Lisdexamfetamine: Difference between revisions

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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 [[prodrug]] of [[Amphetamine#Enantiomers|d-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''', 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|d-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.

[[Subjective effects]] are essentially identical to that of dextroamphetamine except with a slower onset and a longer duration. These include [[stimulation]] ~~(in a small percent of the population paradoxal sedation)~~, [[focus enhancement]], [[motivation enhancement]], [[euphoria]], ~~and~~ in a ~~smaller~~ 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.

[[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.

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. As a result, it is highly advised to use [[harm reduction practices]] if using this 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.

==History and culture==

Lisdexamfetamine was developed by New River Pharmaceuticals as a longer-lasting and ~~less~~-~~easily abused~~ version of [[Amphetamine#Enantiomers|d-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>

Lisdexamfetamine was developed by New River Pharmaceuticals as a longer-lasting and abuse-resistant version of [[Amphetamine#Enantiomers|d-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>

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 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>

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>

==Chemistry==

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===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.

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 the euphoric and [[compulsive redosing]] effects of stimulants.

===Pharmacodymanics===

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==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 l-amphetamine, such as Adderall or the [[racemic]] amphetamine sulphate sold illicitly.

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===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 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.

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.

===~~Overdose~~===

===Psychosis===

~~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.

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===

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*'''Australia''': It is a Schedule 8 drug.{{citation needed}}

*'''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>

*'''France''': Lisdexamfetamine is scheduled as a "stupéfiant", i.e. a recognized drug of abuse, as "lisdexamphétamine". It is illegal to possess, buy, sell or manufacture.<ref>{{Citation | title=Arrêté du 22 février 1990 fixant la liste des substances classées comme stupéfiants | url=https://www.legifrance.gouv.fr/loda/id/JORFTEXT000000533085/2020-11-20/}}</ref>

*'''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.

@@ Line 1: / Line 1: @@
 {{SummarySheet}}
 {{SubstanceBox/Lisdexamfetamine}}
-'''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 [[prodrug]] of [[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''', 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.
-[[Subjective effects]] are essentially identical to that of dextroamphetamine except with a slower onset and a longer duration. These include [[stimulation]] (in a small percent of the population paradoxal sedation), [[focus enhancement]], [[motivation enhancement]], [[euphoria]], and in a smaller 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.
+[[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.
-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. As a result, it is highly advised to use [[harm reduction practices]] if using this 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.
 ==History and culture==
 {{historyStub}}
-Lisdexamfetamine was developed by New River Pharmaceuticals as a longer-lasting and less-easily abused 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>
+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>
-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 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>
+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>
 ==Chemistry==
@@ Line 21: / Line 21: @@
 ===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 <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.
+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===
@@ Line 34: / Line 34: @@
 ==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.
@@ Line 136: / Line 136: @@
 ===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 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.
+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.
-===Overdose===
+===Psychosis===
-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.
+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===
@@ Line 153: / Line 153: @@
 *'''Australia''': It is a Schedule 8 drug.{{citation needed}}
 *'''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>
-*'''France''': Lisdexamfetamine is scheduled as a "stupéfiant", i.e. a recognized drug of abuse, as "lisdexamphétamine". It is illegal to possess, buy, sell or manufacture.<ref>{{Citation | title=Arrêté du 22 février 1990 fixant la liste des substances classées comme stupéfiants  | url=https://www.legifrance.gouv.fr/loda/id/JORFTEXT000000533085/2020-11-20/}}</ref>
 *'''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.