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'''Lisdexamfetamine''' (also known as '''lisdextroamphetamine''', '''L-lysine-dextroamphetamine''', or '''lisdexamfetamine dimesylate''' when under the brand names '''Elvanse''', '''Tyvense''', and '''Vyvanse''') is a [[psychoactive class::stimulant]] substance of the [[chemical class::amphetamine]] class. It is a "mutual [[prodrug]]" ([https://en.wikipedia.org/wiki/Codrug codrug]) for [[Amphetamine#Enantiomers|<small>d</small>-amphetamine]] (dextroamphetamine) that is approved for the treatment of attention deficit hyperactivity disorder (ADHD) and moderate to severe binge-eating disorder.<ref>https://www.drugs.com/pro/vyvanse.html</ref> Like amphetamine, lisdexamfetamine produces its effects by promoting the release of [[neurotransmitters]] [[dopamine]] and [[norepinephrine]] in the brain.
'''Lisdexamfetamine''' (also known as '''Lisdextroamphetamine''', '''L-lysine-dextroamphetamine''' and sold under the brand names '''Vyvanse''' and '''Elvanse''') is a widely-prescribed synthetic [[psychoactive class::stimulant]] pharmaceutical drug of the [[chemical class::amphetamine]] chemical class that produces long-lived, classical [[amphetamine]]-type [[stimulation|stimulating]], [[focus enhancement|focus enhancing]], and [[euphoric]] effects when [[Routes of administration|administered]].
[[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]], [[euphoria]], as well as paradoxical sedation in a small percentage of the population. However, unlike dextroamphetamine, lisdexamfetamine was specifically designed to prevent non-oral forms of administration (marketed as an anti-abuse design). This means that [[insufflation]], [[Route of administration#Smoked|smoking]] or [[Route of administration#Injection|injection]] do not provide faster absorption or onset. It is sometimes sold and used illicitly as a "study drug" as well as a recreational substance.
Lisdexamfetamine is a [[prodrug]] for the [[Enantiomer#Enantiopure|enantiopure]] d-isomer form of [[amphetamine]] (''dextro''amphetamine), 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.<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.
Despite the marketed anti-abuse design, lisdexamfetamine is capable of producing dependence and addiction like other [[euphoric]] stimulants, particularly when it is taken above the recommended dosage. As a result, it is highly advised to use [[harm reduction practices]] if using this substance.
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 drug use|recreational purposes]] due to the [[euphoria]] and prosocial effects it can produce at higher doses.
==History and culture==
{{historyStub}}
Despite the marketed anti-abuse design of the drug, lisdexamfetamine is commonly reported to be capable of producing dependence and addiction like other [[euphoria|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.
Lisdexamfetamine was developed by New River Pharmaceuticals as a longer-lasting and abuse-resistant version of [[Amphetamine#Enantiomers|<small>d</small>-amphetamine]] (dextroamphetamine). <ref name="CNS Spectrums">{{cite journal | vauthors = Mattingly G | title = Lisdexamfetamine dimesylate: a prodrug stimulant for the treatment of ADHD in children and adults | journal = CNS Spectrums | volume = 15 | issue = 5 | pages = 315–325 | date = May 2010 | pmid = 20448522 | doi = 10.1017/S1092852900027541 | s2cid = 46435024 | url = https://digitalcommons.wustl.edu/open_access_pubs/3506 }}</ref>
==History and culture==
The FDA approved lisdexamfetamine for ADHD treatment in adults on the 23th of April 2008 <ref name="FDAAdultApproval">{{Cite web|url=http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2008/021977s001ltr.pdf|title=FDA Adult Approval of Vyvanse – FDA Label and Approval History|website=Accessdate.fda.gov|access-date=12 March 2022}}</ref>, followed by an approval for use in treating binge eating disorder in adults in January 2015. <ref>{{cite press release | title=FDA expands uses of Vyvanse to treat binge-eating disorder | website=U.S. [[Food and Drug Administration]] (FDA) | date=30 January 2015 | url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm432543.htm | archive-url=https://web.archive.org/web/20180126103215/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm432543.htm | archive-date=26 January 2018 | url-status=dead | access-date=19 March 2023}}</ref>
{{historyStub}}
==Chemistry==
==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 (NH<sub>2</sub>) group through an ethyl chain with an additional methyl substitution at R<sub>α</sub>. 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.
