Physical cosmology

From Wikipedia, the free encyclopedia

Physical cosmology is a branch of cosmology concerned with the studies of the largest-scale structures and dynamics of the universe and with fundamental questions about its origin, structure, evolution, and ultimate fate. Cosmology as a science originated with the Copernican principle, which implies that celestial bodies obey identical physical laws to those on Earth, and Newtonian mechanics, which first allowed those physical laws to be understood. Physical cosmology, as it is now understood, began with the development in 1915 of Albert Einstein's general theory of relativity, followed by major observational discoveries in the 1920s: first, Edwin Hubble discovered that the universe contains a huge number of external galaxies beyond the Milky Way; then, work by Vesto Slipher and others showed that the universe is expanding. These advances made it possible to speculate about the origin of the universe, and allowed the establishment of the Big Bang theory, by Georges Lemaître, as the leading cosmological model. A few researchers still advocate a handful of alternative cosmologies; however, most cosmologists agree that the Big Bang theory explains the observations better.
Dramatic advances in observational cosmology since the 1990s, including the cosmic microwave background, distant supernovae and galaxy redshift surveys, have led to the development of a standard model of cosmology. This model requires the universe to contain large amounts of dark matter and dark energy whose nature is currently not well understood, but the model gives detailed predictions that are in excellent agreement with many diverse observations.

Cosmology draws heavily on the work of many disparate areas of research in theoretical and applied physics. Areas relevant to cosmology include particle physics experiments and theory, theoretical and observational astrophysics, general relativity, quantum mechanics, and plasma physics.

Subject history

Modern cosmology developed along tandem tracks of theory and observation. In 1916, Albert Einstein published his theory of general relativity, which provided a unified description of gravity as a geometric property of space and time. At the time, Einstein believed in a static universe, but found that his original formulation of the theory did not permit it. This is because masses distributed throughout the universe gravitationally attract, and move toward each other over time. However, he realized that his equations permitted the introduction of a constant term which could counteract the attractive force of gravity on the cosmic scale. Einstein published his first paper on relativistic cosmology in 1917, in which he added this cosmological constant to his field equations in order to force them to model a static universe. The Einstein model describes a static universe; space is finite and unbounded (analogous to the surface of a sphere, which has a finite area but no edges). However, this so-called Einstein model is unstable to small perturbations—it will eventually start to expand or contract. It was later realized that Einstein's model was just one of a larger set of possibilities, all of which were consistent with general relativity and the cosmological principle. The cosmological solutions of general relativity were found by Alexander Friedmann in the early 1920s. His equations describe the Friedmann–Lemaître–Robertson–Walker universe, which may expand or contract, and whose geometry may be open, flat, or closed. 

History of the Universe – gravitational waves are hypothesized to arise from cosmic inflation, a faster-than-light expansion just after the Big Bang

 

In the 1910s, Vesto Slipher (and later Carl Wilhelm Wirtz) interpreted the red shift of spiral nebulae as a Doppler shift that indicated they were receding from Earth. However, it is difficult to determine the distance to astronomical objects. One way is to compare the physical size of an object to its angular size, but a physical size must be assumed to do this. Another method is to measure the brightness of an object and assume an intrinsic luminosity, from which the distance may be determined using the inverse square law. Due to the difficulty of using these methods, they did not realize that the nebulae were actually galaxies outside our own Milky Way, nor did they speculate about the cosmological implications. In 1927, the Belgian Roman Catholic priest Georges Lemaître independently derived the Friedmann–Lemaître–Robertson–Walker equations and proposed, on the basis of the recession of spiral nebulae, that the universe began with the "explosion" of a "primeval atom"—which was later called the Big Bang. In 1929, Edwin Hubble provided an observational basis for Lemaître's theory. Hubble showed that the spiral nebulae were galaxies by determining their distances using measurements of the brightness of Cepheid variable stars. He discovered a relationship between the redshift of a galaxy and its distance. He interpreted this as evidence that the galaxies are receding from Earth in every direction at speeds proportional to their distance. This fact is now known as Hubble's law, though the numerical factor Hubble found relating recessional velocity and distance was off by a factor of ten, due to not knowing about the types of Cepheid variables.

Given the cosmological principle, Hubble's law suggested that the universe was expanding. Two primary explanations were proposed for the expansion. One was Lemaître's Big Bang theory, advocated and developed by George Gamow. The other explanation was Fred Hoyle's steady state model in which new matter is created as the galaxies move away from each other. In this model, the universe is roughly the same at any point in time.

For a number of years, support for these theories was evenly divided. However, the observational evidence began to support the idea that the universe evolved from a hot dense state. The discovery of the cosmic microwave background in 1965 lent strong support to the Big Bang model, and since the precise measurements of the cosmic microwave background by the Cosmic Background Explorer in the early 1990s, few cosmologists have seriously proposed other theories of the origin and evolution of the cosmos. One consequence of this is that in standard general relativity, the universe began with a singularity, as demonstrated by Roger Penrose and Stephen Hawking in the 1960s.

An alternative view to extend the Big Bang model, suggesting the universe had no beginning or singularity and the age of the universe is infinite, has been presented.

Energy of the cosmos

The lightest chemical elements, primarily hydrogen and helium, were created during the Big Bang through the process of nucleosynthesis. In a sequence of stellar nucleosynthesis reactions, smaller atomic nuclei are then combined into larger atomic nuclei, ultimately forming stable iron group elements such as iron and nickel, which have the highest nuclear binding energies. The net process results in a later energy release, meaning subsequent to the Big Bang. Such reactions of nuclear particles can lead to sudden energy releases from cataclysmic variable stars such as novae. Gravitational collapse of matter into black holes also powers the most energetic processes, generally seen in the nuclear regions of galaxies, forming quasars and active galaxies.

Cosmologists cannot explain all cosmic phenomena exactly, such as those related to the accelerating expansion of the universe, using conventional forms of energy. Instead, cosmologists propose a new form of energy called dark energy that permeates all space. One hypothesis is that dark energy is just the vacuum energy, a component of empty space that is associated with the virtual particles that exist due to the uncertainty principle.

There is no clear way to define the total energy in the universe using the most widely accepted theory of gravity, general relativity. Therefore, it remains controversial whether the total energy is conserved in an expanding universe. For instance, each photon that travels through intergalactic space loses energy due to the redshift effect. This energy is not obviously transferred to any other system, so seems to be permanently lost. On the other hand, some cosmologists insist that energy is conserved in some sense; this follows the law of conservation of energy.

Thermodynamics of the universe is a field of study that explores which form of energy dominates the cosmos – relativistic particles which are referred to as radiation, or non-relativistic particles referred to as matter. Relativistic particles are particles whose rest mass is zero or negligible compared to their kinetic energy, and so move at the speed of light or very close to it; non-relativistic particles have much higher rest mass than their energy and so move much slower than the speed of light. 

