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Draft entry. Written from the cited papers but not yet reviewed by a person. Check the references before relying on any claim.

Adderall

also Mixed amphetamine salts · Mixed amphetamine salts extended release · Adderall XR · MAS · MAS XR

Adderall contains mixed amphetamine salts, with approximately a 3:1 dextro- to levo-amphetamine ratio. Immediate-release tablets and Adderall XR deliver the same mixture at different rates. [1][2] Controlled trials support ADHD symptom reduction; this is treatment evidence, not proof of general cognitive enhancement. [3]

An established stimulant treatment for ADHD; release formulation matters, and higher doses do not reliably mean greater benefit.

No PubChem structure on file.
Established6 papers · 1999–2026 · 5 journals · 4 in humans
  • meta-analysis
  • RCT
  • trial
  • observational
  • preclinical / case
  • review / patent / other
  • retracted
1999 · RCT · A comparison of ritalin and adderall: efficacy and time-course in children with attention-deficit/hyperactivity disorder.2005 · clinical trial · Single- and multiple-dose pharmacokinetics of an oral mixed amphetamine salts extended-release formulation in adults.2006 · RCT · Mixed amphetamine salts extended-release in the treatment of adult ADHD: a randomized, controlled trial.2013 · review · Amphetamine, past and present--a pharmacological and clinical perspective.2018 · meta-analysis · Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis.2026 · other · ADDERALL XR (mixed salts of a single-entity amphetamine product) extended-release capsules, for oral use, CII Initial U.S. Approval: 2001
in its favour
  • + Strong ADHD symptom-control evidence
  • + Immediate- and extended-release formulations
watch for
  • Appetite loss, insomnia and cardiovascular effects
  • Misuse and addiction potential

Overview

Adderall and Adderall XR contain the same mixed amphetamine salts. Their immediate- versus extended-release delivery affects the time course rather than creating a different active drug. [1]

In a 255-adult trial, XR improved ADHD scores versus placebo at all three tested doses. Overall endpoint scores were similar across 20, 40 and 60 mg/day; a suggested advantage of 60 mg in more severe cases came from a post-hoc subgroup analysis. [4]

A small crossover study in 25 children found that immediate-release Adderall and Ritalin both improved behavior and academic productivity. Adderall lasted longer at the tested doses, but the authors noted that those doses were functionally more potent, so the comparison does not establish universal superiority. Nearly one-quarter were judged to gain little incremental benefit from medication on top of intensive behavioral treatment. [5]

Mechanism

Amphetamine is a substrate for monoamine transporters. It enters nerve terminals, changes vesicular storage and drives reverse transport of dopamine and noradrenaline into the synapse. This differs from methylphenidate’s main action as a reuptake blocker. The dextro and levo isomers differ in potency and time course. [1]

Direct targetswhat the molecule itself binds or acts on
  • Dopamine and noradrenaline transporters (DAT/NET)modulates
    Amphetamine acts as a transporter substrate and promotes monoamine release through reverse transport. [1]
    strong
  • Vesicular monoamine transporter 2 (VMAT2)modulates
    Alters intracellular monoamine storage, contributing to release. [1]
    strong

Formulation

how the form changes blood levels

The mixture is commonly described as approximately 3:1 dextro- to levo-amphetamine; the current label gives a 3.1:1 base-equivalent ratio. Adderall XR combines immediate- and delayed-release beads. These are not Vyvanse’s chemically linked prodrug system, and the products’ labeled milligrams do not represent equal amounts of active amphetamine. [1][2]

Dosing

as studied or commonly reported; not a recommendation

Doses below are what studies used or, where marked, what is commonly reported. None is a recommendation.

Oral

  • 7.5 or 12.5 mg per dose (immediate release)
    25 children with ADHD in a behavioral summer-treatment program; comparison with Ritalin and placebo
    twice daily, at 7:45 am and 12:15 pm · 24 randomized treatment days within a 6-week crossover
    human study[5]
  • 20, 40 or 60 mg/day (XR, dose-escalation groups)
    255 adults with combined-type ADHD; randomized placebo-controlled trial
    once daily · 4 weeks
    human study[4]
Form
Mixture of four amphetamine salts; no single PubChem formula or molecular weight represents the whole product. XR uses immediate- and delayed-release beads. [2]
Timing and food
XR is administered on awakening; a high-fat meal delays its concentration peak without reducing overall absorption. [2]
Time to effect
The adult XR trial found improvement during the first treatment week and at assessments 4 and 12 hours after dosing. [4]
Notes
The 40 and 60 mg/day arms describe research doses, not a recommendation. The US XR label recommends 20 mg/day in adults and states that its adult trial did not provide adequate evidence of additional benefit above 20 mg/day. [2]

