Amphetamine

Amphetamine

Systematic (IUPAC) name

1-phenylpropan-2-amine
Clinical data
Trade names Adderall
AHFS/Drugs.com monograph
Pregnancy cat. ? (US)

Legal status Controlled (S8) (AU) Schedule II (CA) ? (UK) Schedule II (US) Prescription only

Routes Oral, Intravenous, Vaporization, Insufflation, Rectal, Sublingual

Pharmacokinetic data
Bioavailability nasal 75%; rectal 9599%; intravenous 100%
Protein binding 1540%
Metabolism Hepatic (CYP2D6)[1]
Half-life 12h average for d-isomer, 13h for l-isomer

Excretion Renal; significant portion unaltered

 Identifiers
CAS number 300-62-9 405-41-4
ATC code N06BA01
PubChem CID 3007
DrugBank DB00182
ChemSpider 13852819
UNII CK833KGX7E
KEGG D07445
ChEBI CHEBI:2679
ChEMBL CHEMBL405
NIAID ChemDB 018564
alpha-methylbenzeneethanamine, alpha-methylphenethylamine, beta-phenyl-
Synonyms
isopropylamine
Chemical data
Formula C9H13N
Mol. mass 135.2084
SMILES[show]
InChI[show]
Physical data
Solubility in
50100 mg/mL (16C) mg/mL (20 C)
water

Amphetamine (USAN, abbreviated from alpha-methylphenethylamine) or

amfetamine (INN) is a psychostimulant drug of the phenethylamine class that
produces increased wakefulness and focus in association with decreased fatigue
and appetite.
Brand names of medications that contain, or metabolize into, amphetamine
include Adderall, Dexedrine, Dextrostat, Desoxyn,[2] Didrex, ProCentra, and
Vyvanse, as well as Benzedrine or Psychedrine in the past.
The drug is also used recreationally and as a performance enhancer.
Recreational users of amphetamine have coined numerous street names for
amphetamine, such as "speed".
 Effects

Data from The Lancet suggests amphetamine is ranked the 8th most addictive
and 6th most harmful of 20 popular recreational drugs.[3]
Physical effects
Physical effects of amphetamine can include hyperactivity, dilated pupils,
vasoconstriction, blood shot eyes, flushing, restlessness, dry mouth, bruxism,
headache, tachycardia, bradycardia, tachypnea, hypertension, hypotension,
fever, diaphoresis, diarrhea, constipation, blurred vision, aphasia, dizziness,
twitching, insomnia, numbness, palpitations, arrhythmias, tremors, dry and/or
itchy skin, acne, pallor, convulsions, and with chronic and/or high doses, seizure,
stroke, coma, heart attack and death can occur.[4][5][6][7][8]
Psychological effects
Psychological effects can include euphoria, anxiety, increased libido,
alertness, concentration, energy, self-esteem, self-confidence, sociability,
irritability, aggression, psychosomatic disorders, psychomotor agitation,
grandiosity, repetitive and obsessive behaviors, paranoia, and with chronic
and/or high doses, amphetamine psychosis can occur.[9][10]
Withdrawal effects
Withdrawal symptoms of amphetamine consist primarily of mental fatigue,
mental depression and increased appetite. Symptoms may last for days with
occasional use and weeks or months with chronic use, with severity dependent on
the length of time and the amount of amphetamine used. Withdrawal symptoms
may also include anxiety, agitation, excessive sleep, vivid or lucid dreams, deep
REM sleep and suicidal ideation.[11][12][13]
 Side effects
Side effects may consist of severe weight loss, also addiction can occur
during use of this drug. Smoking this specific narcotic may induce a higher threat
to addiction for first time users. Speed Amphetamine can also raise heartbeat
levels to dangerous levels.
Contraindications
Amphetamine elevates cardiac output and blood pressure making it
dangerous for use by patients with a history of heart disease or hypertension.
Amphetamine can cause life-threatening complication in patients taking MAOI
antidepressants. The use of amphetamine and amphetamine-like drugs is
contraindicated in patients with narrow-angle glaucoma or anatomically
narrow angles. Like other sympathomimetic amines, amphetamine can induce
transient mydriasis. In patients with narrow angles, pupillary dilation can
provoke an attack of angle-closure glaucoma. These agents should also be avoided
in patients with other forms of glaucoma, as mydriasis may occasionally increase
interocular pressure.[14]
Amphetamine has been shown to pass through into breast milk. Because of
this, mothers taking amphetamine are advised to avoid breastfeeding during
their course of treatment.[15]
Dependence and addiction
Tolerance is developed rapidly in amphetamine abuse; therefore, periods of
extended use require increasing amounts of the drug in order to achieve the same
effect.[16]
Overdose
An amphetamine overdose is rarely fatal but can lead to a number of
different symptoms, including psychosis, chest pain, and hypertension.
Psychosis
Abuse of amphetamines can result in a stimulant psychosis that can present
as a number of psychotic disorders (e.g. paranoia, hallucinations, delusions). In an
Australian study of 309 active amphetamine users, 18% had experienced a
clinical level psychosis in the past year.[17] A Japanese study reported a 64%
recovery rate within 10 days rising to a 82% recovery rate at 30 days after
amphetamine cessation.[18] However it has been suggested that about 5-15% of users
fail to make a complete recovery from the psychosis in the long term.[19][20]
Mechanism of action
Primary sites of action

