoactive substances since the mid-2000s, a review of the Council Decision identified the need to strengthen the EU response. This led to the Council Decision being replaced by new legislation on 23 November 2018. It is the third such legal framework over the last 20 years and builds on the experiences gained during this period. The legislation retains the effective three-step approach while significantly strengthening early warning activities as well as introducing shorter deadlines for each of the three-steps.

The legislation comprises:

• Regulation (EU) 2017/2101 of the European Parliament and of the Council of 15 November 2017 amending Regulation (EC) No 1920/2006 as regards information exchange on, and an early warning system and risk assessment procedure for, new psychoactive substances [97,98]; and

• Directive (EU) 2017/2103 of the European Parliament and of the Council of 15 November 2017 amending Council Framework Decision 2004/757/JHA in order to include new psychoactive substances in the definition of ‘drug’ and repealing Council Decision 2005/387/JHA [61,99].

Together, the two pieces of legislation replace the mechanism established by Council Decision 2005/387/JHA.

As discussed in the first part of this chapter, within the European Union, the definition of a new psychoactive substance is provided in Article 1 of Council Framework Decision 2004/757/JHA (as amended) [61]:

‘new psychoactive substance’ means a substance in pure form or in a preparation that is not covered by the 1961 United Nations Single Convention on Narcotic Drugs, as amended by the 1972 Protocol, or by the 1971 United Nations Convention on Psychotropic Substances but may pose health or social risks similar to those posed by the substances covered by those Conventions.

Based on this definition, Member States should report to the EMCDDA any substance that they judge to meet this definition through the EU Early Warning System (see below).

The definition does not distinguish between synthetic and natural substances. Therefore, substances derived from natural sources (plants, fungi, animals), either purified extracts or other preparations, and that are judged to be new psychoactive substances should be reported. In addition, an active substance used in medicinal products that are judged to be new psychoactive substances should also be reported.

European Monitoring Center for Drugs and Drug Addiction

The EMCDDA is an agency of the European Union. It was established in 1993 in the face of a growing drug problem in Europe and based on the premise that independent, science-based information is an essential resource to help Europe understand the nature of its drug problems and better respond to them. The objective of the EMCDDA is to provide the European Union and its Member States with factual, objective, reliable and comparable information at European level concerning drugs and drug addiction and their consequences [98,100].

The EMCDDA provides policymakers with the data needed for developing informed drug laws and strategies. It also supports professionals and practitioners working in the field to identify best practice and new areas of research. To achieve its task of providing sound and comparable information on drugs in Europe, the EMCDDA has developed an infrastructure and tools to collect country data in a harmonized way. These data are then provided by national drug monitoring centers, known as the Reitox national focal points, to the EMCDDA for analysis, resulting in a variety of information products conveying the broader European picture [101].

In addition to these tasks, the EMCDDA has also played a central role in the EU’s response to NPS since the first piece of legislation came into force in 1997, being responsible for operating an early warning system in close collaboration with Europol, and conducting risk assessments in order to support decision making on the need for control measures on new psychoactive substances at EU-level [61,98,102].

Early warning, risk assessment, and control measures

Early warning

The information exchange and early warning step of Regulation (EC) No 1920/2006 is operationalized as the European Union Early Warning System on New Psychoactive Substances (EU Early Warning System, EWS) [98]. The system is composed of a multi-sectoral, multidisciplinary, and multiagency network, which includes the EMCDDA, 29 national early warning systems (27 Member States, Turkey, and Norway), Europol and its law enforcement networks, the European Medicine Agency, the European Commission, and other partners [102]. The EMCDDA is responsible for collecting, collating, analyzing, assessing, and communicating the information reported by the Network.

Early warning activities are conducted in accordance with the requirements of Regulation (EC) No 1920/2006 and Council Framework Decision 2004/757/JHA, and with respect to accepted scientific principles and required scientific evidence to support evidence-based, defensible decision making. Based on these requirements, the EMCDDA has developed operating guidelines that provide a common understanding for the operation of the EU Early Warning System by detailing the rationale, steps, procedures, roles, and responsibilities. The EMCDDA has also developed a common terminology and definitions for operating the EU Early Warning System [103]. It has also developed a set of common reporting tools in order to harmonies data collection across the Network. Details of specific procedures are provided separately to the guidelines as guidance notes [103]. These include:

• Formal notification of a new psychoactive substance

• Information that should be reported by the Member States on a new psychoactive substance

• Events of potential high impact on public health

• Outbreaks

• Intensive monitoring

• Substances of high concern

Work instructions for carrying out specific reporting tasks and relevant internal EMCDDA processes are also provided to the Network.

Together, the guidelines, guidance notes, reporting tools, and work instructions allow interoperable reporting and communications leading to consistent working across the Network. They also reduce the risk of potentially serious misunderstandings and errors, as well as reduce the burden on the Network in terms of the need for requesting clarifications and corrections. Together, this can greatly improve the operational communication within the Network, and, ultimately, improves the timeliness, accuracy, reliability, and comparability of the information related to new psychoactive substances required for the operation of the EWS, and to support the initial report stage, risk assessment process, and decision making on control measures (see below).

