Lisdexamfetamine

L-lysine-dextroamphetamine

Vyvanse, Elvanse, Tyvense, Lisdextroamphetamine

Psychoactive Class

Chemical Class

Lisdexamfetamine is a central nervous system stimulant of the amphetamine class, designed as a prodrug of dextroamphetamine.¹ First approved by the FDA in 2007,² it was specifically formulated to deter non-oral abuse by requiring metabolic conversion to release its active component.² Prescribed for ADHD and binge eating disorder,¹ it produces typical amphetamine effects including stimulation, focus enhancement, and euphoria, but with slower onset and longer duration than conventional amphetamines.² Despite its anti-abuse design, it retains significant dependence potential.¹

Dosage & Duration

Dosage

Threshold~10 mg

Light10-30 mg

Moderate30-60 mg

Strong60-90 mg

Heavy90+ mg

Bioavailability

~90%

Duration

Onset60-90 minutes

Come Up30-60 minutes

Peak3-5 hours

Offset4-6 hours

After Effects2-6 hours

Total10-14 hours

Half-life

9-11 hours

Subjective Effects

Lisdexamfetamine is an inactive prodrug that must be hydrolyzed by red blood cells into dextroamphetamine before any effect is felt, which gives the experience a characteristically slow and even onset. Effects generally begin within about 90 minutes and can persist for up to 14 hours, producing a long, consistent stimulant plateau rather than a sharp peak. Because activation is rate-limited by conversion in the blood, non-oral routes do not intensify the subjective effects. The overall character is one of increased alertness, motivation, and wakefulness, with euphoria reported at higher or non-medical doses.

Physical

Physical effects include stimulation and wakefulness alongside appetite suppression, increased heart rate, facial flushing, elevated body temperature, and a jittery, restless quality. Gastrointestinal upset such as nausea, vomiting, and abdominal pain is common, and difficulty sleeping is frequent.

Autonomic

Dry mouth

Uncomfortable

Dizziness

Cognitive

The mental state is marked by heightened alertness, improved task motivation, and modest improvements in working memory, attention, and inhibitory control at low doses, while doses above the therapeutic range can instead interfere with working memory and cognitive control. Anxiety, irritability, and paranoia are commonly reported, and psychosis or mania occur rarely.

Emotional

Paranoia

Enhancements

Impairment

Reagent Testing

Expected colorimetric results for common reagent tests. Colors show reaction change over 1–2 minutes.

Marquis(MQ)

Mecke(ME)

No reaction

Mandelin(MD)

No reaction

PROtestkit.eu

Pharmacology

Pharmacodynamics

Lisdexamfetamine is an inactive prodrug that is converted in the body to dextroamphetamine, which is responsible for the drug's pharmacological activity.¹ Following ingestion, lisdexamfetamine is hydrolyzed by enzymes in red blood cells to release dextroamphetamine and L-lysine, with a conversion half-life of approximately one hour.³¹ Dextroamphetamine acts as a full agonist at trace amine-associated receptor 1 (TAAR1), a key regulator of monoamine neurotransmission.⁴ It also inhibits the dopamine transporter, norepinephrine transporter, and vesicular monoamine transporter 2, with weaker affinity for the serotonin transporter.⁴ Through these mechanisms, dextroamphetamine blocks the reuptake of norepinephrine and dopamine into presynaptic neurons while promoting the release of monoamine neurotransmitters into the extracellular space.¹ The parent compound lisdexamfetamine itself does not bind to monoamine reuptake sites.¹

Pharmacokinetics

Lisdexamfetamine is rapidly absorbed from the gastrointestinal tract after oral administration.¹ Unlike amphetamine, its absorption is not significantly affected by gastrointestinal pH.⁵ The prodrug is hydrolyzed by red blood cells to dextroamphetamine and L-lysine, with substantial conversion occurring even at low hematocrit levels.¹ This enzymatic conversion is the rate-limiting step in bioactivation and is not mediated by cytochrome P450 enzymes.⁵¹ Dextroamphetamine readily distributes into most tissues including the brain, with approximately 20% bound to plasma proteins.⁶ Dextroamphetamine is subsequently metabolized by CYP2D6, dopamine β-hydroxylase, flavin-containing monooxygenase 3, and glycine N-acyltransferase through pathways including aromatic para-hydroxylation, aliphatic hydroxylation, N-oxidation, N-dealkylation, and deamination.⁴ Approximately 96% of an oral dose is recovered in urine, with 42% as amphetamine, 25% as hippuric acid, and 2% as intact lisdexamfetamine.¹

Interactions

Dangerous

Highest risk

These combinations are considered extremely harmful and should always be avoided. Reactions to these drugs taken in combination are highly unpredictable and have a potential to cause death.

AMTMAOIsTramadol

Unsafe

Avoid

There is considerable risk of physical harm when taking these combinations, they should be avoided where possible.

