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Revision as of 03:36, 25 October 2013 editSeppi333 (talk | contribs)Autopatrolled, Extended confirmed users, Page movers, New page reviewers, Pending changes reviewers, Template editors35,345 edits fixing drugbox values (added %s in non-linked field, changed drugbank+pubchem inputs to correct values, RM image caption+duplicates, add suppository route and wikilinked routes), rm injection route (fillers in adderall).need to validate these now← Previous edit Latest revision as of 22:31, 20 December 2024 edit undoAryore (talk | contribs)76 editsmNo edit summaryTags: Visual edit Mobile edit Mobile web edit 
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{{Short description|Drug mixture used mainly to treat ADHD and narcolepsy}}
{{Redirect|Adderall|amphetamine base|amphetamine}}
{{About|a common mixture of amphetamine salts|general information about the drug and its racemate|Amphetamine|the 2023 EP by Slipknot|Adderall (EP){{!}}''Adderall'' (EP)}}
{{Drugbox
{{Good article}}
| Verifiedfields = changed
{{Use dmy dates|date=August 2024}}
| verifiedrevid = 477242140
{{cs1 config |name-list-style=vanc |display-authors=6}}
| image = Amphetamine-2D-skeletal.svg
{{Infobox drug
| alt = an image of the amphetamine skeletal formula
| verifiedrevid = 578643702
| drug_name = ]/]<br />] mixture (1:1){{#tag:ref|] of ] and ] are mixed in a (1:1) ratio to produce this drug. Because the ] is composed of equal parts dextroamphetamine and ], this drug can also be described as a mixture of the ''D'' and ''(L)''-] of amphetamine in a (3:1) ratio, although none of the components of the mixture are levoamphetamine salts.<ref name="Amphetamine Formulations Review" /><ref name="Unique Dopamine Pharmacology" />|group=note}}
| type = combo
| image = Amfetamin.svg
| alt = an image of the amphetamine skeletal formula
| caption =
| image2 = D-Amphetamine-3D-balls.png
| alt2 = a 3d image of the dextroamphetamine compound found in Adderall
| caption2 = Top: racemic amphetamine ]<br />
Bottom: ''(D)''-amphetamine ]


<!--Combo data--> <!-- Combo data -->| component1 = amphetamine aspartate monohydrate
| class1 = 25%&nbsp;– ]<br />({{nowrap|12.5%&nbsp;{{abbr|levo|levoamphetamine}}; 12.5%&nbsp;{{abbr|dextro|dextroamphetamine}}}})
| type = combo
| component2 = amphetamine sulfate
| drug_name = Amphetamine mixed salts
| class2 = 25%&nbsp;– stimulant<br />({{nowrap|12.5% {{abbr|levo|levoamphetamine}}; 12.5% {{abbr|dextro|dextroamphetamine}}}})
| component1 = amphetamine aspartate
| component3 = dextroamphetamine saccharate
| class1 =(25%) ]
| class3 = 25%&nbsp;– stimulant<br />({{nowrap|0%&nbsp;{{abbr|levo|levoamphetamine}}; 25%&nbsp;{{abbr|dextro|dextroamphetamine}}}})
| component2 = amphetamine sulfate
| component4 = dextroamphetamine sulfate
| class2 =(25%) psychostimulant
| class4 = 25%&nbsp;– stimulant<br />({{nowrap|0%&nbsp;{{abbr|levo|levoamphetamine}}; 25%&nbsp;{{abbr|dextro|dextroamphetamine}}}})
| component3 = dextroamphetamine saccharate
| class3 =(25%) psychostimulant
| component4 = dextroamphetamine sulfate
| class4 =(25%) psychostimulant


<!--Clinical data--> <!-- Clinical data -->| tradename = Adderall, Adderall XR, Mydayis
| Drugs.com = {{drugs.com|monograph|Adderall}}
| tradename = Adderall<br>Adderall ER<br>Adderall XR
| MedlinePlus = a601234
| Drugs.com = {{drugs.com|monograph|Adderall}}
| DailyMedID = Adderall
| MedlinePlus = a601234
| pregnancy_AU =
| DailyMedID = 1362
| pregnancy_US = C | pregnancy_category =
| legal_AU = S8
| legal_US = Schedule II
| legal_CA = Schedule I
| licence_US = Adderall
| legal_DE = Anlage III
| legal_CA = Schedule I
| legal_NZ = Class B
| legal = Rx-only
| legal_UK = Class B
| dependency_liability = High
| legal_US = ]<ref name=":USAS2">{{Cite web |last=Ingersoll |first=John |date=July 7, 1971 |title=Amphetamine, Methamphetamine, and Optical Isomers |url=https://archives.federalregister.gov/issue_slice/1971/7/7/12730-12734.pdf |url-status=live |archive-url= https://archive.today/20241127164332/https://archives.federalregister.gov/issue_slice/1971/7/7/12730-12734.pdf |archive-date=November 27, 2024 |access-date=November 27, 2024 |website=]|publisher=]}}</ref>
| routes_of_administration = ], ], ], ]
| legal_UN = Psychotropic Schedule II
| legal_status =
| dependency_liability = Moderate<ref name="Vitiello2008">{{cite journal | vauthors = Vitiello B | title = Understanding the risk of using medications for attention deficit hyperactivity disorder with respect to physical growth and cardiovascular function | journal = Child and Adolescent Psychiatric Clinics of North America | volume = 17 | issue = 2 | pages = 459–74, xi | date = April 2008 | pmid = 18295156 | pmc = 2408826 | doi = 10.1016/j.chc.2007.11.010 }}</ref><ref name="GrahamGrahamBanaschewski2010">{{cite journal | vauthors = Graham J, Banaschewski T, Buitelaar J, Coghill D, Danckaerts M, Dittmann RW, Döpfner M, Hamilton R, Hollis C, Holtmann M, Hulpke-Wette M, Lecendreux M, Rosenthal E, Rothenberger A, Santosh P, Sergeant J, Simonoff E, Sonuga-Barke E, Wong IC, Zuddas A, Steinhausen HC, Taylor E | title = European guidelines on managing adverse effects of medication for ADHD | journal = European Child & Adolescent Psychiatry | volume = 20 | issue = 1 | pages = 17–37 | date = January 2011 | pmid = 21042924 | pmc = 3012210 | doi = 10.1007/s00787-010-0140-6 | eissn = 1435-165X }}</ref> – high<ref name="KociancicReedFindling2004">{{cite journal | vauthors = Kociancic T, Reed MD, Findling RL | title = Evaluation of risks associated with short- and long-term psychostimulant therapy for treatment of ADHD in children | journal = Expert Opinion on Drug Safety | volume = 3 | issue = 2 | pages = 93–100 | date = March 2004 | pmid = 15006715 | doi = 10.1517/14740338.3.2.93 | s2cid = 31114829 | eissn = 1744-764X }}</ref><ref name="ClemowWalker2014">{{cite journal | vauthors = Clemow DB, Walker DJ | title = The potential for misuse and abuse of medications in ADHD: a review | journal = Postgraduate Medicine | volume = 126 | issue = 5 | pages = 64–81 | date = September 2014 | pmid = 25295651 | doi = 10.3810/pgm.2014.09.2801 | s2cid = 207580823 | eissn = 1941-9260 }}</ref><ref name="Stahl's Essential Psychopharmacology" />
| routes_of_administration = ], ], ], ]
| bioavailability = Oral: ~90%<ref name="handbook2022" />
| ATC_prefix = N06
| ATC_suffix = BA02
| ATC_supplemental = {{ATC|N06|BA01}}
<!-- Identifiers -->| class = {{abbr|CNS|central nervous system}} ]
| CAS_number = 300-62-9
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_supplemental = {{CAS|51-64-9}}
| PubChem = 3007
| IUPHAR_ligand = 4804
| DrugBank = DB00182
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| ChemSpiderID = 13852819
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| UNII = CK833KGX7E
| UNII_Ref = {{fdacite|correct|FDA}}
| KEGG = D11624
| KEGG_Ref = {{keggcite|correct|kegg}}
| ChEBI = 2679
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 405
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| synonyms = Mixed amphetamine salts; MAS
<!-- Chemical data -->}}


'''Adderall''' and '''Mydayis'''<ref name="Mydayis Launch">{{cite news | vauthors = Sagonowsky E |title=Shire launches new ADHD drug Mydayis as it weighs a neuroscience exit |url =https://www.fiercepharma.com/marketing/shire-launches-new-adhd-drug-mydayis-as-it-weighs-a-neuroscience-exit |newspaper=Fierce Pharma |date=28 August 2017 |publisher=Questex LLC |access-date=2 May 2020 |archive-date=16 December 2019 |archive-url=https://web.archive.org/web/20191216011722/https://www.fiercepharma.com/marketing/shire-launches-new-adhd-drug-mydayis-as-it-weighs-a-neuroscience-exit |url-status=live }}</ref> are ]{{#tag:ref|The ] '''Adderall''' is used primarily throughout this article because the four-salt composition of the drug makes its nonproprietary name (dextroamphetamine sulfate 25%, dextroamphetamine saccharate 25%, amphetamine sulfate 25%, and amphetamine aspartate 25%) excessively lengthy.<ref name="NDCD">{{cite web | title = National Drug Code Amphetamine Search Results | url = http://www.accessdata.fda.gov/scripts/cder/ndc/results.cfm?beginrow=1&numberperpage=160&searchfield=amphetamine&searchtype=ActiveIngredient&OrderBy=ProprietaryName | website = National Drug Code Directory|publisher=United States Food and Drug Administration | access-date = 16 December 2013 | archive-url = https://web.archive.org/web/20131216080856/http://www.accessdata.fda.gov/scripts/cder/ndc/results.cfm?beginrow=1&numberperpage=160&searchfield=amphetamine&searchtype=ActiveIngredient&OrderBy=ProprietaryName | archive-date=16 December 2013}}</ref> '''Mydayis''' is a relatively new trade name that is not commonly used to refer generally to the mixture.<ref name="Mydayis Launch" />|name="Adderall"| group="note"}} for a ] containing four ] of ]. The mixture is composed of equal parts ] amphetamine and ], which produces a (3:1) ratio between dextroamphetamine and ], the two ] of amphetamine.<ref>{{cite journal | vauthors = Babiskin AH, Zhang X | title = Application of Physiologically Based Absorption Modeling for Amphetamine Salts Drug Products in Generic Drug Evaluation | journal = Journal of Pharmaceutical Sciences | volume = 104 | issue = 9 | pages = 3170–3182 | date = September 2015 | pmid = 25973928 | doi = 10.1002/jps.24474 }}</ref> Both enantiomers are ], but differ enough to give Adderall an ] distinct from those of racemic amphetamine or dextroamphetamine,<ref name="Amphetamine Formulations Review">{{cite journal | vauthors = Heal DJ, Smith SL, Gosden J, Nutt DJ | title = Amphetamine, past and present--a pharmacological and clinical perspective | journal = Journal of Psychopharmacology | volume = 27 | issue = 6 | pages = 479–496 | date = June 2013 | pmid = 23539642 | pmc = 3666194 | doi = 10.1177/0269881113482532 }}</ref><ref name="Unique Dopamine Pharmacology">{{cite journal | vauthors = Joyce BM, Glaser PE, Gerhardt GA | title = Adderall produces increased striatal dopamine release and a prolonged time course compared to amphetamine isomers | journal = Psychopharmacology | volume = 191 | issue = 3 | pages = 669–677 | date = April 2007 | pmid = 17031708 | doi = 10.1007/s00213-006-0550-9 | s2cid = 20283057 }}</ref> which are marketed as Evekeo and Dexedrine/Zenzedi, respectively.<ref name="Amphetamine Formulations Review" /><ref name="Arbor Evekeo Pharmacology">{{cite web |title=Pharmacology |url=https://www.evekeo.com/hcp/evekeo-pharmacology |website=Evekeo CII (amphetamine sulfate) HCP |publisher=Arbor Pharmaceuticals, LLC |access-date=2 May 2020 |archive-date=21 September 2020 |archive-url=https://web.archive.org/web/20200921152314/https://www.evekeo.com/hcp/evekeo-pharmacology |url-status=dead }}</ref><ref name="Zenzedi Arbor PI">{{cite web |title=Prescribing Information & Medication Guide |url=https://zenzedi.com/docs/PIandMedicationGuide.pdf |website=Zenzedi (dextroamphetamine sulfate, USP) |publisher=Arbor Pharmaceuticals LLC |access-date=2 May 2020 |archive-date=11 November 2020 |archive-url=https://web.archive.org/web/20201111223440/https://zenzedi.com/docs/PIandMedicationGuide.pdf |url-status=live }}</ref> Adderall is used in the treatment of ] (ADHD) and ]. It is also used illicitly as an ], ], ], and recreationally as a ]. It is a ] (CNS) ] of the ].<ref name="Amphetamine Formulations Review" />
<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 300-62-9
| CAS_supplemental = {{CAS|51-64-9}}
| ATC_prefix = N06
| ATC_suffix = BA02
| ATC_supplemental = {{ATC|N06|BA01}}
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 405
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C9H13N/c1-8(10)7-9-5-3-2-4-6-9/h2-6,8H,7,10H2,1H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = KWTSXDURSIMDCE-UHFFFAOYSA-N
| PubChem = 3007
| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
| DrugBank = DB00182
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 13852819
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D03740
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 2679


At therapeutic doses, Adderall causes emotional and cognitive effects such as ], change in ], increased ], and improved ]. At these doses, it induces physical effects such as a faster reaction time, fatigue resistance, and increased muscle strength. In contrast, much larger doses of Adderall can impair cognitive control, cause ], provoke ]s, or induce ] (e.g., ], ]s, ]s). The side effects vary widely among individuals but most commonly include ], ], ] and ]. The risk of developing an ] or ] is insignificant when Adderall is used as prescribed and at fairly low daily doses, such as those used for treating ADHD. However, the routine use of Adderall in larger and daily doses poses a significant risk of addiction or dependence due to the pronounced ] that are present at high doses. Recreational doses of Adderall are generally much larger than prescribed ]s and also carry a far greater risk of serious adverse effects.{{#tag:ref|<ref name="Libido" /><ref name="Adderall IR" /><ref name="Malenka_2009" /><ref name="Ergogenics" /><ref name="FDA" /><ref name="Cochrane" /><ref name="Stimulant Misuse" /><ref name="NHMH_3e-Addiction doses" /><ref name="Addiction risk" /><ref name="EncycOfPsychopharm">{{Cite book | vauthors = Stolerman IP | veditors = Stolerman IP | title = Encyclopedia of Psychopharmacology | year = 2010 | publisher = Springer | location = Berlin, Germany; London, England | isbn = 9783540686989 | page = 78}}</ref><ref>{{cite journal | vauthors = Howell LL, Kimmel HL | title = Monoamine transporters and psychostimulant addiction | journal = Biochemical Pharmacology | volume = 75 | issue = 1 | pages = 196–217 | date = January 2008 | pmid = 17825265 | doi = 10.1016/j.bcp.2007.08.003 }}</ref>|group="sources"}}
<!--Chemical data-->
| smiles = NC(C)Cc1ccccc1
| InChI = 1/C9H13N/c1-8(10)7-9-5-3-2-4-6-9/h2-6,8H,7,10H2,1H3
| InChIKey = KWTSXDURSIMDCE-UHFFFAOYAO
}}

'''Amphetamine mixed salts''' (also known as '''amphetamine and dextroamphetamine mixed salts''', '''amphetamine salt combo''', or simply '''amphetamine salts''', and sold under the brand name '''Adderall''') is a ] used in the treatment of ] (ADHD) and ]. The ] contained in this medication is a mixture of multiple ] of the ] ]. There is a single commercial formulation only as of 2013, which contains a 3:1 ratio of ] (the ] or "right-handed" enantiomer) to ] (the ] or "left-handed" ]<ref>Enantiomers are molecules that are "mirror images" of one another; they are structurally identical but of the opposite orientation, like left and right hands</ref>). Amphetamine mixed salts are available in immediate release and ] formulations.


