Mixed amphetamine salts: Difference between revisions
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| structure = Amphetamine-white.svg | | structure = Amphetamine-white.svg | ||
| classes = Psychostimulant, Amphetamine | | classes = Psychostimulant, Amphetamine | ||
| uses = <vote slug="inattention">Inattention</vote>, <vote slug="narcolepsy">Narcolepsy</vote> | |||
| uses = <vote slug=" | | starting_dose = 5 mg XR | ||
| | | preparations = IR tabs 5–30 mg; XR caps 5–30 mg; Mydayis caps 12.5–50 mg | ||
| routes = Oral | | routes = Oral | ||
| onset = IR: 30–60 min; XR: 1–2 h to peak effect | | onset = IR: 30–60 min; XR: 1–2 h to peak effect | ||
| Line 14: | Line 14: | ||
| pregnancy = Category C | | pregnancy = Category C | ||
| legal = Schedule II | | legal = Schedule II | ||
| mechanism = TAAR1 agonism, VMAT2 substrate, DAT/NET reverse transport — net release of dopamine and norepinephrine | |||
| intro = '''Mixed amphetamine salts (MAS)''' — marketed primarily as '''Adderall''' — is a 3:1 mixture of dextroamphetamine and levoamphetamine salts (dextroamphetamine sulfate, amphetamine sulfate, dextroamphetamine saccharate, and amphetamine aspartate). Amphetamine was first synthesized in 1887 by Lazăr Edeleanu, then developed as a medicine in the late 1920s. It has a chiral center and two enantiomers, levoamphetamine and dextroamphetamine; the latter is significantly more centrally psychoactive, while the levo enantiomer contributes more to peripheral noradrenergic effects. MAS is FDA-approved for attention-deficit hyperactivity disorder and narcolepsy. As a Schedule II controlled substance it carries substantial dependence and misuse potential, particularly in academic and occupational settings where it is frequently used off-label as a cognitive enhancer. | | intro = '''Mixed amphetamine salts (MAS)''' — marketed primarily as '''Adderall''' — is a 3:1 mixture of dextroamphetamine and levoamphetamine salts (dextroamphetamine sulfate, amphetamine sulfate, dextroamphetamine saccharate, and amphetamine aspartate). Amphetamine was first synthesized in 1887 by Lazăr Edeleanu, then developed as a medicine in the late 1920s. It has a chiral center and two enantiomers, levoamphetamine and dextroamphetamine; the latter is significantly more centrally psychoactive, while the levo enantiomer contributes more to peripheral noradrenergic effects. MAS is FDA-approved for attention-deficit hyperactivity disorder and narcolepsy. As a Schedule II controlled substance it carries substantial dependence and misuse potential, particularly in academic and occupational settings where it is frequently used off-label as a cognitive enhancer. | ||
| pharmacokinetics = '''Absorption:''' Excellent oral bioavailability — sources report ">75%" to "~90%". Food does not significantly affect total absorption but can delay peak concentration. '''Distribution:''' Volume of distribution ~4 L/kg; plasma protein binding less than 20%. Crosses the blood–brain barrier and placenta. '''Metabolism:''' Amphetamine is oxidized to 4-hydroxyamphetamine, α-hydroxyamphetamine, or norephedrine. Norephedrine and 4-hydroxyamphetamine are active metabolites and are further metabolized to 4-hydroxy-norephedrine. Deamination of α-hydroxyamphetamine yields phenylacetone, which is metabolized to benzoic acid and conjugated to its glucuronide and hippuric acid. '''CYP2D6''' is crucial for amphetamine metabolism; genetic polymorphism causes significant inter-patient variability in clearance. Amphetamine itself inhibits monoamine oxidase (MAO), and both CYP1A2 and CYP3A4 contribute to its metabolism.