2C-T-x compounds5-MeO-xxT tryptaminesDOx compoundsDXMNBOMe compoundsPCPPregabalin

Caution

Use caution

These combinations are not usually physically harmful, but may produce undesirable effects, such as physical discomfort or overstimulation. Extreme use may cause physical health issues. Synergistic effects may be unpredictable. Care should be taken when choosing to use this combination.

2C-x compoundsAlcoholCaffeineCannabisCocaineDiphenhydramineDMTGHB/GBLKetamineLSDMDMAMescalineMXEOpioidsPsilocybin mushrooms

TripSit

Tolerance

Full Tolerance

Tolerance develops rapidly with recreational amphetamine use, often requiring increasingly larger doses to achieve the same effect during periods of extended use.¹ Patients prescribed lisdexamfetamine therapeutically may also need dosage increases over time to maintain efficacy, though this occurs more gradually than with recreational abuse patterns.⁷⁸

Cross Tolerance

Amphetamines, Dopaminergic stimulants

Harm Potential

Addiction & Dependence

Psychological

High

Lisdexamfetamine has a high potential for substance abuse and can produce dependence and addiction like other euphoric stimulants, particularly when taken above recommended dosages.¹ While its prodrug design may reduce abuse potential compared to immediate-release amphetamines at therapeutic doses, addiction is a serious risk with heavy recreational use.¹

Physical

Moderate

Tolerance develops rapidly with recreational amphetamine abuse, requiring increasingly larger doses to achieve the same effect.¹ Patients prescribed this drug often must increase their dosage over time to maintain efficacy.¹ Physical dependence can develop with chronic use.¹

Toxicity

Cardiovascular

Cardiovascular effects including arrhythmias, hypertension or hypotension, increased heart rate, and circulatory collapse can occur, particularly in overdose situations.¹ Rare cases of sudden cardiac death have been reported in individuals with underlying heart problems.¹

Central Nervous System

In rodents and primates, sufficiently high doses of amphetamine cause dopaminergic neurotoxicity characterized by reduced transporter and receptor function. There is no evidence that amphetamine is directly neurotoxic in humans at typical doses, though large doses may cause indirect neurotoxicity through increased oxidative stress.

Psychosis Risk

Using amphetamines in very high doses can result in stimulant psychosis which may include paranoia, delusions, and hallucinations.¹ Approximately 5-15% of users who develop stimulant psychosis fail to recover completely.¹⁰ Psychosis very rarely arises from therapeutic use; the combination of prolonged high-dose use with sleep deprivation significantly increases risk.¹¹

Seizure Risk

Convulsions are reported as a manifestation of severe overdose and typically precede fatal poisoning.¹

History & Culture

Development and Synthesis

Lisdexamfetamine was developed by Robert Oberlender at New River Pharmaceuticals¹²¹³ under the developmental name NRP104.² The compound represents the first chemically formulated prodrug stimulant,²…

Legality

International

Lisdexamfetamine is absent from the INCB schedules for the 1961 and 1971 conventions and from the precursor tables of the 1988 Convention. It is therefore not internationally scheduled under those conventions.

By Country

United StatesPrescription onlySchedule II

21 CFR 1308.12⁵²

Controlled under Schedule II of the Controlled Substances Act, indicating high abuse potential with accepted medical use.⁵³ First approved by the FDA in April 2008 for ADHD treatment in adults, with subsequent approval for binge eating disorder in January 2015.

AustriaPrescription onlyNR

Rezeptpflichtverordnung, Anlage A, Teil 2 (Humanarzneimittel)²⁰

Lisdexamfetamine is listed as an NR human medicinal active substance in Austria’s Rezeptpflichtverordnung. NR medicines require a prescription and may not be dispensed repeatedly.

Czech RepublicPrescription onlySeznam č. 5

Government Regulation No. 463/2013 Coll., on Lists of Addictive Substances; Act No. 167/1998 Coll., on Addictive Substances²³²⁴

Lisdexamfetamine is listed in List No. 5 of the Czech Government Regulation on Lists of Addictive Substances. Handling in an unpermitted capacity requires authorization from the Ministry of Health; individuals may acquire the substance for their own use only on a prescription and may keep and use it only as prescribed or directed by a doctor.

IrelandPrescription onlyPrescription-only

HPRA authorised-medicines record for Tyvense 20 mg capsules²⁷

Tyvense, containing lisdexamfetamine dimesylate, is an authorised Irish medicinal product. The HPRA record classifies it as a product subject to medical prescription.

New ZealandIllegalClass B2 controlled drug

Misuse of Drugs Act 1975, Schedule 2, Part 2²⁹³⁰

Lisdexamfetamine is listed as a Class B controlled drug in Part 2 of Schedule 2 to the Misuse of Drugs Act 1975. Medsafe identifies it as a Class B2 controlled drug and states that restrictions apply to its prescribing, supply, and administration.