The two amphetamine enantiomers that compose Adderall, such as Adderall tablets/capsules (levoamphetamine and dextroamphetamine), alleviate the symptoms of ADHD and narcolepsy by increasing the activity of the ]s ] and ] in the ], which results in part from their interactions with ] (hTAAR1) and ] (VMAT2) in ]s. Dextroamphetamine is a more potent ] ({{abbr|CNS|central nervous system}}) stimulant than levoamphetamine, but levoamphetamine has slightly stronger cardiovascular and peripheral effects and a longer ] than dextroamphetamine. The levoamphetamine component of Adderall has been reported to improve the treatment response in some individuals relative to dextroamphetamine alone. The ] in Adderall, amphetamine, shares many chemical and pharmacological properties with the human ]s, particularly ] and {{nowrap|]}}, the latter of which is a ] of amphetamine.{{#tag:ref|<ref name="Malenka_2009_03b" /><ref name="Miller" /><ref name="E Weihe" /><ref name="Trace Amines3">{{cite journal |author=Broadley KJ |title=The vascular effects of trace amines and amphetamines |journal=Pharmacology & Therapeutics |volume=125 |issue=3 |pages=363–375 |date=March 2010 |pmid=19948186 |doi=10.1016/j.pharmthera.2009.11.005 |quote=<!-- '''Fig. 2.''' Synthetic and metabolic pathways for endogenous and exogenously administered trace amines and sympathomimetic amines&nbsp;...<br /> Trace amines are metabolized in the mammalian body via monoamine oxidase (MAO; EC 1.4.3.4) (Berry, 2004) (Fig. 2)&nbsp;... It deaminates primary and secondary amines that are free in the neuronal cytoplasm but not those bound in storage vesicles of the sympathetic neurone&nbsp;...<br />Thus, MAO inhibitors potentiate the peripheral effects of indirectly acting sympathomimetic amines&nbsp;... this potentiation occurs irrespective of whether the amine is a substrate for MAO. An α-methyl group on the side chain, as in amphetamine and ephedrine, renders the amine immune to deamination so that they are not metabolized in the gut. Similarly, β-PEA would not be deaminated in the gut as it is a selective substrate for MAO-B which is not found in the gut&nbsp;...<br /> Brain levels of endogenous trace amines are several hundred-fold below those for the classical neurotransmitters noradrenaline, dopamine and serotonin but their rates of synthesis are equivalent to those of noradrenaline and dopamine and they have a very rapid turnover rate (Berry, 2004). Endogenous extracellular tissue levels of trace amines measured in the brain are in the low nanomolar range. These low concentrations arise because of their very short half-life&nbsp;... -->}}</ref><ref name="Westfall" /><ref name="TAAR1 stereoselective" /><ref name="Child Psychiatry" /><ref name="Arnold" />|group="sources"}} In 2022, Adderall was the fourteenth most commonly prescribed medication in the United States, with more than 34{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Dextroamphetamine; Dextroamphetamine Saccharate; Amphetamine; Amphetamine Aspartate Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/DextroamphetamineDextroamphetamineSaccharateAmphetamineAmphetamineAspartate | access-date = 30 August 2024 }}</ref>
{{TOC limit|3}} {{TOC limit|3}}
== Uses ==
=== Medical ===
Amphetamine mixed salts is generally used for the treatment of ] and ], the two conditions for which the United States ] has approved its use.<ref name="drugs_dot_com" /> However, it is sometimes ] for other conditions such as depression. It has been used to treat obesity, but the ] does not recommend this use.<ref name=AHFS/> Nearly 14 million monthly prescriptions for the condition were written for Americans ages 20 to 39 in 2011, two and a half times the 5.6 million just four years before, according to the data company I.M.S. Health.<ref>{{cite web | url = http://www.nytimes.com/2013/02/03/us/concerns-about-adhd-practices-and-amphetamine-addiction.html?pagewanted=all&_r=0/ | title = Drowned in a Stream of Prescriptions | author = Schwartz A | publisher = New York Times | date =2013-02-13}}</ref>


==Uses==
In non-human primates, long-term exposure to amphetamine throughout adolescence has no discernible adverse effect on their physiology, behavior, or dopamine system development.<ref name="pmid22805599">{{cite journal | author = Soto PL, Wilcox KM, Zhou Y, Kumar A, Ator NA, Riddle MA, Wong DF, Weed MR | title = Long-term exposure to oral methylphenidate or dl-amphetamine mixture in peri-adolescent rhesus monkeys: effects on physiology, behavior, and dopamine system development | journal = Neuropsychopharmacology | volume = 37 | issue = 12 | pages = 2566–79 | year = 2012 | month = November | pmid = 22805599 | doi = 10.1038/npp.2012.119 | pmc = 3473325 }}</ref><ref name="pmid23070200">{{cite journal | author = Volkow ND | title = Long-term safety of stimulant use for ADHD: findings from nonhuman primates | journal = Neuropsychopharmacology | volume = 37 | issue = 12 | pages = 2551–2 | year = 2012 | month = November | pmid = 23070200 | doi = 10.1038/npp.2012.127 | pmc = 3473329 }}</ref>
{{multiple image
<!-- Essential parameters -->
| align = right
| direction = vertical
| width = 300
<!-- Extra parameters -->
| image1=30xAdderall10mg.jpg
| caption1=30 capsules of 10&nbsp;mg Adderall XR
| alt1=30 Adderall XR 10 mg capsules
| image2=Amph salts.jpg
| caption2=A group of 20&nbsp;mg Adderall tablets, some broken in half, with a lengthwise-folded US dollar bill along the bottom (3.07&nbsp;inches; 7.8&nbsp;cm) for size comparison
| alt2=Adderall 20 mg tablets
}}


===Medical===
====Attention deficit hyperactivity disorder====
Adderall is commonly used to treat ] (ADHD) and ] (a sleep disorder).<ref name="Amph Uses">{{cite journal |vauthors=Heal DJ, Smith SL, Gosden J, Nutt DJ | title = Amphetamine, past and present – a pharmacological and clinical perspective | journal =Journal of Psychopharmacology| volume = 27 | issue = 6 | pages = 479–496 | date=June 2013 | pmid = 23539642 | pmc = 3666194 | doi = 10.1177/0269881113482532 | quote = The intravenous use of d-amphetamine and other stimulants still pose major safety risks to the individuals indulging in this practice. Some of this intravenous abuse is derived from the diversion of ampoules of d-amphetamine, which are still occasionally prescribed in the UK for the control of severe narcolepsy and other disorders of excessive sedation.&nbsp;... For these reasons, observations of dependence and abuse of prescription d-amphetamine are rare in clinical practice, and this stimulant can even be prescribed to people with a history of drug abuse provided certain controls, such as daily pick-ups of prescriptions, are put in place (Jasinski and Krishnan, 2009b).}}</ref><ref name="Adderall IR">{{cite web |title=Adderall- dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate, and amphetamine sulfate tablet |website=DailyMed |publisher=Teva Pharmaceuticals USA, Inc. |date=8 November 2019 |url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f22635fe-821d-4cde-aa12-419f8b53db81 |access-date=22 December 2019 |archive-date=2 October 2019 |archive-url=https://web.archive.org/web/20191002150413/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f22635fe-821d-4cde-aa12-419f8b53db81 |url-status=live}}</ref>


====ADHD====
The comparative effectiveness of treatment options for children with ADHD, including different amphetamine medications, has been studied by the US Agency for Health Care Research and Quality,<ref name=ADHD-AHRQ>{{cite journal | author = Charach A, Dashti B, Carson P, Booker L, Lim CG, Lillie E, Yeung E, Ma J, Raina P, Schachar R | title = Attention Deficit Hyperactivity Disorder: Effectiveness of Treatment in At-Risk Preschoolers; Long-Term Effectiveness in All Ages; and Variability in Prevalence, Diagnosis, and Treatment | journal = AHRQ Comparative Effectiveness Reviews | volume = 44 | issue = | pages = | year = 2011 | month = October | pmid = 22191110 | doi = | url = http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0033137/ | publisher = Agency for Healthcare Research and Quality }}</ref> and summarized for parents.<ref name=ADHD-AHRQ-parents>{{cite web|last=John M. Eisenberg Center for Clinical Decisions and Communications Science|title=Treatment Options for ADHD in Children and Teens: A Review of Research for Parents and Caregivers|url=http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0047798/|work=Comparative Effectiveness Review Summary Guides for Consumers|publisher=Agency for Healthcare Research and Quality|accessdate=20 June 2013|month=June|year=2012}}</ref> Amphetamines may improve ADHD in symptoms in children over the age of six, but there is not enough evidence to be sure.<ref name=ADHD-AHRQ /> Use for younger children and use for longer than a year in particular requires further study.<ref name=ADHD-AHRQ />
<!-- PLEASE NOTE: the following content is transcluded from its parent article ]. If you wish to alter content on ADHD, then go to ] and edit the source code there. After you finalise your edit, it will render here accordingly -->
{{#lsth:Amphetamine|ADHD}}


====Narcolepsy====
Amphetamine mixed salts have also been shown to reduce ADHD in adults, but research is limited.<ref name=Castells-CC>{{cite journal | author = Castells X, Ramos-Quiroga JA, Bosch R, Nogueira M, Casas M | title = Amphetamines for Attention Deficit Hyperactivity Disorder (ADHD) in adults | journal = Cochrane Database Syst Rev | volume = | issue = 6 | pages = CD007813 | year = 2011 | pmid = 21678370 | doi = 10.1002/14651858.CD007813.pub2 | url = http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0014629/ | editor1-last = Castells | editor1-first = Xavier }}</ref> According to Millchap et al., "a multicenter, placebo-controlled trial of amphetamine treatment for ADHD in Sweden found significant improvements in attention, hyperactivity, and disruptive behaviors and a mean change in IQ of +4.5 after more than 9 months of amphetamine ;" however, the authors note that the population in the study had a remarkably high incidence of comorbid disorders associated with ADHD.<ref>{{cite book | author = Millichap JG | title = Attention deficit hyperactivity disorder handbook : a physician's guide to ADHD | year = 2010 | publisher = Springer | location = New York | isbn = 978-1-4419-1396-8 | page = 122 | edition = 2nd }}</ref> Consequently, they asserted that other long-term trials of stimulants in ADHD with less comorbidity would be expected to show greater functional improvements and fewer side effects.<ref>{{cite book | author = Millichap JG | title = Attention deficit hyperactivity disorder handbook : a physician's guide to ADHD | year = 2010 | publisher = Springer | location = New York | isbn = 978-1-4419-1396-8 | page = 123 | edition = 2nd }}</ref>
<!-- PLEASE NOTE: the following content is transcluded from its parent article ]. If you wish to alter content on narcolepsy, then go to ] and edit the source code there. After you finalise your edit, it will render here accordingly -->
{{#lsth:Amphetamine|Narcolepsy}}


====Dosing and administration==== ====Available forms====
Adderall is available as ] (IR) tablets and ] (XR) capsules.<ref name="Adderall IR" /><ref name="Adderall XR all pages" /> Mydayis is only available as an extended-release formulation.<ref name="Mydayis medication">{{Cite web|url=http://pi.shirecontent.com/PI/PDFs/Mydayis_USA_ENG.pdf|title=Mydayis medication guide|website=Mydayis.com|language=en|access-date=6 February 2024|date=October 2023}}</ref> Adderall XR is approved to treat ADHD for up to 12 hours in individuals 6 years and older and uses a ]. The capsule can be swallowed like a tablet, or it can be opened and the beads sprinkled over applesauce for comparable absorption.<ref name="Adderall XR all pages" /> Upon ingestion, half of the beads provide immediate administration of medication, while the other half are enveloped in a coating that must dissolve, delaying absorption of its contents. It is designed to provide a therapeutic effect and plasma concentrations identical to taking two doses of Adderall IR four hours apart.<ref name="Adderall XR all pages" /> Mydayis uses a longer-lasting triple-bead formulation and is approved to treat ADHD for up to 16 hours in individuals 13 years and older.<ref name="Mydayis medication" /> In the United States, the immediate and extended-release formulations of Adderall are both available as ]s.<ref>{{Cite web|url=https://www.drugs.com/availability/generic-adderall.html|title=Generic Adderall Availability|website=Drugs.com|language=en|access-date=6 February 2020|archive-date=28 May 2020|archive-url=https://web.archive.org/web/20200528223452/https://www.drugs.com/availability/generic-adderall.html|url-status=live}}</ref><ref>{{Cite web|url=https://www.drugs.com/availability/generic-adderall-xr.html|title=Generic Adderall XR Availability|website=Drugs.com|language=en|access-date=6 February 2020|archive-date=6 February 2020|archive-url=https://web.archive.org/web/20200206144135/https://www.drugs.com/availability/generic-adderall-xr.html|url-status=live}}</ref> Generic formulations of Mydayis became available in the US in October 2023.<ref>{{Cite web|url=https://professionals.optumrx.com/content/dam/optum3/professional-optumrx/news/rxnews/new-generics/newgenerics_mydayis_2023-1012.pdf|title=Mydayis® (mixed-salts of a single-entity amphetamine product) – First-time generic|website=OptumRx|language=en|access-date=6 February 2023}}</ref>
Amphetamine mixed salts is available as immediate release form or extended-release form.<ref name="FDA1"/> The extended release capsule is generally used in the morning.<ref name=MMX-PMH>{{cite web|title=Amphetamine/Dextroamphetamine (by mouth)|url=http://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0008973/?report=details|work=Micromedex consumer medication information|publisher=Truven Health Analytics|accessdate=20 June 2013}}</ref> Generic forms are available in some doses.<ref name=ADHD-AHRQ-parents /> The extended release formulation available under the brand Adderall XR is designed to provide therapeutic effect and plasma concentrations identical to taking two doses 4 hours apart.<ref name="AdderallXR"/>


