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Lisdexamfetamine
L-lysine-dextroamphetamine
Vyvanse, Elvanse, Tyvense, Lisdextroamphetamine
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,citation needed it was specifically formulated to deter non-oral abuse by requiring metabolic conversion to release its active component. 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.citation needed Despite its anti-abuse design, it retains significant dependence potential.
Dosage & Duration
Dosage
Doses are population estimates that vary widely between individuals.
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
Legacy content. A statistically backed ontology from Mindstate Design Labs is coming soon.
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.
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.
Pharmacology
Pharmacodynamics
Lisdexamfetamine is an inactive prodrug that is converted in the body to dextroamphetamine, which is responsible for the drug's pharmacological activity.citation needed 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. Dextroamphetamine acts as a full agonist at trace amine-associated receptor 1 (TAAR1), a key regulator of monoamine neurotransmission. It also inhibits the dopamine transporter, norepinephrine transporter, and vesicular monoamine transporter 2, with weaker affinity for the serotonin transporter. 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. The parent compound lisdexamfetamine itself does not bind to monoamine reuptake sites.
Pharmacokinetics
Lisdexamfetamine is rapidly absorbed from the gastrointestinal tract after oral administration.citation needed Unlike amphetamine, its absorption is not significantly affected by gastrointestinal pH. 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.citation needed Dextroamphetamine readily distributes into most tissues including the brain, with approximately 20% bound to plasma proteins. 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. Approximately 96% of an oral dose is recovered in urine, with 42% as amphetamine, 25% as hippuric acid, and 2% as intact lisdexamfetamine.1
Dangerous
Highest riskThese 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.
Unsafe
AvoidThere is considerable risk of physical harm when taking these combinations, they should be avoided where possible.
Caution
Use cautionThese 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.
Tolerance
Tolerance timelines are rules of thumb, not exact schedules, and vary widely between individuals and use patterns.
Full Tolerance
Tolerance develops rapidly with recreational amphetamine use, often requiring increasingly larger doses to achieve the same effect during periods of extended use.citation needed Patients prescribed lisdexamfetamine therapeutically may also need dosage increases over time to maintain efficacy, though this occurs more gradually than with recreational abuse patterns.
Cross Tolerance
Amphetamines, Dopaminergic stimulants
Harm Potential
Addiction & Dependence
Psychological
HighLisdexamfetamine has a high potential for substance abuse and can produce dependence and addiction like other euphoric stimulants, particularly when taken above recommended dosages.citation needed 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.
Physical
ModerateTolerance develops rapidly with recreational amphetamine abuse, requiring increasingly larger doses to achieve the same effect.citation needed Patients prescribed this drug often must increase their dosage over time to maintain efficacy. 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.citation needed Rare cases of sudden cardiac death have been reported in individuals with underlying heart problems.
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.citation needed Approximately 5-15% of users who develop stimulant psychosis fail to recover completely. Psychosis very rarely arises from therapeutic use; the combination of prolonged high-dose use with sleep deprivation significantly increases risk.
Seizure Risk
Convulsions are reported as a manifestation of severe overdose and typically precede fatal poisoning.citation needed
History & Culture
Development and Synthesis
Lisdexamfetamine was developed by Robert Oberlender at New River Pharmaceuticalscitation needed under the developmental name NRP104. The compound represents the first chemically formulated prodrug stimulant,2 created by covalently attaching…
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
Illegal3
MexicoIllegal (analog/blanket ban)Ley General de Salud, artículo 245, fracción II; artículo 25016
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.
New ZealandIllegal
SingaporeIllegalLisdexamfetamine 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.
Prescription14
United StatesPrescription only
AustraliaPrescription onlyTherapeutic Goods (Poisons Standard—June 2026) Instrument 2026, Schedule 87
Controlled drug requiring a prescription. Schedule 8 substances are drugs of addiction that require strict controls on manufacture, supply, distribution, and possession.
AustriaPrescription onlyRezeptpflichtverordnung, Anlage A, Teil 2 (Humanarzneimittel)8
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 onlyGovernment Regulation No. 463/2013 Coll., on Lists of Addictive Substances; Act No. 167/1998 Coll., on Addictive Substances1112
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 onlyHPRA authorised-medicines record for Tyvense 20 mg capsules15
Tyvense, containing lisdexamfetamine dimesylate, is an authorised Irish medicinal product. The HPRA record classifies it as a product subject to medical prescription.
