Prescription amphetamines have been used for short periods of time in weight-control programs to suppress appetite and to treat narcolepsy. They were used as vasoconstrictors in inhalant therapy to shrink nasal mucous membranes in such conditions as nasal allergies and asthma; now such inhalants have been banned because of their toxicity. For unknown reasons, amphetamines have a paradoxically calming effect on some hyperactive children, but the use of these drugs to treat such children has been controversial.
Popularly known as bennies, crank, speed, pep pills, wakeups, or uppers, amphetamines are addictive and easily abused: users can become psychologically dependent on the drugs and, developing a tolerance for them, can require increasingly large doses (see drug addiction and drug abuse). When the drugs wear off, a long period of sleep ensues, often followed by hunger and depression, which can lead to further use of amphetamines. Amphetamine addiction has been common among such diverse groups as truck drivers, students, and athletes, who have used the drugs for increased energy, alertness, or endurance. Methamphetamine, made from ephedrine and other chemicals in clandestine laboratories in the the United States or Mexico, experienced a resurgence in use in the United States beginning the mid-1990s. Amphetamines are inhaled, taken orally, or injected; as with other injected drugs, needle sharing increases the risk of contracting the AIDS virus. One form of methamphetamine, "ice," is smoked. For law enforcement purposes in the United States, most amphetamines are grouped with such drugs as cocaine and morphine because of the similarity in their effects, medical usefulness, and high potential for abuse.
Amphetamines can produce severe systemic effects, including cardiac irregularities and gastric disturbances. Chronic use often results in insomnia, hyperactivity, irritability, and aggressive behavior. Addiction can result in psychosis or death from overexhaustion or cardiac arrest. Amphetamine-induced psychosis often mimics schizophrenia, with paranoia and hallucinations.
Organic compound, prototype of a class of synthetic amphetamine drugs (e.g., Benzedrine, Dexedrine, methamphetamine), that stimulates the central nervous system. It was first synthesized in 1887. Amphetamines cause wakefulness, euphoria, decreased fatigue, and increased ability to concentrate. Since they dull the appetite, they have been used for weight reduction. Often called “speed,” they are used (often illicitly) to stay awake. In children with attention deficit (hyperactivity) disorder, they have a calming effect, helping them concentrate. Undesirable effects include overstimulation, with paranoia, restlessness, insomnia, tremor, and irritability, and a deep depression when the drug wears off. This, along with rapid development of tolerance requiring increased doses, can lead to drug addiction.
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Amphetamine, and related drugs such as methamphetamine are a group of drugs that act by increasing levels of norepinephrine, serotonin, and dopamine in the brain. It includes prescription CNS drugs commonly used to treat attention-deficit disorder (ADD) and attention-deficit hyperactivity disorder (ADHD) in adults and children. It is also used to treat symptoms of traumatic brain injury and the daytime drowsiness symptoms of narcolepsy and chronic fatigue syndrome. Initially it was more popularly used to diminish the appetite and to control weight.
Brand names of the drugs that contain amphetamine include Vyvanse, Adderall, and Dexedrine. The drug is also used illegally as a recreational club drug and as a performance enhancer. The name amphetamine is derived from its chemical name: alpha-methylphenethylamine. Some biochemistry textbooks also claim that the name 'amphetamine' is derived from an abbreviation for "amphoteric amine," indicating that the compound can act as both an acid (proton donor) and a base (proton acceptor) depending upon its chemical environment. This origin seems unlikely, however, as there is no unique structural feature that makes amphetamine amphoteric; indeed, all primary amines are amphoteric. The name is also used to refer to the class of compounds derived from amphetamine, often referred to as the substituted amphetamines.
The related compound methamphetamine was first synthesized from ephedrine in Japan in 1918 by chemist Akira Ogata via reduction of ephedrine using red phosphorus and iodine. The German military was notorious for their use of methamphetamine in World War II. It is also rumored that Adolf Hitler was receiving daily shots of a medicine secretly named "vitamultine" that contained certain essential vitamins and amphetamines. The pharmaceutical Pervitin was a tablet of methamphetamine which was available in Germany from 1938 and widely used in the Wehrmacht, but by mid-1941 it became a controlled substance, partly because of the amount of time needed for a soldier to rest and recover after use and partly because of abuse. For the rest of the war military doctors continued to issue the drug, but ever less frequently, and with increasing discrimination as the war progressed onwards towards Nazi Germany's and the Axis' eventual defeat in 1945.
In 1997 and 1998, researchers at Texas A&M University reported finding 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 human inventions.
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When used within the recommended doses, side-effects like loss of appetite tend to decrease over time. However, amphetamines last longer in the body than methylphenidate (Ritalin, Concerta, etc.), and tend to have stronger side-effects on appetite and sleep.
Amphetamines are also a standard treatment for narcolepsy, as well as other sleeping disorders. If used within therapeutic limits, amphetamines are generally effective over long periods of time without producing addiction or physical dependence.
Amphetamines are sometimes used to augment anti-depressant therapy in treatment-resistant depression.
Medical use for weight loss is still approved in some countries, but is regarded as obsolete and dangerous in others.
