Lisdexamfetamine: Difference between revisions

'''Lisdexamfetamine''' (also known as '''Lisdextroamphetamine''', '''L-lysine-dextroamphetamine''', or '''lisdexamfetamine dimesylate''' ('''LDX''')<ref>http://www.sciencedirect.com/science/article/pii/S0028390814000781</ref> when under the brand names '''Vyvanse''' and '''Elvanse''') is a [[psychoactive class::stimulant]] substance of the [[chemical class::amphetamine]] class. Lisdextroamphetamine a [[prodrug]] for [[Amphetamine#Enantiomers|<small>d</small>-amphetamine]] (dexamphetamine, or dextroamphetamine) which is known to be a strong central nervous system (CNS) stimulant.  

Lisdexamfetamine is indicated and widely prescribed for the medical treatment of ADHD and moderate to severe binge-eating disorder.<ref>https://www.drugs.com/pro/vyvanse.html</ref> This means that outside of the oral route, its effects are independent of [[route of administration]]. Other routes of administration like [[insufflation]], [[Route of administration#Smoked|smoking]] or [[Route of administration#Injection|injection]] do not provide faster absorption or onset.

[[Subjective effects]] are essentially identical to that of dextroamphetamine except with a slower onset and a longer duration. These include [[stimulation]], [[focus enhancement]], [[motivation enhancement]], and [[euphoria]]. As with amphetamine, it is sometimes sold and used illicitly as a study drug as well as a recreational substance.

Despite the marketed anti-abuse design, many users report that lisdexamfetamine is capable of producing dependence and addiction like other [[euphoric]] stimulants, particularly when it is taken above the recommended dosage. For this reason, it is highly advised to use [[harm reduction practices]] if using this substance.

==History and culture==

{{historyStub}}

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 R_α. 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.

Lisdexamfetamine was developed with the goal of providing a long duration of effect that remains consistent throughout the day as well as reduced potential for abuse. The attachment of the amino acid lysine slows down the relative amount of dextroamphetamine that is released into the bloodstream (lisdexamfetamine dimesylate converts into a total 29.7% its weight in dextroamphetamine). 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.

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 <small>d</small>-amphetamine, a central nervous system stimulant. Thus lisdexamfetamine functions as an extended release version of dexamphetamine. Because <small>d</small>-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 <small>d</small>-amphetamine is enzymatically [[Rate-Limiting Step|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.

Amphetamine is a [[Agonist|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]].<ref>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/</ref><ref>Drug banks amphetamine targets | http://www.drugbank.ca/drugs/DB00182#targets</ref><ref>TA1 receptor | http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=364</ref> 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 [[Thought acceleration|cognitive]] and [[Stimulation|physical stimulation]] within the user.

<small>d</small>-amphetamine's affinity for the TAAR1 receptor is twice that of <small>l</small>-amphetamine.<ref>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3236098/</ref> As a result, <small>d</small>-amphetamine produces three to four times as much central nervous system (CNS) stimulation as <small>l</small>-amphetamine. <small>l</small>-amphetamine, on the other hand, has stronger cardiovascular and peripheral effects.

Roughly 1/3 of the weight of lisdexamfetamine dimesylate (the usual prescribed form) is dexamphetamine, 30 mg lisdexamfetamine dimesylate is equivalent to 8.9 mg of dexamfetamine.<ref>https://www.medicines.org.uk/emc/medicine/27442/SPC/</ref><ref>http://www.uacap.org/uploads/3/2/5/0/3250432/stimulant_equivalency.pdf</ref> 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.

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.

*'''[[Effect::Increased heart rate]]'''{{citation needed}}

*'''[[Effect::Pupil dilation]]''' - This effect is more prominent on the offset of the experience.

*'''[[Effect::Compulsive redosing]]''' - Due to the slow come up of lisdexamfetamine, the full effects may not be felt for up to 3 hours after consumption, causing some to redose during the come up.

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

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

* [https://erowid.org/experiences/subs/exp_Lisdexamfetamine.shtml Erowid Experience Vaults: Lisdexamfetamine]

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.

===Overdose===

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.

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 a controlled substance under Anlage III of the BtMG. It can only be prescribed on a narcotic prescription form.<ref>https://www.gesetze-im-internet.de/btmg_1981/anlage_iii.html</ref>

*'''Canada:''' Lisdexamfetamine, as well as other amphetamines, is a Schedule I drug.<ref>http://laws-lois.justice.gc.ca/eng/acts/C-38.8/page-15.html</ref>

*'''Norway:''' Lisdexamfetamine is a Class A drug under particularly strict control.<ref>http://www.felleskatalogen.no/medisin/elvanse-shire-pharmaceutical-contracts-ltd-588199</ref>

*'''Sweden:''' Lisdexamfetamine is a Class II narcotic, with strict requirements for prescription. It has been placed under "utökad övervakning" (extended surveillance).<ref name="swe">http://www.fass.se/LIF/product?userType=2&nplId=20140730000117</ref>

*'''Schengen Area:''' Lisdexamphetamine requires a special certificate while traveling within the [https://en.wikipedia.org/wiki/Schengen_Area Schengen Area], which covers most of Europe, but not the United Kingdom.<ref name="swe" />

*'''United Kingdom:''' Lisdexamfetamine is a Class B scheduled drug.{{citation needed}}

*'''United States:''' Lisdexamfetamine is a Schedule II controlled drug.{{citation needed}}

*[https://www.drugbank.ca/drugs/DB01255 Lisdexamfetamine (DrugBank)]