Pharmacokinetics

what the body does with it
Half-lifeIn adults, approximately 10 hours for dextroamphetamine and 13 hours for levoamphetamine. [2]
Time to peakThe label gives about 3 hours for immediate release and about 7 hours for XR; food and study conditions matter. A published adult MAS XR PK study reported peaks around 4–5 hours. [2][6]
MetabolismSeveral oxidative pathways contribute; CYP2D6 participates in formation of 4-hydroxyamphetamine. [2]
ExcretionRenal elimination depends strongly on urine pH: acidic urine increases clearance, while alkaline urine reduces it. [2]

Safety

risks and cautions, not medical advice

Common problems include appetite loss, insomnia and increased pulse or blood pressure. The US label carries a boxed warning for abuse, misuse and addiction. Serious cardiac disease, new psychotic or manic symptoms, circulation problems in fingers or toes, and reduced growth in children require clinical attention. Blood pressure, pulse, weight and pediatric growth are monitored during treatment. [2]

Adverse effects
reported, not universal
  • Appetite loss, insomnia, dry mouth, anxiety and increased pulse or blood pressure. [2]
Cautions
who should think twice
  • Prescription stimulant with abuse, misuse and addiction potential. [2]
  • Avoid use in serious cardiac disease; screen for manic or psychotic vulnerability. [2]
Limits of the evidence
what has not been shown
  • The comparative evidence is strongest for short-term ADHD symptom control. The 2018 network meta-analysis had insufficient data at 26 and 52 weeks, and most indirect comparisons had low or very low certainty. It does not establish cognitive enhancement in healthy people. [3]
  • The short adult XR trial does not show that everyone benefits more at 40 or 60 mg/day than at 20 mg/day. [4]

Interactions

documented pairs only, not exhaustive

MAO inhibitors are contraindicated during treatment and for 14 days after stopping the MAO inhibitor because of hypertensive crisis risk. Serotonergic drugs and CYP2D6 inhibitors can increase serotonin-syndrome risk. Urinary alkalinizing agents increase amphetamine exposure; acidifying agents can lower it. These are interactions to review with the prescriber, not ways to adjust a dose independently. [2]

  • Contraindicated during MAOI treatment and for 14 days afterward because of hypertensive crisis risk. [2]
  • Vyvanse
    caution
    Both provide amphetamine. Combined exposure is therapeutic duplication and can intensify stimulant adverse effects; this is a pharmacologic caution, not a studied cognitive stack. [1][2]
  • Additional stimulation may compound insomnia and cardiovascular effects; no general combination benefit is established by the cited monotherapy trials. [2][3]

FAQ

Is Adderall the same as Vyvanse?
No. Adderall supplies mixed dextro- and levo-amphetamine salts; Vyvanse is lisdexamfetamine, which must be converted to dextroamphetamine. [1]

References

entry last reviewed 2026-09-21
  1. [1]
    Amphetamine, past and present--a pharmacological and clinical perspective.
    Heal DJ, Smith SL, Gosden J et al.J Psychopharmacol 2013reviewPMID 23539642◌ unreviewed
  2. [2]
  3. [3]
  4. [4]
    Mixed amphetamine salts extended-release in the treatment of adult ADHD: a randomized, controlled trial.
    Weisler RH, Biederman J, Spencer TJ et al.CNS Spectr 2006RCT · humanPMID 16871129◌ unreviewed
  5. [5]
    A comparison of ritalin and adderall: efficacy and time-course in children with attention-deficit/hyperactivity disorder.
    Pelham WE, Aronoff HR, Midlam JK et al.Pediatrics 1999RCT · humanPMID 10103335◌ unreviewed
  6. [6]
    Single- and multiple-dose pharmacokinetics of an oral mixed amphetamine salts extended-release formulation in adults.
    Clausen SB, Read SC, Tulloch SJCNS Spectr 2005clinical trial · humanPMID 16344836◌ unreviewed