Stimulants such as amphetamines elevate cardiac output and blood pressure making them dangerous for use by patients with a history of heart disease or hypertension. Also, patients with a history of drug dependence or anorexia should not be treated with amphetamines due to their addictive and appetite suppressing properties. Amphetamines can cause a life-threatening complication in patients taking MAOI antidepressants. Amphetamine is not suitable for patients with a history of glaucoma.
Amphetamines have also been shown to pass through into breast milk. Because of this, mothers taking medications containing amphetamines are advised to avoid breastfeeding during their course of treatment.
The major neural systems affected by amphetamine are largely implicated in the brain’s reward circuitry. Moreover, neurotransmitters involved various reward pathways of the brain appear to be the primary targets of amphetamine. One such neurotransmitter is dopamine, a chemical messenger heavily active in the mesolimbic and mesocortical reward pathways. Not surprisingly, the anatomical components of these pathways—including the caudate putamen, the nucleus accumbens, and the ventral striatum—have been found to be primary sites of amphetamine action.
That amphetamines influence neurotransmitter activity specifically in regions implicated in reward provides insight into the behavioral consequences of the drug, such as the stereotyped onset of euphoria. A better understanding of the specific mechanisms by which amphetamines operate may increase our ability to treat amphetamine addiction, as the brain’s reward circuitry has been widely implicated in addictions of many types.
The specific mechanisms by which amphetamines affect dopamine concentrations have been studied extensively. Currently, two major hypotheses have been proposed, which are not mutually exclusive. One theory emphasizes amphetamine’s actions on the vesicular level, increasing concentrations of dopamine in the cytosol of the pre-synaptic neuron. The other focuses on the role of the dopamine transporter DAT, and proposes that amphetamine may interact with DAT to induce reverse transport of dopamine from the presynaptic neuron into the synaptic cleft.
The former hypothesis is backed by data demonstrating that injections of amphetamines result in rapid increases of cytosolic dopamine concentrations. Amphetamine is believed to interact with dopamine-containing vesicles in the axon terminal, called VMATs, in a way that releases dopamine molecules into the cytosol. The redistributed dopamine is then believed to interact with DAT to promote reverse transport. Calcium may be a key molecule involved in the interactions between amphetamine and VMATs.
The latter hypothesis postulates a direct interaction between amphetamine and the DAT transporter. The activity of DAT is believed to depend on specific phosphorylating kinases, such as PCK-β. Upon phosphorylation, DAT undergoes a conformational change that results in the transportation of DAT-bound dopamine from the extracellular to the intracellular environment. In the presence of amphetamine, however, DAT has been observed to function in reverse, spitting dopamine out of the presynaptic neuron and into the synaptic cleft. Thus, beyond inhibiting reuptake of dopamine, amphetamine also stimulates the release of dopamine molecules into the synapse.
In support of the above hypothesis, it has been found that PKC-β inhibitors eliminate the effects of amphetamine on extracellular dopamine concentrations in the striatum of rats. This data suggests that the PKC-β kinase may represent a key point of interaction between amphetamine and the DAT transporter.
The interaction between amphetamine and serotonin is only apparent in particular regions of the brain, such as the mesocorticalimbic projection. Recent studies additionally postulate that amphetamine may indirectly alter the behavior of glutamatergic pathways extending from the ventral tegmental area to the prefrontal cortex. Glutamatergic pathways are strongly correlated with increased excitability at the level of the synapse. Increased extracellular concentrations of serotonin may thus modulate the excitatory activity of glutamatergic neurons.
The proposed ability of amphetamine to increase excitability of glutamatergic pathways may be of significance when considering serotonin-mediated addiction. An additional behavioral consequence may be the stereotyped locomotor stimulation that occurs in response to amphetamine exposure.
Several other neurotransmitters have been linked to amphetamine activity. For instance, extracellular levels of glutamate, the primary excitatory neurotransmitter in the brain, have been shown to increase upon exposure to amphetamine. Consistent with other findings, this effect was found in the areas of the brain implicated in reward; namely, the nucleus accumbens, striatum, and prefrontal cortex.
Additionally, several studies demonstrate increased levels of norepinephrine, a neurotransmitter related to adrenaline, in response to amphetamine. This is believed to occur via reuptake blockage as well as via interactions with the norepinephrine neuronal transport carrier.
At first, the medical drug came as the salt racemic-amphetamine sulfate (racemic-amphetamine contains both isomers in equal amounts). Attention disorders are often treated using Adderall or a generic equivalent, a formulation of mixed amphetamine and dextroamphetamine salts that contain
Amphetamine, both as d-amphetamine (dextroamphetamine) and l-amphetamine (or a racemic mixture of the two isomers), is believed to exert its effects by binding to the monoamine transporters and increasing extracellular levels of the biogenic amines dopamine, norepinephrine (noradrenaline) and serotonin. It is hypothesized that d-amphetamine acts primarily on the dopaminergic systems, while l-amphetamine is comparatively norepinephrinergic (noradrenergic). The primary reinforcing and behavioral-stimulant effects of amphetamine, however, are linked to enhanced dopaminergic activity, primarily in the mesolimbic dopamine system.
