Amphetamine

Amphetamine

Overview
Amphetamine or amfetamine (INN
International Nonproprietary Name
An International Nonproprietary Name is the official nonproprietary or generic name given to a pharmaceutical substance, as designated by the World Health Organization...

) is a psychostimulant drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...

 of the phenethylamine
Phenethylamine
Phenylethylamine or phenethylamine is a natural monoamine alkaloid, trace amine, and also the name of a class of chemicals with many members well known for psychoactive drug and stimulant effects. Studies suggest that phenylethylamine functions as a neuromodulator or neurotransmitter in the...

 class which produces increased wakefulness and focus
Attention
Attention is the cognitive process of paying attention to one aspect of the environment while ignoring others. Attention is one of the most intensely studied topics within psychology and cognitive neuroscience....

 in association with decreased fatigue and appetite
Appetite
The appetite is the desire to eat food, felt as hunger. Appetite exists in all higher life-forms, and serves to regulate adequate energy intake to maintain metabolic needs. It is regulated by a close interplay between the digestive tract, adipose tissue and the brain. Decreased desire to eat is...

.

Brand names of medications that contain, or metabolize into, amphetamine include Adderall
Adderall
Adderall is a brand name of amphetamine salts–based medication used for attention-deficit hyperactivity disorder and narcolepsy. It is a brand-name psychostimulant medication composed of racemic amphetamine aspartate monohydrate, racemic amphetamine sulfate, dextroamphetamine saccharide, and...

, Dexedrine, Dextrostat, Desoxyn
Methamphetamine
Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...

, ProCentra
Dextroamphetamine
Dextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus as well as decreased fatigue and decreased appetite....

, and Vyvanse, as well as Benzedrine
Benzedrine
Benzedrine is the trade name of the racemic mixture of amphetamine . It was marketed under this brandname in the USA by Smith, Kline & French in the form of inhalers, starting in 1928...

 in the past.

The drug is also used recreationally
Recreational drug use
Recreational drug use is the use of a drug, usually psychoactive, with the intention of creating or enhancing recreational experience. Such use is controversial, however, often being considered to be also drug abuse, and it is often illegal...

 and as a performance enhancer.
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Encyclopedia
Amphetamine or amfetamine (INN
International Nonproprietary Name
An International Nonproprietary Name is the official nonproprietary or generic name given to a pharmaceutical substance, as designated by the World Health Organization...

) is a psychostimulant drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...

 of the phenethylamine
Phenethylamine
Phenylethylamine or phenethylamine is a natural monoamine alkaloid, trace amine, and also the name of a class of chemicals with many members well known for psychoactive drug and stimulant effects. Studies suggest that phenylethylamine functions as a neuromodulator or neurotransmitter in the...

 class which produces increased wakefulness and focus
Attention
Attention is the cognitive process of paying attention to one aspect of the environment while ignoring others. Attention is one of the most intensely studied topics within psychology and cognitive neuroscience....

 in association with decreased fatigue and appetite
Appetite
The appetite is the desire to eat food, felt as hunger. Appetite exists in all higher life-forms, and serves to regulate adequate energy intake to maintain metabolic needs. It is regulated by a close interplay between the digestive tract, adipose tissue and the brain. Decreased desire to eat is...

.

Brand names of medications that contain, or metabolize into, amphetamine include Adderall
Adderall
Adderall is a brand name of amphetamine salts–based medication used for attention-deficit hyperactivity disorder and narcolepsy. It is a brand-name psychostimulant medication composed of racemic amphetamine aspartate monohydrate, racemic amphetamine sulfate, dextroamphetamine saccharide, and...

, Dexedrine, Dextrostat, Desoxyn
Methamphetamine
Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...

, ProCentra
Dextroamphetamine
Dextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus as well as decreased fatigue and decreased appetite....

, and Vyvanse, as well as Benzedrine
Benzedrine
Benzedrine is the trade name of the racemic mixture of amphetamine . It was marketed under this brandname in the USA by Smith, Kline & French in the form of inhalers, starting in 1928...

 in the past.

The drug is also used recreationally
Recreational drug use
Recreational drug use is the use of a drug, usually psychoactive, with the intention of creating or enhancing recreational experience. Such use is controversial, however, often being considered to be also drug abuse, and it is often illegal...

 and as a performance enhancer. Recreational users of amphetamine have coined numerous street names for amphetamine, such as "speed". The European Monitoring Centre for Drugs and Drug Addiction
European Monitoring Centre for Drugs and Drug Addiction
The European Monitoring Centre for Drugs and Drug Addiction is an agency of the European Union. Established in 1993, the EMCDDA is located in Lisbon, Portugal.-Mission and role:...

 reports the typical retail price of diluted amphetamine in Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...

 varied between €3 and €15 ($4 to $21.55 USD
United States dollar
The United States dollar , also referred to as the American dollar, is the official currency of the United States of America. It is divided into 100 smaller units called cents or pennies....

) a gram in half of the reporting countries. Racemic amphetamine on the street is typically about 10% pure.

Effects



Physical effects


Physical effects of amphetamine can include hyperactivity, dilated pupils, vasoconstriction
Vasoconstriction
Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, particularly the large arteries, small arterioles and veins. The process is the opposite of vasodilation, the widening of blood vessels. The process is particularly important in...

, blood shot eyes, flushing
Flushing (physiology)
For a person to flush is to become markedly red in the face and often other areas of the skin, from various physiological conditions. Flushing is generally distinguished, despite a close physiological relation between them, from blushing, which is milder, generally restricted to the face, cheeks or...

, restlessness, dry mouth
Xerostomia
Xerostomia is the medical term for the subjective complaint of dry mouth due to a lack of saliva. Xerostomia is sometimes colloquially called pasties, cottonmouth, drooth, or doughmouth. Several diseases, treatments, and medications can cause xerostomia. It can also be exacerbated by smoking or...

, bruxism
Bruxism
Bruxism is characterized by the grinding of the teeth and typically includes the clenching of the jaw. It is an oral parafunctional activity that occurs in most humans at some time in their lives. In most people, bruxism is mild enough not to be a health problem...

, headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...

, tachycardia
Tachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...

, bradycardia
Bradycardia
Bradycardia , in the context of adult medicine, is the resting heart rate of under 60 beats per minute, though it is seldom symptomatic until the rate drops below 50 beat/min. It may cause cardiac arrest in some patients, because those with bradycardia may not be pumping enough oxygen to their heart...

, tachypnea
Tachypnea
Tachypnea means rapid breathing. Any rate between 12-20 breaths per minute is normal. Tachypnea is a respiration rate greater than 20 breaths per minute. - Distinction from other breathing terms :...

, hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

, hypotension
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...

, fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...

, diaphoresis
Diaphoresis
Diaphoresis is excessive sweating commonly associated with shock and other medical emergency conditions.Diaphoretic is the state of perspiring profusely, or something that has the power to cause increased perspiration....

, diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...

, constipation
Constipation
Constipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...

, blurred vision
Blurred vision
-Causes:There are many causes of blurred vision:* Use of atropine or other anticholinergics* Presbyopia -- Difficulty focusing on objects that are close. The elderly are common victims....

, aphasia
Aphasia
Aphasia is an impairment of language ability. This class of language disorder ranges from having difficulty remembering words to being completely unable to speak, read, or write....

, dizziness
Dizziness
Dizziness refers to an impairment in spatial perception and stability. The term is somewhat imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or a non-specific feeling such as giddiness or foolishness....

, twitching, insomnia
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...

, numbness, palpitations, arrhythmias, tremors, dry and/or itchy skin, acne
Acne
Acne is a general term used for acneiform eruptions. It is usually used as a synonym for acne vulgaris, but may also refer to:*Acne aestivalis*Acne conglobata*Acne cosmetica*Acne fulminans*Acne keloidalis nuchae*Acne mechanica...

, pallor
Pallor
Pallor is a reduced amount of oxyhaemoglobin in skin or mucous membrane, a pale color which can be caused by illness, emotional shock or stress, stimulant use, lack of exposure to sunlight, anaemia or genetics....

, convulsions, and with chronic and/or high doses, seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...

, stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...

, coma
Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...

, heart attack
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...

 and death
Death
Death is the permanent termination of the biological functions that sustain a living organism. Phenomena which commonly bring about death include old age, predation, malnutrition, disease, and accidents or trauma resulting in terminal injury....

 can occur.
There is also significant research which highlights the changes amphetamine produces in the dopaminergic system, even in clinical doses. One possible interpretation is that neurotoxic
Neurotoxicity
Neurotoxicity occurs when the exposure to natural or artificial toxic substances, which are called neurotoxins, alters the normal activity of the nervous system in such a way as to cause damage to nervous tissue. This can eventually disrupt or even kill neurons, key cells that transmit and process...

 effects exist even with doses approved for medical use.

Psychological effects


Psychological effects can include euphoria
Euphoria
Euphoria is an emotional and mental state defined as a sense of great elation and well being.Euphoria may also refer to:* Euphoria , a genus of scarab beetles* Euphoria, a genus name previously used for the longan and other trees...

, anxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

, increased libido
Libido
Libido refers to a person's sex drive or desire for sexual activity. The desire for sex is an aspect of a person's sexuality, but varies enormously from one person to another, and it also varies depending on circumstances at a particular time. A person who has extremely frequent or a suddenly...

, alertness
Alertness
Alertness is the state of paying close and continuous attention, being watchful and prompt to meet danger or emergency, or being quick to perceive and act. It is related to psychology as well as to physiology...

, concentration
Concentration
In chemistry, concentration is defined as the abundance of a constituent divided by the total volume of a mixture. Four types can be distinguished: mass concentration, molar concentration, number concentration, and volume concentration...

, energy
Energy
In physics, energy is an indirectly observed quantity. It is often understood as the ability a physical system has to do work on other physical systems...

, self-esteem
Self-esteem
Self-esteem is a term in psychology to reflect a person's overall evaluation or appraisal of his or her own worth. Self-esteem encompasses beliefs and emotions such as triumph, despair, pride and shame: some would distinguish how 'the self-concept is what we think about the self; self-esteem, the...

, self-confidence
Self-confidence
The socio-psychological concept of self-confidence relates to self-assuredness in one's personal judgment, ability, power, etc., sometimes manifested excessively.Being confident in yourself is infectious if you present yourself well, others will want to follow in your foot steps towards...

, sociability, irritability
Irritability
Irritability is an excessive response to stimuli. The term is used for both the physiological reaction to stimuli and for the pathological, abnormal or excessive sensitivity to stimuli; It is usually used to refer to anger or frustration....

, aggression
Aggression
In psychology, as well as other social and behavioral sciences, aggression refers to behavior between members of the same species that is intended to cause humiliation, pain, or harm. Ferguson and Beaver defined aggressive behavior as "Behavior which is intended to increase the social dominance of...

, psychosomatic disorders, psychomotor agitation
Psychomotor agitation
Psychomotor agitation is a series of unintentional and purposeless motions that stem from mental tension and anxiety of an individual. This includes pacing around a room, wringing one's hands, pulling off clothing and putting it back on and other similar actions...

, grandiosity
Grandiosity
Grandiosity is chiefly associated with narcissistic personality disorder, but also commonly features in manic or hypomanic episodes of bipolar disorder....

, repetitive and obsessive
Fixation (psychology)
Fixation: 'concept originated by Sigmund Freud to denote the persistence of anachronistic sexual traits'. Subsequently '"Fixation" acquired a broader connotation...

 behaviors, paranoia
Paranoia
Paranoia [] is a thought process believed to be heavily influenced by anxiety or fear, often to the point of irrationality and delusion. Paranoid thinking typically includes persecutory beliefs, or beliefs of conspiracy concerning a perceived threat towards oneself...

, and with chronic and/or high doses, amphetamine psychosis
Amphetamine psychosis
Stimulant psychosis is a psychotic disorder that appears in some people who use stimulant drugs. Most commonly, stimulant psychosis occurs in drug abusers who take very large doses but, in rare cases, it can also present in patients taking therapeutic doses under medical supervision...

 can occur.

Withdrawal effects


Withdrawal symptoms of amphetamine primarily consist of mental fatigue, mental depression
Depression (mood)
Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...

 and increased appetite
Appetite
The appetite is the desire to eat food, felt as hunger. Appetite exists in all higher life-forms, and serves to regulate adequate energy intake to maintain metabolic needs. It is regulated by a close interplay between the digestive tract, adipose tissue and the brain. Decreased desire to eat is...

. 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
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

, agitation
Psychomotor agitation
Psychomotor agitation is a series of unintentional and purposeless motions that stem from mental tension and anxiety of an individual. This includes pacing around a room, wringing one's hands, pulling off clothing and putting it back on and other similar actions...

, excessive sleep
Sleep
Sleep is a naturally recurring state characterized by reduced or absent consciousness, relatively suspended sensory activity, and inactivity of nearly all voluntary muscles. It is distinguished from quiet wakefulness by a decreased ability to react to stimuli, and is more easily reversible than...

, vivid or lucid dream
Dream
Dreams are successions of images, ideas, emotions, and sensations that occur involuntarily in the mind during certain stages of sleep. The content and purpose of dreams are not definitively understood, though they have been a topic of scientific speculation, philosophical intrigue and religious...

s, deep REM sleep and suicidal ideation
Suicidal ideation
Suicidal ideation is a common medical term for thoughts about suicide, which may be as detailed as a formulated plan, without the suicidal act itself. Although most people who undergo suicidal ideation do not commit suicide, some go on to make suicide attempts...

.

Contraindications


Amphetamine elevates cardiac output and blood pressure making it dangerous for use by patients with a history of heart disease
Heart disease
Heart disease, cardiac disease or cardiopathy is an umbrella term for a variety of diseases affecting the heart. , it is the leading cause of death in the United States, England, Canada and Wales, accounting for 25.4% of the total deaths in the United States.-Types:-Coronary heart disease:Coronary...

 or hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

. Amphetamine can cause a life-threatening complication in patients taking MAOI antidepressants. The use of amphetamine and amphetamine-like drugs is contraindicated in patients with narrow-angle glaucoma
Glaucoma
Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...

 or anatomically narrow angles. Like other sympathomimetic amines, amphetamine can induce transient mydriasis
Mydriasis
Mydriasis is a dilation of the pupil due to disease, trauma or the use of drugs. Normally, the pupil dilates in the dark and constricts in the light to respectively improve vividity at night and to protect the retina from sunlight damage during the day...

. In patients with narrow angles, pupillary dilation can provoke an acute attack of angle-closure glaucoma. These agents should also be avoided in patients with other forms of glaucoma, as mydriasis may occasionally increase intraocular pressure.

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.

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.

Overdose


An amphetamine overdose is rarely fatal but can lead to a number of different symptoms, including psychosis
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...

, chest pain
Chest pain
Chest pain may be a symptom of a number of serious conditions and is generally considered a medical emergency. Even though it may be determined that the pain is non-cardiac in origin, this is often a diagnosis of exclusion made after ruling out more serious causes of the pain.-Differential...

, and hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

.

Psychosis



Abuse of amphetamines can result in a stimulant psychosis that can present as a number of psychotic disorders (e.g. paranoia
Paranoia
Paranoia [] is a thought process believed to be heavily influenced by anxiety or fear, often to the point of irrationality and delusion. Paranoid thinking typically includes persecutory beliefs, or beliefs of conspiracy concerning a perceived threat towards oneself...

, hallucination
Hallucination
A hallucination, in the broadest sense of the word, is a perception in the absence of a stimulus. In a stricter sense, hallucinations are defined as perceptions in a conscious and awake state in the absence of external stimuli which have qualities of real perception, in that they are vivid,...

s, delusion
Delusion
A delusion is a false belief held with absolute conviction despite superior evidence. Unlike hallucinations, delusions are always pathological...

s). The intensity and duration of symptoms may vary, but unlike true psychotic disorders (e.g. schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...

), stimulant psychoses are not considered to be permanent and will eventually resolve upon discontinuation of the drug's use.

Primary sites of action



Amphetamine exerts its behavioral effects by modulating several key neurotransmitters in the brain, including dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

, serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

, and norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...

. However, the activity of amphetamine throughout the brain appears to be specific; certain receptors that respond to amphetamine in some regions of the brain tend not to do so in other regions. For instance, dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 D2 receptors
Dopamine receptor
Dopamine receptors are a class of metabotropic G protein-coupled receptors that are prominent in the vertebrate central nervous system . The neurotransmitter dopamine is the primary endogenous ligand for dopamine receptors....

 in the hippocampus
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...

, a region of the brain associated with forming new memories, appear to be unaffected by the presence of amphetamine.

The major neural systems affected by amphetamine are largely implicated in the brain’s reward circuitry. Moreover, neurotransmitters involved in various reward pathways of the brain appear to be the primary targets of amphetamine. One such neurotransmitter is dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

, a chemical messenger heavily active in the mesolimbic
Mesolimbic pathway
The mesolimbic pathway is one of the dopaminergic pathways in the brain. The pathway begins in the ventral tegmental area of the midbrain and connects to the limbic system via the nucleus accumbens, the amygdala, and the hippocampus as well as to the medial prefrontal cortex...

 and mesocortical
Mesocortical pathway
The mesocortical pathway is a neural pathway that connects the ventral tegmentum to the cerebral cortex, particularly the frontal lobes. It is one of the four major dopamine pathways in the brain...

 reward pathways. Not surprisingly, the anatomical components of these pathways—including the striatum
Striatum
The striatum, also known as the neostriatum or striate nucleus, is a subcortical part of the forebrain. It is the major input station of the basal ganglia system. The striatum, in turn, gets input from the cerebral cortex...

, the nucleus accumbens
Nucleus accumbens
The nucleus accumbens , also known as the accumbens nucleus or as the nucleus accumbens septi , is a collection of neurons and forms the main part of the ventral striatum...

, and the ventral striatum
Ventral striatum
The ventral striatum is generally considered that part of the striatum that is connectionally associated with limbic structures, such as the amygdala, hippocampus, midline thalamus, and certain regions of the prefrontal cortex...

—have been found to be primary sites of amphetamine action.

