Lisdexamfetamine

(2S)-2,6-diamino-N-[(2S)-1-phenylpropan-2-yl]hexanamide

Overview

Lisdexamfetamine belongs to Stimulants.

Key safety note: Once converted, lisdexamfetamine carries the same core risks as dextroamphetamine.^[7]^[3]

Effects

Subjective effects vary. What a substance feels like depends on dose, individual physiology, mindset, and setting. The points below describe commonly reported effects, not guaranteed, uniform, or desirable outcomes.

At therapeutic doses: improved sustained attention, concentration and impulse control, increased alertness and wakefulness, reduced appetite, and often a mild lift in energy or mood.
Common side effects include reduced appetite and weight loss, insomnia, dry mouth, headache, irritability or anxiety, upper-abdominal pain or nausea, and a modestly raised heart rate and blood pressure.
At higher or misused doses: euphoria and marked stimulation, but also a racing heart, restlessness and jitteriness, insomnia and, at high or repeated doses, anxiety, paranoia and stimulant psychosis, typically followed by a 'crash' of fatigue and low mood as amphetamine levels fall.

Dosing & duration

Harm-reduction note: These are commonly cited reference ranges, not a recommendation or a “safe” dose. Potency, purity, body chemistry, tolerance, and drug combinations vary widely. Start low, go slow, wait for full effects before redosing, and never assume an unknown product matches these figures. Missing data is not evidence of safety.

Oral (once daily, in the morning). Medical use is oral only. These are therapeutic figures from the FDA prescribing information, not recreational reference ranges: lisdexamfetamine is a prescription medicine individually titrated by a clinician. It is taken once in the morning. Dosing later in the day can cause insomnia. Amounts are given as lisdexamfetamine dimesylate (roughly 50 mg of the prodrug delivers about 20 mg of dextroamphetamine base). Taking more than prescribed sharply raises the risk of dependence, psychosis and cardiovascular harm, and efficacy and safety above 70 mg/day have not been established.

Dose ranges

ADHD start (children ≥6 and adults)

30 mg once daily

ADHD titration

increase by 10–20 mg at weekly intervals

ADHD maximum

70 mg/day

Binge-eating disorder (adults)

start 30 mg/day, titrate by 20 mg/week to a target of 50–70 mg/day (max 70 mg/day)

Duration

onset

~1.5–2 h (gradual, the prodrug must be converted first)

total

~10–14 h

after effects

Possible rebound fatigue, low mood and increased appetite as levels fall

Chemical & Physical Properties

Formula	C15H25N3O
Molar mass	263.38 g/mol
State	Solid
Melting point	120–122 °C
Boiling point	Not reported
Density	Not reported
Vapor pressure	Not reported
pKa	10.5
LogP	-1.76
Solubility	Freely soluble in water (792 mg/mL, as the dimesylate salt)
Refractive index	Not reported

Identifiers & Synonyms

CAS	608137-32-2
CAS (enantiomer)
PubChem CID	11597698
InChIKey	VOBHXZCDAVEXEY-JSGCOSHPSA-N
InChI	InChI=1S/C15H25N3O/c1-12(11-13-7-3-2-4-8-13)18-15(19)14(17)9-5-6-10-16/h2-4,7-8,12,14H,5-6,9-11,16-17H2,1H3,(H,18,19)/t12-,14-/m0/s1
SMILES	C[C@@H](CC1=CC=CC=C1)NC(=O)[C@H](CCCCN)N

Synonyms

Vyvanse
Elvanse
Lisdexamfetamine
L-lysine-d-amphetamine

Pharmacodynamics & Biochemistry

Lisdexamfetamine is an inactive prodrug: the amino acid L-lysine is covalently bonded to dextroamphetamine (the more stimulating d-enantiomer of amphetamine), and the molecule has essentially no stimulant activity of its own until that bond is cleaved. After oral absorption it is hydrolysed, chiefly by peptidase (aminopeptidase) activity associated with red blood cells, to release L-lysine and active dextroamphetamine. This enzymatic conversion is the rate-limiting step (conversion half-life roughly 1 hour) and, crucially, proceeds at the same rate regardless of route, so crushing, snorting or injecting the drug does not produce a faster or larger amphetamine spike than swallowing it. The liberated dextroamphetamine is a releaser of the catecholamines dopamine and noradrenaline (and, more weakly, serotonin). It is a substrate for the dopamine (DAT) and noradrenaline (NET) transporters and an agonist at trace-amine-associated receptor 1 (TAAR1). By entering the nerve terminal and disrupting vesicular storage via VMAT2 it reverses transporter flux and pushes these neurotransmitters out into the synapse, rather than simply blocking their reuptake as methylphenidate does. The resulting rise in dopamine and noradrenaline, particularly in the prefrontal cortex and striatum, underlies the improvements in attention and impulse control and the wakefulness, appetite suppression and cardiovascular stimulation. Because the prodrug must first be converted, onset is gradual and the effect is smooth and long-lasting (roughly 10–14 hours from a single morning dose), which is the basis of its once-daily use.

