Editing Methylphenidate (section)

== Uses ==
Methylphenidate is most commonly used to treat ADHD and narcolepsy.<ref name="drugbank">{{cite web |title=Methylphenidate |url=https://www.drugbank.ca/drugs/DB00422 |website=DrugBank |access-date=30 January 2019 |archive-url=https://web.archive.org/web/20190131040915/https://www.drugbank.ca/drugs/DB00422 |archive-date=31 January 2019 }}</ref>

=== Attention deficit hyperactivity disorder ===
Methylphenidate is used for the treatment of [[attention deficit hyperactivity disorder]] (ADHD).<ref>{{cite journal | vauthors = Fone KC, Nutt DJ | title = Stimulants: use and abuse in the treatment of attention deficit hyperactivity disorder | journal = Current Opinion in Pharmacology | volume = 5 | issue = 1 | pages = 87–93 | date = February 2005 | pmid = 15661631 | doi = 10.1016/j.coph.2004.10.001 }}</ref> The dosage may vary and is [[dose titration|titrated]] to effect, with some guidelines recommending initial treatment with a low dose.<ref name="Huss Duhan Gandhi Chen 2021 p.">{{cite journal | vauthors = Huss M, Duhan P, Gandhi P, Chen CW, Spannhuth C, Kumar V | title = Methylphenidate dose optimization for ADHD treatment: review of safety, efficacy, and clinical necessity | journal = Neuropsychiatric Disease and Treatment | volume = 13 | pages = 1741–1751 | date = 2 June 2021 | pmid = 28740389 | pmc = 5505611 | doi = 10.2147/NDT.S130444 | doi-access = free }}</ref> Methylphenidate is available in both immediate-release and [[Modified-release dosage|modified-release]] formulations.<ref name="Management 2011 pp. 1007–1022">{{cite journal | vauthors = Wolraich M, Brown L, Brown RT, DuPaul G, Earls M, Feldman HM, Ganiats TG, Kaplanek B, Meyer B, Perrin J, Pierce K, Reiff M, Stein MT, Visser S | title = ADHD: clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit / hyperactivity disorder in children and adolescents | journal = Pediatrics | volume = 128 | issue = 5 | pages = 1007–1022 | date = November 2011 | pmid = 22003063 | pmc = 4500647 | doi = 10.1542/peds.2011-2654 }}</ref><ref name="Neinstein-2009">{{cite book | vauthors = Neinstein L | year=2009 | title=Handbook of Adolescent Health Care | publisher=Wolters Kluwer Health / Lippincott Williams & Wilkins | location=Philadelphia, PA | isbn=978-0-7817-9020-8 | oclc=226304727 }}{{rp|722}}</ref> Methylphenidate is not approved for children under six years of age.<ref>{{cite journal | vauthors = Vitiello B | date = October 2001 | title = Psychopharmacology for young children: clinical needs and research opportunities | journal = Pediatrics | volume = 108 | issue = 4 | pages = 983–989 | pmid = 11581454 | doi = 10.1542/peds.108.4.983 | s2cid = 33417584 }}</ref><ref>{{cite journal | vauthors = Hermens DF, Rowe DL, Gordon E, Williams LM | date = May 2006 | title = Integrative neuroscience approach to predict ADHD stimulant response | journal = Expert Review of Neurotherapeutics | volume = 6 | issue = 5 | pages = 753–763 | pmid = 16734523 | doi = 10.1586/14737175.6.5.753 | s2cid = 15971025 }}</ref>