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
Euphoria
Euphoria is an emotional and mental state defined as a sense of great elation and well being.Euphoria may also refer to:* Euphoria , a genus of scarab beetles* Euphoria, a genus name previously used for the longan and other trees...

. A better understanding of the specific mechanisms by which amphetamine operates may increase our ability to treat amphetamine addiction
Substance use disorder
Substance use disorders include substance abuse and substance dependence. In DSM-IV, the conditions are formally diagnosed as one or the other, but it has been proposed that DSM-5 combine the two into a single condition called "Substance-use disorder"....

, as the brain’s reward circuitry has been widely implicated in addictions of many types.

Endogenous amphetamines


Amphetamine has been found to have several endogenous analogues; that is, molecules of a similar structure found naturally in the brain. l-Phenylalanine
Phenylalanine
Phenylalanine is an α-amino acid with the formula C6H5CH2CHCOOH. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. L-Phenylalanine is an electrically neutral amino acid, one of the twenty common amino acids used to biochemically form...

 and β-Phenethylamine
Phenethylamine
Phenylethylamine or phenethylamine is a natural monoamine alkaloid, trace amine, and also the name of a class of chemicals with many members well known for psychoactive drug and stimulant effects. Studies suggest that phenylethylamine functions as a neuromodulator or neurotransmitter in the...

 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
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

. All of the addictive drugs appear to enhance dopamine neurotransmission, including amphetamine and methamphetamine. Studies have shown that in select regions, amphetamine increases the concentrations of dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 in the synaptic cleft, thereby heightening the response of the post-synaptic neuron. This specific action hints at the hedonic response to the drug as well as to the drug’s 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 amphetamine’s actions on the vesicular
Synaptic vesicle
In a neuron, synaptic vesicles store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulses between neurons and are constantly recreated by the cell...

 level, increasing concentrations of dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 in the cytosol
Cytosol
The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....

 of the pre-synaptic neuron. The other focuses on the role of the dopamine transporter DAT
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

, and proposes that amphetamine may interact with DAT
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

 to induce reverse transport of dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 from the presynaptic neuron into the synaptic cleft.

The former hypothesis is backed by studies from David Sulzer
David Sulzer
David Sulzer is a American neuroscientist and Professor at Columbia University Medical Center in the Departments of Psychiatry, Neurology, and Pharmacology...

's lab at Columbia University
Columbia University
Columbia University in the City of New York is a private, Ivy League university in Manhattan, New York City. Columbia is the oldest institution of higher learning in the state of New York, the fifth oldest in the United States, and one of the country's nine Colonial Colleges founded before the...

 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
Synaptic vesicle
In a neuron, synaptic vesicles store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulses between neurons and are constantly recreated by the cell...

. 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
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 is then believed to interact with DAT
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

 to promote reverse transport. 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. Calcium may be a key molecule involved in the interactions between amphetamine and VMATs.

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
Autophagy
In cell biology, autophagy, or autophagocytosis, is a catabolic process involving the degradation of a cell's own components through the lysosomal machinery. It is a tightly regulated process that plays a normal part in cell growth, development, and homeostasis, helping to maintain a balance...

-related degradation of dopamine axons and dendrites.

The second hypothesis of amphetamine action on the plasma membrane dopamine transporter postulates a direct interaction between amphetamine and the DAT
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

. The activity of DAT
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

 is believed to depend on specific phosphorylating kinases, such as protein kinase c
Protein kinase C
Protein kinase C also known as PKC is a family of enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and threonine amino acid residues on these proteins. PKC enzymes in turn are activated by signals such as increases in...

, specifically PKC-β
PRKCB1
Protein kinase C beta type is an enzyme that in humans is encoded by the PRKCB gene..-Interactions:PRKCB1 has been shown to interact with RIPK4, Beta adrenergic receptor kinase, PDLIM5 and GNB2L1.-Further reading:-See also:*Protein kinase C...

. Upon phosphorylation, DAT
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

 undergoes a conformational change that results in the transportation of DAT-bound dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 from the extracellular to the intracellular environment. In the presence of amphetamine, however, DAT
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

 has been observed to function in reverse, spitting dopamine out of the presynaptic neuron and into the synaptic cleft. Thus, beyond inhibiting reuptake of dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

, amphetamine also stimulates the release of dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 molecules into the synapse.

In support of the above hypothesis, it has been found that PKC-β
PRKCB1
Protein kinase C beta type is an enzyme that in humans is encoded by the PRKCB gene..-Interactions:PRKCB1 has been shown to interact with RIPK4, Beta adrenergic receptor kinase, PDLIM5 and GNB2L1.-Further reading:-See also:*Protein kinase C...

 inhibitors eliminate the effects of amphetamine on extracellular dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 concentrations in the striatum of rats. This data suggests that the PKC-β
PRKCB1
Protein kinase C beta type is an enzyme that in humans is encoded by the PRKCB gene..-Interactions:PRKCB1 has been shown to interact with RIPK4, Beta adrenergic receptor kinase, PDLIM5 and GNB2L1.-Further reading:-See also:*Protein kinase C...

 kinase may represent a key point of interaction between amphetamine and the DAT
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

 transporter.

Additional actions of amphetamine contribute to its ability to release dopamine from neurons, including action as an inhibitor of monoamine oxidase
Monoamine oxidase
L-Monoamine oxidases are a family of enzymes that catalyze the oxidation of monoamines. They are found bound to the outer membrane of mitochondria in most cell types in the body. The enzyme was originally discovered by Mary Bernheim in the liver and was named tyramine oxidase...

, an enzyme responsible for dopamine breakdown in the cytosol; an ability to enhance dopamine synthesis apparently via actions on the enzyme tyrosine hydroxylase
Tyrosine hydroxylase
Tyrosine hydroxylase or tyrosine 3-monooxygenase is the enzyme responsible for catalyzing the conversion of the amino acid L-tyrosine to dihydroxyphenylalanine . It does so using tetrahydrobiopterin as a coenzyme. DOPA is a precursor for dopamine, which, in turn, is a precursor for norepinephrine ...

, which synthesizes the dopamine precursor L-DOPA; and some blockade of the DAT, an action that amphetamine shares with cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...

. 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.

Serotonin


Amphetamine has been found to exert similar effects on serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

 as on dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

. Like DAT
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

, the serotonin transporter SERT
Serotonin transporter
The serotonin transporter is a monoamine transporter protein.This protein is an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. This transport of serotonin by the SERT protein terminates the action of serotonin and recycles it...

 can be induced to operate in reverse upon stimulation by amphetamine. This mechanism is thought to rely on the actions of calcium ions, as well as on the proximity of certain transporter proteins.

The interaction between amphetamine and serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

 is only apparent in particular regions of the brain, such as the mesocorticolimbic projection
Mesocortical pathway
The mesocortical pathway is a neural pathway that connects the ventral tegmentum to the cerebral cortex, particularly the frontal lobes. It is one of the four major dopamine pathways in the brain...

. Recent studies additionally postulate that amphetamine may indirectly alter the behavior of glutamatergic pathways extending from the ventral tegmental area to the prefrontal cortex
Prefrontal cortex
The prefrontal cortex is the anterior part of the frontal lobes of the brain, lying in front of the motor and premotor areas.This brain region has been implicated in planning complex cognitive behaviors, personality expression, decision making and moderating correct social behavior...

. Glutamatergic pathways are strongly correlated with increased excitability at the level of the synapse. Increased extracellular concentrations of serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

 may thus modulate the excitatory activity of glutamatergic neurons.

The proposed ability of amphetamine to increase excitability of glutamatergic pathways may be of significance when considering serotonin-mediated addiction. An additional behavioral consequence may be the stereotyped locomotor stimulation that occurs in response to amphetamine exposure.

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
Nucleus accumbens
The nucleus accumbens , also known as the accumbens nucleus or as the nucleus accumbens septi , is a collection of neurons and forms the main part of the ventral striatum...

, striatum
Striatum
The striatum, also known as the neostriatum or striate nucleus, is a subcortical part of the forebrain. It is the major input station of the basal ganglia system. The striatum, in turn, gets input from the cerebral cortex...

, and prefrontal cortex
Prefrontal cortex
The prefrontal cortex is the anterior part of the frontal lobes of the brain, lying in front of the motor and premotor areas.This brain region has been implicated in planning complex cognitive behaviors, personality expression, decision making and moderating correct social behavior...

. Additionally, several studies demonstrate increased levels of norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...

, 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. The long-term effects of amphetamines use on neural development
Neural development
Neural development comprises the processes that generate, shape, and reshape the nervous system, from the earliest stages of embryogenesis to the final years of life. The study of neural development aims to describe the cellular basis of brain development and to address the underlying mechanisms...

 in children has not been well established. Based on a study in rats, amphetamine use during adolescence may impair adult working memory
Working memory
Working memory has been defined as the system which actively holds information in the mind to do verbal and nonverbal tasks such as reasoning and comprehension, and to make it available for further information processing...

.

Chemical properties



Amphetamine is a chiral
Chirality (chemistry)
A chiral molecule is a type of molecule that lacks an internal plane of symmetry and thus has a non-superimposable mirror image. The feature that is most often the cause of chirality in molecules is the presence of an asymmetric carbon atom....

 compound. The racemic
Racemic
In chemistry, a racemic mixture, or racemate , is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule. The first known racemic mixture was "racemic acid", which Louis Pasteur found to be a mixture of the two enantiomeric isomers of tartaric acid.- Nomenclature :A...

 mixture can be divided into its optical isomers: levo-
Levoamphetamine
Levoamphetamine is a psychostimulant known to increase wakefulness and focus in association with decreased appetite and fatigue. Levoamphetamine is the levorotary stereoisomer of the amphetamine molecule...

 and dextro-amphetamine
Dextroamphetamine
Dextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus as well as decreased fatigue and decreased appetite....

. Amphetamine is the parent compound of its own structural class, comprising a broad range of psychoactive derivatives
Derivative (chemistry)
In chemistry, a derivative is a compound that is derived from a similar compound by some chemical or physical process. In the past it was also used to mean a compound that can be imagined to arise from another compound, if one atom is replaced with another atom or group of atoms, but modern...

, from empathogens, MDA (3,4-Methylenedioxyamphetamine)
3,4-Methylenedioxyamphetamine
3,4-Methylenedioxyamphetamine , also known as tenamfetamine , is a psychedelic and entactogenic drug of the phenethylamine and amphetamine chemical classes...

 and MDMA (3,4-Methylenedioxy-N-methamphetamine) known as ecstasy, to the N-methylated form, methamphetamine
Methamphetamine
Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...

 known as 'meth', and to decongestants such as ephedrine (EPH)
Ephedrine
Ephedrine is a sympathomimetic amine commonly used as a stimulant, appetite suppressant, concentration aid, decongestant, and to treat hypotension associated with anaesthesia....

 . Amphetamine is a homologue
Homologous series
In chemistry, a homologous series is a series of compounds with a similar general formula, possessing similar chemical properties due to the presence of the same functional group, and showing a gradation in physical properties as a result of increase in molecular size and mass...

 of phenethylamine
Phenethylamine
Phenylethylamine or phenethylamine is a natural monoamine alkaloid, trace amine, and also the name of a class of chemicals with many members well known for psychoactive drug and stimulant effects. Studies suggest that phenylethylamine functions as a neuromodulator or neurotransmitter in the...

.

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
Adderall
Adderall is a brand name of amphetamine salts–based medication used for attention-deficit hyperactivity disorder and narcolepsy. It is a brand-name psychostimulant medication composed of racemic amphetamine aspartate monohydrate, racemic amphetamine sulfate, dextroamphetamine saccharide, and...

 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
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

 (DAT) to increase concentrations of dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 in the neuronal terminal.

Amphetamine, both as d-amphetamine (dextroamphetamine
Dextroamphetamine
Dextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus as well as decreased fatigue and decreased appetite....

) 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
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

, norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...

 (noradrenaline) and serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

. It is hypothesized that d-amphetamine acts primarily on the dopaminergic systems, while l-amphetamine is comparatively norepinephrinergic (noradrenergic). The primary reinforcing and behavioral-stimulant effects of amphetamine, however, are linked to enhanced dopaminergic activity, primarily in the mesolimbic dopamine system.

Amphetamine and other amphetamine-type stimulants principally act to release dopamine into the synaptic cleft. 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. 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
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

 (DAT) into the synapse. In addition, amphetamine binds reversibly to the DATs and blocks the transporter's ability to clear DA from the synaptic space. Amphetamine also acts in this way with norepinephrine (noradrenaline) and to a lesser extent serotonin.

In addition, amphetamine binds to a group of receptors called Trace Amine Associated Receptors (TAAR). TAAR are a newly discovered receptor system which seems to be affected by a range of amphetamine-like substances called trace amines.

History


Amphetamine was first synthesized in 1887 by the Romania
Romania
Romania is a country located at the crossroads of Central and Southeastern Europe, on the Lower Danube, within and outside the Carpathian arch, bordering on the Black Sea...

n chemist Lazăr Edeleanu
Lazar Edeleanu
Lazăr Edeleanu was a Romanian chemist of Jewish origin.He was the first chemist to synthesize amphetamine at the University of Berlin and the inventor of the modern method of refining crude oil.- His childhood and studies:...

 in Berlin, Germany
Berlin
Berlin is the capital city of Germany and is one of the 16 states of Germany. With a population of 3.45 million people, Berlin is Germany's largest city. It is the second most populous city proper and the seventh most populous urban area in the European Union...

. He named the compound phenylisopropylamine. It was one of a series of compounds related to the plant derivative ephedrine
Ephedrine
Ephedrine is a sympathomimetic amine commonly used as a stimulant, appetite suppressant, concentration aid, decongestant, and to treat hypotension associated with anaesthesia....

, which had been isolated from Ma-Huang that same year by Nagayoshi Nagai
Nagayoshi Nagai
was a notable Japanese organic chemist and pharmacologist, best known for his study of ephedrine.-Early life:Nagai was born in Myodo District, Awa Province as the son of a doctor and started studying rangaku medicine at the Dutch Medical School of Nagasaki in 1864...

. No pharmacological use was found for amphetamine until 1927, when pioneer psychopharmacologist
Psychopharmacology
Psychopharmacology is the scientific study of the actions of drugs and their effects on mood, sensation, thinking, and behavior...

 Gordon Alles
Gordon Alles
Gordon A. Alles , was an American chemist and pharmacologist who did much research on the isolation and properties of insulin for the treatment of diabetics. He is also credited with discovering and publishing the psychological effects of amphetamine, as well as for MDA...

 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
Inhaler
An inhaler or puffer is a medical device used for delivering medication into the body via the lungs. It is mainly used in the treatment of asthma and Chronic Obstructive Pulmonary Disease . Zanamivir , used to treat influenza, must be administered via inhaler...

 under the trade name
Trade name
A trade name, also known as a trading name or a business name, is the name which a business trades under for commercial purposes, although its registered, legal name, used for contracts and other formal situations, may be another....

 Benzedrine
Benzedrine
Benzedrine is the trade name of the racemic mixture of amphetamine . It was marketed under this brandname in the USA by Smith, Kline & French in the form of inhalers, starting in 1928...

, useful as a decongestant but readily usable for other purposes. 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". 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
Controlled Substances Act
The Controlled Substances Act was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. The CSA is the federal U.S. drug policy under which the manufacture, importation, possession, use and distribution of certain...

 in 1971.

The related compound methamphetamine
Methamphetamine
Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...

 was first synthesized from ephedrine
Ephedrine
Ephedrine is a sympathomimetic amine commonly used as a stimulant, appetite suppressant, concentration aid, decongestant, and to treat hypotension associated with anaesthesia....

 in Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...

 in 1920 by chemist Akira Ogata
Akira Ogata
was a Japanese chemist and the first to synthesize methamphetamine in crystalline form in 1919....

, via reduction of ephedrine using red phosphorus and iodine
Iodine
Iodine is a chemical element with the symbol I and atomic number 53. The name is pronounced , , or . The name is from the , meaning violet or purple, due to the color of elemental iodine vapor....

. The pharmaceutical Pervitin was a tablet of methamphetamine which was available in Germany from 1938 and widely used in the Wehrmacht
Wehrmacht
The Wehrmacht – from , to defend and , the might/power) were the unified armed forces of Nazi Germany from 1935 to 1945. It consisted of the Heer , the Kriegsmarine and the Luftwaffe .-Origin and use of the term:...

, 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.

In 1997 and 1998, researchers at Texas A&M University
Texas A&M University
Texas A&M University is a coeducational public research university located in College Station, Texas . It is the flagship institution of the Texas A&M University System. The sixth-largest university in the United States, A&M's enrollment for Fall 2011 was over 50,000 for the first time in school...

 claimed to have found amphetamine and methamphetamine in the foliage of two Acacia
Acacia
Acacia is a genus of shrubs and trees belonging to the subfamily Mimosoideae of the family Fabaceae, first described in Africa by the Swedish botanist Carl Linnaeus in 1773. Many non-Australian species tend to be thorny, whereas the majority of Australian acacias are not...

 species native to Texas
Texas
Texas is the second largest U.S. state by both area and population, and the largest state by area in the contiguous United States.The name, based on the Caddo word "Tejas" meaning "friends" or "allies", was applied by the Spanish to the Caddo themselves and to the region of their settlement in...

, A. berlandieri
Acacia berlandieri
Acacia berlandieri is a shrub native to the Southwestern United States and northeast Mexico that belongs to the subfamily Mimosoideae of Fabaceae . It grows tall, with blossoms that are spherical and white, occurring from February through April...

and A. rigidula
Acacia rigidula
Acacia rigidula, commonly known as Blackbrush Acacia or Chaparro Prieto, is a species of shrub or small tree in the legume family, Fabaceae. Its native range stretches from Texas in the United States south to central Mexico. This perennial is closely related to A. berlandieri and is not listed as...

. 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
Alexander Shulgin
Alexander "Sasha" Theodore Shulgin is an American pharmacologist, chemist, artist, and drug developer.Shulgin is credited with the popularization of MDMA, commonly known as ecstasy, in the late 1970s and early 1980s, especially for psychopharmaceutical use and the treatment of depression and...

