Adderall

Adderall is the brand name of a fixed-dose combination medication used for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It is also used as an athletic performance enhancer, cognitive enhancer, appetite suppressant, and recreationally as a euphoriant. Such uses are illegal in many countries. It is a central nervous system (CNS) stimulant of the phenethylamine class. It contains the amphetamines dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate, and amphetamine sulfate. It is taken by mouth. At therapeutic doses, Adderall causes emotional and cognitive effects such as euphoria, change in sex drive, increased wakefulness, and improved cognitive control. At these doses, it induces physical effects such as a faster reaction time, fatigue resistance, and increased muscle strength. In contrast, much larger doses of Adderall can impair cognitive control, cause rapid muscle breakdown, provoke panic attacks, or induce psychosis (e.g., paranoia, delusions, hallucinations). The side effects vary widely among individuals but most commonly include insomnia, dry mouth, loss of appetite and weight loss. The routine use of Adderall at higher-than-prescribed doses poses a significant risk of addiction or dependence due to the pronounced reinforcing effects that are present at high doses.…

Adderall is the brand name of a fixed-dose combination medication used for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It is also used as an athletic performance enhancer, cognitive enhancer, appetite suppressant, and recreationally as a euphoriant. Such uses are illegal in many countries. It is a central nervous system (CNS) stimulant of the phenethylamine class. It contains the amphetamines dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate, and amphetamine sulfate. It is taken by mouth. At therapeutic doses, Adderall causes emotional and cognitive effects such as euphoria, change in sex drive, increased wakefulness, and improved cognitive control. At these doses, it induces physical effects such as a faster reaction time, fatigue resistance, and increased muscle strength. In contrast, much larger doses of Adderall can impair cognitive control, cause rapid muscle breakdown, provoke panic attacks, or induce psychosis (e.g., paranoia, delusions, hallucinations). The side effects vary widely among individuals but most commonly include insomnia, dry mouth, loss of appetite and weight loss. The routine use of Adderall at higher-than-prescribed doses poses a significant risk of addiction or dependence due to the pronounced reinforcing effects that are present at high doses. Recreational doses of Adderall are generally much larger than prescribed therapeutic doses and also carry a far greater risk of serious adverse effects. The two amphetamine enantiomers that compose Adderall, such as Adderall tablets/capsules (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 than dextroamphetamine. The active ingredient in Adderall, amphetamine, shares many chemical and pharmacological properties with the human trace amines, particularly phenethylamine and , the latter of which is a positional isomer of amphetamine. In 2023, Adderall was the fifteenth most commonly prescribed medication in the United States, with more than 32 million prescriptions. ==Uses== ===Medical=== Adderall is indicated for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. ====ADHD==== ====Narcolepsy==== ====Available forms==== Adderall is available as immediate-release (IR) tablets and extended-release (XR) capsules. Mydayis is available as an extended-release formulation. Adderall XR is approved to treat attention deficit hyperactivity disorder for up to 12 hours in individuals 6 years and older and uses a double-bead formulation. The capsule can be swallowed like a tablet, or it can be opened and the beads sprinkled over applesauce for comparable absorption. Upon ingestion, half of the beads provide immediate administration of medication, while the other half are enveloped in a coating that must dissolve, delaying absorption of its contents. It is designed to provide a therapeutic effect and plasma concentrations identical to taking two doses of Adderall IR four hours apart. Mydayis uses a longer-lasting triple-bead formulation and is approved to treat attention deficit hyperactivity disorder for up to 16 hours in individuals aged 13 years of age and older. In the United States, the immediate and extended-release formulations of Adderall are available as generic medications. Generic formulations of Mydayis became available in the US in October 2023. ===Enhancing performance=== Adderall is banned by the National Football League (NFL), Major League Baseball (MLB), the National Basketball Association (NBA), the National Collegiate Athletic Association (NCAA), and the National Hockey League (NHL). In leagues such as the National Football League, there is a very rigorous process required to obtain an exemption to this rule even when the athlete has been medically prescribed the drug by their physician. ===Recreational=== Adderall has a high potential for misuse as a recreational drug. Adderall tablets can either be swallowed, crushed and snorted, or dissolved in water and injected. Injection into the bloodstream can be dangerous because insoluble fillers within the tablets can block small blood vessels. Many postsecondary students have reported using Adderall for study purposes in different parts of the developed world. Among these students, some of the risk factors for misusing ADHD stimulants recreationally include: Inadequate accommodation of disability, basing