Ball-and-stick model of amphetamine

 Amphetamine exerts its behavioral effects by modulating several key
neurotransmitters in the brain, including dopamine, serotonin, and
norepinephrine. However, the activity of amphetamine throughout the brain
appears to be specific;[21] certain receptors that respond to amphetamine in some
regions of the brain tend not to do so in other regions. For instance, dopamine D2
receptors in the hippocampus, a region of the brain associated with forming new
memories, appear to be unaffected by the presence of amphetamine.[21]
The major neural systems affected by amphetamine are largely implicated
in the brains reward circuitry. Moreover, neurotransmitters involved in various
reward pathways of the brain appear to be the primary targets of
amphetamine.[22] One such neurotransmitter is dopamine, a chemical messenger
heavily active in the mesolimbic and mesocortical reward pathways. Therefore,
the anatomical components of these pathways including the striatum, the
nucleus accumbens, and the ventral striatum have been found to be primary
sites of amphetamine action.[23][24]
The fact that amphetamine influences neurotransmitter activity
specifically in regions implicated in reward provides insight into the behavioral
consequences of the drug, such as the stereotyped onset of euphoria.[24] A better
understanding of the specific mechanisms by which amphetamine operates may
increase our ability to treat amphetamine addiction, as the brains reward
circuitry has been widely implicated in addictions of many types.[25]
Endogenous amphetamines
Amphetamine has been found to have several endogenous analogues; that
is, molecules of a similar structure found naturally in the brain.[26] l-
Phenylalanine and -Phenethylamine are two examples, which are formed in the
peripheral nervous system as well as in the brain itself. These molecules are
thought to modulate levels of excitement and alertness, among other related
affective states.
Dopamine
The most widely studied neurotransmitter with regard to amphetamine
action in the central nervous system is dopamine. All of the addictive drugs
appear to enhance dopamine neurotransmission, including amphetamine and
methamphetamine.[27] Studies have shown that, in select regions, amphetamine
increases the concentrations of dopamine in the synaptic cleft, thereby
heightening the response of the post-synaptic neuron.[28] This specific action hints
at the hedonic response to the drug as well as to the drugs addictive quality.
The specific mechanisms by which amphetamine affects dopamine
concentrations have been studied extensively. Currently, two major hypotheses
have been proposed, which are not mutually exclusive. One theory emphasizes
amphetamines actions on the vesicular level, increasing concentrations of
dopamine in the cytosol of the pre-synaptic neuron.[26][29] 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.[22][30][31][32]
The former hypothesis is backed by studies from David Sulzer's lab at
Columbia University demonstrating that injections of amphetamine result in
rapid increases of cytosolic dopamine concentrations, while the drug decreases
the number of dopamine molecules inside the synaptic vesicle.[33][34] Amphetamine
is a substrate for a specific neuronal synaptic vesicle uptake transporter called
VMAT2. When amphetamine is taken up by VMAT2, the vesicle releases
dopamine molecules into the cytosol in exchange. The redistributed dopamine is
then believed to interact with DAT to promote reverse transport.[26]
Amphetamine and amphetamine derivatives are also weak bases that accept