, 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.

Performance-enhancing use


Adderall
Adderall
Adderall is a brand name of amphetamine salts–based medication used for attention-deficit hyperactivity disorder and narcolepsy. It is a brand-name psychostimulant medication composed of racemic amphetamine aspartate monohydrate, racemic amphetamine sulfate, dextroamphetamine saccharide, and...

, an amphetamine mixture, is used by some college and high-school students as a study and test-taking aid. 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 and the RAF used so many that "Methedrine won the Battle of Britain" according to one report. American bomber pilots use amphetamine ("go pills") to stay awake during long missions. The Tarnak Farm incident
Tarnak Farm incident
The Tarnak Farm incident refers to the killing of four Canadian soldiers and the injury of eight others from the Third Battalion of Princess Patricia's Canadian Light Infantry on the night of April 17, 2002, by an American F-16 fighter jet. The aircraft, piloted by U.S...

, in which an American F-16 pilot killed several friendly Canadian soldiers on the ground, was blamed by the pilot on his use of amphetamine. A nonjudicial hearing rejected the pilot's claim.

Amphetamine is also used by some professional, collegiate and high school athletes for its strong stimulant effect. Energy levels are perceived to be dramatically increased and sustained, which is believed to allow for more vigorous and longer play. However, at least one study has found that this effect is not measurable. The use of amphetamine during strenuous physical activity can be extremely dangerous, especially when combined with alcohol, and athletes have died as a result, for example, British cyclist Tom Simpson
Tom Simpson
Tom Simpson was the most successful English road racing cyclist of the post-war years. He infamously died of exhaustion on the slopes of Mont Ventoux during the 13th stage of the Tour de France in 1967...

.

Amphetamine use has historically been especially common among Major League Baseball
Major League Baseball
Major League Baseball is the highest level of professional baseball in the United States and Canada, consisting of teams that play in the National League and the American League...

 players and is usually known by the slang term "greenies". In 2006, the MLB banned the use of amphetamine. The ban is enforced through periodic drug-testing. However, the MLB has received some criticism because the consequences for amphetamine use are dramatically less severe than for anabolic steroid
Anabolic steroid
Anabolic steroids, technically known as anabolic-androgen steroids or colloquially simply as "steroids", are drugs that mimic the effects of testosterone and dihydrotestosterone in the body. They increase protein synthesis within cells, which results in the buildup of cellular tissue ,...

 use, with the first offense bringing only a warning and further testing.

Amphetamine was formerly in widespread use by truck drivers to combat symptoms of somnolence and to increase their concentration during driving, especially in the decades prior to the signing by former president Ronald Reagan
Ronald Reagan
Ronald Wilson Reagan was the 40th President of the United States , the 33rd Governor of California and, prior to that, a radio, film and television actor....

 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 driver—Implementation 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.

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
Goth subculture
The goth subculture is a contemporary subculture found in many countries. It began in England during the early 1980s in the gothic rock scene, an offshoot of the post-punk genre. The goth subculture has survived much longer than others of the same era, and has continued to diversify...

, gangsters, and casuals
Casuals
The casual subculture is a subsection of association football culture that is typified by football hooliganism and the wearing of expensive European designer clothing. The subculture originated in the United Kingdom in the early 1980s when many hooligans started wearing designer labels and...

 in all night soul and ska dances, punk concerts, basement show
Basement show
A basement show is a musical performance, often of the punk rock or hardcore punk variety, that is held in the basement of a residential home, rather than at a traditional venue. These are also sometimes referred to as "house shows" as they can happen anywhere in a residential house, not just in...

s and fighting on the terraces
Football hooliganism
Football hooliganism, sometimes referred to by the British media as the English Disease, is unruly and destructive behaviour—such as brawls, vandalism and intimidation—by association football club fans...

 by casuals.

The hippie
Hippie
The hippie subculture was originally a youth movement that arose in the United States during the mid-1960s and spread to other countries around the world. The etymology of the term 'hippie' is from hipster, and was initially used to describe beatniks who had moved into San Francisco's...

 counterculture
Counterculture
Counterculture is a sociological term used to describe the values and norms of behavior of a cultural group, or subculture, that run counter to those of the social mainstream of the day, the cultural equivalent of political opposition. Counterculture can also be described as a group whose behavior...

 was very critical of amphetamines due to the behaviors they cause; in an interview with the Los Angeles Free Press
Los Angeles Free Press
The Los Angeles Free Press , also called “the Freep”, was among the most widely distributed underground newspapers of the 1960s. It is often cited as the first such newspaper...

 in 1965, beat writer Allen Ginsberg
Allen Ginsberg
Irwin Allen Ginsberg was an American poet and one of the leading figures of the Beat Generation in the 1950s. He vigorously opposed militarism, materialism and sexual repression...

 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".

In literature


The writers of the Beat Generation
Beat generation
The Beat Generation refers to a group of American post-WWII writers who came to prominence in the 1950s, as well as the cultural phenomena that they both documented and inspired...

 used amphetamine extensively, mainly under the Benzedrine
Benzedrine
Benzedrine is the trade name of the racemic mixture of amphetamine . It was marketed under this brandname in the USA by Smith, Kline & French in the form of inhalers, starting in 1928...

 brand name. Jack Kerouac
Jack Kerouac
Jean-Louis "Jack" Lebris de Kerouac was an American novelist and poet. He is considered a literary iconoclast and, alongside William S. Burroughs and Allen Ginsberg, a pioneer of the Beat Generation. Kerouac is recognized for his spontaneous method of writing, covering topics such as Catholic...

 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.

Scottish author Irvine Welsh
Irvine Welsh
Irvine Welsh is a contemporary Scottish novelist, best known for his novel Trainspotting. His work is characterised by raw Scottish dialect, and brutal depiction of the realities of Edinburgh life...

 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
Trainspotting (novel)
Trainspotting is the first novel by Scottish writer Irvine Welsh. It is written in the form of short chapters narrated in the first person by various residents of Leith, Edinburgh, who either use heroin, are friends of the core group of heroin users, or engage in destructive activities that are...

 and Porno
Porno (novel)
Porno is a novel by Scottish writer Irvine Welsh, and is the sequel to Trainspotting.The book describes the characters of Trainspotting ten years after the events of the earlier book, as their paths cross again, this time with the pornography business as the backdrop rather than heroin use...

 reflect the changes in drug use and culture during the years that elapse between the two texts.

Amphetamine is frequently mentioned in the work of American journalist Hunter S. Thompson
Hunter S. Thompson
Hunter Stockton Thompson was an American journalist and author who wrote The Rum Diary , Fear and Loathing in Las Vegas and Fear and Loathing on the Campaign Trail '72 .He is credited as the creator of Gonzo journalism, a style of reporting where reporters involve themselves in the action to...

. Speed appears not only amongst 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, such as in his "Author's Note" in Fear and Loathing on the Campaign Trail '72
Fear and Loathing on the Campaign Trail '72
Fear and Loathing: On the Campaign Trail '72 is a collection of articles covering the 1972 presidential campaign written by the gonzo journalist Hunter S Thompson and illustrated by Ralph Steadman...

.


"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 Bowl
Super Bowl
The Super Bowl is the championship game of the National Football League , the highest level of professional American football in the United States, culminating a season that begins in the late summer of the previous calendar year. The Super Bowl uses Roman numerals to identify each game, rather...

s. ... Meanwhile,
Amphetamine (USAN
United States Adopted Name
United States Adopted Names are unique nonproprietary names assigned to pharmaceuticals marketed in the United States. Each name is assigned by the USAN Council, which is co-sponsored by the American Medical Association , the United States Pharmacopeial Convention , and the American Pharmacists...

, abbreviated from alpha-methyl
Methyl group
Methyl group is a functional group derived from methane, containing one carbon atom bonded to three hydrogen atoms —CH3. The group is often abbreviated Me. Such hydrocarbon groups occur in many organic compounds. The methyl group can be found in three forms: anion, cation and radical. The anion...

phenethylamine
Phenethylamine
Phenylethylamine or phenethylamine is a natural monoamine alkaloid, trace amine, and also the name of a class of chemicals with many members well known for psychoactive drug and stimulant effects. Studies suggest that phenylethylamine functions as a neuromodulator or neurotransmitter in the...

) or amfetamine (INN
International Nonproprietary Name
An International Nonproprietary Name is the official nonproprietary or generic name given to a pharmaceutical substance, as designated by the World Health Organization...

) is a psychostimulant drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...

 of the phenethylamine
Phenethylamine
Phenylethylamine or phenethylamine is a natural monoamine alkaloid, trace amine, and also the name of a class of chemicals with many members well known for psychoactive drug and stimulant effects. Studies suggest that phenylethylamine functions as a neuromodulator or neurotransmitter in the...

 class which produces increased wakefulness and focus
Attention
Attention is the cognitive process of paying attention to one aspect of the environment while ignoring others. Attention is one of the most intensely studied topics within psychology and cognitive neuroscience....

 in association with decreased fatigue and appetite
Appetite
The appetite is the desire to eat food, felt as hunger. Appetite exists in all higher life-forms, and serves to regulate adequate energy intake to maintain metabolic needs. It is regulated by a close interplay between the digestive tract, adipose tissue and the brain. Decreased desire to eat is...

.

Brand names of medications that contain, or metabolize into, amphetamine include Adderall
Adderall
Adderall is a brand name of amphetamine salts–based medication used for attention-deficit hyperactivity disorder and narcolepsy. It is a brand-name psychostimulant medication composed of racemic amphetamine aspartate monohydrate, racemic amphetamine sulfate, dextroamphetamine saccharide, and...

, Dexedrine, Dextrostat, Desoxyn
Methamphetamine
Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...

, ProCentra
Dextroamphetamine
Dextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus as well as decreased fatigue and decreased appetite....

, and Vyvanse, as well as Benzedrine
Benzedrine
Benzedrine is the trade name of the racemic mixture of amphetamine . It was marketed under this brandname in the USA by Smith, Kline & French in the form of inhalers, starting in 1928...

 in the past.

The drug is also used recreationally
Recreational drug use
Recreational drug use is the use of a drug, usually psychoactive, with the intention of creating or enhancing recreational experience. Such use is controversial, however, often being considered to be also drug abuse, and it is often illegal...

 and as a performance enhancer. Recreational users of amphetamine have coined numerous street names for amphetamine, such as "speed". The European Monitoring Centre for Drugs and Drug Addiction
European Monitoring Centre for Drugs and Drug Addiction
The European Monitoring Centre for Drugs and Drug Addiction is an agency of the European Union. Established in 1993, the EMCDDA is located in Lisbon, Portugal.-Mission and role:...

 reports the typical retail price of diluted amphetamine in Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...

 varied between €3 and €15 ($4 to $21.55 USD
United States dollar
The United States dollar , also referred to as the American dollar, is the official currency of the United States of America. It is divided into 100 smaller units called cents or pennies....

) a gram in half of the reporting countries. Racemic amphetamine on the street is typically about 10% pure.

Effects



Physical effects


Physical effects of amphetamine can include hyperactivity, dilated pupils, vasoconstriction
Vasoconstriction
Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, particularly the large arteries, small arterioles and veins. The process is the opposite of vasodilation, the widening of blood vessels. The process is particularly important in...

, blood shot eyes, flushing
Flushing (physiology)
For a person to flush is to become markedly red in the face and often other areas of the skin, from various physiological conditions. Flushing is generally distinguished, despite a close physiological relation between them, from blushing, which is milder, generally restricted to the face, cheeks or...

, restlessness, dry mouth
Xerostomia
Xerostomia is the medical term for the subjective complaint of dry mouth due to a lack of saliva. Xerostomia is sometimes colloquially called pasties, cottonmouth, drooth, or doughmouth. Several diseases, treatments, and medications can cause xerostomia. It can also be exacerbated by smoking or...

, bruxism
Bruxism
Bruxism is characterized by the grinding of the teeth and typically includes the clenching of the jaw. It is an oral parafunctional activity that occurs in most humans at some time in their lives. In most people, bruxism is mild enough not to be a health problem...

, headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...

, tachycardia
Tachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...

, bradycardia
Bradycardia
Bradycardia , in the context of adult medicine, is the resting heart rate of under 60 beats per minute, though it is seldom symptomatic until the rate drops below 50 beat/min. It may cause cardiac arrest in some patients, because those with bradycardia may not be pumping enough oxygen to their heart...

, tachypnea
Tachypnea
Tachypnea means rapid breathing. Any rate between 12-20 breaths per minute is normal. Tachypnea is a respiration rate greater than 20 breaths per minute. - Distinction from other breathing terms :...

, hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

, hypotension
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...

, fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...

, diaphoresis
Diaphoresis
Diaphoresis is excessive sweating commonly associated with shock and other medical emergency conditions.Diaphoretic is the state of perspiring profusely, or something that has the power to cause increased perspiration....

, diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...

, constipation
Constipation
Constipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...

, blurred vision
Blurred vision
-Causes:There are many causes of blurred vision:* Use of atropine or other anticholinergics* Presbyopia -- Difficulty focusing on objects that are close. The elderly are common victims....

, aphasia
Aphasia
Aphasia is an impairment of language ability. This class of language disorder ranges from having difficulty remembering words to being completely unable to speak, read, or write....

, dizziness
Dizziness
Dizziness refers to an impairment in spatial perception and stability. The term is somewhat imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or a non-specific feeling such as giddiness or foolishness....

, twitching, insomnia
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...

, numbness, palpitations, arrhythmias, tremors, dry and/or itchy skin, acne
Acne
Acne is a general term used for acneiform eruptions. It is usually used as a synonym for acne vulgaris, but may also refer to:*Acne aestivalis*Acne conglobata*Acne cosmetica*Acne fulminans*Acne keloidalis nuchae*Acne mechanica...

, pallor
Pallor
Pallor is a reduced amount of oxyhaemoglobin in skin or mucous membrane, a pale color which can be caused by illness, emotional shock or stress, stimulant use, lack of exposure to sunlight, anaemia or genetics....

, convulsions, and with chronic and/or high doses, seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...

, stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...

, coma
Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...

, heart attack
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...

 and death
Death
Death is the permanent termination of the biological functions that sustain a living organism. Phenomena which commonly bring about death include old age, predation, malnutrition, disease, and accidents or trauma resulting in terminal injury....

 can occur.
There is also significant research which highlights the changes amphetamine produces in the dopaminergic system, even in clinical doses. One possible interpretation is that neurotoxic
Neurotoxicity
Neurotoxicity occurs when the exposure to natural or artificial toxic substances, which are called neurotoxins, alters the normal activity of the nervous system in such a way as to cause damage to nervous tissue. This can eventually disrupt or even kill neurons, key cells that transmit and process...

 effects exist even with doses approved for medical use.

Psychological effects


Psychological effects can include euphoria
Euphoria
Euphoria is an emotional and mental state defined as a sense of great elation and well being.Euphoria may also refer to:* Euphoria , a genus of scarab beetles* Euphoria, a genus name previously used for the longan and other trees...

, anxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

, increased libido
Libido
Libido refers to a person's sex drive or desire for sexual activity. The desire for sex is an aspect of a person's sexuality, but varies enormously from one person to another, and it also varies depending on circumstances at a particular time. A person who has extremely frequent or a suddenly...

, alertness
Alertness
Alertness is the state of paying close and continuous attention, being watchful and prompt to meet danger or emergency, or being quick to perceive and act. It is related to psychology as well as to physiology...

, concentration
Concentration
In chemistry, concentration is defined as the abundance of a constituent divided by the total volume of a mixture. Four types can be distinguished: mass concentration, molar concentration, number concentration, and volume concentration...

, energy
Energy
In physics, energy is an indirectly observed quantity. It is often understood as the ability a physical system has to do work on other physical systems...

, self-esteem
Self-esteem
Self-esteem is a term in psychology to reflect a person's overall evaluation or appraisal of his or her own worth. Self-esteem encompasses beliefs and emotions such as triumph, despair, pride and shame: some would distinguish how 'the self-concept is what we think about the self; self-esteem, the...

, self-confidence
Self-confidence
The socio-psychological concept of self-confidence relates to self-assuredness in one's personal judgment, ability, power, etc., sometimes manifested excessively.Being confident in yourself is infectious if you present yourself well, others will want to follow in your foot steps towards...

, sociability, irritability
Irritability
Irritability is an excessive response to stimuli. The term is used for both the physiological reaction to stimuli and for the pathological, abnormal or excessive sensitivity to stimuli; It is usually used to refer to anger or frustration....

, aggression
Aggression
In psychology, as well as other social and behavioral sciences, aggression refers to behavior between members of the same species that is intended to cause humiliation, pain, or harm. Ferguson and Beaver defined aggressive behavior as "Behavior which is intended to increase the social dominance of...

, psychosomatic disorders, psychomotor agitation
Psychomotor agitation
Psychomotor agitation is a series of unintentional and purposeless motions that stem from mental tension and anxiety of an individual. This includes pacing around a room, wringing one's hands, pulling off clothing and putting it back on and other similar actions...

, grandiosity
Grandiosity
Grandiosity is chiefly associated with narcissistic personality disorder, but also commonly features in manic or hypomanic episodes of bipolar disorder....

, repetitive and obsessive
Fixation (psychology)
Fixation: 'concept originated by Sigmund Freud to denote the persistence of anachronistic sexual traits'. Subsequently '"Fixation" acquired a broader connotation...

 behaviors, paranoia
Paranoia
Paranoia [] is a thought process believed to be heavily influenced by anxiety or fear, often to the point of irrationality and delusion. Paranoid thinking typically includes persecutory beliefs, or beliefs of conspiracy concerning a perceived threat towards oneself...

, and with chronic and/or high doses, amphetamine psychosis
Amphetamine psychosis
Stimulant psychosis is a psychotic disorder that appears in some people who use stimulant drugs. Most commonly, stimulant psychosis occurs in drug abusers who take very large doses but, in rare cases, it can also present in patients taking therapeutic doses under medical supervision...

 can occur.

