The amphetamine molecule can exist as one of two chiral enantiomers, levoamphetamine or dextropamphetamine. These molecules are identical, except for that they are mirror images of one another, much like a left and right hand. The name "amphetamine" technically refers to an even mix of both enantiomers, called the racemic combination, but informally it can refer to any combination of the enantiomers. Most pharmaceutical preparations of amphetamine contain a unique mixture of the two, and are described by the ratio of the enantiomers; Adderall contains three parts dextroamphetamine and one levoamphetamine, while Vyvanse contains exclusively dextroamphetamine. While the distinct enantiomers of some drugs have markedly different effects, amphetamines behave very similarly, except that levoamphetamine is a more potent cardiovascular stimulant and appetite suppressant, while dextroamphetamine is a more potent central nervous system stimulant.
Amphetamine causes a surge of activity in the brain's chemistry. It works mainly by stimulating the activity of two neurotransmitters, dopamine and norepinephrine; it doesn't create any additional dopamine or norepinephrine, but rather prompts its release from storage sites in presynaptic nerve groupings. Additionally, it causes the release of other neurotransmitters, serotonin and histamine, and the hormone epinephrine. It also causes the synthesis of a neuropeptide called CART, an acronym for cocaine- and amphetamine-regulated transcript; neuropeptides are molecules that are similar to (but distinct from) proteins which help neurons to transmit signals more efficiently.
By stimulating this combination of neurotransmitters, hormones, and neuropeptides, therapeutic doses of amphetamine typically prompt small yet quantifiable improvements in attention, short- and long-term memory, and other aspects of cognition. One study indicated that amphetamine boosts users' IQ by approximately five points when used as directed. It is also sometimes used as a physical performance-enhancing drug; virtually all professional and collegiate sports leagues ban its non-medical use due to its effects on focus and endurance. However, excessively high doses of amphetamine can have the opposite effects, impairing focus and reducing athletic performance.
Amphetamine was first discovered in 1887 by Lazar Edeleanu, a Romanian chemist working in Germany; he initially named the drug phenylisopropylamine. Its stimulant properties, however, were not recognized until 1927 when it was independently rediscovered by another chemist named Gordon Alles. Its potential as a medicine remained unnoticed for still another six years, when the pharmaceutical company Smith, Kline and French introduced its Benzedrine inhaler. Three years later, they developed Benzedrine sulfate, an oral version of the drug that was soon widely prescribed and abused.
Today, amphetamine is commercially sold under many names and concentrations. Among the most common in the United States are Adderall and Adderall XR (extended release), Mydayis, Vyvanse, Adenzys, and Evekeo.
Within years of its commercial introduction in 1933, amphetamine sold as Benzedrine had permeated many corners of culture, for both licit and off-label use. It was used copiously during the second World War by both sides, and recreational or nootropic use of amphetamine has been widely referenced in literature and music. Amphetamine continues to be widely abused; self-reported surveys of American college students indicate that between 5 and 35% of them have used amphetamine illicitly to complete assignments, and the United Nations Office on Drugs and Crime notes that amphetamine and similar stimulants are the second most widely abused recreational drugs on the planet, following only cannabis.
Since it stimulates the neurotransmitters involved in the brain's reward pathway, amphetamine is powerfully addictive when used in excess. Users quickly begin to crave more, then find that they need increasingly larger doses to achieve the same effect as they develop a tolerance. Recovering from amphetamine addiction can be particularly difficult, since no drug currently exists that can attenuate cravings, but research indicates that regular cardiovascular exercise can help significantly when heavy users are ready to stop. One large survey indicated a common pattern among amphetamine addicts as they quit, with a notable "crash" in the first week without the drug but a significant improvement in cravings and cognition by their fourth week.
Amphetamine's addictive properties had became apparent by the early 1970s, and it began to come under scrutiny by both national and international policymakers. The treaty emerging from the United Nation's 1971 Convention on Psychotropic Substances defined amphetamine as a schedule II controlled substance, and it's been tightly regulated by most countries ever since. Some nations, including Japan and South Korea, have banned amphetamines for even medical use, but most acknowledge its medical purpose and allow it when prescribed by a doctor. In the United States, it is classified as a Schedule II drug, meaning it has a recognized legitimate medical use, but also a high potential for abuse and addiction. Schedule II drugs are illegal to possess without a prescription.
Amphetamine is also the parent of a large class of drugs, called substituted amphetamines. Substituted amphetamines are a highly varied group of drugs, ranging from decongestants like ephedrine to dangerous drugs of abuse such as MDMA and methamphetamine. Substituted amphetamines are developed by replacing one or more of the molecule's hydrogen atoms.
Amphetamine can cause a variety of physical and psychological side effects. Dosage is particularly important in determining the types, degree, and duration of various reactions, and each individual will react differently. While heavy or prolonged use can become dangerous, normal therapeutic doses are very safe for the vast majority of patients. Interestingly, the side effects of amphetamine can be so varied between patients that some of those listed below are in fact opposites.
