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Lisdexamfetamine

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Summary sheet: Lisdexamfetamine
Lisdexamfetamine
Chemical Nomenclature
Common names Lisdexamfetamine, Vyvanse, Elvanse
Substitutive name L-lysine-dextroamphetamine
Systematic name (2S)-2,6-Diamino-N-[(2S)-1-phenylpropan-2-yl]hexanamide
Class Membership
Psychoactive class Stimulant
Chemical class Amphetamine
Routes of Administration

WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.



⇣ Oral
Dosage
Bioavailability >96.4%[1]
Threshold 10 mg
Light 20 - 30 mg
Common 30 - 60 mg
Strong 60 - 90 mg
Heavy 90 mg +
Duration
Total 10 - 14 hours
Onset 60 - 90 minutes
Come up 30 - 60 minutes
Peak 3 - 5 hours
Offset 4 - 6 hours
After effects 2 - 6 hours









DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.

Interactions
Alcohol
GHB
GBL
Opioids
Cannabis
Caffeine
Ketamine
Methoxetamine
Psychedelics
Cocaine
DXM
PCP
25x-NBOMe
2C-T-x
5-MeO-xxT
DOx
Tramadol
aMT
MAOIs


Lisdexamfetamine (also known as Lisdextroamphetamine, L-lysine-dextroamphetamine and sold under the brand names Vyvanse, and Elvanse) is a widely prescribed synthetic stimulant pharmaceutical drug of the amphetamine chemical class that produces long-lived, classical amphetamine-type stimulating, focus enhancing, and euphoric effects when administered. It is a prodrug for the enantiopure d-isomer form of amphetamine (i.e. dextroamphetamine) which is known to be a strong central nervous system (CNS) stimulant. Its chemical structure consists of dextroamphetamine coupled with the essential amino acid L-lysine.

Lisdexamfetamine is indicated and widely prescribed for the medical treatment of ADHD and moderate to severe binge-eating disorder.[2] It was designed to act as a less abusable, slow-release analog of dextroamphetamine as it is inactive prior to its absorption and the subsequent rate-limited enzymatic cleavage of the molecule's L-lysine portion upon oral ingestion, meaning it cannot be crushed up and insufflated in the manner that traditional pharmaceutical amphetamines (e.g. "Adderall" or "Dexedrine") are able to be. This means that outside of the oral route, its effects are independent of route of administration. Other routes of administration like insufflation, smoking or injection do not provide faster absorption.

Unlike other amphetamine formulations such as racemic street "speed" or Adderall, lisdexamfetamine, once it is converted into its active form, is pure dextroamphetamine. Dextroamphetamine is known to produce stronger central and weaker peripheral nervous system effects relative to its opposite enantiomer, levoamphetamine. For this reason, it is commonly used both illicitly as a study drug and for recreational purposes due to the euphoria and prosociability it can produce at higher doses. Despite the marketed anti-abuse design of the drug, lisdexamfetamine is commonly reported to be capable of producing dependence and addiction like other euphoria-producing stimulants, particularly when it is taken above the recommended dosage. For this reason, it is highly advised to use harm reduction practices if choosing to use this drug.

History and culture

This History and culture section is a stub.

As a result, it may contain incomplete or wrong information. You can help by expanding it.

Chemistry

Lisdexamphetamine consists of the dextro-rotary stereoisomer of amphetamine bonded to the essential amino acid L-Lysine. Amphetamine is comprised of a phenethylamine core featuring a phenyl ring bound to an amino (NH2) group through an ethyl chain with an additional methyl substitution at Rα. It can be referred to as a methyl homologue of phenethylamine as it has the same general formula, differing only in the addition of one methyl group.

Pharmacology

Lisdexamfetamine was developed with the goal of providing a long duration of effect that is consistent throughout the day, with reduced potential for abuse. The attachment of the amino acid lysine slows down the relative amount of dextroamphetamine that is released into the blood stream. Because no free dextroamphetamine is present in lisdexamfetamine capsules, dextroamphetamine does not become available through mechanical manipulation, such as crushing or simple extraction. There is, therefore, no way to speed up absorption via alternate routes of administration, such as via insufflation, vaporization, or injection, making the drug theoretically less abusable.

A relatively sophisticated biochemical process is needed to produce dextroamphetamine from lisdexamfetamine. While amphetamine sulphate contains 50% L-amphetamine, and the ADHD medication Adderall contains a mix of four amphetamine salts totaling 75% D-amphetamine and 25% L-amphetamine, lisdexamfetamine is a single enantiomer formulation, and a prodrug to one of the least common forms of pharmaceutical amphetamines, dextroamphetamine (trade-name "Dexedrine" among many others).