Lisdexamphetamine is a [https://en.wikipedia.org/wiki/Codrug codrug] composed of the amino acid <small>L</small>-lysine, covalently bonded to dextroamphetamine.<ref name="pmid17407369">{{cite journal | vauthors = Blick SK, Keating GM | title = Lisdexamfetamine | journal = Paediatric Drugs | volume = 9 | issue = 2 | pages = 129–135; discussion 136–138 | date = 2007 | pmid = 17407369 | doi = 10.2165/00148581-200709020-00007 | url = }}</ref> Amphetamine is comprised of a [[phenethylamine]] core featuring a phenyl ring bound to an amino (NH<sub>2</sub>) group through an ethyl chain with an additional methyl substitution at R<sub>α</sub>. 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==
==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.
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. 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===
===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-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.<ref>http://www.sciencedirect.com/science/article/pii/S0028390814000781</ref>
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 the euphoric and [[compulsive redosing]] effects of stimulants.
===Pharmacodymanics===
===Pharmacodymanics===
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.
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>{{cite journal | vauthors=((Miller, G. M.)) | journal=Journal of neurochemistry | title=The Emerging Role of Trace Amine Associated Receptor 1 in the Functional Regulation of Monoamine Transporters and Dopaminergic Activity | volume=116 | issue=2 | pages=164–176 | date= January 2011 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005101/ | issn=0022-3042 | doi=10.1111/j.1471-4159.2010.07109.x}}</ref><ref>{{Citation |title=Drug banks amphetamine targets |url=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.
D-amphetamine's affinity for the TAAR1 receptor is twice that of L-amphetamine.<ref>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3236098/</ref> 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.
<small>d</small>-amphetamine's affinity for the TAAR1 receptor is twice that of <small>l</small>-amphetamine.<ref>{{cite journal | vauthors=((Lewin, A. H.)), ((Miller, G. M.)), ((Gilmour, B.)) | journal=Bioorganic & medicinal chemistry | title=Trace amine-associated receptor 1 is a stereoselective binding site for compounds in the amphetamine class | volume=19 | issue=23 | pages=7044–7048 | date=1 December 2011 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3236098/ | issn=0968-0896 | doi=10.1016/j.bmc.2011.10.007}}</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.
===Conversion rate===
===Conversion rate===
Roughly 1/3 of the mass of lisdexamfetamine is dexamphetamine, such that a dose of 70mg lisdexamfetamine is equivalent to 21mg dexamfetamine.<ref>https://www.medicines.org.uk/emc/medicine/27442/SPC/Elvanse+30mg,+50mg+%26+70mg+Capsules,+hard/</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.
29.7% 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>{{Citation | title=Elvanse 20mg, 30mg, 40mg, 50mg, 60mg & 70mg Capsules, hard - Summary of Product Characteristics (SmPC) - (emc) | url=https://www.medicines.org.uk/emc/medicine/27442/SPC/}}</ref><ref>[https://39f93cda-b262-4d28-a694-bf36a6802943.filesusr.com/ugd/1da6d0_55267f5b04204cb58bcc848398c0286f.pdf Stimulant Equivalency Table]</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.
==Subjective effects==
==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.
While the subjective effects are essential identical to that of dextroamphetamine, and thus [[amphetamine]], lisdexamfetamine is significantly longer in duration and more consistent in intensity due to its slow release. 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.
Peripheral effects (such as increased heart rate and higher body temperature) are reported to be less prominent than formulations that partly contain <small>l</small>-amphetamine, such as Adderall or the [[racemic]] amphetamine sulphate sold illicitly.