As the universe expands, both matter and radiation in it become diluted. However, the energy densities of radiation and matter dilute at different rates. As a particular volume expands, mass energy density is changed only by the increase in volume, but the energy density of radiation is changed both by the increase in volume and by the increase in the wavelength of the photons that make it up. Thus the energy of radiation becomes a smaller part of the universe's total energy than that of matter as it expands. The very early universe is said to have been 'radiation dominated' and radiation controlled the deceleration of expansion. Later, as the average energy per photon becomes roughly 10 eV and lower, matter dictates the rate of deceleration and the universe is said to be 'matter dominated'. The intermediate case is not treated well analytically. As the expansion of the universe continues, matter dilutes even further and the cosmological constant becomes dominant, leading to an acceleration in the universe's expansion.

History of the universe

The history of the universe is a central issue in cosmology. The history of the universe is divided into different periods called epochs, according to the dominant forces and processes in each period. The standard cosmological model is known as the Lambda-CDM model.

Equations of motion

Within the standard cosmological model, the equations of motion governing the universe as a whole are derived from general relativity with a small, positive cosmological constant. The solution is an expanding universe; due to this expansion, the radiation and matter in the universe cool down and become diluted. At first, the expansion is slowed down by gravitation attracting the radiation and matter in the universe. However, as these become diluted, the cosmological constant becomes more dominant and the expansion of the universe starts to accelerate rather than decelerate. In our universe this happened billions of years ago.

Particle physics in cosmology

During the earliest moments of the universe the average energy density was very high, making knowledge of particle physics critical to understanding this environment. Hence, scattering processes and decay of unstable elementary particles are important for cosmological models of this period.

As a rule of thumb, a scattering or a decay process is cosmologically important in a certain epoch if the time scale describing that process is smaller than, or comparable to, the time scale of the expansion of the universe. The time scale that describes the expansion of the universe is ${\displaystyle 1/H}$ with ${\displaystyle H}$ being the Hubble parameter, which varies with time. The expansion timescale ${\displaystyle 1/H}$ is roughly equal to the age of the universe at each point in time.

Timeline of the Big Bang

Observations suggest that the universe began around 13.8 billion years ago. Since then, the evolution of the universe has passed through three phases. The very early universe, which is still poorly understood, was the split second in which the universe was so hot that particles had energies higher than those currently accessible in particle accelerators on Earth. Therefore, while the basic features of this epoch have been worked out in the Big Bang theory, the details are largely based on educated guesses. Following this, in the early universe, the evolution of the universe proceeded according to known high energy physics. This is when the first protons, electrons and neutrons formed, then nuclei and finally atoms. With the formation of neutral hydrogen, the cosmic microwave background was emitted. Finally, the epoch of structure formation began, when matter started to aggregate into the first stars and quasars, and ultimately galaxies, clusters of galaxies and superclusters formed. The future of the universe is not yet firmly known, but according to the ΛCDM model it will continue expanding forever.

Areas of study

Below, some of the most active areas of inquiry in cosmology are described, in roughly chronological order. This does not include all of the Big Bang cosmology, which is presented in Timeline of the Big Bang.

Very early universe

The early, hot universe appears to be well explained by the Big Bang from roughly 10⁻³³ seconds onwards, but there are several problems. One is that there is no compelling reason, using current particle physics, for the universe to be flat, homogeneous, and isotropic (see the cosmological principle). Moreover, grand unified theories of particle physics suggest that there should be magnetic monopoles in the universe, which have not been found. These problems are resolved by a brief period of cosmic inflation, which drives the universe to flatness, smooths out anisotropies and inhomogeneities to the observed level, and exponentially dilutes the monopoles. The physical model behind cosmic inflation is extremely simple, but it has not yet been confirmed by particle physics, and there are difficult problems reconciling inflation and quantum field theory. Some cosmologists think that string theory and brane cosmology will provide an alternative to inflation.

Another major problem in cosmology is what caused the universe to contain far more matter than antimatter. Cosmologists can observationally deduce that the universe is not split into regions of matter and antimatter. If it were, there would be X-rays and gamma rays produced as a result of annihilation, but this is not observed. Therefore, some process in the early universe must have created a small excess of matter over antimatter, and this (currently not understood) process is called baryogenesis. Three required conditions for baryogenesis were derived by Andrei Sakharov in 1967, and requires a violation of the particle physics symmetry, called CP-symmetry, between matter and antimatter. However, particle accelerators measure too small a violation of CP-symmetry to account for the baryon asymmetry. Cosmologists and particle physicists look for additional violations of the CP-symmetry in the early universe that might account for the baryon asymmetry.

Both the problems of baryogenesis and cosmic inflation are very closely related to particle physics, and their resolution might come from high energy theory and experiment, rather than through observations of the universe.

Big Bang Theory

Big Bang nucleosynthesis is the theory of the formation of the elements in the early universe. It finished when the universe was about three minutes old and its temperature dropped below that at which nuclear fusion could occur. Big Bang nucleosynthesis had a brief period during which it could operate, so only the very lightest elements were produced. Starting from hydrogen ions (protons), it principally produced deuterium, helium-4, and lithium. Other elements were produced in only trace abundances. The basic theory of nucleosynthesis was developed in 1948 by George Gamow, Ralph Asher Alpher, and Robert Herman. It was used for many years as a probe of physics at the time of the Big Bang, as the theory of Big Bang nucleosynthesis connects the abundances of primordial light elements with the features of the early universe. Specifically, it can be used to test the equivalence principle, to probe dark matter, and test neutrino physics. Some cosmologists have proposed that Big Bang nucleosynthesis suggests there is a fourth "sterile" species of neutrino.

Standard model of Big Bang cosmology

The ΛCDM (Lambda cold dark matter) or Lambda-CDM model is a parametrization of the Big Bang cosmological model in which the universe contains a cosmological constant, denoted by Lambda (Greek Λ), associated with dark energy, and cold dark matter (abbreviated CDM). It is frequently referred to as the standard model of Big Bang cosmology.

Cosmic microwave background

Evidence of gravitational waves in the infant universe may have been uncovered by the microscopic examination of the focal plane of the BICEP2 radio telescope.

 

The cosmic microwave background is radiation left over from decoupling after the epoch of recombination when neutral atoms first formed. At this point, radiation produced in the Big Bang stopped Thomson scattering from charged ions. The radiation, first observed in 1965 by Arno Penzias and Robert Woodrow Wilson, has a perfect thermal black-body spectrum. It has a temperature of 2.7 kelvins today and is isotropic to one part in 10⁵. Cosmological perturbation theory, which describes the evolution of slight inhomogeneities in the early universe, has allowed cosmologists to precisely calculate the angular power spectrum of the radiation, and it has been measured by the recent satellite experiments (COBE and WMAP) and many ground and balloon-based experiments (such as Degree Angular Scale Interferometer, Cosmic Background Imager, and Boomerang). One of the goals of these efforts is to measure the basic parameters of the Lambda-CDM model with increasing accuracy, as well as to test the predictions of the Big Bang model and look for new physics. The results of measurements made by WMAP, for example, have placed limits on the neutrino masses.