Withdrawal effects


Withdrawal symptoms of amphetamine primarily consist of mental fatigue, mental depression
Depression (mood)
Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...

 and increased appetite
Appetite
The appetite is the desire to eat food, felt as hunger. Appetite exists in all higher life-forms, and serves to regulate adequate energy intake to maintain metabolic needs. It is regulated by a close interplay between the digestive tract, adipose tissue and the brain. Decreased desire to eat is...

. 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
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

, agitation
Psychomotor agitation
Psychomotor agitation is a series of unintentional and purposeless motions that stem from mental tension and anxiety of an individual. This includes pacing around a room, wringing one's hands, pulling off clothing and putting it back on and other similar actions...

, excessive sleep
Sleep
Sleep is a naturally recurring state characterized by reduced or absent consciousness, relatively suspended sensory activity, and inactivity of nearly all voluntary muscles. It is distinguished from quiet wakefulness by a decreased ability to react to stimuli, and is more easily reversible than...

, vivid or lucid dream
Dream
Dreams are successions of images, ideas, emotions, and sensations that occur involuntarily in the mind during certain stages of sleep. The content and purpose of dreams are not definitively understood, though they have been a topic of scientific speculation, philosophical intrigue and religious...

s, deep REM sleep and suicidal ideation
Suicidal ideation
Suicidal ideation is a common medical term for thoughts about suicide, which may be as detailed as a formulated plan, without the suicidal act itself. Although most people who undergo suicidal ideation do not commit suicide, some go on to make suicide attempts...

.

Contraindications


Amphetamine elevates cardiac output and blood pressure making it dangerous for use by patients with a history of heart disease
Heart disease
Heart disease, cardiac disease or cardiopathy is an umbrella term for a variety of diseases affecting the heart. , it is the leading cause of death in the United States, England, Canada and Wales, accounting for 25.4% of the total deaths in the United States.-Types:-Coronary heart disease:Coronary...

 or hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

. Amphetamine can cause a life-threatening complication in patients taking MAOI antidepressants. The use of amphetamine and amphetamine-like drugs is contraindicated in patients with narrow-angle glaucoma
Glaucoma
Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...

 or anatomically narrow angles. Like other sympathomimetic amines, amphetamine can induce transient mydriasis
Mydriasis
Mydriasis is a dilation of the pupil due to disease, trauma or the use of drugs. Normally, the pupil dilates in the dark and constricts in the light to respectively improve vividity at night and to protect the retina from sunlight damage during the day...

. In patients with narrow angles, pupillary dilation can provoke an acute attack of angle-closure glaucoma. These agents should also be avoided in patients with other forms of glaucoma, as mydriasis may occasionally increase intraocular pressure.

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.

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.

Overdose


An amphetamine overdose is rarely fatal but can lead to a number of different symptoms, including psychosis
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...

, chest pain
Chest pain
Chest pain may be a symptom of a number of serious conditions and is generally considered a medical emergency. Even though it may be determined that the pain is non-cardiac in origin, this is often a diagnosis of exclusion made after ruling out more serious causes of the pain.-Differential...

, and hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

.

Psychosis



Abuse of amphetamines can result in a stimulant psychosis that can present as a number of psychotic disorders (e.g. paranoia
Paranoia
Paranoia [] is a thought process believed to be heavily influenced by anxiety or fear, often to the point of irrationality and delusion. Paranoid thinking typically includes persecutory beliefs, or beliefs of conspiracy concerning a perceived threat towards oneself...

, hallucination
Hallucination
A hallucination, in the broadest sense of the word, is a perception in the absence of a stimulus. In a stricter sense, hallucinations are defined as perceptions in a conscious and awake state in the absence of external stimuli which have qualities of real perception, in that they are vivid,...

s, delusion
Delusion
A delusion is a false belief held with absolute conviction despite superior evidence. Unlike hallucinations, delusions are always pathological...

s). The intensity and duration of symptoms may vary, but unlike true psychotic disorders (e.g. schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...

), stimulant psychoses are not considered to be permanent and will eventually resolve upon discontinuation of the drug's use.

Primary sites of action



Amphetamine exerts its behavioral effects by modulating several key neurotransmitters in the brain, including dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

, serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

, and norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...

. However, the activity of amphetamine throughout the brain appears to be specific; certain receptors that respond to amphetamine in some regions of the brain tend not to do so in other regions. For instance, dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 D2 receptors
Dopamine receptor
Dopamine receptors are a class of metabotropic G protein-coupled receptors that are prominent in the vertebrate central nervous system . The neurotransmitter dopamine is the primary endogenous ligand for dopamine receptors....

 in the hippocampus
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...

, a region of the brain associated with forming new memories, appear to be unaffected by the presence of amphetamine.

The major neural systems affected by amphetamine are largely implicated in the brain’s reward circuitry. Moreover, neurotransmitters involved in various reward pathways of the brain appear to be the primary targets of amphetamine. One such neurotransmitter is dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

, a chemical messenger heavily active in the mesolimbic
Mesolimbic pathway
The mesolimbic pathway is one of the dopaminergic pathways in the brain. The pathway begins in the ventral tegmental area of the midbrain and connects to the limbic system via the nucleus accumbens, the amygdala, and the hippocampus as well as to the medial prefrontal cortex...

 and mesocortical
Mesocortical pathway
The mesocortical pathway is a neural pathway that connects the ventral tegmentum to the cerebral cortex, particularly the frontal lobes. It is one of the four major dopamine pathways in the brain...

 reward pathways. Not surprisingly, the anatomical components of these pathways—including the striatum
Striatum
The striatum, also known as the neostriatum or striate nucleus, is a subcortical part of the forebrain. It is the major input station of the basal ganglia system. The striatum, in turn, gets input from the cerebral cortex...

, the nucleus accumbens
Nucleus accumbens
The nucleus accumbens , also known as the accumbens nucleus or as the nucleus accumbens septi , is a collection of neurons and forms the main part of the ventral striatum...

, and the ventral striatum
Ventral striatum
The ventral striatum is generally considered that part of the striatum that is connectionally associated with limbic structures, such as the amygdala, hippocampus, midline thalamus, and certain regions of the prefrontal cortex...

—have been found to be primary sites of amphetamine action.

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
Euphoria
Euphoria is an emotional and mental state defined as a sense of great elation and well being.Euphoria may also refer to:* Euphoria , a genus of scarab beetles* Euphoria, a genus name previously used for the longan and other trees...

. A better understanding of the specific mechanisms by which amphetamine operates may increase our ability to treat amphetamine addiction
Substance use disorder
Substance use disorders include substance abuse and substance dependence. In DSM-IV, the conditions are formally diagnosed as one or the other, but it has been proposed that DSM-5 combine the two into a single condition called "Substance-use disorder"....

, as the brain’s reward circuitry has been widely implicated in addictions of many types.

Endogenous amphetamines


Amphetamine has been found to have several endogenous analogues; that is, molecules of a similar structure found naturally in the brain. l-Phenylalanine
Phenylalanine
Phenylalanine is an α-amino acid with the formula C6H5CH2CHCOOH. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. L-Phenylalanine is an electrically neutral amino acid, one of the twenty common amino acids used to biochemically form...

 and β-Phenethylamine
Phenethylamine
Phenylethylamine or phenethylamine is a natural monoamine alkaloid, trace amine, and also the name of a class of chemicals with many members well known for psychoactive drug and stimulant effects. Studies suggest that phenylethylamine functions as a neuromodulator or neurotransmitter in the...

 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
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

. All of the addictive drugs appear to enhance dopamine neurotransmission, including amphetamine and methamphetamine. Studies have shown that in select regions, amphetamine increases the concentrations of dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 in the synaptic cleft, thereby heightening the response of the post-synaptic neuron. This specific action hints at the hedonic response to the drug as well as to the drug’s 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 amphetamine’s actions on the vesicular
Synaptic vesicle
In a neuron, synaptic vesicles store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulses between neurons and are constantly recreated by the cell...

 level, increasing concentrations of dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 in the cytosol
Cytosol
The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....

 of the pre-synaptic neuron. The other focuses on the role of the dopamine transporter DAT
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

, and proposes that amphetamine may interact with DAT
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

 to induce reverse transport of dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 from the presynaptic neuron into the synaptic cleft.

The former hypothesis is backed by studies from David Sulzer
David Sulzer
David Sulzer is a American neuroscientist and Professor at Columbia University Medical Center in the Departments of Psychiatry, Neurology, and Pharmacology...

's lab at Columbia University
Columbia University
Columbia University in the City of New York is a private, Ivy League university in Manhattan, New York City. Columbia is the oldest institution of higher learning in the state of New York, the fifth oldest in the United States, and one of the country's nine Colonial Colleges founded before the...

 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
Synaptic vesicle
In a neuron, synaptic vesicles store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulses between neurons and are constantly recreated by the cell...

. 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
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 is then believed to interact with DAT
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

 to promote reverse transport. 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. Calcium may be a key molecule involved in the interactions between amphetamine and VMATs.

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
Autophagy
In cell biology, autophagy, or autophagocytosis, is a catabolic process involving the degradation of a cell's own components through the lysosomal machinery. It is a tightly regulated process that plays a normal part in cell growth, development, and homeostasis, helping to maintain a balance...

-related degradation of dopamine axons and dendrites.

The second hypothesis of amphetamine action on the plasma membrane dopamine transporter postulates a direct interaction between amphetamine and the DAT
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

. The activity of DAT
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

 is believed to depend on specific phosphorylating kinases, such as protein kinase c
Protein kinase C
Protein kinase C also known as PKC is a family of enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and threonine amino acid residues on these proteins. PKC enzymes in turn are activated by signals such as increases in...

, specifically PKC-β
PRKCB1
Protein kinase C beta type is an enzyme that in humans is encoded by the PRKCB gene..-Interactions:PRKCB1 has been shown to interact with RIPK4, Beta adrenergic receptor kinase, PDLIM5 and GNB2L1.-Further reading:-See also:*Protein kinase C...

. Upon phosphorylation, DAT
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

 undergoes a conformational change that results in the transportation of DAT-bound dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 from the extracellular to the intracellular environment. In the presence of amphetamine, however, DAT
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

 has been observed to function in reverse, spitting dopamine out of the presynaptic neuron and into the synaptic cleft. Thus, beyond inhibiting reuptake of dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

, amphetamine also stimulates the release of dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 molecules into the synapse.

In support of the above hypothesis, it has been found that PKC-β
PRKCB1
Protein kinase C beta type is an enzyme that in humans is encoded by the PRKCB gene..-Interactions:PRKCB1 has been shown to interact with RIPK4, Beta adrenergic receptor kinase, PDLIM5 and GNB2L1.-Further reading:-See also:*Protein kinase C...

 inhibitors eliminate the effects of amphetamine on extracellular dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 concentrations in the striatum of rats. This data suggests that the PKC-β
PRKCB1
Protein kinase C beta type is an enzyme that in humans is encoded by the PRKCB gene..-Interactions:PRKCB1 has been shown to interact with RIPK4, Beta adrenergic receptor kinase, PDLIM5 and GNB2L1.-Further reading:-See also:*Protein kinase C...

 kinase may represent a key point of interaction between amphetamine and the DAT
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

 transporter.

Additional actions of amphetamine contribute to its ability to release dopamine from neurons, including action as an inhibitor of monoamine oxidase
Monoamine oxidase
L-Monoamine oxidases are a family of enzymes that catalyze the oxidation of monoamines. They are found bound to the outer membrane of mitochondria in most cell types in the body. The enzyme was originally discovered by Mary Bernheim in the liver and was named tyramine oxidase...

, an enzyme responsible for dopamine breakdown in the cytosol; an ability to enhance dopamine synthesis apparently via actions on the enzyme tyrosine hydroxylase
Tyrosine hydroxylase
Tyrosine hydroxylase or tyrosine 3-monooxygenase is the enzyme responsible for catalyzing the conversion of the amino acid L-tyrosine to dihydroxyphenylalanine . It does so using tetrahydrobiopterin as a coenzyme. DOPA is a precursor for dopamine, which, in turn, is a precursor for norepinephrine ...

, which synthesizes the dopamine precursor L-DOPA; and some blockade of the DAT, an action that amphetamine shares with cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...

. 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.

Serotonin


Amphetamine has been found to exert similar effects on serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

 as on dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

. Like DAT
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

, the serotonin transporter SERT
Serotonin transporter
The serotonin transporter is a monoamine transporter protein.This protein is an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. This transport of serotonin by the SERT protein terminates the action of serotonin and recycles it...

 can be induced to operate in reverse upon stimulation by amphetamine. This mechanism is thought to rely on the actions of calcium ions, as well as on the proximity of certain transporter proteins.

The interaction between amphetamine and serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

 is only apparent in particular regions of the brain, such as the mesocorticolimbic projection
Mesocortical pathway
The mesocortical pathway is a neural pathway that connects the ventral tegmentum to the cerebral cortex, particularly the frontal lobes. It is one of the four major dopamine pathways in the brain...

. Recent studies additionally postulate that amphetamine may indirectly alter the behavior of glutamatergic pathways extending from the ventral tegmental area to the prefrontal cortex
Prefrontal cortex
The prefrontal cortex is the anterior part of the frontal lobes of the brain, lying in front of the motor and premotor areas.This brain region has been implicated in planning complex cognitive behaviors, personality expression, decision making and moderating correct social behavior...

. Glutamatergic pathways are strongly correlated with increased excitability at the level of the synapse. Increased extracellular concentrations of serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

 may thus modulate the excitatory activity of glutamatergic neurons.

The proposed ability of amphetamine to increase excitability of glutamatergic pathways may be of significance when considering serotonin-mediated addiction. An additional behavioral consequence may be the stereotyped locomotor stimulation that occurs in response to amphetamine exposure.

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
Nucleus accumbens
The nucleus accumbens , also known as the accumbens nucleus or as the nucleus accumbens septi , is a collection of neurons and forms the main part of the ventral striatum...

, striatum
Striatum
The striatum, also known as the neostriatum or striate nucleus, is a subcortical part of the forebrain. It is the major input station of the basal ganglia system. The striatum, in turn, gets input from the cerebral cortex...

, and prefrontal cortex
Prefrontal cortex
The prefrontal cortex is the anterior part of the frontal lobes of the brain, lying in front of the motor and premotor areas.This brain region has been implicated in planning complex cognitive behaviors, personality expression, decision making and moderating correct social behavior...

. Additionally, several studies demonstrate increased levels of norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...

, 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. The long-term effects of amphetamines use on neural development
Neural development
Neural development comprises the processes that generate, shape, and reshape the nervous system, from the earliest stages of embryogenesis to the final years of life. The study of neural development aims to describe the cellular basis of brain development and to address the underlying mechanisms...

 in children has not been well established. Based on a study in rats, amphetamine use during adolescence may impair adult working memory
Working memory
Working memory has been defined as the system which actively holds information in the mind to do verbal and nonverbal tasks such as reasoning and comprehension, and to make it available for further information processing...

.

Chemical properties



Amphetamine is a chiral
Chirality (chemistry)
A chiral molecule is a type of molecule that lacks an internal plane of symmetry and thus has a non-superimposable mirror image. The feature that is most often the cause of chirality in molecules is the presence of an asymmetric carbon atom....

 compound. The racemic
Racemic
In chemistry, a racemic mixture, or racemate , is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule. The first known racemic mixture was "racemic acid", which Louis Pasteur found to be a mixture of the two enantiomeric isomers of tartaric acid.- Nomenclature :A...

 mixture can be divided into its optical isomers: levo-
Levoamphetamine
Levoamphetamine is a psychostimulant known to increase wakefulness and focus in association with decreased appetite and fatigue. Levoamphetamine is the levorotary stereoisomer of the amphetamine molecule...

 and dextro-amphetamine
Dextroamphetamine
Dextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus as well as decreased fatigue and decreased appetite....

. Amphetamine is the parent compound of its own structural class, comprising a broad range of psychoactive derivatives
Derivative (chemistry)
In chemistry, a derivative is a compound that is derived from a similar compound by some chemical or physical process. In the past it was also used to mean a compound that can be imagined to arise from another compound, if one atom is replaced with another atom or group of atoms, but modern...

, from empathogens, MDA (3,4-Methylenedioxyamphetamine)
3,4-Methylenedioxyamphetamine
3,4-Methylenedioxyamphetamine , also known as tenamfetamine , is a psychedelic and entactogenic drug of the phenethylamine and amphetamine chemical classes...

 and MDMA (3,4-Methylenedioxy-N-methamphetamine) known as ecstasy, to the N-methylated form, methamphetamine
Methamphetamine
Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...

 known as 'meth', and to decongestants such as ephedrine (EPH)
Ephedrine
Ephedrine is a sympathomimetic amine commonly used as a stimulant, appetite suppressant, concentration aid, decongestant, and to treat hypotension associated with anaesthesia....

 . Amphetamine is a homologue
Homologous series
In chemistry, a homologous series is a series of compounds with a similar general formula, possessing similar chemical properties due to the presence of the same functional group, and showing a gradation in physical properties as a result of increase in molecular size and mass...

 of phenethylamine
Phenethylamine
Phenylethylamine or phenethylamine is a natural monoamine alkaloid, trace amine, and also the name of a class of chemicals with many members well known for psychoactive drug and stimulant effects. Studies suggest that phenylethylamine functions as a neuromodulator or neurotransmitter in the...

.

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
Adderall
Adderall is a brand name of amphetamine salts–based medication used for attention-deficit hyperactivity disorder and narcolepsy. It is a brand-name psychostimulant medication composed of racemic amphetamine aspartate monohydrate, racemic amphetamine sulfate, dextroamphetamine saccharide, and...

 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
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

 (DAT) to increase concentrations of dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 in the neuronal terminal.

Amphetamine, both as d-amphetamine (dextroamphetamine
Dextroamphetamine
Dextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus as well as decreased fatigue and decreased appetite....

) 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
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

, norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...

 (noradrenaline) and serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

. It is hypothesized that d-amphetamine acts primarily on the dopaminergic systems, while l-amphetamine is comparatively norepinephrinergic (noradrenergic). The primary reinforcing and behavioral-stimulant effects of amphetamine, however, are linked to enhanced dopaminergic activity, primarily in the mesolimbic dopamine system.