{{Preamble/SubjectiveEffects}}
{{Preamble/SubjectiveEffects}}
{{effects/base
{{effects/base
|{{effects/physical|
|{{effects/physical|
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.
*'''[[Effect::Spontaneous physical sensations]]''' - The "body high" of lisdexamfetamine can be described as a moderate euphoric tingling sensation that encompasses the entire body, radiating from the core. This sensation maintains a consistent presence that steadily rises with the onset and hits its limit once the peak has been reached.
*'''[[Effect::Stimulation]]''' - Lisdexamfetamine is reported to be very energetic and stimulating in a manner similar to [[amphetamine]]. It can encourage physical activities such as dancing, socializing, running, or cleaning. The particular style of stimulation which lisdexamfetamine produces can be described as forced. This means that, at higher dosages, it becomes difficult or impossible to keep still as jaw clenching, involuntary bodily shakes and vibrations become present, resulting in extreme shaking of the entire body, unsteadiness of the hands, and a general loss of fine motor control. This effect is replaced with mild fatigue and general exhaustion during the offset of the experience.
*'''[[Effect::Physical euphoria]]'''
*'''[[Effect::Spontaneous bodily sensations]]''' - The "body high" of lisdexamphetamine can be described as a moderate euphoric tingling sensation that encompasses the entire body. This sensation maintains a consistent presence that steadily rises with the onset and hits its limit once the peak has been reached.
*'''[[Effect::Tactile enhancement]]''' - Feelings of enhanced tactile sensation are consistently present at mild to moderate levels proportional to dosage.
*'''[[Effect::Appetite suppression]]''' - This effect is more pronounced compared to [[amphetamine]], sometimes causing people to not eat for the entire duration of action. Lisdexamfetamine is sometimes prescribed to treat binge eating disorder due to its strong appetite suppressing effect.
The visual effects of lisdexamfetamine are usually less consistent and only mildly noticeable at higher dosages. They are somewhat comparable to the visual effects of [[deliriants]] and occur more readily in darker areas.
====Enhancements====
*'''[[Effect::Visual acuity enhancement]]'''
*'''[[Effect::Visual acuity enhancement]]'''
*'''[[Effect::Double vision]]''' - Amphetamines can cause double vision at high doses.
====Distortions====
*'''[[Effect::Visual drifting|Drifting]]''' ''([[Visual drifting#Breathing|breathing]] and [[Visual drifting#Morphing|morphing]])'' - This effect is usually subtle and only occurs at higher doses, after long periods of being awake, or when combined with [[cannabis]]. Commonly this consists of level 1-2 drifting.
*'''[[Effect::Brightness alteration]]''' - Lisdexamfetamine can make spaces seem brighter as a result of its pupil dilating effects.
====Hallucinatory states====
*'''[[Effect::Transformations]]''' - This effect occurs very rarely, and typically only when the user has taken high doses, is coming down, or has been awake for unusually long periods. They are usually very mild when they do occur.
}}
}}
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*'''[[Effect::Analysis enhancement]]'''
*'''[[Effect::Analysis enhancement]]'''
*'''[[Effect::Anxiety]]''' - This effect occurs more frequently on the offset phase of the experience.
*'''[[Effect::Creativity enhancement]]'''
*'''[[Effect::Creativity enhancement]]'''
*'''[[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. Compulsive redosing is more common if heavy doses are taken.
*'''[[Effect::Ego inflation]]'''
*'''[[Effect::Ego inflation]]'''
*'''[[Effect::Emotion suppression]]''' - This effect is more commonly reported with lisdexamfetamine, in comparison to other [[amphetamine]]s such as [[dextroamphetamine]] and [[methamphetamine]]. It is usually most intense at low and common doses.
*'''[[Effect::Focus enhancement]]'''
*'''[[Effect::Focus enhancement]]'''
*'''[[Effect::Irritability]]'''
*'''[[Effect::Irritability]]''' - This effect occurs more frequently on the offset phase of the experience.
