Adderall is a combination medication containing four salts of amphetamine. Adderall is used in the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It is also used as an athletic performance enhancer and cognitive enhancer, and recreationally as an aphrodisiac and euphoriant. It is a central nervous system (CNS) stimulant of the phenethylamine class. By salt content, the active ingredients are 25% levoamphetamine salts (the levorotatory or ‘left-handed’ enantiomer) and 75% dextroamphetamine salts (the dextrorotatory or ‘right-handed’ enantiomer).
Adderall is generally well-tolerated and effective in treating the symptoms of ADHD and narcolepsy. At therapeutic doses, Adderall causes emotional and cognitive effects such as euphoria, change in desire for sex, increased wakefulness, and improved cognitive control. At these doses, it induces physical effects such as faster reaction time, fatigue resistance, and increased muscle strength. In contrast, much larger doses of Adderall can impair cognitive control, cause rapid muscle breakdown, or induce a psychosis (e.g., delusions and paranoia). The side effects of Adderall vary widely among individuals but most commonly include insomnia, dry mouth, and loss of appetite. The risk of developing an addiction is insignificant when Adderall is used as prescribed at fairly low daily doses, such as those used for treating ADHD; however, the routine use of Adderall in larger daily doses poses a significant risk of addiction due to the pronounced reinforcing effects that are present at high doses. Recreational doses of amphetamine are generally much larger than prescribed therapeutic doses and carry a far greater risk of serious adverse effects.
The two amphetamine enantiomers that compose Adderall (i.e., levoamphetamine and dextroamphetamine) alleviate the symptoms of ADHD and narcolepsy by increasing the activity of the neurotransmitters norepinephrine and dopamine in the brain, which results in part from their interactions with human trace amine-associated receptor 1 (hTAAR1) and vesicular monoamine transporter 2 (VMAT2) in neurons. Dextroamphetamine is a more potent CNS stimulant than levoamphetamine, but levoamphetamine has slightly stronger cardiovascular and peripheral effects and a longer elimination half-life (i.e., it remains in the body longer) than dextroamphetamine. The levoamphetamine component of Adderall has been reported to improve the treatment response in some individuals relative to dextroamphetamine alone. Adderall’s active ingredient, amphetamine, shares many chemical and pharmacological properties with the human trace amines, particularly phenethylamine and N-methylphenethylamine, the latter of which is a positional isomer of amphetamine. In 2017, Adderall was the 27th most prescribed medication in the United States, with more than 24 million prescriptions.