Amphetamines

What Kind of Drug Is It?

Amphetamines are stimulant drugs that improve concentration, reduce appetite, and help keep users awake. Stimulants heighten the activity of a living being. In the 2003 edition of their book Drugs 101: An Overview for Teens, Margaret O. Hyde and John F. Setaro defined stimulants as "drugs used to increase alertness, relieve fatigue, [and make users] feel stronger and more decisive." Caffeine, nicotine, cocaine, ecstasy (MDMA), and steroids are all stimulants. (An entry for each of these substances is available in this encyclopedia.) However, amphetamines have a great potential for abuse. The "high" created by stimulants makes people feel good, but only temporarily. "They may elevate mood," wrote John B. Murray in the Journal of Psychology, but "their effects are short-lived."

Overview

Although they were discovered late in the nineteenth century, amphetamines did not receive much attention in the medical community until 1927, when a University of California researcher named Gordon Alles began studying their effects. Alles found that the drugs gave people a lot of energy, allowing them to do more and stay awake longer without getting tired. This effect of "speeding up" people's actions explains how amphetamines eventually came to be known by the street names "speed" and "uppers."

There are several different types of amphetamines. (For more information, see individual entries on Adderall, dextroamphetamine, and methamphetamine in this encyclopedia.) Generally, all amphetamines act the same way: as stimulants.

Official Drug Name: Amphetamine (am-FETT-uh-meen); Benzedrine (BENZ-uh-dreen)

Also Known As: Amp, bennies, pep pills, speed, and uppers

Drug Classifications: Schedule II, stimulant

Early Amphetamines Treat Breathing Problems

The first amphetamine was made in a laboratory by a German chemist in the late 1880s. The drug was not used for medical purposes, however, until more than forty years later. By that time, scientists were looking to create a drug that would mimic the effects of ephedra, a natural Chinese remedy for asthma. When boiled in water, stems from the ephedra bush produce a tea that helps dilate, or open up, the small sacs of the lungs. The active ingredient in this tea apparently eases breathing in asthmatics who drink it. (An entry on ephedra is also available in this encyclopedia.)

Research on asthma medications led to the manufacture of Benzedrine, the earliest and most basic form of amphetamine. In 1931, the pharmaceutical company Smith, Kline, and French introduced the Benzedrine inhaler to relieve the discomfort of nasal congestion due to colds, allergies, and asthma. As Murray pointed out, these first Benzedrine users reported trouble sleeping when they were on the drug. This sparked yet another branch of research on the effects of amphetamines. By 1935, drug companies were marketing amphetamines for the treatment of a daytime sleeping disorder known as narcolepsy. Researchers did not yet realize that amphetamine use could be dangerous.

The ADHD Connection

As far back as 1937, doctors were looking for ways to help children who had problems concentrating. At the time, the condition that is now referred to as attention-eficit/hyperactivity disorder (adhd) was called "minimal brain dysfunction." Little was known about the disorder, and it was believed to affect only children. Since then, the misleading name "minimal brain dysfunction" has been dropped, and medical researchers have learned more about ADHD and its effects.

ADHD is a disorder that begins during childhood, although in many cases it goes undiagnosed until adulthood. It is very difficult for people with ADHD to focus their attention and control their behavior. Children with ADHD are easily distracted and have difficulty concentrating, especially on schoolwork. They may also talk excessively, interrupt conversations, and have trouble waiting their turn. In many cases, people diagnosed with ADHD display impulsive behavior, which frequently persists into adulthood.

According to the Schaffer Library of Drug Policy's 1972 entry on amphetamines, early use of amphetamines in young patients with ADHD produced surprising results. "Instead of making them even more jittery, as might be expected, the amphetamines calm many of these children and noticeably improve their concentration and performance," commented the authors of the article. The use of amphetamines for ADHD in children and adults continues into the twenty-first century.

Usage Spikes after World War II

During World War II (1939–1945), soldiers used amphetamines to maintain alertness during combat. In the years following the war, many service personnel had trouble functioning without the drug. One major instance of widespread amphetamine abuse occurred in Japan after the war. Much of the country was devastated by bombs dropped during World War II, and the Japanese had to work long hours to rebuild their country. Japanese men who had been soldiers recalled how amphetamines had helped them face one battle after another when the war was in full swing. Demand for the drug increased, and amphetamines were released for sale in Japan without a prescription. This led to a decade of abuse throughout the nation. In the mid-1950s, though, the Japanese government restricted access to amphetamines and passed stricter laws against illegal amphetamine use.

Around the same time, Americans were becoming hooked on amphetamines, too. Users found they could lose weight quickly and effortlessly. Amphetamines quickly earned a reputation as a "wonder drug" that allowed users to work harder without feeling tired. "Pharmaceutical companies encouraged doctors to prescribe amphetamines to depressed housewives in the 1960s," wrote Andrew Weil and Winifred Rosen in From Chocolate to Morphine. The drugs were even given to racehorses, since it was thought the drug would make them run faster. Throughout the decade, public health authorities noted a new and disturbing trend in amphetamine use among drug users in San Francisco, California. Individuals, soon to be known as "speed freaks," were injecting liquefied amphetamines into their veins.

Amphetamine use also went up dramatically in the United Kingdom in the 1960s. According to Hilary Klee in the Journal of Drug Issues, "the 'Swinging Sixties' was a period of revolutionary social change and experimentation with psychoactive drugs…. 'Pop idols' became major… influences on British youth. The role models in the United Kingdom were… young and working class, like many of their fans. Amphetamine was popular among them because it provided the energy to perform all night and survive periods on tour."

The massive increase in drug use in the 1960s prompted countries throughout the world to pass new anti-drug laws and regulations. In the United States, Congress passed the Controlled Substances Act (CSA) of 1970, which cut down considerably on the production, importation, and prescription of amphetamines. Many forms of amphetamine, particularly diet pills, were removed from the over-the-counter market. But this crackdown on amphetamines led to the development of illegal labs in many countries. By the 1990s, illicit amphetamine production had emerged worldwide, with large numbers of illegal labs being reported especially in the western United States, the United Kingdom, and eastern Europe. The problem persisted into the early twenty-first century, especially among unemployed youth.

What Is It Made Of?

Amphetamines do not occur naturally; they cannot be grown in a garden or dug up from the ground. Rather, amphetamines are synthetic, or manufactured, substances that consist of the elements carbon, hydrogen, and nitrogen.

"Speed Kills"

The people who made the phrase "SpeedKills" popular were not talking about driving responsibly. The saying was used in the psychedelic era of the 1960s and early 1970s. It was coined by people who saw many of their peers fall victim to intravenous (IV) drug abuse.

Shooting amphetamines directly into the bloodstream is the most dangerous of all methods of use. This is because of the "speed" with which the drug flows throughout the body. The high is almost immediate, the shock to the system is intense, and the results can be deadly. Long-term speed use increases the risk of a drug-related fatality. Users build up a tolerance for the drug, meaning that they need more and more speed to get the same high. Taking higher and higher doses of the drug can lead to overdose and even death.

The phrase "Speed Kills" was not just used by anti-drug activists. It was also popular among drug users who knew firsthand the dangers of amphetamine abuse. The slogan appeared on

various mementos of the psychedelic era. The anti-amphetamine message adorned buttons, posters, and even stickers that schoolchildren put on their notebooks.

The chemical structure of amphetamines is related to two natural substances known to boost energy within the human body. Those substances are ephedrine and adrenaline. Ephedrine is a

natural stimulant found in the ephedra bush. It is the active ingredient in a Chinese herbal drug that relieves the symptoms of asthma. Adrenaline is a natural stimulant that the human body produces all by itself. It sets off the body's "fight or flight" reaction in times of emergency. When adrenaline is released, heart rate and blood pressure increase, the muscles that control breathing relax, and the pupils of the eyes dilate.

How Is It Taken?

Amphetamines come in both tablets and capsules and are usually swallowed. However, drug abusers sometimes crack open the capsule to get to the flecks of the drug inside it, or they grind the tablets into a fine powder. Amphetamine powder obtained from either method is then inhaled or "snorted." Users also mix it with tobacco or marijuana and then smoke it.

Beginning in the 1960s, some hardcore drug abusers started mixing the amphetamine powder into a liquid and then injecting it. This is called intravenous, or iv, drug abuse. When injected, the amphetamine high occurs almost immediately, increasing the danger of addiction. Weil and Rosen described the physical and mental effects of a few weeks of continued intravenous use. Addicts "became emaciated and generally unhealthy," the authors reported. "They stayed up for days on end, then 'crashed' into stupors. They became jumpy, paranoid, and even psychotic."

Many high-dose amphetamine abusers become psychotic, or mentally deranged, after a week or so of continuous use. A disruption occurs in the way their minds function, making it difficult for people suffering from a psychotic episode to distinguish between what is real and what is imagined. Users who increase "their dose rapidly to enormous levels… swallowing whole handfuls of amphetamine tablets" can develop an "amphetamine psychosis." According to the Schaffer Library of Drug Policy, this condition makes them feel as if "ants, insects, or snakes [are] crawling over or under the skin."

Are There Any Medical Reasons for Taking This Substance?

Historically, amphetamines have been prescribed by doctors as an appetite suppressant and as a treatment for both ADHD and an unusual sleep disorder called narcolepsy.

Amphetamines tend to decrease feelings of hunger in people who take them, making them an often-abused drug among dieters. Although the use of amphetamines for weight control was popular in the 1950s and again in the 1980s and part of the 1990s, this practice is no longer common. Amphetamine use for weight loss can be very dangerous. Most doctors agree that the best way to regulate weight is through moderate exercise and a healthy diet.

As of 2005, amphetamines were most commonly prescribed to treat ADHD and narcolepsy. Amphetamines are successful in the treatment of ADHD because they help improve the user's ability to concentrate. In prescription form, amphetamines also have been found to be helpful in treating narcolepsy, a fairly rare condition that causes people to fall asleep quickly and unexpectedly. Amphetamines speed up bodily functions, producing a much-desired feeling of alertness in people with narcolepsy.

Usage Trends

Amphetamine abuse is very widespread and often unintended. Cynthia Kuhn and her coauthors summarized the dangers of amphetamines in their book Buzzed: The Straight Facts about the Most Used and Abused Drugs from Alcohol to Ecstasy. In a word, the buzz from

amphetamines is "pleasurable." Overuse typically stems from the drug's effects. Amphetamines make most users feel good, at least in the short term. Experimentation with amphetamines can get out of hand quite easily, though. Even legal users—those individuals taking the drug with a doctor's prescription—can get hooked.