protons, and can collapse acidic pH gradients in the vesicles that would otherwise
provide free energy for neurotransmitter accumulation: the "weak base
hypothesis" of amphetamine action suggests that collapse of this free energy
contributes to redistribution of dopamine from very high (molar) concentrations
in the vesicles to the cytosol.[27][35] Calcium may be a key molecule involved in the
interactions between amphetamine and VMATs.[29]
The increase of cytosolic dopamine appears to trigger neurotoxicity, as
dopamine readily auto-oxidizes, so that amphetamine or methamphetamine's
increase in cytosolic dopamine can lead to oxidative stress in the cytosol that in
turn promotes autophagy-related degradation of dopamine axons and
dendrites.[36]
The second hypothesis of amphetamine action on the plasma membrane
dopamine transporter postulates a direct interaction between amphetamine and
the DAT. The activity of DAT is believed to depend on specific phosphorylating
kinases, such as protein kinase c, to be specific PKC-.[32] Upon phosphorylation,
DAT undergoes a conformational change that results in the transportation of
DAT-bound dopamine from the extracellular to the intracellular environment.[31]
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.[30] Thus, beyond inhibiting reuptake of dopamine, amphetamine also
stimulates the release of dopamine molecules into the synapse.[22]
In support of the above hypothesis, it has been found that PKC- inhibitors
eliminate the effects of amphetamine on extracellular dopamine concentrations
in the striatum of rats.[32] This data suggests that the PKC- kinase may represent
a key point of interaction between amphetamine and the DAT transporter.
Additional actions of amphetamine contribute to its ability to release
dopamine from neurons, including action as an inhibitor of monoamine oxidase,
an enzyme responsible for dopamine breakdown in the cytosol; an ability to
enhance dopamine synthesis it is presumed via actions on the enzyme tyrosine
hydroxylase, which synthesizes the dopamine precursor L-DOPA; and some
blockade of the DAT, an action that amphetamine shares with cocaine.[37] Due to
the combination of these actions and its long half-life, amphetamine can release
far more dopamine than can cocaine or other addictive drugs.[27][38]
Serotonin
Amphetamine has been found to exert similar effects on serotonin as on
dopamine.[39] Like DAT, the serotonin transporter SERT can be induced to operate
in reverse upon stimulation by amphetamine.[40] This mechanism is thought to
rely on the actions of calcium ions, as well as on the proximity of certain
transporter proteins.[40]
 The interaction between amphetamine and serotonin is apparent only in
particular regions of the brain, such as the mesocorticolimbic 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.[39] 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.[39]
The proposed ability of amphetamine to increase excitability of
glutamatergic pathways may be of significance when considering serotonin-
mediated addiction.[39] An additional behavioral consequence may be the
stereotyped locomotor stimulation that occurs in response to amphetamine
exposure.[28]
Other relevant neurotransmitters
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. In addition, 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.[41] The long-term
effects of amphetamines use on neural development in children has not been well
established.[42] Based on a study in rats, amphetamine use during adolescence may
impair adult working memory.[43]
Pharmacology
Chemical properties