*'''[[Effect::Immersion enhancement]]'''
*'''[[Effect::Immersion enhancement]]'''
*'''[[Effect::Increased music appreciation]]'''
*'''[[Effect::Increased music appreciation]]'''
*'''[[Effect::Memory enhancement]]'''
*'''[[Effect::Memory enhancement]]'''
*'''[[Effect::Motivation enhancement]]'''
*'''[[Effect::Motivation enhancement]]'''
*'''[[Effect::Increased libido]]''' or '''[[Effect::Decreased libido]]'''
*'''[[Effect::Novelty enhancement]]'''
*'''[[Effect::Novelty enhancement]]'''
*'''[[Effect::Increased libido]]'''
*'''[[Effect::Novelty enhancement]]'''
*'''[[Effect::Personal bias suppression]]'''
*'''[[Effect::Time distortion]]''' - This can be described as the experience of time speeding up and passing much quicker than it usually would when sober.
*'''[[Effect::Time distortion]]''' - This can be described as the experience of time speeding up and passing much quicker than it usually would when sober.
*'''[[Effect::Thought acceleration]]'''
*'''[[Effect::Thought acceleration]]'''
*'''[[Effect::Thought organization]]'''
*'''[[Effect::Thought organization]]'''
*'''[[Effect::Time distortion]]'''
*'''[[Effect::Wakefulness]]'''
*'''[[Effect::Wakefulness]]'''
*'''[[Effect::Cognitive euphoria]]'''
*'''[[Effect::Cognitive euphoria]]'''
*'''[[Effect::Depersonalization]]''' - This drug is commonly reported to induce depersonalization on the second half of the duration due to an accumulation of dopamine depletion mixed with the residual stimulation of the substance.
*'''[[Effect::Auditory hallucinations|Hallucinations]]''' - Use of lisdexamfetamine and other amphetamines, at a strong or heavy dose, can occasionally cause mild auditory hallucinations. These hallucinations most commonly occur amongst a source of white noise, such as a fan, and typically consist of quiet phantom music or voices. Lisdexamfetamine may also cause auditory hallucinations in the form of stimulant psychosis.
}}
}}
{{effects/aftereffects|
{{effects/aftereffects|
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:
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. The comedown produced by lisdexamfetamine, depending on the user, is often reported to be much less intense, or much more intense than its metabolite, [[dextroamphetamine]], due to its extended release mechanism. Its effects commonly include:
*'''[[Effect::Anxiety]]'''
*'''[[Effect::Anxiety]]'''
*'''[[Effect::Appetite suppression]]'''
*'''[[Effect::Appetite suppression]]'''
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*'''[[Effect::Wakefulness]]'''
*'''[[Effect::Wakefulness]]'''
Making sure to eat and drink, as well as the use of mild sedatives are common strategies for dealing with stimulant comedowns.
Making sure to eat well and to hydrate are recommended to decrease the severity of comedown effects. Using mild sedatives is also a common strategy for stimulant comedowns.
}}
}}
}}
}}
===Experience reports===
===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:
Anecdotal reports which describe the effects of this compound within our [[experience index]] include:
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.
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 [[responsible drug use|harm reduction practices]] when using this drug.
It is strongly recommended that one use [[responsible drug use|harm reduction practices]] when using this drug.
===Tolerance and addiction potential===
===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.
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 often require increasingly larger doses of the drug in order to achieve the same effect. Repeated use of lisdexamfetamine results 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.
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.
===Psychosis===
Using amphetamines in very high doses can result in [[stimulant psychosis]] which may include 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
===Dangerous interactions===
===Dangerous interactions===
{{DangerousInteractions/Intro}}
{{DangerousInteractions/Intro}}
*'''[[Stimulants]]''' - Amphetamine can be potentially dangerous in combination with other [[stimulant]]s as it can [[increased heart rate|increase one's heart rate]] and [[increased blood pressure|blood pressure]] to dangerous levels.