Underpinning each of the national early-warning systems, and, in turn, the EU Early Warning System, is the dissemination of data on the chemical identification of new substances from forensic and toxicology laboratories in Europe [104]. Principally, these laboratories handle casework related to seizures of novel psychoactive substances by law enforcement agencies (including shipments detained for inspection that are made by customs or border agencies) and from non-fatal and fatal poisonings (such as those from hospital emergency departments and medico-legal death investigations). Overall, such an approach allows the collection and rapid reporting of event-based information on the appearance of, and, harms caused by, NPS at national level to the EMCDDA. These data are complemented by an annual situation report, which includes aggregated data on seizures by law enforcement and from serious adverse events, such as poisonings. The organization and functioning of the national early warning systems is a national responsibility. While these systems have developed to meet national needs, they draw on a common format and guidelines to report information to the EMCDDA [103].

Most NPS are identified for the first time following the chemical analysis of a seizure made by law enforcement. They may also come from analysis of collected samples (such as test purchases) and biological samples (typically from serious adverse events such as poisonings). When a substance is judged by a Member State to meet the definition of a NPS as defined by Article 1 of Council Framework Decision 2004/757/JHA (as amended), the national early warning system reports this to the EMCDDA. This includes chemical and analytical information, as well as the circumstances of the event. The submission of analytical data is also required; to a certain extent, such data are substitutes for reference standards, which are often not available when a substance is first identified [103].

Following a review of the reported information, the EMCDDA identifies other relevant information that may be found in the literature. If confirmed as a new psychoactive substance, then a formal notification is issued to the Member States on behalf of the reporting country. The notification includes the names and identifiers of the substance, chemical and physical properties, analytical methodologies for its identification, pharmacology, toxicology, circumstances of the detection, and any other relevant information. At this stage, the EMCDDA begins to formally monitor the substance. The formal notification process is one of the cornerstones of a successful early warning system as it strengthens situational awareness and allows relevant preparedness and response measures to be identified and implemented in a timely manner at national and EU level. Critically, by ensuring that members of the network are alerted as soon as possible to the detection of a new substance in Europe, it allows potential threats to be identified and analyzed, as well as for forensic and toxicology laboratories to begin the process of including the substance in their analytical screening allowing it to be identified and therefore monitored.

What substances are included within the scope of the eu early warning system?

The primary role of the EU Early Warning System is to exchange information on new psychoactive substances, and, through monitoring, to detect, assess, and respond to public health and social threats. This includes threats that may not be directly caused by a new psychoactive substance but due to other hazards that are associated with their use. Examples include harmful adulterants, diluents, synthesis-related impurities and contaminants, the biological contamination of substances/products (such as anthrax and botulism), as well as the transmission of infectious diseases [103]. In addition to this role, the EWS may also be used to exchange information on new trends in the use of existing psychoactive substances and/or new combinations of psychoactive substances which pose a potential risk to public health as well as information on possible measures related to public health [98].

Early detection, reporting, assessment, and response

The aim of the EU Early Warning System is to ensure that timely, accurate, and sufficiently detailed information on new psychoactive substances reaches the right people, at the right place, at the right time in order to allow them to assess the information, and, where necessary, respond through timely and effective actions to prevent or reduce the risk of harm.

The different types of preparedness and response actions taken depend on the substance of interest, type and level of threat, the individuals who are at risk, as well as the role of the organization and people who are responding. Actions may be taken at the level of practice, policy, and research.

As mentioned, at national level, the formal notification of a new psychoactive substance ensures that members of the Network are alerted as soon as possible following the identification of a new psychoactive substance on the drug market in Europe. This allows the network to identify, analyze, and assess any potential threats, as well as to identify and implement any response measures that might be required. Importantly, the information provided in the formal notification allows forensic science and toxicology laboratories to include the substance in their analytical screening allowing it to be identified and therefore monitored. Action may also include communicating risk to relevant agencies, as well as people who use drugs, such as when a toxic or otherwise dangerous substance or situation is detected; it may also include ensuring that sufficient preparations have been made to deal with an event or situation that has the potential to cause an outbreak, including mass poisoning events; related to this, it may also extend to ensuring that there is a sufficient supply and availability of medical countermeasures, such as the antidote naloxone should there be a sudden increase in the availability of highly potent opioids; while in other cases, actions may include formal risk assessment that leads to restrictive measures that are intended to reduce the supply and availability of a substance.

As the amount of information is usually limited when a substance is first identified on the drug market, actions may also include research in order to better understand the risks of a particular substance. This may include research to understand its pharmacological and toxicological effects as well to understand its epidemiology (such as who is using the substance, how many people are using it, and how it is being used, etc.).

Data reported by early warning systems can be used to: [105]

• Identify the appearance of an NPS on the drug market for the first time

• Identify other substances of interest, in particular toxic agents, related to mis-selling, adulteration, contamination, or dilution

• Describe, analyze, and assess the distribution, use, and spread of NPS

• Identify and estimate the magnitude of a public health or social threat caused by an NPS, including outbreaks

• Monitor changes in the NPS market

• Identify research needs and to facilitate epidemiologic and laboratory research

• Facilitate planning

• Detect changes in use and patterns of use

• Evaluate response measures, including restrictive measures

It is a task of the Member States to implement the requirements of Article 5a of Regulation (EC) No 1920/2006 and to ensure that its Reitox national focal point and