===Performance-enhancing=== ===Enhancing performance===
{{transcluded section|source=Amphetamine|part=yes}}
Therapeutic doses of psychostimulants, like amphetamine and ], improve performance on working memory tests both in normal functioning individuals and those with ADHD; moreover, these stimulants also act on general levels of arousal and, within the ], improve task ].<ref name="Malenka_2009" /> Thus, stimulants improve performance on effortful and tedious tasks as well.<ref name="Malenka_2009">{{cite book| author = Malenka EJ, Nestler SE, Hyman RC | title = Molecular neuropharmacology: a foundation for clinical neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York | isbn = 978-0-07-148127-4 | page = 318 | edition = 2nd | chapter = Chapter 13: Higher Cognitive Function and Behavioral Control }}</ref> Consequently, ], an amphetamine mixture, is used by some college and high-school students as a study and test-taking aid.<ref>{{cite web | publisher = JS Online | author = Twohey M | title = Pills become an addictive study aid | accessdate =2 December 2007 | date= 25 March 2006 | url = http://www.jsonline.com/story/index.aspx?id=410902 | archiveurl = http://web.archive.org/web/20070815200239/http://www.jsonline.com/story/index.aspx?id=410902 | archivedate = 15 August 2007}}</ref> In contrast, at abused (much higher) doses, stimulants can interfere with working memory and cognitive control.<ref name="Malenka_2009" />
{{trim|{{#section-h:Amphetamine|Enhancing performance}}}}


Adderall has been banned in the ] (NFL), ] (MLB), ] (NBA), and the National Collegiate Athletics Association (NCAA).<ref name="Leon">{{cite web| vauthors = Moore DL |title=Do pro sports leagues have an Adderall problem?|publisher=USA TODAY|access-date=4 May 2014|url= https://www.usatoday.com/story/sports/nfl/2012/11/27/adderall-in-pro-sports/1730431/ |archive-date=23 November 2014|archive-url= https://web.archive.org/web/20141123131934/http://www.usatoday.com/story/sports/nfl/2012/11/27/adderall-in-pro-sports/1730431/ |url-status=live}}</ref> In leagues such as the NFL, there is a very rigorous process required to obtain an exemption to this rule even when the athlete has been medically prescribed the drug by their physician.<ref name="Leon" />
In addition, amphetamine is also used by some professional, collegiate and high school athletes for its strong stimulant effects;<ref>{{Cite journal | volume = 25 | issue = 3 | pages = 434–451 | author = Yesalis CE, Bahrke M | title = Anabolic Steroid and Stimulant Use in North American Sport between 1850 and 1980 | journal = Sport in History | accessdate =2 December 2007 | date= 2005-12 | url = http://www.informaworld.com/smpp/content~content=a727721070~db=all | doi = 10.1080/17460260500396251 }}</ref><ref name="NCAA">{{cite web| title=National Study of Substance Use Trends Among NCAA College Student-Athletes| url=http://www.ncaapublications.com/productdownloads/SAHS09.pdf| work=NCAA Publications|publisher=NCAA|accessdate=8 October 2013}}</ref><ref name="Ergogenics" /> in competitive sports, this form of use is prohibited by anti-doping regulations.<ref name="Ergogenics">{{cite journal|last=Liddle|first=DG|coauthors=Connor, DJ|title=Nutritional supplements and ergogenic AIDS|journal=Primary care|date=2013 Jun|volume=40|issue=2|pages=487–505|pmid=23668655|doi=10.1016/j.pop.2013.02.009}}</ref> At moderate therapeutic doses, amphetamine has been shown to increase physical strength,<ref name="Ergogenics" /> acceleration,<ref name="Ergogenics" /> stamina,<ref name="Ergogenics" /><ref name="Roelands_2013" /> and endurance,<ref name="Ergogenics" /><ref name="Roelands_2013" /> while reducing reaction time.<ref name="Ergogenics" /> Like ] and ], amphetamine increases stamina and endurance in humans primarily through reuptake inhibition and effluxion of dopamine in the central nervous system.<ref name="Roelands_2013">{{cite journal | author = Roelands B, de Koning J, Foster C, Hettinga F, Meeusen R | title = Neurophysiological determinants of theoretical concepts and mechanisms involved in pacing | journal = Sports Med | volume = 43 | issue = 5 | pages = 301–11 | year = 2013 | month = May | pmid = 23456493 | doi = 10.1007/s40279-013-0030-4 | url = }}</ref>


===Recreational=== ===Recreational===
{{See also|History and culture of substituted amphetamines}}
Amphetamine is considered to have a high potential for misuse and a high liability for dependence and listed as Schedule II in the US,<ref>{{cite web|author=|url=http://www.drugabuse.gov/drugs-abuse/commonly-abused-drugs/commonly-abused-prescription-drugs-chart |title=Commonly Abused Prescription Drugs Chart |publisher=National Institute on Drug Abuse|date= |accessdate=2012-05-07}}</ref><ref>{{cite web|last=|first=|url=http://www.drugabuse.gov/publications/infofacts/stimulant-adhd-medications-methylphenidate-amphetamines |title=Stimulant ADHD Medications - Methylphenidate and Amphetamines |publisher=National Institute on Drug Abuse, |date= |accessdate=2012-05-07}}</ref> Schedule II in the UN ] and Schedule I in Canada (CSA).<ref name=GOC-SchedI>{{cite web|last=Government of Canada|title=Controlled Drugs and Substances Act|url=http://laws-lois.justice.gc.ca/eng/acts/C-38.8/page-24.html#h-28|work=S.C. 1996, c. 19, last amended on 2012-11-06|publisher=Government of Canada|accessdate=20 June 2013}}</ref> Amphetamine mixed salts is a drug of abuse.<ref name="urlwww.justice.gov">{{cite web | url = http://www.justice.gov/dea/druginfo/drug_data_sheets/Amphetamines.pdf | title = Amphetamines | author = | date = | format = PDF | work = Drug Fact Sheet | publisher = U.S. Drug Enforcement Administration }}</ref> Amphetamine salts can be crushed, and snorted or dissolved in water and injected.<ref name=NIDA>{{cite web|title=National Institute on Drug Abuse. 2009. Stimulant ADHD Medications - Methylphenidate and Amphetamines|url=http://www.drugabuse.gov/publications/drugfacts/stimulant-adhd-medications-methylphenidate-amphetamines|publisher=National Institute on Drug Abuse|accessdate=27 February 2013}}</ref> Injection into the bloodstream can be dangerous because insoluble fillers within the tablets can block small blood vessels.<ref name=NIDA />


Adderall has a high potential for misuse as a ].<ref>{{cite web |url=http://www.drugabuse.gov/drugs-abuse/commonly-abused-drugs/commonly-abused-prescription-drugs-chart |title=Commonly Abused Prescription Drugs Chart |publisher=National Institute on Drug Abuse |access-date=7 May 2012 |archive-url=https://web.archive.org/web/20120501092302/http://www.drugabuse.gov/drugs-abuse/commonly-abused-drugs/commonly-abused-prescription-drugs-chart |archive-date=1 May 2012 |url-status=dead }}</ref><ref>{{cite web |url=http://www.drugabuse.gov/publications/infofacts/stimulant-adhd-medications-methylphenidate-amphetamines |title=Stimulant ADHD Medications – Methylphenidate and Amphetamines |publisher=National Institute on Drug Abuse |access-date=7 May 2012 |archive-date=2 May 2012 |archive-url=https://web.archive.org/web/20120502072325/http://www.drugabuse.gov/publications/infofacts/stimulant-adhd-medications-methylphenidate-amphetamines |url-status=dead }}</ref><ref name="Abelman 68">{{Cite journal| vauthors = Abelman DD |date=6 October 2017|title=Mitigating risks of students use of study drugs through understanding motivations for use and applying harm reduction theory: a literature review|journal=Harm Reduction Journal|volume=14|issue=1|pages=68|doi=10.1186/s12954-017-0194-6|pmid=28985738|pmc=5639593|issn=1477-7517 |doi-access=free }}</ref> Adderall tablets can either be swallowed, crushed and snorted, or dissolved in water and injected.<ref name="NIDA">{{cite web|title=National Institute on Drug Abuse. 2009. Stimulant ADHD Medications – Methylphenidate and Amphetamines|url=http://www.drugabuse.gov/publications/drugfacts/stimulant-adhd-medications-methylphenidate-amphetamines|publisher=National Institute on Drug Abuse|access-date=27 February 2013|archive-url=https://web.archive.org/web/20130312110514/http://www.drugabuse.gov/publications/drugfacts/stimulant-adhd-medications-methylphenidate-amphetamines|archive-date=12 March 2013|url-status=dead}}</ref> Injection into the bloodstream can be dangerous because ] can block small blood vessels.<ref name="NIDA" />
Recreational use of amphetamines is exceedingly dangerous, especially when used at very high doses. Research has shown that amphetamine binges in lab animals cause neurotoxicity in dopaminergic pathways, resulting in permanent but not irreversible cognitive impairments.<ref>{{cite journal|last=Berman|first=S M|coauthors=Kuczenski, R; McCracken, J T; London, E D|title=Potential adverse effects of amphetamine treatment on brain and behavior: a review|journal=Molecular Psychiatry|date=12 August 2008|volume=14|issue=2|pages=123–142|doi=10.1038/mp.2008.90|pmid=18698321|pmc=2670101}}</ref> Moreover, extremely high doses of amphetamine can induce ], ], ], and ].<ref name="Amph OD">{{cite web | author = Oskie SM, Rhee JW | title = Amphetamine Poisoning | url = http://emergency.unboundmedicine.com/emergency/ub/view/5-Minute_Emergency_Consult/307063/all/Amphetamine_Poisoning | work = Emergency Central | publisher = Wolters Kluwer Health Lippincott Williams & Wilkins | date = 11 February 2011 | accessdate = 11 June 2013 }}</ref><ref name="Isbister2007">{{cite journal|last=Isbister|first=GK|coauthors=Buckley, NA; Whyte, IM|title=Serotonin toxicity: a practical approach to diagnosis and treatment|journal=The Medical journal of Australia|date=2007 Sep 17|volume=187|issue=6|pages=361–5|pmid=17874986}}</ref> An amphetamine overdose is rarely fatal with appropriate care.<ref name="pmid23757186">{{cite journal | author = Spiller HA, Hays HL, Aleguas A | title = Overdose of Drugs for Attention-Deficit Hyperactivity Disorder: Clinical Presentation, Mechanisms of Toxicity, and Management | journal = CNS Drugs | volume = 27| issue = 7| pages = 531–43| year = 2013 | month = June | pmid = 23757186 | doi = 10.1007/s40263-013-0084-8 }}</ref>


Many postsecondary students have reported using Adderall for study purposes in different parts of the developed world.<ref name="Abelman 68"/> Among these students, some of the ]s for misusing ADHD stimulants recreationally include: possessing ] characteristics (i.e., exhibiting delinquent or deviant behavior), inadequate accommodation of disability, basing one's ] on external validation, low ], earning poor grades, and having an untreated ].<ref name="Abelman 68"/>
==Psychological effects==
Psychological effects can include ], ], increased ], ], ], energy, ], ], ], ], ], ], ], repetitive and ] behaviors, and ]. With chronic and/or high doses, ] can occur. Occasionally this psychosis can occur at therapeutic doses during chronic therapy as a treatment emergent side effect.<ref name="Berman-2009">{{cite journal | author = Berman SM, Kuczenski R, McCracken JT, London ED | title = Potential adverse effects of amphetamine treatment on brain and behavior: a review | journal = Mol. Psychiatry | volume = 14 | issue = 2 | pages = 123–42 | year = 2009 | month = February | pmid = 18698321 | pmc = 2670101 | doi = 10.1038/mp.2008.90 }}</ref><ref name="Merck_Manual_Amphetamines">{{cite web | url = http://www.merckmanuals.com/professional/special_subjects/drug_use_and_dependence/amphetamines.html | title = Amphetamines | author = O'Connor PG | publisher = Merck Sharp & Dohme Corp | work = Merck Manual for Health Care Professionals | accessdate = 8 May 2012 }}</ref> According to the US FDA, "there is no systematic evidence that stimulants cause aggressive behavior or hostility."<ref name="FDA side effects" />


