Number 3 AMPHETAMINE-TYPE STIMULANTS A GLOBAL REVIEW Prepared by UNDCP at the request of the Commission on Narcotic Drugs Contents Introduction ...........................................................................................................................1 Part One Chapter THE LICIT SIDE OF THE EQUATION: THE AMPHETAMINE-TYPE STIMULANTS (ATS) AS MEDICINE ..........................................................6 I. The economic significance of ATS in the pharmaceutical industry....................6 II. The relative significance of ATS among psychotropic substances...................10 III. Global manufacture and trade of licit ATS.....................................................13 IV. The therapeutic significance of ATS ..............................................................25 V. Conclusion....................................................................................................31 Part Two THE ILLICIT SIDE OF THE EQUATION: MANUFACTURE, TRAFFICKING AND ABUSE OF AMPHETAMINE-TYPE STIMULANTS (ATS)..................................................................................35 VI. Prescription drug misuse and diversions from licit trade.................................38 VII. Illicit manufacture of ATS.............................................................................44 VIII. Precursors of ATS ........................................................................................50 IX. Trafficking of ATS........................................................................................67 X. Economic incentives for manufacture, trafficking and consumption of ATS ...82 XI. Extent of abuse of ATS.................................................................................99 XII. Impact of consumption of ATS ...................................................................119 XIII. Conclusion..................................................................................................125 References .........................................................................................................................129 1 Introduction In the ever-widening discourse on substance abuse, it is frequently asserted that the key problem of the future will be associated with what are commonly known as synthetic drugs. The present paper is an attempt to assess the validity of this proposition. The subject is too vast and intricate to cover in a single review, but guidance for achieving a manageable focus can be found in two areas: the level of international consensus in defining a critical area and the nature of the substances themselves. With regard to defining the key area, the Economic and Social Council, reflecting the common concerns of many States Members of the United Nations, adopted resolution 1995/20 calling for a thorough study of psychotropic substances, particularly stimulants and their precursors. Even the category >stimulants=, however, is a very wide one, covering a large range of substances whose principal pharmacological effect is to stimulate the central nervous system of the body. There is some pragmatic justification, detailed in Table 1, in narrowing this category down to a group of substances that are similar, not only in their pharmacological effect but also in chemical structure: the amphetamine-type stimulants (abbreviated, throughout this review, as ATS). Historically, the demand for ATS as medicines was satisfied by the licit pharmaceutical industry. Amphetamine, for instance, was synthesized in 1887 but only marketed (as Benzedrine7, in the form of an inhaler to relieve nasal congestion) in 1932. Probably as a result of its instrumental use during the Second World War, the post-war generation witnessed a proliferation of ATS being prescribed and abused, followed by isolated national control measures. By the 1970s, however, the therapeutic usefulness of these substances was recognized to be limited, but actual abuse had grown. Control measures, national and international, consequently became more stringent. Decline in licit pharmaceutical manufacture followed. Demand, however, did not a show commensurate decline, and clandestine manufacture gradually became the major source of supply for some of these substances. Two factors supported this increase in illicit manufacture: the number and simplicity of synthetic routes to manufacture the end product and the easy access to a variety of potential starting materials. While it is clear that there is sufficient basis to justify an international review, the utility of such a review will depend on resolving a number of fundamental questions at the outset. What are the magnitudes, in absolute and relative terms, of the problem as compared to the principal plant-based drugs of abuse? Is the provenance of the ATS problem limited to certain countries, or can it be deemed a global one? With what comparable phenomenon do we have a basis for comparison? International drug control has traditionally been dominated by the three plant-based drugs: opium, cocaine and cannabis. This factor sometimes over shadows other issues and may even prevent, or at any rate delay, the recognition of a new problem when it appears. The phenomenon of synthetic drugs, and of ATS within the category, could be a test case here. While it may be true that the illicit market for synthetic drugs merely complements the much larger illicit market for the plant-based drugs, it is clear that the driving forces, dynamism and potential for diversification of the former have not been sufficiently investigated. A good deal of work has been done in the area, but it has usually covered individual segments of the problem: the licit pharmaceutical industry, illicit markets for particular synthetic drugs, the precursors needed to produce the substances, the epidemiology of particular substances. These studies and reviews will be referenced in relevant chapters of the paper. What should be noted here is that the individual 2 segments they represent need to be integrated horizontally into a composite assessment: the present paper attempts to do this. There is much evidence that the problem associated with synthetic psychotropic substances has been growing over the last two decades. Since the Convention on Psychotropic Substances of 1971 entered into force, there has been a three fold increase in the number of substances put under international control. No comparable increase was recorded for the number of narcotic drugs under the purview of the Single Convention on Narcotic Drugs of 1961. Figure 1 illustrates the trend for two categories of substances. If the stimulants, anorectics and the >ecstasy= group are taken together, as they are in the context of this review, then the number of ATS scheduled increased nearly five fold between 1971 and 1995. The sedative-hypnotic and tranquillizer category shows a four fold increase, primarily due to the scheduling of the benzodiazepines, which doubled the number of substances in the category in 1984. Number of substances under international control (1971 Convention) *Note: In this figure, all ring-substituted amphetamine derivatives have been put in the same category (‘ecstasy’ group). Figure 1 The scheduling of psychotropic substances under the 1971 Convention is based upon an assessment of the relationship between two variables: the therapeutic usefulness and the public health risk caused by abuse in a number of countries. The four schedules use a sliding scale of the two variables: Schedule I implies high public health risk and low therapeutic utility; Schedule IV the opposite - lower public health risk and higher therapeutic utility. Most of the ATS being discussed in this paper fall under Schedules I and II (except amfepramone, pemoline and phentermine, which are all in Schedule IV); this shows that there has been a general decline in 3 their therapeutic application and an increase in their abuse, confirming the historical trend noted above. The nature of control regimes, national as well as international, is germane to this discussion. First principles of drug control seem to be perfectly clear: to ensure that drugs are available only for medical and scientific purposes, but not for uses that compromise individual and public health. There is, unfortunately, a grey area between these two propositions, and the technological innovation that is characteristic of our age appears to thrive within it. The ATS provide something of a paradigm to illustrate this. The synthesis of a psychoactive substance may offer therapeutic utility but also, very often, a potential for abuse. If the potential is realized, it becomes necessary to put the substance under control. Technological innovation in the grey area then drives the abuse by finding ways of circumventing the control. Breaking the law, or circumventing it, are two quite different propositions. The nature of the law will obviously determine, at least to some extent, whether loopholes will be found for circumvention: it can anticipate innovation, thereby closing the possible loopholes, or it can be simply reactive, setting in place some mechanism for modifications as and when the need arises. It will be argued, later in this paper, that the 1971 Convention is reactive in nature, and the evolution, development and scheduling of the ATS together provide the best documentary evidence. The application of a lengthy and laborious scheduling process, particularly if it applies to clandestinely manufactured drugs, would appear to imply that illicit markets will always stay