Newer experiments, such as QUIET and the Atacama Cosmology Telescope, are trying to measure the polarization of the cosmic microwave background. These measurements are expected to provide further confirmation of the theory as well as information about cosmic inflation, and the so-called secondary anisotropies, such as the Sunyaev-Zel'dovich effect and Sachs-Wolfe effect, which are caused by interaction between galaxies and clusters with the cosmic microwave background.

On 17 March 2014, astronomers of the BICEP2 Collaboration announced the apparent detection of B-mode polarization of the CMB, considered to be evidence of primordial gravitational waves that are predicted by the theory of inflation to occur during the earliest phase of the Big Bang. However, later that year the Planck collaboration provided a more accurate measurement of cosmic dust, concluding that the B-mode signal from dust is the same strength as that reported from BICEP2. On 30 January 2015, a joint analysis of BICEP2 and Planck data was published and the European Space Agency announced that the signal can be entirely attributed to interstellar dust in the Milky Way.

Formation and evolution of large-scale structure

Understanding the formation and evolution of the largest and earliest structures (i.e., quasars, galaxies, clusters and superclusters) is one of the largest efforts in cosmology. Cosmologists study a model of hierarchical structure formation in which structures form from the bottom up, with smaller objects forming first, while the largest objects, such as superclusters, are still assembling. One way to study structure in the universe is to survey the visible galaxies, in order to construct a three-dimensional picture of the galaxies in the universe and measure the matter power spectrum. This is the approach of the Sloan Digital Sky Survey and the 2dF Galaxy Redshift Survey.

Another tool for understanding structure formation is simulations, which cosmologists use to study the gravitational aggregation of matter in the universe, as it clusters into filaments, superclusters and voids. Most simulations contain only non-baryonic cold dark matter, which should suffice to understand the universe on the largest scales, as there is much more dark matter in the universe than visible, baryonic matter. More advanced simulations are starting to include baryons and study the formation of individual galaxies. Cosmologists study these simulations to see if they agree with the galaxy surveys, and to understand any discrepancy.

Other, complementary observations to measure the distribution of matter in the distant universe and to probe reionization include:

• The Lyman-alpha forest, which allows cosmologists to measure the distribution of neutral atomic hydrogen gas in the early universe, by measuring the absorption of light from distant quasars by the gas.
• The 21 centimeter absorption line of neutral atomic hydrogen also provides a sensitive test of cosmology.
• Weak lensing, the distortion of a distant image by gravitational lensing due to dark matter.

These will help cosmologists settle the question of when and how structure formed in the universe.

Dark matter

Evidence from Big Bang nucleosynthesis, the cosmic microwave background, structure formation, and galaxy rotation curves suggests that about 23% of the mass of the universe consists of non-baryonic dark matter, whereas only 4% consists of visible, baryonic matter. The gravitational effects of dark matter are well understood, as it behaves like a cold, non-radiative fluid that forms haloes around galaxies. Dark matter has never been detected in the laboratory, and the particle physics nature of dark matter remains completely unknown. Without observational constraints, there are a number of candidates, such as a stable supersymmetric particle, a weakly interacting massive particle, a gravitationally-interacting massive particle, an axion, and a massive compact halo object. Alternatives to the dark matter hypothesis include a modification of gravity at small accelerations (MOND) or an effect from brane cosmology.

Dark energy

If the universe is flat, there must be an additional component making up 73% (in addition to the 23% dark matter and 4% baryons) of the energy density of the universe. This is called dark energy. In order not to interfere with Big Bang nucleosynthesis and the cosmic microwave background, it must not cluster in haloes like baryons and dark matter. There is strong observational evidence for dark energy, as the total energy density of the universe is known through constraints on the flatness of the universe, but the amount of clustering matter is tightly measured, and is much less than this. The case for dark energy was strengthened in 1999, when measurements demonstrated that the expansion of the universe has begun to gradually accelerate.

Apart from its density and its clustering properties, nothing is known about dark energy. Quantum field theory predicts a cosmological constant (CC) much like dark energy, but 120 orders of magnitude larger than that observed. Steven Weinberg and a number of string theorists have invoked the 'weak anthropic principle': i.e. the reason that physicists observe a universe with such a small cosmological constant is that no physicists (or any life) could exist in a universe with a larger cosmological constant. Many cosmologists find this an unsatisfying explanation: perhaps because while the weak anthropic principle is self-evident (given that living observers exist, there must be at least one universe with a cosmological constant which allows for life to exist) it does not attempt to explain the context of that universe. For example, the weak anthropic principle alone does not distinguish between:

• Only one universe will ever exist and there is some underlying principle that constrains the CC to the value we observe.
• Only one universe will ever exist and although there is no underlying principle fixing the CC, we got lucky.
• Lots of universes exist (simultaneously or serially) with a range of CC values, and of course ours is one of the life-supporting ones.

Other possible explanations for dark energy include quintessence or a modification of gravity on the largest scales. The effect on cosmology of the dark energy that these models describe is given by the dark energy's equation of state, which varies depending upon the theory. The nature of dark energy is one of the most challenging problems in cosmology.

A better understanding of dark energy is likely to solve the problem of the ultimate fate of the universe. In the current cosmological epoch, the accelerated expansion due to dark energy is preventing structures larger than superclusters from forming. It is not known whether the acceleration will continue indefinitely, perhaps even increasing until a big rip, or whether it will eventually reverse, lead to a big freeze, or follow some other scenario.

Gravitational waves

Gravitational waves are ripples in the curvature of spacetime that propagate as waves at the speed of light, generated in certain gravitational interactions that propagate outward from their source. Gravitational-wave astronomy is an emerging branch of observational astronomy which aims to use gravitational waves to collect observational data about sources of detectable gravitational waves such as binary star systems composed of white dwarfs, neutron stars, and black holes; and events such as supernovae, and the formation of the early universe shortly after the Big Bang.

In 2016, the LIGO Scientific Collaboration and Virgo Collaboration teams announced that they had made the first observation of gravitational waves, originating from a pair of merging black holes using the Advanced LIGO detectors. On 15 June 2016, a second detection of gravitational waves from coalescing black holes was announced. Besides LIGO, many other gravitational-wave observatories (detectors) are under construction.