Not Just a Nasal Spray

Generations ago, over-the-counter nasal inhalers contained amphetamines. The reasoning behind amphetamine treatment for nasal congestions was quite simple: stimulants are known to constrict blood vessels. Constricting the blood vessels in the nose and sinuses cuts down on congestion because it shrinks the nasal tissues, allowing air to flow more freely through the nose. This effect is only temporary, though, and when it wears off, a "rebound effect" occurs. The nasal passages actually end up more severely blocked than they were before the amphetamine was inhaled.

The first users of any new drug are a bit like human guinea pigs. "Because of the incredible complexity of the brain," explained Kuhn, "most drugs that affect it have actions in addition to those for which they were developed." Aside from the problems with the rebound effect, some users of early nasal inhalers "experienced general stimulation from them" as well, wrote Weil and Rosen. "Some got high, and some became dependent." Because of their side effects and the potential for abuse, amphetamines are no longer dispensed in over-the-counter decongestants.

Who's Using Amphetamines?

The results of the 2004 Monitoring the Future (MTF) study were released to the public on December 21, 2004. Conducted by the University of Michigan (U of M), it was sponsored by research grants from the National Institute on Drug Abuse (NIDA). Since 1991, U of M has tracked patterns of drug use and attitudes toward drugs among students in the eighth, tenth, and twelfth grades. (Prior to that, from 1975 to 1990, the MTF survey was limited to twelfth graders.)

The 2004 MTF survey results indicate that nonprescription amphetamine use among students in the eighth and tenth grades had fallen. Researchers noted "a steady decline among eighth graders since 1996; in fact, their annual… use has fallen by almost half since then," from 9.1 to 4.9 percent. Amphetamine use was also down among tenth graders, "but not among twelfth graders, who… remain near their recent peak levels of use." According to MTF charts for 2003 to 2004, about one in every ten high school seniors reported using amphetamines "in the last twelve months." The ease with which seniors said they would be able to get the drug held steady. More than half of the twelfth graders surveyed said it would be "fairly easy" or "very easy" to obtain amphetamines.

The MTF survey does not track drug use among people after their high school years. However, amphetamine use in the general population can be determined by other data. Experts in the field of drug research periodically gather together all of the information available on certain drugs to create a profile, or description, of a typical user. Based on these studies, the typical amphetamine user of the 1960s, 1970s, 1980s, and part of the 1990s was young, white, male, single, and often unemployed. More recent findings cited in the Journal of Psychology in 1998 indicate that the population of amphetamine users is becoming broader and now includes:

• more women
• more married, divorced, and widowed people
• fewer whites
• people of all age groups, from middle school students to retirees.

In mid-2003, Alcoholism & Drug Abuse Weekly reported the results of the Quest Diagnostics 2002 Drug Testing Index, a measure of drug use among American workers. Based on 7 million urine tests performed by the lab throughout 2002, the overall use of drugs in the workplace apparently decreased. The incidence of amphetamine usage, however, went up significantly. According to Quest, positive test results among U.S. workers "increased 70 percent over the past five years" from 1998 through 2002.

The use and abuse of amphetamine-like stimulants is a growing global problem that poses "a serious threat to the health, social and economic fabric of families, communities and nations," according to the World Health Organization Web site. The United Nations estimated that in the year 2000, 29 million people around the world had abused various types of amphetamine stimulants in the previous decade.

Effects on the Body

Amphetamines are psychostimulants. As a prescription drug for the treatment of ADHD, amphetamines have been shown to increase performance accuracy, improve short-term memory, improve reaction time, aid in solving mathematical problems, increase problem-solving abilities in games, and help individuals concentrate.

"If stimulants simply increased energy and alertness," commented Kuhn, "they indeed would be [a] miracle medicine.… How ever, these drugs also cause an unmistakable euphoria and sense of well-being that is the basis of addiction." The effect of amphetamines is similar to the effect of cocaine, another widely abused psychostimulant. However, amphetamine highs are generally longer lasting.

Amphetamine users often feel that the drug puts them in a better mood and increases their level of confidence. "It gives me a lot of energy," remarked one user in an interview with Klee. "I can get out and do things, meet people, things like that. And you don't let anything get to you. You're on top of the world."

Amphetamines are often abused by people who want to boost their energy and enhance their physical performance. Athletes on amphetamines may find that they can play longer, harder, and better. Students on speed can endure longer studying sessions and remain focused on their homework for hours, sometimes without even taking a break to eat. Truck drivers who take amphetamines are able to cover more miles without falling asleep at the wheel. But the high generated by amphetamines eventually wears off.

After the Buzz

"A single oral dose of amphetamine usually stimulates the body for at least four hours," wrote Weil and Rosen. After that, more of the drug is needed to maintain the high. Once the buzz of uppers has worn off, users who felt awake, energized, and full find themselves very tired, grumpy, and extremely hungry. A person coming down from an amphetamine high may sleep an entire day away before the drug leaves his or her system entirely.

"Irritability and/or aggression is common when 'coming down' off the drug, when using [it] heavily, and when [it is] combined with alcohol," reported Klee. "You get to the point where you're shouting at people and causing trouble and the amphetamine gives you the energy to do it… which is a problem," noted one of the users Klee quoted. Such behavior can ruin longstanding relationships and, in some cases, result in social rejection for users.

Addiction and Other Dangers

Long-term amphetamine use can result in a psychological addiction or psychological dependence. Psychological dependence can develop quickly, especially in people who already show signs of depression. As Kuhn put it, "We know that the drive to use cocaine or amphetamine is considerably stronger than that for any of the other addictive drugs."

The use of amphetamines can cause an upset stomach, diarrhea, headache, dizziness, nervousness, weight loss, and insomnia. The drug can also lead users to perform bizarre, repetitive actions. "Assembling and disassembling radios, cars, and gadgets is common among… users. [They] are aware that their activity is meaningless but report not being able to stop," noted Murray. Higher doses result in fever, an unusually fast heartbeat, chest pain, blurred vision, tics, tremors, and antisocial behavior.

Amphetamines can kill. Prolonged abuse of amphetamines can lead to tolerance. Taking greater quantities of amphetamines increases the chance of an overdose. Signs of an overdose include convulsions, followed by coma, and then possibly death. The cause of death may be from the bursting of blood vessels in the brain, a heart attack, or an extremely high fever.

Lab Studies

The National Academy of Sciences revealed in 2003 that exposure to amphetamines can reduce "the ability of certain brain cells to change in response to life experiences." With funding provided by the National Institute on Drug Abuse (NIDA), drug researchers from the University of Lethbridge in Canada and U of M-Ann Arbor worked together, conducting experiments with amphetamines on lab rats.

Amphetamine-treated rats seemed confused by changes that were introduced to their surroundings during the course of the testing. Rats that were not given amphetamines, however, had no problems maneuvering around ramps, bridges, tunnels, and toys that had been relocated in their cages. Even after three and a half months, the amphetamine-treated rats were unable to adjust to changes in their environment. Analysis of the brains of both treated and untreated rats showed definite differences in their physical appearance.

These findings correspond with drug experiments conducted by three researchers on human volunteers in 1969. Those experiments, according to Murray, indicated that high doses of amphetamines affect the brain. The volunteers, who were hospitalized for the six-week-long study, experienced wide mood swings that began with euphoria, or a feeling of great happiness, and ended with deep depression. They also went for days without eating or sleeping well, talked nonstop for hours at a time, and showed signs of paranoia before the experiment was concluded.

Reactions with Other Drugs or Substances

Amphetamines are dangerous drugs. The dangers increase when they are taken with other addictive substances. Amphetamines are frequently combined with other drugs to prolong or add to the high they produce alone. Caffeine is one substance that is known to add to the effects of amphetamines. When combined with alcohol, "amphetamines have the potential to produce unprovoked, random, and often senseless violence," noted Murray. Amphetamines raise blood pressure, so they should not be taken by people who are on medication to reduce their blood pressure. In addition, the drug should not be taken with over-thecounter cold medications or with certain antidepressant medications.

Treatment for Habitual Users

Tolerance to amphetamines occurs quickly. In an attempt to sustain the high that results from amphetamine use, users often begin taking more of the drug than they should. They then find themselves unable to stop on their own. The withdrawal process can last days or weeks. Besides feeling intense cravings for the drug, longtime users who attempt to kick their habit experience other unpleasant effects. These include extreme anxiety, abdominal pain, shortness of breath, vivid or unpleasant dreams, fever, decreased energy, and depression. Even "long after the withdrawal period, past users may experience urgings and cravings," added Murray. Addiction experts consider behavioral therapy and emotional support essential for the successful treatment and rehabilitation of amphetamine abusers.

Consequences

Amphetamines can be extremely toxic. When uppers are "used without medical supervision, they are potentially dangerous, even for first-time users," warned Murray. People who are high on amphetamines are more likely to take chances and engage in riskier behavior than they would if they were not high. This increases the danger of becoming infected with HIV (the human immunodeficiency virus), which can lead to AIDS (acquired immunodeficiency syndrome), either through unsafe sex or by sharing needles.

Drug abuse among young people is associated with early sexual activity, increased involvement in criminal activities, and higher

school dropout rates. Amphetamine users often take other drugs along with uppers. This can increase the likelihood of becoming involved in accidents. It can also contribute to the development of physical, mental, and emotional problems, including high rates of infection, phobias, depression, and suicidal tendencies.

Infants born to mothers dependent on amphetamines have an increased risk of premature delivery and low birth weight. The infants may actually experience symptoms of drug withdrawal. Mothers taking the drug should not breast-feed their babies, since amphetamine is excreted in human milk. A number of studies using rodents as test animals indicate that women should not take amphetamines at all when pregnant.

The Law

Amphetamines are controlled substances: their use is regulated by certain federal laws. The Controlled Substances Act (CSA) of 1970 called for the assignment of all controlled drug substances into one of five categories called schedules. These schedules are based on a substance's medicinal value, harmfulness, and potential for abuse and addiction. Schedule I is reserved for the most dangerous drugs that have no recognized medical use. Amphetamines fall under Schedule II: dangerous drugs with genuine medical uses that also have a high potential for abuse and addiction.

Possessing amphetamines without a medical doctor's prescription is against the law and can result in imprisonment and stiff fines. The length of the jail sentence and the amount of the fine are increased when a person is convicted of a second or third offense of amphetamine possession. People convicted of distributing amphetamines—selling or giving away prescribed drugs—face lengthy prison terms and fines of up to $2 million.

For More Information

Books

Bayer, Linda. Amphetamines and Other Uppers. Broomall, PA: Chelsea House Publishers, 2000.

Clayton, Lawrence. Amphetamines and Other Stimulants. New York: Rosen Publishing Group, 1994.

