History and culture of substituted amphetamines
and methamphetamine are central nervous system stimulants used to treat a variety of conditions. When used recreationally, they are colloquially known as "speed" or sometimes "crank". Amphetamine was first synthesized in 1887 in Germany by Romanian chemist Lazăr Edeleanu, who named it phenylisopropylamine. Around the same time, Japanese organic chemist Nagai Nagayoshi isolated ephedrine from the Chinese ephedra plant and later developed a method for ephedrine synthesis. Methamphetamine was synthesized from ephedrine in 1893 by Nagayoshi. Neither drug had a pharmacological use until 1934, when Smith, Kline & French began selling amphetamine as an inhaler under the trade name Benzedrine for congestion.
During World War II, amphetamine and methamphetamine were used extensively by Allied and Axis forces for their stimulant and performance-enhancing effects. As the addictive properties of the drugs became known, governments began to place strict controls on these drugs. On October 27, 1970, with the enactment of the Controlled Substances Act, amphetamine was made a Schedule III controlled substance in the United States, but it was later moved to Schedule II. Amphetamine is currently indicated in the United States for ADHD and narcolepsy, with lisdexamfetamine indicated for binge eating disorder; and methamphetamine is indicated for ADHD, though prescribed at significantly lower rates compared to amphetamine.
Despite strict government controls, recreational amphetamine and methamphetamine use is extremely prevalent worldwide. Due to the large underground market for these drugs, they are often illegally synthesized by clandestine chemists, trafficked, and sold on the black market. Based on seizures of drugs and precursor chemicals, illicit amphetamine production and trafficking is much less prevalent than that of methamphetamine.
History of amphetamine and methamphetamine
Amphetamine was first synthesized in 1887 in Germany by Romanian chemist, Lazăr Edeleanu, who named the drug phenylisopropylamine. This concoction was one of a series of compounds related to the plant derivative ephedrine, which had been isolated from the Chinese ephedra plant that same year by Nagai Nagayoshi. Shortly after the first synthesis of amphetamine, Nagai synthesized methamphetamine from ephedrine in 1893. In 1919, methamphetamine hydrochloride, also known as crystal meth, was synthesized by pharmacologist Akira Ogata via reduction of ephedrine using red phosphorus and iodine. The sympathomimetic properties of amphetamine were unknown until 1927, when pioneer psychopharmacologist Gordon Alles independently resynthesized it and tested it on himself while searching for an artificial replacement for ephedrine. At the time, Alles referred to the amphetamine compound as Benzedrine, a term derived from the name benzyl-methyl carbinamine. In 1934, Smith, Kline & French made the first amphetamine pharmaceutical when they began selling a decongestant inhaler containing the volatile amphetamine free base under the trade name Benzedrine. One of the first attempts at using amphetamine in a scientific study was done by M. Nathanson, a Los Angeles physician, in 1935. He studied the subjective effects of amphetamine in 55 hospital workers who were each given 20 mg of Benzedrine. The two most commonly reported drug effects were "a sense of well being and a feeling of exhilaration" and "lessened fatigue in reaction to work".During World War II, both the Allied and Axis forces experimented with giving amphetamine and methamphetamine to select servicemen for their stimulant and performance-enhancing effects. In the 1950s, there was a rise in the legal prescription of methamphetamine to the American public. Methamphetamine constituted half of the amphetamine salts for the original formulation for the diet drug Obetrol. Methamphetamine was also marketed for sinus inflammation or non-medicinal purposes as "pep pills" or "bennies". A thriving black market in pep pills among long-haul truck drivers in the 1950s and 1960s, linked to long drive times and intense competitive pressures within the industry, contributed to federal efforts by the late 1960s to curtail non-medical use of the substance.
Also in the 1950s, the Japanese Ministry of Health banned stimulant production, although drug companies continued to produce stimulants that wound up on the black market. From 1951 to 1954, a series of acts were passed by the Japanese government to try to stop the production and sale of stimulants; however, the production and sale of stimulant drugs continued through criminal syndicates such as Yakuza criminal organizations. On the streets, it is also known as S, Shabu, and Speed, in addition to its old trademarked name.
The United States in the 1960s saw the start of significant use of clandestinely manufactured methamphetamine, most of which was produced by motorcycle gangs. A notable part of the 1960s mod subculture in the UK was recreational amphetamine use, which was used to fuel all-night dances at clubs like Manchester's Twisted Wheel. Newspaper reports described dancers emerging from clubs at 5 a.m. with dilated pupils. Mods used the drug for stimulation and alertness, which they viewed as different from the intoxication caused by alcohol and other drugs. Dr. Andrew Wilson argues that for a significant minority, "amphetamines symbolised the smart, on-the-ball, cool image" and that they sought "stimulation not intoxication greater awareness, not escape" and "confidence and articulacy" rather than the "drunken rowdiness of previous generations." Wilson argues that the significance of amphetamines to the mod culture was similar to that of LSD and cannabis within the subsequent hippie counterculture. Dick Hebdige argues that mods used amphetamines to extend their leisure time into the early hours of the morning and as a way of bridging the gap between their hostile and daunting everyday work lives and the "inner world" of dancing and dressing up in their off-hours.
