View source for Adderall

{{Short description|Drug mixture used mainly to treat ADHD and narcolepsy}}
{{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)}}
{{Good article}}
{{Use dmy dates|date=August 2024}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Infobox drug
| verifiedrevid      = 578643702
| drug_name          = [[Amphetamine]]/[[dextroamphetamine]]<br />[[Salt (chemistry)|salt]] mixture (1:1){{#tag:ref|[[Salt (chemistry)|Salts]] of [[amphetamine|racemic amphetamine]] and [[dextroamphetamine]] are mixed in a (1:1) ratio to produce this drug. Because the [[racemate]] is composed of equal parts dextroamphetamine and [[levoamphetamine]], this drug can also be described as a mixture of the ''D'' and ''(L)''-[[Chirality (chemistry)|enantiomers]] 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 [[Skeletal formula|skeleton]]<br />
Bottom: ''(D)''-amphetamine [[ball-and-stick model]]

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

<!-- Clinical data -->| tradename          = Adderall, Adderall XR, Mydayis
| Drugs.com          = {{drugs.com|monograph|Adderall}}
| MedlinePlus        = a601234
| DailyMedID         = Adderall
| pregnancy_AU       = 
| pregnancy_category = 
| legal_AU           = S8
| legal_CA           = Schedule I
| legal_DE           = Anlage III
| legal_NZ           = Class B
| legal_UK           = Class B
| legal_US           = Schedule II
| 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 = [[By mouth]], [[Insufflation (medicine)|insufflation]], [[rectal administration|rectal]], [[sublingual]]
| bioavailability    = Oral: ~90%<ref name="handbook2022" />
| ATC_prefix         = N06
| ATC_suffix         = BA02
| ATC_supplemental   = {{ATC|N06|BA01}}
<!-- Identifiers -->| class              = {{abbr|CNS|central nervous system}} [[stimulant]]
| 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 [[Drug nomenclature#Drug brands|trade names]]{{#tag:ref|The [[Drug nomenclature#Drug brands|trade name]] '''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 [[combination drug]] containing four [[salt (chemistry)|salts]] of [[amphetamine]]. The mixture is composed of equal parts [[racemic mixture|racemic]] amphetamine and [[dextroamphetamine]], which produces a (3:1) ratio between dextroamphetamine and [[levoamphetamine]], the two [[enantiomers]] 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 [[stimulants]], but differ enough to give Adderall an [[Pharmacodynamics|effects profile]] 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 [[attention deficit hyperactivity disorder]] (ADHD) and [[narcolepsy]]. It is also used illicitly as an [[Performance-enhancing substance|athletic performance enhancer]], [[Nootropic|cognitive enhancer]], [[anorectic|appetite suppressant]], and recreationally as a [[euphoriant]]. It is a [[central nervous system]] (CNS) [[stimulant]] of the [[substituted phenethylamine|phenethylamine class]].<ref name="Amphetamine Formulations Review" />

At therapeutic doses, Adderall causes emotional and cognitive effects such as [[euphoria]], change in [[Libido|sex drive]], increased [[wakefulness]], and improved [[Executive functions|cognitive control]]. 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 [[Rhabdomyolysis|rapid muscle breakdown]], provoke [[panic attack]]s, or induce a [[psychosis]] (e.g., [[paranoia]], [[delusion]]s, [[hallucination]]s). The side effects vary widely among individuals but most commonly include [[insomnia]], [[dry mouth]], [[Anorexia (symptom)|loss of appetite]] and [[weight loss]]. The risk of developing an [[addiction]] or [[Substance dependence|dependence]] 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 [[reinforcement|reinforcing effects]] that are present at high doses. Recreational doses of Adderall are generally much larger than prescribed [[therapeutic dose]]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"}}

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 [[neurotransmitter]]s [[norepinephrine]] and [[dopamine]] in the [[human brain|brain]], which results in part from their interactions with [[human trace amine-associated receptor&nbsp;1]] (hTAAR1) and [[vesicular monoamine transporter 2]] (VMAT2) in [[neuron]]s. Dextroamphetamine is a more potent [[Central nervous system]] ({{abbr|CNS|central nervous system}}) stimulant than levoamphetamine, but levoamphetamine has slightly stronger cardiovascular and peripheral effects and a longer [[elimination half-life]] than dextroamphetamine. The levoamphetamine component of Adderall has been reported to improve the treatment response in some individuals relative to dextroamphetamine alone. The [[active ingredient]] in Adderall, amphetamine, shares many chemical and pharmacological properties with the human [[trace amine]]s, particularly [[phenethylamine]] and {{nowrap|[[N-methylphenethylamine|''N''-methylphenethylamine]]}}, the latter of which is a [[positional isomer]] 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}}

==Uses==
{{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===
{{transcluded section|source=Amphetamine|part=yes}}
Adderall is commonly used to treat [[attention deficit hyperactivity disorder]] (ADHD) and [[narcolepsy]] (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>
{{trim|{{#section-h:Amphetamine|Medical}}}}

