Amphetamine[note 2] is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity; it is also used to treat binge eating disorder in the form of its inactive prodrug lisdexamfetamine. Amphetamine was discovered as a chemical in 1887 by Lazăr Edeleanu, and then as a drug in the late 1920s. It exists as two enantiomers:[note 3] levoamphetamine and dextroamphetamine. Amphetamine properly refers to a specific chemical, the racemic free base, which is equal parts of the two enantiomers in their pure amine forms. The term is frequently used informally to refer to any combination of the enantiomers, or to either of them alone. Historically, it has been used to treat nasal congestion and depression. Amphetamine is also used as an athletic performance enhancer and cognitive enhancer, and recreationally as an aphrodisiac and euphoriant. It is a prescription drug in many countries, and unauthorized possession and distribution of amphetamine are often tightly controlled due to the significant health risks associated with recreational use.[sources 1]
The first amphetamine pharmaceutical was Benzedrine, a brand which was used to treat a variety of conditions. Pharmaceutical amphetamine is prescribed as racemic amphetamine, Adderall,[note 4] dextroamphetamine, or the inactive prodrug lisdexamfetamine. Amphetamine increases monoamine and excitatory neurotransmission in the brain, with its most pronounced effects targeting the norepinephrine and dopamine neurotransmitter systems.[sources 2]
At therapeutic doses, amphetamine causes emotional and cognitive effects such as euphoria, change in desire for sex, increased wakefulness, and improved cognitive control. It induces physical effects such as improved reaction time, fatigue resistance, decreased appetite, elevated heart rate, and increased muscle strength. Larger doses of amphetamine may impair cognitive function and induce rapid muscle breakdown. Addiction is a serious risk with heavy recreational amphetamine use, but is unlikely to occur from long-term medical use at therapeutic doses. Very high doses can result in psychosis (e.g., hallucinations, delusions, and paranoia) which rarely occurs at therapeutic doses even during long-term use. Recreational doses are generally much larger than prescribed therapeutic doses and carry a far greater risk of serious side effects.[sources 3]
Amphetamine belongs to the phenethylamine class. It is also the parent compound of its own structural class, the substituted amphetamines,[note 5] which includes prominent substances such as bupropion, cathinone, MDMA, and methamphetamine. As a member of the phenethylamine class, amphetamine is also chemically related to the naturally occurring trace amine neuromodulators, specifically phenethylamine and N-methylphenethylamine, both of which are produced within the human body. Phenethylamine is the parent compound of amphetamine, while N-methylphenethylamine is a positional isomer of amphetamine that differs only in the placement of the methyl group.[sources 4]
Uses
Medical
Amphetamine is used to treat attention deficit hyperactivity disorder (ADHD), narcolepsy, obesity, and, in the form of lisdexamfetamine, binge eating disorder.[1][35][36] It is sometimes prescribed off-label for its past medical indications, particularly for depression and chronic pain.[1][51]
ADHD
Long-term amphetamine exposure at sufficiently high doses in some animal species is known to produce abnormal dopamine system development or nerve damage,[52][53] but, in humans with ADHD, long-term use of pharmaceutical amphetamines at therapeutic doses appears to improve brain development and nerve growth.[54][55][56] Reviews of magnetic resonance imaging (MRI) studies suggest that long-term treatment with amphetamine decreases abnormalities in brain structure and function found in subjects with ADHD, and improves function in several parts of the brain, such as the right caudate nucleus of the basal ganglia.[54][55][56]