Gahlinger, Paul M. Illegal Drugs: A Complete Guide to Their History, Chemistry, Use, and Abuse. Las Vegas, NV: Sagebrush Press, 2001.

Hyde, Margaret O., and John F. Setaro. Drugs 101: An Overview for Teens. Brookfield, CT: Twenty-first Century Books, 2003.

Kuhn, Cynthia, Scott Swartzwelder, Wilkie Wilson, and others. Buzzed: The Straight Facts about the Most Used and Abused Drugs from Alcohol to Ecstasy, 2nd ed. New York: W.W. Norton, 2003.

Pellowski, Michael J. Amphetamine Drug Dangers. Berkeley Heights, NJ: Enslow Publishers, Inc., 2001.

Schull, Patricia Dwyer. Nursing Spectrum Drug Handbook. King of Prussia, PA: Nursing Spectrum, 2005.

Weil, Andrew, and Winifred Rosen. From Chocolate to Morphine. New York: Houghton Mifflin, 1993, rev. 2004.

Westcott, Patsy. Why Do People Take Drugs? Austin, TX, and New York: Raintree Steck-Vaughn Publishers, 2001.

Periodicals

Klee, Hilary. "The Love of Speed." Journal of Drug Issues (Winter, 1998): pp. 33-55.

Murray, John B. "Psychophysiological Aspects of Amphetamine-Methamphetamine Abuse." Journal of Psychology (March, 1998): pp. 227-237.

"Workplace Drug Use Declines, Amphetamine Use Increases." Alcoholism & Drug Abuse Weekly (June 16, 2003): p. 8.

Web Sites

"The Amphetamines." Schaffer Library of Drug Policy.http://www.druglibrary.org/schaffer/ (accessed June 16, 2005).

"Amphetamine-Type Stimulants." World Health Organization.http://www.who.int/substance_abuse/facts/ATS/en/ (accessed June 16, 2005).

"Mind over Matter: Stimulants." NIDA for Teens: The Science behind Drug Abuse.http://teens.drugabuse.gov/mom/mom_stim2.asp (accessed June 16, 2005).

Monitoring the Future.http://www.monitoringthefuture.org/ and http://www.nida.nih.gov/Newsroom/04/2004MTFDrug.pdf (both accessed June 16, 2005).

Proceedings of the National Academy of Sciences of the United States of America.http://www.pnas.org/ (accessed June 16, 2005).

See also: Adderall; Cocaine; Dextroamphetamine; Diet pills; Ephedra; Methamphetamine

AMPHETAMINES

OFFICIAL NAMES: Amphetamine (Adderall), laevoamphetamine (Benzedrine), dextroamphetamine (Dexedrine), methamphetamine (Methedrine)

STREET NAMES: Black dex, bens, bennies, benz, black and white, blackbirds, black bombers, black Cadillacs, black mollies, blacks, blue boys, blue mollies, brain pills, brain ticklers, brownies, browns, bumblebees, chicken powder, co-pilot, coasts-to-coasts, crisscross, cross tops, dex, dexies, diamonds, diet pills, dominoes, double cross, drivers, eye openers, fives, footballs, forwards, french blues, go, greenies, head drugs, hearts, horse heads, ice, jelly baby, jugs, leapers, lid poppers, lid proppers, lightning, MAP, minibennies, morning shot, nugget, oranges, peaches, pep pills, pink hearts, pixies, rhythm, rippers, road dope, rosa, roses, snap, snow pallets, sparkle plenty, sparklers, speed, spivias, splash, splivins, sweeties, sweets, tens, thrusters, truck drivers, turnabout, uppers, uppies, wake ups, West Coast turnarounds, whiffledust

DRUG CLASSIFICATIONS: Schedule II, stimulant

OVERVIEW

Amphetamine was first synthesized in 1886 by a German chemist, though it was not used for medical purposes until the early 1930s. Amphetamine dilates the small sacs of the lungs, providing relief to patients with breathing disorders. In 1931, the pharmaceutical company Smith, Kline, and French introduced the Benzedrine Inhaler to relieve the discomfort of nasal congestion due to colds, hay fever, and asthma. Soon after, the sulfate form of amphetamine was also aggressively marketed. Amphetamine was promoted as a sort of "wonder drug" without knowledge of its potentially addictive properties.

Because users complained of sleeplessness, druggists started compounding tablets for the treatment of a sleeping disorder known as narcolepsy in 1935. Amphetamine then became popular because it delayed fatigue. "Pep pills" soon became available over-the-counter. Truckers were quick to use the pills to keep awake during long-haul deliveries. The first reports of college students using amphetamines to beat fatigue while studying surfaced in 1936. Businessmen and their secretaries also began using amphetamines to induce increased alertness.

By 1937 amphetamine was being used to treat a condition known as minimal brain dysfunction, a disorder later renamed attention deficit hyperactivity disorder (ADHD). The use of amphetamine for that disorder continues into the twenty-first century.

During World War II, soldiers on both sides of the war used amphetamines to maintain alertness and increase stamina. Historians speculate that overuse produced states of uncontrolled aggression that may have contributed to "berserker" charges by soldiers on both sides during many battles. Historians have said that from 1942 until his suicide, Hitler received daily methamphetamine (MAP), a kind of amphetamine, injections from his doctor. Many historians believe that the amphetamine abuse corrupted Hitler's judgement, undermined his health, and probably influenced the course of the war.

Unfortunately, as the use of amphetamine spread, so did its abuse. The first major epidemic of modern times occurred in Japan after the end of World War II. Much of the country was devastated during the war, and the Japanese had to work long hours to rebuild their country. Japanese men who had been soldiers recalled how amphetamine kept them going during the war and sought to acquire the drug. As a result of that demand, inventories of amphetamines were released for sale without prescription. This led to a national epidemic that only ended in the mid-1950s after the Japanese government restricted access to amphetamines and passed stricter laws against illegal amphetamine use.

Major epidemics of amphetamine abuse and dependence occurred in the 1950s, 1960s, and again in the 1990s in the United States and western Europe, particularly in Denmark, Finland, Sweden, and the United Kingdom. In the United States during the 1950s, the availability of over-the-counter amphetamine "diet" pills fueled the epidemic. Amphetamines were even given to race horses during that time since it was believed the drug made them run faster.

In the 1960s, public health authorities noted the first epidemic of intravenous drug use centered around the Haight-Asbury district of San Francisco, California. Individuals, soon to be known as "speed freaks," had learned how to melt amphetamine down and inject the liquefied substance into their veins.

The new drug counterculture of the early 1960s prompted increased control measures. Countries throughout the world passed new laws and regulations in the 1960s and 1970s. In the United States, Congress passed the Controlled Substance Act (CSA) of 1970. The CSA included amendments to the federal food and drug laws that put strict controls on the production, import, and prescription of amphetamines. Many amphetamine forms, particularly diet pills, were removed from the over-the-counter market though they remain available by prescription.

As a result of those laws and regulations, and similar laws in other nations, a black market for amphetamines emerged in many countries. In the 1990s, illicit amphetamine production was increasingly reported in the western United States and eastern Europe, particularly in Poland and Hungary.

CHEMICAL/ORGANIC COMPOSITION

All amphetamines are synthetic, or manufactured, substances derived from alpha-methyl-beta-phenyl-ethylamine, a colorless liquid consisting of carbon, hydrogen, and nitrogen. In terms of their chemical structures, amphetamines are related to two natural substances known to boost energy within the human body. Those substances are ephedrine and adrenaline. Ephedrine is a natural stimulant found in plants of the genus Ephedra. It is the active ingredient in the Chinese herbal drug ma huang. Adrenaline is the body's "fight or flight" hormone.

According to the U.S. Department of Justice's Drug Enforcement Administration (DEA), amphetamine, dextroamphetamine, laevoamphetamine, and methamphetamine (MAP) are all referred to as amphetamines because their chemical properties and actions are "so similar" that "even experienced users have difficulty knowing which drug they have taken." Consequently, it doesn't matter what an amphetamine pill or capsule is called. The only difference between amphetamine and dextroamphetamine, for instance, is a few molecules of dextrose, a type of sugar.

The composition of amphetamine or dexamphetamine pills or capsules actually is a combination of the various types of amphetamine "salts." For instance, the

5 mg amphetamine tablet known as Adderall contains 1.25 mg of dextroamphetamine saccharate, 1.25 mg of amphetamine aspartate, 1.25 mg of dextroamphetamine sulfate, and 1.25 mg of amphetamine sulfate.

Methamphetamine is composed of the above named forms of amphetamine with the addition of ephedrine or pseudoephedrine. Many users consider MAP to have more of a "kick," which is why many who abuse amphetamines prefer methamphetamine. The legal form of methamphetamine is the prescription pill Methedrine. Most illegal forms of MAP come from illegal laboratories. MAP is relatively easy to manufacture and does not require sophisticated equipment. Illicit production has occurred in home kitchens, trailers, recreational vehicles, and rural cabins. It is often converted to its water-soluble form, a salt-like substance. However, MAP manufacturing can be dangerous. Combined in the wrong ways, the chemicals used in the process can explode. Illegal "chemists" and innocent victims have been maimed and killed by explosions and resulting fires.

In an attempt to limit the illegal manufacture of MAP in the latter part of the twentieth century, many governments, including the U.S. government, passed laws limiting the sale of ephedrine. Those laws were ineffective because the illicit drug makers learned how to use a chemical called pseudoephedrine to make methamphetamine. Pseudoephedrine is an ingredient found in many over-the-counter medicines used for colds, allergies, and the flu. Since it is readily available, the illegal drug makers have been able to continue to manufacture illicit MAP.

INGESTION METHODS

Prescription amphetamines come in tablet or capsule form. The most common way amphetamines are ingested is by swallowing amphetamine pills or capsules. However, drug abusers also crack open the capsules for the amphetamine powder or grind the tablets into a powder. That powder can then be inhaled or "snorted." Mixed with tobacco or marijuana, it can be smoked. The "ice" form of methamphetamine looks like shaved glass slivers or rock salt and can be smoked in a glass pipe.

Some hardcore drug abusers liquify the powder and the "ice" forms of MAP and inject the solution directly into their bloodstreams. When injected, the "high" or "rush" occurs almost immediately, increasing the danger of addiction to amphetamines, which experts compare to that of heroin or cocaine. An additional concern is the tendency for drug users to reuse and share syringes, dramatically increasing the risks of blood poisoning and contracting HIV/AIDS, hepatitis, or other diseases.

THERAPEUTIC USE

Amphetamines, in prescription form, have been found to be helpful in treating narcolepsy, a condition in which a person suffers from excessive or sudden, recurrent daytime sleepiness. However, narcolepsy is a fairly rare disease.