{{DangerousInteractions/Amphetamines}}
*'''[https://en.wikipedia.org/wiki/Tricyclic_antidepressant Tricyclic antidepressants]''' - Amphetamine may increase the effects of tricyclic antidepressants to dangerous levels.<ref>Adderall Prescription info | http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021303s026lbl.pdf</ref>
*'''[[MDMA]]''' - The neurotoxic effects of [[MDMA]] may be increased when combined with amphetamines.
{{DangerousInteractions/MAOI|nt=dopamine}}
*'''[[Cocaine]]''' - This combination may increase strain on the heart to dangerous levels.
==Legal status==
==Legal status==
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}}
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}}<br />
It 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" /><ref>http://www.felleskatalogen.no/medisin/elvanse-shire-pharmaceutical-contracts-ltd-588199</ref>
*'''Australia''': It is a Schedule 8 drug.{{citation needed}}
*'''Australia''': It is a Schedule 8 drug.{{citation needed}}
*'''Germany''': Lisdexamfetamine is scheduled in Anlage III.<ref>https://en.wikipedia.org/wiki/Drugs_controlled_by_the_German_Bet%C3%A4ubungsmittelgesetz#Anlage_III</ref>
*'''Canada''': Lisdexamfetamine, as well as other amphetamines, is a Schedule I drug.<ref>{{Citation | year=2022 | title=Consolidated federal laws of Canada, Controlled Drugs and Substances Act | url=https://laws-lois.justice.gc.ca/eng/acts/C-38.8/page-15.html}}</ref>
*'''Canada''': Lisdexamfetamine is a Schedule I drug.{{citation needed}}
*'''Germany''': Lisdexamfetamine is controlled under Anlage III BtMG (''Narcotics Act, Schedule III'')<ref>{{cite web|url=https://www.gesetze-im-internet.de/btmg_1981/anlage_iii.html|title=Anlage III BtMG|publisher=Bundesministerium der Justiz und für Verbraucherschutz|access-date=December 19, 2019|language=de}}</ref> as of July 17, 2013.<ref>{{cite web|url=https://www.bgbl.de/xaver/bgbl/start.xav#__bgbl__//*%5B@attr_id=%27bgbl113s2274.pdf%27%5D|title=Siebenundzwanzigste Verordnung zur Änderung betäubungsmittelrechtlicher Vorschriften|publisher=Bundesanzeiger Verlag|access-date=December 19, 2019|language=de}}</ref> It can only be prescribed on a narcotic prescription form.<ref>{{cite web|url=https://www.gesetze-im-internet.de/btmvv_1998/__8.html|title=§ 8 BtMVV|publisher=Bundesministerium der Justiz und für Verbraucherschutz|access-date=December 19, 2019|language=de}}</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>
*'''Norway''': Lisdexamfetamine is a Class A drug under particularly strict control.