The International Consensus Statement on ADHD shows that the results from [[systematic review]]s, [[Meta-analysis|meta-analyses]] and large scale studies are clear: methylphenidate is safe and among the most efficacious drugs in all of medicine; treatment in the long-term substantially reduces accidental injuries, traumatic brain injury, substance abuse, cigarette smoking, educational underachievement, bone fractures, sexually transmitted infections, depression, suicide, criminal activity, teenage pregnancy, vehicle crashes, burn injuries and overall-cause mortality, and eliminates the increased risk for obesity.<ref name="Faraone_2021">{{cite journal |vauthors=Faraone SV, Banaschewski T, Coghill D, Zheng Y, Biederman J, Bellgrove MA, Newcorn JH, Gignac M, Al Saud NM, Manor I, Rohde LA, Yang L, Cortese S, Almagor D, Stein MA, Albatti TH, Aljoudi HF, Alqahtani MM, Asherson P, Atwoli L, Bölte S, Buitelaar JK, Crunelle CL, Daley D, Dalsgaard S, Döpfner M, Espinet S, Fitzgerald M, Franke B, Gerlach M, Haavik J, Hartman CA, Hartung CM, Hinshaw SP, Hoekstra PJ, Hollis C, Kollins SH, Sandra Kooij JJ, Kuntsi J, Larsson H, Li T, Liu J, Merzon E, Mattingly G, Mattos P, McCarthy S, Mikami AY, Molina BS, Nigg JT, Purper-Ouakil D, Omigbodun OO, Polanczyk GV, Pollak Y, Poulton AS, Rajkumar RP, Reding A, Reif A, Rubia K, Rucklidge J, Romanos M, Ramos-Quiroga JA, Schellekens A, Scheres A, Schoeman R, Schweitzer JB, Shah H, Solanto MV, Sonuga-Barke E, Soutullo C, Steinhausen HC, Swanson JM, Thapar A, Tripp G, van de Glind G, van den Brink W, Van der Oord S, Venter A, Vitiello B, Walitza S, Wang Y |date=September 2021 |title=The World Federation of ADHD International Consensus Statement: 208 Evidence-based conclusions about the disorder |journal=Neuroscience and Biobehavioral Reviews |volume=128 |pages=789–818 |doi=10.1016/j.neubiorev.2021.01.022 |pmc=8328933 |pmid=33549739}}</ref>

One committee from the [[World Health Organization]] (WHO) responsible for the [[World Health Organization Essential Medicines List]] rejected an application in 2019, and a second application endorsed by 51 professional medical groups in 2021, for methylphenidate's inclusion due to uncertainty about its efficacy and safety.<ref>{{cite web |title=eEML - Electronic Essential Medicines List |url=https://list.essentialmeds.org/recommendations/1200 |publisher=World Health Organization |access-date=26 March 2020 |archive-date=26 March 2020 |archive-url=https://web.archive.org/web/20200326025659/https://list.essentialmeds.org/recommendations/1200 |url-status=live }}</ref><ref>{{Cite web |title=A.21 Methylphenidate – attention-deficit hyperactivity disorder – EML and EMLc |url=https://www.who.int/groups/expert-committee-on-selection-and-use-of-essential-medicines/23rd-expert-committee/a21-methylphenidate |access-date=1 May 2024 |publisher=World Health Organization}}</ref> However, in November 2023, the WHO Mental Health Gap Action Programme Guidelines for mental, neurological, and substance use disorders recommended that methylphenidate should be considered for children aged 6 years and older who have ADHD, noting specifically that, "methylphenidate treatment shows substantial effects on symptom reduction",<ref>{{Cite web |title=Mental Health Gap Action Programme (mhGAP) guideline for mental, neurological and substance use disorders |url=https://www.who.int/publications-detail-redirect/9789240084278  |access-date=1 May 2024 |publisher=World Health Organization |date=20 November 2023 |edition=Third}}</ref> in addition to other WHO publications.<ref>{{cite web |url=https://applications.emro.who.int/docs/EMRPUB_leaflet_2019_mnh_214_en.pdf |title=Attention Deficit Hyperactivity Disorder (ADHD) |publisher=World Health Organization |date=2019 |access-date=13 January 2025}}</ref> In 2024, the [[European Child & Adolescent Psychiatry|European Society for Child and Adolescent Psychiatry]] (ESCAP) and the [[American Academy of Pediatrics|American Academy of Paediatrics]] (AAP) endorsed the inclusion of methylphenidate in the WHO EML.<ref>{{cite journal | vauthors = Cortese S, Coghill D, Fegert JM, Mattingly GW, Rohde LA, Wong IC, Faraone SV | title = ESCAP endorses the inclusion of methylphenidate in the WHO model lists of essential medicines and in the Union list of critical medicines | journal = European Child & Adolescent Psychiatry | volume = 33 | issue = 5 | pages = 1605–1608 | date = May 2024 | pmid = 38662057 | doi = 10.1007/s00787-024-02443-5 }}</ref><ref>{{cite journal | vauthors = Cortese S, Coghill D, Mattingly GW, Rohde LA, Thom RP, Wilens TE, Wong IC, Faraone SV | title = AACAP Endorses the Inclusion of Methylphenidate in the WHO Model Lists of Essential Medicines | journal = Journal of the American Academy of Child and Adolescent Psychiatry | volume = 63 | issue = 7 | pages = 663–665 | date = July 2024 | pmid = 38428579 | doi = 10.1016/j.jaac.2024.02.008 | url = https://eprints.soton.ac.uk/492445/1/AACAP_endorses.docx }}</ref> A new application for methylphenidate's inclusion is currently pending review,<ref>{{Cite web |title=A.19 Methylphenidate - attention deficit hyperactivity disorder |url=https://www.who.int/groups/expert-committee-on-selection-and-use-of-essential-medicines/25th-expert-committee-on-selection-and-use-of-essential-medicines/a.19-methylphenidate-attention-deficit-hyperactivity-disorder |access-date=2025-03-22 |website=www.who.int |language=en}}</ref> having sparked debate in the comment process among researchers engaged in the evaluation of the evidence-base.<ref>{{Cite web |last=Storebø |first=Ole Jakob |title=Correspondence with the 2025 WHO Expert Committee: A.19 Methylphenidate – attention deficit hyperactivity disorder |url=https://cdn.who.int/media/docs/default-source/2025-eml-expert-committee/comments/a.19_comments-storeb.pdf?sfvrsn=db66ddce_1}}</ref><ref>{{Cite web |last=Bleazard |first=Ryan |title=Correspondence with the 2025 WHO Expert Committee: A.19 Methylphenidate – attention deficit hyperactivity disorder |url=https://cdn.who.int/media/docs/default-source/2025-eml-expert-committee/comments/a.19_comments_bleazard.pdf?sfvrsn=a7894ebc_1}}</ref><ref>{{Cite web |last=Manor |first=Iris |title=Correspondence with the 2025 WHO Expert Committee: A.19 Methylphenidate – attention deficit hyperactivity disorder |url=https://cdn.who.int/media/docs/default-source/2025-eml-expert-committee/comments/a.19_comments-manor74645dfb-3b22-4640-a7d3-d632e6d1a84f.pdf?sfvrsn=c34bd1e2_1}}</ref>