The most common physical side effects are a reduced appetite and mild nausea. Unusually high or low blood pressure, reduced blood flow to the hands and feet (called Raynaud's phenomenon), and abdominal pain are also relatively common. Less common side effects include profuse sweating, nasal congestion, blurry vision, dry mouth, diarrhea, constipation, grinding of the teeth, nosebleed, and muscle tics. Amphetamine also causes faster and deeper breathing, which is usually not noticeable at therapeutic doses but may be in patients whose respiration is already compromised. Some men develop erectile dysfunction while using amphetamine, while others experience priapism or find that their libido increases significantly.
While a modestly raised heart rate is a common side effect, patients should immediately stop using amphetamine and contact their doctor if their heart rate exceeds 100 beats per minute while resting.
Amphetamine can also cause psychological side effects. Most patients experience the desired changes in cognition: increased alertness, concentration, and motivation. However, some patients have unpleasant reactions, including mood swings and anxiety. Difficulty sleeping is probably the most common unpleasant psychological effect, and is especially likely if the drug is taken too close to bedtime.
Some patients report blurred vision after amphetamine; users should avoid driving or using heavy machinery after beginning amphetamine or changing their dose until they understand how it effects them.
Heavy or long-time users, even those who have taken only therapeutic doses for long periods of time, can in rare cases develop amphetamine psychosis. The most common symptoms of amphetamine psychosis are delusions and paranoia; users should stop using amphetamine immediately and contact their doctor if they begin to notice any unusual changes in their mental state.
Amphetamine is available in a variety of doses, ranging from 5 to nearly 19 milligrams, in immediate and extended release formulations. It should be taken first thing in the morning, with or without food. Amphetamine should never be taken late at night, since this can result in serious insomnia.
Children between 6 and 17 years old prescribed amphetamine for attention deficit hyperactivity disorder typically begin with a 5 mg dose, taken once or twice per day. The dose may be raised by 5 mg each week until the patient responds as desired. Only in very rare cases do pediatric patients need more than 40 mg per day, and patients using the extended release formulation should never take more than 20 mg per day.
Adults taking amphetamine for ADHD typically begin with a 12.5 mg dose once daily, then adjust their dosage as necessary. About 50 to 70% of children outgrow ADHD during adolescence, but many continue to require therapy as adults. Methylphenidate is typically the first-line drug used for adult ADHD, but amphetamine appears to be have fewer negative cardiovascular side effects.
Patients may react differently between extended and immediate release formulations of amphetamine, and may need different doses of each.
Adults using amphetamine to treat narcolepsy typically begin treatment with 10 mg over the course of each day: one initial dose after waking up, and then additional doses four to six hours later. Eventually, the patient's dose will be adjusted; most take between 5 and 60 mg of amphetamine per day.
Adults using amphetamine for obesity typically take a 5 mg tablet, 30 to 60 minutes before each meal. They should take no more than 30 mg each day, and should use this treatment for at most a few weeks.
If a patient misses a dose, they should take it as soon as they remember, but not too late in the day. If a patient forgets until the late afternoon, they should skip it. Patients should never take extra to make up for a missed dose.
Amphetamine treatment should be occasionally paused to determine if the drug is still necessary or the dosage could be reduced. It should always be taken at the very lowest dose necessary to reduce the likelihood of physical dependence.
The human body develops a tolerance for amphetamine over time, meaning it almost inevitably requires a larger dose to achieve the same effect as time goes on. This is a concern for both legitimate and illegal use, and can be very dangerous when recreational users begin to take increasingly large amounts. Recreational users with very high tolerances have reported using up to five grams of amphetamine in one day, one hundred times the largest available therapeutic dose.
Overdoses of amphetamine can be fatal. If an individual has taken too much, call 911 or Poison Help (1-800-222-1222 in the United States) immediately. Treatment of overdose typically involves sedation with a barbiturate, and in rare cases an intravenous dose of phentolamine for patients with dangerously high blood pressure.
Amphetamine should never be used alongside other drugs that stimulate the neurotransmitter serotonin - this can cause a dangerous condition called serotonin syndrome. These include antidepressants such as SSRIs, SNRIs, MAOIs, and TCAs, herbal supplements such as St. John's wort, the common cough suppressant dextromthorphan, and drugs of abuse such as MDMA or cocaine. Using these drugs in combination with amphetamine can release too much serotonin into the central nervous system at once, leading to dangerously elevated body temperature, tremors, profuse sweating, diarrhea, and in very serious cases, seizures. Serotonin syndrome has been deadly, including the high-profile death of college student Libby Zion. Treatment for serious cases may require actively cooling the body or providing a serotonin antagonist drug to suppress its effects.
MAO inhibitors pose the greatest risk for serotonin syndrome; patients should not use amphetamine within 14 days of taking an MAO inhibitor. Common MAO inhibitors include isocarboxazid, linezolid, phenelzine, rasagiline, and selegiline.