Reviews of clinical stimulant research have established the safety and effectiveness of long-term continuous amphetamine use for the treatment of ADHD.[44][57][58] Randomized controlled trials of continuous stimulant therapy for the treatment of ADHD spanning 2 years have demonstrated treatment effectiveness and safety.[44][57] Two reviews have indicated that long-term continuous stimulant therapy for ADHD is effective for reducing the core symptoms of ADHD (i.e., hyperactivity, inattention, and impulsivity), enhancing quality of life and academic achievement, and producing improvements in a large number of functional outcomes[note 6] across 9 categories of outcomes related to academics, antisocial behavior, driving, non-medicinal drug use, obesity, occupation, self-esteem, service use (i.e., academic, occupational, health, financial, and legal services), and social function.[44][58] Additionally, a 2024 meta-analytic systematic review reported moderate improvements in quality of life when amphetamine treatment is used for ADHD.[60] One review highlighted a nine-month randomized controlled trial of amphetamine treatment for ADHD in children that found an average increase of 4.5 IQ points, continued increases in attention, and continued decreases in disruptive behaviors and hyperactivity.[57] Another review indicated that, based upon the longest follow-up studies conducted to date, lifetime stimulant therapy that begins during childhood is continuously effective for controlling ADHD symptoms and reduces the risk of developing a substance use disorder as an adult.[44]
Models of ADHD suggest that it is associated with functional impairments in some of the brain’s neurotransmitter systems;[61] these functional impairments involve impaired dopamine neurotransmission in the mesocorticolimbic projection and norepinephrine neurotransmission in the noradrenergic projections from the locus coeruleus to the prefrontal cortex.[61] Stimulants like methylphenidate and amphetamine are effective in treating ADHD because they increase neurotransmitter activity in these systems.[26][61][62] Approximately 80% of those who use these stimulants see improvements in ADHD symptoms.[63] Children with ADHD who use stimulant medications generally have better relationships with peers and family members, perform better in school, are less distractible and impulsive, and have longer attention spans.[64][65] The Cochrane reviews[note 7] on the treatment of ADHD in children, adolescents, and adults with pharmaceutical amphetamines stated that short-term studies have demonstrated that these drugs decrease the severity of symptoms, but they have higher discontinuation rates than non-stimulant medications due to their adverse side effects.[67][68] However, a 2025 meta-analytic systematic review of 113 randomized controlled trials found that stimulant medications were the only intervention with robust short-term efficacy, and were associated with lower all-cause treatment discontinuation rates than non-stimulant medications (e.g., atomoxetine).[note 8][69] A Cochrane review on the treatment of ADHD in children with tic disorders such as Tourette syndrome indicated that stimulants in general do not make tics worse, but high doses of dextroamphetamine could exacerbate tics in some individuals.[70]
Binge eating disorder
Binge eating disorder (BED) is characterized by recurrent and persistent episodes of compulsive binge eating.[71] These episodes are often accompanied by marked distress and a feeling of loss of control over eating.[71] The pathophysiology of BED is not fully understood, but it is believed to involve dysfunctional dopaminergic reward circuitry along the cortico-striatal-thalamic-cortical loop.[72][73] As of July 2024, lisdexamfetamine is the only USFDA– and TGA-approved pharmacotherapy for BED.[36][74] Evidence suggests that lisdexamfetamine’s treatment efficacy in BED is underpinned at least in part by a psychopathological overlap between BED and ADHD, with the latter conceptualized as a cognitive control disorder that also benefits from treatment with lisdexamfetamine.[72][73]
Lisdexamfetamine’s therapeutic effects for BED primarily involve direct action in the central nervous system after conversion to its pharmacologically active metabolite, dextroamphetamine.[74] Centrally, dextroamphetamine increases neurotransmitter activity of dopamine and norepinephrine in prefrontal cortical regions that regulate cognitive control of behavior.[72][74] Similar to its therapeutic effect in ADHD, dextroamphetamine enhances cognitive control and may reduce impulsivity in patients with BED by enhancing the cognitive processes responsible for overriding prepotent feeding responses that precede binge eating episodes.[72][76][77] Dextroamphetamine is also a full agonist of trace amine-associated receptor 1 (TAAR1), a G-protein coupled receptor that regulates monoaminergic systems in the brain;[78][79] Activation of TAAR1 may restore impaired dopaminergic signaling in the prefrontal cortex and thereby correct deficits in inhibitory control associated with binge eating behaviors.