Novel Psychoactive Substances

Classification, Pharmacology and Toxicology

Paul I. Dargan, David M. Wood, Paul Dargan, David Wood

• Publisher: Academic Press
• Year: 2013
• eBook ISBN: 9780124159112
• Topic: Medicine
• Subtopic: Pharmacology

Novel Psychoactive Substances: Classification, Pharmacology and Toxicology provides readers with background on the classification, detection, supply and availability of novel psychoactive substances, otherwise known as "legal highs." This book also 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 followed by a discussion of the acute and chronic harm or toxicity associated with the substance. Written by international experts in the field, this multi-authored book is a valuable reference for scientists, clinicians, academics, and regulatory and law enforcement professionals.- Includes chapters written by international experts in the field.- Provides a comprehensive look at 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 mephedrone and the synthetic cannabinoid receptors in 'spice' / 'K2'.

Section 1

Background

Outline

Chapter 1 Legal Classification of Novel Psychoactive Substances

Chapter 2 Monitoring Novel Psychoactive Substances

Chapter 3 Availability and Supply of Novel Psychoactive Substances

Chapter 4 Epidemiology of Use of Novel Psychoactive Substances

Chapter 5 Social Issues in the Use of Novel Psychoactive Substances

Chapter 1

Legal Classification of Novel Psychoactive Substances

An International Comparison

Leslie A. King, Former part-time advisor to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), Lisbon, Portugal

In recent years, the appearance on the illicit market of large numbers of novel psychoactive substances has created legislative problems for governments. Stemming from the international drug control treaties, a central principle is that harmful properties need to be demonstrated before a substance can be scheduled. Yet for many of these substances, little is known about their pharmacology and toxicology. Furthermore, reliable population surveys and information on prevalence may not become available until a substance is well-established. While not requiring extensive resources, the basic properties of new substances could be investigated, but governments often wish to act before use becomes widespread. The existing systems of drug legislation are discussed, some of which (i.e. generic definitions and analogue control) originated in an earlier period of concern about ‘designer drugs’. There is a common view in many countries that existing drug law is inadequate and that new solutions must be found. Some of these new approaches to drug control are described here.

Keywords

Designer drugs; legal highs; psychoactivity; analogues; law; scheduling

Introduction

Historical Background

Limited drug control began in the early years of the 20th century, following the Shanghai Opium Commission in 1909 and the League of Nations Conventions of 1925 and 1931. These early controls were largely restricted to traditional plant products (e.g. opium, cannabis, cocaine) and semi-synthetics such as heroin. To a great extent, the drug legislation of most countries now originates from the precepts of the United Nations (UN) Treaties, namely the Single Convention of 1961 and the UN 1971 Convention on Psychotropic Substances. The schedules of the two UN Conventions comprise mostly traditional drugs [1,2] and, as discussed later, apart from a few phenethylamines, do not include any examples of the more recent drug groups. The organisation of chemical entities into various schedules in the UN Conventions is partly based on whether the substances have any therapeutic value and partly on the risk of harm associated with their use. However, national legislatures have often incorporated the UN scheduling scheme as a basis for determining penalties associated with various offences such as possession, supply, production, importation etc. A notable exception to this rule is the United Kingdom (UK). In the UK the schedules of the Misuse of Drugs Regulations 2001 [3] largely reflect the UN classification, but the separate Misuse of Drug Act, 1971 sets out the same substances (known as controlled drugs) in three Classes (A, B and C). In other words, the Regulations set out what should be done, i.e. their use within a clinical context, while the Act sets out what should not be done.

The term ‘Novel Psychoactive Substance’ is the latest in a series of expressions to describe a relatively recent phenomenon. A few miscellaneous phenethylamines, such as STP (2,5-dimethoxy-4-methamphetamine) and its bromine analogue DOB (bromo-STP; 4-bromo-2,5-dimethoxyamphetamine) had been misused in the United States (US) since at least the early-1960s; in the UK an illicit tablet was found to contain STP [4] in 1969. However, it was the appearance in the US, during the early 1980s, of derivatives of the narcotic analgesics fentanyl and α-prodine (where desmethylprodine is the reverse ester of pethidine/meperidine) that gave rise to major concerns. In particular, two of the substituted fentanyls (α-methylfentanyl and 3-methylfentanyl) were typically several hundred times more potent analgesics than morphine. Not surprisingly, these high potencies led to many accidental, often fatal, overdoses. The α-prodine series caused a major public health issue when it was found that a by-product of clandestine synthesis (MPTP; 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine) produced a rapid and irreversible chemically-induced Parkinsonism. These events[5] led to the coining of the term ‘designer drugs’, which were defined as:

Analogues, or chemical cousins, of controlled substances that are designed to produce effects similar to the controlled substances they mimic.

Following the publication of the book PIHKAL[6] (‘Phenethylamines I have known and loved’) in 1991, large numbers of mostly ring-substituted phenethylamines began to appear in Europe. These raised questions about possible health risks and the problems that could arise if such substances were arbitrarily controlled in some Member States, but not in others. It was agreed that progress could be made by sharing information and by establishing a risk-assessment procedure and a mechanism for their eventual control across the European Union (EU). This led, in 1997, to the ‘Joint action concerning the information exchange, risk assessment and control of new synthetic drugs’. These ‘new synthetic drugs’ were defined as those that had a limited therapeutic value and were not at that time listed in the 1971 United Nations (UN) Convention on Psychotropic Substances, yet posed as serious a threat to public health as the substances listed in Schedules I and II of that Convention. The ‘Joint action’ was superseded by an EU Council Decision of 2005 [7,8], leading to a more comprehensive and robust system for monitoring what then became known as ‘New Psychoactive Substances’. The Council Decision introduced procedures for risk assessment and EU-wide control in appropriate cases. The definition of these substances is:

Narcotic or psychotropic drugs that are not scheduled under the United Nations 1961 or 1971 Conventions, but which may pose a threat to public health comparable to scheduled substances.