==Contraindications==
==Side effects==
{{Excerpt|Amphetamine|Contraindications}}
===Physical===
At normal therapeutic doses, the physical side effects of amphetamine vary widely by age and among individuals;<ref name="FDA side effects" /> these side effects can include ], ], ], ], ], ], ], ], ], ], ], dry and/or itchy skin, ], ], ], ], ], ] or ], ], ], loss of appetite, ], ], ], ], ], ], ], reduced ], restlessness, ], ], ], ] or ], ], and ].<ref name="FDA side effects">{{cite web | title = Adderall XR Prescribing Information| url = http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021303s024lbl.pdf | author = | work = United States Food and Drug Administration | publisher = United States Food and Drug Administration | accessdate = 7 October 2013}}</ref><ref name="pmid18295156">{{cite journal | author = Vitiello B | title = Understanding the risk of using medications for attention deficit hyperactivity disorder with respect to physical growth and cardiovascular function | journal = Child Adolesc Psychiatr Clin N Am | volume = 17 | issue = 2 | pages = 459–74 | year = 2008 | month = April | pmid = 18295156 | pmc = 2408826 | doi = 10.1016/j.chc.2007.11.010 }}</ref> Dangerous physical side effects are exceedingly rare in typical pharmaceutical doses.<ref name="TrevorKatzung2012">{{cite book| author = Trevor AJ, Katzung BG, Masters SB, Knuidering-Hall M | title = Katzung & Trevor's Pharmacology Examination and Board Review | edition = 10th | chapter = Chapter 32. Drugs of Abuse | page = 279–286 | url = http://www.accesspharmacy.com/content.aspx?aID=56982610 | year = 2012 | publisher = McGraw Hill Professional | isbn = 978-0-07-178924-0 }}</ref> Amphetamines stimulate the ], which increases the rate of respiration and produces deeper breaths.<ref name="Westfall, David P. 2013">{{cite book | editor =Brunton LL, Chabner BA, Knollmann BC | title = Goodman & Gilman's Pharmacological Basis of Therapeutics | year = 2010 | publisher = McGraw-Hill | location = New York | isbn = 978-0071624428 | author = Westfall DP, Westfall TC | chapter = 12: Adrenergic Agonist and Antagonists | page = 277–334 | edition = 12th }}</ref> In a normal individual, amphetamines do not noticeably increase the rate of respiration or produce deeper breaths, but when respiration is already compromised, amphetamines may stimulate respiration.<ref name="Westfall, David P. 2013" />


==Adverse effects==
Recent studies by the FDA indicate that, in children, young adults, and adults, there is no association between serious adverse cardiovascular events (], ], and ]) and the use of amphetamines or other ADHD stimulants.<ref>{{cite web | title = ADHD Medications and Risk of Stroke In Young and Middle-Aged Adults | author = Adverse Effects of Psychostimulant Medications Working Group | work = Effective Health Care Program Research Report No. 36 AHRQ Publication No. 12-EHC011-EF | publisher = Agency for Health Care Research and Quality, United States Department of Health and Human Services | url = http://www.fda.gov/downloads/Drugs/DrugSafety/UCM279877.pdf | accessdate = 11 June 2013}}</ref><ref>{{cite web | title = ADHD Medications and Risk of Serious Coronary Heart Disease in Young and Middle-Aged Adults | author = Adverse Effects of Psychostimulant Medications Working Group | work = Effective Health Care Program Research Report No. 36. AHRQ Publication No. 12-EHC011-EF | publisher = Agency for Health Care Research and Quality, United States Department of Health and Human Services | url = http://www.effectivehealthcare.ahrq.gov/ehc/products/394/884/DEcIDE36_ADHDMeds-Adults_20111220.pdf | accessdate = 11 June 2013 }}</ref><ref>{{cite web | title = Attention Deficit Hyperactivity Disorder Medications and Risk of Serious Cardiovascular Disease in Children and Youth | author = Adverse Effects of Psychostimulant Medications Working Group | work = Effective Health Care Program Research Report No. 12-EHC006-EF| publisher = Agency for Health Care Research and Quality, United States Department of Health and Human Services | date = November 2011 | url = http://www.effectivehealthcare.ahrq.gov/ehc/products/395/885/DEcIDE35_YouthADHD_20111031.pdf | accessdate = 11 June 2013 }}</ref>
{{transcluded section|source=Amphetamine|part=yes}}
The ] of Adderall are many and varied, but the amount of substance consumed is the primary factor in determining the likelihood and severity of side effects.<ref name="FDA" /><ref name="Westfall" /> Adderall is currently approved for long-term therapeutic use by the USFDA.<ref name="FDA" /> ] of Adderall generally involves far larger doses and is therefore significantly more dangerous, involving a much greater risk of serious adverse drug effects than dosages used for therapeutic purposes.<ref name="Westfall" />
{{trim|{{#section-h:Amphetamine|Adverse effects}}}}


==Overdose==
Amphetamine mixed salts is in ] C.<ref name="drugs_dot_com">{{cite web|title=Adderall|url=http://www.drugs.com/pro/adderall.html|publisher=Drugs.com|accessdate=20 May 2013}}</ref> Drugs assigned category C have been demonstrated to have adverse effect on fetus in animal studies, but no adequate studies on human are available.<ref name="urldepts.washington.edu">{{cite web | url = http://depts.washington.edu/druginfo/Formulary/Pregnancy.pdf | title = FDA Pregnancy Categories | author = | date = | format = PDF | work = | publisher = University of Washington Drug Information Center }}</ref> Studies on rats show long-term neurological and behavioral changes resulting from prenatal and early postnatal exposure to amphetamines.<ref name="xrPIsheet"/><ref name="isbn1-60623-710-1">{{cite book | author = Barkley RA | title = Taking Charge of Adult ADHD | publisher = The Guilford Press | location = New York | year = 2010 | page = 122 | isbn = 1-60623-710-1 }}</ref>
{{Excerpt|Amphetamine|Overdose}}


==Interactions==
A study on comparative effects between amphetamine mixed salts and ] in children who have been treated for a year or more have shown a temporary decrease in growth rate that does not affect final adult height. Change in weight was reported as slightly greater for amphetamine mixed salts and authors concluded that the result may be clinically insignificant.<ref name="comparative">{{cite journal | author = Pliszka SR, Matthews TL, Braslow KJ, Watson MA | title = Comparative effects of methylphenidate and mixed salts amphetamine on height and weight in children with attention-deficit/hyperactivity disorder | journal = J Am Acad Child Adolesc Psychiatry | volume = 45 | issue = 5 | pages = 520–6 | year = 2006 | month = May | pmid = 16670648 | doi = 10.1097/01.chi.0000205702.48324.fd }}</ref>
* ]s (MAOIs) taken with amphetamine may result in a ] if taken within two weeks after last use of an MAOI type drug.<ref name="FDA Interactions">{{cite web | title = Adderall XR Prescribing Information | url = http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021303s026lbl.pdf | pages = 8–10 | website = United States Food and Drug Administration | date = December 2013 | access-date = 30 December 2013 | archive-date = 30 December 2013 | archive-url = https://web.archive.org/web/20131230233702/http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021303s026lbl.pdf | url-status = live }}</ref>
* ] that directly metabolize amphetamine (particularly ] and ]) will prolong the elimination of amphetamine and increase drug effects.<ref name="FDA Interactions" /><ref name="FMO" /><ref name="Mydayis">{{cite web|title=Mydayis Prescribing Information|url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022063s000lbl.pdf|website=United States Food and Drug Administration|publisher=Shire US Inc.|access-date=8 August 2017|pages=1–21|date=June 2017|archive-date=9 June 2019|archive-url=https://web.archive.org/web/20190609083453/https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022063s000lbl.pdf|url-status=live}}</ref>
* ] drugs (such as most ]) co-administered with amphetamine increases the risk of ].<ref name="Mydayis" />
* ] and ] (]s and ]s) may increase (decrease) the drug effects of amphetamine, and vice versa.<ref name="FDA Interactions" />
* Gastrointestinal and urinary ] affect the ] and ] of amphetamine, respectively. Gastrointestinal alkalinizing agents increase the absorption of amphetamine. Urinary alkalinizing agents increase the concentration of non-ionized species, decreasing urinary excretion.<ref name="FDA Interactions" />
* ]s (PPIs) modify the absorption of Adderall XR and Mydayis.<ref name="FDA Interactions" /><ref name="Mydayis" />
* ] may reduce the ] of amphetamine when it is used for the treatment of ADHD.{{#tag:ref|The human ] contains a ] extracellular zinc ] which, upon zinc binding, inhibits dopamine ] and amplifies amphetamine-induced ] '']''.<ref name="Zinc binding sites + ADHD review">{{cite journal | vauthors = Krause J | title = SPECT and PET of the dopamine transporter in attention-deficit/hyperactivity disorder | journal = Expert Rev. Neurother. | volume = 8 | issue = 4 | pages = 611–625 | date = April 2008 | pmid = 18416663 | doi = 10.1586/14737175.8.4.611 | s2cid = 24589993 | quote = Zinc binds at&nbsp;... extracellular sites of the DAT , serving as a DAT inhibitor. In this context, controlled double-blind studies in children are of interest, which showed positive effects of zinc on symptoms of ADHD . It should be stated that at this time with zinc is not integrated in any ADHD treatment algorithm.}}</ref><ref name="Review - cites 2002 amph-zinc primary study">{{cite journal | vauthors = Sulzer D | title = How addictive drugs disrupt presynaptic dopamine neurotransmission | journal = Neuron | volume = 69 | issue = 4 | pages = 628–649 | date = February 2011 | pmid = 21338876 | pmc = 3065181 | doi = 10.1016/j.neuron.2011.02.010 | quote = They did not confirm the predicted straightforward relationship between uptake and release, but rather that some compounds including AMPH were better releasers than substrates for uptake. Zinc, moreover, stimulates efflux of intracellular DA despite its concomitant inhibition of uptake (Scholze et al., 2002).}}</ref><ref name="Primary 2002 amph-zinc study">{{cite journal | vauthors = Scholze P, Nørregaard L, Singer EA, Freissmuth M, Gether U, Sitte HH | title = The role of zinc ions in reverse transport mediated by monoamine transporters | journal = J. Biol. Chem. | volume = 277 | issue = 24 | pages = 21505–21513 | date = June 2002 | pmid = 11940571 | doi = 10.1074/jbc.M112265200 | quote = The human dopamine transporter (hDAT) contains an endogenous high affinity Zn<sup>2+</sup> binding site with three coordinating residues on its extracellular face (His193, His375, and Glu396).&nbsp;... Although Zn<sup>2+</sup> inhibited uptake, Zn<sup>2+</sup> facilitated MPP+ release induced by amphetamine, MPP+, or K+-induced depolarization specifically at hDAT but not at the human serotonin and the norepinephrine transporter (hNET).&nbsp;... Surprisingly, this amphetamine-elicited efflux was markedly enhanced, rather than inhibited, by the addition of 10&nbsp;μM Zn<sup>2+</sup> to the superfusion buffer (Fig. 2 A, open squares). We stress that Zn<sup>2+</sup> per se did not affect basal efflux (Fig. 2 A).&nbsp;... In many brain regions, Zn<sup>2+</sup> is stored in synaptic vesicles and co-released together with glutamate; under basal conditions, the extracellular levels of Zn<sup>2+</sup> are low (~10&nbsp;nM; see Refs. 39, 40). Upon neuronal stimulation, however, Zn<sup>2+</sup> is co-released with the neurotransmitters and, consequently, the free Zn<sup>2+</sup> concentration may transiently reach values that range from 10–20&nbsp;μM (10) up to 300&nbsp;μM (11). The concentrations of Zn<sup>2+</sup> shown in this study, required for the stimulation of dopamine release (as well as inhibition of uptake), covered this physiologically relevant range, with maximum stimulation occurring at 3–30&nbsp;μM. It is therefore conceivable that the action of Zn<sup>2+</sup> on hDAT does not merely reflect a biochemical peculiarity but that it is physiologically relevant.&nbsp;... Thus, when Zn<sup>2+</sup> is co-released with glutamate, it may greatly augment the efflux of dopamine.| doi-access = free}}</ref> The human ] and ] do not contain zinc binding sites.<ref name="Primary 2002 amph-zinc study" />|group="note"}}<ref name="Zinc and PEA">{{cite journal |vauthors=Scassellati C, Bonvicini C, Faraone SV, Gennarelli M | title = Biomarkers and attention-deficit/hyperactivity disorder: a systematic review and meta-analyses | journal = J. Am. Acad. Child Adolesc. Psychiatry | volume = 51 | issue = 10 | pages = 1003–1019.e20 | date = October 2012 | pmid = 23021477 | doi = 10.1016/j.jaac.2012.08.015 | quote = Although we did not find a sufficient number of studies suitable for a meta-analysis of PEA and ADHD, three studies<sup>20,57,58</sup> confirmed that urinary levels of PEA were significantly lower in patients with ADHD compared with controls.&nbsp;... Administration of D-amphetamine and methylphenidate resulted in a markedly increased urinary excretion of PEA,<sup>20,60</sup> suggesting that ADHD treatments normalize PEA levels.&nbsp;... Similarly, urinary biogenic trace amine PEA levels could be a biomarker for the diagnosis of ADHD,<sup>20,57,58</sup> for treatment efficacy,<sup>20,60</sup> and associated with symptoms of inattentivenesss.<sup>59</sup>&nbsp;... With regard to zinc supplementation, a placebo controlled trial reported that doses up to 30&nbsp;mg/day of zinc were safe for at least 8&nbsp;weeks, but the clinical effect was equivocal except for the finding of a 37%&nbsp;reduction in amphetamine optimal dose with 30&nbsp;mg per day of zinc.<sup>110</sup>}}</ref>