*'''Sweden''': Lisdexamfetamine is a Class II narcotic, with strict requirements for prescription. It has been placed under "utökad övervåkande" (extended surveillance).<ref name="swe">http://www.fass.se/LIF/product?userType=2&nplId=20140730000117</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">{{Citation | title=Elvanse - FASS Allmänhet | url=https://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"></ref>
*'''Switzerland''': Lisdexamphetamine is a controlled substance as of October 1, 2014 specifically named under Verzeichnis A. Medicinal use is permitted.<ref>{{cite web|url=https://www.admin.ch/opc/de/classified-compilation/20101220/index.html|title=Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien|publisher=Bundeskanzlei [Federal Chancellery of Switzerland]|access-date=January 1, 2020|language=de}}</ref>
*'''United Kingdom''': Lisdexamfetamine is a Class B scheduled drug.{{citation needed}}
*'''United Kingdom''': Lisdexamfetamine is a Schedule II, Class B controlled drug.<ref>https://www.gov.uk/government/publications/controlled-drugs-list--2/list-of-most-commonly-encountered-drugs-currently-controlled-under-the-misuse-of-drugs-legislation</ref>
*'''United States''': Lisdexamfetamine is a Schedule II controlled drug.{{citation needed}}
*'''United States''': Lisdexamfetamine is a Schedule II controlled drug.<ref>{{Citation | title=21 U.S. Code § 812 - Schedules of controlled substances | url=https://www.law.cornell.edu/uscode/text/21/812#b_4}}</ref>
*[https://medlineplus.gov/druginfo/meds/a601234.html Dextroamphetamine and Amphetamine (MedicinePlus)]
==Literature==
==See also==
*Galli, A., Poulsen, N.W., Sulzer, D., & Sonders, M.S. (2005). Mechanisms of neurotransmitter release by amphetamines: a review. Progress in Neurobiology, 75 6, 406-33. https://doi.org/10.1016/j.pneurobio.2005.04.003
*[[Responsible use]]
*Berman, S. M., Kuczenski, R., McCracken, J. T., & London, E. D. (2009). Potential adverse effects of amphetamine treatment on brain and behavior: a review. Molecular Psychiatry, 14(2), 123. https://doi.org/10.1038/mp.2008.90.
WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.
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, or lisdexamfetamine dimesylate when under the brand names Elvanse, Tyvense, and Vyvanse) is a stimulant substance of the amphetamine class. It is a "mutual prodrug" (codrug) for d-amphetamine (dextroamphetamine) that is approved for the treatment of attention deficit hyperactivity disorder (ADHD) and moderate to severe binge-eating disorder.[2] Like amphetamine, lisdexamfetamine produces its effects by promoting the release of neurotransmittersdopamine and norepinephrine in the brain.
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, euphoria, as well as paradoxical sedation in a small percentage of the population. However, unlike dextroamphetamine, lisdexamfetamine was specifically designed to prevent non-oral forms of administration (marketed as an anti-abuse design). This means that insufflation, smoking or injection do not provide faster absorption or onset. It is sometimes sold and used illicitly as a "study drug" as well as a recreational substance.
Despite the marketed anti-abuse design, lisdexamfetamine is capable of producing dependence and addiction like other euphoric stimulants, particularly when it is taken above the recommended dosage. As a result, it is highly advised to use harm reduction practices if using this substance.
As a result, it may contain incomplete or wrong information. You can help by expanding it.
Lisdexamfetamine was developed by New River Pharmaceuticals as a longer-lasting and abuse-resistant version of d-amphetamine (dextroamphetamine). [3]
The FDA approved lisdexamfetamine for ADHD treatment in adults on the 23th of April 2008 [4], followed by an approval for use in treating binge eating disorder in adults in January 2015. [5]
Chemistry
Lisdexamphetamine is a codrug composed of the amino acid L-lysine, covalently bonded to dextroamphetamine.[6] 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 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. 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.
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 the euphoric and compulsive redosing effects of stimulants.
d-amphetamine's affinity for the TAAR1 receptor is twice that of l-amphetamine.[10] 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
29.7% of the weight of lisdexamfetamine dimesylate (the usual prescribed form) is dexamphetamine: 30 mg lisdexamfetamine dimesylate is equivalent to 8.9 mg of dexamfetamine.[11][12]
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 essential identical to that of dextroamphetamine, and thus amphetamine, lisdexamfetamine is significantly longer in duration and more consistent in intensity due to its slow release. 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.
Peripheral effects (such as increased heart rate and higher body temperature) are reported to be less prominent than formulations that partly contain l-amphetamine, such as Adderall or the racemic amphetamine sulphate sold illicitly.
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 PsychonautWikicontributors. 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
Stimulation - Lisdexamfetamine is reported to be very energetic and stimulating in a manner similar to amphetamine. It can encourage physical activities such as dancing, socializing, running, or cleaning. The particular style of stimulation which lisdexamfetamine produces can be described as forced. This means that, at higher dosages, it becomes difficult or impossible to keep still as jaw clenching, involuntary bodily shakes and vibrations become present, resulting in extreme shaking of the entire body, unsteadiness of the hands, and a general loss of fine motor control. This effect is replaced with mild fatigue and general exhaustion during the offset of the experience.