Pharmacokinetics

As a prodrug, lisdexamfetamine is inactive in the form administered. Once ingested, it is enzymatically cleaved into two parts: L-lysine, a naturally occurring essential amino acid, and D-amphetamine, a central nervous system stimulant. Thus lisdexamfetamine functions as an extended release version of dexamphetamine. Because D-amphetamine needs to be liberated from lysine via contact with red blood cells, effects are independent of route of administration. Conversion of lisdexamphetamine into active D-amphetamine is enzymatically rate-limited, slowing down the time to achieve peak concentrations and decreasing its magnitude and dampening consequent striatal dopamine release, which is thought to be responsible for its euphoric and compulsive redosing effects.[3]

Pharmacodymanics

Amphetamine is a full agonist of the trace amine-associated receptor 1 (TAAR1), which is a key regulator of common and trace brain monoamines such as dopamine, serotonin and noradrenaline.[4][5][6] The agonism of this set of receptors results in the release of increased concentrations of dopamine, serotonin and noradrenaline in the synaptic cleft. This leads to cognitive and physical stimulation within the user.

D-amphetamine's affinity for the TAAR1 receptor is twice that of L-amphetamine.[7] As a result, D-amphetamine produces three to four times as much central nervous system (CNS) stimulation as L-amphetamine. L-amphetamine, on the other hand, has stronger cardiovascular and peripheral effects.

Conversion rate

Roughly 1/3 of the mass of lisdexamphetamine is dexamphetamine, such that a dose of 70mg lisdexamphetamine is equivalent to 21mg dexamfetamine.[8][9] The subjective experience will differ due to the slower, more steady release of active substance in the prodrug. An equivalent dose of dexamphetamine will have a higher peak plasma concentration and shorter duration.

Subjective effects

While the subjective effects are almost identical to that of amphetamine, lisdexamfetamine is significantly longer in its duration and more consistent in its intensity due to the slow release metabolism. Although this drug is rate-limited in its metabolism, sufficiently high doses are comparable to its instant release counterparts once the peak has been reached.

Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWiki contributors. As a result, they should be viewed with a healthy degree of skepticism.

It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.

Physical effects

Peripheral effects (such as increased heart rate and higher body temperature) are less intense than formulations that partly contain L-amphetamine, such as Adderall or the racemic amphetamine sulphate sold illicitly.

Cognitive effects

Lisdexamfetamine shares most of its cognitive effects with other amphetamines, although it is less forceful in its come up due to the slow release mechanism. It produces a variety of cognitive enhancements associated with stimulants. However, during the latter part of the duration, these cognitive enhancements may compete with or be nullified by the accumulated dopamine depletion and its effects.

The most prominent of these cognitive effects generally include:

Visual effects

After effects

The effects which occur during the offset of a stimulant experience generally feel negative and uncomfortable in comparison to the effects which occurred during its peak. This is often referred to as a "comedown" and occurs because of neurotransmitter depletion. Its effects commonly include:

Making sure to eat and drink, as well as the use of mild sedatives are common strategies for dealing with stimulant comedowns.

Experience reports

There are currently no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:

Toxicity and Harm Potential

In rodents and primates, sufficiently high doses of amphetamine cause dopaminergic neurotoxicity, or damage to dopamine neurons, which is characterized by reduced transporter and receptor function. There is no evidence that amphetamine is directly neurotoxic in humans. However, large doses of amphetamine may cause indirect neurotoxicity as a result of increased oxidative stress from reactive oxygen species and autoxidation of dopamine.

A severe amphetamine overdose can result in a stimulant psychosis that may involve a variety of symptoms, such as paranoia, delusions, and hallucinations, including the infamous Shadow people. A Cochrane Collaboration review on treatment for amphetamine, dextroamphetamine, and methamphetamine psychosis states that about 5–15% of users fail to recover completely. According to the same review, there is at least one trial that shows antipsychotic medications effectively resolve the symptoms of acute amphetamine psychosis. Psychosis very rarely arises from therapeutic use. The combination of prolonged use of high doses with sleep deprivation significantly increases the risk of stimulant psychosis.

It is strongly recommended that one use harm reduction practices when using this drug.

Tolerance and addiction potential

Addiction is a serious risk with heavy recreational amphetamine use but is unlikely to arise from typical long-term medical use at therapeutic doses. Lisdexamphetamine has been posited to have less potential for abuse and addiction than other pharmaceutical amphetamines due to the slower onset and the self-limiting metabolism, which puts a cap on the maximum peak plasma concentration and consequent dopamine release. Caution is nonetheless advised, as with other drugs in the amphetamine class.

Drug tolerance develops rapidly in amphetamine abuse (i.e., a recreational amphetamine overdose), so periods of extended use require increasingly larger doses of the drug in order to achieve the same effect. Repeated use of lisdexamfetmine will result in a gradual tolerance proportional to the dosage taken. Patients prescribed this drug often must increase their dosage after a time to maintain its efficacy.

Dangerous interactions

Warning: Many psychoactive substances that are reasonably safe to use on their own can suddenly become dangerous and even life-threatening when combined with certain other substances. The following list provides some known dangerous interactions (although it is not guaranteed to include all of them).

Always conduct independent research (e.g. Google, DuckDuckGo, PubMed) to ensure that a combination of two or more substances is safe to consume. Some of the listed interactions have been sourced from TripSit.