==Pharmacology==
The numerous possible physical effects of Adderall, including but not limited to hallucinations, seizures, and uncontrolled shaking or body movements, resemble symptoms of cocaine usage. Bodily side effects, when combined with with off- label use, ultimately mean that students are taking highly addictive medications without consulting a medical professional or even truly understanding the physical or mental risks associated with self- medication. <ref>{{cite journal|last=Schiffner|first=Jennifer|title=Harder, Better, Faster Stronger: Regulating Illicit Adderall Use Among Law Students and Law Schools|journal=Selected Works|year=2010|month=January|pages=13|url=http://works.bepress.com/cgi/viewcontent.cgi?article=1000&context=jennifer_schiffner|accessdate=October 24, 2013}}</ref>
===Mechanism of action===
{{For|a more complete and detailed description of amphetamine pharmacodynamics|Amphetamine#Pharmacodynamics}}
{| class="wikitable floatright" style="font-size:small;"
|+ {{Nowrap|] of ] and related agents ({{Abbrlink|EC<sub>50</sub>|Half maximal effective concentration}}, nM)}}
|-
! Compound !! data-sort-type="number" | {{abbrlink|NE|Norepinephrine}} !! data-sort-type="number" | {{abbrlink|DA|Dopamine}} !! data-sort-type="number" | {{abbrlink|5-HT|Serotonin}} !! Ref
|-
| ] || 10.9 || 39.5 || >10000 || <ref name="ReithBLoughHong2015">{{cite journal | vauthors = Reith ME, Blough BE, Hong WC, Jones KT, Schmitt KC, Baumann MH, Partilla JS, Rothman RB, Katz JL | title = Behavioral, biological, and chemical perspectives on atypical agents targeting the dopamine transporter | journal = Drug and Alcohol Dependence | volume = 147 | issue = | pages = 1–19 | date = February 2015 | pmid = 25548026 | pmc = 4297708 | doi = 10.1016/j.drugalcdep.2014.12.005 }}</ref><ref name="Forsyth2012" /><ref name="Blough2008" />
|-
| ] || 6.6–7.2 || 5.8–24.8 || 698–1765 || <ref name="RothmanBaumannDersch2001">{{cite journal | vauthors = Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, Partilla JS | title = Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin | journal = Synapse | volume = 39 | issue = 1 | pages = 32–41 | date = January 2001 | pmid = 11071707 | doi = 10.1002/1098-2396(20010101)39:1<32::AID-SYN5>3.0.CO;2-3 | url = }}</ref><ref name="BaumannPartillaLehner2013">{{cite journal | vauthors = Baumann MH, Partilla JS, Lehner KR, Thorndike EB, Hoffman AF, Holy M, Rothman RB, Goldberg SR, Lupica CR, Sitte HH, Brandt SD, Tella SR, Cozzi NV, Schindler CW | title = Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive 'bath salts' products | journal = Neuropsychopharmacology | volume = 38 | issue = 4 | pages = 552–562 | year = 2013 | pmid = 23072836 | pmc = 3572453 | doi = 10.1038/npp.2012.204 }}</ref>
|-
| ] || 9.5 || 27.7 || {{abbr|ND|No data}} || <ref name="Forsyth2012">{{cite journal | last=Forsyth | first=Andrea N | title=Synthesis and Biological Evaluation of Rigid Analogues of Methamphetamines | website=ScholarWorks@UNO | date=22 May 2012 | url=https://scholarworks.uno.edu/td/1436/ | access-date=4 November 2024}}</ref><ref name="Blough2008">{{cite book | vauthors = Blough B | chapter = Dopamine-releasing agents | veditors = Trudell ML, Izenwasser S | title = Dopamine Transporters: Chemistry, Biology and Pharmacology | pages = 305–320 | date = July 2008 | isbn = 978-0-470-11790-3 | oclc = 181862653 | ol = OL18589888W | publisher = Wiley | location = Hoboken | doi = | url = https://books.google.com/books?id=QCagLAAACAAJ | chapter-url = https://bitnest.netfirms.com/external/Books/Dopamine-releasing-agents_c11.pdf }}</ref>
|-
| ] || 12.3–13.8 || 8.5–24.5 || 736–1291.7 || <ref name="RothmanBaumannDersch2001" /><ref name="BaumannAyestasPartilla2012">{{cite journal | vauthors = Baumann MH, Ayestas MA, Partilla JS, Sink JR, Shulgin AT, Daley PF, Brandt SD, Rothman RB, Ruoho AE, Cozzi NV | title = The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue | journal = Neuropsychopharmacology | volume = 37 | issue = 5 | pages = 1192–1203 | year = 2012 | pmid = 22169943 | pmc = 3306880 | doi = 10.1038/npp.2011.304 }}</ref>
|-
| ] || 28.5 || 416 || 4640 || <ref name="RothmanBaumannDersch2001" />
|-
| colspan="7" style="width: 1px; background-color:#eaecf0; text-align: center;" | '''Notes:''' The smaller the value, the more strongly the drug releases the neurotransmitter. See also ] for a larger table with more compounds. '''Refs:''' <ref name="RothmanBaumann2003">{{cite journal | vauthors = Rothman RB, Baumann MH | title = Monoamine transporters and psychostimulant drugs | journal = Eur J Pharmacol | volume = 479 | issue = 1–3 | pages = 23–40 | date = October 2003 | pmid = 14612135 | doi = 10.1016/j.ejphar.2003.08.054 | url = }}</ref><ref name="RothmanBaumann2006">{{cite journal | vauthors = Rothman RB, Baumann MH | title = Therapeutic potential of monoamine transporter substrates | journal = Current Topics in Medicinal Chemistry | volume = 6 | issue = 17 | pages = 1845–1859 | year = 2006 | pmid = 17017961 | doi = 10.2174/156802606778249766 | url = https://zenodo.org/record/1235860 }}</ref>
|}
{{Amphetamine pharmacodynamics}}
Amphetamine, the active ingredient of Adderall, works primarily by increasing the activity of the ]s ] and ] in the brain.<ref name="Malenka_2009_03b">{{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY |title=Molecular Neuropharmacology: A Foundation for Clinical Neuroscience |year=2009 |publisher=McGraw-Hill Medical |location=New York, USA |isbn=9780071481274 |pages=154–157 |edition=2nd |chapter=Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin}}</ref><ref name="cognition enhancers" /> It also triggers the release of several other hormones (e.g., ]) and neurotransmitters (e.g., ] and ]) as well as the synthesis of certain ]s (e.g., ] (CART) peptides).<ref name="E Weihe" /><ref name="PubChem Targets">{{cite web |title=Amphetamine: Biomolecular Interactions and Pathways |url=https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3007#x301 |website=PubChem Compound | publisher=National Center for Biotechnology Information |access-date=13 October 2013 |archive-date=13 October 2013 |archive-url=https://web.archive.org/web/20131013122604/http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3007#x301 |url-status=live}}</ref> Both active ingredients of Adderall, ] and ], bind to the same ]s,<ref name="Westfall"/><ref name="TAAR1 stereoselective" /> but their ] (that is, ]) differ somewhat.<ref name="Westfall"/><ref name="TAAR1 stereoselective" /> Dextroamphetamine and levoamphetamine are both potent ]s (activating compounds) of ] (TAAR1) and interact with ] (VMAT2), with dextroamphetamine being the more potent agonist of TAAR1.<ref name="TAAR1 stereoselective" /> Consequently, dextroamphetamine produces more {{abbr|CNS|central nervous system}} stimulation than levoamphetamine;<ref name="TAAR1 stereoselective">{{cite journal |vauthors=Lewin AH, Miller GM, Gilmour B |title=Trace amine-associated receptor 1 is a stereoselective binding site for compounds in the amphetamine class |journal=Bioorg. Med. Chem. |date=December 2011 |volume=19 |issue=23 |pages=7044–7048 |pmid=22037049 |doi=10.1016/j.bmc.2011.10.007 |pmc=3236098}}</ref><ref>{{cite journal |vauthors=Smith RC, Davis JM |title=Comparative effects of d-amphetamine, l-amphetamine, and methylphenidate on mood in man |journal=] |volume=53 |issue=1 |pages=1–12 |date=June 1977 |pmid=407607 |doi=10.1007/bf00426687 |s2cid=37967136}}</ref> however, levoamphetamine has slightly greater cardiovascular and peripheral effects.<ref name="Westfall" /> It has been reported that certain children have a better clinical response to levoamphetamine.<ref name="Child Psychiatry">{{cite book |title=Explorations in Child Psychiatry |url=https://books.google.com/books?id=Ob7eBwAAQBAJ |publisher=Springer Science & Business Media |date=11 November 2013 |isbn=9781468421279 |vauthors=Anthony E |pages=93–94 |access-date=28 April 2015 |archive-date=21 May 2016 |archive-url=https://web.archive.org/web/20160521053637/https://books.google.com/books?id=Ob7eBwAAQBAJ |url-status=live}}</ref><ref name="Arnold">{{cite journal |title=Methyiphenidate vs. Amphetamine: Comparative review |year=2000 |author=Arnold LE |s2cid=15901046 |journal=Journal of Attention Disorders |volume=3 |issue=4 |pages=200–211 |doi=10.1177/108705470000300403}}</ref>


In the absence of amphetamine, {{abbr|VMAT2|vesicular monoamine transporter 2}} will normally move ]s (e.g., ], ], ], ], etc.) from the ] of a monoamine ] into its ]s, which store neurotransmitters for later release (via ]) into the synaptic cleft.<ref name="E Weihe">{{cite journal |vauthors=Eiden LE, Weihe E |title=VMAT2: a dynamic regulator of brain monoaminergic neuronal function interacting with drugs of abuse |journal=Ann. N. Y. Acad. Sci. |volume=1216 |issue=1 |pages=86–98 |date=January 2011 |pmid=21272013 |doi=10.1111/j.1749-6632.2010.05906.x |quote=VMAT2 is the CNS vesicular transporter for not only the biogenic amines DA, NE, EPI, 5-HT, and HIS, but likely also for the trace amines TYR, PEA, and thyronamine (THYR)&nbsp;... neurons in mammalian CNS would be identifiable as neurons expressing VMAT2 for storage, and the biosynthetic enzyme aromatic amino acid decarboxylase (AADC). |pmc=4183197 |bibcode=2011NYASA1216...86E }}</ref> When amphetamine enters a neuron and interacts with VMAT2, the transporter reverses its direction of transport, thereby releasing stored monoamines inside synaptic vesicles back into the neuron's intracellular fluid.<ref name="E Weihe" /> Meanwhile, when amphetamine activates {{abbr|TAAR1|trace amine-associated receptor 1}}, the receptor causes the neuron's ]-bound ]s (i.e., the ], ], or ]) to either stop transporting monoamines altogether (via transporter ]) or ];<ref name="Miller" /> in other words, the reversed membrane transporter will push dopamine, norepinephrine, and serotonin out of the neuron's intracellular fluid and into the ].<ref name="Miller" /> In summary, by interacting with both VMAT2 and TAAR1, amphetamine releases neurotransmitters from synaptic vesicles (the effect from VMAT2) into the intracellular fluid where they subsequently exit the neuron through the membrane-bound, reversed monoamine transporters (the effect from TAAR1).<ref name="Miller" /><ref name="E Weihe" />
===Overdose===
An amphetamine overdose is rarely fatal with appropriate care,<ref name="pmid23757186" /> but can lead to a number of different symptoms that vary widely among individuals.<ref name="FDA side effects" /> A moderate overdose may induce symptoms including: ], ], ], ], ] or ], ], ], ], ], ], and ].<ref name="FDA side effects" /><ref name="Westfall, David P. 2013"/> An extremely large overdose may produce symptoms such as ], ], ], ], ], ], ], ], ], ], and ].<ref name="FDA side effects" /><ref name="Merck_Manual_Amphetamines" /><ref name="Westfall, David P. 2013"/><ref>{{cite book | author = Knoben JE, Anderson PO | title = Handbook of Clinical Drug Data | publisher = Drug Intelligence Publications, Inc. | year = 1988 | edition = 6th | page = 90 | url = http://toxnet.nlm.nih.gov/cgi-bin/sis/search/a?dbs+hsdb:@term+@DOCNO+6374 }}</ref><ref name="Albertson_2011">{{cite book| editor = Olson KR, Anderson IB, Benowitz NL, Blanc PD, Kearney TE, Kim-Katz SY, Wu AHB | title = Poisoning & Drug Overdose | author = Albertson TE| year = 2011 | publisher = McGraw-Hill Medical | location = New York | isbn = 978-0071668330 | chapter = Amphetamines | page = 77–79 | edition = 6th }}</ref><ref name="Amph OD" /><ref name="Isbister2007" /> Fatal amphetamine poisoning usually also involves ] and ].<ref name="FDA side effects" />

===Dependence, addiction and withdrawal===

] is developed rapidly in amphetamine abuse; therefore, periods of extended use require increasing amounts of the drug in order to achieve the same effect.<ref>{{cite web
| title=Amphetamines: Drug Use and Abuse: Merck Manual Home Edition | publisher = Merck | url=http://www.merckmanuals.com/home/special_subjects/drug_use_and_abuse/amphetamines.html | accessdate=28 February 2007 |archiveurl = http://web.archive.org/web/20070217053619/http://www.merck.com/mmhe/sec07/ch108/ch108g.html <!-- Bot retrieved archive --> |archivedate = 17 February 2007}}</ref> According to a Cochrane Collaboration review on the topic, "when chronic heavy users abruptly discontinue amphetamine use, many report a time-limited withdrawal syndrome that occurs within 24 hours of their last dose."<ref name="Cochrane Withdrawal">{{cite journal | author = Shoptaw SJ, Kao U, Heinzerling K, Ling W | title = Treatment for amphetamine withdrawal | journal = Cochrane Database Syst Rev | volume = | issue = 2 | pages = CD003021 | year = 2009 | pmid = 19370579 | doi = 10.1002/14651858.CD003021.pub2 | editor1-last = Shoptaw | editor1-first = Steven J }}</ref> This review noted that withdrawal symptoms in chronic, heavy users are frequent, occurring in up to 87.6% of cases, and persists for three to four weeks with a marked "crash" phase occurring during the first week.<ref name="Cochrane Withdrawal" /> Amphetamine withdrawal symptoms can include ], ], ], ], ] or ], ], ] or ], ], and ].<ref name="Cochrane Withdrawal" />