Safety and efficacy data have been reviewed extensively by medical regulators (e.g., the US [[Food and Drug Administration]] and the [[European Medicines Agency]]), the developers of evidence-based national guidelines (e.g., the UK [[National Institute for Health and Care Excellence]] and the [[American Academy of Pediatrics]]), and government agencies who have endorsed these guidelines (e.g., the Australian [[National Health and Medical Research Council]]). These professional groups unanimously conclude, based on the scientific evidence, that methylphenidate is safe and effective and should be considered as a first-line treatment for ADHD.<ref name="Faraone_2021" />

Since ADHD diagnosis has increased around the world, methylphenidate may be misused as a "study drug" by some populations, which may be harmful.<ref name="Abelman 68">{{cite journal | vauthors = Abelman DD | 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 | page = 68 | date = October 2017 | pmid = 28985738 | pmc = 5639593 | doi = 10.1186/s12954-017-0194-6 | doi-access = free }}</ref> This also applies to people who may be experiencing a different issue and are [[Medical error|misdiagnosed]] with ADHD.<ref name="Abelman 68" /> People in this category are prone to experience the negative side-effects of the drug, which can worsen their condition.<ref name="Abelman 68" />

Long-term meta-analyses and systematic reviews show that the medications used to treat ADHD are not associated with observed deficits in brain structure, but with improved brain development and functioning, most prominently in inferior frontal and striatal regions.<ref name="Faraone_2021" /> The most comprehensive meta-analysis available (19 studies with over 3.9 million participants) found "no statistically significant association between ADHD medications [including methylphenidate] and the risk of cardiovascular event among children and adolescents, young and middle-aged adults, or older adults";<ref>{{cite journal | vauthors = Zhang L, Yao H, Li L, Du Rietz E, Andell P, Garcia-Argibay M, D'Onofrio BM, Cortese S, Larsson H, Chang Z | title = Risk of Cardiovascular Diseases Associated With Medications Used in Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-analysis | journal = JAMA Network Open | volume = 5 | issue = 11 | pages = e2243597 | date = November 2022 | pmid = 36416824 | pmc = 9685490 | doi = 10.1001/jamanetworkopen.2022.43597 }}</ref> as do other systematic reviews and meta-analyses.<ref>{{cite journal | vauthors = Liang EF, Lim SZ, Tam WW, Ho CS, Zhang MW, McIntyre RS, Ho RC | title = The Effect of Methylphenidate and Atomoxetine on Heart Rate and Systolic Blood Pressure in Young People and Adults with Attention-Deficit Hyperactivity Disorder (ADHD): Systematic Review, Meta-Analysis, and Meta-Regression | journal = International Journal of Environmental Research and Public Health | volume = 15 | issue = 8 | pages = 1789 | date = August 2018 | pmid = 30127314 | pmc = 6121294 | doi = 10.3390/ijerph15081789 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Liu H, Feng W, Zhang D | title = Association of ADHD medications with the risk of cardiovascular diseases: a meta-analysis | journal = European Child & Adolescent Psychiatry | volume = 28 | issue = 10 | pages = 1283–1293 | date = October 2019 | pmid = 30143889 | doi = 10.1007/s00787-018-1217-x }}</ref><ref>{{cite journal | vauthors = Habel LA, Cooper WO, Sox CM, Chan KA, Fireman BH, Arbogast PG, Cheetham TC, Quinn VP, Dublin S, Boudreau DM, Andrade SE, Pawloski PA, Raebel MA, Smith DH, Achacoso N, Uratsu C, Go AS, Sidney S, Nguyen-Huynh MN, Ray WA, Selby JV | title = ADHD medications and risk of serious cardiovascular events in young and middle-aged adults | journal = JAMA | volume = 306 | issue = 24 | pages = 2673–2683 | date = December 2011 | pmid = 22161946 | pmc = 3350308 | doi = 10.1001/jama.2011.1830 }}</ref>