[79] Beyond central nervous system mechanisms, peripheral actions of dextroamphetamine may also contribute to its treatment efficacy in BED. Through noradrenergic signaling pathways, dextroamphetamine triggers lipolysis in adipose fat cells, thereby prompting the release of triglycerides into blood plasma to be utilized as a fuel substrate.[73][80] Moreover, dextroamphetamine induces synthesis of the cocaine- and amphetamine-regulated transcript (CART), a peptide neurotransmitter that regulates food intake.[81] Within the hypothalamus, CART interacts with leptin signaling pathways to promote appetite suppression.[81] Dextroamphetamine also activates TAAR1 in peripheral organs along the gastrointestinal tract that are involved in the regulation of food intake and body weight.[79][75] Together, these actions confer an anorexigenic effect that promotes satiety in response to feeding and may decrease binge eating as a secondary effect.[77][75] While lisdexamfetamine’s anorexigenic effects contribute to its efficacy in BED, evidence indicates that the enhancement of cognitive control is necessary and sufficient for addressing the disorder’s underlying psychopathology.[72][82] This view is supported by the failure of anti-obesity medications and other appetite suppressants to significantly reduce BED symptom severity, despite their capacity to induce weight loss.[82]
Medical reviews of randomized controlled trials have demonstrated that lisdexamfetamine, at doses between 50–70 mg, is safe and effective for the treatment of moderate-to-severe BED in adults.[sources 5] These reviews suggest that lisdexamfetamine is persistently effective at treating BED and is associated with significant reductions in the number of binge eating days and binge eating episodes per week.[sources 5] Furthermore, a meta-analytic systematic review highlighted an open-label, 12-month extension safety and tolerability study that reported lisdexamfetamine remained effective at reducing the number of binge eating days for the duration of the study.[77] In addition, both a review and a meta-analytic systematic review found lisdexamfetamine to be superior to placebo in several secondary outcome measures, including persistent binge eating cessation, reduction of obsessive-compulsive related binge eating symptoms, reduction of body-weight, and reduction of triglycerides.[73][77] Lisdexamfetamine, like all pharmaceutical amphetamines, has direct appetite suppressant effects that may be therapeutically useful in both BED and its comorbidities.[36][77] Based on reviews of neuroimaging studies involving BED-diagnosed participants, therapeutic neuroplasticity in dopaminergic and noradrenergic pathways from long-term use of lisdexamfetamine may be implicated in lasting improvements in the regulation of eating behaviors that are observed.[36][74][77]
Narcolepsy
Narcolepsy is a chronic sleep-wake disorder that is associated with excessive daytime sleepiness, cataplexy, and sleep paralysis.[84] Patients with narcolepsy are diagnosed as either type 1 or type 2, with only the former presenting cataplexy symptoms.[85] Type 1 narcolepsy results from the loss of approximately 70,000 orexin-releasing neurons in the lateral hypothalamus, leading to significantly reduced cerebrospinal orexin levels;[16][86] this reduction is a diagnostic biomarker for type 1 narcolepsy.[85] Lateral hypothalamic orexin neurons innervate every component of the ascending reticular activating system (ARAS), which includes noradrenergic, dopaminergic, histaminergic, and serotonergic nuclei that promote wakefulness.[86][87]
Amphetamine’s therapeutic mode of action in narcolepsy primarily involves increasing monoamine neurotransmitter activity in the ARAS.[16][88][89] This includes noradrenergic neurons in the locus coeruleus, dopaminergic neurons in the ventral tegmental area, histaminergic neurons in the tuberomammillary nucleus, and serotonergic neurons in the dorsal raphe nucleus.[87][89] Dextroamphetamine, the more dopaminergic enantiomer of amphetamine, is particularly effective at promoting wakefulness because dopamine release has the greatest influence on cortical activation and cognitive arousal, relative to other monoamines.[16][90] In contrast, levoamphetamine may have a greater effect on cataplexy, a symptom more sensitive to the effects of norepinephrine and serotonin.[16] Noradrenergic and serotonergic nuclei in the ARAS are involved in the regulation of the REM sleep cycle and function as “REM-off” cells, with amphetamine’s effect on norepinephrine and serotonin contributing to the suppression of REM sleep and a possible reduction of cataplexy at high doses.[16][85][87]