After decades of reported abuse, in 1965 the United States Food and Drug Administration limited amphetamine to prescription use, but non-medical use remained common. Amphetamine became a schedule III controlled substance in the U.S. under the Controlled Substances Act in 1971. That same year, the United Nations enacted the Convention on Psychotropic Substances, and amphetamine became a schedule II controlled substance, a highly restrictive category under the treaty. By the 1990s, roughly 180 state parties were signatories to the treaty and consequently, it became heavily regulated in most countries. Beginning in the 1990s in the United States, the production of methamphetamine in users' own homes for personal use became popular as well.
In 1997 and 1998, researchers at Texas A&M University claimed to have found amphetamine and methamphetamine in the foliage of two Acacia species native to Texas, A. berlandieri and A. rigidula. Previously, both of these compounds had been thought to be purely synthetic. These findings have never been duplicated and consequently the validity of the report has come into question.
Substituted amphetamine use has historically been especially common among Major League Baseball players and is usually known by the slang term "greenies". In 2006, the MLB banned the use of amphetamine. The ban is enforced through periodic drug-testing. However, the MLB has received some criticism because the punitive consequences for amphetamine use are dramatically less severe than for anabolic steroid use, with the first offense bringing only a warning and further testing.
Methamphetamine was formerly in widespread use by truck drivers to combat symptoms of somnolence and to increase their concentration during driving, especially in the decades prior to the signing by former president Ronald Reagan of Executive Order 12564, which initiated mandatory random drug testing of all truck drivers and employees of other DOT-regulated industries.
Up to a quarter of college students use Adderall to help them focus on their studies instead of its intended purpose of helping people with ADHD. This use sometimes continues after the student graduates college due to its addictive properties.
In recent decades, amphetamines, especially Adderall, have been increasingly used by young white-collar workers who work long hours at demanding work. Many felt drug use was necessary to perform adequately. In the period following the Covid-19 pandemic prescription of ADHD medication increased by over 14%, contributing to shortages of Adderall which reach their peak during October of 2022. Young adults and women make up a notable proportion of these new prescriptions.
Military use
One of the earliest uses of amphetamine and methamphetamine was during World War II when they were used by Axis and Allied forces.As early as 1919, Akira Ogata synthesized methamphetamine via reduction of ephedrine using red phosphorus and iodine. Later, the chemists Hauschild and Dobke from the German pharmaceutical company Temmler developed an easier method for converting ephedrine to methamphetamine. As a result, Temmler could market it on a large scale as a nonprescription drug under the trade name Pervitin. Pervitin was commonly used by the German and Finnish militaries. Adolf Hitler is rumored to have begun using amphetamine occasionally after 1937, and to have become addicted to it in late 1942; although this is disputed by historians who argue he was suffering from health issues.
It was widely distributed across German military ranks and divisions, from elite forces to tank crews and aircraft personnel, with millions of tablets being distributed for its stimulant effects and to induce extended wakefulness.
More than 35 million three-milligram doses of Pervitin were manufactured for the German army and air force between April and July 1940; however, this amounts to only three tablets per serviceman a month. Use of Pervitin was restricted by the Wehrmacht and Nazi Germany as a whole under the Opium Law, which required the drug be obtained through a physician's prescription.
After April 1941 the drug was no longer distributed to servicemen on a mass scale due to its dangerous side effects, and several deaths were attributed to Pervitin. Use continued albeit closely monitored. In the military, Pervitin was discouraged during combat due to its negative side effects, it was more commonly abused behind the front lines.
Despite the new controls, authorities observed that Pervitin consumption rose rapidly, and so did civilian production, from about seven and a half million tablets in 1941 to nine million tablets in 1942 and a similar amount the following year, to eight million tablets in 1944. As a rule, military production was about half of civilian production. These numbers can be misleading as Nazi Germany had a population of over 80 million during the war, individuals acquired only small numbers of doses at a time and were required to report usage to the authorities.
In Japan, methamphetamine was sold under the registered trademark of Philopon by Dainippon Pharmaceuticals for civilian and military use. It has been estimated that one billion Philopon pills were produced between 1939 and 1945. As with the rest of the world at the time, the side effects of methamphetamine were not well studied, and regulation was not seen as necessary. In the 1940s and 1950s, the drug was widely administered to Japanese industrial workers to increase their productivity. In Finland, Pervitin was colloquially known as höökipulveri. Its use was essentially restricted to special forces, especially to long-range commandos.
Amphetamine was also given to Allied bomber pilots during World War II to sustain them by fighting off fatigue and enhancing focus during long flights. During the Persian Gulf War, amphetamine became the drug of choice for American bomber pilots, being used voluntarily by roughly half of U.S. Air Force pilots. The Tarnak Farm incident during the War in Afghanistan, in which an American F-16 pilot killed several friendly Canadian soldiers on the ground, was blamed by the pilot on his use of amphetamine. A nonjudicial U.S. Air Force hearing rejected the pilot's claim.
The USAF banned the use of dextroamphetamine, and due to amphetamines' addiction potential in some people, newer wakefulness-promoting drugs such as modafinil have been seen as possible safer alternatives for military use in some countries, including the United States.