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The previous chapters have reviewed the various uses and abuses of amphetamines in different societies. These man-made chemicals had a great impact on life in the 20th century and seem set to continue as major players — for good as well as evil. This concluding chapter attempts to put some perspective on the use and abuse of these drugs and attempts some predictions of future trends. It also explores the medical uses of amphetamines, particularly in cases of ADHD; the continuing spread of illicit amphetamine abuse; and the possible treatments for amphetamine addiction.

The resemblance between amphetamine-induced psychosis and some forms of schizophrenia generated much interest in the research community. New lines of research sought to examine how close the parallels were and to probe their underlying neurochemical and neuropharmacological bases. This work was of great importance in supporting the ‘dopamine hypothesis’ of schizophrenia and providing insight into the mechanism of action of the anti-psychotic drugs used to treat schizophrenia as dopamine antagonists. Although no short-term drug-induced effects can ever accurately mimic the symptoms of complex and chronic psychosis, amphetamine comes closer than any other. Research on amphetamine in animals and in human subjects has contributed importantly to these ideas.

Chapter 5 assesses how northern soul was practised and experienced by its participants, focusing on the centrality of DJs to the scene, their relationship with fans and the way in which fans lived and related to northern soul, including its well-documented involvement with illegal drug abuse. It explains how northern soul’s perception of itself as ‘different’ and detached conflicted with what were viewed by many as attempts to commercialise the scene. This contributed to the emergence of cleavages and tensions and to the development of a form of ‘penny capitalism’ that was complemented by the entrepreneurial pursuit of profit through the sale of rare recordings. Such activity strengthened the transatlantic links that the scene had engendered between Britain and several North American cities and resulted in the enhancement or rehabilitation of a number of US artistic careers. However, it was specific commercial practices relating to recordings that undermined the rhetorical discourse of ‘togetherness’ apparent in northern soul. The chapter evaluates the tensions within the scene and determines the extent to which commercialisation and the scene’s association with illegal drugs led to its demise.

Amphetamines come in many different forms and have powerful effects for good and evil. An epidemic of methamphetamine abuse is sweeping through the USA and Southeast Asia — from Hawaii, where the epidemic started in the 1980s, and from Thailand. Meanwhile another amphetamine-like chemical, methylphenidate (Ritalin) has proved popular for the treatment of children, and more recently adults, with attention deficit hyperactivity disorder (ADHD) on both sides of the Atlantic. This book seeks to review the positive and negative aspects of amphetamines — man-made chemicals which had a great impact on the 20th century and continue to do so in the new millennium.

This chapter discusses the chemistry of amphetamines and their effects on the brain. Amphetamines are easily administered by a variety of routes and they penetrate readily and rapidly into the central nervous system (CNS). They act by stimulating the release of natural neurotransmitters. In peripheral tissues, amphetamine stimulates the release of norepinephrine from the nerve endings of the ‘sympathetic nervous system’ which controls a variety of peripheral functions. Because of its ability to stimulate functions normally controlled by the sympathetic nervous system, amphetamine has long been recognised as a ‘sympathomimetic amine’. This chapter also discusses the effects of amphetamines on human mood, cognitive performance, sexual function, and the stereotyped behaviour in human amphetamine users.

A United Nations report (United Nations 2003) estimated a worldwide total of 34 million people who regularly abuse amphetamine-like stimulants and 8 million who use ecstasy. This exceeds the number of heroin and cocaine abusers combined. D-Amphetamine and D-methamphetamine are among the most widely used of all illicit drugs, ranking second in popularity only to cannabis in many countries. It is now generally recognized that amphetamines are drugs of addiction. This chapter reviews the evidence for this and explores the underlying brain mechanisms. It also reviews the social history of amphetamine abuse in various parts of the world.

All drugs, even such apparently innocuous ones as aspirin, carry some health risks. But how dangerous are the amphetamines? Can an overdose kill someone? Does amphetamine abuse cause damage to the health and social lives of the users and those around them? Are there any long-term irreversible adverse effects of chronic use? This chapter attempts to answer some of these questions and reviews the extensive literature on the neurotoxicity of amphetamines studied in animal experiments. Overall, the use of high-dose amphetamine is associated with an alarming series of adverse risks for both the user and those around him.