Spontaneous bodily sensations - The "body high" of lisdexamphetamine can be described as a moderate euphoric tingling sensation that encompasses the entire body. This sensation maintains a consistent presence that steadily rises with the onset and hits its limit once the peak has been reached.
Appetite suppression - This effect is more pronounced compared to amphetamine, sometimes causing people to not eat for the entire duration of action. Lisdexamfetamine is sometimes prescribed to treat binge eating disorder due to its strong appetite suppressing effect.
The visual effects of lisdexamfetamine are usually less consistent and only mildly noticeable at higher dosages. They are somewhat comparable to the visual effects of deliriants and occur more readily in darker areas.
Double vision - Amphetamines can cause double vision at high doses.
Distortions
Drifting(breathing and morphing) - This effect is usually subtle and only occurs at higher doses, after long periods of being awake, or when combined with cannabis. Commonly this consists of level 1-2 drifting.
Brightness alteration - Lisdexamfetamine can make spaces seem brighter as a result of its pupil dilating effects.
Hallucinatory states
Transformations - This effect occurs very rarely, and typically only when the user has taken high doses, is coming down, or has been awake for unusually long periods. They are usually very mild when they do occur.
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:
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. Compulsive redosing is more common if heavy doses are taken.
Hallucinations - Use of lisdexamfetamine and other amphetamines, at a strong or heavy dose, can occasionally cause mild auditory hallucinations. These hallucinations most commonly occur amongst a source of white noise, such as a fan, and typically consist of quiet phantom music or voices. Lisdexamfetamine may also cause auditory hallucinations in the form of stimulant psychosis.
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. The comedown produced by lisdexamfetamine, depending on the user, is often reported to be much less intense, or much more intense than its metabolite, dextroamphetamine, due to its extended release mechanism. Its effects commonly include:
Making sure to eat well and to hydrate are recommended to decrease the severity of comedown effects. Using mild sedatives is also a common strategy for stimulant comedowns.
Experience reports
Anecdotal reports which describe the effects of this compound within our experience index include:
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.
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 often require increasingly larger doses of the drug in order to achieve the same effect. Repeated use of lisdexamfetamine results 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.
Psychosis
Using amphetamines in very high doses can result in stimulant psychosis which may include 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
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.
Alcohol - Drinking alcohol on stimulants is considered risky because it reduces the sedative effects of the alcohol that the body uses to gauge drunkenness. This often leads to excessive drinking with greatly reduced inhibitions, increasing the risk of liver damage and increased dehydration. The effects of stimulants will also allow one to drink past a point where they might normally pass out, increasing the risk. If you do decide to do this then you should set a limit of how much you will drink each hour and stick to it, bearing in mind that you will feel the alcohol and the stimulant less.
GHB/GBL - Stimulants increase respiration rate allowing a higher dose of sedatives. If the stimulant wears off first then the depressant effects of the GHB/GBL may overcome the user and cause respiratory arrest.
Opioids - Stimulants increase respiration rate allowing a higher dose of opiates. If the stimulant wears off first then the opiate may overcome the patient and cause respiratory arrest.
Cocaine - The rewarding effects of cocaine are mediated by DAT inhibition, and an increase of exocytosis of dopamine through the cell membrane. Amphetamine reverses the direction of DAT and the direction vesicular transports within the cell by a pH mediated mechanism of displacement, thus excludes the regular mechanism of dopamine release through means of exocytosis because the effects Na+/K+ ATPase are inhibited. You will find cardiac effects with the combination of cocaine and amphetamine due to a SERT mediated mechanism from the subsequent activation of 5-HT2B, which is an effect of serotonin-related valvulopathy. Amphetamines generally cause hypertension in models of abuse, and this combination can increase the chances of syncope due to turbulent blood flow during valve operation. The rewarding mechanisms of cocaine are reversed by administration of amphetamine.[14][15]
Cannabis - Stimulants increase anxiety levels and the risk of thought loops and paranoia which can lead to negative experiences.