Amphetamine and other amphetamine-type stimulants principally act to release dopamine into the synaptic cleft. 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. 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
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

 (DAT) into the synapse. In addition, amphetamine binds reversibly to the DATs and blocks the transporter's ability to clear DA from the synaptic space. Amphetamine also acts in this way with norepinephrine (noradrenaline) and to a lesser extent serotonin.

In addition, amphetamine binds to a group of receptors called Trace Amine Associated Receptors (TAAR). TAAR are a newly discovered receptor system which seems to be affected by a range of amphetamine-like substances called trace amines.

History


Amphetamine was first synthesized in 1887 by the Romania
Romania
Romania is a country located at the crossroads of Central and Southeastern Europe, on the Lower Danube, within and outside the Carpathian arch, bordering on the Black Sea...

n chemist Lazăr Edeleanu
Lazar Edeleanu
Lazăr Edeleanu was a Romanian chemist of Jewish origin.He was the first chemist to synthesize amphetamine at the University of Berlin and the inventor of the modern method of refining crude oil.- His childhood and studies:...

 in Berlin, Germany
Berlin
Berlin is the capital city of Germany and is one of the 16 states of Germany. With a population of 3.45 million people, Berlin is Germany's largest city. It is the second most populous city proper and the seventh most populous urban area in the European Union...

. He named the compound phenylisopropylamine. It was one of a series of compounds related to the plant derivative ephedrine
Ephedrine
Ephedrine is a sympathomimetic amine commonly used as a stimulant, appetite suppressant, concentration aid, decongestant, and to treat hypotension associated with anaesthesia....

, which had been isolated from Ma-Huang that same year by Nagayoshi Nagai
Nagayoshi Nagai
was a notable Japanese organic chemist and pharmacologist, best known for his study of ephedrine.-Early life:Nagai was born in Myodo District, Awa Province as the son of a doctor and started studying rangaku medicine at the Dutch Medical School of Nagasaki in 1864...

. No pharmacological use was found for amphetamine until 1927, when pioneer psychopharmacologist
Psychopharmacology
Psychopharmacology is the scientific study of the actions of drugs and their effects on mood, sensation, thinking, and behavior...

 Gordon Alles
Gordon Alles
Gordon A. Alles , was an American chemist and pharmacologist who did much research on the isolation and properties of insulin for the treatment of diabetics. He is also credited with discovering and publishing the psychological effects of amphetamine, as well as for MDA...

 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
Inhaler
An inhaler or puffer is a medical device used for delivering medication into the body via the lungs. It is mainly used in the treatment of asthma and Chronic Obstructive Pulmonary Disease . Zanamivir , used to treat influenza, must be administered via inhaler...

 under the trade name
Trade name
A trade name, also known as a trading name or a business name, is the name which a business trades under for commercial purposes, although its registered, legal name, used for contracts and other formal situations, may be another....

 Benzedrine
Benzedrine
Benzedrine is the trade name of the racemic mixture of amphetamine . It was marketed under this brandname in the USA by Smith, Kline & French in the form of inhalers, starting in 1928...

, useful as a decongestant but readily usable for other purposes. 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". 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
Controlled Substances Act
The Controlled Substances Act was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. The CSA is the federal U.S. drug policy under which the manufacture, importation, possession, use and distribution of certain...

 in 1971.

The related compound methamphetamine
Methamphetamine
Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...

 was first synthesized from ephedrine
Ephedrine
Ephedrine is a sympathomimetic amine commonly used as a stimulant, appetite suppressant, concentration aid, decongestant, and to treat hypotension associated with anaesthesia....

 in Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...

 in 1920 by chemist Akira Ogata
Akira Ogata
was a Japanese chemist and the first to synthesize methamphetamine in crystalline form in 1919....

, via reduction of ephedrine using red phosphorus and iodine
Iodine
Iodine is a chemical element with the symbol I and atomic number 53. The name is pronounced , , or . The name is from the , meaning violet or purple, due to the color of elemental iodine vapor....

. The pharmaceutical Pervitin was a tablet of methamphetamine which was available in Germany from 1938 and widely used in the Wehrmacht
Wehrmacht
The Wehrmacht – from , to defend and , the might/power) were the unified armed forces of Nazi Germany from 1935 to 1945. It consisted of the Heer , the Kriegsmarine and the Luftwaffe .-Origin and use of the term:...

, 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.

In 1997 and 1998, researchers at Texas A&M University
Texas A&M University
Texas A&M University is a coeducational public research university located in College Station, Texas . It is the flagship institution of the Texas A&M University System. The sixth-largest university in the United States, A&M's enrollment for Fall 2011 was over 50,000 for the first time in school...

 claimed to have found amphetamine and methamphetamine in the foliage of two Acacia
Acacia
Acacia is a genus of shrubs and trees belonging to the subfamily Mimosoideae of the family Fabaceae, first described in Africa by the Swedish botanist Carl Linnaeus in 1773. Many non-Australian species tend to be thorny, whereas the majority of Australian acacias are not...

 species native to Texas
Texas
Texas is the second largest U.S. state by both area and population, and the largest state by area in the contiguous United States.The name, based on the Caddo word "Tejas" meaning "friends" or "allies", was applied by the Spanish to the Caddo themselves and to the region of their settlement in...

, A. berlandieri
Acacia berlandieri
Acacia berlandieri is a shrub native to the Southwestern United States and northeast Mexico that belongs to the subfamily Mimosoideae of Fabaceae . It grows tall, with blossoms that are spherical and white, occurring from February through April...

and A. rigidula
Acacia rigidula
Acacia rigidula, commonly known as Blackbrush Acacia or Chaparro Prieto, is a species of shrub or small tree in the legume family, Fabaceae. Its native range stretches from Texas in the United States south to central Mexico. This perennial is closely related to A. berlandieri and is not listed as...

. 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
Alexander Shulgin
Alexander "Sasha" Theodore Shulgin is an American pharmacologist, chemist, artist, and drug developer.Shulgin is credited with the popularization of MDMA, commonly known as ecstasy, in the late 1970s and early 1980s, especially for psychopharmaceutical use and the treatment of depression and...

, 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.

Performance-enhancing use


Adderall
Adderall
Adderall is a brand name of amphetamine salts–based medication used for attention-deficit hyperactivity disorder and narcolepsy. It is a brand-name psychostimulant medication composed of racemic amphetamine aspartate monohydrate, racemic amphetamine sulfate, dextroamphetamine saccharide, and...

, an amphetamine mixture, is used by some college and high-school students as a study and test-taking aid. 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 and the RAF used so many that "Methedrine won the Battle of Britain" according to one report. American bomber pilots use amphetamine ("go pills") to stay awake during long missions. The Tarnak Farm incident
Tarnak Farm incident
The Tarnak Farm incident refers to the killing of four Canadian soldiers and the injury of eight others from the Third Battalion of Princess Patricia's Canadian Light Infantry on the night of April 17, 2002, by an American F-16 fighter jet. The aircraft, piloted by U.S...

, in which an American F-16 pilot killed several friendly Canadian soldiers on the ground, was blamed by the pilot on his use of amphetamine. A nonjudicial hearing rejected the pilot's claim.

Amphetamine is also used by some professional, collegiate and high school athletes for its strong stimulant effect. Energy levels are perceived to be dramatically increased and sustained, which is believed to allow for more vigorous and longer play. However, at least one study has found that this effect is not measurable. The use of amphetamine during strenuous physical activity can be extremely dangerous, especially when combined with alcohol, and athletes have died as a result, for example, British cyclist Tom Simpson
Tom Simpson
Tom Simpson was the most successful English road racing cyclist of the post-war years. He infamously died of exhaustion on the slopes of Mont Ventoux during the 13th stage of the Tour de France in 1967...

.

Amphetamine use has historically been especially common among Major League Baseball
Major League Baseball
Major League Baseball is the highest level of professional baseball in the United States and Canada, consisting of teams that play in the National League and the American League...

 players and is usually known by the slang term "greenies". In 2006, the MLB banned the use of amphetamine. The ban is enforced through periodic drug-testing. However, the MLB has received some criticism because the consequences for amphetamine use are dramatically less severe than for anabolic steroid
Anabolic steroid
Anabolic steroids, technically known as anabolic-androgen steroids or colloquially simply as "steroids", are drugs that mimic the effects of testosterone and dihydrotestosterone in the body. They increase protein synthesis within cells, which results in the buildup of cellular tissue ,...

 use, with the first offense bringing only a warning and further testing.

Amphetamine was formerly in widespread use by truck drivers to combat symptoms of somnolence and to increase their concentration during driving, especially in the decades prior to the signing by former president Ronald Reagan
Ronald Reagan
Ronald Wilson Reagan was the 40th President of the United States , the 33rd Governor of California and, prior to that, a radio, film and television actor....

 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 driver—Implementation 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.

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
Goth subculture
The goth subculture is a contemporary subculture found in many countries. It began in England during the early 1980s in the gothic rock scene, an offshoot of the post-punk genre. The goth subculture has survived much longer than others of the same era, and has continued to diversify...

, gangsters, and casuals
Casuals
The casual subculture is a subsection of association football culture that is typified by football hooliganism and the wearing of expensive European designer clothing. The subculture originated in the United Kingdom in the early 1980s when many hooligans started wearing designer labels and...

 in all night soul and ska dances, punk concerts, basement show
Basement show
A basement show is a musical performance, often of the punk rock or hardcore punk variety, that is held in the basement of a residential home, rather than at a traditional venue. These are also sometimes referred to as "house shows" as they can happen anywhere in a residential house, not just in...

s and fighting on the terraces
Football hooliganism
Football hooliganism, sometimes referred to by the British media as the English Disease, is unruly and destructive behaviour—such as brawls, vandalism and intimidation—by association football club fans...

 by casuals.

The hippie
Hippie
The hippie subculture was originally a youth movement that arose in the United States during the mid-1960s and spread to other countries around the world. The etymology of the term 'hippie' is from hipster, and was initially used to describe beatniks who had moved into San Francisco's...

 counterculture
Counterculture
Counterculture is a sociological term used to describe the values and norms of behavior of a cultural group, or subculture, that run counter to those of the social mainstream of the day, the cultural equivalent of political opposition. Counterculture can also be described as a group whose behavior...

 was very critical of amphetamines due to the behaviors they cause; in an interview with the Los Angeles Free Press
Los Angeles Free Press
The Los Angeles Free Press , also called “the Freep”, was among the most widely distributed underground newspapers of the 1960s. It is often cited as the first such newspaper...

 in 1965, beat writer Allen Ginsberg
Allen Ginsberg
Irwin Allen Ginsberg was an American poet and one of the leading figures of the Beat Generation in the 1950s. He vigorously opposed militarism, materialism and sexual repression...

 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".

In literature


The writers of the Beat Generation
Beat generation
The Beat Generation refers to a group of American post-WWII writers who came to prominence in the 1950s, as well as the cultural phenomena that they both documented and inspired...

 used amphetamine extensively, mainly under the Benzedrine
Benzedrine
Benzedrine is the trade name of the racemic mixture of amphetamine . It was marketed under this brandname in the USA by Smith, Kline & French in the form of inhalers, starting in 1928...

 brand name. Jack Kerouac
Jack Kerouac
Jean-Louis "Jack" Lebris de Kerouac was an American novelist and poet. He is considered a literary iconoclast and, alongside William S. Burroughs and Allen Ginsberg, a pioneer of the Beat Generation. Kerouac is recognized for his spontaneous method of writing, covering topics such as Catholic...

 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.

Scottish author Irvine Welsh
Irvine Welsh
Irvine Welsh is a contemporary Scottish novelist, best known for his novel Trainspotting. His work is characterised by raw Scottish dialect, and brutal depiction of the realities of Edinburgh life...

 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
Trainspotting (novel)
Trainspotting is the first novel by Scottish writer Irvine Welsh. It is written in the form of short chapters narrated in the first person by various residents of Leith, Edinburgh, who either use heroin, are friends of the core group of heroin users, or engage in destructive activities that are...

 and Porno
Porno (novel)
Porno is a novel by Scottish writer Irvine Welsh, and is the sequel to Trainspotting.The book describes the characters of Trainspotting ten years after the events of the earlier book, as their paths cross again, this time with the pornography business as the backdrop rather than heroin use...

 reflect the changes in drug use and culture during the years that elapse between the two texts.

Amphetamine is frequently mentioned in the work of American journalist Hunter S. Thompson
Hunter S. Thompson
Hunter Stockton Thompson was an American journalist and author who wrote The Rum Diary , Fear and Loathing in Las Vegas and Fear and Loathing on the Campaign Trail '72 .He is credited as the creator of Gonzo journalism, a style of reporting where reporters involve themselves in the action to...

. Speed appears not only amongst 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, such as in his "Author's Note" in Fear and Loathing on the Campaign Trail '72
Fear and Loathing on the Campaign Trail '72
Fear and Loathing: On the Campaign Trail '72 is a collection of articles covering the 1972 presidential campaign written by the gonzo journalist Hunter S Thompson and illustrated by Ralph Steadman...

.


"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 Bowl
Super Bowl
The Super Bowl is the championship game of the National Football League , the highest level of professional American football in the United States, culminating a season that begins in the late summer of the previous calendar year. The Super Bowl uses Roman numerals to identify each game, rather...

s. ... Meanwhile,
Amphetamine (USAN
United States Adopted Name
United States Adopted Names are unique nonproprietary names assigned to pharmaceuticals marketed in the United States. Each name is assigned by the USAN Council, which is co-sponsored by the American Medical Association , the United States Pharmacopeial Convention , and the American Pharmacists...

, abbreviated from alpha-methyl
Methyl group
Methyl group is a functional group derived from methane, containing one carbon atom bonded to three hydrogen atoms —CH3. The group is often abbreviated Me. Such hydrocarbon groups occur in many organic compounds. The methyl group can be found in three forms: anion, cation and radical. The anion...

phenethylamine
Phenethylamine
Phenylethylamine or phenethylamine is a natural monoamine alkaloid, trace amine, and also the name of a class of chemicals with many members well known for psychoactive drug and stimulant effects. Studies suggest that phenylethylamine functions as a neuromodulator or neurotransmitter in the...

) or amfetamine (INN
International Nonproprietary Name
An International Nonproprietary Name is the official nonproprietary or generic name given to a pharmaceutical substance, as designated by the World Health Organization...

) is a psychostimulant drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...

 of the phenethylamine
Phenethylamine
Phenylethylamine or phenethylamine is a natural monoamine alkaloid, trace amine, and also the name of a class of chemicals with many members well known for psychoactive drug and stimulant effects. Studies suggest that phenylethylamine functions as a neuromodulator or neurotransmitter in the...

 class which produces increased wakefulness and focus
Attention
Attention is the cognitive process of paying attention to one aspect of the environment while ignoring others. Attention is one of the most intensely studied topics within psychology and cognitive neuroscience....

 in association with decreased fatigue and appetite
Appetite
The appetite is the desire to eat food, felt as hunger. Appetite exists in all higher life-forms, and serves to regulate adequate energy intake to maintain metabolic needs. It is regulated by a close interplay between the digestive tract, adipose tissue and the brain. Decreased desire to eat is...

.

Brand names of medications that contain, or metabolize into, amphetamine include Adderall
Adderall
Adderall is a brand name of amphetamine salts–based medication used for attention-deficit hyperactivity disorder and narcolepsy. It is a brand-name psychostimulant medication composed of racemic amphetamine aspartate monohydrate, racemic amphetamine sulfate, dextroamphetamine saccharide, and...

, Dexedrine, Dextrostat, Desoxyn
Methamphetamine
Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...

, ProCentra
Dextroamphetamine
Dextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus as well as decreased fatigue and decreased appetite....

, and Vyvanse, as well as Benzedrine
Benzedrine
Benzedrine is the trade name of the racemic mixture of amphetamine . It was marketed under this brandname in the USA by Smith, Kline & French in the form of inhalers, starting in 1928...

 in the past.

The drug is also used recreationally
Recreational drug use
Recreational drug use is the use of a drug, usually psychoactive, with the intention of creating or enhancing recreational experience. Such use is controversial, however, often being considered to be also drug abuse, and it is often illegal...

 and as a performance enhancer. Recreational users of amphetamine have coined numerous street names for amphetamine, such as "speed". The European Monitoring Centre for Drugs and Drug Addiction
European Monitoring Centre for Drugs and Drug Addiction
The European Monitoring Centre for Drugs and Drug Addiction is an agency of the European Union. Established in 1993, the EMCDDA is located in Lisbon, Portugal.-Mission and role:...

 reports the typical retail price of diluted amphetamine in Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...

 varied between €3 and €15 ($4 to $21.55 USD
United States dollar
The United States dollar , also referred to as the American dollar, is the official currency of the United States of America. It is divided into 100 smaller units called cents or pennies....

) a gram in half of the reporting countries. Racemic amphetamine on the street is typically about 10% pure.

Effects



Physical effects


Physical effects of amphetamine can include hyperactivity, dilated pupils, vasoconstriction
Vasoconstriction
Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, particularly the large arteries, small arterioles and veins. The process is the opposite of vasodilation, the widening of blood vessels. The process is particularly important in...

, blood shot eyes, flushing
Flushing (physiology)
For a person to flush is to become markedly red in the face and often other areas of the skin, from various physiological conditions. Flushing is generally distinguished, despite a close physiological relation between them, from blushing, which is milder, generally restricted to the face, cheeks or...

, restlessness, dry mouth
Xerostomia
Xerostomia is the medical term for the subjective complaint of dry mouth due to a lack of saliva. Xerostomia is sometimes colloquially called pasties, cottonmouth, drooth, or doughmouth. Several diseases, treatments, and medications can cause xerostomia. It can also be exacerbated by smoking or...

, bruxism
Bruxism
Bruxism is characterized by the grinding of the teeth and typically includes the clenching of the jaw. It is an oral parafunctional activity that occurs in most humans at some time in their lives. In most people, bruxism is mild enough not to be a health problem...

, headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...

, tachycardia
Tachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...

