AMPHETAMINES

87. Amphetamines are synthetic amines which are in many ways similar to the body's own adrenaline (epinephrine). These drugs generally evoke an arousal or activating response not unlike one's normal reaction to emergency or stress. Amphetamines were first synthesized in the early part of the century and entered medical use by the 1930s. Although a variety of related drugs and mixtures currently exist, the most common amphetamine substances are amphetamine (Benzedrine*), dextroamphetamine (Dexedrine*), and methamphetamine (Methedrine* or Desoxyn*), with Benzedrine* being the least potent. Generally, if the dose is adjusted, the psychological effects of these various drugs are similar and, consequently, they will be discussed as a group. Other drugs with somewhat similar pharmacological properties are phenmetrazine (Preludin*), methylphenidate (Ritalin*) and pipradol (Meratran*). Common slang terms for amphetamines include: 'speed', 'crystal', 'meth', 'bennies', 'dexies', 'A', 'uppers', 'pep pills', 'diet pills', 'jolly beans', 'truck drivers', 'co-pilots', 'eye openers', 'wake-ups', 'hearts' and 'footballs'.

The stimulating effects of the amphetamines were widely used by soldiers during World War II to counteract fatigue. Since then, they have been commonly used both medically and non-medically by vehicle drivers on long trips, night-shift workers, fatigued housewives, students studying for exams and others who must meet deadlines, athletes for increasing performance, and others for general stimulation, pleasure or fun.

88. In the 1940s, much of the wartime stockpile was dumped on the world market and in many countries amphetamines were available on a non-prescription 'over the counter' basis. Widespread use followed in most industrialized areas with numerous unpleasant consequences. Use reached epidemic proportions, for example, in Japan in the 1950s - a country which had never had a previous serious drug problem.34 Since this time, amphetamines have been quite uniformly put under governmental control and in some countries (e.g., Sweden) are currently prohibited from medical and non medical applications. Although the popularity of both medical and non-medical rise of these drugs spread rapidly in all age groups and social classes in North America after the war, heavy use was apparently largely confined to delinquents and to members of the criminal-addict population of a few decades ago. The drug was usually taken orally, sometimes injected by heroin addicts, or sniffed. In many instances it was used interchangeably with cocaine (a shortacting but powerful stimulant). Frequent use was made of 'dismantled' Denzedrine inhalers, which were on the unrestricted legal market at that time.

More recently, major concern has developed in many circles for a relatively new amphetamine phenomenon - that of massive doses used intravenously by persons often referred to as ,speed freaks'. Although this practice has been most frequently noted among youthful multi-drug-taking individuals, considerable opposition to such use of amphetamines has developed within the 'hip' community. The 'speed trip' is in many respects the antithesis of the experience sought with the psychedelic drugs. Instead of the orientation towards the 'consciousness expansion', personal insight, and aesthetic and religious awareness often attributed to the psychedelic drug experience by users, the speed phenomenon is usually characterized by action, power, arrogance and physical pleasure ('kicks'), and regularly leads to suspicion, paranoia, hostility and often aggression. In addition to these undesirable personality changes, which render 'speed freaks' highly unpopular in the community, such individuals generally present a picture of chronic ill-health unparalleled among youthful drug users.

89. The message received by the Commission at public and private hearings, and in written communications with youthful drug users has been mostly negative towards 'speed'. Many experienced illicit drug users consider amphetamines extremely dangerous and undesirable, and have expressed surprisingly hostile attitudes towards these drugs in no uncertain terms. Recently, numerous persons well known to youth, who have had considerable influence on drug attitudes during the past decade (e.g.,, John Lennon and the Beatles, Frank Zappa and the Mothers of Invention, Timothy Leary, and Donovan), have made public statements against the use of 'speed' and related drugs.

Many physicians have suggested that the supply of amphetamines legitimately imported and manufactured in Canada greatly exceeds medical need. As with other prescription drugs which are widely used, such as the barbiturates and tranquillizers, the distinction between medical and non-medical use is not always easily made.