<ref>https://www.ncbi.nlm.nih.gov/sites/books/NBK507808/</ref> '''Elimination:''' Primarily renal — ~30–40% recovered as unchanged amphetamine, the rest as metabolites. Due to its pK<sub>a</sub> of 9.9, urinary elimination is highly pH-dependent: alkaline urine reduces ionization and decreases renal clearance, while acidic urine and high flow rates accelerate clearance via active tubular secretion. '''Half-life:''' The D-enantiomer has a half-life of 9 hours in children (6–12 y), 11 hours in adolescents (13–17 y), and 10 hours in adults. The L-enantiomer is consistently longer-lived: 11 hours in children, 13–14 hours in adolescents, 13 hours in adults. | | pharmacokinetics = '''Absorption:''' Excellent oral bioavailability — sources report ">75%" to "~90%". Food does not significantly affect total absorption but can delay peak concentration. '''Distribution:''' Volume of distribution ~4 L/kg; plasma protein binding less than 20%. Crosses the blood–brain barrier and placenta. '''Metabolism:''' Amphetamine is oxidized to 4-hydroxyamphetamine, α-hydroxyamphetamine, or norephedrine. Norephedrine and 4-hydroxyamphetamine are active metabolites and are further metabolized to 4-hydroxy-norephedrine. Deamination of α-hydroxyamphetamine yields phenylacetone, which is metabolized to benzoic acid and conjugated to its glucuronide and hippuric acid. '''CYP2D6''' is crucial for amphetamine metabolism; genetic polymorphism causes significant inter-patient variability in clearance. Amphetamine itself inhibits monoamine oxidase (MAO), and both CYP1A2 and CYP3A4 contribute to its metabolism.<ref>https://www.ncbi.nlm.nih.gov/sites/books/NBK507808/</ref> '''Elimination:''' Primarily renal — ~30–40% recovered as unchanged amphetamine, the rest as metabolites. Due to its pK<sub>a</sub> of 9.9, urinary elimination is highly pH-dependent: alkaline urine reduces ionization and decreases renal clearance, while acidic urine and high flow rates accelerate clearance via active tubular secretion. '''Half-life:''' The D-enantiomer has a half-life of 9 hours in children (6–12 y), 11 hours in adolescents (13–17 y), and 10 hours in adults. The L-enantiomer is consistently longer-lived: 11 hours in children, 13–14 hours in adolescents, 13 hours in adults. | ||
| Line 28: | Line 29: | ||
* Narcolepsy | * Narcolepsy | ||
* Off-label: treatment-resistant depression (augmentation), excessive daytime sleepiness in shift-work disorder, cognitive symptoms in chronic illness | * Off-label: treatment-resistant depression (augmentation), excessive daytime sleepiness in shift-work disorder, cognitive symptoms in chronic illness | ||
| dosing = | | dosing = <titration slug="typical-adult" title="Typical Adult" author="MDElliottMD"> | ||
<titration slug="typical-adult" title="Typical Adult" author="MDElliottMD"> | Start at 5 mg XR; may increase by 5 mg each day until the desired effect is reached, up to 30 mg XR to start, and up to 60 mg XR eventually if necessary, in 10 mg increments. | ||
Start at | |||
Occasionally can go higher if no notable effects (good or bad) at 60 mg — proceed with caution. | |||
If not long enough acting: | If not long enough acting: add a tail dose of Adderall IR at [XR dose]/2. | ||
If too long acting (e.g. disrupting sleep) | If too long acting (e.g. disrupting sleep): switch to IR entirely (again at half the XR dose). | ||
</titration> | </titration> | ||
| effects = | | effects = ==== Therapeutic ==== | ||
* <effect slug="attention" label="Attention and focus" author="MDElliottMD">Improved attention, executive function, and working memory.</effect> | |||
==== Therapeutic ==== | * <effect slug="reduced-impulsivity" label="Reduced impulsivity and hyperactivity" author="MDElliottMD"/> | ||
* <effect slug="attention" label="Attention and focus">Improved attention, executive function, and working memory.</effect> | * <effect slug="wakefulness" label="Wakefulness" author="MDElliottMD"/> | ||
* <effect slug="reduced-impulsivity" label="Reduced impulsivity and hyperactivity"/> | * <effect slug="motivation" label="Motivation and drive" author="MDElliottMD"/> | ||
* <effect slug="wakefulness" label="Wakefulness"/> | * <effect slug="euphoria" label="Mild euphoria" author="MDElliottMD"/> | ||
* <effect slug="motivation" label="Motivation and drive"/> | |||
* <effect slug="euphoria" label="Mild euphoria"/> | |||
==== Common ==== | ==== Common ==== | ||
* <effect slug="decreased-appetite" label="Decreased appetite">Often dose-limiting; may produce weight loss over time.</effect> | * <effect slug="decreased-appetite" label="Decreased appetite" author="MDElliottMD">Often dose-limiting; may produce weight loss over time.</effect> | ||
* <effect slug="insomnia" label="Insomnia">Especially with late-afternoon dosing.</effect> | * <effect slug="insomnia" label="Insomnia" author="MDElliottMD">Especially with late-afternoon dosing.</effect> | ||
