Lisdexamfetamine

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Summary sheet: Lisdexamfetamine
Lisdexamfetamine
Molecular structure of Lisdexamfetamine
Lisdexamfetamine.svg
Chemical Nomenclature
Common names Lisdexamfetamine, Vyvanse
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 Substituted 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
Threshold 10 - 20 mg
Light 20 - 40 mg
Common 40 - 60 mg
Strong 60 - 100 mg
Heavy 100 mg +
Duration
Total 10 - 14 hours
Onset 60 - 90 minutes (delayed by up to 1 hour when taken with a high fat meal)
Peak 4 - 6 hours
Offset 6 - 12 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.

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.

Lisdexamfetamine is a prodrug for the enantiopure d-isomer form of amphetamine (dextroamphetamine), which is known to be a strong central nervous system (CNS) stimulant. It is indicated and widely prescribed for the medical treatment of ADHD and moderate to severe binge-eating disorder.[1] 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 or onset.

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 prosocial effects 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

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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 bloodstream. 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 lisdexamfetamine 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.[2]

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.[3][4][5] 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.[6] 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 lisdexamfetamine is dexamphetamine, such that a dose of 70mg lisdexamfetamine is equivalent to 21mg dexamfetamine.[7][8] 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.

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. The listed effects should be taken with a grain of salt and will rarely (if ever) occur all at once, but heavier doses will increase the chances and are more likely to induce a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include injury or death.

Physical effects
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Cognitive effects
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After effects
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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 combined 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. Lisdexamfetamine 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.

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 lisdexamfetamine 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

Although many psychoactive substances are safe on their own, they can become dangerous and even life-threatening when combined with other substances. The list below contains some common potentially dangerous combinations, but may not include all of them. Certain combinations may be safe in low doses of each but still increase the potential risk of death. Independent research should always be done to ensure that a combination of two or more substances is safe before consumption.

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.[citation needed]
  • Germany: Lisdexamfetamine is scheduled in Anlage III.[11]
  • Canada: Lisdexamfetamine is a Schedule I drug.[citation needed]
  • Norway: Lisdexamfetamine is a Class A drug under particularly strict control.[12]
  • Sweden: Lisdexamfetamine is a Class II narcotic, with strict requirements for prescription. It has been placed under "utökad övervåkande" (extended surveillance).[13]
  • Schengen Area: Lisdexamphetamine requires a special certificate while traveling within the Schengen Area, which covers most of Europe, but not the United Kingdom.[13]
  • United Kingdom: Lisdexamfetamine is a Class B scheduled drug.[citation needed]
  • United States: Lisdexamfetamine is a Schedule II controlled drug.[citation needed]

External links

See also

References

  1. https://www.drugs.com/pro/vyvanse.html
  2. http://www.sciencedirect.com/science/article/pii/S0028390814000781
  3. 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/
  4. Drug banks amphetamine targets | http://www.drugbank.ca/drugs/DB00182#targets
  5. TA1 receptor | http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=364
  6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3236098/
  7. https://www.medicines.org.uk/emc/medicine/27442/SPC/Elvanse+30mg,+50mg+%26+70mg+Capsules,+hard/
  8. http://www.uacap.org/uploads/3/2/5/0/3250432/stimulant_equivalency.pdf
  9. Adderall Prescription info | http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021303s026lbl.pdf
  10. Gillman, P. K. (2005). Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. British Journal of Anaesthesia, 95(4), 434-441. https://doi.org/10.1093/bja/aei210
  11. https://en.wikipedia.org/wiki/Drugs_controlled_by_the_German_Bet%C3%A4ubungsmittelgesetz#Anlage_III
  12. http://www.felleskatalogen.no/medisin/elvanse-shire-pharmaceutical-contracts-ltd-588199
  13. 13.0 13.1 http://www.fass.se/LIF/product?userType=2&nplId=20140730000117