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Dextroamphetamine

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Dextroamphetamine

Dextroamphetamine is a central nervous system (CNS) stimulant and enantiomer of amphetamine that is used in the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It is also used illicitly to enhance cognitive and athletic performance, and recreationally as an aphrodisiac and euphoriant. Dextroamphetamine is generally regarded as the prototypical stimulant.

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

Side effects of dextroamphetamine at therapeutic doses include elevated mood, decreased appetite, dry mouth, excessive grinding of the teeth, headache, increased heart rate, increased wakefulness or insomnia, anxiety, and irritability, among others. At excessive doses, psychosis (i.e., hallucinations, delusions), addiction, and rapid muscle breakdown may occur. However, for individuals with pre-existing psychotic disorders, there may be a risk of psychosis even at therapeutic doses.

Dextroamphetamine, like other amphetamines, elicits its stimulating effects via several distinct actions: it inhibits or reverses the transporter proteins for the monoamine neurotransmitters (namely the serotonin, norepinephrine and dopamine transporters) either via trace amine-associated receptor 1 (TAAR1) or in a TAAR1 independent fashion when there are high cytosolic concentrations of the monoamine neurotransmitters and it releases these neurotransmitters from synaptic vesicles via vesicular monoamine transporter 2 (VMAT2). It also shares many chemical and pharmacological properties with human trace amines, particularly phenethylamine and N-methylphenethylamine, the latter being an isomer of amphetamine produced within the human body. It is available as a generic medication. In 2022, mixed amphetamine salts (Adderall) was the 14th most commonly prescribed medication in the United States, with more than 34 million prescriptions.

Dextroamphetamine is used to treat attention deficit hyperactivity disorder (ADHD) and narcolepsy, and is sometimes prescribed off-label for depression and obesity.

Long-term amphetamine exposure at sufficiently high doses in some animal species is known to produce abnormal dopamine system development or nerve damage, but, in humans with ADHD, long-term use of pharmaceutical amphetamines at therapeutic doses appears to improve brain development and nerve growth. Reviews of magnetic resonance imaging (MRI) studies suggest that long-term treatment with amphetamine decreases abnormalities in brain structure and function found in subjects with ADHD, and improves function in several parts of the brain, such as the right caudate nucleus of the basal ganglia.

Reviews of clinical stimulant research have established the safety and effectiveness of long-term continuous amphetamine use for the treatment of ADHD. Randomized controlled trials of continuous stimulant therapy for the treatment of ADHD spanning 2 years have demonstrated treatment effectiveness and safety. Two reviews have indicated that long-term continuous stimulant therapy for ADHD is effective for reducing the core symptoms of ADHD (i.e., hyperactivity, inattention, and impulsivity), enhancing quality of life and academic achievement, and producing improvements in a large number of functional outcomes across 9 categories of outcomes related to academics, antisocial behavior, driving, non-medicinal drug use, obesity, occupation, self-esteem, service use (i.e., academic, occupational, health, financial, and legal services), and social function. Additionally, a 2024 meta-analytic systematic review reported moderate improvements in quality of life when amphetamine treatment is used for ADHD. One review highlighted a nine-month randomized controlled trial of amphetamine treatment for ADHD in children that found an average increase of 4.5 IQ points, continued increases in attention, and continued decreases in disruptive behaviors and hyperactivity. Another review indicated that, based upon the longest follow-up studies conducted to date, lifetime stimulant therapy that begins during childhood is continuously effective for controlling ADHD symptoms and reduces the risk of developing a substance use disorder as an adult.

Models of ADHD suggest that it is associated with functional impairments in some of the brain's neurotransmitter systems; these functional impairments involve impaired dopamine neurotransmission in the mesocorticolimbic projection and norepinephrine neurotransmission in the noradrenergic projections from the locus coeruleus to the prefrontal cortex. Stimulants like methylphenidate and amphetamine are effective in treating ADHD because they increase neurotransmitter activity in these systems. Approximately 80% of those who use these stimulants see improvements in ADHD symptoms. Children with ADHD who use stimulant medications generally have better relationships with peers and family members, perform better in school, are less distractible and impulsive, and have longer attention spans. The Cochrane reviews on the treatment of ADHD in children, adolescents, and adults with pharmaceutical amphetamines stated that short-term studies have demonstrated that these drugs decrease the severity of symptoms, but they have higher discontinuation rates than non-stimulant medications due to their adverse side effects. 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). 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.

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