They have also sometimes been found useful for the treatment of ADHD, a condition that interferes with the learning ability of affected individuals. Millions of children have been diagnosed as having ADHD. Many of those children and increasing numbers of adults are treated with amphetamine-like drugs such as Ritalin and Cylert. The generic name for those amphetamine-like drugs is methylphenidate. Some children with ADHD do not respond to the various forms of methylphenidate and are placed on amphetamines instead.

Amphetamines have also been used and often misused for the treatment of obesity. Medical studies show that dieters who use prescription amphetamines usually do quite well at losing weight initially. However, when those dieters are taken off of amphetamines almost all regain their lost weight and become even heavier over a five-year period. Although the use of amphetamines for weight loss was popular in the 1950s and again in the 1980s and part of the 1990s, most medical doctors do not prescribe amphetamines for weight loss. Nonamphetamine weight-loss drugs are used instead. It remains uncertain as to whether those drugs will be any more effective over the long term in helping people keep off excess weight.

A 2001 study demonstrated a potential new therapeutic role for dextroamphetamine. The study indicated that it may help some stroke survivors recover faster from the stroke-caused speech disorder known as aphasia. Officially, however, amphetamine has been approved only for the treatment of narcolepsy, attention deficit hyperactivity disorder (ADHD), and obesity.

USAGE TRENDS

The use and abuse of amphetamine-like stimulants is a growing global problem, according to the World Health Organization (WHO). The United Nations estimated that in the year 2000, 29 million people around the world abused various types of amphetamine stimulants in the previous decade. That figure was larger than the number of people consuming cocaine and opiates combined. According to the 1999 National Household Survey on Drug Abuse, 9.4 million Americans had tried the MAP form of amphetamine during their lifetimes.

Scope and severity

No specific total amphetamine-use statistics are available. However, according to the year 2000 report of the Drug Abuse Warning Network, there was a 35% increase from 1999 to 2000 in the number of hospital emergency department (ED) cases in which amphetamines were mentioned. DAWN is a national surveillance system that collects data on drug-related emergency department visits.

Age, ethnic, and gender trends

There are few studies revealing age, ethnic, and gender trends in amphetamine abuse. According to a 1998 article in Journal of Psychology, the demographic characteristics of amphetamine/methamphetamine abusers changed in the mid-1990s compared to a period only five years previously. Young Caucasian white men who are unemployed and single have been especially likely to be amphetamine users, according to researcher John B. Murray. However, "more married, widowed, and divorced people" and fewer Caucasians were reported in outpatient and inpatient populations studied in 1994–1995 compared to a previous 1989–1994 study.

MENTAL EFFECTS

Amphetamines stimulate the central nervous system (CNS), producing feelings of euphoria, providing relief from fatigue, and increasing alertness. CNS stimulation provoked by amphetamines can also intensify emotions, increase aggression, and alter self-esteem.

As a prescription drug for the treatment of ADHD, amphetamines have been shown to increase performance accuracy, improve short-term memory, improve reaction time, aid in mathematical computation, increase problem-solving abilities in games, and help individuals concentrate.

Unfortunately, chronic amphetamine use can result in a psychological addiction, the belief that a person needs the drug in order to function. Psychological dependence can develop quickly, especially in people who already have clinical depression.

PHYSIOLOGICAL EFFECTS

Increased pulse rate and increased blood pressure are normal with amphetamine use. But even short-term use can cause adverse physical effects, including intoxication, irregular heartbeats (tachycardia), and excessive body warmth, a dangerous and sometimes deadly condition known as hyperthermia.

Prolonged abuse of amphetamine can lead to tolerance, making it necessary to take higher doses of the drug to get the effect or high originally experienced. Taking greater quantities of the drug increases the chance of an overdose. An overdose can increase blood sugar, cause an irregular heartbeat, and cause circulatory collapse. In other words, an overdose can kill. Fatal overdose reactions are usually preceded by convulsions, then coma. Death may occur due to burst blood vessels in the brain, heart attacks, or very high fever.

Chronic use can lead to dangerous changes within the body which cause cravings for the drug, agitation, decreased energy, increased appetite, insomnia, and a craving for sleep. Once the drug taking is temporarily stopped, abusers have been known to drop into deep sleeps that last up to 48 hours. Drivers of cars and trucks coming down from an amphetamine high have been known to fall asleep behind the wheel and cause deadly crashes.

Harmful side effects

Side effects include delayed and impaired judgment, sleep onset, reduced appetite, weight loss, tics, stomachache, headache, and jitteriness. Convulsions and coma may occur. Individuals who ingest amphetamine by dissolving the tablets in water and injecting the mixture risk complications due to the insoluble fillers used in the tablets. When injected, those materials block small blood vessels and can cause serious damage to the lungs and retina of the eye.

Chronic amphetamine users can demonstrate compulsive behavior and talk excessively and disjointedly. Affected individuals can become exhausted and lose insight into their actions, often insulting or otherwise alienating friends and family without obvious cause. High-dose amphetamine consumption causes abusers to become paranoid, or unrealistically suspicious of everyone, and experience hallucinations. Most high-dose amphetamine abusers become psychotic, or mentally deranged, within a week after continuous use. They experience delusions of being persecuted and auditory and visual hallucinations. Chronic amphetamine abuse is also associated with violence, criminal assault, homicides, suicides, and traffic accidents.

Infants born to mothers dependent on amphetamines have an increased risk of premature delivery and low birth weight. The infants may experience symptoms of drug withdrawal. Mothers taking the drug should refrain from nursing, since amphetamine is excreted in human milk. A number of studies using rodents as test animals indicate that women should not take amphetamines when pregnant.

Long-term health effects

Since amphetamines increase blood pressure, the chances for a stroke increases in users. Abusers of amphetamine may also be prone to degenerative disorders of the nervous system such as Parkinson's disease. Research published in the March 2001 issue of American Journal of Psychiatry indicates that MAP abuse leads to long-lasting changes in the human brain that are linked to impaired coordination and memory.

Medical studies indicate that five to 15% of the amphetamine users who become psychotic fail to recover completely even after physical withdrawal symptoms pass. Psychiatrists in Japan did a study demonstrating that amphetamine psychosis can persist for several years.

REACTIONS WITH OTHER DRUGS OR SUBSTANCES

Amphetamines are frequently combined with other drugs to prolong the "rush" or "high" or to add a psychedelic, or hallucinogenic, component to the experience. Despite the number of years that amphetamines have been abused, there are relatively few studies about their abuse potential and effects, and apparently there are no studies about the effects of amphetamine when combined with other drugs of abuse.

It is known that amphetamines may counter the sedative effect of antihistamines and other sedating agents. Amphetamines raise blood pressure, so abusers who take prescription anti-hypertension pills do not get the full benefit from those anti-hypertensives.

Amphetamines do not mix well with a class of antidepressant medication known as MAO inhibitors. Mixing the two types of drugs can cause headaches, increase blood pressure, and even result in death.

TREATMENT AND REHABILITATION

Withdrawal can be unpleasant, and feelings of cravings and depression can return long after the withdrawal period. During the withdrawal period, individuals may experience abdominal pain, increased fatigue, fever, infection, loss of appetite, diarrhea, shortness of breath, nausea, vomiting, dizziness, emotional upset, insomnia, nervousness, and weight loss. Amphetamine withdrawal brings on intense cravings for the drug, which often leads to relapse. Intense craving is experienced by 87% of all amphetamine abusers who attempt to abstain from the drug.

Current research has demonstrated that there are no medical treatments effective for treating amphetamine abuse. This means that other drugs cannot be substituted to assist in the weaning process. However, thousands of individuals have successfully gone through withdrawal and continue to abstain from amphetamine use despite the long and uncomfortable process. Twelve-step programs are helpful for many substance abusers in recovery.

Besides intense amphetamine cravings, other unpleasant withdrawal side affects include agitation, anxiety, vivid or unpleasant dreams, decreased energy, increased appetite, lethargy, and increased sleep. People in withdrawal lose interest in the pleasure of other activities. Their physical movements are slowed, and clinical depression is prevalent. Although symptoms may lessen after just four or five days, some symptoms can continue for weeks or even months.

While medical literature indicates that other drugs have limited benefits during the recovery process, the psychological/behavioral literature on addiction rehabilitation reveals that although relapse rates are high, rehabilitation is possible. Addiction experts say that amphetamine withdrawal and treatment is a time-consuming process, and behavioral and emotional support is essential for success. Organizations such Phoenix House, Freedom House, and SAFE (Substance Abuse Family Education) run withdrawal treatment and rehabilitation programs for teens that last for as long as a year at live-in residence centers.

PERSONAL AND SOCIAL CONSEQUENCES

Authorities point out that few people are capable of questioning the value of a drug that makes them feel good and is considered to have beneficial effects. However, occasional experimentation can easily become compulsive drug use and abuse. Abusers frequently do not recognize the effects amphetamines have on their failures and also often do not see how that "upper" has negative effects on their relationships with others.

Early onset of drug abuse is associated with early sexual activity, crime, and educational failure. Young amphetamine users risk exploitation by adults and are more likely to become involved in criminal or violent behavior and prostitution—having to resort to sex for survival. Consequently, they are also more likely to become infected with HIV or other sexually transmitted diseases and by tuberculosis or other bacterial, fungal, or viral infections. Chronic amphetamine abusers are also more at risk for mental and emotional disorders including anxiety, phobias, and depression. They are at higher risk of suicide.

Amphetamines have the potential to produce "unprovoked, random, and often senseless violence," according to the World Health Organization (WHO). They are likely to demonstrate paranoia, antisocial behavior, become overly verbally and physically aggressive, and start fights over literally nothing.

The social consequences of amphetamine abuse include higher rates of accidents, violence, and crime. This is a worldwide phenomenon, says WHO. According to the National Institute on Drug Abuse (NIDA), drug abuse cost American society $97.7 billion during1992. That estimate included costs for substance abuse treatment and prevention, related health care, reduced job productivity, lost earnings, and other costs to society such as crime and social welfare. How much of that is due to amphetamine misuse is unknown, but the study estimated that the costs were borne almost equally by governments (46%) and by those who abuse drugs and members of their families (44%). More than half of the estimated costs of drug abuse were associated with drug-related crime.

LEGAL CONSEQUENCES

Individuals who buy, sell, or transport illegal amphetamines, or those who buy, sell, or otherwise traffic in the equipment to manufacture illegal amphetamines risk hefty fines and imprisonment. In the United States, the consequences of illegal possession, sale, or even freely sharing amphetamines without a medical doctor's prescription can be severe under terms of the Controlled Substance Act (CSA) of 1970.