* <effect slug="dry-mouth" label="Dry mouth"/> | * <effect slug="dry-mouth" label="Dry mouth" author="MDElliottMD"/> | ||
* <effect slug="irritability" label="Irritability"/> | * <effect slug="irritability" label="Irritability" author="MDElliottMD"/> | ||
* <effect slug="anxiety" label="Anxiety"/> | * <effect slug="anxiety" label="Anxiety" author="MDElliottMD"/> | ||
* <effect slug="hr-bp-elevation" label="Elevated heart rate / blood pressure">Usually mild but dose-dependent.</effect> | * <effect slug="hr-bp-elevation" label="Elevated heart rate / blood pressure" author="MDElliottMD">Usually mild but dose-dependent.</effect> | ||
* <effect slug="headache" label="Headache"/> | * <effect slug="headache" label="Headache" author="MDElliottMD"/> | ||
* <effect slug="bruxism" label="Jaw clenching / bruxism">May produce TMJ symptoms over time.</effect> | * <effect slug="bruxism" label="Jaw clenching / bruxism" author="MDElliottMD">May produce TMJ symptoms over time.</effect> | ||
* <effect slug="weight-loss" label="Weight loss"/> | * <effect slug="weight-loss" label="Weight loss" author="MDElliottMD"/> | ||
==== Cardiovascular ==== | ==== Cardiovascular ==== | ||
* <effect slug="palpitations" label="Palpitations"/> | * <effect slug="palpitations" label="Palpitations" author="MDElliottMD"/> | ||
* <effect slug="cardiac-event" label="Serious cardiac event">Rare reports of sudden cardiac death in patients with structural heart disease (FDA warning).</effect> | * <effect slug="cardiac-event" label="Serious cardiac event" author="MDElliottMD">Rare reports of sudden cardiac death in patients with structural heart disease (FDA warning).</effect> | ||
==== Psychiatric ==== | ==== Psychiatric ==== | ||
* <effect slug="agitation" label="Agitation"/> | * <effect slug="agitation" label="Agitation" author="MDElliottMD"/> | ||
* <effect slug="psychosis" label="Psychosis">Rare; higher risk in patients with bipolar predisposition.</effect> | * <effect slug="psychosis" label="Psychosis" author="MDElliottMD">Rare; higher risk in patients with bipolar predisposition.</effect> | ||
* <effect slug="mania" label="Mania">Rare; higher risk in patients with bipolar predisposition.</effect> | * <effect slug="mania" label="Mania" author="MDElliottMD">Rare; higher risk in patients with bipolar predisposition.</effect> | ||
==== Other adverse ==== | ==== Other adverse ==== | ||
* <effect slug="dependence" label="Dependence / misuse">Schedule II controlled substance; high abuse liability, particularly when crushed, insufflated, or injected.</effect> | * <effect slug="dependence" label="Dependence / misuse" author="MDElliottMD">Schedule II controlled substance; high abuse liability, particularly when crushed, insufflated, or injected.</effect> | ||
* <effect slug="tolerance" label="Tolerance">To therapeutic effects, with chronic high-dose use.</effect> | * <effect slug="tolerance" label="Tolerance" author="MDElliottMD">To therapeutic effects, with chronic high-dose use.</effect> | ||
* <effect slug="growth-suppression" label="Growth suppression">Modest reduction in height/weight velocity in chronically-treated children.</effect> | * <effect slug="growth-suppression" label="Growth suppression" author="MDElliottMD">Modest reduction in height/weight velocity in chronically-treated children.</effect> | ||
* <effect slug="serotonin-syndrome" label="Serotonin syndrome">Especially in combination with serotonergic agents or MAOIs.</effect> | * <effect slug="serotonin-syndrome" label="Serotonin syndrome" author="MDElliottMD">Especially in combination with serotonergic agents or MAOIs.</effect> | ||
* <effect slug="stereotypies" label="Stereotyped behaviors">Skin-picking, repetitive movements at higher doses.</effect> | * <effect slug="stereotypies" label="Stereotyped behaviors" author="MDElliottMD">Skin-picking, repetitive movements at higher doses.</effect> | ||
* <effect slug="vasculopathy" label="Peripheral vasculopathy">Raynaud-like phenomenon, rare digital ischemia.</effect> | * <effect slug="vasculopathy" label="Peripheral vasculopathy" author="MDElliottMD">Raynaud-like phenomenon, rare digital ischemia.</effect> | ||