Other areas of inquiry

Cosmologists also study:

• Whether primordial black holes were formed in our universe, and what happened to them.
• Detection of cosmic rays with energies above the GZK cutoff, and whether it signals a failure of special relativity at high energies.
• The equivalence principle, whether or not Einstein's general theory of relativity is the correct theory of gravitation, and if the fundamental laws of physics are the same everywhere in the universe.
• The increasing complexity of universal structures, an example being the progressively greater energy rate density.

Dextroamphetamine

From Wikipedia, the free encyclopedia

Dextroamphetamine

Clinical data
Pronunciation	/ˌdɛkstroʊæmˈfɛtəmiːn/
Trade names	Dexedrine, Metamina, Attentin, Zenzedi, Procentra, Amfexa
Synonyms	D-Amphetamine
AHFS/Drugs.com	Monograph
MedlinePlus	a605027
License data	US FDA: Dextroamphetamine
Pregnancy category	AU: B3 US: C (Risk not ruled out)
Dependence liability	Moderate
Addiction liability	High
Routes of administration	By mouth
ATC code	N06BA02 (WHO)
Legal status
Legal status	AU: S8 (Controlled) CA: Schedule I DE: Anlage III (Special prescription form required) UK: Class B US: Schedule II
Pharmacokinetic data
Bioavailability	Oral: 75–100%
Protein binding	15–40%
Metabolism	CYP2D6, DBH, FMO3
Onset of action	IR dosing: 0.5–1.5 hours XR dosing: 1.5–2 hours
Elimination half-life	9–11 hourspH-dependent: 7–34 hours
Duration of action	IR dosing: 3–6 hoursXR dosing: 8–12 hours
Excretion	Renal (45%); urinary pH-dependent
Identifiers
CAS Number	51-64-9
PubChem CID	5826
IUPHAR/BPS	2147
DrugBank	DB01576
ChemSpider	5621
UNII	TZ47U051FI
KEGG	D03740
ChEBI	CHEBI:4469
ChEMBL	ChEMBL612
CompTox Dashboard (EPA)	DTXSID8022907
ECHA InfoCard	100.000.103
Chemical and physical data
Formula	C9H13N
Molar mass	135.210 g·mol−1
3D model (JSmol)	Interactive image
Density	0.913 g/cm3
Boiling point	201.5 °C (394.7 °F)
Solubility in water	20 mg/mL (20 °C)

Dextroamphetamine is a central nervous system (CNS) stimulant and an amphetamine enantiomer that is prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It is also used as an athletic performance and cognitive enhancer, and recreationally as an aphrodisiac and euphoriant. Dextroamphetamine was also used by military air, tank and special forces as a 'go-pill' during fatigue-inducing missions such as night-time bombing missions or extended combat operations.

The amphetamine molecule exists as two enantiomers, levoamphetamine and dextroamphetamine. Dextroamphetamine is the dextrorotatory, or 'right-handed', enantiomer and exhibits more pronounced effects on the central nervous system than levoamphetamine. Pharmaceutical dextroamphetamine sulfate is available as both a brand name and generic drug in a variety of dosage forms. Dextroamphetamine is sometimes prescribed as the inactive prodrug lisdexamfetamine dimesylate, which is converted into dextroamphetamine after absorption.

Dextroamphetamine, like other amphetamines, elicits its stimulating effects via several distinct actions: it inhibits or reverses the transporter proteins for the monoamine neurotransmitters (namely the serotonin, norepinephrine and dopamine transporters) either via trace amine-associated receptor 1 (TAAR1) or in a TAAR1 independent fashion when there are high cytosolic concentrations of the monoamine neurotransmitters and it releases these neurotransmitters from synaptic vesicles via vesicular monoamine transporter 2. It also shares many chemical and pharmacological properties with human trace amines, particularly phenethylamine and N-methylphenethylamine, the latter being an isomer of amphetamine produced within the human body.

Uses

Medical

Dexedrine IR tablets

 

Dexedrine Spansule 5, 10 and 15 mg capsules

 

Dextroamphetamine is used to treat attention deficit hyperactivity disorder (ADHD) and narcolepsy (a sleep disorder), and is sometimes prescribed off-label for its past medical indications, such as depression and obesity. Long-term amphetamine exposure at sufficiently high doses in some animal species is known to produce abnormal dopamine system development or nerve damage, but, in humans with ADHD, pharmaceutical amphetamines appear to improve brain development and nerve growth. Reviews of magnetic resonance imaging (MRI) studies suggest that long-term treatment with amphetamine decreases abnormalities in brain structure and function found in subjects with ADHD, and improves function in several parts of the brain, such as the right caudate nucleus of the basal ganglia.

Reviews of clinical stimulant research have established the safety and effectiveness of long-term continuous amphetamine use for the treatment of ADHD. Randomized controlled trials of continuous stimulant therapy for the treatment of ADHD spanning 2 years have demonstrated treatment effectiveness and safety. Two reviews have indicated that long-term continuous stimulant therapy for ADHD is effective for reducing the core symptoms of ADHD (i.e., hyperactivity, inattention, and impulsivity), enhancing quality of life and academic achievement, and producing improvements in a large number of functional outcomes across 9 categories of outcomes related to academics, antisocial behavior, driving, non-medicinal drug use, obesity, occupation, self-esteem, service use (i.e., academic, occupational, health, financial, and legal services), and social function. One review highlighted a nine-month randomized controlled trial of amphetamine treatment for ADHD in children that found an average increase of 4.5 IQ points, continued increases in attention, and continued decreases in disruptive behaviors and hyperactivity. Another review indicated that, based upon the longest follow-up studies conducted to date, lifetime stimulant therapy that begins during childhood is continuously effective for controlling ADHD symptoms and reduces the risk of developing a substance use disorder as an adult.

As of 2009, models of ADHD suggest that it is associated with functional impairments in some of the brain's neurotransmitter systems; these functional impairments involve impaired dopamine neurotransmission in the mesocorticolimbic projection and norepinephrine neurotransmission in the noradrenergic projections from the locus coeruleus to the prefrontal cortex. Psychostimulants like methylphenidate and amphetamine are effective in treating ADHD because they increase neurotransmitter activity in these systems. Approximately 80% of those who use these stimulants see improvements in ADHD symptoms. Children with ADHD who use stimulant medications generally have better relationships with peers and family members, perform better in school, are less distractible and impulsive, and have longer attention spans. The Cochrane reviews on the treatment of ADHD in children, adolescents, and adults with pharmaceutical amphetamines stated that short-term studies have demonstrated that these drugs decrease the severity of symptoms, but they have higher discontinuation rates than non-stimulant medications due to their adverse side effects. A Cochrane review on the treatment of ADHD in children with tic disorders such as Tourette syndrome indicated that stimulants in general do not make tics worse, but high doses of dextroamphetamine could exacerbate tics in some individuals.