, bradycardia
Bradycardia
Bradycardia , in the context of adult medicine, is the resting heart rate of under 60 beats per minute, though it is seldom symptomatic until the rate drops below 50 beat/min. It may cause cardiac arrest in some patients, because those with bradycardia may not be pumping enough oxygen to their heart...

, tachypnea
Tachypnea
Tachypnea means rapid breathing. Any rate between 12-20 breaths per minute is normal. Tachypnea is a respiration rate greater than 20 breaths per minute. - Distinction from other breathing terms :...

, hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

, hypotension
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...

, fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...

, diaphoresis
Diaphoresis
Diaphoresis is excessive sweating commonly associated with shock and other medical emergency conditions.Diaphoretic is the state of perspiring profusely, or something that has the power to cause increased perspiration....

, diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...

, constipation
Constipation
Constipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...

, blurred vision
Blurred vision
-Causes:There are many causes of blurred vision:* Use of atropine or other anticholinergics* Presbyopia -- Difficulty focusing on objects that are close. The elderly are common victims....

, aphasia
Aphasia
Aphasia is an impairment of language ability. This class of language disorder ranges from having difficulty remembering words to being completely unable to speak, read, or write....

, dizziness
Dizziness
Dizziness refers to an impairment in spatial perception and stability. The term is somewhat imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or a non-specific feeling such as giddiness or foolishness....

, twitching, insomnia
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...

, numbness, palpitations, arrhythmias, tremors, dry and/or itchy skin, acne
Acne
Acne is a general term used for acneiform eruptions. It is usually used as a synonym for acne vulgaris, but may also refer to:*Acne aestivalis*Acne conglobata*Acne cosmetica*Acne fulminans*Acne keloidalis nuchae*Acne mechanica...

, pallor
Pallor
Pallor is a reduced amount of oxyhaemoglobin in skin or mucous membrane, a pale color which can be caused by illness, emotional shock or stress, stimulant use, lack of exposure to sunlight, anaemia or genetics....

, convulsions, and with chronic and/or high doses, seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...

, stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...

, coma
Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...

, heart attack
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...

 and death
Death
Death is the permanent termination of the biological functions that sustain a living organism. Phenomena which commonly bring about death include old age, predation, malnutrition, disease, and accidents or trauma resulting in terminal injury....

 can occur.
There is also significant research which highlights the changes amphetamine produces in the dopaminergic system, even in clinical doses. One possible interpretation is that neurotoxic
Neurotoxicity
Neurotoxicity occurs when the exposure to natural or artificial toxic substances, which are called neurotoxins, alters the normal activity of the nervous system in such a way as to cause damage to nervous tissue. This can eventually disrupt or even kill neurons, key cells that transmit and process...

 effects exist even with doses approved for medical use.

Psychological effects


Psychological effects can include euphoria
Euphoria
Euphoria is an emotional and mental state defined as a sense of great elation and well being.Euphoria may also refer to:* Euphoria , a genus of scarab beetles* Euphoria, a genus name previously used for the longan and other trees...

, anxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

, increased libido
Libido
Libido refers to a person's sex drive or desire for sexual activity. The desire for sex is an aspect of a person's sexuality, but varies enormously from one person to another, and it also varies depending on circumstances at a particular time. A person who has extremely frequent or a suddenly...

, alertness
Alertness
Alertness is the state of paying close and continuous attention, being watchful and prompt to meet danger or emergency, or being quick to perceive and act. It is related to psychology as well as to physiology...

, concentration
Concentration
In chemistry, concentration is defined as the abundance of a constituent divided by the total volume of a mixture. Four types can be distinguished: mass concentration, molar concentration, number concentration, and volume concentration...

, energy
Energy
In physics, energy is an indirectly observed quantity. It is often understood as the ability a physical system has to do work on other physical systems...

, self-esteem
Self-esteem
Self-esteem is a term in psychology to reflect a person's overall evaluation or appraisal of his or her own worth. Self-esteem encompasses beliefs and emotions such as triumph, despair, pride and shame: some would distinguish how 'the self-concept is what we think about the self; self-esteem, the...

, self-confidence
Self-confidence
The socio-psychological concept of self-confidence relates to self-assuredness in one's personal judgment, ability, power, etc., sometimes manifested excessively.Being confident in yourself is infectious if you present yourself well, others will want to follow in your foot steps towards...

, sociability, irritability
Irritability
Irritability is an excessive response to stimuli. The term is used for both the physiological reaction to stimuli and for the pathological, abnormal or excessive sensitivity to stimuli; It is usually used to refer to anger or frustration....

, aggression
Aggression
In psychology, as well as other social and behavioral sciences, aggression refers to behavior between members of the same species that is intended to cause humiliation, pain, or harm. Ferguson and Beaver defined aggressive behavior as "Behavior which is intended to increase the social dominance of...

, psychosomatic disorders, psychomotor agitation
Psychomotor agitation
Psychomotor agitation is a series of unintentional and purposeless motions that stem from mental tension and anxiety of an individual. This includes pacing around a room, wringing one's hands, pulling off clothing and putting it back on and other similar actions...

, grandiosity
Grandiosity
Grandiosity is chiefly associated with narcissistic personality disorder, but also commonly features in manic or hypomanic episodes of bipolar disorder....

, repetitive and obsessive
Fixation (psychology)
Fixation: 'concept originated by Sigmund Freud to denote the persistence of anachronistic sexual traits'. Subsequently '"Fixation" acquired a broader connotation...

 behaviors, paranoia
Paranoia
Paranoia [] is a thought process believed to be heavily influenced by anxiety or fear, often to the point of irrationality and delusion. Paranoid thinking typically includes persecutory beliefs, or beliefs of conspiracy concerning a perceived threat towards oneself...

, and with chronic and/or high doses, amphetamine psychosis
Amphetamine psychosis
Stimulant psychosis is a psychotic disorder that appears in some people who use stimulant drugs. Most commonly, stimulant psychosis occurs in drug abusers who take very large doses but, in rare cases, it can also present in patients taking therapeutic doses under medical supervision...

 can occur.

Withdrawal effects


Withdrawal symptoms of amphetamine primarily consist of mental fatigue, mental depression
Depression (mood)
Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...

 and increased appetite
Appetite
The appetite is the desire to eat food, felt as hunger. Appetite exists in all higher life-forms, and serves to regulate adequate energy intake to maintain metabolic needs. It is regulated by a close interplay between the digestive tract, adipose tissue and the brain. Decreased desire to eat is...

. 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
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

, agitation
Psychomotor agitation
Psychomotor agitation is a series of unintentional and purposeless motions that stem from mental tension and anxiety of an individual. This includes pacing around a room, wringing one's hands, pulling off clothing and putting it back on and other similar actions...

, excessive sleep
Sleep
Sleep is a naturally recurring state characterized by reduced or absent consciousness, relatively suspended sensory activity, and inactivity of nearly all voluntary muscles. It is distinguished from quiet wakefulness by a decreased ability to react to stimuli, and is more easily reversible than...

, vivid or lucid dream
Dream
Dreams are successions of images, ideas, emotions, and sensations that occur involuntarily in the mind during certain stages of sleep. The content and purpose of dreams are not definitively understood, though they have been a topic of scientific speculation, philosophical intrigue and religious...

s, deep REM sleep and suicidal ideation
Suicidal ideation
Suicidal ideation is a common medical term for thoughts about suicide, which may be as detailed as a formulated plan, without the suicidal act itself. Although most people who undergo suicidal ideation do not commit suicide, some go on to make suicide attempts...

.

Contraindications


Amphetamine elevates cardiac output and blood pressure making it dangerous for use by patients with a history of heart disease
Heart disease
Heart disease, cardiac disease or cardiopathy is an umbrella term for a variety of diseases affecting the heart. , it is the leading cause of death in the United States, England, Canada and Wales, accounting for 25.4% of the total deaths in the United States.-Types:-Coronary heart disease:Coronary...

 or hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

. Amphetamine can cause a life-threatening complication in patients taking MAOI antidepressants. The use of amphetamine and amphetamine-like drugs is contraindicated in patients with narrow-angle glaucoma
Glaucoma
Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...

 or anatomically narrow angles. Like other sympathomimetic amines, amphetamine can induce transient mydriasis
Mydriasis
Mydriasis is a dilation of the pupil due to disease, trauma or the use of drugs. Normally, the pupil dilates in the dark and constricts in the light to respectively improve vividity at night and to protect the retina from sunlight damage during the day...

. In patients with narrow angles, pupillary dilation can provoke an acute attack of angle-closure glaucoma. These agents should also be avoided in patients with other forms of glaucoma, as mydriasis may occasionally increase intraocular pressure.

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.

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.

Overdose


An amphetamine overdose is rarely fatal but can lead to a number of different symptoms, including psychosis
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...

, chest pain
Chest pain
Chest pain may be a symptom of a number of serious conditions and is generally considered a medical emergency. Even though it may be determined that the pain is non-cardiac in origin, this is often a diagnosis of exclusion made after ruling out more serious causes of the pain.-Differential...

, and hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

.

Psychosis



Abuse of amphetamines can result in a stimulant psychosis that can present as a number of psychotic disorders (e.g. paranoia
Paranoia
Paranoia [] is a thought process believed to be heavily influenced by anxiety or fear, often to the point of irrationality and delusion. Paranoid thinking typically includes persecutory beliefs, or beliefs of conspiracy concerning a perceived threat towards oneself...

, hallucination
Hallucination
A hallucination, in the broadest sense of the word, is a perception in the absence of a stimulus. In a stricter sense, hallucinations are defined as perceptions in a conscious and awake state in the absence of external stimuli which have qualities of real perception, in that they are vivid,...

s, delusion
Delusion
A delusion is a false belief held with absolute conviction despite superior evidence. Unlike hallucinations, delusions are always pathological...

s). The intensity and duration of symptoms may vary, but unlike true psychotic disorders (e.g. schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...

), stimulant psychoses are not considered to be permanent and will eventually resolve upon discontinuation of the drug's use.

Primary sites of action



Amphetamine exerts its behavioral effects by modulating several key neurotransmitters in the brain, including dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

, serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

, and norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...

. However, the activity of amphetamine throughout the brain appears to be specific; certain receptors that respond to amphetamine in some regions of the brain tend not to do so in other regions. For instance, dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 D2 receptors
Dopamine receptor
Dopamine receptors are a class of metabotropic G protein-coupled receptors that are prominent in the vertebrate central nervous system . The neurotransmitter dopamine is the primary endogenous ligand for dopamine receptors....

 in the hippocampus
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...

, a region of the brain associated with forming new memories, appear to be unaffected by the presence of amphetamine.

The major neural systems affected by amphetamine are largely implicated in the brain’s reward circuitry. Moreover, neurotransmitters involved in various reward pathways of the brain appear to be the primary targets of amphetamine. One such neurotransmitter is dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

, a chemical messenger heavily active in the mesolimbic
Mesolimbic pathway
The mesolimbic pathway is one of the dopaminergic pathways in the brain. The pathway begins in the ventral tegmental area of the midbrain and connects to the limbic system via the nucleus accumbens, the amygdala, and the hippocampus as well as to the medial prefrontal cortex...

 and mesocortical
Mesocortical pathway
The mesocortical pathway is a neural pathway that connects the ventral tegmentum to the cerebral cortex, particularly the frontal lobes. It is one of the four major dopamine pathways in the brain...

 reward pathways. Not surprisingly, the anatomical components of these pathways—including the striatum
Striatum
The striatum, also known as the neostriatum or striate nucleus, is a subcortical part of the forebrain. It is the major input station of the basal ganglia system. The striatum, in turn, gets input from the cerebral cortex...

, the nucleus accumbens
Nucleus accumbens
The nucleus accumbens , also known as the accumbens nucleus or as the nucleus accumbens septi , is a collection of neurons and forms the main part of the ventral striatum...

, and the ventral striatum
Ventral striatum
The ventral striatum is generally considered that part of the striatum that is connectionally associated with limbic structures, such as the amygdala, hippocampus, midline thalamus, and certain regions of the prefrontal cortex...

—have been found to be primary sites of amphetamine action.

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
Euphoria
Euphoria is an emotional and mental state defined as a sense of great elation and well being.Euphoria may also refer to:* Euphoria , a genus of scarab beetles* Euphoria, a genus name previously used for the longan and other trees...

. A better understanding of the specific mechanisms by which amphetamine operates may increase our ability to treat amphetamine addiction
Substance use disorder
Substance use disorders include substance abuse and substance dependence. In DSM-IV, the conditions are formally diagnosed as one or the other, but it has been proposed that DSM-5 combine the two into a single condition called "Substance-use disorder"....

, as the brain’s reward circuitry has been widely implicated in addictions of many types.

Endogenous amphetamines


Amphetamine has been found to have several endogenous analogues; that is, molecules of a similar structure found naturally in the brain. l-Phenylalanine
Phenylalanine
Phenylalanine is an α-amino acid with the formula C6H5CH2CHCOOH. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. L-Phenylalanine is an electrically neutral amino acid, one of the twenty common amino acids used to biochemically form...

 and β-Phenethylamine
Phenethylamine
Phenylethylamine or phenethylamine is a natural monoamine alkaloid, trace amine, and also the name of a class of chemicals with many members well known for psychoactive drug and stimulant effects. Studies suggest that phenylethylamine functions as a neuromodulator or neurotransmitter in the...

 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
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

. All of the addictive drugs appear to enhance dopamine neurotransmission, including amphetamine and methamphetamine. Studies have shown that in select regions, amphetamine increases the concentrations of dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 in the synaptic cleft, thereby heightening the response of the post-synaptic neuron. This specific action hints at the hedonic response to the drug as well as to the drug’s 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 amphetamine’s actions on the vesicular
Synaptic vesicle
In a neuron, synaptic vesicles store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulses between neurons and are constantly recreated by the cell...

 level, increasing concentrations of dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 in the cytosol
Cytosol
The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....

 of the pre-synaptic neuron. The other focuses on the role of the dopamine transporter DAT
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

, and proposes that amphetamine may interact with DAT
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

 to induce reverse transport of dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 from the presynaptic neuron into the synaptic cleft.

The former hypothesis is backed by studies from David Sulzer
David Sulzer
David Sulzer is a American neuroscientist and Professor at Columbia University Medical Center in the Departments of Psychiatry, Neurology, and Pharmacology...

's lab at Columbia University
Columbia University
Columbia University in the City of New York is a private, Ivy League university in Manhattan, New York City. Columbia is the oldest institution of higher learning in the state of New York, the fifth oldest in the United States, and one of the country's nine Colonial Colleges founded before the...

 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
Synaptic vesicle
In a neuron, synaptic vesicles store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulses between neurons and are constantly recreated by the cell...

. 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
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 is then believed to interact with DAT
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

 to promote reverse transport. 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. Calcium may be a key molecule involved in the interactions between amphetamine and VMATs.

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
Autophagy
In cell biology, autophagy, or autophagocytosis, is a catabolic process involving the degradation of a cell's own components through the lysosomal machinery. It is a tightly regulated process that plays a normal part in cell growth, development, and homeostasis, helping to maintain a balance...

-related degradation of dopamine axons and dendrites.

The second hypothesis of amphetamine action on the plasma membrane dopamine transporter postulates a direct interaction between amphetamine and the DAT
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

. The activity of DAT
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

 is believed to depend on specific phosphorylating kinases, such as protein kinase c
Protein kinase C
Protein kinase C also known as PKC is a family of enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and threonine amino acid residues on these proteins. PKC enzymes in turn are activated by signals such as increases in...

, specifically PKC-β
PRKCB1
Protein kinase C beta type is an enzyme that in humans is encoded by the PRKCB gene..-Interactions:PRKCB1 has been shown to interact with RIPK4, Beta adrenergic receptor kinase, PDLIM5 and GNB2L1.-Further reading:-See also:*Protein kinase C...

. Upon phosphorylation, DAT
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

 undergoes a conformational change that results in the transportation of DAT-bound dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 from the extracellular to the intracellular environment. In the presence of amphetamine, however, DAT
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

 has been observed to function in reverse, spitting dopamine out of the presynaptic neuron and into the synaptic cleft. Thus, beyond inhibiting reuptake of dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

, amphetamine also stimulates the release of dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 molecules into the synapse.

In support of the above hypothesis, it has been found that PKC-β
PRKCB1
Protein kinase C beta type is an enzyme that in humans is encoded by the PRKCB gene..-Interactions:PRKCB1 has been shown to interact with RIPK4, Beta adrenergic receptor kinase, PDLIM5 and GNB2L1.-Further reading:-See also:*Protein kinase C...

 inhibitors eliminate the effects of amphetamine on extracellular dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 concentrations in the striatum of rats. This data suggests that the PKC-β
PRKCB1
Protein kinase C beta type is an enzyme that in humans is encoded by the PRKCB gene..-Interactions:PRKCB1 has been shown to interact with RIPK4, Beta adrenergic receptor kinase, PDLIM5 and GNB2L1.-Further reading:-See also:*Protein kinase C...

 kinase may represent a key point of interaction between amphetamine and the DAT
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

 transporter.

Additional actions of amphetamine contribute to its ability to release dopamine from neurons, including action as an inhibitor of monoamine oxidase
Monoamine oxidase
L-Monoamine oxidases are a family of enzymes that catalyze the oxidation of monoamines. They are found bound to the outer membrane of mitochondria in most cell types in the body. The enzyme was originally discovered by Mary Bernheim in the liver and was named tyramine oxidase...

, an enzyme responsible for dopamine breakdown in the cytosol; an ability to enhance dopamine synthesis apparently via actions on the enzyme tyrosine hydroxylase
Tyrosine hydroxylase
Tyrosine hydroxylase or tyrosine 3-monooxygenase is the enzyme responsible for catalyzing the conversion of the amino acid L-tyrosine to dihydroxyphenylalanine . It does so using tetrahydrobiopterin as a coenzyme. DOPA is a precursor for dopamine, which, in turn, is a precursor for norepinephrine ...

, which synthesizes the dopamine precursor L-DOPA; and some blockade of the DAT, an action that amphetamine shares with cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...