* <effect slug="seizure" label="Lowered seizure threshold">Caution in epilepsy.</effect> | * <effect slug="seizure" label="Lowered seizure threshold" author="MDElliottMD">Caution in epilepsy.</effect> | ||
* <effect slug="hyperthermia" label="Hyperthermia">Risk in hot environments or with vigorous exercise.</effect> | * <effect slug="hyperthermia" label="Hyperthermia" author="MDElliottMD">Risk in hot environments or with vigorous exercise.</effect> | ||
* <effect slug="withdrawal" label="Withdrawal / " | * <effect slug="withdrawal" label="Withdrawal / "crash"" author="MDElliottMD">Fatigue, depression, hypersomnia, increased appetite on abrupt discontinuation.</effect> | ||
| contraindications = * Hypersensitivity to amphetamines | | contraindications = * Hypersensitivity to amphetamines | ||
* Concurrent MAOI use, or within 14 days of MAOI discontinuation | * Concurrent MAOI use, or within 14 days of MAOI discontinuation | ||
| Line 109: | Line 107: | ||
* Report chest pain, palpitations, severe agitation, hallucinations, or signs of poor circulation in extremities. | * Report chest pain, palpitations, severe agitation, hallucinations, or signs of poor circulation in extremities. | ||
* Sudden discontinuation can cause a fatigue/depression "crash" — taper or plan for it. | * Sudden discontinuation can cause a fatigue/depression "crash" — taper or plan for it. | ||
| anecdotes = | | anecdotes = <anecdote slug="2026-05-12" perspective="provider" author="MDElliottMD"> | ||
<anecdote slug="2026-05-12" perspective="provider" author="MDElliottMD"> | |||
I've started warning people about increased bowel motility with this medicine, encouraging people to not trust their farts too much :) | I've started warning people about increased bowel motility with this medicine, encouraging people to not trust their farts too much :) | ||
</anecdote> | </anecdote> | ||
Revision as of 00:04, 13 May 2026
Psychostimulant, Amphetamine
Mixed amphetamine salts
Adderall, Adderall XR, Mydayis
Mixed amphetamine salts (MAS) — marketed primarily as Adderall — is a 3:1 mixture of dextroamphetamine and levoamphetamine salts (dextroamphetamine sulfate, amphetamine sulfate, dextroamphetamine saccharate, and amphetamine aspartate). Amphetamine was first synthesized in 1887 by Lazăr Edeleanu, then developed as a medicine in the late 1920s. It has a chiral center and two enantiomers, levoamphetamine and dextroamphetamine; the latter is significantly more centrally psychoactive, while the levo enantiomer contributes more to peripheral noradrenergic effects. MAS is FDA-approved for attention-deficit hyperactivity disorder and narcolepsy. As a Schedule II controlled substance it carries substantial dependence and misuse potential, particularly in academic and occupational settings where it is frequently used off-label as a cognitive enhancer.
Absorption: Excellent oral bioavailability — sources report ">75%" to "~90%". Food does not significantly affect total absorption but can delay peak concentration. Distribution: Volume of distribution ~4 L/kg; plasma protein binding less than 20%. Crosses the blood–brain barrier and placenta. Metabolism: Amphetamine is oxidized to 4-hydroxyamphetamine, α-hydroxyamphetamine, or norephedrine. Norephedrine and 4-hydroxyamphetamine are active metabolites and are further metabolized to 4-hydroxy-norephedrine. Deamination of α-hydroxyamphetamine yields phenylacetone, which is metabolized to benzoic acid and conjugated to its glucuronide and hippuric acid. CYP2D6 is crucial for amphetamine metabolism; genetic polymorphism causes significant inter-patient variability in clearance. Amphetamine itself inhibits monoamine oxidase (MAO), and both CYP1A2 and CYP3A4 contribute to its metabolism.[1] Elimination: Primarily renal — ~30–40% recovered as unchanged amphetamine, the rest as metabolites. Due to its pKa of 9.9, urinary elimination is highly pH-dependent: alkaline urine reduces ionization and decreases renal clearance, while acidic urine and high flow rates accelerate clearance via active tubular secretion. Half-life: The D-enantiomer has a half-life of 9 hours in children (6–12 y), 11 hours in adolescents (13–17 y), and 10 hours in adults. The L-enantiomer is consistently longer-lived: 11 hours in children, 13–14 hours in adolescents, 13 hours in adults.