A first offense of simple possession of amphetamine without a doctor's prescription can result in imprisonment for not more than one year and a fine of $1,000 or both. A second offense can result in imprisonment for up to two years and a fine of $2,500. A third illegal possession offense can result in up to three years of prison time and a fine of $5,000.

Distribution, which includes selling or giving away more than 100 grams of amphetamine is illegal under CSA section 841. It is an offense punishable by prison terms of a minimum of five years and up to 40 years with fines of up to $2 million. If death or injury results from illegal distribution, the penalties become imprisonment for a minimum of 20 years to more than life and a fine of $2 million. A person convicted of selling amphetamines to someone under 21 years of age is subject to twice the maximum punishment.

Legal history

Before 1970, amphetamines were subject to numerous and sometimes confusing laws regulating their manufacture and distribution. In 1970, the U.S. Congress passed the Comprehensive Drug Abuse Prevention and Control Act, which has been the legal foundation of the U.S. government's fight against the abuse of amphetamines and other drugs since its passage. The Controlled Substances Act (CSA) is title II of that legislation. The CSA placed all drug substances that had been regulated under existing federal laws into one of five schedules based on the substance's medicinal value, harmfulness, and potential for abuse and addiction. Schedule I is reserved for the most dangerous drugs that have no recognized medical use. Amphetamines fall under Schedule II, dangerous drugs with useful and legitimate medical uses that also have a high potential for abuse and addiction.

See also Designer drugs; Ecstasy (MDMA); Methamphetamine; Methylphenidate

RESOURCES

Books

Bayer, Linda. Amphetamines and Other Uppers. Broomall, PA., Chelsea House Publishers, 2000.

Cobb, Alice B. Speed and Your Brain: The Incredibly Disgusting Story. New York: Rosen Publishing group, 2000.

Kuhn, Cynthia. Buzzed: The Straight Facts About the Most Used and Abused Drugs from Alcohol to Ecstacy. New York: W.W. Norton & Company, Inc., 1998.

Littell, Mary Ann. Speed and Methamphetamine Drug Dangers. Berkeley Heights, NJ: Enslow Publishers, Inc., 1999.

Pellowski, Michael J. Amphetamine Drug Dangers. Berkeley Heights, NJ: Enslow Publishers, Inc., 2001.

Periodicals

"All They Need is the Love Clinic: A Dallas Program Helps Kids to Say No to Sex and Drugs." Christianity Today 45, no. 15 (December 3, 2001): 62-65.

Gilbert, Laura. "Just Say Know: The Truth About Drugs." Teen Magazine 45, no. 7 (July 2001): 90.

"Kicking Drugs: A Recovery Diary: Stacia Litchfield Had It All-Including A Hardcore Drug Addiction That Drove Her To Trade Sex For A High. Now, After A Grueling Three Years In Rehab, She's Emerged-Clean And Ready For A New Life." Teen People 4, no. 16 (August 1, 2001): 138+.

Other

"Confessions of a Teenage Drug Addict." May 2001. <http://www.thailandlife.com/drugs/index.html>.

Stocker, Steven. "Overall Teen Drug Use Stays Level, Use of MDMA and Steroids Increases." NIDA Notes 15, no. 1 (March2000). <www.nida.gov>.

Organizations

American Council for Drug Education (ACDE), 204 Monroe Street, Rockville, MD, USA, 20852, (301) 294-0600, mail@add.org.

Narcotic Educational Foundation of America (NEFA), 28245 Avenue Crocker, Suite 230, Santa Clarita, CA, USA, 91355-1201, (661) 775-6968, mail@add.org, <http://www.cnoa.org/NEFA.htm>.

National Clearinghouse for Alcohol & Drug Information (NCADI), P.O. Box 2345, Rockville, MD, USA, 20852, (800) 729-6686, mail@add.org, <http://www.samhsa.gov/centers/clearinghouse/clearinghouses.html>.

National Families in Action, 2957 Clairmont Road, Suite 150, Atlanta, GA, USA, 30329, (404) 248-9676, mail@add.org, <http://www.emory.edu/NFIA/>.

Substance Abuse and Mental Health Services Administration (SAMHSA), U.S. Dept. of Health and Human Services, 5600 Fishers Lane, Rockville, MD, USA, 20857, (301)443-6239, (800) 622-Help, mail@add.org, <http://www.samhsa.gov/centers/clearinghouse/clearinghouses.html>.

University of Kentucky Center for Prevention Research, 1151 Red Mile Rd. Ste.1-A, Lexington, KY, USA, 40504, (606) 257-5588, <http://www.uky.edu/RGS/PreventionResearch/welcome.html>.

Maury M. Breecher, PhD, MPH

AMPHETAMINE

Amphetamine was first synthesized in 1887, but its central nervous system (CNS) stimulant effects were not noted at that time. After rediscovery, in the early 1930s, its use as a respiratory stimulant was established and its properties as a central nervous system stimulant were described. Reports of abuse soon followed. As had occurred with cocaine products when they were first introduced in the 1880s, amphetamine was promoted as being an effective cure for a wide range of ills without any risk of addiction. The medical profession enthusiastically explored the potentials of amphetamine, recommending it as a cure for everything from alcohol hangover and depression to the vomiting of pregnancy and weight reduction. These claims that it was a miracle drug contributed to public interest in the amphetamines, and they rapidly became the stimulant of choice—since they were inexpensive, readily available, and had a long duration of action.

Derivatives of amphetamine, such as Methamphetamine, were soon developed and both oral and intravenous preparations became available for therapeutic uses. Despite early reports of an occasional adverse reaction, enormous quantities were consumed in the 1940s and 1950s, and their liability for abuse was not recognized. During World War II, the amphetamines, including methamphetamine, were widely used as stimulants by the military in the United States, Great Britain, Germany, and Japan, to counteract fatigue, to increase alertness during battle and night watches, to increase endurance, and to elevate mood. It has been estimated that approximately 200 million Benzedrine (amphetamine) tablets were dispensed to the U.S. armed forces during World War II. In fact, much of the research on performance effects of the amphetamines was carried out on enlisted personnel during this period, as the various countries sought ways of maintaining an alert and productive armed force. Although amphetamine was found to increase alertness, little data were collected supporting its ability to enhance performance.

Since 1945, use of the amphetamines and Co-Caine appears to have alternated in popularity, with several stimulant epidemics occurring in the United States. There was a major epidemic of amphetamine and methamphetamine abuse (both oral and intravenous) in Japan right after the war. The epidemic was reported to have involved, at its peak, some half-million users and was related to the release with minimal regulatory controls of huge quantities of surplus amphetamines that had been made for use by the Japanese military. Despite this experience, there were special regulations governing their manufacture, sale, or prescription in the United States until 1964 (Kalant, 1973).

The first major amphetamine epidemic in the United States peaked in the mid-1960s, with approximately 13.5 percent of the university population estimated, in 1969, to have used amphetamines at least once. By 1978, use of the amphetamines had declined substantially, contrasting with the increase of cocaine use by that time. The major amphetamine of concern in the United States in the 1990s is methamphetamine, with pockets of "ice" (smoked methamphetamine) abuse.

Amphetamines are now controlled under Schedule II of the Controlled Substances Act. Substances classified within this schedule are found to have a high potential for abuse as well as currently accepted medical use within the United States. Amphetamine, methamphetamine, cocaine, Methylphenidate, and phenmetrazine are all stimulants included in this schedule.

MEDICAL UTILITY

Amphetamines are frequently prescribed for the treatment of narcolepsy, obesity, and for childhood Attention Deficit Disorder. They are clearly efficacious in the treatment of narcolepsy, one of the first conditions to be successfully treated with these drugs. Although patients with this disorder can require large doses of amphetamine for prolonged periods of time, attacks of sleep can generally be prevented. Interestingly, tolerance does not seem to develop to the therapeutic effects of these drugs, and most patients can be maintained on the same dose for years.

Although the amphetamines have been used extensively in the treatment of obesity, considerable evidence exists for a rapid development of tolerance to the anorectic (appetite loss) effects of this drug, with continued use having little therapeutic effect. These drugs are extremely effective appetite suppressants, but after several weeks of use the dose must be increased to achieve the same appetite-suppressant effect. People remaining on the amphetamines for prolonged periods of time to decrease food intake can reach substantial doses, resulting in toxic side effects (e.g., insomnia, irritability, increased heart rate and blood pressure, and tremulousness). Therefore, these drugs should only be taken for relatively short periods of time (4-6 weeks). In addition, long-term follow-up studies of patients who were prescribed amphetamines for weight loss have not found any advantage in using this medication to maintain weight loss. Data indicate that weight lost under amphetamine maintenance is rapidly gained when amphetamine use is discontinued. In addition to the lack of long-term efficacy, the dependence-producing effects of amphetamines make them a poor choice of maintenance medication for this problem.

The use of amphetamines in the treatment of attention deficit disorders in children, remains extremely controversial. It has been found that the amphetamines have a dramatic effect in reducing restlessness and distractibility as well as lengthening attention span, but there are side effects. These include reports of growth impairment in children, insomnia, and increases in heart rate. Those promoting their use point to their potential benefits and they advocate care in limiting treatment dose and duration. Opponents of their use, while agreeing that they provide some short-term benefits, conclude that these do not outweigh their disadvantages. Amphetamine therapy has also been attempted, but with little success, in the treatment of Parkinson's disease, and both amphetamine and cocaine have been suggested for the treatment of depression, although the evidence to support their efficacy does not meet current standards demanded by the U.S. Food and Drug Administration.

PHARMACOLOGY

The amphetamines act by increasing concentrations of the neurotransmitters Dopamine and Norepinephrine at the neuronal synapse, thereby augmenting release and blocking uptake. It is the augmentation of release that differentiates amphetamines from cocaine, which also blocks uptake of these transmitters. Humans given a single moderate dose of amphetamine generally show an increase in activity and talkativeness, and they report euphoria, a general sense of well-being, and a decrease in both food intake and fatigue. At higher doses repetitive motor activity (i.e., stereotyped behavior) is often seen, and further increases in dose can lead to convulsions, coma, and death. This class of drugs increases heart rate, respiration, diastolic and systolic blood pressure, and high doses can cause cardiac arrhythmias. In addition, the amphetamines have a suppressant effect on both rapid eye movement sleep (REM)—the stage of sleep associated with dreaming—and total sleep. The half-life of amphetamine is about ten hours, quite long when compared to a stimulant like cocaine, which has a half-life of approximately one hour, or even methamphetamine which has a half-life of about five hours.