PortugalPrescription onlyPrescription-only

INFARMED public assessment report for Elvanse³³

Elvanse, containing lisdexamfetamine dimesylate, is assessed by INFARMED as a medicinal product. It is supplied through Portugal's prescription-medicine system.

South KoreaPrescription only별표 4

Narcotics Control Act Enforcement Decree, Annex 4^37383940

Lisdexamfetamine is listed as a psychotropic drug under Annex 4 to the Narcotics Control Act Enforcement Decree. Annex 4 covers the Act’s Article 2(3)(b) category, which is reserved for drugs with a high risk of misuse or abuse that are used only for very limited medical purposes. The Narcotics Control Act prohibits narcotics use other than in accordance with the Act, so lawful medical handling is subject to its licensed and prescription controls.

SwedenPrescription onlyFörteckning II

Läkemedelsverkets föreskrifter (LVFS 2011:10) om förteckningar över narkotika, Förteckning II; lag (1992:860) om kontroll av narkotika⁴³⁴⁴

Lisdexamfetamine is listed in Sweden's Förteckning II, the national narcotics schedule for substances with medical use. Under the Act on Control of Narcotic Drugs, narcotic medicines may be dispensed only on an order from a physician, dentist, or veterinarian, and possession is limited to authorized handlers and persons supplied under that framework.

United KingdomPrescription onlyClass B · Schedule 2

Misuse of Drugs Act 1971, Schedule 2, Part II; Misuse of Drugs Regulations 2001, Schedule 2^4748495051

Lisdexamfetamine, listed in the legislation as lisdexamphetamine, is a Class B controlled drug under the Misuse of Drugs Act 1971 and a Schedule 2 controlled drug under the Misuse of Drugs Regulations 2001. Unauthorised possession, production, and supply are offences under the Act, while the Schedule 2 regulations govern its lawful handling and prescribing.

AustraliaPrescription onlySchedule 8

Therapeutic Goods (Poisons Standard—June 2026) Instrument 2026, Schedule 8¹⁹

Controlled drug requiring a prescription. Schedule 8 substances are drugs of addiction that require strict controls on manufacture, supply, distribution, and possession.

CanadaPrescription onlySchedule I

Controlled Drugs and Substances Act, Schedule I²¹

Lisdexamfetamine, along with other amphetamines, is classified as a Schedule I controlled substance under the Controlled Drugs and Substances Act.²² Approved for medical use with prescription since February 2009.

GermanyPrescription onlyAnlage III

Betäubungsmittelgesetz (BtMG), Anlage III²⁵²⁶

Controlled under Anlage III of the Betäubungsmittelgesetz (Narcotics Act) since July 17, 2013.²⁵ Can only be prescribed using a narcotic prescription form (Betäubungsmittelrezept). Medical use is permitted under strict controls.

MexicoIllegal (analog/blanket ban)Fracción II

Ley General de Salud, artículo 245, fracción II; artículo 250²⁸

Lisdexamfetamine is covered as a chemical derivative of dexamphetamine under Article 245, fraction II, of Mexico’s General Health Law. The law subjects fraction-II psychotropic substances to the controls in Chapter V, including the special-prescription regime for controlled substances.

NorwayPrescription onlyNarkotikalisten

Forskrift om narkotika (narkotikaforskriften) §§ 4–5 and Narkotikalisten; legemiddelloven §§ 23–24³¹³²

Lisdexamfetamine is listed in Norway's Narkotikalisten as a narcotic subject to the strict controls in § 5 of the Narkotikaforskriften. Manufacture, acquisition, sale, import, export, storage, possession, and use are prohibited unless an exception is granted for medical or scientific need. The legemiddelloven permits narcotics to be supplied only for medical and scientific use and prohibits possession or use without lawful access.

SingaporeIllegalClass A

Misuse of Drugs Act 1973, First Schedule, Class A Drugs³⁴³⁵³⁶

Lisdexamfetamine and its stereoisomers are listed as a Class A controlled drug in the First Schedule to Singapore’s Misuse of Drugs Act 1973, effective 1 May 2019. Its trafficking, manufacture, import, export, possession, and consumption constitute offences under the Act.

SpainPrescription onlyPrescription-only

AEMPS CIMA product information for Elvanse⁴¹⁴²

Elvanse containing lisdexamfetamine dimesylate is authorised in Spain. The AEMPS product information states that it is subject to medical prescription.

SwitzerlandPrescription onlyVerzeichnis A

Betäubungsmittelverzeichnisverordnung (BetmVV-EDI), Verzeichnis a⁴⁵

Specifically named as a controlled substance under Verzeichnis A since October 1, 2014.⁴⁶ Medical use is permitted with appropriate prescription.

References

Source Pages

Citations

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Lisdexamfetamine

L-lysine-dextroamphetamine

Vyvanse, Elvanse, Tyvense, Lisdextroamphetamine

Psychoactive Class

Stimulant

Chemical Class

Amphetamine (substituted)