Medical Use

90. As early as 1935, amphetamines (in doses from 20-200 mg) were found to be a specific treatment for narcolepsy, an uncommon illness which is characterized by sudden attacks of sleep and weakness. Since the 1940s, amphetamines (in doses of 10-50 mg) have been used in the treatment of overactive children who showed disorders of attention and impairment of learning capacity. In the last few years, several investigators have again published results of clinical trials which revealed that amphetamines and methylphenidate were among the most effective treatments for these childhood disorders.

Psychiatrists have frequently used intravenous injections of methedrine (in doses of 15-30mg) for diagnostic purposes. Administered in this fashion, the drug induces a state of excitation, elation and increased talkativeness, during which a previously inhibited patient might reveal information and symptoms which may be considered important for the understanding of his disorder. He might also express, more freely, previously suppressed emotions. It has been observed that some patients with a borderline psychosis show typical psychotic symptoms more clearly following an injection of amphetamines.

At one time, these drugs were used in the treatment of alcoholism and opiate narcotic dependency, but this practice was abandoned because amphetamines often produce dependency when taken for longer than two or three weeks. Since alcoholism is a chronic condition, some alcoholics who took this treatment for long periods of time became dependent on amphetamines and alcohol.

91. Early hopes that amphetamines would prove to be an effective general treatment for severe depression were soon disappointed. Although these drugs are powerful stimulants and increase a depressed person's activity, they may also make him more anxious and agitated, deprive him of sleep, and may fail to elevate his mood or to reverse the fundamental depressive process. In some individuals, these drugs have been effective in relieving mild depression and chronic fatigue, however.

Amphetamines, and some related drugs, have a strong suppressive effect on appetite. Most so-called 'diet pills' contain amphetamines or similar preparations. However, the appetite suppressing action of amphetamines usually disappears after about two weeks, together with the pleasant stimulating effects, unless the dose is continuously increased.

Amphetamines have also been occasionally used to treat petit mal epilepsy, parkinsonism, pregnancy nausea, asthma, nasal congestion and sedative poisoning. Many observers feel that because of the risk of dependency and undesirable personality change with amphetamines, even the medical use of these substances should be severely restricted.

Administration, Absorption, Distribution and Physiological Fate

92. Amphetamines are available in a variety of tablets, capsules (both in immediate and delayed release forms), elixirs, injections and, until recently, inhalers. These drugs also appear in powder ('crystal') form on the black market. Amphetamines are available commercially combined with such drugs as barbiturates (e.g., Dexamyl*) and other sedatives, atropine, caffeine, vitamins and minerals, thyroid extract, and, on the illicit market, amphetamines are reportedly sometimes added to LSD. One of the most esoteric pharmaceutical combinations has been described as follows:133 'This is a multi-coated tablet of pentobarbital on the outside to induce sleep rapidly, phenobarbital under a delayed dissolving coating to extend the sleep, and under another coating, an amphetamine to awaken the patient in the morning.'

Amphetamines are usually administered orally and are readily absorbed from the gastrointestinal tract. Occasionally both intramuscular and intravenous injections are used medically. In the past, an amphetamine-base inhaler was also available. Non-medical users may employ any of these administration routes, including sniffing 'crystal', although chronic 'speed freaks' prefer intravenous injections.

About half of the amphetamine which enters the body is excreted unchanged in the urine, the remainder being previously deactivated or chemically altered in the liver prior to elimination. Although excretion is generally rather rapid, traces of the drug can be found in the urine up to a week after withdrawal. Because of the considerable proportion excreted unchanged, certain individuals have been known to extract and reuse crystals obtained from the urine. (This general practice of 'reclaiming' excreted drugs is not new and such procedures have been recorded for centuries.)

Effects

93. Both the psychological and physiological response to amphetamines vary profoundly with dose, and the effects of intravenous injections of massive quantities may differ greatly in character from, and bear little resemblance to, responses to low doses administered orally. These effects vary continuously over the full dosage range, but for clarification in the following discussions, the use of moderate quantities of amphetamines will be separated from the discussion of the practice of high-dose intravenous injection.