Molecular structure of amphetamine. Methamphetamine has the same structure,

with the addition of a methyl group attached to the nitrogen.
Chart comparing the chemical structures of different amphetamine derivatives.
Amphetamine is a chiral compound. The racemic mixture can be divided
into its optical isomers: levo- and dextro-amphetamine. Amphetamine is the
parent compound of its own structural class, comprising a broad range of
psychoactive derivatives, from empathogens, MDA (3,4-
Methylenedioxyamphetamine) and MDMA (3,4-Methylenedioxy-N-
methamphetamine) known as ecstasy, to the N-methylated form,
methamphetamine known as 'meth', and to decongestants such as ephedrine
(EPH) . Amphetamine is a homologue of phenethylamine.
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

1/4 dextro-amphetamine saccharate

1/4 dextro-amphetamine sulfate
1/4 (racemic amphetamine) aspartate monohydrate
1/4 (racemic amphetamine) sulfate
Pharmacodynamics
Amphetamine has been shown to both diffuse through the cell membrane and
travel via the dopamine transporter (DAT) to increase concentrations of
dopamine in the neuronal terminal.
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 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 act principally to
release dopamine into the synaptic cleft. Amphetamine, unlike dopamine
transporter inhibitor cocaine, acts as a substrate for DAT and slows reuptake by
a secondary acting mechanism through the phosphorylation of dopamine
transporters.[44] A primary action of amphetamine is mediated by vesicular
monoamine transporters (VMATs); the transporters appear to provide a channel
through which dopamine and other transmitters can exit the vesicle to the
cytosol. According to the "weak base hypothesis" this is exacerbated by
amphetamine acting to alkalinize the vesicle, which depletes the free energy
favoring vesicle accummlation so that transmitter is redistributed to the cytosol.
Together, these actions cause the release of dopamine, norepinephrine, and
serotonin from monoamine vesicles, thereby increasing cytosolic concentrations
of transmitter. This increase in concentration assists in the "reverse transport" of
dopamine via the dopamine transporter (DAT) into the synapse.[45] 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.
Amphetamine has been identified as a potent agonist of TAAR1, a newly
discovered GPCR important for regulation of monoaminergic systems in the
brain.[46] Activation of TAAR1 increases cAMP production via adenylyl cyclase
activation and inhibits transporter function.[46][47][48][49][50] These effects increase
monoamine efflux and prolong the amount of time monoamines remain in the
synapse.
History
Amphetamine was first synthesized in 1887 by the Romanian chemist Lazr
Edeleanu in Berlin, Germany.[51] He named the compound phenylisopropylamine.
It was one of a series of compounds related to the plant derivative ephedrine,
which had been isolated from Ma-Huang that same year by Nagayoshi Nagai.[52]
No pharmacological use was found for amphetamine until 1927, when pioneer
psychopharmacologist Gordon Alles resynthesized and tested it on himself, in
search of an artificial replacement for ephedrine. From 1933 or 1934 Smith, Kline
and French began selling the volatile base form of the drug as an inhaler under
the trade name Benzedrine, useful as a decongestant but readily usable for other
purposes.[53] One of the first attempts at using amphetamine as a scientific study
was done by M. H. 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".[54] During World War II amphetamine was extensively used to combat
fatigue and increase alertness in soldiers. After decades of reported abuse, the
FDA banned Benzedrine inhalers, and limited amphetamine to prescription use
in 1965, but non-medical use remained common. Amphetamine became a schedule
II drug in the USA under the Controlled Substances Act in 1971.
The related compound methamphetamine, in its crystallized form, was first
synthesized from ephedrine in Japan in 1920 by chemist Akira Ogata, via
reduction of ephedrine using red phosphorus and iodine. The pharmaceutical
Pervitin was a tablet of 3 mg methamphetamine that 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 less frequently and with
increasing discrimination.[55]
In 1997 and 1998,[56][57] 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 human inventions. These findings have never
been duplicated, and the analyses are believed by many biochemists to be the
result of experimental error, and as such the validity of the report has come into
question. Alexander Shulgin, one of the most experienced biochemical