Amphetamine may reduce the effectiveness of many heart medications, including those for blood pressure and arrythmia. Patients with heart problems should usually avoid amphetamine altogether, even if their condition is well controlled with medication.
Amphetamine may interact dangerously with antidepressants or other psychiatric medicines, sometimes causing severe anxiety. Like patients with heart problems, those with significant mental health issues are typically advised to avoid amphetamine, even if their condition is under control. Most antidepressant drugs work by influencing serotonin, and are thus risk factors for serotonin syndrome, mentioned above.
Vitamin C is known to impair the absorption of amphetamine in the body; supplements or foods containing large concentrations of vitamin C should be consumed only several hours after taking amphetamine.
Amphetamine has a high potential for abuse; patients with a history of drug or alcohol abuse should not use it.
Stimulant drugs such as amphetamine can be very dangerous for patients with heart problems. Patients with high blood pressure, heart disease, arrhythmia, or other heart defects should be very cautious if using amphetamine. In rare cases, amphetamine has caused strokes and heart attacks in patients with compromised cardiovascular systems.
Pregnant women should not use amphetamine. It is not known with certainty whether or not amphetamine directly harms developing fetuses (although studies on animals strongly indicate that it does), but it is known to complicate pregnancies by causing premature birth, unusually low birth weight, and withdrawal symptoms in the newborn child. Furthermore, amphetamine should not be used by mothers who are breastfeeding, because it is known to secrete into breast milk.
All patients using amphetamine should have their blood pressure, heart rate, and psychological health regularly monitored to identify any irregularities as early as possible. Amphetamine patients should also have their weight and growth regularly checked, since stimulants have been known to delay growth and cause significant weight loss, due to both appetite suppression and an enhanced metabolism.
Immediate release amphetamine is not approved for use in patients younger than three years of age, and the extended release formulation is not approved for patients younger than six. There have been no longitudinal studies examining amphetamine's long-term health effects when use begins in childhood, and for this reason many parents are wary of prescribing it to young children.
Amphetamine can reportedly reduce the threshold for seizures in some patients, making them more likely to experience one. Patients with epilepsy or other conditions predisposing them to seizures should be very cautious with amphetamine, and avoid it if possible. Further research is needed to better understand the relationship between amphetamine and seizures.
Patients with moderate or severe anxiety should avoid amphetamine; it can worsen anxiety symptoms.
Amphetamine should not be used by patients with hyperthyroidism, because they often already experience an elevated heart rate and body temperature, which could be dangerously compounded if they experience these as side effects of amphetamine.
Abruptly stopping amphetamine therapy can result in withdrawal symptoms, especially in users who have taken it for a long period of time, or at a particularly high dosage. Withdrawal symptoms can include difficulty concentrating (beyond ADHD symptoms the drug may have treated), craving for amphetamine, anxiety and depression, difficulty sleeping, or vivid dreams. Older patients tend to experience withdrawal symptoms more intensely. Individuals can often avoid withdrawal symptoms by gradually lowering their dose before stopping. Withdrawal symptoms typically last for at most four weeks for even for the most dependent users, and the first week is the most difficult for virtually all patients. While withdrawal from amphetamine after prolonged use is certainly unpleasant, it is not dangerous.
Amphetamine can in rare cases induce psychosis; this is most commonly seen in cases of recreational abuse of the drug, but can occur even if used as directed for therapeutic purposes. Symptoms of amphetamine psychosis typically include paranoia and delusions; users experiencing these even mildly should stop taking amphetamine immediately and seek medical attention. Patients with a history of mental health issues, including depression or bipolar disorder, may be more vulnerable to this, and should be especially mindful of their mental health if using amphetamine.
Amphetamine should be stored at room temperature (approximately 77 degrees Fahrenheit, or 25 degrees Celsius), in a firmly sealed container well outside the reach of children and pets.
Amphetamine is sold in pill, orally disintegrating tablet, and liquid forms. The orally disintegrating tablets must be kept dry to avoid early activation, and thus must be opened only with dry hands and never stored in a bathroom that fills with steam when bathing. The orally disintegrating tablets are distributed in sealed travel cases designed to keep them safe from moisture, and they should be kept in this case during storage.
Due to its potential for abuse, unused amphetamine should always be disposed of in secure prescription drop-off locations, such as at police or fire departments.
Amphetamine has helped millions of people, though unfortunately, its widespread misuse has likely hurt just as many. If used as directed, amphetamine can change lives with its remarkable effects on concentration and memory, and thus academic and professional performance. When used recreationally or irresponsibly, however, it can be powerfully addictive, acutely dangerous to internal organs, and even deadly.
Patients using amphetamine should regularly consult with their doctor about the drug's benefits and effectiveness, especially younger children. Due to its negative side effects and potential for dependence and abuse, many patients eschew amphetamine for treating ADHD and explore "skills not pills" therapies; for some patients, these can be equally effective in cultivating focus and motivation. However, amphetamine has undoubtedly improved the lives of millions of patients, and its legitimate medical uses should not be overlooked.