Dextroamphetamine, Lisdexamfetamine, Methylphenidate, Dexmethylphenidate, Modafinil, Atomoxetine, Methamphetamine
Experience
2 personal reports · avg efficacy 90.0/100 · avg side-effect burden 30.0/100 · median use 8 months · median dose 17.5 mg/day · 100% still taking it
No clinical reports yet
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Problems
- Attention-deficit hyperactivity disorder (ADHD) in children, adolescents, and adults
- Narcolepsy
- Off-label: treatment-resistant depression (augmentation), excessive daytime sleepiness in shift-work disorder, cognitive symptoms in chronic illness
Titration strategies
Typical Adult+1
Start at 5 mg XR; may increase by 5 mg each day until the desired effect is reached, up to 30 mg XR to start, and up to 60 mg XR eventually if necessary, in 10 mg increments.
Occasionally can go higher if no notable effects (good or bad) at 60 mg — proceed with caution.
If not long enough acting: add a tail dose of Adderall IR at [XR dose]/2.
If too long acting (e.g. disrupting sleep): switch to IR entirely (again at half the XR dose).Effects
Therapeutic
- Attention and focus 100% +100.0 (n=1) ~95% +100.0 (n=1)Improved attention, executive function, and working memory.Did you experience this?How often have you seen this?How was it? (-100 worst, +100 best)How was it? (-100 worst, +100 best)
- Reduced impulsivity and hyperactivity 100% +33.0 (n=1) ~66% +67.0 (n=1)Did you experience this?How often have you seen this?How was it? (-100 worst, +100 best)How was it? (-100 worst, +100 best)
- Wakefulness 100% +100.0 (n=1) ~80% +67.0 (n=1)Did you experience this?How often have you seen this?How was it? (-100 worst, +100 best)How was it? (-100 worst, +100 best)
- Motivation and drive 100% +100.0 (n=1) ~66% +100.0 (n=1)Did you experience this?How often have you seen this?How was it? (-100 worst, +100 best)How was it? (-100 worst, +100 best)
- Mild euphoria 100% +100.0 (n=1) ~80% +67.0 (n=1)Did you experience this?How often have you seen this?How was it? (-100 worst, +100 best)How was it? (-100 worst, +100 best)
Common
- Decreased appetite 100% +33.0 (n=1) ~50% +33.0 (n=1)Often dose-limiting; may produce weight loss over time.Did you experience this?How often have you seen this?How was it? (-100 worst, +100 best)How was it? (-100 worst, +100 best)
- Insomnia 0% — (n=1) ~20% -67.0 (n=1)Especially with late-afternoon dosing.Did you experience this?How often have you seen this?How was it? (-100 worst, +100 best)How was it? (-100 worst, +100 best)
- Dry mouth 100% -33.0 (n=1) ~66% -67.0 (n=1)Did you experience this?How often have you seen this?How was it? (-100 worst, +100 best)How was it? (-100 worst, +100 best)
- Irritability 0% — (n=1) ~5% -67.0 (n=1)Did you experience this?How often have you seen this?How was it? (-100 worst, +100 best)How was it? (-100 worst, +100 best)
- Anxiety 0% — (n=1) ~20% -33.0 (n=1)Did you experience this?How often have you seen this?How was it? (-100 worst, +100 best)How was it? (-100 worst, +100 best)
- Elevated heart rate / blood pressure 100% -33.0 (n=1) ~50% -33.0 (n=1)Usually mild but dose-dependent.Did you experience this?How often have you seen this?How was it? (-100 worst, +100 best)How was it? (-100 worst, +100 best)
- Headache 0% — (n=1) ~5% -33.0 (n=1)Did you experience this?How often have you seen this?How was it? (-100 worst, +100 best)How was it? (-100 worst, +100 best)
- Jaw clenching / bruxism 100% -33.0 (n=1) ~33% -33.0 (n=1)May produce TMJ symptoms over time.Did you experience this?How often have you seen this?How was it? (-100 worst, +100 best)How was it? (-100 worst, +100 best)