====Available forms====

Adderall is available as [[immediate-release]] (IR) tablets and [[extended-release]] (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 [[Modified-release dosage|double-bead formulation]]. 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 which 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 [[generic drug]]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>

===Enhancing performance===
{{transcluded section|source=Amphetamine|part=yes}}
{{trim|{{#section-h:Amphetamine|Enhancing performance}}}}

Adderall has been banned in the [[National Football League]] (NFL), [[Major League Baseball]] (MLB), [[National Basketball Association]] (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" />

===Recreational===
{{See also|History and culture of substituted amphetamines}}

Adderall has high potential for misuse as a [[recreational drug use|recreational drug]].<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 [[Excipient|insoluble fillers within the tablets]] can block small blood vessels.<ref name="NIDA" />

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 [[risk factor]]s for misusing ADHD stimulants recreationally include: possessing [[deviance (sociology)|deviant personality]] characteristics (i.e., exhibiting delinquent or deviant behavior), inadequate accommodation of disability, basing one's [[self-worth]] on external validation, low [[self-efficacy]], earning poor grades, and having an untreated [[mental health disorder]].<ref name="Abelman 68"/>

==Contraindications==
{{Excerpt|Amphetamine|Contraindications}}

==Adverse effects==
{{transcluded section|source=Amphetamine|part=yes}}
The [[adverse effects|adverse side effects]] 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" /> [[Recreational drug use#Stimulants|Recreational use]] 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==
{{Excerpt|Amphetamine|Overdose}}

==Interactions==
* [[Monoamine oxidase inhibitor]]s (MAOIs) taken with amphetamine may result in a [[hypertensive crisis]] 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>
* [[Enzyme inhibitor|Inhibitors of enzymes]] that directly metabolize amphetamine (particularly [[CYP2D6]] and [[FMO3]]) 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>
* [[Serotonin|Serotonergic]] drugs (such as most [[antidepressants]]) co-administered with amphetamine increases the risk of [[serotonin syndrome]].<ref name="Mydayis" />
* [[Stimulants]] and [[antidepressants]] ([[sedative]]s and [[depressant]]s) may increase (decrease) the drug effects of amphetamine, and vice versa.<ref name="FDA Interactions" />
* Gastrointestinal and urinary [[pH]] affect the [[absorption (pharmacology)|absorption]] and [[elimination (pharmacology)|elimination]] of amphetamine, respectively. Gastrointestinal alkalinizing agents increase the absorption of amphetamine. Urinary alkalinizing agents increase concentration of non-ionized species, decreasing urinary excretion.<ref name="FDA Interactions" />
* [[Proton-pump inhibitor]]s (PPIs) modify the absorption of Adderall XR and Mydayis.<ref name="FDA Interactions" /><ref name="Mydayis" />
* [[Zinc supplementation]] may reduce the [[minimum effective dose]] of amphetamine when it is used for the treatment of ADHD.{{#tag:ref|The human [[dopamine transporter]] contains a [[affinity (pharmacology)|high affinity]] extracellular zinc [[binding site]] which, upon zinc binding, inhibits dopamine [[reuptake]] and amplifies amphetamine-induced [[neurotransmitter efflux|dopamine efflux]] ''[[in vitro]]''.<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 [103], serving as a DAT inhibitor. In this context, controlled double-blind studies in children are of interest, which showed positive effects of zinc [supplementation] on symptoms of ADHD [105,106]. It should be stated that at this time [supplementation] 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 [3H]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 [3H]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 [[serotonin transporter]] and [[norepinephrine transporter]] 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==
===Mechanism of action===
{{For|a more complete and detailed description of amphetamine pharmacodynamics|Amphetamine#Pharmacodynamics}}
{| class="wikitable floatright" style="font-size:small;"
|+ {{Nowrap|[[Monoamine releasing agent|Monoamine release]] of [[amphetamine]] 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
|-
| [[Phenethylamine]] || 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" />
|-
| [[Dextroamphetamine]] || 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>
|-
| [[Levoamphetamine]] || 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 | title = Dopamine Transporters: Chemistry, Biology and Pharmacology | pages = 305–320 | date = July 2008 | isbn = 978-0-470-11790-3 | publisher = Wiley | location = Hoboken [NJ] | doi = | chapter-url = https://archive.org/details/dopaminetranspor0000unse/page/310/ | archive-url = https://archive.today/20241104022653/https://archive.org/details/dopaminetranspor0000unse/page/310/mode/2up | archive-date = 4 November 2024 | quote = TABLE 11-2 Comparison of the DAT- and NET-Releasing Activity of a Series of Amphetamines [...]}}</ref>
|-
| [[Dextromethamphetamine]] || 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>
|-
| [[Levomethamphetamine]] || 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 [[Monoamine releasing agent#Activity profiles|Monoamine releasing agent § Activity profiles]] 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 [[neurotransmitter]]s [[dopamine]] and [[norepinephrine]] 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., [[epinephrine]]) and neurotransmitters (e.g., [[serotonin]] and [[histamine]]) as well as the synthesis of certain [[neuropeptide]]s (e.g., [[cocaine and amphetamine regulated transcript]] (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, [[dextroamphetamine]] and [[levoamphetamine]], bind to the same [[biological target]]s,<ref name="Westfall"/><ref name="TAAR1 stereoselective" /> but their [[binding affinities]] (that is, [[Potency (pharmacology)|potency]]) differ somewhat.<ref name="Westfall"/><ref name="TAAR1 stereoselective" /> Dextroamphetamine and levoamphetamine are both potent [[full agonist]]s (activating compounds) of [[trace amine-associated receptor&nbsp;1]] (TAAR1) and interact with [[vesicular monoamine transporter 2]] (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=[[Psychopharmacology (journal)|Psychopharmacology]] |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 [[monoamine]]s (e.g., [[dopamine]], [[histamine]], [[serotonin]], [[norepinephrine]], etc.) from the [[intracellular fluid]] of a monoamine [[neuron]] into its [[synaptic vesicle]]s, which store neurotransmitters for later release (via [[exocytosis]]) 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;... [Trace aminergic] 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 [[cell membrane]]-bound [[monoamine transporter]]s (i.e., the [[dopamine transporter]], [[norepinephrine transporter]], or [[serotonin transporter]]) to either stop transporting monoamines altogether (via transporter [[endocytosis|internalization]]) or [[reverse transport|transport monoamines out of the neuron]];<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 [[synaptic cleft]].<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" />