===Contraindications, interactions, and precautions===
*MAOIs (]s, e.g., ], ], ], etc.)&nbsp;—There is a high risk of a ] if amphetamine is administered within two weeks after last use of an MAOI type drug. Preliminary trials of low-dose amphetamine and MAOIs being administered together are in progress. However, this is to be done only under strict supervision of the prescribing parties.
*SSRIs (]s, e.g., ], ], ], etc.)&nbsp;— While a common combination, and although rare, the risk for ] exists. (Use only when directed)
*NRIs (]s, e.g., ], etc.)&nbsp;— NRI medications and ] both enhance noradrenergic activity. Possible augmentation/potentiation of effects. (Use only when directed)
*SNRIs (selective ]s)&nbsp;— See SSRIs and NRIs.
*] &nbsp;— Both bupropion and amphetamine have noradrenergic and dopaminergic activity. Bupropion is a potent CYP2D6 inhibitor. Bupropion has pro-convulsant properties that may be enhanced or cumulatively potentiated by amphetamine.<ref name="pmid15361919">{{cite journal | author = Stahl SM, Pradko JF, Haight BR, Modell JG, Rockett CB, Learned-Coughlin S | title = A Review of the Neuropharmacology of Bupropion, a Dual Norepinephrine and Dopamine Reuptake Inhibitor | journal = Prim Care Companion J Clin Psychiatry | volume = 6 | issue = 4 | pages = 159–166 | year = 2004 | pmid = 15361919 | pmc = 514842 | doi = 10.4088/PCC.v06n0403 }}</ref> (Use only when directed)
*Monoaminergic ] &nbsp;— See NRIs, SNRIs, and SSRIs. Possible potentiation of serotonin-, dopamine-, and/or norepinephrine-related drug effects. The combination of monoaminergic tricyclics and amphetamine compounds has been associated with increased sympathomimetic effects. The exceptions to this class (i.e. non-monoaminergic tricyclic antidepressants) include the ] tricyclic ] and ] tricyclic ].
*], e.g., Bupropion and most ]s such as fluoxetine, citalopram, paroxetine, etc. Some ]s such as ], ], and ], as well as ], the opioid agonist ], and others. It is important to determine if any medication or drug taken is a CYP2D6 inhibitor. Taking a CYP2D6-inhibiting drug along with amphetamine will lead to an elevated level of amphetamine in the system, resulting in the drug's remaining in the body for a longer period, which can lead to undesirable and possibly serious side effects.
*Individuals with pre-existing cardiac conditions or mental illnesses.
*Individuals with a history of drug abuse

===Psychosis===
{{Main|Stimulant psychosis}}
Abuse of amphetamines can result in a stimulant psychosis which may present with a variety of symptoms (e.g. ], ]s, ]s). A ] review on treatment for amphetamine, dextroamphetamine, and methamphetamine induced psychosis<ref name="Cochrane"/> states that about 5-15% of users fail to recover completely.<ref name="Hoffman">Hofmann FG. A handbook on drug and alcohol abuse: the biomedical aspects. 2nd Edition. New York: Oxford University Press, 1983.</ref> The same review asserts that, based upon at least one trial, antipsychotic medications effectively resolve the symptoms of acute amphetamine psychosis.<ref name="Cochrane">{{cite journal | author = Shoptaw SJ, Kao U, Ling W | title = Treatment for amphetamine psychosis (Review) | url = | journal = Cochrane Database of Systematic Reviews | year = 2009 | issue = 1 }}</ref> An ] may also develop occasionally as a treatment-emergent side effect.<ref name="Berman-2009" />

== Mechanism of action ==
{{main|Amphetamine#Pharmacology}}

Amphetamine has been identified as a potent ] of ] (aka "TAAR1"), a ], discovered in 2001, that is important for regulation of ] systems in the brain.<ref name="pmid11723224">{{cite journal | author = Bunzow JR, Sonders MS, Arttamangkul S, Harrison LM, Zhang G, Quigley DI, Darland T, Suchland KL, Pasumamula S, Kennedy JL, Olson SB, Magenis RE, Amara SG, Grandy DK | title = Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor | journal = Mol. Pharmacol. | volume = 60 | issue = 6 | pages = 1181–8 | year = 2001 | month = December | pmid = 11723224 | doi = }}</ref> Activation of TAAR1 increases ] production via ] activation and inhibits the function of the ], ], and ], as well as induce effluxion of these neurotransmitters.<ref name="pmid11723224"/><ref name="pmid11459929">{{cite journal | author = Borowsky B, Adham N, Jones KA, Raddatz R, Artymyshyn R, Ogozalek KL, Durkin MM, Lakhlani PP, Bonini JA, Pathirana S, Boyle N, Pu X, Kouranova E, Lichtblau H, Ochoa FY, Branchek TA, Gerald C | title = Trace amines: identification of a family of mammalian G protein-coupled receptors | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 98 | issue = 16 | pages = 8966–71 | year = 2001 | month = July | pmid = 11459929 | pmc = 55357 | doi = 10.1073/pnas.151105198 |bibcode = 2001PNAS...98.8966B }}</ref><ref name="pmid18310473">{{cite journal | author = Xie Z, Westmoreland SV, Miller GM | title = Modulation of monoamine transporters by common biogenic amines via trace amine-associated receptor 1 and monoamine autoreceptors in human embryonic kidney 293 cells and brain synaptosomes | journal = J. Pharmacol. Exp. Ther. | volume = 325 | issue = 2 | pages = 629–40 | year = 2008 | month = May | pmid = 18310473 | doi = 10.1124/jpet.107.135079 }}</ref><ref name="pmid17234900">{{cite journal | author = Xie Z, Westmoreland SV, Bahn ME, Chen GL, Yang H, Vallender EJ, Yao WD, Madras BK, Miller GM | title = Rhesus monkey trace amine-associated receptor 1 signaling: enhancement by monoamine transporters and attenuation by the D2 autoreceptor in vitro | journal = J. Pharmacol. Exp. Ther. | volume = 321 | issue = 1 | pages = 116–27 | year = 2007 | month = April | pmid = 17234900 | doi = 10.1124/jpet.106.116863 }}</ref><ref name="Miller">{{cite journal|last=Miller|first=GM|title=The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity|journal=Journal of Neurochemistry|date=2011 Jan|volume=116|issue=2|pages=164–76|pmid=21073468|doi=10.1111/j.1471-4159.2010.07109.x|pmc=3005101}}</ref> Amphetamine is a substrate for a specific neuronal synaptic vesicle uptake transporter called ].<ref name="E Weihe" /> When amphetamine is taken up by ], the vesicle releases (effluxes) dopamine, norepinephrine, and serotonin, among other monoamines, into the cytosol in exchange.<ref name="E Weihe">{{cite journal|last=Eiden|first=LE|coauthors=Weihe, E|title=VMAT2: a dynamic regulator of brain monoaminergic neuronal function interacting with drugs of abuse|journal=Annals of the New York Academy of Sciences|date=2011 Jan|volume=1216|pages=86–98|pmid=21272013|doi=10.1111/j.1749-6632.2010.05906.x}}</ref>

] (the ] ]) and ] (the ] enantiomer) have different pharmacological properties.<ref name=BehavioralNS>{{cite book | author = Heal DJ, Smith SL, Findling RL | chapter = ADHD: Current and Future Therapeutics | editor = Tannock R, Clare S | title = Behavioral Neuroscience of Attention Deficit Hyperactivity Disorder and Its Treatment | series = Current Topics in Behavioral Neurosciences | edition = | language = | publisher = Springer | location = Berlin | year = 2012 | origyear = | pages = | quote = | isbn = 3-642-24611-7 | url = http://books.google.com/books?id=aH2qWZRpcf0C&pg=PA365 }}</ref> Dextroamphetamine is several times more potent in the ] than levoamphetamine, but the two isomers have comparable activity in the ].<ref name="isbn0-683-30737-1">{{cite book | author = Lemke TL, Williams DH, Foye WO | title = Foye's principles of medicinal chemistry | edition = 5th, illustrated | publisher = Lippincott Williams & Wilkins | location = Hagerstwon, MD | year = 2002 | page = 445 | quote = | isbn = 0-683-30737-1 | chapter = Hallucinogens, stimulants, and related drugs of abuse | chapterurl = http://books.google.com.au/books?id=KGLF4ZudTyAC&pg=PA445&lpg=PA445&dq=caffiene+is+works+in+the+same+way+as+amphetamine+only+less+potent&source=bl&ots=6y9FDsWGPB&sig=v9HY-NwUzxzbEqs30oBkcemDipU&hl=en&ei=b2_IScTmMNeGkAXuu-joAg&sa=X&oi=book_result&resnum=1&ct=result }}</ref> The overall greater potency of dextroamphetamine to central actions suggests that this form may have a higher potential for abuse.<ref name="isbn1-58562-060-2">{{cite book | author = Nemeroff CB, Schatzberg AF | authorlink = | editor = | others = | title = The American Psychiatric Publishing textbook of psychopharmacology | edition = | language = | publisher = American Psychiatric Pub | location = Washington, DC | year = 2004 | pages = | isbn = 1-58562-060-2 | url = http://books.google.com/?id=5QfL19H5nVkC }}</ref>

Levoamphetamine provides mixed amphetamine salts quicker onset and longer-lasting effects than dextroamphetamine alone.<ref name="pmid15719230">{{cite journal | author = Glaser PE, Thomas TC, Joyce BM, Castellanos FX, Gerhardt GA | title = Differential effects of amphetamine isomers on dopamine release in the rat striatum and nucleus accumbens core | journal = Psychopharmacology (Berl.) | volume = 178 | issue = 2–3 | pages = 250–8 | year = 2005 | month = March | pmid = 15719230 | doi = 10.1007/s00213-004-2012-6 }}</ref>
It has been reported that certain children have a better clinical response to levoamphetamine.<ref name="Arnold">{{cite journal | title = Methyiphenidate vs. Amphetamine: Comparative review | year = 2000 | author = Arnold LE | journal = Journal of Attention Disorders | volume = 3 | issue = 4 | pages = 200–11 | doi=10.1177/108705470000300403 }}</ref>


===Pharmacokinetics=== ===Pharmacokinetics===
{{transcluded section|source=Amphetamine#Pharmacokinetics}}
{{trim|{{#section-h:Amphetamine|Pharmacokinetics}}}}
{{clear}}


===Pharmacomicrobiomics===
The ] of amphetamines vary with age and ], with dextroamphetamine being processed faster than levoamphetamine.<ref name="FDA side effects" /> The half life for D-amphetamine is 9 hours for children of ages 6-12, 11 hours in adolescents aged 13-17, and 10 hours in adults.<ref name="FDA side effects" /> For L-amphetamine, the half-life is 11 hours for children of aged 6-12, 13-14 hours in adolescents aged 13-17, and 13 hours in adults; and 11 hours in children aged 6 to 12 years.<ref name="FDA side effects" /> Both isomers reach peak plasma concentrations at 3 hours post-dose.<ref name="FDA side effects" /> Metabolism occurs mostly in the liver by the cytochrome P450 (CYP) detoxification system, with ] serving as the only currently known metabolic enzyme.<ref name="FDA side effects" /><ref>{{cite web|title=Amphetamine|url=http://www.drugbank.ca/drugs/DB00182|work=DrugBank|accessdate=30 September 2013}}</ref> Amphetamine has a variety of excreted metabolic products, some of which are also biologically active.<ref name="FDA side effects" /> Known metabolites of amphetamine include ], 4-hydroxynorephedrine, α-hydroxyamphetamine, ], ], ], ], and phenylisopropanol.<ref name="FDA side effects" /><ref name="Pubchem Kinetics">{{cite web|title=Amphetamine: Biomedical Effects and Toxicity|url=http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3007#x332|work=NCBI|publisher=Pubchem Compound|accessdate=12 October 2013}}</ref>
{{Excerpt|Amphetamine|Pharmacomicrobiomics}}


===Related endogenous compounds===
The main metabolic pathways involve aromatic para-hydroxylation, aliphatic alpha- and beta-hydroxylation, N-oxidation, N-dealkylation, and deamination.<ref name="FDA side effects" /><ref name="Pubchem Kinetics" /> These pathways include:
{{transcluded section|source=Amphetamine#Related endogenous compounds}}
{{trim|{{#section-h:Amphetamine|Related endogenous compounds}}}}
{{clear}}


== History ==
amphetamine <math>\rightarrow \;</math> α-hydroxyamphetamine <math>\rightarrow \;</math> phenylacetone <math>\rightarrow \;</math> benzoic acid <math>\rightarrow \;</math> hippuric acid.<ref name="FDA side effects" />
{{main|History and culture of substituted amphetamines}}


The pharmaceutical company Rexar reformulated their popular weight loss drug ] following its mandatory withdrawal from the market in 1973 under the ] to the ] due to the results of the ] program (which indicated a lack of efficacy). The new formulation simply replaced the two methamphetamine components with dextroamphetamine and amphetamine components of the same weight (the other two original dextroamphetamine and amphetamine components were preserved), preserved the Obetrol branding, and despite it lacking FDA approval, it still made it onto the market and was marketed and sold by Rexar for many years.
amphetamine <math>\rightarrow \;</math> 4-hydroxyamphetamine <math>\rightarrow \;</math> 4-hydroxynorephedrine.<ref name="FDA side effects" />


In 1994, Richwood Pharmaceuticals acquired Rexar and began promoting Obetrol as a treatment for ADHD (and later narcolepsy as well), now marketed under the new brand name of Adderall, a contraction of the phrase "A.D.D. for All" intended to convey that "it was meant to be kind of an inclusive thing" for marketing purposes.<ref name="Schwarz2013">{{Cite news|url=https://www.nytimes.com/2013/12/15/health/the-selling-of-attention-deficit-disorder.html|title=The Selling of Attention Deficit Disorder| vauthors = Schwarz A |date=14 December 2013|work=The New York Times|access-date=22 April 2017|issn=0362-4331|archive-date=1 March 2015|archive-url=https://web.archive.org/web/20150301054334/http://www.nytimes.com/2013/12/15/health/the-selling-of-attention-deficit-disorder.html|url-status=live}}</ref> The FDA cited the company for numerous significant CGMP violations related to Obetrol discovered during routine inspections following the acquisition (including issuing a formal warning letter for the violations), then later issued a second formal warning letter to Richwood Pharmaceuticals specifically due to violations of "the new drug and misbranding provisions of the FD&C Act". Following extended discussions with Richwood Pharmaceuticals regarding the resolution of a large number of issues related to the company's numerous violations of FDA regulations, the FDA formally approved the first Obetrol labeling/sNDA revisions in 1996, including a name change to Adderall and a restoration of its status as an approved drug product.<ref name="fda-obetrol-adderall-collection">{{cite web|title=(Collection of internal FDA information pertaining to the topic of Obetrol/Adderall)|url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/11522S010_Adderall.pdf|website=www.accessdata.fda.gov|publisher=US Food and Drug Administration|access-date=27 April 2017|archive-date=17 May 2017|archive-url=https://web.archive.org/web/20170517033551/https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/11522S010_Adderall.pdf|url-status=live}}</ref><ref name=HND>{{cite news|title=REGULATORY NEWS: Richwood's Adderall|url=http://www.elsevierbi.com/Publications/Health-News-Daily/1996/2/22/REGULATORY-NEWS-Richwoods-Adderall|archive-url=http://arquivo.pt/wayback/20160523200531/http://www.elsevierbi.com/Publications/Health-News-Daily/1996/2/22/REGULATORY-NEWS-Richwoods-Adderall|url-status=dead|archive-date=23 May 2016|access-date=29 May 2013|newspaper=Health News Daily|date=22 February 1996}}</ref> In 1997 Richwood Pharmaceuticals was acquired by Shire Pharmaceuticals in a $186 million transaction.<ref name="Schwarz2013" />
amphetamine <math>\rightarrow \;</math> norephedrine <math>\rightarrow \;</math> 4-hydroxynorephedrine.<ref name="FDA side effects" />