The American Academy of Sleep Medicine (AASM) 2021 clinical practice guideline conditionally recommends dextroamphetamine for the treatment of both type 1 and type 2 narcolepsy.[91] Treatment with pharmaceutical amphetamines is generally less preferred relative to other stimulants (e.g., modafinil) and is considered a third-line treatment option.[47][92][93] Medical reviews indicate that amphetamine is safe and effective for the treatment of narcolepsy.[16][47][91] Amphetamine appears to be most effective at improving symptoms associated with hypersomnolence, with three reviews finding clinically significant reductions in daytime sleepiness in patients with narcolepsy.[16][47][91] Additionally, these reviews suggest that amphetamine may dose-dependently improve cataplexy symptoms.[16][47][91] However, the quality of evidence for these findings is low and is consequently reflected in the AASM’s conditional recommendation for dextroamphetamine as a treatment option for narcolepsy.[91]
Enhancing performance
Cognitive performance
In 2015, a systematic review and a meta-analysis of high quality clinical trials found that, when used at low (therapeutic) doses, amphetamine produces modest yet unambiguous improvements in cognition, including working memory, long-term episodic memory, inhibitory control, and some aspects of attention, in normal healthy adults;[94][95] these cognition-enhancing effects of amphetamine are known to be partially mediated through the indirect activation of both dopamine D1 receptor and α2-adrenergic receptor in the prefrontal cortex.[26][94] A systematic review from 2014 found that low doses of amphetamine also improve memory consolidation, in turn leading to improved recall of information.[96] Therapeutic doses of amphetamine also enhance cortical network efficiency, an effect which mediates improvements in working memory in all individuals.[26][97] Amphetamine and other ADHD stimulants also improve task saliency (motivation to perform a task) and increase arousal (wakefulness), in turn promoting goal-directed behavior.[26][98][99] Stimulants such as amphetamine can improve performance on difficult and boring tasks and are used by some students as a study and test-taking aid.[26][99][100] Based upon studies of self-reported illicit stimulant use, 5–35% of college students use diverted ADHD stimulants, which are primarily used for enhancement of academic performance rather than as recreational drugs.[101][102][103] However, high amphetamine doses that are above the therapeutic range can interfere with working memory and other aspects of cognitive control.[26][99]
Physical performance
Amphetamine is used by some athletes for its psychological and athletic performance-enhancing effects, such as increased endurance and alertness;[27][40] however, non-medical amphetamine use is prohibited at sporting events that are regulated by collegiate, national, and international anti-doping agencies.[104][105] In healthy people at oral therapeutic doses, amphetamine has been shown to increase muscle strength, acceleration, athletic performance in anaerobic conditions, and endurance (i.e., it delays the onset of fatigue), while improving reaction time.[27][106][107] Amphetamine improves endurance and reaction time primarily through reuptake inhibition and release of dopamine in the central nervous system.[106][107][108] Amphetamine and other dopaminergic drugs also increase power output at fixed levels of perceived exertion by overriding a “safety switch”, allowing the core temperature limit to increase in order to access a reserve capacity that is normally off-limits.[107][109][110] At therapeutic doses, the adverse effects of amphetamine do not impede athletic performance;[27][106] however, at much higher doses, amphetamine can induce effects that severely impair performance, such as rapid muscle breakdown and elevated body temperature.[28][106]
Recreational