94. Moderate dose effects. At typical therapeutic doses (e.g., 5-30 mg), amphetamines produce electrophysiological signs of central nervous system (CNS) activation along with a variety of adrenaline-like peripheral (sympathomimetic) effects such as increased blood pressure, pulse-rate and blood sugar, slight dilation of some blood vessels and constriction of others, widening of the pupils, increased respiration rate, depression of appetite and some relaxation of smooth muscle. Such effects might last 3-4 hours.

The psychological response varies considerably among individuals, but might typically include increased wakefulness, alertness, and vigilance, improvement in concentration and a feeling of clearer thinking, greater responsiveness to environmental stimuli, decreased fatigue and boredom, elevation of mood, mild euphoria, a feeling of sociability, increased initiative and energy, and increased verbal and other behavioural activity. There may be an improvement in some simple mental tasks, and athletic performance may be increased. In general, improved functioning is most likely to occur when prior performance was at a subnormal state due to drowsiness, fatigue or boredom.

On the other hand, a moderate dose of amphetamines in different individuals (or perhaps even in the same individual at different times) might produce irritation, restlessness, insomnia, blurred vision, tremor, nausea, headache, inability to concentrate, dizziness, heart palpitation, confusion, anxiety, chest pains, chilliness, diarrhoea or constipation, and other adverse symptoms. In cases of higher dose or hypersensitivity, delirium, panic, aggression, psychosis, hallucinations and cardiovascular abnormalities may occur in some individuals. Although deaths are rare, some have been reported among athletes.15

95. After continued administration of moderate doses, recovery may be associated with fatigue, drowsiness and, not infrequently, emotional depression. The increased energy and alertness elicited by the drug merely postpones the need for rest and clearly provides no long-term substitute for it. Many regular users of stimulants rely on the drug for energy when fatigued and often do not get proper rest for long periods of time.

The amphetamine toxic psychosis may be indistinguishable from schizophrenia.56 While this syndrome is generally associated with high-dose use, many of the symptoms have been observed with the use of more moderate amounts. There does not appear to be any irreversible physiological damage associated with long-term use of moderate doses of amphetamines although temporary disorders do occur.

96. Tolerance and dependence with moderate doses. Tolerance to the various drug effects develops at different rates and to different degrees - some responses 'drop out' in chronic use sooner than others. The tendency to increase dose depends upon which of the potential drug effects is rewarding or reinforcing drug use. Many individuals, for instance, who use amphetamines to control narcolepsy, may reach a stabilized dose and show very little need for increased quantity over a period of years. On the other hand, those using the drug to control appetite generally increase their dose. Many psychological effects, such as the mood-elevating response, may show a considerable sensitivity to tolerance, and individuals who either began using the drug to obtain these effects, or who acquired the taste for them after initially using amphetamines for other purposes, generally show a marked tendency to increase dose over time. Tolerance to some of the toxic properties occurs, and certain chronic users administer thousands of milligrams intravenously in a day, while even a fraction of that quantity would be extremely toxic in a non-tolerant user. As with other drugs, the rate of development of tolerance to the different pharmacological effects depends on the doses used, the frequency of administration and various individual factors. No suggestion of physiological dependence on amphetamines occurs with moderate doses; but psychological dependence on even low doses is frequently reported, and is considered a major hazard in both medical and non-medical amphetamine use.