. 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.

Serotonin


Amphetamine has been found to exert similar effects on serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

 as on dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

. Like DAT
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

, the serotonin transporter SERT
Serotonin transporter
The serotonin transporter is a monoamine transporter protein.This protein is an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. This transport of serotonin by the SERT protein terminates the action of serotonin and recycles it...

 can be induced to operate in reverse upon stimulation by amphetamine. This mechanism is thought to rely on the actions of calcium ions, as well as on the proximity of certain transporter proteins.

The interaction between amphetamine and serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

 is only apparent in particular regions of the brain, such as the mesocorticolimbic projection
Mesocortical pathway
The mesocortical pathway is a neural pathway that connects the ventral tegmentum to the cerebral cortex, particularly the frontal lobes. It is one of the four major dopamine pathways in the brain...

. Recent studies additionally postulate that amphetamine may indirectly alter the behavior of glutamatergic pathways extending from the ventral tegmental area to the prefrontal cortex
Prefrontal cortex
The prefrontal cortex is the anterior part of the frontal lobes of the brain, lying in front of the motor and premotor areas.This brain region has been implicated in planning complex cognitive behaviors, personality expression, decision making and moderating correct social behavior...

. Glutamatergic pathways are strongly correlated with increased excitability at the level of the synapse. Increased extracellular concentrations of serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

 may thus modulate the excitatory activity of glutamatergic neurons.

The proposed ability of amphetamine to increase excitability of glutamatergic pathways may be of significance when considering serotonin-mediated addiction. An additional behavioral consequence may be the stereotyped locomotor stimulation that occurs in response to amphetamine exposure.

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
Nucleus accumbens
The nucleus accumbens , also known as the accumbens nucleus or as the nucleus accumbens septi , is a collection of neurons and forms the main part of the ventral striatum...

, striatum
Striatum
The striatum, also known as the neostriatum or striate nucleus, is a subcortical part of the forebrain. It is the major input station of the basal ganglia system. The striatum, in turn, gets input from the cerebral cortex...

, and prefrontal cortex
Prefrontal cortex
The prefrontal cortex is the anterior part of the frontal lobes of the brain, lying in front of the motor and premotor areas.This brain region has been implicated in planning complex cognitive behaviors, personality expression, decision making and moderating correct social behavior...

. Additionally, several studies demonstrate increased levels of norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...

, 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. The long-term effects of amphetamines use on neural development
Neural development
Neural development comprises the processes that generate, shape, and reshape the nervous system, from the earliest stages of embryogenesis to the final years of life. The study of neural development aims to describe the cellular basis of brain development and to address the underlying mechanisms...

 in children has not been well established. Based on a study in rats, amphetamine use during adolescence may impair adult working memory
Working memory
Working memory has been defined as the system which actively holds information in the mind to do verbal and nonverbal tasks such as reasoning and comprehension, and to make it available for further information processing...

.

Chemical properties



Amphetamine is a chiral
Chirality (chemistry)
A chiral molecule is a type of molecule that lacks an internal plane of symmetry and thus has a non-superimposable mirror image. The feature that is most often the cause of chirality in molecules is the presence of an asymmetric carbon atom....

 compound. The racemic
Racemic
In chemistry, a racemic mixture, or racemate , is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule. The first known racemic mixture was "racemic acid", which Louis Pasteur found to be a mixture of the two enantiomeric isomers of tartaric acid.- Nomenclature :A...

 mixture can be divided into its optical isomers: levo-
Levoamphetamine
Levoamphetamine is a psychostimulant known to increase wakefulness and focus in association with decreased appetite and fatigue. Levoamphetamine is the levorotary stereoisomer of the amphetamine molecule...

 and dextro-amphetamine
Dextroamphetamine
Dextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus as well as decreased fatigue and decreased appetite....

. Amphetamine is the parent compound of its own structural class, comprising a broad range of psychoactive derivatives
Derivative (chemistry)
In chemistry, a derivative is a compound that is derived from a similar compound by some chemical or physical process. In the past it was also used to mean a compound that can be imagined to arise from another compound, if one atom is replaced with another atom or group of atoms, but modern...

, from empathogens, MDA (3,4-Methylenedioxyamphetamine)
3,4-Methylenedioxyamphetamine
3,4-Methylenedioxyamphetamine , also known as tenamfetamine , is a psychedelic and entactogenic drug of the phenethylamine and amphetamine chemical classes...

 and MDMA (3,4-Methylenedioxy-N-methamphetamine) known as ecstasy, to the N-methylated form, methamphetamine
Methamphetamine
Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...

 known as 'meth', and to decongestants such as ephedrine (EPH)
Ephedrine
Ephedrine is a sympathomimetic amine commonly used as a stimulant, appetite suppressant, concentration aid, decongestant, and to treat hypotension associated with anaesthesia....

 . Amphetamine is a homologue
Homologous series
In chemistry, a homologous series is a series of compounds with a similar general formula, possessing similar chemical properties due to the presence of the same functional group, and showing a gradation in physical properties as a result of increase in molecular size and mass...

 of phenethylamine
Phenethylamine
Phenylethylamine or phenethylamine is a natural monoamine alkaloid, trace amine, and also the name of a class of chemicals with many members well known for psychoactive drug and stimulant effects. Studies suggest that phenylethylamine functions as a neuromodulator or neurotransmitter in the...

.

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
Adderall
Adderall is a brand name of amphetamine salts–based medication used for attention-deficit hyperactivity disorder and narcolepsy. It is a brand-name psychostimulant medication composed of racemic amphetamine aspartate monohydrate, racemic amphetamine sulfate, dextroamphetamine saccharide, and...

 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
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

 (DAT) to increase concentrations of dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 in the neuronal terminal.

Amphetamine, both as d-amphetamine (dextroamphetamine
Dextroamphetamine
Dextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus as well as decreased fatigue and decreased appetite....

) 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
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

, norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...

 (noradrenaline) and serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

. It is hypothesized that d-amphetamine acts primarily on the dopaminergic systems, while l-amphetamine is comparatively norepinephrinergic (noradrenergic). The primary reinforcing and behavioral-stimulant effects of amphetamine, however, are linked to enhanced dopaminergic activity, primarily in the mesolimbic dopamine system.

Amphetamine and other amphetamine-type stimulants principally act to release dopamine into the synaptic cleft. 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. 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
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

 (DAT) into the synapse. In addition, amphetamine binds reversibly to the DATs and blocks the transporter's ability to clear DA from the synaptic space. Amphetamine also acts in this way with norepinephrine (noradrenaline) and to a lesser extent serotonin.

In addition, amphetamine binds to a group of receptors called Trace Amine Associated Receptors (TAAR). TAAR are a newly discovered receptor system which seems to be affected by a range of amphetamine-like substances called trace amines.

History


Amphetamine was first synthesized in 1887 by the Romania
Romania
Romania is a country located at the crossroads of Central and Southeastern Europe, on the Lower Danube, within and outside the Carpathian arch, bordering on the Black Sea...

n chemist Lazăr Edeleanu
Lazar Edeleanu
Lazăr Edeleanu was a Romanian chemist of Jewish origin.He was the first chemist to synthesize amphetamine at the University of Berlin and the inventor of the modern method of refining crude oil.- His childhood and studies:...

 in Berlin, Germany
Berlin
Berlin is the capital city of Germany and is one of the 16 states of Germany. With a population of 3.45 million people, Berlin is Germany's largest city. It is the second most populous city proper and the seventh most populous urban area in the European Union...

. He named the compound phenylisopropylamine. It was one of a series of compounds related to the plant derivative ephedrine
Ephedrine
Ephedrine is a sympathomimetic amine commonly used as a stimulant, appetite suppressant, concentration aid, decongestant, and to treat hypotension associated with anaesthesia....

, which had been isolated from Ma-Huang that same year by Nagayoshi Nagai
Nagayoshi Nagai
was a notable Japanese organic chemist and pharmacologist, best known for his study of ephedrine.-Early life:Nagai was born in Myodo District, Awa Province as the son of a doctor and started studying rangaku medicine at the Dutch Medical School of Nagasaki in 1864...

. No pharmacological use was found for amphetamine until 1927, when pioneer psychopharmacologist
Psychopharmacology
Psychopharmacology is the scientific study of the actions of drugs and their effects on mood, sensation, thinking, and behavior...

 Gordon Alles
Gordon Alles
Gordon A. Alles , was an American chemist and pharmacologist who did much research on the isolation and properties of insulin for the treatment of diabetics. He is also credited with discovering and publishing the psychological effects of amphetamine, as well as for MDA...

 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
Inhaler
An inhaler or puffer is a medical device used for delivering medication into the body via the lungs. It is mainly used in the treatment of asthma and Chronic Obstructive Pulmonary Disease . Zanamivir , used to treat influenza, must be administered via inhaler...

 under the trade name
Trade name
A trade name, also known as a trading name or a business name, is the name which a business trades under for commercial purposes, although its registered, legal name, used for contracts and other formal situations, may be another....

 Benzedrine
Benzedrine
Benzedrine is the trade name of the racemic mixture of amphetamine . It was marketed under this brandname in the USA by Smith, Kline & French in the form of inhalers, starting in 1928...

, useful as a decongestant but readily usable for other purposes. 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". 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
Controlled Substances Act
The Controlled Substances Act was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. The CSA is the federal U.S. drug policy under which the manufacture, importation, possession, use and distribution of certain...

 in 1971.

The related compound methamphetamine
Methamphetamine
Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...

 was first synthesized from ephedrine
Ephedrine
Ephedrine is a sympathomimetic amine commonly used as a stimulant, appetite suppressant, concentration aid, decongestant, and to treat hypotension associated with anaesthesia....

 in Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...

 in 1920 by chemist Akira Ogata
Akira Ogata
was a Japanese chemist and the first to synthesize methamphetamine in crystalline form in 1919....

, via reduction of ephedrine using red phosphorus and iodine
Iodine
Iodine is a chemical element with the symbol I and atomic number 53. The name is pronounced , , or . The name is from the , meaning violet or purple, due to the color of elemental iodine vapor....

. The pharmaceutical Pervitin was a tablet of methamphetamine which was available in Germany from 1938 and widely used in the Wehrmacht
Wehrmacht
The Wehrmacht – from , to defend and , the might/power) were the unified armed forces of Nazi Germany from 1935 to 1945. It consisted of the Heer , the Kriegsmarine and the Luftwaffe .-Origin and use of the term:...

, 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.

In 1997 and 1998, researchers at Texas A&M University
Texas A&M University
Texas A&M University is a coeducational public research university located in College Station, Texas . It is the flagship institution of the Texas A&M University System. The sixth-largest university in the United States, A&M's enrollment for Fall 2011 was over 50,000 for the first time in school...

 claimed to have found amphetamine and methamphetamine in the foliage of two Acacia
Acacia
Acacia is a genus of shrubs and trees belonging to the subfamily Mimosoideae of the family Fabaceae, first described in Africa by the Swedish botanist Carl Linnaeus in 1773. Many non-Australian species tend to be thorny, whereas the majority of Australian acacias are not...

 species native to Texas
Texas
Texas is the second largest U.S. state by both area and population, and the largest state by area in the contiguous United States.The name, based on the Caddo word "Tejas" meaning "friends" or "allies", was applied by the Spanish to the Caddo themselves and to the region of their settlement in...

, A. berlandieri
Acacia berlandieri
Acacia berlandieri is a shrub native to the Southwestern United States and northeast Mexico that belongs to the subfamily Mimosoideae of Fabaceae . It grows tall, with blossoms that are spherical and white, occurring from February through April...

and A. rigidula
Acacia rigidula
Acacia rigidula, commonly known as Blackbrush Acacia or Chaparro Prieto, is a species of shrub or small tree in the legume family, Fabaceae. Its native range stretches from Texas in the United States south to central Mexico. This perennial is closely related to A. berlandieri and is not listed as...

. 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
Alexander Shulgin
Alexander "Sasha" Theodore Shulgin is an American pharmacologist, chemist, artist, and drug developer.Shulgin is credited with the popularization of MDMA, commonly known as ecstasy, in the late 1970s and early 1980s, especially for psychopharmaceutical use and the treatment of depression and...

, 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.

Performance-enhancing use


Adderall
Adderall
Adderall is a brand name of amphetamine salts–based medication used for attention-deficit hyperactivity disorder and narcolepsy. It is a brand-name psychostimulant medication composed of racemic amphetamine aspartate monohydrate, racemic amphetamine sulfate, dextroamphetamine saccharide, and...

, an amphetamine mixture, is used by some college and high-school students as a study and test-taking aid. 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 and the RAF used so many that "Methedrine won the Battle of Britain" according to one report. American bomber pilots use amphetamine ("go pills") to stay awake during long missions. The Tarnak Farm incident
Tarnak Farm incident
The Tarnak Farm incident refers to the killing of four Canadian soldiers and the injury of eight others from the Third Battalion of Princess Patricia's Canadian Light Infantry on the night of April 17, 2002, by an American F-16 fighter jet. The aircraft, piloted by U.S...

, in which an American F-16 pilot killed several friendly Canadian soldiers on the ground, was blamed by the pilot on his use of amphetamine. A nonjudicial hearing rejected the pilot's claim.

Amphetamine is also used by some professional, collegiate and high school athletes for its strong stimulant effect. Energy levels are perceived to be dramatically increased and sustained, which is believed to allow for more vigorous and longer play. However, at least one study has found that this effect is not measurable. The use of amphetamine during strenuous physical activity can be extremely dangerous, especially when combined with alcohol, and athletes have died as a result, for example, British cyclist Tom Simpson
Tom Simpson
Tom Simpson was the most successful English road racing cyclist of the post-war years. He infamously died of exhaustion on the slopes of Mont Ventoux during the 13th stage of the Tour de France in 1967...

.

Amphetamine use has historically been especially common among Major League Baseball
Major League Baseball
Major League Baseball is the highest level of professional baseball in the United States and Canada, consisting of teams that play in the National League and the American League...

 players and is usually known by the slang term "greenies". In 2006, the MLB banned the use of amphetamine. The ban is enforced through periodic drug-testing. However, the MLB has received some criticism because the consequences for amphetamine use are dramatically less severe than for anabolic steroid
Anabolic steroid
Anabolic steroids, technically known as anabolic-androgen steroids or colloquially simply as "steroids", are drugs that mimic the effects of testosterone and dihydrotestosterone in the body. They increase protein synthesis within cells, which results in the buildup of cellular tissue ,...

 use, with the first offense bringing only a warning and further testing.

Amphetamine was formerly in widespread use by truck drivers to combat symptoms of somnolence and to increase their concentration during driving, especially in the decades prior to the signing by former president Ronald Reagan
Ronald Reagan
Ronald Wilson Reagan was the 40th President of the United States , the 33rd Governor of California and, prior to that, a radio, film and television actor....

 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 driver—Implementation 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.

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
Goth subculture
The goth subculture is a contemporary subculture found in many countries. It began in England during the early 1980s in the gothic rock scene, an offshoot of the post-punk genre. The goth subculture has survived much longer than others of the same era, and has continued to diversify...

, gangsters, and casuals
Casuals
The casual subculture is a subsection of association football culture that is typified by football hooliganism and the wearing of expensive European designer clothing. The subculture originated in the United Kingdom in the early 1980s when many hooligans started wearing designer labels and...

 in all night soul and ska dances, punk concerts, basement show
Basement show
A basement show is a musical performance, often of the punk rock or hardcore punk variety, that is held in the basement of a residential home, rather than at a traditional venue. These are also sometimes referred to as "house shows" as they can happen anywhere in a residential house, not just in...

s and fighting on the terraces
Football hooliganism
Football hooliganism, sometimes referred to by the British media as the English Disease, is unruly and destructive behaviour—such as brawls, vandalism and intimidation—by association football club fans...

 by casuals.

The hippie
Hippie
The hippie subculture was originally a youth movement that arose in the United States during the mid-1960s and spread to other countries around the world. The etymology of the term 'hippie' is from hipster, and was initially used to describe beatniks who had moved into San Francisco's...

 counterculture
Counterculture
Counterculture is a sociological term used to describe the values and norms of behavior of a cultural group, or subculture, that run counter to those of the social mainstream of the day, the cultural equivalent of political opposition. Counterculture can also be described as a group whose behavior...

 was very critical of amphetamines due to the behaviors they cause; in an interview with the Los Angeles Free Press
Los Angeles Free Press
The Los Angeles Free Press , also called “the Freep”, was among the most widely distributed underground newspapers of the 1960s. It is often cited as the first such newspaper...

 in 1965, beat writer Allen Ginsberg
Allen Ginsberg
Irwin Allen Ginsberg was an American poet and one of the leading figures of the Beat Generation in the 1950s. He vigorously opposed militarism, materialism and sexual repression...

 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".

In literature


The writers of the Beat Generation
Beat generation
The Beat Generation refers to a group of American post-WWII writers who came to prominence in the 1950s, as well as the cultural phenomena that they both documented and inspired...

 used amphetamine extensively, mainly under the Benzedrine
Benzedrine
Benzedrine is the trade name of the racemic mixture of amphetamine . It was marketed under this brandname in the USA by Smith, Kline & French in the form of inhalers, starting in 1928...

 brand name. Jack Kerouac
Jack Kerouac
Jean-Louis "Jack" Lebris de Kerouac was an American novelist and poet. He is considered a literary iconoclast and, alongside William S. Burroughs and Allen Ginsberg, a pioneer of the Beat Generation. Kerouac is recognized for his spontaneous method of writing, covering topics such as Catholic...

 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.

Scottish author Irvine Welsh
Irvine Welsh
Irvine Welsh is a contemporary Scottish novelist, best known for his novel Trainspotting. His work is characterised by raw Scottish dialect, and brutal depiction of the realities of Edinburgh life...

 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
Trainspotting (novel)
Trainspotting is the first novel by Scottish writer Irvine Welsh. It is written in the form of short chapters narrated in the first person by various residents of Leith, Edinburgh, who either use heroin, are friends of the core group of heroin users, or engage in destructive activities that are...

 and Porno
Porno (novel)
Porno is a novel by Scottish writer Irvine Welsh, and is the sequel to Trainspotting.The book describes the characters of Trainspotting ten years after the events of the earlier book, as their paths cross again, this time with the pornography business as the backdrop rather than heroin use...

 reflect the changes in drug use and culture during the years that elapse between the two texts.