The amphetamine molecule has two isomers: the d -(+) and l -(-) isomers. There is marked stereo-selectivity in their biological actions, with the d -isomer (dextroamphetamine) considerably more potent. For example, it is more potent as a locomotor stimulant, in inducing stereotyped behavior patterns, and in eliciting central nervous system excitatory effects. The isomers appear to be equipotent as cardiovascular stimulants. The basic amphetamine molecule has been modified in a number of ways to accentuate various of its actions. For example, in an effort to obtain appetite suppressants with reduced cardiovascular and central nervous system effects, structural modifications yielded such medications as diethylproprion and fenfluramine, while other structural modifications have enhanced the central nervous system stimulant effects and reduced the cardiovascular and anorectic actions, yielding medications such as methylphenidate and phenmetrazine. These substances share, to a greater or lesser degree, the properties of amphetamine.

TOXICITY

A major toxic effect of amphetamine in humans is the development of a schizophrenia-like psychosis after repeated long-term use. The first report of an amphetamine psychosis occurred in 1938, but the condition was considered rare. Administration of amphetamine to normal volunteers with no histories of psychosis (Griffith et al., 1968) resulted in a clear-cut paranoid psychosis in five of the six subjects who received d -amphetamine for one to five days (120-220 mg/day), which cleared when the drug was discontinued. Unless the user continues to take the drug, the psychosis usually clears within a week, although the possibility exists for prolonged symptomology. This amphetamine psychosis has been thought to represent a reasonably accurate model of schizophrenia, including symptoms of persecution, hyperactivity and excitation, visual and auditory hallucinations, and changes in body image. In addition, it has been suggested that there is sensitization to the development of a stimulant psychosis—once an individual has experienced this toxic effect, it is readily reinitiated, sometimes at lower doses and even following long drug-free periods.

Amphetamine abusers taking repeated doses of the drug can develop repetitive behavior patterns which persist for hours at a time. These can take the form of cleaning, the repeated dismantling of small appliances, or the endless picking at wounds on the extremities. Such repetitive stereotyped patterns of behavior are also seen in nonhumans administered repeated doses of amphetamines and other stimulant drugs, and they appear to be related to dopaminergic facilitation. Cessation of amphetamine use after high-dose chronic intake is generally accompanied by lethargy, depression, and abnormal sleep patterns. This pattern of behavior, opposite to the direct effects of amphetamine, does not appear to be a classical abstinence syndrome. The symptoms may be related to the long-term lack of sleep and food intake that accompany chronic stimulant use as well as to the catecholamine depletion that occurs as a result of chronic use.

Animals given unlimited access to amphetamine will self-administer it reliably, alternating days of high intake with days of low intake. They become restless, tremulous, and ataxic, eating and sleeping little. If allowed to continue self-administering the drug, most will take it until they die. Animals maintained on high doses of amphetamines develop tolerance to many of the physically and behaviorally debilitating effects, but they also develop irreversible damage in some parts of the brain, including long-lasting depletion of dopamine. It has been suggested that the prolonged anhedonia seen after long-term human amphetamine use may be related to this, although the evidence for this is not very strong.

BEHAVIORAL EFFECTS

Nonhumans.

As with all Psychomotor Stimulant drugs, at low doses animals are active and alert, showing increases in responding maintained by other reinforcers, but often decreasing food intake. Higher doses produce species-specific repetitive behavior patterns (stereotyped behavior), and further increases in dose are followed, as in humans, by convulsions, hyperthermia, and death. Tolerance (loss of response to a certain dose) develops to many of amphetamine's central effects, and cross-tolerance among the stimulants has been demonstrated in rats. Thus, for example, animals tolerant to the anorectic effects of amphetamine also show tolerance to cocaine's anorectic effects. Although there is tolerance development to many of amphetamine's effects, sensitization develops to amphetamine's effects on locomotor activity. Thus, with repeated administration, doses of amphetamine that initially did not result in hyperactivity or stereotypy can, with repeated use, begin to induce those behaviors when injected daily for several weeks. In addition, there is cross-sensitization to this effect, such that administration of one stimulant can induce sensitization to another one. In contrast to cocaine, however (in which an increased sensitivity to its convulsant effects develops with repeated use), amphetamines have an anticonvulsive effect.

Learned behaviors, typically generated by operant schedules of reinforcement, are generally affected by the amphetamines in a rate-dependent fashion. Thus, behaviors that occur at relatively low rates in the absence of the drug tend to be increased at low-to-moderate doses of amphetamine, while behaviors occurring at relatively high frequencies tend to be suppressed by those doses of amphetamine. In addition, with high doses most behaviors tend to be suppressed. As is seen with other stimulants, such as cocaine, environmental variables and behavioral context can play a role in modulating these effects. For example, behavior under strong stimulus control shows tolerance to repeated amphetamine administration much more rapidly than does behavior under weak stimulus control. In addition, if the amphetamine-induced behavioral disruption has the effect of interfering with reinforcement delivery, tolerance to that effect develops rapidly. Tolerance does not develop to the amphetamine-induced disruptions when reinforcement density is increased or remains the same.

Amphetamines can serve as reinforcers in nonhumans and, as described above, can produce severely toxic consequences when available in an unlimited fashion. However, when available for a few hours a day, animals will take them in a regular fashion, showing little or no tolerance to their reinforcing effects.

Humans.

A substantial number of studies have been carried out evaluating the effects of amphetamines on learning, cognition, and other aspects of performance. The data indicate that under most conditions the amphetamines are not general performance enhancers. When there is improvement in performance associated with amphetamine administration, it can usually be attributed to a reduction in the deterioration of performance due to fatigue or boredom. Attention lapses that impair performance after sleep deprivation appear to be reduced by amphetamine administration; however, as sleep deprivation is prolonged, this effect is reduced. A careful review of the literature in this area (Laties & Weiss, 1981) concluded that improvement is more obvious with complex, as compared with simple, tasks.

In addition, in trained athletes, whose behavior shows little variability, only very small improvements can be seen. Laties and Weiss have argued persuasively, however, that the small changes in performance induced by amphetamines can result in the 1 to 2 percent improvement that may make the difference in a close athletic competition. Although the facilitation in performance after amphetamine does not appear to be substantial, it is sufficient to "spell the difference between a gold medal" and any other. Unfortunately, such data have led athletes to take stimulants prior to athletic events, particularly those in which strenuous activity is required over prolonged periods (e.g., bicycle racing), leading to hyperthermia, collapse, and even death in some cases.

The mood-elevating effects of the amphetamines are generally believed to be related to their abuse. Their use is accompanied by reports of increased self-confidence, elation, frequently euphoria, friendliness, and positive mood. When amphetamine is administered repeatedly, tolerance develops rapidly to many of its subjective effects (such that the same dose no longer exerts much of an effect). This means that the user must take increasingly larger amounts of amphetamine to achieve the same effect. As with nonhuman research subjects, there is however, little or no evidence for the development of tolerance to amphetamine's reinforcing effects.

Experienced stimulant users, given a variety of stimulant drugs, often cannot differentiate among cocaine, amphetamine, methamphetamine, and methlyphenidate—all of which appear to have similar profiles of action. Since these drugs have different durations of action, however, it becomes easier to make this differentiation over time.

ABUSE

In the United States in the 1950s, nonmedical amphetamine use was prevalent among college students, athletes, truck drivers, and housewives. The drug was widely publicized by the media when very little evidence of amphetamine toxicity was available. Pills were the first form to be widely abused. Use of the drug expanded as production of amphetamine and methamphetamine increased significantly, and abusers began to inject it. An extensive black market in amphetamines developed, and it has been estimated that 50 to 90 percent of the quantity commercially produced was diverted into illicit channels. In the 1970s, manufacture of amphetamines was substantially curtailed, amphetamines were placed in Schedule II of the Controlled Substances Act, and abuse of these substances was substantially reduced. Perhaps only by coincidence, as amphetamine use declined, cocaine use increased.

The amphetamines, as with other stimulants, are generally abused in multiple-dose cycles (i.e., binges), in which people take the drug repeatedly for some period of time, followed by a period in which they take no drug. Amphetamines are often taken every three or four hours for periods as long as three or four days, and dosage can escalate dramatically as tolerance develops. Like cocaine binges, these amphetamine-taking occasions are followed by a "crash" period in which the user sleeps, eats, and does not use the drug. Abrupt cessation from amphetamine use is usually accompanied by depression. Mood generally returns to normal within a week, although craving for the drug can last for months.

There is little evidence for the development of physical dependence to the amphetamines. Although some experts view the "crash" (with lethargy, depression, exhaustion, and increased appetite) that can follow a few days of moderate-to-high dose use as meeting the criteria for a withdrawal syndrome, others believe that the symptoms can also be related to the effects of chronic stimulant use. When using stimulants people do not eat or sleep very much and, as well, catecholamine depletion may well be contributing to these behavioral changes.

TREATMENT

As of the mid-1990s, little information is available about the treatment of amphetamine abusers, and no reports of successful pharmacological interventions exist in the treatment literature. As with cocaine abuse, the most promising nonpharmacological approaches include behavioral therapy, Relapse Prevention, rehabilitation (e.g., vocational, educational, and social-skills training), and supportive psychotherapy. Unlike cocaine, however, minimal clinical trials with potential treatment medications for amphetamine abuse have been carried out. The few that have been attempted report no success in reducing a return to amphetamine use.

(See also: Amphetamine Epidemics ; Pharmacokinetics ; Treatment )

BIBLIOGRAPHY

Angrist, B., & Sudilovsky, A. (1978). Central nervous system stimulants: Historical aspects and clinical effects. In L. L. Iversen, S. D. Iverson, & S. H. Snyder (Eds.), Handbook of psychopharmacology. New York: Plenum.

Griffith, J. D., et al. (1970). E. Costa and S. Garattini (Eds.), Amphetamines and related compounds. New York: Raven Press.

Grilly, D. M. (1989). Drugs and human behavior. Needham, MA: Allyn & Bacon.

Kalant, O. J. (1973). The amphetamines: Toxicity and addiction. Springfield, IL: Charles C. Thomas.

Laties, V.G., & Weiss, B. (1981). Federation proceedings, 40, 2689-2692.

Marian W. Fischman

Amphetamines

History

Ice

Action

Physical and psychological effects

Treatment

Resources

Amphetamines are a group of nervous system stimulants that includes amphetamine (alpha-methylphenethylamine), dextroamphetamine, and methamphetamine. They are used to induce a state of alert wakefulness and euphoria, and since they inhibit appetite, they also serve as diet pills. Sometimes they are used recreationally and for performance enhancement.