Caffeine - This combination of stimulants is generally considered unnecessary and may increase strain on the heart, as well as potentially causing anxiety and physical discomfort.
Tramadol - Tramadol and stimulants both increase the risk of seizures.
DXM - Both substances raise heart rate, in extreme cases, panic attacks caused by these substances have led to more serious heart issues.
Ketamine - Combining amphetamine and ketamine may result in psychoses that resemble schizophrenia, but not worse than the psychoses produced by either substance alone, but this is debatable. This is due to amphetamines ability to attenuated the disruption of working memory caused by ketamine. Amphetamine alone may result in grandiosity, paranoia, or somatic delusions with little to no effect on negative symptoms. Ketamine, however, will result in thought disorders, disruption of executive functioning, and delusions due to a modification of conception. These mechanisms are due to an increase of dopaminergic activity in the mesolimbic pathway caused by amphetamine due to its pharmacology effecting dopamine, and due to a disruption of dopaminergic functioning in the mesocortical pathways via NMDA antagonism effects of ketamine. Combining the two, you may expect mainly thought disorder along with positive symptoms.[16]
PCP - Increases risk of tachycardia, hypertension, and manic states.
Methoxetamine - Increases risk of tachycardia, hypertension, and manic states.
25x-NBOMe - Amphetamines and NBOMes both provide considerable stimulation that when combined they can result in tachycardia, hypertension, vasoconstriction and, in extreme cases, heart failure. The anxiogenic and focusing effects of stimulants are also not good in combination with psychedelics as they can lead to unpleasant thought loops. NBOMes are known to cause seizures and stimulants can increase this risk.
2C-T-x - Suspected of mild MAOI properties. May increase the risk of hypertensive crisis.
5-MeO-xxT - Suspected of mild MAOI properties. May increase the risk of hypertensive crisis.
DOx
aMT - aMT has MAOI properties which may interact unfavorably with amphetamines.
MAOIs - MAO-B inhibitors can increase the potency and duration of phenethylamines unpredictably. MAO-A inhibitors with amphetamine can lead to hypertensive crises.
Legal status
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]
It requires a special certificate while traveling within the Schengen Area, which covers most of Europe, but not the United Kingdom.[17][18]
Canada: Lisdexamfetamine, as well as other amphetamines, is a Schedule I drug.[19]
Germany: Lisdexamfetamine is controlled under Anlage III BtMG (Narcotics Act, Schedule III)[20] as of July 17, 2013.[21] It can only be prescribed on a narcotic prescription form.[22]
Norway: Lisdexamfetamine is a Class A drug under particularly strict control.
Sweden: Lisdexamfetamine is a Class II narcotic, with strict requirements for prescription. It has been placed under "utökad övervakning" (extended surveillance).[17]
Switzerland: Lisdexamphetamine is a controlled substance as of October 1, 2014 specifically named under Verzeichnis A. Medicinal use is permitted.[23]
United Kingdom: Lisdexamfetamine is a Schedule II, Class B controlled drug.[24]
United States: Lisdexamfetamine is a Schedule II controlled drug.[25]
Galli, A., Poulsen, N.W., Sulzer, D., & Sonders, M.S. (2005). Mechanisms of neurotransmitter release by amphetamines: a review. Progress in Neurobiology, 75 6, 406-33. https://doi.org/10.1016/j.pneurobio.2005.04.003
Berman, S. M., Kuczenski, R., McCracken, J. T., & London, E. D. (2009). Potential adverse effects of amphetamine treatment on brain and behavior: a review. Molecular Psychiatry, 14(2), 123. https://doi.org/10.1038/mp.2008.90.