Stimulants are typically prescribed for their positive effects on mood, motivation, alertness, arousal, and energy. They are believed to exert their pharmacologic effects by increasing synaptic release of endogenous catecholamines (norepinephrine and dopamine) while simultaneously blocking catecholamine reuptake at the nerve terminals. Themost commonly used ‘‘traditional’’ agents are methylphenidate and dextroamphetamine. Methylphenidate reaches peak blood levels in 1 to 3 hours and has an elimination half-life of 2 to 3 hours. Dextroamphetamine reaches peak levels in 2 to 4 hours and has an elimination half-life of 3 to 6 hours. Controlled-release formulations are available, allowing for dosing once daily. Dextroamphetamine is excreted primarily in the urine in unchanged form, whereas methylphenidate is excreted mainly as ritalinic acid. The newer generation stimulant modafinil has been marketed in the United States since 1998. Initially used in the treatment of narcolepsy, it is now prescribed for a wider range of conditions because of its positive effects on wakefulness, vigilance, cognitive performance, and mood. Its pharmacologic effects are thought to result primarily from the stimulation of wakefulness-promoting orexinergic neurons in the anterior hypothalamus. Inhibition of norepinephrine reuptake in the ventrolateral preoptic nucleus and of dopamine reuptake (by binding to the transporter) may contribute to its action. Modafinil is administered orally, achieves peak plasma concentrations in 2 to 4 hours, and has an elimination half-life of 12 to 15 hours. It is 90% metabolized in the liver, and its metabolites are excreted in the urine. The ergot alkaloids bromocriptine and pergolide are familiar to most neurologists in their use in the treatment of Parkinson’s disease (PD) and migraine headache. These dopamine receptor agonists are also used in neuropsychiatry in the treatment of apathetic states in patients recovering from brain trauma, cerebral anoxia, and strokes. Amantadine is another familiar agent used in the treatment of PD and drug-induced parkinsonism. In addition to other effects in the central nervous system (CNS), amantadine facilitates dopamine release and inhibits its reuptake. It thus has modest ‘‘stimulant-like’’ effects useful in the treatment of executive dysfunction syndromes, particularly in patients with dementia. Bupropion is a dopamine and norepinephrine reuptake inhibitor. It usually is prescribed as a ‘‘nonsedating’’ antidepressant, but its potentiation of catecholamine neurotransmission results in modest stimulant-like clinical effects.

This chapter discusses three categories of drugs that people become addicted to. The first of these, morphine-like substances, or “opioids,” are probably the psychoactive drugs whose use goes the furthest back in the history of mankind. The next drug group—cocaine and amphetamine-like drugs—which can be bundled under the label “psychostimulants,” is important because it hooks right into the core of the brain systems thought to mediate approach behaviors and reward. Finally, alcohol makes up a substance category of its own but is probably able to fill up a catalog of actions more extensive than any other drug category. It is also, for that very reason, the addictive drug where individual differences in drug effects are the greatest.

The regulation of amphetamines, starting in 1968 and resulting in their prohibition under the revised Opium Act of 1976 led to the development of an underground production. In the 1990s this underground chemistry expanded. It supplied Europe with a large part of its illegal synthetic drugs. The geographical position of the Netherlands, its logistical infrastructure and excellent transport routes by car or ferry into the rest of Europe all contributed to the rise of this export industry. So too did the presence of a chemical industry that supplied the underground with the necessary raw materials and precursor chemicals. Different cultures came together in the constitution of underground chemistry and trade. Idealists convinced they could create a better world by a better chemistry set up an illegal LSD production and trade that was embedded in the counterculture of the 1960s and 1970s and remained rather apart from amphetamine and XTC production. Idealists were also involved in establishing the first production lines of MDMA and related compounds. When regulation made markets illegal while demand soared, criminal entrepreneurs noticed and took their chances and came to dominate the supply side. Criminal entrepreneurs connected to the smuggling cultures of the south of the Netherlands, as well as from the cities in other parts of the country, and later outlaw motorcycle gangs moved in on the amphetamine and XTC production and trade, sometimes in alliance with idealists.

