Editing Adderall (section)

{{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)}}
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{{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 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
| image_class = skin-invert-image
| 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 = [[List of Schedule II controlled substances (U.S.)|Schedule II]]<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=[[Federal Register]]|publisher=[[Bureau of Narcotics and Dangerous Drugs]]}}</ref>
| legal_UN = Psychotropic Schedule II
| legal_status = 
| dependency_liability = Moderate<ref>{{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>{{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>{{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>{{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 = [[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> Adderall is indicated 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 [[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.<ref>{{Cite web |last=Susan |first=Dr |date=2025-03-29 |title=The Adderall Crisis 2025: Your Complete Guide to Safe Medication Access |url=https://pharmacarenet.com/adderall-shortage-2025-safe-access-alternatives/ |access-date=2025-04-03 |website=Pharma Care |language=en}}</ref> 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>{{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 CNS stimulant than levoamphetamine, but levoamphetamine has slightly stronger cardiovascular and peripheral effects and a longer [[elimination half-life]] than dextroamphetamine. 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>{{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>
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