97. High-dose effects. The chronic high-dose intravenous amphetamine syndrome has recently been described by several authors.124, 71 The cycle or pattern of use usually begins with several days of repeated injections (usually of Methedrine*), gradually increasing in magnitude and frequency. Some users may 'shoot' or 'crank' up to several thousand milligrams in a single day. Initially the user may feel energetic, talkative, enthusiastic, happy, confident and powerful, and may initiate and complete highly ambitious tasks. He does not sleep and usually eats very little. After the first few days, however, toxic unpleasant symptoms become stronger, especially as the dose is increased. These toxic effects may be similar to those described earlier for lower doses, but appear in amplified form. Some symptoms commonly reported at this stage are: confused and disorganized patterns of thought and behaviour, compulsive repetition of meaningless acts, irritability, self-consciousness, suspiciousness, fear, and hallucinations and delusions which may take on the characteristics of a paranoid psychosis. Aggressive and anti-social behaviour may occur at this time. Severe chest pains, abdominal pain mimicking appendicitis and fainting have also been reported .207

Towards the end of the 'run' (usually less than a week), the toxic symptoms dominate; the drug is discontinued, fatigue sets in, and prolonged sleep follows, sometimes lasting several days. Upon awakening, the user is usually lethargic, often emotionally depressed and ravenously hungry. The user may overcome these effects with another injection - thus initiating the cycle anew. Runs are often separated by days or weeks, however, at a time. In certain instances, 'down' drugs, such as barbiturates or tranquillizers, or even opiate narcotics may be used to 'crash' or terminate a run which has become intolerable or otherwise unpleasant.

98. The immediate effects of the intravenous injection of amphetamines are a sudden, overwhelming pleasurable 'rush' or 'flash' which has been described by users as 'an instant total body orgasm'. This effect is qualitatively different from the warm, drifting sensation associated with the opiate narcotics, but is reported to be initially similar to the 'splash' produced by intravenous cocaine.124 Some users claim that the immediate pleasure of the injection is the prime motivation for the drug use and that other effects are secondary.

Some individuals report that sexual activity is prolonged, and may continue for hours. When orgasm finally comes it may be more pleasurable than normal, although, on the other hand, some describe an inability to reach a climax. While only a minority of users report increased sexual activity, some people give this reason as a primary one for taking the drug. 124,23

Some investigators have reported that many users claim that they take the drug for euphoria or 'kicks', or because it enables them to be more confident and active. In addition, there are reports of 'needle freaks', in whom the use of the hypodermic syringe has special rewarding connotations.

99. The clinical picture of the chronic 'speed freak', is a distressing one indeed. Continued use of massive doses of amphetamines often leads to considerable weight loss, sores and non-healing ulcers, brittle fingernails, tooth grinding, chronic chest infections, liver disease, a variety of hypertensive disorders, and in some cases, cerebral haemorrhage. 124 The extent to which these effects are the direct result of the drug or the secondary consequences of poor eating habits, over exertion and improper rest is unclear. Further complications may be caused by unsterile injections, including hepatitis and a variety of other infections.47 Although some users feel that certain of their mental abilities have been impaired by amphetamine use, no clear picture of permanent brain damage has been demonstrated.

100. Heavy use of amphetamines frequently precipitates a psychosis which is indistinguishable from paranoid schizophrenia. In addition, several investigators contend that schizophrenics, and others with borderline psychotic conditions, are more likely to use the drug intravenously than are other individuals. In one study, 41 % of those requiring hospital admission for treatment of amphetamine disorders were thought to be schizophrenic before taking the drug.100 However, there is still no reliable information on what proportion of users develop psychoses and what the predisposing factors actually are. The majority of acute psychotic reactions occur towards the end of a run, and such symptoms are usually dissipated by a few days rest.

'Speed freaks' are generally unpopular within the multi-drug taking community and are often shunned. Consequently, these individuals may live together in 'flash houses' totally occupied by amphetamine users. Frequent 'hassles', aggression and violence have been reported in such dwellings. Heavy users are generally unable to hold a steady job because of the drug habit and often have a parasitic relationship with the rest of the illicit drug-using community. There are reports that many users support themselves through petty crime.184, 23