This chapter discusses the history of drug use in Major League Baseball (MLB). It begins with Twentieth-Century Fox's baseball fantasy It Happens Every Spring, the story of a nerdy chemistry professor, and diehard baseball fanatic, who relies on a secret chemical formula in order to moonlight as a phenom pitcher for the St. Louis Cardinals. The problem with the film was that it was “the story of a cheat, winning a pennant and a World's Championship series.” In real-life baseball, cheating has quite a long history. This chapter examines the emergence of a generation of pioneering trainers and team doctors who introduced new methods to ease pain, spur healing, and enhance the performance of baseball players, including the injection of tranquilizers and the use of amphetamines. It also considers the case of Sandy Koufax and the league's refusal to admit that there was a doping problem in the sport; in short, baseball players did not use drugs.

In this gallery we will look at the portraits of molecules which can affect us very profoundly, and not only ourselves, but also the life we carry inside us, or the life we would like to create. In a private room at the end of the gallery are a few portraits that were not thought suitable for public exhibition, but which selected individuals will be allowed to view. These are molecules that are deemed undesirable, but their eradication is proving difficult, if not impossible. Few things are more important than creating new life, and yet nature has an almost cavalier attitude to the process, investing in gross overproduction of the raw materials necessary. Women have the ability to produce around three hundred eggs in a lifetime, and men to manufacture three hundred million sperm a week. Despite this abundance the human population has been kept in check in many ways—high infant mortality, famine, disease, war; but even so, today we have a world that is overpopulated with humans. This has come about through the success of science, which has lifted the first three of these natural scourges, although it has made the fourth much worse. Sadly science has so far not elicited the response of better birth control in many parts of the world, but it has made it possible to plan parenthood carefully. Science has also made it possible to ensure that if you decide to have a baby, then the baby you bring into the world should be perfect. The only prayer that potential parents in developed nations deem necessary is ‘please let our baby be all right.’ There are a few simple precautions that a woman can take to ensure her baby has a good chance of avoiding some risks that would seriously affect it. In this part of the gallery there are two molecules that she needs to think about. Folic acid is found in plants, animals and microorganisms such as fungi and yeasts. It is present in grass, butterflies’ wings and fish scales. Humans need it also, as an essential component for several metabolic processes.

The main characteristics of generalized anxiety disorder (GAD) are chronic pathological worry, other manifestations of nonphobic anxiety, and various symptoms of tension. Physical symptoms of anxiety are usually less prominent in GAD than in panic disorder, but they can still be an important component of clinical presentation. Behaviors that are often seen in other anxiety disorders, such as overt avoidance, are conspicuously absent. Unlike all other anxiety disorders, it is more likely for GAD in clinical setting to co-occur with a primary condition for which help has been sought–usually depression or other anxiety disorder–than to be the main reason for seeking professional help. Generalized anxiety disorder is one of the more controversial members of the family of anxiety disorders: it seems that almost every aspect of GAD has provoked debates that do not show signs of abating. Paradox, disagreement, debate, and controversy are the words most commonly associated with GAD. It is small wonder then that the list of ‘‘hot topics’’ related to GAD could be very long indeed. Listed below is a selection of issues thought to represent adequately a more comprehensive list…. 1. What are the characteristic features of GAD that would help in its conceptualization? Pathological worry, other cognitive aspects of anxiety, manifestations of tension, and/or (some) symptoms of autonomic arousal? What combination of these features would ensure that GAD is diagnosed adequately and recognized in clinical practice? 2. What is the relationship between pathological worry and GAD? 3. How can different views on what constitutes the essence of GAD be reconciled? Is GAD a single entity or are there two or more ‘‘types’’ of GAD with distinct clinical characteristics? 4. How is GAD related to depressive disorders, other anxiety disorders, and personality disturbance? Where are its boundaries? In view of its close relationship with depression, should GAD be classified along with depression and perhaps renamed accordingly? 5. Can GAD exist on its own, without depression or other anxiety disorders? What could be features specific enough for GAD that would allow it to establish itself as an independent and valid psychopathological and diagnostic entity? 6. What are the pathophysiological correlates of pathological worry and other aspects of chronic anxiety in GAD? 7. What are the underlying mechanisms and purpose of pathological worry in GAD? What is the meaning of chronic anxiety?