Enhancing performance

Cognitive performance

In 2015, a systematic review and a meta-analysis of high quality clinical trials found that, when used at low (therapeutic) doses, amphetamine produces modest yet unambiguous improvements in cognition, including working memory, long-term episodic memory, inhibitory control, and some aspects of attention, in normal healthy adults; these cognition-enhancing effects of amphetamine are known to be partially mediated through the indirect activation of both dopamine receptor D₁ and adrenoceptor α₂ in the prefrontal cortex. A systematic review from 2014 found that low doses of amphetamine also improve memory consolidation, in turn leading to improved recall of information. Therapeutic doses of amphetamine also enhance cortical network efficiency, an effect which mediates improvements in working memory in all individuals. Amphetamine and other ADHD stimulants also improve task saliency (motivation to perform a task) and increase arousal (wakefulness), in turn promoting goal-directed behavior. Stimulants such as amphetamine can improve performance on difficult and boring tasks and are used by some students as a study and test-taking aid. Based upon studies of self-reported illicit stimulant use, 5–35% of college students use diverted ADHD stimulants, which are primarily used for enhancement of academic performance rather than as recreational drugs. However, high amphetamine doses that are above the therapeutic range can interfere with working memory and other aspects of cognitive control.

Physical performance

Amphetamine is used by some athletes for its psychological and athletic performance-enhancing effects, such as increased endurance and alertness; however, non-medical amphetamine use is prohibited at sporting events that are regulated by collegiate, national, and international anti-doping agencies. In healthy people at oral therapeutic doses, amphetamine has been shown to increase muscle strength, acceleration, athletic performance in anaerobic conditions, and endurance (i.e., it delays the onset of fatigue), while improving reaction time. Amphetamine improves endurance and reaction time primarily through reuptake inhibition and release of dopamine in the central nervous system. Amphetamine and other dopaminergic drugs also increase power output at fixed levels of perceived exertion by overriding a "safety switch", allowing the core temperature limit to increase in order to access a reserve capacity that is normally off-limits. At therapeutic doses, the adverse effects of amphetamine do not impede athletic performance; however, at much higher doses, amphetamine can induce effects that severely impair performance, such as rapid muscle breakdown and elevated body temperature.

Recreational

Dextroamphetamine is also used recreationally as a euphoriant and aphrodisiac, and like other amphetamines is used as a club drug for its energetic and euphoric high. Dextroamphetamine is considered to have a high potential for misuse in a recreational manner since individuals typically report feeling euphoric, more alert, and more energetic after taking the drug. Large recreational doses of dextroamphetamine may produce symptoms of dextroamphetamine overdose. Recreational users sometimes open dexedrine capsules and crush the contents in order to snort it or subsequently dissolve it in water and inject it. Injection into the bloodstream can be dangerous because insoluble fillers within the tablets can block small blood vessels. Chronic overuse of dextroamphetamine can lead to severe drug dependence, resulting in withdrawal symptoms when drug use stops.

Contraindications

According to the International Programme on Chemical Safety (IPCS) and the U.S. Food and Drug Administration (USFDA), amphetamine is contraindicated in people with a history of drug abuse, cardiovascular disease, severe agitation, or severe anxiety. It is also contraindicated in people experiencing advanced arteriosclerosis (hardening of the arteries), glaucoma (increased eye pressure), hyperthyroidism (excessive production of thyroid hormone), or moderate to severe hypertension. These agencies indicate that people who have experienced allergic reactions to other stimulants or who are taking monoamine oxidase inhibitors (MAOIs) should not take amphetamine, although safe concurrent use of amphetamine and monoamine oxidase inhibitors has been documented. These agencies also state that anyone with anorexia nervosa, bipolar disorder, depression, hypertension, liver or kidney problems, mania, psychosis, Raynaud's phenomenon, seizures, thyroid problems, tics, or Tourette syndrome should monitor their symptoms while taking amphetamine. Evidence from human studies indicates that therapeutic amphetamine use does not cause developmental abnormalities in the fetus or newborns (i.e., it is not a human teratogen), but amphetamine abuse does pose risks to the fetus. Amphetamine has also been shown to pass into breast milk, so the IPCS and the USFDA advise mothers to avoid breastfeeding when using it. Due to the potential for reversible growth impairments, the USFDA advises monitoring the height and weight of children and adolescents prescribed an amphetamine pharmaceutical.

Adverse effects

Physical

At normal therapeutic doses, the physical side effects of amphetamine vary widely by age and from person to person. Cardiovascular side effects can include hypertension or hypotension from a vasovagal response, Raynaud's phenomenon (reduced blood flow to the hands and feet), and tachycardia (increased heart rate). Sexual side effects in males may include erectile dysfunction, frequent erections, or prolonged erections. Gastrointestinal side effects may include abdominal pain, constipation, diarrhea, and nausea. Other potential physical side effects include appetite loss, blurred vision, dry mouth, excessive grinding of the teeth, nosebleed, profuse sweating, rhinitis medicamentosa (drug-induced nasal congestion), reduced seizure threshold, tics (a type of movement disorder), and weight loss. Dangerous physical side effects are rare at typical pharmaceutical doses.

Amphetamine stimulates the medullary respiratory centers, producing faster and deeper breaths. In a normal person at therapeutic doses, this effect is usually not noticeable, but when respiration is already compromised, it may be evident. Amphetamine also induces contraction in the urinary bladder sphincter, the muscle which controls urination, which can result in difficulty urinating. This effect can be useful in treating bed wetting and loss of bladder control. The effects of amphetamine on the gastrointestinal tract are unpredictable. If intestinal activity is high, amphetamine may reduce gastrointestinal motility (the rate at which content moves through the digestive system); however, amphetamine may increase motility when the smooth muscle of the tract is relaxed. Amphetamine also has a slight analgesic effect and can enhance the pain relieving effects of opioids.

USFDA-commissioned studies from 2011, indicate that in children, young adults, and adults there is no association between serious adverse cardiovascular events (sudden death, heart attack, and stroke) and the medical use of amphetamine or other ADHD stimulants. However, amphetamine pharmaceuticals are contraindicated in individuals with cardiovascular disease.

Psychological

At normal therapeutic doses, the most common psychological side effects of amphetamine include increased alertness, apprehension, concentration, initiative, self-confidence and sociability, mood swings (elated mood followed by mildly depressed mood), insomnia or wakefulness, and decreased sense of fatigue. Less common side effects include anxiety, change in libido, grandiosity, irritability, repetitive or obsessive behaviors, and restlessness; these effects depend on the user's personality and current mental state. Amphetamine psychosis (e.g., delusions and paranoia) can occur in heavy users. Although very rare, this psychosis can also occur at therapeutic doses during long-term therapy. According to the USFDA, "there is no systematic evidence" that stimulants produce aggressive behavior or hostility.