Richwood Pharmaceuticals, which later merged with ], introduced the current Adderall brand in 1996 as an instant-release tablet.<ref>{{cite web|title=APPROVAL LETTER|url=http://www.accessdata.fda.gov/drugsatfda_docs/nda/96/11522S010_Adderall.pdf|website=United States Food and Drug Administration|access-date=30 December 2013|archive-date=22 August 2013|archive-url=https://web.archive.org/web/20130822033454/http://www.accessdata.fda.gov/drugsatfda_docs/nda/96/11522S010_Adderall.pdf|url-status=live}}</ref> In 2006, Shire agreed to sell rights to the Adderall name for the instant-release form of the medication to ].<ref name="Duramed">{{cite web | title = August 2006 News Archives: Barr and Shire Sign Three Agreements | publisher = GenericsWeb | url = http://www.genericsweb.com/news/generics_industry_news_archive/August2006.html | access-date = 30 December 2013 | quote = WOODCLIFF LAKE, N.J., Aug. 14 /PRNewswire-FirstCall/ – Barr Pharmaceuticals, Inc. today announced that its subsidiary Duramed Pharmaceuticals, Inc. and Shire plc have signed a Product Acquisition Agreement for ADDERALL(R) (immediate-release mixed amphetamine salts) tablets and a Product Development Agreement for six proprietary products, and that its subsidiary Barr Laboratories, Inc. (Barr) has signed a Settlement and License Agreement relating to the resolution of two pending patent cases involving Shire's ADDERALL XR(R)&nbsp;... | archive-date = 8 February 2014 | archive-url = https://web.archive.org/web/20140208010946/http://www.genericsweb.com/news/generics_industry_news_archive/August2006.html | url-status = dead }}</ref> DuraMed Pharmaceuticals was acquired by ] in 2008 during their ] of ], including Barr's Duramed division.<ref name="test">{{cite web |url=https://www.drugs.com/news/teva-completes-acquisition-barr-15356.html |title=Teva Completes Acquisition of Barr |publisher=Drugs.com |access-date=31 October 2011 |archive-date=8 March 2012 |archive-url=https://web.archive.org/web/20120308020446/http://www.drugs.com/news/teva-completes-acquisition-barr-15356.html |url-status=live }}</ref>
Amphetamine is eliminated renally with a fraction of the drug being excreted unchanged (.30-.40%) at normal urinary ph.<ref name="FDA side effects" /> Amphetamine is usually eliminated within two days of the last oral dose.<ref name="Pubchem Kinetics" /> Amphetamine is a weak base with a ]; consequently, when the urinary pH is basic, more of the drug is in its free base form and less is excreted.<ref name="FDA side effects" /> For each unit of pH increase, plasma half life of amphetamine sulfate is increased by 7 hours.<ref name=delmar>{{cite book | author = Nobles S | authorlink = | title = Delmar's drug reference for health care professionals | publisher = Delmar | location = Albany, N.Y | year = 2002 | page = 10 | quote = | isbn = 0-7668-2523-X }}</ref> Apparent half-life and duration of effect increase with repeated use and accumulation of drug.<ref name="Shargel_2012">{{cite book | author = Shargel L, Wu-Pong S, Andrew BC | title = Applied Biopharmaceutics & Pharmacokinetics | year = 2012 | publisher = McGraw-Hill Medical | location = New York | isbn = 978-0071603935 | edition = 6th}}</ref><ref name="Flomenbaum_2006">{{cite book | author = Flomenbaum NE, Goldfrank LR, Hoffman RS, Howland MA, Lewin NA, Nelson LS | title = Goldfrank's Toxicologic Emergencies | year = 2006 | publisher = McGraw-Hill Medical | location = New York | isbn = 978-0071437639 | edition = 8th}}</ref>


The first generic version of Adderall IR was introduced to the market in 2002.<ref name="NDCD" /> Later on, Barr and Shire reached a settlement agreement permitting Barr to offer a generic form of the extended-release drug beginning in April 2009.<ref name="NDCD" /><ref>{{cite news| url=https://www.forbes.com/feeds/ap/2009/04/02/ap6248888.html| title=Teva sells 1st generic of Adderall XL in US| date=2 April 2009| access-date=22 April 2009| agency=Associated Press| work=Forbes Magazine| archive-url=https://web.archive.org/web/20090409082544/http://www.forbes.com/feeds/ap/2009/04/02/ap6248888.html| archive-date= 9 April 2009}}</ref>
===Detection of use===
Techniques such as ] may cross-react with a number of ], so ] methods specific for amphetamine should be employed to prevent false-positive results. ] techniques may be employed to help distinguish the source of the drug, whether obtained legally (by prescription) or illegally or possibly as a result of formation from a ] such as ] or ]. Chiral separation can be used to differentiate amphetamine mixed salts use from use of another prescription form of amphetamine or from use of illicit amphetamine<ref name="pmid15516315">{{cite journal | author = Cody JT, Valtier S, Nelson SL | title = Amphetamine excretion profile following multidose administration of mixed salt amphetamine preparation | journal = J Anal Toxicol | volume = 28 | issue = 7 | pages = 563–74 | year = 2004 | month = October | pmid = 15516315 | doi = 10.1093/jat/28.7.563 }}</ref><ref name="pmid15516295">{{cite journal | author = Paul BD, Jemionek J, Lesser D, Jacobs A, Searles DA | title = Enantiomeric Separation and Quantitation of (±)-Amphetamine, (±)-Methamphetamine, (±)-MDA, (±)-MDMA, and (±)-MDEA in Urine Specimens by GC-EI-MS after Derivatization with (R)-(−)- or (S)-(+)-α-Methoxy-α-(trifluoromethy)phenylacetyl Chloride (MTPA) | journal = J Anal Toxicol | volume = 28 | issue = 6 | pages = 449–55 | year = 2004 | month = September | pmid = 15516295 | doi = 10.1093/jat/28.6.449 }}</ref><ref>{{cite book | author =Baselt R | title = Disposition of Toxic Drugs and Chemicals in Man | edition = 9th | publisher = Biomedical Publications | location = Seal Beach, CA | year = 2011 | pages = 85–8 }}</ref>


===Commercial formulation===
==History==
Chemically, Adderall is a mixture of four amphetamine salts; specifically, it is composed of equal parts (by ]) of amphetamine ], amphetamine ], dextroamphetamine sulfate, and dextroamphetamine ].<ref name="Adderall XR all pages" /> This drug mixture has slightly stronger {{abbr|CNS|central nervous system}} effects than racemic amphetamine due to the higher proportion of dextroamphetamine.<ref name="Miller">{{cite journal | author = Miller GM | title = The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity | journal = J. Neurochem. | volume = 116 | issue = 2 | pages = 164–76 |date=January 2011| pmid = 21073468 | pmc = 3005101 | doi = 10.1111/j.1471-4159.2010.07109.x }}</ref><ref name="Westfall" /> Adderall is produced as both an immediate-release (IR) and extended-release (XR) formulation.<ref name="NDCD" /><ref name="Adderall IR"/><ref name="Adderall XR all pages">{{cite web | title = Adderall XR Prescribing Information | url = http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021303s026lbl.pdf | publisher = Shire US Inc | website = United States Food and Drug Administration | date = December 2013 | access-date = 30 December 2013 | archive-date = 30 December 2013 | archive-url = https://web.archive.org/web/20131230233702/http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021303s026lbl.pdf | url-status = live }}</ref> {{As of|2013|12}}, ten different companies produced generic Adderall IR, while ], ], and ] manufactured generic Adderall XR.<ref name="NDCD" /> {{As of|2013}}, ], the company that held the original patent for Adderall and Adderall XR, still manufactured brand name Adderall XR, but not Adderall IR.<ref name="NDCD" />
Adderall is available as an instant-release (IR) and an extended-release (XR) drug. Adderall instant-release is manufactured today by Teva and Barr Pharmaceuticals. ], the creator of Adderall IR, no longer produces it. However, Shire does continue to manufacture the extended-release version of Adderall ("Adderall XR").
Richwood Pharmaceuticals (later merged with Shire) introduced the Adderall brand in 1996 in the form of a multi-dose, instant-release tablet derived from an original formula of the weight management drug ]. In 2006, Shire agreed to sell rights to the Adderall name for this instant-release medication to ]<ref name="adderallxr">{{cite press release
| title = Barr and Shire Sign Three Agreements
| publisher = Barr Pharmaceuticals
| date = 2006-08-14
| url = http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=/www/story/08-14-2006/0004416042
| accessdate = 2009-06-23}}
</ref> DuraMed Pharmaceuticals was acquired by ] in 2008 when Teva completed its acquisition of ] (including Barr's Duramed division).<ref name="test">{{cite web|url=http://www.drugs.com/news/teva-completes-acquisition-barr-15356.html |title=Teva Completes Acquisition of Barr |publisher=Drugs.com |date= |accessdate=2011-10-31}}</ref> Therefore, following its acquisition of Duramed, Teva is in the somewhat unusual position of manufacturing both a generic formulation of Adderall instant-release (under its Barr Division) as well as "brand name" Adderall (under its DuraMed division.)


===Comparison to other formulations===
In 2001, Shire introduced an ] preparation of these ingredients in a variety of dosages under the brand name "Adderall XR," on which Shire retains exclusive patent rights until the patent expires, expected in 2018.<ref>{{cite press release
Adderall is one of several formulations of pharmaceutical amphetamine, including singular or mixed enantiomers and as an enantiomer prodrug. The table below compares these medications (based on U.S.-approved forms):
| title = Shire’s Adderall XRTM receives patent protection
{{Amphetamine base in marketed amphetamine medications}}
| publisher = Shire Pharmaceuticals
| date = 2001-11-28
| format = PDF
| url = http://www.shire.com/shire/uploads/press/shire/28112001B.pdf
| accessdate = 2009-06-23
}}{{dead link|date=October 2011}}</ref> Shire was unable to extend patents by ] and generic version of Adderall XR became available in 2009.<ref>{{cite news
| title = Shire in deal with Barr to delay launch of rival to its ADHD drug
| first = Stephen
| last = Foley
| url = http://www.independent.co.uk/news/business/news/shire-in-deal-with-barr-to-delay-launch-of-rival-to-its-adhd-drug-412102.html
| publisher = The Independent
| location = London
| date = 2006-08-16
| accessdate = 2006-06-23
}}
</ref> In 2009, Barr and Shire reached a settlement agreement permitting Barr to offer a generic form of the drug beginning April 1, 2009.<ref>{{cite news
|url=http://www.forbes.com/feeds/ap/2009/04/02/ap6248888.html
|title=Teva sells 1st generic of Adderall XL in US
|date=2009-04-02
|accessdate=2009-04-22
|agency=Associated Press
|publisher=Forbes Magazine
| archiveurl= http://web.archive.org/web/20090409082544/http://www.forbes.com/feeds/ap/2009/04/02/ap6248888.html| archivedate= 9 April 2009 <!-- Bot retrieved archive -->| deadurl= no}} {{Dead link|date=October 2010|bot=H3llBot}}</ref>