A 68-year-old woman was admitted via the emergency department with shortness of breath and a productive cough. Her symptoms had started three days previously. She visited her GP, who advised her to take amoxicillin and clarithromycin for a suspected lower respiratory tract infection.

She had a past medical history of depression for which she had been treated with fluoxetine successfully for many years. She was a non-smoker.

A right-sided lobar pneumonia was confirmed on a chest X-ray and she was admitted to the acute medical unit for intravenous co-amoxiclav and clarythromicin.

Overnight, she became confused and agitated. On examination, her mini-mental state examination was 5/10. Her temperature was 38.4°C, her pulse rate was 135 beats per minute and blood pressure was 186/104 mmHg. Her respiratory rate was 28 breaths per minute and oxygen saturation 96% on 5 L per minute of oxygen via a Hudson facemask. Her pupils were dilated and sluggish, her tone was significantly increased globally, as were her reflexes, and she had bilateral sustained ankle clonus.

This concluding chapter discusses the rise of consumption of amphetamine-type stimulants (ATS) in Southeast Asia, and examines policy implications of research findings. It argues that China and Burma are crucial in the region as well as in the world in curtailing the production and transportation of heroin and ATS drugs. Although Afghanistan has replaced Burma as the major supplier of opium and heroin in the world, the warlord-controlled regions in northern Burma continue to exert influence in the world drug market. The rapid increase in ATS production and distribution in this region since the mid-1990s deserves serious attention from regional governments as well as Western countries. The chapter ends with a call for more comparative study on drug markets.

Dopamine and the elements of incentive learning explains how, in lever pressing for food tasks, incentive learning produces a gradient of attractiveness of environment stimuli: during magazine training, food activates dopaminergic neurons and the click and food cup become conditioned incentive stimuli, acquiring the ability to elicit approach and other responses; during lever-press training, the click activates dopaminergic neurons and the lever and lever-related stimuli become conditioned incentive stimuli. In conditioned place preference, amphetamine enhances dopaminergic neurotransmission and stimuli paired with amphetamine become conditioned incentive stimuli. In conditioned activity experiments, test-box stimuli paired with a dopamine-enhancer, e.g., cocaine, produce greater activity revealing incentive learning. In conditioned avoidance, the offset of an aversive warning stimulus putatively activates dopaminergic neurons leading safety-related stimuli to become conditioned incentive stimuli. If trained animals are treated with a dopamine receptor blocker, the initially intact ability of conditioned incentive stimuli to control responding declines over trials.

Quantifying the number of young people who are high risk because of substance abuse is complicated by the ambiguity of existing definitions and the absence of ideal data. Among other definitional problems, the term substance abuse covers a multitude of “sins”—smoking, drinking, use of marijuana, and use of a whole range of drugs from over-the-counter diet pills to illicit heroin and cocaine. In recent years, chewing smokeless tobacco and wine coolers have been added to the menu. To add to the confusion, the substance abuse field has not produced an adequate response to the question: Who is at risk of long-term consequences? In the teen pregnancy field, the problem is generally defined using the outcome to be prevented, early childbearing (see Chapter 5). Teen fertility is quantifiable, measured from official statistics (Vital Statistics), and the characteristics of those at risk can be determined by studying the outcome date. In the delinquency field, there are official arrest figures. In the education field, school records and selfreports can be used to define low achievers and dropouts. In the substance abuse field, research suggests that there are important differences between occasional users and those who ever tried these substances (but are not abstainers), and the subset who become heavy users. It is the subset of heavy users who should be the prime targets of interventions, and yet it appears that most prevention is aimed at the larger group. The task of defining risk groups for substance-abuse prevention programs would be facilitated if one could turn to a data set that had all the requisite parts: a large random sample of 10- to 17-year-olds, followed longitudinally, and rich in detail about precursors and the social environment. From such a resource, we could better understand the antecedents of drug and alcohol use, current use patterns by different subgroups of the population, and the consequences that followed from that use. A number of researchers have produced important work on what they describe as the etiology or the causes of substance abuse, others have focused on the consequences, and many surveys have been conducted to track prevalence patterns.