NorwayPrescription onlyForskrift om narkotika (narkotikaforskriften) §§ 4–5 and Narkotikalisten; legemiddelloven §§ 23–241920
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.
PortugalPrescription onlyINFARMED public assessment report for Elvanse21
Elvanse, containing lisdexamfetamine dimesylate, is assessed by INFARMED as a medicinal product. It is supplied through Portugal's prescription-medicine system.
South KoreaPrescription onlyLisdexamfetamine 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 onlyLäkemedelsverkets föreskrifter (LVFS 2011:10) om förteckningar över narkotika, Förteckning II; lag (1992:860) om kontroll av narkotika3132
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 onlyMisuse of Drugs Act 1971, Schedule 2, Part II; Misuse of Drugs Regulations 2001, Schedule 23536373839
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.
References
Source Pages
Citations
- Vyvanse- lisdexamfetamine dimesylate capsule; Vyvanse- lisdexamfetamine dimesylate tablet, chewable. DailyMed (10 March 2022). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=704e4378-ca83-445c-8b45-3cfa51c1ecad1234567
- David W Goodman. (May 2010). Lisdexamfetamine dimesylate (vyvanse), a prodrug stimulant for attention-deficit/hyperactivity disorder. P & T, 35(5), 273–287. https://pubmed.ncbi.nlm.nih.gov/20514273/12
- Takeda Completes Acquisition of Shire, Becoming a Global, Values-based, R&D-Driven Biopharmaceutical Leader. Takeda Pharmaceutical Company (2019-01-08). https://www.takeda.com/newsroom/newsreleases/2019/takeda-completes-acquisition-of-shire-becoming-a-global-values-based-rd-driven-biopharmaceutical-leader/1
- FDA approves first and only stimulant prodrug VYVANSE as a novel ADHD treatment. EurekAlert! (Shire/New River Pharmaceuticals press release) (2007-02-23). https://www.eurekalert.org/news-releases/6498011
- Vyvanse (lisdexamfetamine dimesylate) Capsules CII Becomes First and Only Treatment Approved by the FDA for Adults with Moderate to Severe Binge Eating Disorder. PR Newswire (Shire press release) (2015-01-30). https://www.prnewswire.com/news-releases/vyvanse-lisdexamfetamine-dimesylate-capsules-cii-becomes-first-and-only-treatment-approved-by-the-fda-for-adults-with-moderate-to-severe-binge-eating-disorder-290381781.html1
- Lisdexamfetamine Drug Usage Statistics, United States, 2014 - 2023. ClinCalc (n.d.). https://clincalc.com/DrugStats/Drugs/Lisdexamfetamine12
- Therapeutic Goods (Poisons Standard—June 2026) Instrument 2026, Schedule 8. legislation.gov.au (n.d.). https://www.legislation.gov.au/F2026L00633/latest/text1
- Rezeptpflichtverordnung, Anlage A, Teil 2 (Humanarzneimittel). ris.bka.gv.at (n.d.). https://www.ris.bka.gv.at/GeltendeFassung.wxe?Abfrage=Bundesnormen&Gesetzesnummer=100103581
- Controlled Drugs and Substances Act, Schedule I. laws-lois.justice.gc.ca (n.d.). https://laws-lois.justice.gc.ca/eng/acts/C-38.8/section-sched96974.html1
- VYVANSE (Lisdexamfetamine Dimesylate) – Drug Product Database. Health Canada (2021-04-19). https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=808431
Further Reading
Article Status
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Josie Kins · Updated the article · also 1,4-Butanediol, 1B-LSD, 1cP-AL-LAD and 573 more
Josie Kins · Updated the article · also 1,4-Butanediol, 1B-LSD, 1cP-AL-LAD and 573 more
Josie Kins · Updated the article · also 1,4-Butanediol, 1B-LSD, 1cP-AL-LAD and 573 more
Josie Kins · Updated the article · also 1,4-Butanediol, 1B-LSD, 1cP-AL-LAD and 573 more
Josie Kins · Updated the article · also 1,4-Butanediol, 1B-LSD, 1cP-AL-LAD and 573 more
Josie Kins · Updated the article · also 1,4-Butanediol, 1B-LSD, 1cP-AL-LAD and 573 more
Josie Kins · Updated the article · also 1,4-Butanediol, 1B-LSD, 1cP-AL-LAD and 573 more
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