  • Stimulants - Amphetamine can be potentially dangerous in combination with other stimulants as it can increase one's heart rate and blood pressure to dangerous levels.
  • Tricyclic antidepressants - Amphetamine may increase the effects of tricyclic antidepressants to dangerous levels.[10]
  • "[[DangerousInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] & "[[DangerousInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - 25x compounds are highly stimulating and physically straining. Combinations with Lisdexamfetamine should be strictly avoided due to the risk of excessive stimulation and heart strain. This can result in increased blood pressure, vasoconstriction, panic attacks, thought loops, seizures, and heart failure in extreme cases.
  • "[[UncertainInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Combining alcohol with stimulants can be dangerous due to the risk of accidental over-intoxication. Stimulants mask alcohol's depressant effects, which is what most people use to assess their degree of intoxication. Once the stimulant wears off, the depressant effects will be left unopposed, which can result in blackouts and severe respiratory depression. If mixing, the user should strictly limit themselves to only drinking a certain amount of alcohol per hour.
  • "[[UnsafeInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Combinations with DXM should be avoided due to its inhibiting effects on serotonin and norepinephrine reuptake. There is an increased risk of panic attacks and hypertensive crisis, or serotonin syndrome with serotonin releasers (MDMA, methylone, mephedrone, etc.). Monitor blood pressure carefully and avoid strenuous physical activity.
  • "[[UnsafeInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Any neurotoxic effects of MDMA are likely to be increased when other stimulants are present. There is also a risk of excessive blood pressure and heart strain (cardiotoxicity).
  • "[[UncertainInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Some reports suggest combinations with MXE may dangerously increase blood pressure and increase the risk of mania and psychosis.
  • "[[UncertainInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Both classes carry a risk of delusions, mania and psychosis, and these risk may be multiplied when combined.
  • "[[UnsafeInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Lisdexamfetamine may be dangerous to combine with other stimulants like cocaine as they can increase one's heart rate and blood pressure to dangerous levels.
  • "[[DangerousInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Tramadol is known to lower the seizure threshold[11] and combinations with stimulants may further increase this risk.
  • MDMA - The neurotoxic effects of MDMA may be increased when combined with amphetamines.
  • "[[DangerousInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - This combination may increase the amount of neurotransmitters such as dopamine to dangerous or even fatal levels. Examples include syrian rue, banisteriopsis caapi, and some antidepressants.[12]
  • Cocaine - This combination may increase strain on the heart.

Legality

Lisdexamphetamine is approved for medical use with a doctor's prescription, but in most countries it is illegal to sell or possess without a prescription.[citation needed]

  • Australia: It is a Schedule 8 drug.
  • Germany: Lisdexamphetamine is scheduled in Anlage III.[13]
  • Canada: Lisdexamphetamine is a Schedule I drug.
  • Norway: Elvanse is a Class A drug under particularly strict control.[14]
  • Sweden: Elvanse is a Class II narcotic, with strict requirements for prescription. It has been placed under "utökad övervåkande" (extended surveillance).[15]
  • Schengen Area: Lisdexamphetamine requires a special certificate while traveling within the Schengen Area, which covers most of Europe, but not the United Kingdom.[15]
  • United Kingdom: Lisdexamphetamine is a Class B scheduled drug.
  • United States: It is a Schedule II controlled drug.


See also

References

  1. ↑ https://web.archive.org/web/20140826115717/http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con261790.pdf
  2. ↑ https://www.drugs.com/pro/vyvanse.html
  3. ↑ http://www.sciencedirect.com/science/article/pii/S0028390814000781
  4. ↑ The Emerging Role of Trace Amine Associated Receptor 1 in the Functional Regulation of Monoamine Transporters and Dopaminergic Activity (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005101/
  5. ↑ Drug banks amphetamine targets | http://www.drugbank.ca/drugs/DB00182#targets
  6. ↑ TA1 receptor | http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=364
  7. ↑ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3236098/
  8. ↑ https://www.medicines.org.uk/emc/medicine/27442/SPC/Elvanse+30mg,+50mg+%26+70mg+Capsules,+hard/
  9. ↑ http://www.uacap.org/uploads/3/2/5/0/3250432/stimulant_equivalency.pdf
  10. ↑ Adderall Prescription info | http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021303s026lbl.pdf
  11. ↑ Talaie, H.; Panahandeh, R.; Fayaznouri, M. R.; Asadi, Z.; Abdollahi, M. (2009). "Dose-independent occurrence of seizure with tramadol". Journal of Medical Toxicology. 5 (2): 63–67. doi:10.1007/BF03161089. eISSN 1937-6995. ISSN 1556-9039. OCLC 163567183. 
  12. ↑ Gillman, P. K. (2005). "Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity". British Journal of Anaesthesia. 95 (4): 434–441. doi:10.1093/bja/aei210 Freely accessible. eISSN 1471-6771. ISSN 0007-0912. OCLC 01537271. PMID 16051647. 
  13. ↑ https://en.wikipedia.org/wiki/Drugs_controlled_by_the_German_Bet%C3%A4ubungsmittelgesetz#Anlage_III
  14. ↑ http://www.felleskatalogen.no/medisin/elvanse-shire-pharmaceutical-contracts-ltd-588199
  15. ↑ 15.0 15.1 http://www.fass.se/LIF/product?userType=2&nplId=20140730000117


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