Amphetamine, specifically the more dopaminergic dextrorotatory enantiomer (dextroamphetamine), is also used recreationally as a euphoriant and aphrodisiac, and like other amphetamines; is used as a club drug for its energetic and euphoric high. Dextroamphetamine (d-amphetamine) is considered to have a high potential for misuse in a recreational manner since individuals typically report feeling euphoric, more alert, and more energetic after taking the drug.[111][112][113] A notable part of the 1960s mod subculture in the UK was recreational amphetamine use, which was used to fuel all-night dances at clubs like Manchester’s Twisted Wheel. Newspaper reports described dancers emerging from clubs at 5 a.m. with dilated pupils.[114] Mods used the drug for stimulation and alertness, which they viewed as different from the intoxication caused by alcohol and other drugs.[114] Dr. Andrew Wilson argues that for a significant minority, “amphetamines symbolised the smart, on-the-ball, cool image” and that they sought “stimulation not intoxication […] greater awareness, not escape” and “confidence and articulacy” rather than the “drunken rowdiness of previous generations.”[114] Dextroamphetamine’s dopaminergic (rewarding) properties affect the mesocorticolimbic circuit; a group of neural structures responsible for incentive salience (i.e., “wanting”; desire or craving for a reward and motivation), positive reinforcement and positively-valenced emotions, particularly ones involving pleasure.[115] Large recreational doses of dextroamphetamine may produce symptoms of dextroamphetamine overdose.[113] Recreational users sometimes open dexedrine capsules and crush the contents in order to insufflate (snort) it or subsequently dissolve it in water and inject it.[113] Immediate-release formulations have higher potential for abuse via insufflation (snorting) or intravenous injection due to a more favorable pharmacokinetic profile and easy crushability (especially tablets).[116][117] Injection into the bloodstream can be dangerous because insoluble fillers within the tablets can block small blood vessels.[113] Chronic overuse of dextroamphetamine can lead to severe drug dependence, resulting in withdrawal symptoms when drug use stops.[113]
Contraindications
See also: Amphetamine § Drug interactions
According to the International Programme on Chemical Safety (IPCS) and the U.S. Food and Drug Administration (FDA),[note 9] amphetamine is contraindicated in people with a history of drug abuse,[note 10] cardiovascular disease, severe agitation, or severe anxiety.[35][28][119] It is also contraindicated in individuals with advanced arteriosclerosis (hardening of the arteries), glaucoma (increased eye pressure), hyperthyroidism (excessive production of thyroid hormone), or moderate to severe hypertension.[35][28][119] These agencies indicate that people who have experienced allergic reactions to other stimulants or who are taking monoamine oxidase inhibitors (MAOIs) should not take amphetamine,[35][28][119] although safe concurrent use of amphetamine and monoamine oxidase inhibitors has been documented.[120][121] These agencies also state that anyone with anorexia nervosa, bipolar disorder, depression, hypertension, liver or kidney problems, mania, psychosis, Raynaud’s phenomenon, seizures, thyroid problems, tics, or Tourette syndrome should monitor their symptoms while taking amphetamine.[28][119] Evidence from human studies indicates that therapeutic amphetamine use does not cause developmental abnormalities in the fetus or newborns (i.e., it is not a human teratogen), but amphetamine abuse does pose risks to the fetus.[119] Amphetamine has also been shown to pass into breast milk, so the IPCS and the FDA advise mothers to avoid breastfeeding when using it.[28][119] Due to the potential for reversible growth impairments,[note 11] the FDA advises monitoring the height and weight of children and adolescents prescribed an amphetamine pharmaceutical.[28]
Adverse effects
The adverse side effects of amphetamine are many and varied, and the amount of amphetamine used is the primary factor in determining the likelihood and severity of adverse effects.[28][40] Amphetamine products such as Adderall, Dexedrine, and their generic equivalents are currently approved by the U.S. FDA for long-term therapeutic use.[37][28] Recreational use of amphetamine generally involves much larger doses, which have a greater risk of serious adverse drug effects than dosages used for therapeutic purposes.[40]
Physical
Cardiovascular side effects can include hypertension or hypotension from a vasovagal response, Raynaud’s phenomenon (reduced blood flow to the hands and feet), and tachycardia (increased heart rate).[28][40][122] Sexual side effects in males may include erectile dysfunction, frequent erections, or prolonged erections.[28] Gastrointestinal side effects may include abdominal pain, constipation, diarrhea, and nausea.[1][28][123] Other potential physical side effects include appetite loss, blurred vision, dry mouth, excessive grinding of the teeth, nosebleed, profuse sweating, rhinitis medicamentosa (drug-induced nasal congestion), reduced seizure threshold, tics (a type of movement disorder), and weight loss.[sources 6] Dangerous physical side effects are rare at typical pharmaceutical doses.[40]