investigators and the discoverer of many new psychotropic substances, has tried
to contact the Texas A&M researchers and verify their findings. The authors of
the paper have not responded; natural amphetamine remains an unconfirmed
discovery.[58]
Performance-enhancing use
Adderall, an amphetamine mixture, is used by some college and high-school
students as a study and test-taking aid.[59] Amphetamine works by increasing
energy levels, concentration, and motivation, thus allowing students to study for
an extended period of time.
Amphetamine has been, and is still, used by militaries around the world.
British troops used 72 million amphetamine tablets in the second world war[60]
and the RAF used so many that "Methedrine won the Battle of Britain"
according to one report.[61] American bomber pilots use amphetamine ("go pills") to
stay awake during long missions. The Tarnak Farm incident, 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.[62] A nonjudicial hearing rejected
the pilot's claim.[citation needed]
Amphetamine is also used by some professional,[63] collegiate[64] and high
school[64] 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.[65] The use of amphetamine during strenuous physical activity
can be extremely dangerous, especially when combined with alcohol, 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".[66] 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
consequences for amphetamine use are dramatically less severe than for anabolic
steroid use, with the first offense bringing only a warning and further
testing.[67][68][69]
Amphetamine was formerly in widespread use by truck drivers[70] 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. Although
implementation of the order on the trucking industry was kept to a gradual rate
in consideration of its projected effects on the national economy, in the decades
following the order, amphetamine and other drug abuse by truck drivers has
since dropped drastically. (See also Truck driverImplementation of drug
detection).
Detection in body fluids
Amphetamine is frequently measured in urine as part of a drug abuse testing
program, in plasma or serum to confirm a diagnosis of poisoning in hospitalized
victims, or in whole blood to assist in the forensic investigation of a traffic or
other criminal violation or a case of sudden death. Techniques such as
immunoassay may cross-react with a number of sympathomimetics drugs, so
chromatographic methods specific for amphetamine should be employed to
prevent false positive results. Chiral techniques may be employed to help
distinguish the source of the drug, whether obtained legally (via prescription) or
illicitly, or possibly as a result of formation from a prodrug such as
lisdexamfetamine or selegiline. Chiral separation is needed to assess the possible
contribution of l-methamphetamine (Vicks Inhaler) toward a positive test
result.[71][72][73]
Society and culture
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, gangsters, and casuals
in all night soul and ska dances, punk concerts, basement shows and fighting on
the terraces by casuals.[citation needed]
The hippie counterculture was very critical of amphetamines due to the
behaviors they cause; in an interview with the Los Angeles Free Press in 1965,
beat writer Allen Ginsberg commented that "Speed is antisocial, paranoid
making, it's a drag... all the nice gentle dope fiends are getting screwed up by the
real horror monster Frankenstein speed freaks who are going round stealing and
bad-mouthing everybody".[74]
In literature
The writers of the Beat Generation used amphetamine extensively, mainly
under the Benzedrine brand name. Jack Kerouac was a particularly avid user of
amphetamine, which was said to provide him with the stamina needed to work
on his novels for extended periods of time.[75]
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.[76]
Amphetamine is frequently mentioned in the work of American journalist
Hunter S. Thompson. Speed not only appears among the inventory of drugs
Thompson consumed for what could broadly be defined as recreational purposes
but also receives frequent, explicit mention as an essential component of his
writing toolkit,[77] such as in his "Author's Note" in Fear and Loathing on the
Campaign Trail '72.[78]
"One afternoon about three days ago [the publishers] showed up at my door
with no warning, and loaded about forty pounds of supplies into the room: two
cases of Mexican beer, four quarts of gin, a dozen grapefruits, and enough speed
to alter the outcome of six Super Bowls. ... Meanwhile, [...] with the final chapter
still unwritten and the presses scheduled to start rolling in twenty-four hours . . . .