After World War II (1939–1945), they were widely prescribed by physicians as diet pills, but they are generally no longer recommended for weight loss programs since there are too many hazards in the prolonged use of amphetamines. Prolonged exposure may result in organ impairment, affecting particularly the kidneys. Amphetamines are addictive and may lead to compulsive behavior, hallucinations, paranoia, and suicidal actions. Their medical use has currently been narrowed to treating only two disorders. One is a condition known as attention-deficit hyperactivity disorder (ADHD) in children. When used to treat over-active children, amphetamines are carefully administered under controlled situations as part of a larger program. The other condition for which amphetamines are prescribed is a sleep disorder known as narcolepsy, the sudden uncontrollable urge to sleep during the hours of wakefulness.

In street language, amphetamines are known as pep pills, as speed (when injected), and as ice (when smoked in a crystalline form). The popularity of amphetamines as a street drug appears to have been facilitated originally by pilfering from the drug companies manufacturing the pills. They are now also illegally manufactured in secret laboratories.

History

Amphetamines were first synthesized in 1887 by Romanian chemist Lazar Edeleanu (1861–1941), while at the University of Berlin (Germany). They was further developed by the drug company Smith, Kline and French in that same year. However, amphetamines were not marketed until 1932, however, as Benzedrine^® inhalers for relief from nasal congestion due to hay fever, colds, or asthma. In 1935, after noting its stimulant effects, the drug company encouraged prescription of the drug for the chronic sleep disorder narcolepsy. Clinical enthusiasm for the drug led to its misapplication for the treatment of various conditions, including addiction to opiates. The harmful effects of the drug were first noted by the British press and, in 1939, amphetamines were placed on a list of toxic substances for the United Kingdom.

The early abuse of Benzedrine^® inhalers involved the removal of the strip containing the amphetamines from the casing of the inhaler. The strips were then either chewed or placed in coffee to produce an intense stimulant reaction. Since the inhalers were inexpensive and easily obtainable at local drug stores, they were purchased by young people searching for ways of getting stimulated (high). But amphetamines became particularly popular in World War II. Soldiers on both sides were given large amounts of amphetamines as a way of fighting fatigue and boosting morale. The British issued 72 million tablets to the armed forces. Records also show that kamikaze pilots and German panzer troops were given large doses of the drug to motivate their fighting spirit. Adolph Hitler’s own medical records show that he received eight injections a day of methamphetamine, a drug known to create paranoia and unpredictable behavior when administered in large dosages.

The demand for amphetamines was high in the 1950s and early 1960s. They were used by people who had to stay awake for long periods of time. Truck drivers who had to make long hauls used them to drive through the night. Those who had long tours of duty in the armed forces relied on them to stay awake. High school and college students cramming for tests took them to study through the nights before their examinations. Athletes looked to amphetamines for more energy, while English and American popular musicians structured their lives and music around them. The U.S. Food and Drug Administration (FDA) estimated that there were well over 200 million amphetamine pills in circulation by 1962 in the United States alone.

During that period of time about half of the quantity of amphetamines produced were used outside of the medically prescribed purposes mandated by the legal system. Of the 19 companies producing amphetamines then, nine were not required to show their registry of buyers to the FDA. It is believed that these nine companies supplied much of the illegal traffic in amphetamines for that period.

By 1975, a large number of street preparations were being passed off as amphetamine tablets. Tests indicated that only about 10% of the street drugs represented as amphetamines contained any amphetamine substance at all. The false amphetamines were in fact mixtures of caffeine and other drugs that resembled amphetamine, such as phenethylamine, an over-the-counter drug used to relieve coughs and asthma or to inhibit appetite. Other false amphetamine tablets contained such over-the-counter drugs as ephedrine and pseudoephedrine. These bootleg preparations came under such names as Black Beauty, Hustler, and Penthouse, and they were promoted in magazines that catered to counterculture sentiment.

The use of amphetamines and drugs like amphetamine showed a sharp decrease in the 1980s. The decrease was probably due to the increasing use of cocaine, which was introduced in the mid-1970s and continues to be a major street drug at the present time. Another reason was the introduction of newer types of appetite suppressants and stimulants on the pharmacological market and then to the street trade. Still, a survey done in 1987 showed that a large number of high school seniors (12%) had used drugs of the amphetamine type during the previous year.

Ice

Illegal users of methamphetamine originally took the drug in pill form or prepared it for injection. More recently, however, a crystalline form of the drug that is smoked like crack cocaine has appeared on the market. The practice of smoking methamphetamine began in Hawaii and, then, spread to California. Various names are given to smokable methamphetamine, such as Ice, LA Ice, and Crank. Ice is much cheaper than crack because it is made from easily available chemicals and does not require complicated equipment for its production. An illegal drug manufacturer can produce ice at a much lower cost than cocaine and therefore realize a much greater profit margin. Like cocaine, amphetamine reaches the brain faster when it is smoked. Users have begun to prefer ice over crack because the high lasts much longer, persisting for well over 14 hours. The side effects of an ice high can be quite severe, however. Side effects such as paranoia, hallucinations, impulsive behavior, and other psychotic effects may last for several days after a prolonged high from ice.

Action

Amphetamines, according to recent research, act on the neurotransmitters of the brain to produce their mood-altering effects. The two main neurotransmitters affected are dopamine and norepinephrine, produced by cells in the brain. Amphetamines appear to stimulate the production of these two neurotransmitters and then prevent their uptake by other cells. They further increase the amount of surplus neurotransmitters by inhibiting the action of enzymes that help to absorb them into the nervous system. It is believed that the excess amount of neurotransmitters caused by the amphetamines are also responsible for the behavioral changes that follow a high.

Drugs that pose a high risk of addiction like amphetamines, opiates, and cocaine all seem to arouse the centers of the brain that control the urge to seek out pleasurable sensations. Addictive drugs overcome those centers and displace the urge to find pleasure in food, sex, or sleep, or other types of activity that motivate people not addicted to drugs. The drug addict’s primary concern is to relive the pleasure of the drug high, even at the risk of crashing (coming down from the high in a painful way) and in the face of the social disapproval the habit inevitably entails. Laboratory experiments have shown that animals self-administering amphetamines will reject food and water in favor of the drug. They eventually perish in order to keep up their supply of the drug.

Withdrawal symptoms for chronic users include depression, anxiety, and the need for prolonged periods of sleep.

Physical and psychological effects

Amphetamines inhibit appetite and stimulate respiration as a result. On an oral dose of 10 to 15 mg daily an individual feels more alert and more confident in performing both physical and mental work and is able to show an increase in levels of activity. It has not been determined how the drug affects the quality of work done under its influence. The drug also results in a rise in bloodpressure and an increased, though sometimes irregular, heartrate.

Psychological dependency arises from the desire to continue and heighten the euphoric effects of the drug. During an amphetamine euphoria, the individual feels an enlargement of physical, mental, and sexual powers along with the absence of the urge to eat or sleep. Those who inject the drug feel a rush of the euphoric effect moments after the injection. They will feel energized and focused in an unusual way.

Depending on the user’s medical history, the dosage, and the manner in which the drug was delivered to the body, a number of toxic effects can accompany amphetamine abuse. Large intravenous dosages can lead to delirium, seizures, restlessness, the acting out of paranoic fantasies, and hallucinations. In hot weather there is a danger of heat stroke, since amphetamines raise the body temperature. The increased blood pressure can lead to stroke. Heart conditions such as arrhythmia (irregular heartbeat) can develop and become fatal, especially for those with heart disease. Since the dosage levels of street drugs are not reliable, it is possible to overdose unknowingly when using the drug intravenously. The results can be coma and death. Chronic users will show much weight loss and chronic skin lesions. Those who are shooting up (injecting) street versions of amphetamine face the further dangers from contaminated substances, adulterations in the chemicals used, and a lack of sterilized needles. These conditions carry the same risks associated with heroin use, such as hepatitis

KEY TERMS

AIDS— Acquired immunodeficiency syndrome; a fatal viral disease contracted by a virus transmitted through the blood or body fluids.

Attention-deficit hyperactivity disorder (ADHD)— A childhood condition marked by extreme restlessness and the inability to concentrate, which is sometimes treated with amphetamines.

Crashing— Coming down from a prolonged drug high such as that produced by amphetamines.

Euphoria— Feelings of elation and well being produced by drugs like amphetamines.

HIV— Human immunodeficiency virus, which leads to AIDS.

Ice— Crystalline methamphetamine that is smoked to produce a high.

Neurotransmitters— Chemicals produced in the brain, which are responsible for different emotional states.

Paranoia— Delusions of persecution; one of the main psychotic conditions produced by an excess use of amphetamines.

Speed— An injectable form of methamphetamine.

Tranquilizers— Drugs used to pacify anxiety attacks.

and infections to vital organs, along with irreversible damage to blood vessels. Contaminated needles may also transmit HIV (human immunodeficiency virus) that causes AIDS (acquired immunodeficiency syndrome).

Treatment

It takes several days to help a person recover from an acute amphetamine reaction. It is important to control body temperature and to reassure a person undergoing the psychological effects of the drug. In order to control violent behavior, tranquilizers are administered to quiet the patient. Treatment of the depression, which is an after-effect of heavy usage, is also required. Patients will seek to deal with the fatigue that comes after the body has eliminated the drug by resuming its use. A long-term program for maintaining abstinence from the drug has to be adhered to. Just as in the case of recovery from alcoholism and other forms of drug abuse, recovering addicts benefit from support groups.

Resources

BOOKS

Conolly, Sean. Amphetamines (Just the Facts). Oxford, UK: Heinemann Library, 2000.

Ecstasy and Amphetamines: Global Survey 2003. Vienna, Austria: United Nations Office on Drugs and Crime, 2003.

Klaassen, Curtis D. Casarett and Doull’s Toxicology. 6th ed. Columbus, OH: McGraw-Hill, Inc., 2001.

Iversen, Leslie L. Speed, Ecstasy, Ritalin: The Science of Amphetamines. Oxford, UK, and New York: Oxford University Press, 2006.

Obert, Jeanne L. A Clinician’s Guide to Methamphetamine. Center City, MN: Hazelden, 2005.

O’Neil, Maryadele J. Merck Index: An Encyclopedia of Chemicals, Drugs, & Biologicals. 13th ed. Whitehouse Station, NJ: Merck & Co., 2001.

PERIODICALS

Kiefer, D.M. “Chemistry Chronicles: Miracle Medicines.” Today’s Chemist 10, no. 6 (June 2001): 59-60.

Steele, M.T. “Screening for Stimulant Use in Adult Emergency Department Seizure Cases.” Journal of Toxocology 38, no.6 (2001): 609-613.