Amphetamine stimulates the medullary respiratory centers, producing faster and deeper breaths.[40] In a normal person at therapeutic doses, this effect is usually not noticeable, but when respiration is already compromised, it may be evident.[40] Amphetamine also induces contraction in the urinary bladder sphincter, the muscle which controls urination, which can result in difficulty urinating.[40] This effect can be useful in treating bed wetting and loss of bladder control.[40] The effects of amphetamine on the gastrointestinal tract are unpredictable.[40] If intestinal activity is high, amphetamine may reduce gastrointestinal motility (the rate at which content moves through the digestive system);[40] however, amphetamine may increase motility when the smooth muscle of the tract is relaxed.[40] Amphetamine also has a slight analgesic effect and can enhance the pain relieving effects of opioids.[1][40]
FDA-commissioned studies from 2011 indicate that in children, young adults, and adults there is no association between serious adverse cardiovascular events (sudden death, heart attack, and stroke) and the medical use of amphetamine or other ADHD stimulants.[sources 7] These findings were subsequently corroborated by a 2022 meta-analysis that sampled nearly four million participants, which found no association between therapeutic use of amphetamine and the development of cardiovascular disease in any age group.[129] However, amphetamine pharmaceuticals are contraindicated in individuals with preexisting cardiovascular disease.[sources 8]
Psychological
At normal therapeutic doses, the most common psychological side effects of amphetamine include increased alertness, apprehension, concentration, initiative, self-confidence and sociability, mood swings (elated mood followed by mildly depressed mood), insomnia or wakefulness, and decreased sense of fatigue.[28][40] Less common side effects include anxiety, change in libido, grandiosity, irritability, repetitive or obsessive behaviors, and restlessness;[sources 9] these effects depend on the user’s personality and current mental state.[40] Amphetamine psychosis (e.g., delusions and paranoia) can occur in heavy users.[28][41][42] Although very rare, this psychosis can also occur at therapeutic doses during long-term therapy.[28][42][43] According to the FDA, “there is no systematic evidence” that stimulants produce aggressive behavior or hostility.[28]
Amphetamine has also been shown to produce a conditioned place preference in humans taking therapeutic doses,[67][131] meaning that individuals acquire a preference for spending time in places where they have previously used amphetamine.[131][132]
What is the drug amphetamine used for?
Amphetamine is a medication used in the management and treatment of ADHD and narcolepsy. It is classified as a central nervous system stimulant. This activity reviews the indications, action, and contraindications for amphetamine as an agent in treating ADHD and narcolepsy.
Is amphetamine a white powder?
About amphetamine
A synthetic substance. Normally seen as a white powder, it acts as a stimulant of the central nervous system (CNS). It is believed that amphetamine was first manufactured in the 1880s by the German chemist Leuckart, although evidence for this is lacking.
Which products contain amphetamine?
What are the brand names of amphetamines?
- Amphetamine: Adzenys®, Evekeo®
- Amphetamine combinations: Adderall®, Dyanavel®, Mydayis®
- Benzphetamine: Didrex®
- Dextroamphetamine: Dexedrine®, Dextrostat®, Procentra®, Xelstrym®, Zenzedi®
- Lisdexamfetamine: Vyvanse®
- Methamphetamine: Desoxyn®
- Phentermine: Adipex®, Lomaira®
Does amphetamine make you sleepy?
Adderall is an amphetamine, which generally makes people energetic. However, it has a calming effect for people with ADHD. This calming effect can make some people sleepy. In clinical trials, fatigue affected approximately 2 to 4 percent of people who took Adderall.
Does amphetamine give energy?
Amphetamines increase energy and produce a sense of pleasure and peace. The drug can fight fatigue and allow people to work around the clock. It induces exhilarating feelings of power, strength, energy, self-assertion, focus, and enhanced motivation.