unless somebody shows up pretty soon with extremely powerful speed, there
might not be a final chapter. About four fingers of king-hell Crank would do the
trick, but I am not optimistic."
In music
Many songs have been written about amphetamine, for example in the track
entitled "St. Ides Heaven" from singer/songwriter, Elliott Smith's self-titled album.
Semi Charmed Life by Third Eye Blind also references amphetamine. Another
blatant example would be the song simply labelled "Amphetamine" by
Alternative rock band Everclear, the song "20 Dollar nose bleed" by the Pop-rock
band Fall Out Boy, and the song Headfirst For Halos by My Chemical Romance.
It has also influenced the aesthetics of many rock'n'roll bands (especially in the
garage rock, mod R&B, death rock, punk/hardcore, gothic rock and extreme
heavy metal genres). Hsker D, Jesus and Mary Chain's and The Who were keen
amphetamine users early in their existence. Land Speed Record is an allusion to
Hsker D's amphetamine use.[citation needed] Amphetamine was widely abused in the
1980s underground punk-rock scene. Pop-punk band NOFX have incorporated
references to Amphetamines and other stimulants, the two most obvious being
the song "Three on Speed" from the "Surfer" 8" LP (in reference to the three guys
being on Amphetamine while recording the album), and earlier the album "The
Longest Line" is in reference to a "line" of Amphetamine ready for insufflation.
The Rolling Stones referenced the drug in their song "Can't You Hear Me
Knocking" on the album Sticky Fingers ("Y'all got cocaine eyes / Yeah, ya got
speed-freak jive now"). Lou Reed refers explicitly to the drug on his album Berlin,
in the song "How Do You Think It Feels?". Reed's band The Velvet Underground,
a creation of Andy Warhol's Factory Years, was fueled by amphetamines, as well
as naming their second album White Light/White Heat after the drug and
making reference to the song in "Sister Ray.". The Pulp song Sorted for E's & Wizz
refers to British slang terms for ecstasy and amphetamines. English gothic rock
band The Sisters of Mercy refers to the drug in their song "Amphetamine Logic"
from their first album, First and Last and Always, and their singer Andrew
Eldritch used amphetamines repeatedly. The Byrds referenced amphetamines in
the 1968 song "Artificial Energy" on the album "The Notorious Byrd Brothers."
 Many rock'n'roll bands have named themselves after amphetamine and drug
slang surrounding it. For example Mod revivalists, The Purple Hearts named
themselves after the amphetamine tablets popular with mods during the 1960s, as
did the Australian band of the same name during the mid-1960s.[citation needed] The
Amphetameanies, a ska-punk band, are also named after amphetamine, but also
imitate its effects. Dexys Midnight Runners, of number one hit "Come On Eileen",
are named after Dexedrine. Motrhead derived their name from the song of the
same name, originally by Hawkwind where Ian "Lemmy" Kilminster was on bass
before leaving to form Motrhead. Lemmy Kilmister is a long-term user of speed.
Underground rock singer-songwriter Robert Caruso's song Speed is a sort of
hymn to amphetamines. He originally recorded the song in the 1980s with his
band Rob Leer & The Electric Kids, and then again on his album Revelation in
2011.
An American electronic music duo The Crystal Method has a reference to
methamphetamine (Crystal Meth) in its name.
A hip hop artist by the name of Yelawolf references Adderall in his song "Billy
Crystal" featuring Rock City off of his album "Trunk Muzik 0-60".
The Northern Soul scene, a offshoot of the mods, had people taking
amphetamines to keep dancing all night. One DJ, Roger Eagle, got out of the
Northern Soul scene saying: "All they wanted was fast-tempo black dance music...
[but they were] too blocked on amphetamines to articulate exactly which Jackie
Wilson record they wanted me to play."[79]
In film
Producer David O. Selznick was an amphetamine user, and would often
dictate long and rambling memos under the influence of amphetamine to his
directors.[80] The documentary Shadowing The Third Man relates that Selznick
introduced The Third Man director Carol Reed to the use of amphetamine, which
allowed Reed to bring the picture in below budget and on schedule by filming
nearly 22 hours at a time.[81]
The title of the 2009 movie Amphetamine plays on the double meaning of the
word in Chinese - besides the name for the drug it also means 'isn't this his fate?'
which figuratively ties to the movie's plot. The word is transliterated as
- "n fi t mng" - and as commonly happens with transliteration of non-Chinese
terms each character has independent meaning as an individual unrelated word.