Amphetamine is frequently mentioned in the work of American journalist Hunter S. Thompson
Hunter S. Thompson
Hunter Stockton Thompson was an American journalist and author who wrote The Rum Diary , Fear and Loathing in Las Vegas and Fear and Loathing on the Campaign Trail '72 .He is credited as the creator of Gonzo journalism, a style of reporting where reporters involve themselves in the action to...

. Speed appears not only amongst 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, such as in his "Author's Note" in Fear and Loathing on the Campaign Trail '72
Fear and Loathing on the Campaign Trail '72
Fear and Loathing: On the Campaign Trail '72 is a collection of articles covering the 1972 presidential campaign written by the gonzo journalist Hunter S Thompson and illustrated by Ralph Steadman...

.


"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 Bowl
Super Bowl
The Super Bowl is the championship game of the National Football League , the highest level of professional American football in the United States, culminating a season that begins in the late summer of the previous calendar year. The Super Bowl uses Roman numerals to identify each game, rather...

s. ... 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
Elliott Smith
Steven Paul "Elliott" Smith was an American singer-songwriter and musician. Smith was born in Omaha, Nebraska, raised primarily in Texas, and resided for a significant portion of his life in Portland, Oregon, where he first gained popularity...

'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
Everclear (band)
Everclear is a rock band formed in Portland, Oregon in 1992 best known for their radio hits spanning more than a decade. For most of its existence, Everclear has consisted of Art Alexakis , Craig Montoya , and Greg Eklund . Eklund replaced original drummer Scott Cuthbert in 1994...

, the song "20 Dollar nose bleed" by the Pop-rock band Fall Out Boy
Fall Out Boy
Fall Out Boy is an American rock band from Wilmette, Illinois, formed in 2001. The band consists of vocalist, guitarist and composer Patrick Stump, bassist and lyricist Pete Wentz, guitarist Joe Trohman, and drummer Andy Hurley. The band released five studio albums from 2003–2008...

, and the song Headfirst For Halos
Headfirst for Halos
"Headfirst for Halos" is the sixth track and third single from My Chemical Romance's debut album, I Brought You My Bullets, You Brought Me Your Love. It is also their third overall single. The cover of the single was seen in the "old school" music video for the song "I'm Not Okay ", featured on...

 by My Chemical Romance
My Chemical Romance
My Chemical Romance is an American alternative rock band from New Jersey, formed in 2001. The band consists of lead vocalist Gerard Way, guitarists Ray Toro and Frank Iero, and bassist Mikey Way and have a diverse sound incorporating elements of punk, emo, glam metal, and progressive rock...

. It has also influenced the aesthetics of many rock'n'roll bands (especially in the garage rock
Garage rock
Garage rock is a raw form of rock and roll that was first popular in the United States and Canada from about 1963 to 1967. During the 1960s, it was not recognized as a separate music genre and had no specific name...

, mod R&B, death rock, punk/hardcore, gothic rock
Gothic rock
Gothic rock is a musical subgenre of post-punk and alternative rock that formed during the late 1970s. Gothic rock bands grew from the strong ties they had to the English punk rock and emerging post-punk scenes...

 and extreme heavy metal genres). Hüsker Dü
Hüsker Dü
Hüsker Dü was an American rock band formed in Saint Paul, Minnesota in 1979. The band's continual members were guitarist Bob Mould, bassist Greg Norton, and drummer Grant Hart....

, Jesus and Mary Chain's and The Who
The Who
The Who are an English rock band formed in 1964 by Roger Daltrey , Pete Townshend , John Entwistle and Keith Moon . They became known for energetic live performances which often included instrument destruction...

 were keen amphetamine users early in their existence. Land Speed Record
Land Speed Record (album)
Land Speed Record is the first full-length record by Hüsker Dü, released in January 1982. It was recorded live on August 15, 1981 at the 7th Street Entry, a venue in Minneapolis, Minnesota. The album is a fast and furious hardcore workout that bears almost no resemblance to the melodic post-punk...

 is an allusion to Hüsker Dü's amphetamine use. 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
The Rolling Stones
The Rolling Stones are an English rock band, formed in London in April 1962 by Brian Jones , Ian Stewart , Mick Jagger , and Keith Richards . Bassist Bill Wyman and drummer Charlie Watts completed the early line-up...

 referenced the drug in their song "Can't You Hear Me Knocking" on the album Sticky Fingers
Sticky Fingers
-Personnel:The Rolling Stones*Mick Jagger – lead vocals, acoustic guitar on "Dead Flowers", electric guitar on "Sway", percussion*Keith Richards – electric guitar, six & twelve string acoustic guitar, backing vocals...

 ("Y'all got cocaine eyes / Yeah, ya got speed-freak jive now"). Lou Reed
Lou Reed
Lewis Allan "Lou" Reed is an American rock musician, songwriter, and photographer. He is best known as guitarist, vocalist, and principal songwriter of The Velvet Underground, and for his successful solo career, which has spanned several decades...

 refers explicitly to the drug on his album Berlin
Berlin
Berlin is the capital city of Germany and is one of the 16 states of Germany. With a population of 3.45 million people, Berlin is Germany's largest city. It is the second most populous city proper and the seventh most populous urban area in the European Union...

, in the song "How Do You Think It Feels?". Reed's band The Velvet Underground
The Velvet Underground
The Velvet Underground was an American rock band formed in New York City. First active from 1964 to 1973, their best-known members were Lou Reed and John Cale, who both went on to find success as solo artists. Although experiencing little commercial success while together, the band is often cited...

, a creation of Andy Warhol
Andy Warhol
Andrew Warhola , known as Andy Warhol, was an American painter, printmaker, and filmmaker who was a leading figure in the visual art movement known as pop art...

's Factory Years, was fueled by amphetamines, as well as naming their second album White Light/White Heat
White Light/White Heat
The album briefly appeared on the Billboard 200, although only peaking at number 199. Despite its poor sales, the distorted, feedback-driven, and roughly recorded sound on White Light/White Heat became a notable influence on punk and experimental rock...

 after the drug and making reference to the song in "Sister Ray
Sister Ray
Sister Ray may mean one of the following:* "Sister Ray", 1968 song by The Velvet Underground* A fictional enormous laser cannon in the video game Final Fantasy VII* Sister Ray , a punk rock band from Youngstown, Ohio...

.". The Pulp
Pulp (band)
Pulp are an English alternative rock band formed in Sheffield in 1978. Their lineup consists of Jarvis Cocker , Russell Senior , Candida Doyle , Mark Webber , Steve Mackey and Nick Banks ....

 song Sorted for E's & Wizz
Sorted for E's & Wizz
"Sorted for E's & Wizz" is a song by the English band Pulp. Taken from their UK number one album Different Class, it was released as a double A-sided single with "Mis-Shapes" in September 1995 and reached number two in the UK charts...

refers to British slang terms for ecstasy and amphetamines.

Many rock'n'roll bands have named themselves after amphetamine and drug slang surrounding it. For example Mod revival
Mod Revival
The mod revival was a music genre and subculture that started in England in 1978 and later spread to other countries . The mod revival's mainstream popularity was relatively short, although its influence has lasted for decades...

ists, The Purple Hearts
Purple Hearts (UK band)
The Purple Hearts were often considered one of the best English mod revival groups, the NME calling them "one of the few mod bands to actually cut it on rock’n’roll terms”.-Career:...

 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. The Amphetameanies, a ska-punk band, are also named after amphetamine, but also imitate its effects. Dexy's Midnight Runners, of number one hit "Come On Eileen
Come on Eileen
"Come On Eileen" was a single released by Dexys Midnight Runners in 1982. The song was written by Kevin Rowland, "Big" Jim Paterson, and Billy Adams; it was produced by Clive Langer and Alan Winstanley. It also appeared on the album Too-Rye-Ay...

", are named after Dexedrine. Motörhead derived their name from the British slang for 'speed freak' and Motorhead's Lemmy Kilmister is a long-term user of speed.

An American electronic music duo The Crystal Method
The Crystal Method
The Crystal Method is an American electronic music duo that was created in Los Angeles, California by Ken Jordan and Scott Kirkland in the early 1990s. The Crystal Method's music has appeared in numerous TV shows, films, video games, and advertisements. The most prominent is the US television...

 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."

In film



Producer David O. Selznick
David O. Selznick
David O. Selznick was an American film producer. He is best known for having produced Gone with the Wind and Rebecca , both of which earned him an Oscar for Best Picture.-Early years:...

 was an amphetamine user, and would often dictate long and rambling memos under the influence of amphetamine to his directors. The documentary Shadowing The Third Man relates that Selznick introduced The Third Man
The Third Man
The Third Man is a 1949 British film noir, directed by Carol Reed and starring Joseph Cotten, Alida Valli, Orson Welles, and Trevor Howard. Many critics rank it as a masterpiece, particularly remembered for its atmospheric cinematography, performances, and unique musical score...

 director Carol Reed
Carol Reed
Sir Carol Reed was an English film director best known for Odd Man Out , The Fallen Idol , The Third Man and Oliver!...

 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.
The title of the 2009 movie Amphetamine
Amphetamine (2009 film)
Amphetamine is a 2010 Hong Kong film starring Byron Pang and Thomas Price. It revolves around the story of a Chinese fitness trainer, Kafka, who meets Daniel, a business executive. The film is directed by acclaimed Hong Kong Chinese film-maker Scud, the stage name of Danny Cheng Wan-Cheung. It was...

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 安 非 他 命 - "ān fēi tā mìng" - and as commonly happens with transliteration of non-Chinese terms each character has independent meaning as an individual unrelated word.

Legal status

  • In the United Kingdom, amphetamines are regarded as Class B
    Misuse of Drugs Act 1971
    The Misuse of Drugs Act 1971 is an Act of Parliament which represents UK action in line with treaty commitments under the Single Convention on Narcotic Drugs, the Convention on Psychotropic Substances, and the United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic...

     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.
  • In the Netherlands, amphetamine and methamphetamine are List I drugs of the Opium Law
    Opium Law
    The Opium Law is the section of the Dutch law which covers nearly all psychotropic drugs. All non-psychotropic, but prescription-only drugs are covered by the Medicine Act.- Origin and history :...

    , but the dextro isomer of amphetamine is indicated for ADD/ADHD and narcolepsy and available for prescription as 5 and generic tablets, and 5 and gel capsules.
  • In the United States, amphetamine and methamphetamine are Schedule II drugs, classified as CNS (central nervous system) stimulants. 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 III 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.


Internationally, amphetamine is a Schedule II drug under the Convention on Psychotropic Substances
Convention on Psychotropic Substances
The Convention on Psychotropic Substances of 1971 is a United Nations treaty designed to control psychoactive drugs such as amphetamines, barbiturates, benzodiazepines, and psychedelics signed at Vienna on February 21, 1971...

.

Prodrugs


A number of substances have been shown to produce amphetamine and/or methamphetamine as metabolite
Metabolite
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...

s, including amfecloral
Amfecloral
Amfecloral , also known as amphecloral , is a stimulant drug of the phenethylamine and amphetamine chemical classes that was used as an appetite suppressant under the trade name Acutran, but is now no longer marketed...

, amphetaminil
Amphetaminil
Amphetaminil is a stimulant drug derived from amphetamine, which was developed in the 1970s and used for the treatment of obesity, ADHD, and narcolepsy. It has largely been withdrawn from clinical use following problems with abuse....

, benzphetamine
Benzphetamine
Benzphetamine is an anorectic drug marketed under this brand in the USA by Pharmacia. Benzphetamine is used as a short term adjunct in management of exogenous obesity. It is closely related to amphetamine.- Pharmacology :...

, clobenzorex
Clobenzorex
Clobenzorex is a stimulant drug of the phenethylamine and amphetamine chemical classes used as an appetite suppressant...

, dimethylamphetamine
Dimethylamphetamine
Dimethylamphetamine , also referred to as dimetamfetamine and N,N-dimethylamphetamine, is a stimulant drug of the phenethylamine and amphetamine chemical classes. Dimethylamphetamine has weaker stimulant effects than amphetamine or methamphetamine and is considerably less addictive and less...

, ethylamphetamine
Ethylamphetamine
Ethylamphetamine , also known as etilamfetamine or N-ethylamphetamine, is a stimulant drug of the phenethylamine and amphetamine chemical classes...

, famprofazone
Famprofazone
Famprofazone is a non-steroidal anti-inflammatory agent of the pyrazolone series which is available over-the-counter in some countries such as Taiwan. It has analgesic, anti-inflammatory, and antipyretic effects. Famprofazone has been known to produce methamphetamine as an active metabolite, with...

, fencamine
Fencamine
Fencamine is a psychostimulant drug of the amphetamine class. It is closely related to fenethylline....

, fenethylline
Fenethylline
Fenethylline, also spelled phenethylline, is a synthetic prodrug used as a stimulant and marketed under the brand name Captagon.-History:...

, fenproporex
Fenproporex
Fenproporex is a stimulant drug of the phenethylamine and amphetamine chemical classes which was developed in the 1960s. It is used as an appetite suppressant for the treatment of obesity....

, furfenorex
Furfenorex
Furfenorex , also known as furfurylmethylamphetamine, is a stimulant drug which was developed in the 1960s and used as an appetite suppressant. It produces methamphetamine as a metabolite, and is no longer marketed, due to possible problems with abuse.- References :...

, lisdexamfetamine, mefenorex
Mefenorex
Mefenorex is a stimulant drug which was used as an appetite suppressant. It is an amphetamine derivative which was developed in the 1970s and used for the treatment of obesity...

, mesocarb
Mesocarb
Mesocarb is a stimulant drug which was developed in the USSR in the 1970s. It has been shown to act as a dopamine reuptake inhibitor which is slower acting but longer lasting and less neurotoxic than dextroamphetamine....

, prenylamine
Prenylamine
Prenylamine is a calcium channel blocker of the amphetamine chemical class which is used as a vasodilator in the treatment of angina pectoris. It has been shown to partially metabolize to amphetamine and can cause false positives for it in drug tests...

, propylamphetamine
Propylamphetamine
Propylamphetamine is a psychoactive drug and research chemical of the phenethylamine and amphetamine chemical classes which acts as a stimulant. It was first developed in the 1970s, mainly for research into the metabolism of, and as a comparison tool to other amphetamines...

, and selegiline
Selegiline
Selegiline is a drug used for the treatment of early-stage Parkinson's disease, depression and senile dementia. In normal clinical doses it is a selective irreversible MAO-B inhibitor, however in larger doses it loses its specificity and also inhibits MAO-A...

, among others. These compounds may produce positive results for amphetamine on drug test
Drug test
A drug test is a technical analysis of a biological specimen – for example urine, hair, blood, sweat, or oral fluid / saliva – to determine the presence or absence of specified parent drugs or their metabolites...

s.

Derivatives


Amphetamine derivatives are a class of potent drugs that act by increasing levels of dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 and norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...

 in the brain, inducing euphoria
Euphoria
Euphoria is an emotional and mental state defined as a sense of great elation and well being.Euphoria may also refer to:* Euphoria , a genus of scarab beetles* Euphoria, a genus name previously used for the longan and other trees...

. The class includes prescription CNS
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

 drugs commonly used to treat attention-deficit hyperactivity disorder
Attention-deficit hyperactivity disorder
Attention deficit hyperactivity disorder is a developmental disorder. It is primarily characterized by "the co-existence of attentional problems and hyperactivity, with each behavior occurring infrequently alone" and symptoms starting before seven years of age.ADHD is the most commonly studied and...

 (ADHD). It is also used to treat symptoms of traumatic brain injury
Traumatic brain injury
Traumatic brain injury , also known as intracranial injury, occurs when an external force traumatically injures the brain. TBI can be classified based on severity, mechanism , or other features...

 (TBI) and the daytime drowsiness symptoms of narcolepsy
Narcolepsy
Narcolepsy is a chronic sleep disorder, or dyssomnia, characterized by excessive sleepiness and sleep attacks at inappropriate times, such as while at work. People with narcolepsy often experience disturbed nocturnal sleep and an abnormal daytime sleep pattern, which often is confused with insomnia...

, postural orthostatic tachycardia syndrome
Postural orthostatic tachycardia syndrome
Postural orthostatic tachycardia syndrome is a condition of dysautonomia, more specifically orthostatic intolerance, in which a change from the supine position to an upright position causes an abnormally large increase in heart rate, called tachycardia...

 (POTS) and chronic fatigue syndrome
Chronic fatigue syndrome
Chronic fatigue syndrome is the most common name used to designate a significantly debilitating medical disorder or group of disorders generally defined by persistent fatigue accompanied by other specific symptoms for a minimum of six months, not due to ongoing exertion, not substantially...

 (CFS).

Smuggling


The 213 kg of amphetamine worth 40 million AED
AED
AED may refer to:* Anhidrotic ectodermal dysplasia, a genetic disorder* Automated external defibrillator, a portable electronic device that diagnoses and can correct arrhythmia of the heart....

 was seized by the UAE Drug combat authorities, on 30 November 2011 from an Iran
Iran
Iran , officially the Islamic Republic of Iran , is a country in Southern and Western Asia. The name "Iran" has been in use natively since the Sassanian era and came into use internationally in 1935, before which the country was known to the Western world as Persia...

ian ship which was supposed to deliver the consingment in Malaysia and made a port stop in Sharjah
Sharjah
Sharjah is one of the emirates of the United Arab Emirates . The emirate covers 2,600 km² and has a population of over 800,000...

.

The Gulf News
Gulf News
Gulf News is a daily English language newspaper published from Dubai, in the United Arab Emirates with a December 2009 BPA audited circulation of over 117,036 qualified copies...

 published on 30th November 2011, says "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.

External links

(D-form—dextroamphetamine) (L-form and D, L-forms) (L-form—Levamphetamine or L-amphetamine)