- Weight loss 0% — (n=1) ~20% +33.0 (n=1)Did you experience this?How often have you seen this?How was it? (-100 worst, +100 best)How was it? (-100 worst, +100 best)
Cardiovascular
- Palpitations 0% — (n=1) ~5% -33.0 (n=1)Did you experience this?How often have you seen this?How was it? (-100 worst, +100 best)How was it? (-100 worst, +100 best)
- Serious cardiac event 0% — (n=1) ~0% — (n=1)Rare reports of sudden cardiac death in patients with structural heart disease (FDA warning).Did you experience this?How often have you seen this?How was it? (-100 worst, +100 best)How was it? (-100 worst, +100 best)
Psychiatric
- Agitation 0% — (n=1) ~5% -67.0 (n=1)Did you experience this?How often have you seen this?How was it? (-100 worst, +100 best)How was it? (-100 worst, +100 best)
- Psychosis 0% — (n=1) ~5% -100.0 (n=1)Rare; higher risk in patients with bipolar predisposition.Did you experience this?How often have you seen this?How was it? (-100 worst, +100 best)How was it? (-100 worst, +100 best)
- Mania 0% — (n=1) ~5% -100.0 (n=1)Rare; higher risk in patients with bipolar predisposition.Did you experience this?How often have you seen this?How was it? (-100 worst, +100 best)How was it? (-100 worst, +100 best)
Other adverse
- Dependence / misuse 0% — (n=1) ~5% -67.0 (n=1)Schedule II controlled substance; high abuse liability, particularly when crushed, insufflated, or injected.Did you experience this?How often have you seen this?How was it? (-100 worst, +100 best)How was it? (-100 worst, +100 best)
- Tolerance 0% — (n=1) ~5% -33.0 (n=1)To therapeutic effects, with chronic high-dose use.Did you experience this?How often have you seen this?How was it? (-100 worst, +100 best)How was it? (-100 worst, +100 best)
- Growth suppression 0% — (n=1) ~0% — (n=1)Modest reduction in height/weight velocity in chronically-treated children.Did you experience this?How often have you seen this?How was it? (-100 worst, +100 best)How was it? (-100 worst, +100 best)
- Serotonin syndrome 0% — (n=1) ~0% — (n=1)Especially in combination with serotonergic agents or MAOIs.Did you experience this?How often have you seen this?How was it? (-100 worst, +100 best)How was it? (-100 worst, +100 best)
- Stereotyped behaviors 100% -33.0 (n=1) ~5% -67.0 (n=1)Skin-picking, repetitive movements at higher doses.Did you experience this?How often have you seen this?How was it? (-100 worst, +100 best)How was it? (-100 worst, +100 best)
- Peripheral vasculopathy 0% — (n=1) ~5% — (n=1)Raynaud-like phenomenon, rare digital ischemia.Did you experience this?How often have you seen this?How was it? (-100 worst, +100 best)How was it? (-100 worst, +100 best)
- Lowered seizure threshold 0% — (n=1) ~0% — (n=1)Caution in epilepsy.Did you experience this?How often have you seen this?How was it? (-100 worst, +100 best)How was it? (-100 worst, +100 best)
- Hyperthermia 0% — (n=1) ~5% -33.0 (n=1)Risk in hot environments or with vigorous exercise.Did you experience this?How often have you seen this?How was it? (-100 worst, +100 best)How was it? (-100 worst, +100 best)
- Withdrawal / "crash" 100% — (n=1) ~50% -67.0 (n=1)Fatigue, depression, hypersomnia, increased appetite on abrupt discontinuation.Did you experience this?How often have you seen this?How was it? (-100 worst, +100 best)How was it? (-100 worst, +100 best)
Pharmacokinetics
Pharmacodynamics
Amphetamine produces its effects through several converging mechanisms at monoaminergic terminals:
- Trace amine-associated receptor 1 (TAAR1) agonism — activates TAAR1 in monoaminergic neurons, triggering PKA/PKC signaling that phosphorylates the dopamine and norepinephrine transporters (DAT, NET), causing them to internalize and reverse direction.