Amphetamine has also been shown to produce a conditioned place preference in humans taking therapeutic doses, meaning that individuals acquire a preference for spending time in places where they have previously used amphetamine.

Reinforcement disorders

Addiction

Addiction is a serious risk with heavy recreational amphetamine use, but is unlikely to occur from long-term medical use at therapeutic doses; in fact, lifetime stimulant therapy for ADHD that begins during childhood reduces the risk of developing substance use disorders as an adult. Pathological overactivation of the mesolimbic pathway, a dopamine pathway that connects the ventral tegmental area to the nucleus accumbens, plays a central role in amphetamine addiction. Individuals who frequently self-administer high doses of amphetamine have a high risk of developing an amphetamine addiction, since chronic use at high doses gradually increase the level of accumbal ΔFosB, a "molecular switch" and "master control protein" for addiction. Once nucleus accumbens ΔFosB is sufficiently overexpressed, it begins to increase the severity of addictive behavior (i.e., compulsive drug-seeking) with further increases in its expression. While there are no effective drugs for treating amphetamine addiction as of 2015, regularly engaging in sustained aerobic exercise appears to reduce the risk of developing such an addiction. Sustained aerobic exercise on a regular basis also appears to be an effective treatment for amphetamine addiction; exercise therapy improves clinical treatment outcomes and may be used as a combination therapy with cognitive behavioral therapy, which is the best clinical treatment available as of 2015.

Biomolecular mechanisms

Chronic use of amphetamine at excessive doses causes alterations in gene expression in the mesocorticolimbic projection, which arise through transcriptional and epigenetic mechanisms. The most important transcription factors that produce these alterations are Delta FBJ murine osteosarcoma viral oncogene homolog B (ΔFosB), cAMP response element binding protein (CREB), and nuclear factor-kappa B (NF-κB). ΔFosB is the most significant biomolecular mechanism in addiction because ΔFosB overexpression (i.e., an abnormally high level of gene expression which produces a pronounced gene-related phenotype) in the D1-type medium spiny neurons in the nucleus accumbens is necessary and sufficient for many of the neural adaptations and regulates multiple behavioral effects (e.g., reward sensitization and escalating drug self-administration) involved in addiction. Once ΔFosB is sufficiently overexpressed, it induces an addictive state that becomes increasingly more severe with further increases in ΔFosB expression. It has been implicated in addictions to alcohol, cannabinoids, cocaine, methylphenidate, nicotine, opioids, phencyclidine, propofol, and substituted amphetamines, among others.

ΔJunD, a transcription factor, and G9a, a histone methyltransferase enzyme, both oppose the function of ΔFosB and inhibit increases in its expression. Sufficiently overexpressing ΔJunD in the nucleus accumbens with viral vectors can completely block many of the neural and behavioral alterations seen in chronic drug abuse (i.e., the alterations mediated by ΔFosB). ΔFosB also plays an important role in regulating behavioral responses to natural rewards, such as palatable food, sex, and exercise. Since both natural rewards and addictive drugs induce the expression of ΔFosB (i.e., they cause the brain to produce more of it), chronic acquisition of these rewards can result in a similar pathological state of addiction. Consequently, ΔFosB is the most significant factor involved in both amphetamine addiction and amphetamine-induced sexual addictions, which are compulsive sexual behaviors that result from excessive sexual activity and amphetamine use. These sexual addictions are associated with a dopamine dysregulation syndrome which occurs in some patients taking dopaminergic drugs.

The effects of amphetamine on gene regulation are both dose- and route-dependent. Most of the research on gene regulation and addiction is based upon animal studies with intravenous amphetamine administration at very high doses. The few studies that have used equivalent (weight-adjusted) human therapeutic doses and oral administration show that these changes, if they occur, are relatively minor. This suggests that medical use of amphetamine does not significantly affect gene regulation.

Pharmacological treatments

As of 2015, there is no effective pharmacotherapy for amphetamine addiction. Reviews from 2015 and 2016 indicated that TAAR1-selective agonists have significant therapeutic potential as a treatment for psychostimulant addictions; however, as of February 2016, the only compounds which are known to function as TAAR1-selective agonists are experimental drugs. Amphetamine addiction is largely mediated through increased activation of dopamine receptors and co-localized NMDA receptors in the nucleus accumbens; magnesium ions inhibit NMDA receptors by blocking the receptor calcium channel. One review suggested that, based upon animal testing, pathological (addiction-inducing) psychostimulant use significantly reduces the level of intracellular magnesium throughout the brain. Supplemental magnesium treatment has been shown to reduce amphetamine self-administration (i.e., doses given to oneself) in humans, but it is not an effective monotherapy for amphetamine addiction.

Behavioral treatments

Cognitive behavioral therapy is the most effective clinical treatment for psychostimulant addictions as of 2009. Additionally, research on the neurobiological effects of physical exercise suggests that daily aerobic exercise, especially endurance exercise (e.g., marathon running), prevents the development of drug addiction and is an effective adjunct therapy (i.e., a supplemental treatment) for amphetamine addiction. Exercise leads to better treatment outcomes when used as an adjunct treatment, particularly for psychostimulant addictions. In particular, aerobic exercise decreases psychostimulant self-administration, reduces the reinstatement (i.e., relapse) of drug-seeking, and induces increased dopamine receptor D₂ (DRD2) density in the striatum. This is the opposite of pathological stimulant use, which induces decreased striatal DRD2 density. One review noted that exercise may also prevent the development of a drug addiction by altering ΔFosB or c-Fos immunoreactivity in the striatum or other parts of the reward system.

Dependence and withdrawal

Drug tolerance develops rapidly in amphetamine abuse (i.e., recreational amphetamine use), so periods of extended abuse require increasingly larger doses of the drug in order to achieve the same effect. According to a Cochrane review on withdrawal in individuals who compulsively use amphetamine and methamphetamine, "when chronic heavy users abruptly discontinue amphetamine use, many report a time-limited withdrawal syndrome that occurs within 24 hours of their last dose." This review noted that withdrawal symptoms in chronic, high-dose users are frequent, occurring in roughly 88% of cases, and persist for 3–4 weeks with a marked "crash" phase occurring during the first week. Amphetamine withdrawal symptoms can include anxiety, drug craving, depressed mood, fatigue, increased appetite, increased movement or decreased movement, lack of motivation, sleeplessness or sleepiness, and lucid dreams. The review indicated that the severity of withdrawal symptoms is positively correlated with the age of the individual and the extent of their dependence. Mild withdrawal symptoms from the discontinuation of amphetamine treatment at therapeutic doses can be avoided by tapering the dose.