=== Patent disputes === == Society and culture ==
=== Legal status ===
Manufacturer's claims of instant release have been disputed. A US patent granted for Adderall<ref name = "US6384020">{{ cite patent | country = US | number = 6384020 | status = patent | title = A pharmaceutical composition comprising lactitol and one or more amphetamine salts in a rapid-release formulation | pubdate = | gdate = 2002-05-07 | fdate = | pridate = | inventor = Flanner HH, Chang R-K, Pinkett JE, Wassink SE, White LR | assign1 = Shire Lab Inc. }}</ref> was a pharmaceutical composition patent listing a rapid immediate-release oral dosage form. No claim of increased or smooth drug delivery was made. A study by James and colleague as published in the November 2001 issue of the Journal of the American Academy of Child and Adolescent Psychiatry, ]-controlled ] conducted among 35 children ages 5–12 indicated that patients behaved similarly to those having taken other immediate-release amphetamines. The authors found that sustained-release dextro-amphetamine (the main isomeric-amphetamine component of Adderall) had a longer duration of action; however, D-amphetamine was less effective in the first few hours.<ref name = "Buck_2002" >{{cite journal | author =Buck ML | month = March | year=2002 | title = Amphetamines in the Treatment of Attention-Deficit/Hyperactivity Disorder | journal = Pediatric Pharmacotherapy | volume = 8 | issue = 3 | url = http://www.medicine.virginia.edu/clinical/departments/pediatrics/education/pharm-news/2001-2005/200203.pdf }}</ref>
* In Canada, amphetamines are in Schedule I of the ], and can only be obtained by prescription.<ref>{{cite web|url=http://laws-lois.justice.gc.ca/eng/acts/C-38.8/|title=Controlled Drugs and Substances Act (S.C. 1996, c. 19)|date=25 April 2017|access-date=23 May 2013|archive-date=3 April 2011|archive-url=https://web.archive.org/web/20110403004630/http://laws-lois.justice.gc.ca/eng/acts/C-38.8/|url-status=live}}</ref>
* In Japan, the use, production, and import of any medicine containing amphetamines is prohibited.<ref name="url_Japan_import">{{cite web | url = http://www.mhlw.go.jp/english/topics/import/ | title = Importing or Bringing Medication into Japan for Personal Use | publisher = Japan Ministry of Health, Labour and Welfare | access-date = 13 October 2013 | archive-date = 13 July 2013 | archive-url = https://web.archive.org/web/20130713064422/http://www.mhlw.go.jp/english/topics/import/ | url-status = live }}</ref>
* In South Korea, amphetamines are prohibited.<ref name="urlMoving to Korea brings medical, social changes">{{cite web | url = https://www.koreatimes.co.kr/www/news/nation/2012/10/319_111757.html | title = Moving to Korea brings medical, social changes | author = P. | publisher = The Korean Times | date = 25 May 2012 | access-date = 8 February 2013 | archive-date = 3 October 2014 | archive-url = https://web.archive.org/web/20141003122116/http://www.koreatimes.co.kr/www/news/nation/2012/10/319_111757.html | url-status = live }}</ref>
* In Taiwan, amphetamines including Adderall are Schedule 2 drugs with a minimum five-year prison term for possession.<ref>{{cite web|url=http://www.taipeitimes.com/News/feat/archives/2002/08/11/0000159895/4|title=Caught in the Dragnet|date=2 August 2002|access-date=18 November 2018|archive-date=19 November 2018|archive-url=https://web.archive.org/web/20181119010732/http://www.taipeitimes.com/News/feat/archives/2002/08/11/0000159895/4|url-status=live}}</ref> On the contrary, ] can be legally prescribed as a form of treatment of ADHD.<ref>{{cite web|url=https://www.commonhealth.com.tw/article/88370|title=吃「聰明藥」反而變笨？小孩能吃嗎？利他能副作用公開|date=28 June 2023}}</ref>
* In Thailand, amphetamines are classified as Type 1 Narcotics.<ref>{{cite web|url=http://narcotic.fda.moph.go.th/faq/upload/Thai%20Narcotic%20Act%202012.doc._37ef.pdf |title=Thailand Law |publisher=Government of Thailand |access-date=23 May 2013 |url-status=dead |archive-url=https://web.archive.org/web/20140308001155/http://narcotic.fda.moph.go.th/faq/upload/Thai%20Narcotic%20Act%202012.doc._37ef.pdf |archive-date= 8 March 2014 }}</ref>
* In the United Kingdom, amphetamines are regarded as ] drugs. The maximum penalty for unauthorized possession is five years in prison and an unlimited fine. The maximum penalty for illegal supply is 14&nbsp;years in prison and an unlimited fine.<ref>{{cite web|title=Class A, B and C drugs |publisher=Home Office, Government of the United Kingdom |url=http://www.homeoffice.gov.uk/drugs/drugs-law/Class-a-b-c/ |access-date=23 July 2007 |archive-url=https://web.archive.org/web/20070804233232/http://www.homeoffice.gov.uk/drugs/drugs-law/Class-a-b-c/ |archive-date=4 August 2007 |url-status=dead }}</ref>
* In the United States, amphetamine is a ] prescription drug, classified as a central nervous system (CNS) stimulant.<ref name=":USAS2" />
* Internationally, amphetamine is in Schedule II of the ].<ref name="isbn92-1-148223-2">{{cite book | author = United Nations Office on Drugs and Crime | title = Preventing Amphetamine-type Stimulant Use Among Young People: A Policy and Programming Guide | publisher = United Nations | location = New York | year = 2007 | isbn = 978-92-1-148223-2 | url = http://www.unodc.org/pdf/youthnet/ATS.pdf | access-date = 7 February 2012 | archive-date = 16 October 2013 | archive-url = https://web.archive.org/web/20131016082310/http://www.unodc.org/pdf/youthnet/ATS.pdf | url-status = live }}</ref><ref>{{cite web|title=List of psychotropic substances under international control |author=International Narcotics Control Board |publisher=United Nations |location=Vienna |url=http://www.incb.org/pdf/e/list/green.pdf |access-date=19 November 2005 |archive-url=https://web.archive.org/web/20051205125434/http://www.incb.org/pdf/e/list/green.pdf |archive-date=5 December 2005 |url-status=dead }}</ref>


=== Shortages ===
==Commercial formulations==
In February 2023, news organizations began reporting on shortages of Adderall in the United States that have lasted for over five months.<ref>{{cite news |title=The ADHD medication shortage is getting worse. What went wrong?—Neither drugmakers nor the DEA anticipated a sharp rise in ADHD diagnoses during the pandemic. Now an entire class of medications may be in short supply. |date=6 February 2023 |publisher=NBC |url=https://www.nbcnews.com/health/health-news/adderall-shortage-adhd-drugs-affected-will-end-rcna66766 |access-date=25 February 2023}}</ref><ref>{{cite news |title=Adderall shortage raises questions about widespread dependency on the drug |date=25 November 2022 |work=PBS Newshour |url=https://www.pbs.org/newshour/show/adderall-shortage-raises-questions-about-widespread-dependency-on-the-drug |access-date=25 February 2023}}</ref> The ] first reported the shortage in October 2022.<ref>{{cite news | vauthors = Hart B |title=Where's the Urgency on the Adderall Shortage? |url=https://nymag.com/intelligencer/2023/03/wheres-the-urgency-on-the-adderall-shortage.html |access-date=27 March 2023 |work=Intelligencer |date=27 March 2023 |language=en-us}}</ref> In May 2023, seven months into the shortage, the ] commissioner ] stated that "a number of generic drugs are in shortage at any given time because there's not enough profit". He points out that Adderall is a special case because it is a ] and the amount available for prescription is controlled by the ]. He also faults a "tremendous increase in prescribing" due to virtual prescribing and general overprescribing and overdiagnosing, adding that "if only the people that needed these drugs got them, there probably wouldn't be a shortage".<ref>{{cite news |title='Exciting Time': FDA Commissioner Talks AI and Misinformation |date=31 May 2023|publisher=WebMD|url=https://www.webmd.com/a-to-z-guides/news/20230530/fda-commissioner-talks-ai-and-misinformation}}</ref><ref>{{cite news |title=FDA Commissioner Blames Adderall Shortage on Stimulant Overuse, Telehealth, Generics |date=2 June 2023|publisher=Anni Layne Rodgers via Additidemag|url=https://www.additudemag.com/adderall-shortage-stimulant-use-telehealth-califf/amp/}}</ref> The shortage has continued into 2024.<ref>{{Cite web|url=https://www.pharmamanufacturing.com/articles/2024/adderall-shortage-continues/|title=Adderall Shortage Persists in 2024|website=Pharma Manufacturing|date=1 June 2024|access-date=12 July 2024}}</ref><ref>{{Cite news|last=Smith|first=Jane|title=Ongoing Adderall Shortage Affects Millions|url=https://www.healthnews.com/adderall-shortage-2024|work=Health News|date=15 May 2024|access-date=12 July 2024}}</ref><ref>{{Cite web|url=https://www.fda.gov/drugs/drug-safety-and-availability/adderall-shortage-2024-update|title=FDA Update on Adderall Shortage|website=U.S. Food and Drug Administration|date=20 June 2024|access-date=12 July 2024}}</ref> It has led to the creation and expansion of businesses that outsource the search for Adderall. One company charges $50 per U.S. customer to hire workers in the Philippines or another country to make phone calls to all the pharmacies located near the customer and check whether they have any Adderall. ] have contributed to the increased demand for Adderall and the weight-loss drug ], raising concerns that patients who cannot afford to outsource their search would be left behind.<ref>{{Cite web |last=Maiberg |first=Emanuel |date=2024-06-11 |title=Americans Are Hiring People in the Philippines to Help Them Find Adderall |url=https://www.404media.co/people-in-the-philippines-are-calling-us-pharmacies-to-help-americans-find-adderall/ |access-date=2024-10-08 |website=404 Media |language=en}}</ref>


=== Historical === == Notes ==
<!-- Notes list -->
{{reflist|group=note}}
;Image legend
{{reflist|group=Color legend}}


==Reference notes==
Rexar, a pharmaceutical company, reformulated another drug, branded as Obetrol, to exclude methamphetamine and continued to sell this new formulation under the same brand name. This new unapproved formulation was later rebranded and sold as Adderall by Richwood after it acquired Rexar resulting in FDA warning in 1994. Richwood submitted this formulation as NDA 11-522 and Adderall gained FDA approval for the treatment of attention-deficit/hyperactivity disorder therapy on February 13, 1996.<ref name=HND>{{cite news|title=REGULATORY NEWS: Richwood's Adderall|url=http://www.elsevierbi.com/Publications/Health-News-Daily/1996/2/22/REGULATORY-NEWS-Richwoods-Adderall|accessdate=29 May 2013|newspaper=Health News Daily|date=22 Feb 1996}}</ref>
{{Reflist|group="sources"}}


=== Current === ==References==
{{Reflist}}


==External links==
Amphetamine mixed salts is a ] medication used primarily for the treatment of ] and ].<ref name=AHFS>{{cite web|title= Adderall|url=http://www.drugs.com/monograph/adderall.html|work=The American Society of Health-System Pharmacists|accessdate=24 May 2013}}</ref>
* {{cite web | title=Amphetamine | website=MedlinePlus | url=https://medlineplus.gov/druginfo/meds/a616004.html }}

It is a mixture of amphetamine salts consisting of equal amounts by ] of:<ref name="AdderallXR">{{cite web|title=Medication Guide Adderall XR|url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021303s015lbl.pdf|publisher=US Food and Drug Administration (FDA)|accessdate=19 May 2013}}</ref>
*amphetamine ] ] (])
*amphetamine ] (racemic)
*] sulfate
*dextroamphetamine ]

This mixture acts as a ], ], ], ] and can be mildly ].<ref name="xrPIsheet">{{cite web
|title = Adderall XR prescribing information
|url = http://pi.shirecontent.com/PI/PDFs/AdderallXR_USA_ENG.PDF
|publisher = Shire US
|month = March
|year = 2009
|accessdate = 2009-06-23
}}</ref>

Amphetamine mixed salts are available in immediate release and extended release formulations. The immediate release formulation is ] for use in ADHD and narcolepsy,.<ref name="FDA1">{{cite web
|title = ADDERALL (CII)
|url = http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/011522s040lbl.pdf
|publisher = Food and Drug Administration
|format = PDF
|month = February
|year = 2007
|accessdate = 2009-06-23
}}</ref> The extended release formulation only approved for the treatment of ADHD.<ref name="xrPIsheet"/>

==Legal status==
* In Canada, amphetamines are in Schedule I of the ], and can only be obtained by prescription.<ref name="urlControlled Drugs and Substances Act">{{cite web | url = http://laws-lois.justice.gc.ca/eng/acts/C-38.8/page-24.html#h-28 | title = Controlled Drugs and Substances Act | author = The Minister and Attorney General | date = | work = Justice Laws Website | publisher = Government of Canada }}</ref>
* In Japan, the use, production, and import of any medicine containing amphetamine are prohibited.<ref name="url_Japan_import">{{cite web | url = http://www.mhlw.go.jp/english/topics/import/ | title = Importing or Bringing Medication into Japan for Personal Use | author = | date = | work = | publisher = Japan Ministry of Health, Labour and Welfare }}</ref><ref></ref>
* In South Korea, amphetamines are prohibited.<ref name="urlMoving to Korea brings medical, social changes">{{cite web | url = http://www.koreatimes.co.kr/www/news/nation/2012/10/319_111757.html | title = Moving to Korea brings medical, social changes | author = Dr. P. | date = | work = | publisher = Tne Korean Times }}</ref>
* In Thailand, Amphetamines are classified as Type 1 Narcotics.<ref>{{cite web|url=http://narcotic.fda.moph.go.th/faq/upload/Thai%20Narcotic%20Act%202012.doc._37ef.pdf |title=Thailand Law |publisher=Government of Thailand |accessdate=2013-05-23}}</ref>
* In the United Kingdom, amphetamines are regarded as ] drugs. The maximum penalty for unauthorized possession is five years in prison and an unlimited fine. The maximum penalty for illegal supply is 14 years in prison and an unlimited fine.<ref>{{cite web | title = Class A, B and C drugs | publisher = Home Office, Government of the United Kingdom | url = http://www.homeoffice.gov.uk/drugs/drugs-law/Class-a-b-c/ | accessdate = 23 July 2007 | archiveurl = http://web.archive.org/web/20070804233232/http://www.homeoffice.gov.uk/drugs/drugs-law/Class-a-b-c/ | archivedate= 4 August 2007 <!-- Bot retrieved archive -->| deadurl= no}}</ref>
* In the United States, amphetamine is a ] prescription drug, classified as a CNS (central nervous system) stimulant.<ref>{{cite web | title=Trends in Methamphetamine/Amphetamine Admissions to Treatment: 1993–2003| author = Substance Abuse and Mental Health Services Administration | publisher = United States Department of Health and Human Services | work = The Drug and Alcohol Services Information System (DASIS) Report | url = http://www.oas.samhsa.gov/2k6/methTX/methTX.htm | accessdate = 28 February 2007 }}</ref>
* Internationally (]), amphetamine is in Schedule II of the ]<ref name="isbn92-1-148223-2">{{cite book | author = United Nations Office on Drugs and Crime | title = Preventing Amphetamine-type Stimulant Use Among Young People: A Policy and Programming Guide | publisher = United Nations | location = New York | year = 2007 | isbn = 92-1-148223-2 | url = http://www.unodc.org/pdf/youthnet/ATS.pdf }}</ref><ref>{{cite web | title = List of psychotropic substances under international control | author = International Narcotics Control Board | publisher = United Nations | location = Vienna | url = http://www.incb.org/pdf/e/list/green.pdf | format = PDF | accessdate = 19 November 2005 | archiveurl = http://web.archive.org/web/20051205125434/http://www.incb.org/pdf/e/list/green.pdf | archivedate= 5 December 2005 <!-- Bot retrieved archive -->| deadurl= no}}</ref>
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* In New Zealand, International travelers with valid prescriptions must declare them, the drugs will be taken, and the patient must go to a dispensary daily to receive their medications.
* In the Netherlands, amphetamine is a List I drugs of the ], but the dextro isomer of amphetamine is indicated for ADD/ADHD and narcolepsy and available for prescription as 5 and {{nowrap|10 mg}} generic tablets, and 5 and {{nowrap|10 mg}} gel capsules.
* In Australia, the dextro isomer of amphetamine is sold under the name dexamphetamine, and is a Schedule 8 controlled drug (available for certain indications with authority, illegal to possess otherwise).
* In India, the drug is included in the psychotropic drugs listed by the Narcotics Bureau.
-->

==References==
{{Reflist|35em}}


{{Amphetamine|state=expanded}} {{Amphetamine|state=expanded}}
{{Amphetamines}} {{Amphetamines}}
{{Stimulants}}
{{Psychostimulants, agents used for ADHD and nootropics}}
{{ADHD pharmacotherapies}}
{{stimulants}}
{{Monoamine releasing agents}}
{{TAAR ligands}}
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