101. High-dose dependency. The question of physical dependence on amphetamines depends on the definition of the withdrawal symptoms necessary to meet the criterion. While it is clear that withdrawing amphetamine from chronic users does not produce the dramatic, physically painful and often dangerous abstinence syndrome associated with alcohol, barbiturates, or opiate narcotics, many investigators feel that the fatigue, prolonged sleep, brain wave (EEG) changes, voracious appetite, cardiovascular abnormalities, occasional gastrointestinal cramps, lethargy and, often, severe emotional depression following the 'speed binge' constitute a physiological reaction analogous to the more dramatic withdrawal seen with depressant drugs. 56,207

The tendency for tolerance-producing drugs to manifest a 'rebound' type of physiological and psychological pattern upon withdrawal has been given considerable attention; amphetamine abstinence in chronic users is generally characterized by a profound sedation, and depression of mood and physiological function, while drugs such as the sedatives and the opiate narcotics (all of which produce sleep in high doses) generally exhibit a withdrawal syndrome of severe and toxic overstimulation (in some instances to the point of convulsions).

The fact that amphetamines have, it any, a physically rather benign withdrawal syndrome, clearly indicates that a profound physical dependence is not a necessary component in an overall severe drug dependency situation. Subjective psychological factors seem to have considerably greater motivational importance in many instances - especially with chronic high-dose amphetamine use.

102. 'Speed Kills'. In recent years, the slogan 'Speed Kills' has received much attention, and the idea appears to play a significant role in the attitude that some users and non-users have towards the drug. One commonly hears the view that once you're 'on speed' you have only two to five years left to live. Some chronic 'speed freaks' incorporate this notion into the identity they present to others and the image they entertain of themselves. Many observers contend that the chronic use of intravenous amphetamines reflects a thinly disguised suicidal tendency, as well as an attention and sympathy gaining device. 'Hello, I'm Philbert Desanex; I'm a speed freak and I'm going to be dead by fall', is only a slightly exaggerated caricature of the image purposefully projected by some of these individuals.

103. What is the evidence, in fact, that 'Speed Kills' in the literal direct physical sense? Fatalities due to acute overdose are rarely reported. We have no reliable knowledge of the extent of intravenous amphetamine use, and although we hear many dire predictions, there is no good information on the long-term prognosis or outcome of such use. It would certainly appear, however, that chronic adherence to this practice is most detrimental to the individual and, often, to those with whom he interacts.

Although there is no clear evidence that the life expectancy of 'speed freaks' is lower than others living under similar circumstances, many investigators suspect this to be so. While there are few cases in the literature of death directly attributed to chronic amphetamine use, Clement, Solursh and Van Ast47 '... have recently become aware of a number of cases of death on the streets (of Toronto) apparently related to high-dose amphetamine abuse. At autopsy, however, pathological evidence of death directly due to amphetamines is rare in such cases'. After a thorough review of the literature, Cox and Smart of the Addiction Research Foundation reported: 'Currently there is no evidence available on mortality rates among speed users and it is not certain that speed itself is a lethal drug. There is no evidence to support or deny that "Speed Kills".60

The slogan was originally borrowed from a highway traffic campaign of the last decade and it has been suggested that, originally, in adopting this phrase, drug users were referring to the 'death' of the personality, the 'spirit', or the freedom of the individual when he becomes dependent on amphetamines, rather than to physical mortality.

Amphetamines and Other Drugs

1. As noted earlier, amphetamines are frequently used in conjunction, or in alternation, with a variety of depressant drugs such as barbiturates, alcohol and even heroin. The barbiturate and amphetamine up-down cycle has been described in both youthful and 'respectable' adult users at a variety of doses. Amphetamines intensify, prolong or otherwise alter the effects of LSD and it is reported that the two drugs are sometimes mixed. In addition, it would appear that the majority of youthful speed users have also had experience with a variety of psychedelic and other illicit drugs. Persons dependent on the opiate narcotics also frequently make use of stimulants such as cocaine and amphetamine - either as mixtures of drugs or used separately on different occasions. It is interesting to note that STP (DOM) and the newer MDA, both extremely potent psychedelic-hallucinogenic drugs, are chemically closely related to amphetamine.