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

===Pharmacomicrobiomics===
{{Excerpt|Amphetamine|Pharmacomicrobiomics}}

===Related endogenous compounds===
{{transcluded section|source=Amphetamine#Related endogenous compounds}}
{{trim|{{#section-h:Amphetamine|Related endogenous compounds}}}}
{{clear}}

== History ==
{{main|History and culture of substituted amphetamines}}

The pharmaceutical company Rexar reformulated their popular weight loss drug [[Obetrol]] following its mandatory withdrawal from the market in 1973 under the [[Kefauver Harris Amendment]] to the [[Federal Food, Drug, and Cosmetic Act]] due to the results of the [[Drug Efficacy Study Implementation|Drug Efficacy Study Implementation (DESI)]] 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.

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" />

Richwood Pharmaceuticals, which later merged with [[Shire plc]], 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 [[Duramed Pharmaceuticals]].<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 [[Teva Pharmaceuticals]] in 2008 during their [[Mergers and acquisitions|acquisition]] of [[Barr Pharmaceuticals]], 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>

The first generic version of Adderall IR was introduced to 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>

===Commercial formulation===
Chemically, Adderall is a mixture of four amphetamine salts; specifically, it is composed of equal parts (by [[mass]]) of amphetamine [[aspartic acid|aspartate monohydrate]], amphetamine [[sulfate]], dextroamphetamine sulfate, and dextroamphetamine [[saccharic acid|saccharate]].<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 [[Teva Pharmaceutical Industries]], [[Actavis]], and [[Barr Pharmaceuticals]] manufactured generic Adderall XR.<ref name="NDCD" /> {{As of|2013}}, [[Shire plc]], 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" />

===Comparison to other formulations===
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):
{{Amphetamine base in marketed amphetamine medications}}

== Society and culture ==
=== Legal status ===
* In Canada, amphetamines are in Schedule I of the [[Controlled Drugs and Substances Act]], 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 years 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, [[Ritalin]] 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 [[Misuse of Drugs Act 1971|Class B]] 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 [[Controlled Substances Act#Schedule II controlled substances|Schedule II]] prescription drug, classified as a central nervous system (CNS) 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 |website=The Drug and Alcohol Services Information System (DASIS) Report |url=http://www.oas.samhsa.gov/2k6/methTx/methTX.htm |access-date=6 May 2016 |url-status=dead |archive-url=https://web.archive.org/web/20130305100340/http://www.oas.samhsa.gov/2k6/methTx/methTX.htm |archive-date=5 March 2013 }}</ref>
* Internationally, amphetamine is in Schedule II of the [[Convention on Psychotropic Substances]].<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 ===
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 [[Food and Drug Administration]] 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 [[Food and Drug Administration]] commissioner [[Robert Califf]] 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 [[controlled substance]] and the amount available for prescription is controlled by the [[Drug Enforcement Administration]]. 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 [stimulant medication] 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. [[Celebrity branding|Celebrity endorsements]] have contributed to the increased demand for Adderall and the weight-loss drug [[semaglutide]], 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>

== Notes ==
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==Reference notes==
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==References==
{{Reflist}}

==External links==
* {{cite web | title=Amphetamine | website=MedlinePlus | url=https://medlineplus.gov/druginfo/meds/a616004.html }}

{{Amphetamine|state=expanded}}
{{Amphetamines}}
{{Stimulants}}
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[[Category:Adderall| ]]
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