Jordan Richman

Amphetamines

Amphetamines are a group of nervous system stimulants that includes amphetamine, dextroamphetamine, and methamphetamine. They are used to induce a state of alert wakefulness and euphoria, and since they inhibit appetite, they also serve as diet pills. After World War II, they were widely prescribed by physicians as diet pills, but they are generally no longer recommended for weight loss programs since there are too many hazards in the prolonged use of amphetamines. Prolonged exposure may result in organ impairment, affecting particularly the kidneys. Amphetamines are addictive and may lead to compulsive behavior , hallucinations, paranoia, and suicidal actions. Their medical use has currently been narrowed to treating only two disorders. One is a condition known as attention-deficit hyperactivity disorder (ADHD) in children. When used to treat overactive children, amphetamines are carefully administered under controlled situations as part of a larger program. The other condition for which amphetamines are prescribed is a sleep disorder known as narcolepsy, the sudden uncontrollable urge to sleep during the hours of wakefulness.

In street language, amphetamines are known as pep pills, as speed (when injected), and as ice (when smoked in a crystalline form). The popularity of amphetamines as a street drug appears to have been facilitated originally by pilfering from the drug companies manufacturing the pills. They are now also illegally manufactured in secret laboratories.

History

Amphetamines were first synthesized in 1887 by the drug company Smith, Kline and French. They were not marketed until 1932, however, as Benzedrine inhalers for relief from nasal congestion due to hay fever, colds, or asthma . In 1935, after noting its stimulant effects, the drug company encouraged prescription of the drug for the chronic sleep disorder narcolepsy. Clinical enthusiasm for the drug led to its misapplication for the treatment of various conditions, including addiction to opiates. The harmful effects of the drug were first noted by the British press, and in 1939 amphetamines were placed on a list of toxic substances for the United Kingdom.

The early abuse of Benzedrine inhalers involved the removal of the strip containing the amphetamines from the casing of the inhaler. The strips were then either chewed or placed in coffee to produce an intense stimulant reaction. Since the inhalers were inexpensive and easily obtainable at local drug stores, they were purchased by young people searching for ways of getting "high." But amphetamines became particularly popular in World War II. Soldiers on both sides were given large amounts of amphetamines as a way of fighting fatigue and boosting morale. The British issued 72 million tablets to the armed forces. Records also show that kamikaze pilots and German panzer troops were given large doses of the drug to motivate their fighting spirit. Hitler's own medical records show that he received eight injections a day of methamphetamine, a drug known to create paranoia and unpredictable behavior when administered in large dosages.

The demand for amphetamines was high in the 1950s and early 1960s. They were used by people who had to stay awake for long periods of time. Truck drivers who had to make long hauls used them to drive through the night. Those who had long tours of duty in the armed forces relied on them to stay awake. High school and college students cramming for tests took them to study through the nights before their examinations. Athletes looked to amphetamines for more energy , while English and American popular musicians structured their lives and music around them. The Food and Drug Administration (FDA) estimated that there were well over 200 million amphetamine pills in circulation by 1962 in the United States alone.

During that period of time about half of the quantity of amphetamines produced were used outside of the medically prescribed purposes mandated by the legal system. Of the 19 companies producing amphetamines then, nine were not required to show their registry of buyers to the FDA. It is believed that these nine companies supplied much of the illegal traffic in amphetamines for that period.

By 1975 a large number of street preparations were being passed off as amphetamine tablets. Tests indicated that only about 10% of the street drugs represented as amphetamines contained any amphetamine substance at all. The false amphetamines were in fact mixtures of caffeine and other drugs that resembled amphetamine, such as phenethylamine, an over-the-counter drug used to relieve coughs and asthma or to inhibit appetite. Other false amphetamine tablets contained such over-thecounter drugs as ephedrine and pseudoephedrine. These bootleg preparations came under such names as Black Beauty, Hustler, and Penthouse, and they were promoted in magazines that catered to counterculture sentiment.

The use of amphetamines and drugs like amphetamine showed a sharp decrease in the 1980s. The decrease was probably due to the increasing use of cocaine , which was introduced in the mid-1970s and continues to be a major street drug at the present time. Another reason was the introduction of newer types of appetite suppressants and stimulants on the pharmacological market and then to the street trade. Still, a survey done in 1987 showed that a large number of high school seniors (12%) had used drugs of the amphetamine type during the previous year.

Ice

Illegal users of methamphetamine originally took the drug in pill form or prepared it for injection. More recently, however, a crystalline form of the drug that is smoked like crack cocaine has appeared on the market. The practice of smoking methamphetamine began in Hawaii and then spread to California. Various names are given to smokable methamphetamine, such as Ice, LA Ice, and Crank. Ice is much cheaper than crack because it is made from easily available chemicals and does not require complicated equipment for its production. An illegal drug manufacturer can produce ice at a much lower cost than cocaine and therefore realize a much greater profit margin. Like cocaine, amphetamine reaches the brain faster when it is smoked. Users have begun to prefer ice over crack because the high lasts much longer, persisting for well over 14 hours. The side effects of an ice high can be quite severe, however. Side effects such as paranoia, hallucinations, impulsive behavior, and other psychotic effects may last for several days after a prolonged high from ice.

Action

Amphetamines, according to recent research, act on the neurotransmitters of the brain to produce their mood-altering effects. The two main neurotransmitters affected are dopamine and norepinephrine, produced by cells in the brain. Amphetamines appear to stimulate the production of these two neurotransmitters and then prevent their uptake by other cells. They further increase the amount of surplus neurotransmitters by inhibiting the action of enzymes that help to absorb them into the nervous system. It is believed that the excess amount of neurotransmitters caused by the amphetamines are also responsible for the behavioral changes that follow a high.

Drugs that pose a high risk of addiction like amphetamines, opiates, and cocaine all seem to arouse the centers of the brain that control the urge to seek out pleasurable sensations. Addictive drugs overcome those centers and displace the urge to find pleasure in food, sex, or sleep, or other types of activity that motivate people not addicted to drugs. The drug addict's primary concern is to relive the pleasure of the drug high, even at the risk of "crashing" (coming down from the high in a painful way) and in the face of the social disapproval the habit inevitably entails. Laboratory experiments have shown that animals self-administering amphetamines will reject food and water in favor of the drug. They eventually perish in order to keep up their supply of the drug.

Withdrawal symptoms for chronic users include depression , anxiety , and the need for prolonged periods of sleep.

Physical and psychological effects

Amphetamines inhibit appetite and stimulate respiration as a result. On an oral dose of 10-15 mg daily an individual feels more alert and more confident in performing both physical and mental work and is able to show an increase in levels of activity. It has not been determined how the drug affects the quality of work done under its influence. The drug also results in a rise in blood pressure and an increased, though sometimes irregular, heart rate .

Psychological dependency arises from the desire to continue and heighten the euphoric effects of the drug. During an amphetamine euphoria, the individual feels an enlargement of physical, mental, and sexual powers along with the absence of the urge to eat or sleep. Those who inject the drug feel a "rush" of the euphoric effect moments after the injection. They will feel energized and focused in an unusual way.

Depending on the user's medical history, the dosage, and the manner in which the drug was delivered to the body, a number of toxic effects can accompany amphetamine abuse. Large intravenous dosages can lead to delirium, seizures, restlessness, the acting out of paranoic fantasies, and hallucinations. In hot weather there is a danger of heat stroke, since amphetamines raise the body temperature . The increased blood pressure can lead to stroke. Heart conditions such as arrhythmia (irregular heartbeat) can develop and become fatal, especially for those with heart disease . Since the dosage levels of street drugs are not reliable, it is possible to overdose unknowingly when using the drug intravenously. The results can be coma and death. Chronic users will show much weight loss and chronic skin lesions. Those who are "shooting up" (injecting) street versions of amphetamine face the further dangers from contaminated substances, adulterations in the chemicals used, and a lack of sterilized needles. These conditions carry the same risks associated with heroin use, such as hepatitis and infections to vital organs, along with irreversible damage to blood vessels. Contaminated needles may also transmit the HIV virus that causes AIDS .

Treatment

It takes several days to help a person recover from an acute amphetamine reaction. It is important to control body temperature and to reassure a person undergoing the psychological effects of the drug. In order to control violent behavior, tranquilizers are administered to quiet the patient. Treatment of the depression which is an after-effect of heavy usage is also required. Patients will seek to deal with the fatigue that comes after the body has eliminated the drug by resuming its use. A long-term program for maintaining abstinence from the drug has to be adhered to. Just as in the case of recovery from alcoholism and other forms of drug abuse, recovering addicts benefit from support groups.

Resources

books

Clayton, Lawrence. Amphetamines and Other Stimulants. New York: Rosen Publishing Group, 1998.

Conolly, Sean. Amphetamines (Just the Facts). Oxford: Heinemann Library, 2000.

Klaassen, Curtis D. Casarett and Doull's Toxicology. 6th ed. Columbus: McGraw-Hill, Inc., 2001.

O'Neil, Maryadele J. Merck Index: An Encyclopedia of Chemicals, Drugs, & Biologicals. 13th ed. Whitehouse Station, NJ: Merck & Co., 2001.

Shapiro, Harry. Waiting for the Man. New York: William Morrow, 1988.

Stimmel, Barry. The Facts About Drug Use. New York: Haworth Medical Press, 1991.

periodicals

Chan, Paul, et al. "Fatal and Nonfatal Methamphetamine Intoxication in the Intensive Care Unit." Journal of Toxicology: Clinical Toxicology 32 (June 1994): 147-56.

Kiefer, D.M. "Chemistry Chronicles: Miracle Medicines." Today's Chemist 10, no. 6 (June 2001): 59-60.

Steele, M.T. "Screening for Stimulant Use in Adult Emergency Department Seizure Cases." Journal of Toxocology 38, no.6 (2001): 609-613.

Jordan Richman

KEY TERMS

AIDS

—Acquired immunodeficiency syndrome; a fatal viral disease contracted by a virus transmitted through the blood or body fluids.

Attention-deficit hyperactivity disorder (ADHD)

—A childhood condition marked by extreme restlessness and the inability to concentrate, which is sometimes treated with amphetamines.

Crashing

—Coming down from a prolonged drug high such as that produced by amphetamines.

Euphoria

—Feelings of elation and well being produced by drugs like amphetamines.

HIV

—Human immunodeficiency virus, which leads to AIDS.

Ice

—Crystalline methamphetamine that is smoked to produce a high.

Neurotransmitters

—Chemicals produced in the brain, which are responsible for different emotional states.

Paranoia

—Delusions of persecution; one of the main psychotic conditions produced by an excess use of amphetamines.

Speed

—An injectable form of methamphetamine.

Tranquilizers

—Drugs used to pacify anxiety attacks.