Overdose

An amphetamine overdose can lead to many different symptoms, but is rarely fatal with appropriate care. The severity of overdose symptoms increases with dosage and decreases with drug tolerance to amphetamine. Tolerant individuals have been known to take as much as 5 grams of amphetamine in a day, which is roughly 100 times the maximum daily therapeutic dose. Symptoms of a moderate and extremely large overdose are listed below; fatal amphetamine poisoning usually also involves convulsions and coma. In 2013, overdose on amphetamine, methamphetamine, and other compounds implicated in an "amphetamine use disorder" resulted in an estimated 3,788 deaths worldwide (3,425–4,145 deaths, 95% confidence).

Toxicity

In rodents and primates, sufficiently high doses of amphetamine cause dopaminergic neurotoxicity, or damage to dopamine neurons, which is characterized by dopamine terminal degeneration and reduced transporter and receptor function. There is no evidence that amphetamine is directly neurotoxic in humans. However, large doses of amphetamine may indirectly cause dopaminergic neurotoxicity as a result of hyperpyrexia, the excessive formation of reactive oxygen species, and increased autoxidation of dopamine. Animal models of neurotoxicity from high-dose amphetamine exposure indicate that the occurrence of hyperpyrexia (i.e., core body temperature ≥ 40 °C) is necessary for the development of amphetamine-induced neurotoxicity. Prolonged elevations of brain temperature above 40 °C likely promote the development of amphetamine-induced neurotoxicity in laboratory animals by facilitating the production of reactive oxygen species, disrupting cellular protein function, and transiently increasing blood–brain barrier permeability.

Psychosis

An amphetamine overdose can result in a stimulant psychosis that may involve a variety of symptoms, such as delusions and paranoia. A Cochrane review on treatment for amphetamine, dextroamphetamine, and methamphetamine psychosis states that about 5–15% of users fail to recover completely. According to the same review, there is at least one trial that shows antipsychotic medications effectively resolve the symptoms of acute amphetamine psychosis. Psychosis rarely arises from therapeutic use.

Interactions

Many types of substances are known to interact with amphetamine, resulting in altered drug action or metabolism of amphetamine, the interacting substance, or both. Inhibitors of the enzymes that metabolize amphetamine (e.g., CYP2D6 and FMO3) will prolong its elimination half-life, meaning that its effects will last longer. Amphetamine also interacts with MAOIs, particularly monoamine oxidase A inhibitors, since both MAOIs and amphetamine increase plasma catecholamines (i.e., norepinephrine and dopamine); therefore, concurrent use of both is dangerous. Amphetamine modulates the activity of most psychoactive drugs. In particular, amphetamine may decrease the effects of sedatives and depressants and increase the effects of stimulants and antidepressants. Amphetamine may also decrease the effects of antihypertensives and antipsychotics due to its effects on blood pressure and dopamine respectively. Zinc supplementation may reduce the minimum effective dose of amphetamine when it is used for the treatment of ADHD.

Pharmacology

Pharmacodynamics

Amphetamine and its enantiomers have been identified as potent full agonists of trace amine-associated receptor 1 (TAAR1), a GPCR, discovered in 2001, that is important for regulation of monoaminergic systems in the brain. Activation of TAAR1 increases cAMP production via adenylyl cyclase activation and inhibits the function of the dopamine transporter, norepinephrine transporter, and serotonin transporter, as well as inducing the release of these monoamine neurotransmitters (effluxion). Amphetamine enantiomers are also substrates for a specific neuronal synaptic vesicle uptake transporter called VMAT2. When amphetamine is taken up by VMAT2, the vesicle releases (effluxes) dopamine, norepinephrine, and serotonin, among other monoamines, into the cytosol in exchange.

Dextroamphetamine (the dextrorotary enantiomer) and levoamphetamine (the levorotary enantiomer) have identical pharmacodynamics, but their binding affinities to their biomolecular targets vary. Dextroamphetamine is a more potent agonist of TAAR1 than levoamphetamine. Consequently, dextroamphetamine produces roughly three to four times more central nervous system (CNS) stimulation than levoamphetamine; however, levoamphetamine has slightly greater cardiovascular and peripheral effects.

Related endogenous compounds

Amphetamine has a very similar structure and function to the endogenous trace amines, which are naturally occurring neuromodulator molecules produced in the human body and brain. Among this group, the most closely related compounds are phenethylamine, the parent compound of amphetamine, and N-methylphenethylamine, an isomer of amphetamine (i.e., it has an identical molecular formula). In humans, phenethylamine is produced directly from L-phenylalanine by the aromatic amino acid decarboxylase (AADC) enzyme, which converts L-DOPA into dopamine as well. In turn, N-methylphenethylamine is metabolized from phenethylamine by phenylethanolamine N-methyltransferase, the same enzyme that metabolizes norepinephrine into epinephrine. Like amphetamine, both phenethylamine and N-methylphenethylamine regulate monoamine neurotransmission via TAAR1; unlike amphetamine, both of these substances are broken down by monoamine oxidase B, and therefore have a shorter half-life than amphetamine.

Pharmacokinetics

The oral bioavailability of amphetamine varies with gastrointestinal pH; it is well absorbed from the gut, and bioavailability is typically over 75% for dextroamphetamine. Amphetamine is a weak base with a pK_a of 9.9; consequently, when the pH is basic, more of the drug is in its lipid soluble free base form, and more is absorbed through the lipid-rich cell membranes of the gut epithelium. Conversely, an acidic pH means the drug is predominantly in a water-soluble cationic (salt) form, and less is absorbed. Approximately 15–40% of amphetamine circulating in the bloodstream is bound to plasma proteins. Following absorption, amphetamine readily distributes into most tissues in the body, with high concentrations occurring in cerebrospinal fluid and brain tissue.

The half-lives of amphetamine enantiomers differ and vary with urine pH. At normal urine pH, the half-lives of dextroamphetamine and levoamphetamine are 9–11 hours and 11–14 hours, respectively. Highly acidic urine will reduce the enantiomer half-lives to 7 hours; highly alkaline urine will increase the half-lives up to 34 hours. The immediate-release and extended release variants of salts of both isomers reach peak plasma concentrations at 3 hours and 7 hours post-dose respectively. Amphetamine is eliminated via the kidneys, with 30–40% of the drug being excreted unchanged at normal urinary pH. When the urinary pH is basic, amphetamine is in its free base form, so less is excreted. When urine pH is abnormal, the urinary recovery of amphetamine may range from a low of 1% to a high of 75%, depending mostly upon whether urine is too basic or acidic, respectively. Following oral administration, amphetamine appears in urine within 3 hours. Roughly 90% of ingested amphetamine is eliminated 3 days after the last oral dose.