Amphetamine and other amphetamine-type stimulants principally act to release dopamine into the synaptic cleft. The increased amphetamine concentration releases endogenous stores of dopamine from vesicular monoamine transporters (VMATs), thereby increasing intra-neuronal concentrations of transmitter. This increase in concentration effectively reverses transport of dopamine via the dopamine transporter (DAT) into the synapse. In addition, amphetamine binds reversibly to the DATs and blocks the transporter's ability to clear DA from the synaptic space. Amphetamine also acts in this way with norepinephrine (noradrenaline) and to a lesser extent serotonin.
In addition, amphetamine binds to a group of receptors called TrAce Amine Receptors (TAAR). TAAR are a newly discovered receptor system which seems to be affected by a range of amphetamine-like substances called trace amines.
Young adults who abuse amphetamines may be at greater risk of suffering a heart attack. In a study published in the journal Drug and Alcohol Dependence, researchers examined data from more than 3 million people between 18 and 44 years old hospitalized from 2000 through 2003 in Texas. After controlling for cocaine abuse, alcohol abuse, tobacco use, hypertension, diabetes mellitus, lipid disorders, obesity, congenital defects, and coagulation defects, they found a relationship between a diagnosis of amphetamine abuse and heart attack.
Because of the abuse of amphetamines in the U.S., brands discontinued by the 1990s, including Preludin, known on the street as "slams", whose coating was peeled and then injected. Amphetamines are still produced in the United States: those prescribed for narcolepsy, attention-deficit hyperactivity disorder, treatment-resistant depression, and extreme obesity.
Amphetamines have been, and are still, used by militaries around the world. British troops used 72 million amphetamine tablets in the second world war and the RAF used so many that "Methedrine won the Battle of Britain" according to one report. American bomber pilots use amphetamines ("go pills") to stay awake during long missions. The Tarnak Farm incident, in which an American F16-pilot killed several friendly soldiers on the ground, was blamed by the pilot on his use of amphetamine. A nonjudicial hearing rejected the pilot's claim.
Amphetamine is also used by professional, collegiate and high school athletes for its strong stimulant effect. Energy levels are perceived to be dramatically increased and sustained, which is believed to allow for more vigorous and longer play. However, at least one study has found that this effect is not measurable. The use of amphetamine during strenuous physical activity can be extremely dangerous, and athletes have died as a result, for example, British cyclist Tom Simpson.
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 amphetamines. The ban is enforced through periodic drug-testing. If a player tests positive for amphetamine, the consequences are significant. However, the MLB has received some criticism because the consequences for amphetamine use are dramatically less severe than for anabolic steroid use, with the first offense bringing only a warning and further testing.
Truck drivers, especially long-haul drivers, often take amphetamine to combat symptoms of somnolence and to increase their concentration on driving.
The social and cultural impact of amphetamine has been, and continues to be, quite extensive.
From the 1960s onward, amphetamine has been popular with many youth subcultures in Britain (and other parts of the world) as a recreational drug. It has been commonly used by mods, skinheads, punks, goths and casuals in all night soul and ska dances, punk concerts, basement shows and fighting on the terraces by casuals. Amphetamine is also used by homosexual men, and in the rave culture, to break down inhibitions, as well as keep dancing or having sex for prolonged periods (though in these subcultures, methamphetamine is arguably equally as popular).
The hippie counterculture was very critical of amphetamines due to the behaviors they cause; beat writer Allen Ginsberg wrote that users ran the risk of becoming a "Frankenstein speed freak". The mods, being working class, were often opposed to the slower, more contemplative, meditative ideals and lifestyle of the hippies. Amphetamines therefore suited their high energy and aggressive aesthetics and lifestyle, whether it was dancing to soul music at all night parties, or fighting rockers.
Scottish author Irvine Welsh often portrays drug use in his novels, though in one of his journalism works he comments on how drugs (including amphetamine) have become part of consumerism and how his novels Trainspotting and Porno reflect the changes in drug use and culture during the years that elapse between the two texts.
Black Metal band Cradle of Filth's song, Nymphetamine, is a pun on the word "amphetamine" itself. The lyrics liken the submission to a succubus to amphetamine addiction, though it could also be seen as a reference to amphetamine psychosis through the hallucinations and paranoia that are a symptom of the condition.
Advertising has also alluded to and portrayed the effects of amphetamine in both serious and humorous ways, especially in anti-drug campaigns. The Montana Meth Project has commissioned a series of public information films showing the effects of methamphetamine on both the user, and society in general. The Partnership for a Drug-Free America has also commissioned public information films depicting the of impact amphetamine use on communities, with both social and environmental consequences.
On the other hand, advertisements for Red bull energy drinks often allude to effects similar to amphetamine in a tongue-in-cheek manner, with the slogan "Red bull gives you wings". One American anti-drug public information film uses humor, parodying a Folgers coffee jingle to raise awareness of the effects of amphetamine abuse.
Internationally, amphetamine is a Schedule II drug under the Convention on Psychotropic Substances.