The words ‘new’ and ‘novel’ refer to the fact that these substances are newly-misused, but some of them had been first synthesised many years ago. In the meantime, other expressions have appeared to describe the phenomenon, including ‘legal highs’, ‘research chemicals’, ‘party pills’ and specific phrases such as ‘plant food’ or ‘bath salts’ (often used to describe white powders) and ‘incense’ as a euphemism for smoking mixtures containing synthetic cannabinoid receptor agonists (cannabimimetics). The term novel psychoactive substance is used to refer to all of these in this textbook.

Legal Concerns

The appearance of novel substances has continued to cause problems for drug control authorities in many countries. Following the lead of the UN Treaties, it has been an accepted part of drug legislation that a substance should only be brought under control (scheduled) if it can be shown to be harmful, either to individuals, to society or both. And therein lies the central difficulty: almost nothing is known about the pharmacology of many new substances or their potential for abuse. Some were developed by academic laboratories or the pharmaceutical industry as potential medicines, but never succeeded to market authorisation. The synthesis and basic chemical properties of these ‘failed pharmaceuticals’ will often have been described in the scientific or patent literature, yet apart from in vitro studies and occasional limited animal testing, their pharmacodynamic and pharmacokinetic properties and metabolic fate in humans usually remain largely unexplored. Other substances are closer to the original definition of a designer drug; in other words they have been deliberately created as entirely novel compounds by clandestine laboratories and synthesised by analogy with better-known substances. Their properties have never been published and even the most basic information is lacking; what little we do know comes from occasional fatal poisonings in humans and clinical observations of intoxicated patients. Anecdotal reports from users, such as may be found on Internet ‘chat rooms’, must be treated with caution since the exact identity of the substances concerned may be unknown, often being described by street terms or product names, the composition of which often changes with time.

In the UK, the Misuse of Drugs Act, 1971 provides greater room for manoeuvre [9]. Thus, there is no strict requirement to demonstrate actual harm, provided that the substance concerned might have the potential for harm. In Section 1(2) of the Act, which sets out the duties of the Advisory Council on the Misuse of Drugs (ACMD), there is a definition of what constitutes a controlled drug. Thus, the Council should:

… keep under review the situation in the United Kingdom with respect to drugs which are being or appear to them likely to be misused and of which the misuse is having or appears to them capable of having harmful effects sufficient to constitute a social problem…

This flexibility has allowed the UK to introduce a wide range of generic controls. These are described in more detail later, but an inevitable consequence is that an essentially infinite group of substances will be subsumed where, for most, information is unavailable, and is never likely to become available. And it is quite certain that some substances will not only be harmless, but will have no physiological effect of any kind.

While the basic properties of new substances could be investigated by relatively inexpensive research programs, perhaps using in vitro receptor binding, metabolic studies and other methods, governments often wish to act at an early stage of misuse. There is a belief that it is better to control a substance because of the severe consequences of permitting open sale of a substance that later turns out to be harmful. On the other hand, restricting a substance that is later shown to be harmless has far fewer negative consequences. The problem is made worse by the number of compounds involved and the rapid replacement of controlled substances by non-controlled analogues. Thus even those substances that remain uncontrolled often have a short lifetime on the illicit market. Furthermore, reliable population surveys and information on prevalence may not become available until a substance is well-established, assuming it ever is.

There is a general view in many countries that existing drug law is inadequate to deal with new substances, and that better solutions are needed. A recent review commissioned by the UK Drug Policy Commission [10] has elaborated on the problems and opportunities for restricting new substances. This is just one of many reviews in the past few years that have scrutinised drug policy in the most general sense. For example, the UK has seen numerous reports that have been specifically targeted at the working of the Misuse of Drugs Act, 1971 [11–14]. During 2012, two separate Committees of the UK Parliament undertook reviews of drug policy. The All-Party Parliamentary Group on Drug Policy Reform was specifically focused on novel substances, while one of the terms of reference of the Home Affairs Select Committee was ‘the availability of “legal highs” and the challenges associated with adapting the legal framework to deal with new substances’. The reports from both Committees were published in late 2012 [15, 16].

Increasingly, questions are now asked almost daily and at an international level about whether drug prohibition, and particularly prohibition of possession, is the right course of action in the modern world. This wider debate is largely driven by attitudes to established drugs of misuse, but it cannot be entirely separated from prohibitions surrounding new substances. Although it is beyond the scope of this chapter to examine them in detail, questions are also being asked about whether scheduling substances under the criminal law has any impact on usage, whether ‘drugs of misuse’ might have benefits to the user, to what extent penalties should reflect the harm caused to individuals and society and whether some controls do more harm than good. These issues will be explored in more depth in Chapter 5, ‘Social issues in the use of novel psychoactive substances’, of this book Finally, there is the question of whether law enforcement agencies consider drug misuse, and particularly misuse of new substances, a priority issue, particularly at a time when police budgets are being reduce...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Forewords
• List of Contributors
• Section 1: Background
• Section 2: Analytical Techniques
• Section 3: Individual Novel Psychoactive Substances
• Index