CYP2D6, dopamine β-hydroxylase (DBH), flavin-containing monooxygenase 3 (FMO3), butyrate-CoA ligase (XM-ligase), and glycine N-acyltransferase (GLYAT) are the enzymes known to metabolize amphetamine or its metabolites in humans. Amphetamine has a variety of excreted metabolic products, including 4-hydroxyamphetamine, 4-hydroxynorephedrine, 4-hydroxyphenylacetone, benzoic acid, hippuric acid, norephedrine, and phenylacetone. Among these metabolites, the active sympathomimetics are 4-hydroxyamphetamine, 4-hydroxynorephedrine, and norephedrine. The main metabolic pathways involve aromatic para-hydroxylation, aliphatic alpha- and beta-hydroxylation, N-oxidation, N-dealkylation, and deamination.

The primary active metabolites of amphetamine are 4-hydroxyamphetamine and norephedrine; at normal urine pH, about 30–40% of amphetamine is excreted unchanged and roughly 50% is excreted as the inactive metabolites (bottom row). The remaining 10–20% is excreted as the active metabolites. Benzoic acid is metabolized by XM-ligase into an intermediate product, benzoyl-CoA, which is then metabolized by GLYAT into hippuric acid.

History, society, and culture

Racemic amphetamine was first synthesized under the chemical name "phenylisopropylamine" in Berlin, 1887 by the Romanian chemist Lazar Edeleanu. It was not widely marketed until 1932, when the pharmaceutical company Smith, Kline & French (now known as GlaxoSmithKline) introduced it in the form of the Benzedrine inhaler for use as a bronchodilator. Notably, the amphetamine contained in the Benzedrine inhaler was the liquid free-base, not a chloride or sulfate salt.

Three years later, in 1935, the medical community became aware of the stimulant properties of amphetamine, specifically dextroamphetamine, and in 1937 Smith, Kline, and French introduced tablets under the tradename Dexedrine. In the United States, Dexedrine was approved to treat narcolepsy, attention disorders, and obesity. In Canada indications once included epilepsy and parkinsonism. Dextroamphetamine was marketed in various other forms in the following decades, primarily by Smith, Kline, and French, such as several combination medications including a mixture of dextroamphetamine and amobarbital (a barbiturate) sold under the tradename Dexamyl and, in the 1950s, an extended release capsule (the "Spansule"). Preparations containing dextroamphetamine were also used in World War II as a treatment against fatigue.

It quickly became apparent that dextroamphetamine and other amphetamines had a high potential for misuse, although they were not heavily controlled until 1970, when the Comprehensive Drug Abuse Prevention and Control Act was passed by the United States Congress. Dextroamphetamine, along with other sympathomimetics, was eventually classified as Schedule II, the most restrictive category possible for a drug with a government-sanctioned, recognized medical use. Internationally, it has been available under the names AmfeDyn (Italy), Curban (US), Obetrol (Switzerland), Simpamina (Italy), Dexedrine/GSK (US & Canada), Dexedrine/UCB (United Kingdom), Dextropa (Portugal), and Stild (Spain).

In October 2010, GlaxoSmithKline sold the rights for Dexedrine Spansule to Amedra Pharmaceuticals (a subsidiary of CorePharma).

The U.S. Air Force uses dextroamphetamine as one of its "go pills", given to pilots on long missions to help them remain focused and alert. Conversely, "no-go pills" are used after the mission is completed, to combat the effects of the mission and "go-pills". The Tarnak Farm incident was linked by media reports to the use of this drug on long term fatigued pilots. The military did not accept this explanation, citing the lack of similar incidents. Newer stimulant medications or awakeness promoting agents with different side effect profiles, such as modafinil, are being investigated and sometimes issued for this reason.

Formulations

Dextroamphetamine sulfate

Dexamphetamine 5 mg generic name tablets

 

In the United States, immediate release (IR) formulations of dextroamphetamine sulfate are available generically as 5 mg and 10 mg tablets, marketed by Barr (Teva Pharmaceutical Industries), Mallinckrodt Pharmaceuticals, Wilshire Pharmaceuticals, Aurobindo Pharmaceutical USA and CorePharma. Previous IR tablets sold by the brand names of Dexedrine and Dextrostat have been discontinued but in 2015 IR tablets became available by the brand name Zenzedi, offered as 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg and 30 mg tablets. Dextroamphetamine sulfate is also available as a controlled-release (CR) capsule preparation in strengths of 5 mg, 10 mg, and 15 mg under the brand name Dexedrine Spansule, with generic versions marketed by Barr and Mallinckrodt. A bubblegum flavored oral solution is available under the brand name ProCentra, manufactured by FSC Pediatrics, which is designed to be an easier method of administration in children who have difficulty swallowing tablets, each 5 mL contains 5 mg dextroamphetamine. The conversion rate between dextroamphetamine sulfate to amphetamine free base is .728.

In Australia, dexamphetamine is available in bottles of 100 instant release 5 mg tablets as a generic drug. or slow release dextroamphetamine preparations may be compounded by individual chemists. Similarly, in the United Kingdom it is only available in 5 mg instant release sulfate tablets under the generic name dextroamphetamine sulphate having had been available under the brand name Dexedrine prior to UCB Pharma disinvesting the product to another pharmaceutical company (Auden Mckenzie).

Lisdexamfetamine

Dextroamphetamine is the active metabolite of the prodrug lisdexamfetamine (L-lysine-dextroamphetamine), available by the brand name Vyvanse (Elvanse in the European market) (lisdexamfetamine dimesylate). Dextroamphetamine is liberated from lisdexamfetamine enzymatically following contact with red blood cells. The conversion is rate-limited by the enzyme, which prevents high blood concentrations of dextroamphetamine and reduces lisdexamfetamine's drug liking and abuse potential at clinical doses. Vyvanse is marketed as once-a-day dosing as it provides a slow release of dextroamphetamine into the body. Vyvanse is available as capsules, and chewable tablets, and in seven strengths; 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, and 70 mg. The conversion rate between lisdexamfetamine dimesylate (Vyvanse) to dextroamphetamine base is 29.5%.

Adderall

Adderall 20 mg tablets, some broken in half, with a lengthwise-folded US dollar bill along the bottom

 

Another pharmaceutical that contains dextroamphetamine is commonly known by the brand name Adderall. It is available as immediate release (IR) tablets and extended release (XR) capsules. Adderall contains equal amounts of four amphetamine salts:

One-quarter racemic (d,l-)amphetamine aspartate monohydrate

One-quarter dextroamphetamine saccharate

One-quarter dextroamphetamine sulfate

One-quarter racemic (d,l-)amphetamine sulfate

Adderall has a total amphetamine base equivalence of 63%. While the enantiomer ratio by dextroamphetamine salts to levoamphetamine salts is 3:1, the amphetamine base content is 75.9% dextroamphetamine, 24.1% levoamphetamine.