- VMAT2 substrate — enters the presynaptic terminal, displaces dopamine and norepinephrine from vesicles into the cytoplasm.
- Reverse transport via DAT/NET — the elevated cytoplasmic monoamine pool is then ejected into the synaptic cleft via the now-reversed transporters. This is the primary mechanism of action — release, not reuptake inhibition.
- Weak reuptake inhibition at DAT and NET (secondary to release).
- MAO inhibition at higher concentrations, slowing presynaptic catabolism of monoamines.
- Serotonergic effects at high or supratherapeutic doses (relevant to overdose and serotonin syndrome risk).
Interactions
- MAOIs (phenelzine, tranylcypromine, selegiline, linezolid) — hypertensive crisis, serotonin syndrome; contraindicated
- Serotonergic agents (SSRIs, SNRIs, triptans, tramadol) — serotonin syndrome risk
- Tricyclic antidepressants — additive cardiovascular effects
- Acidifying agents (ammonium chloride, ascorbic acid in large doses, fruit juices) — increase urinary clearance, reduce efficacy
- Alkalinizing agents (sodium bicarbonate, acetazolamide, antacids) — decrease clearance, prolong/intensify effects
- CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion) — elevated amphetamine levels
- Antihypertensives — may be antagonized by amphetamine's pressor effects
- Sympathomimetics (pseudoephedrine, phenylephrine) — additive cardiovascular effects
- Alcohol — may mask intoxication; cardiac risk
- Caffeine — additive stimulant effects, anxiety
Pregnancy and lactation
Monitoring
- Baseline: cardiovascular history, blood pressure, heart rate, weight/height, mental health history (especially for psychosis/bipolar/substance use risk)
- Consider ECG if cardiac risk factors present
- At each visit: blood pressure, heart rate, weight (and height in children), efficacy, side effects, signs of misuse or diversion
- Periodically reassess continued need; consider drug holidays in children to assess ongoing benefit and minimize growth effects
- Sleep quality (insomnia is dose-limiting)
Patient counseling
- Take in the morning to minimize insomnia; avoid afternoon dosing.
- Do not crush, chew, or split Adderall XR or Mydayis capsules — disrupts the controlled-release mechanism. (Capsules may be opened and sprinkled on applesauce if needed.)
- Take with or without food; high-acid beverages (orange juice, vitamin C) may reduce absorption.
- Stay well-hydrated, especially in heat or during exercise.
- Eat regular meals despite appetite suppression.
- Do not combine with alcohol — masks effects of both, increases cardiac strain.
- Do not share or sell — federal Schedule II controlled substance; serious legal and clinical consequences.
- Report chest pain, palpitations, severe agitation, hallucinations, or signs of poor circulation in extremities.
- Sudden discontinuation can cause a fatigue/depression "crash" — taper or plan for it.
Relevant anecdote
⚕️ Provider +1
I've started warning people about increased bowel motility with this medicine, encouraging people to not trust their farts too much :)
Relevant Literature
No literature entries yet.
Log in to submit relevant literature.
See also
Summary
Classes
Psychostimulant, Amphetamine
Common uses
- Distractibility4.0n=1
- Excessive daytime sleepiness in shift-work disorder4.0n=1
- Impaired persistent attention4.0n=2
- Cognitive symptoms in chronic illness3.0n=1
- Impulsivity3.0n=1
Pharmacy
Starting dose
5 mg XR
Preparations
IR tabs 5–30 mg; XR caps 5–30 mg; Mydayis caps 12.5–50 mg
Pharmacology
Routes
Oral
Onset
IR: 30–60 min; XR: 1–2 h to peak effect
Duration
IR 4–6 h; XR 10–12 h; Mydayis 14–16 h
Half-life
D-amphetamine ~10 h; L-amphetamine ~13 h (adults)
Bioavailability
~75–90% (oral)
Pregnancy
Category C
Legal status
Schedule II
Purported mechanism
TAAR1 agonism, VMAT2 substrate, DAT/NET reverse transport — net release of dopamine and norepinephrine