one's self-worth on external validation, low self-efficacy, earning poor grades, and having an untreated mental health disorder. ==Contraindications== ==Adverse effects== The adverse side effects of Adderall are many and varied, but the amount of substance consumed is the primary factor in determining the likelihood and severity of side effects. Adderall is currently approved for long-term therapeutic use by the USFDA. Recreational use of Adderall generally involves far larger doses and is therefore significantly more dangerous, involving a much greater risk of serious adverse drug effects than dosages used for therapeutic purposes. ==Overdose== ==Interactions== Monoamine oxidase inhibitors (MAOIs) taken with amphetamine may result in a hypertensive crisis if taken within two weeks after last use of an MAOI type drug. Inhibitors of enzymes that directly metabolize amphetamine (particularly CYP2D6 and FMO3) will prolong the elimination of amphetamine and increase drug effects. Serotonergic drugs (such as most antidepressants) co-administered with amphetamine increases the risk of serotonin syndrome. Stimulants and antidepressants (sedatives and depressants) may increase (decrease) the drug effects of amphetamine, and vice versa. Gastrointestinal and urinary pH affect the absorption and elimination of amphetamine, respectively. Gastrointestinal alkalinizing agents increase the absorption of amphetamine. Urinary alkalinizing agents increase the concentration of non-ionized species, decreasing urinary excretion. Proton-pump inhibitors (PPIs) modify the absorption of Adderall XR and Mydayis. Zinc supplementation may reduce the minimum effective dose of amphetamine when it is used for the treatment of ADHD. Norepinephrine reuptake inhibitors (NRIs) like atomoxetine prevent norepinephrine release induced by amphetamines and have been found to reduce the stimulant, euphoriant, and sympathomimetic effects of dextroamphetamine in humans. ==Pharmacology== ===Mechanism of action=== Amphetamine, the active ingredient of Adderall, works primarily by increasing the activity of the neurotransmitters dopamine and norepinephrine in the brain. It also triggers the release of several other hormones (e.g., epinephrine) and neurotransmitters (e.g., serotonin and histamine) as well as the synthesis of certain neuropeptides (e.g., cocaine and amphetamine regulated transcript (CART) peptides). Both active ingredients of Adderall, dextroamphetamine and levoamphetamine, bind to the same biological targets, but their binding affinities (that is, potency) differ somewhat. Dextroamphetamine and levoamphetamine are both potent full agonists (activating compounds) of trace amine-associated receptor 1 (TAAR1) and interact with vesicular monoamine transporter 2 (VMAT2), with dextroamphetamine being the more potent agonist of TAAR1. Consequently, dextroamphetamine produces more stimulation than levoamphetamine; however, levoamphetamine has slightly greater cardiovascular and peripheral effects. It has been reported that certain children have a better clinical response to levoamphetamine. In the absence of amphetamine, will normally move monoamines (e.g., dopamine, histamine, serotonin, norepinephrine, etc.) from the intracellular fluid of a monoamine neuron into its synaptic vesicles, which store neurotransmitters for later release (via exocytosis) into the synaptic cleft. When amphetamine enters a neuron and interacts with VMAT2, the transporter reverses its direction of transport, thereby releasing stored monoamines inside synaptic vesicles back into the neuron's intracellular fluid. Meanwhile, when amphetamine activates , the receptor causes the neuron's cell membrane-bound monoamine transporters (i.e., the dopamine transporter, norepinephrine transporter, or serotonin transporter) to either stop transporting monoamines altogether (via transporter internalization) or transport monoamines out of the neuron; in other words, the reversed membrane transporter will push dopamine, norepinephrine, and serotonin out of the neuron's intracellular fluid and into the synaptic cleft. In summary, by interacting with both VMAT2 and TAAR1, amphetamine releases neurotransmitters from synaptic vesicles (the effect from VMAT2) into the intracellular fluid where they subsequently exit the neuron through the membrane-bound, reversed monoamine transporters (the effect from TAAR1). ===Pharmacokinetics=== ===Pharmacomicrobiomics=== ===Related endogenous compounds=== ===Commercial formulation=== Chemically, Adderall is a mixture of four amphetamine salts; specifically, it is composed of equal parts (by mass) of amphetamine aspartate monohydrate, amphetamine sulfate, dextroamphetamine sulfate, and dextroamphetamine saccharate. This drug mixture has slightly stronger effects than racemic amphetamine due to the higher proportion of dextroamphetamine. Adderall is produced as both an immediate-release (IR) and extended-release (XR) formulation. , ten different companies produced generic Adderall IR, while Teva Pharmaceutical Industries, Actavis, and Barr Pharmaceuticals manufactured generic Adderall XR. , Shire plc, the company that held the original patent for Adderall and Adderall XR, still manufactured brand name Adderall XR, but not Adderall IR. ===Comparison to other formulations=== Adderall is one of several formulations of pharmaceutical amphetamine, including singular or mixed enantiomers and as an enantiomer prodrug. The table below compares these medications (based on US-approved forms): ==Reference notes== ==References==

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