Biological targets

DAT
NET
VMAT2
TAAR1

Pharmacokinetics

Bioavailability	Oral (prodrug), rate-limited conversion gives smooth profile
T_max	Dexamphetamine ≈3.5 h
Half-life	Prodrug <1 h, dexamphetamine ≈10–12 h
V_d	Not reported
Protein binding	Not reported
Metabolism	Hydrolysed in red blood cells to dexamphetamine + lysine
Excretion	Renal

Toxicology & Safety

Harm-reduction note: Toxicity and risk depend on dose, route, purity, combinations, setting, and individual health factors. Missing harms should never be interpreted as evidence of safety.

Not reported

Once converted, lisdexamfetamine carries the same core risks as dextroamphetamine. It is a Schedule II stimulant with genuine abuse and dependence potential: although the prodrug design blunts the 'rush' and lowers abuse liability at normal doses (no free amphetamine can be released by crushing or extraction, and the blood conversion is rate-limited and route-independent), that protection is dose-dependent and is largely lost when the dose is greatly exceeded. It raises heart rate and blood pressure and has been linked to rare sudden cardiac events, so it is used cautiously or avoided in significant cardiovascular disease. It can trigger or worsen anxiety, agitation, insomnia, tics, mania and, at high or repeated doses, stimulant psychosis, and it suppresses appetite (with weight loss and, in children, possible slowing of growth). Combining it with an MAO inhibitor can cause a life-threatening hypertensive crisis, and combining it with serotonergic drugs can cause serotonin syndrome. Abrupt discontinuation after heavy use produces a 'crash' of fatigue, low mood and increased appetite.^[7]^[3]

Legal Status

Legal note: Legal status can change over time and may vary by country, region, formulation, analogue status, prescription context, and enforcement practice. Always confirm with current official sources before relying on this section.

US: Schedule II. UK: Class B. DE: BtMG Anlage III

Interactions & Contraindications

Drug interactions

MAOIs Contraindicated, or within 14 days, the combination can trigger a hypertensive crisis.^[7]^[3]

SSRIs, SNRIs, Triptans, Tramadol, Lithium Raise the risk of serotonin syndrome.^[7]

Stimulants (amphetamines, cocaine), Caffeine Add to cardiovascular and stimulant effects (other amphetamines, decongestants, high-dose caffeine).^[7]

Strong CYP2D6 inhibitors (e.g. paroxetine, fluoxetine) Can increase dextroamphetamine exposure and serotonin-syndrome risk (paroxetine, fluoxetine, bupropion, quinidine).^[7]

Urinary acidifiers or alkalinisers Acidifying agents speed excretion and shorten the effect, alkalinising agents slow it and prolong and intensify it.^[7]^[3]

Contraindications

Concurrent MAOI, SSRI/SNRI or other serotonergic medication concurrent MAOI use, or within 14 days of stopping one.^[7]

Cardiovascular disease, hypertension or arrhythmia symptomatic disease, moderate-to-severe hypertension or advanced arteriosclerosis.^[7]

Hyperthyroidism^[7]

History of stimulant or substance use disorder or marked anxiety or agitation.^[7]

Closed-angle glaucoma^[7]

Usage & Context

A once-daily prescription stimulant (Vyvanse in the US, Elvanse, Tyvense, Venvanse and related brands elsewhere) for attention-deficit/hyperactivity disorder (ADHD) in children aged 6 and over and in adults, usually alongside behavioural and educational support.
The only medicine approved for moderate-to-severe binge-eating disorder (BED) in adults. It is not approved, and should not be used, for weight loss or obesity.
Like other prescription stimulants it is sometimes misused for wakefulness, studying, appetite suppression or euphoria. The prodrug design makes it less attractive for snorting or injecting than immediate-release amphetamine, but oral misuse at higher-than-prescribed doses still carries real dependence and cardiovascular risk.

Sources & Evidence

Further Information

More in this subclass