In mathematics
One of the greatest mathematicians of the 20th century, Paul Erds, took
amphetamines after the age of 58 until his death at the age of 83 (he had
previously sustained himself on copious amounts of coffee). He took
amphetamines despite the concern of his friends, one of whom (Ron Graham) bet
him $500 that he could not stop taking the drug for a month.[82] Erds won the bet,
but complained that during his abstinence mathematics had been set back by a
month: "Before, when I looked at a piece of blank paper my mind was filled with
ideas. Now all I see is a blank piece of paper." After he won the bet, he promptly
resumed his amphetamine use.
Legal status
In the United Kingdom, amphetamines are regarded as Class B drugs. The
maximum penalty for unauthorized possession is five years in prison and
an unlimited fine. The maximum penalty for illegal supply is 14 years in
prison and an unlimited fine.[83]
In the Netherlands, amphetamine and methamphetamine are List I drugs
of the Opium Law, but the dextro isomer of amphetamine is indicated for
ADD/ADHD and narcolepsy and available for prescription as 5 and 10 mg
generic tablets, and 5 and 10 mg gel capsules.
In the United States, amphetamine and methamphetamine are Schedule II
drugs, classified as CNS (central nervous system) stimulants.[84] A Schedule II
drug is classified as one that has a high potential for abuse, has a currently
accepted medical use and is used under severe restrictions, and has a high
possibility of severe psychological and physiological dependence.
In Canada, possession of amphetamines is a criminal offence under Schedule
I of the Controlled Drugs and Substances Act, with a maximum penalty for
repeat offenders of fines of up to $2,000, imprisonment for up to one year,
or both.[85]
Internationally, amphetamine is a Schedule II drug under the Convention on
Psychotropic Substances.[86]
Prodrugs
A number of substances have been shown to produce amphetamine and/or
methamphetamine as metabolites, including amfecloral, amphetaminil,
benzphetamine, clobenzorex, dimethylamphetamine, ethylamphetamine,
famprofazone, fencamine, fenethylline, fenproporex, furfenorex,
lisdexamfetamine, mefenorex, mesocarb, prenylamine, propylamphetamine, and
selegiline, among others.[87][88] These compounds may produce positive results for
amphetamine on drug tests.[87][88]
Derivatives
Amphetamine derivatives are a class of potent drugs that act by increasing
levels of dopamine, norepinephrine, and serotonin in the brain, inducing
euphoria.[89][90][91] The class includes prescription CNS drugs commonly used to treat
attention-deficit hyperactivity disorder (ADHD). It is also used to treat
symptoms of traumatic brain injury (TBI) and the daytime drowsiness symptoms
of narcolepsy, postural orthostatic tachycardia syndrome (POTS) and chronic
fatigue syndrome (CFS).
Smuggling
213 kg of amphetamine worth 40 million AED was seized by the United Arab
Emirate Drug combat authorities on 30 November 2011 from an Iranian ship
that was supposed to deliver the consignment in Malaysia and made a port stop
in Sharjah.
The Gulf News published on 30 November 2011, saying "This is the biggest drug
bust of its kind in 2011 and the second big one in the last three years worldwide,"
said Dr. Wadia Maalouf, International expert at the United Nation's Drug and
Crime office.[92]