=== Narcolepsy ===
[[Narcolepsy]], a [[chronic condition|chronic]] [[sleep disorder]] characterized by overwhelming daytime drowsiness and uncontrollable sleep, is treated primarily with stimulants. Methylphenidate is considered effective in increasing [[wakefulness]], vigilance, and performance.<ref name="pmid9484423">{{cite journal | vauthors = Fry JM | title = Treatment modalities for narcolepsy | journal = Neurology | volume = 50 | issue = 2 Suppl 1 | pages = S43–S48 | date = February 1998 | pmid = 9484423 | doi = 10.1212/WNL.50.2_Suppl_1.S43 | s2cid = 36824088 }}</ref> Methylphenidate improves measures of [[somnolence]] on [[medical test|standardized tests]], such as the [[Multiple Sleep Latency Test]] (MSLT), but performance does not improve to levels comparable to healthy people.<ref name="pmid7701190">{{cite journal | vauthors = Mitler MM | title = Evaluation of treatment with stimulants in narcolepsy | journal = Sleep | volume = 17 | issue = 8 Suppl | pages = S103–S106 | date = December 1994 | pmid = 7701190 | doi = 10.1093/sleep/17.suppl_8.S103 | doi-access = free }}</ref>

=== Other medical uses ===
Methylphenidate may also be prescribed for [[off-label use]] in [[treatment-resistant depression|treatment-resistant cases]] of [[bipolar disorder]] and [[major depressive disorder]].<ref name="pmid25312027">{{cite journal | vauthors = Dell'Osso B, Dobrea C, Cremaschi L, Arici C, Altamura AC | title = Wake-promoting pharmacotherapy for psychiatric disorders | journal = Current Psychiatry Reports | volume = 16 | issue = 12 | page = 524 | date = December 2014 | pmid = 25312027 | doi = 10.1007/s11920-014-0524-2 | s2cid = 26314915 }}</ref> It can also improve depression in several groups, including [[stroke]], [[cancer]], and [[HIV-positive]] patients.<ref name="pmid15079851">{{cite journal | vauthors = Leonard BE, McCartan D, White J, King DJ | title = Methylphenidate: A review of its neuropharmacological, neuropsychological, and adverse clinical effects | journal = Human Psychopharmacology | volume = 19 | issue = 3 | pages = 151–180 | date = April 2004 | pmid = 15079851 | doi = 10.1002/hup.579 | s2cid = 21173346 }}</ref> There is weak evidence in favor of methylphenidate's effectiveness for depression,<ref>{{cite journal | vauthors = Bahji A, Mesbah-Oskui L | title = Comparative efficacy and safety of stimulant-type medications for depression: A systematic review and network meta-analysis | journal = Journal of Affective Disorders | volume = 292 | pages = 416–423 | date = September 2021 | pmid = 34144366 | doi = 10.1016/j.jad.2021.05.119 }}</ref> including providing additional benefit in combination with [[antidepressant]]s.<ref>{{cite journal | vauthors = Pary R, Scarff JR, Jijakli A, Tobias C, Lippmann S | title = A Review of Psychostimulants for Adults With Depression | journal = Federal Practitioner | volume = 32 | issue = Suppl 3 | pages = 30S–37S | date = April 2015 | pmid = 30766117 | pmc = 6375494 }}</ref> In individuals with [[terminal illness|terminal cancer]], methylphenidate can be used to counteract [[opioid]]-induced [[somnolence]], to increase the [[analgesic]] effects of opioids, to treat depression, and to improve cognitive function.<ref name="pmid11773187">{{cite journal | vauthors = Rozans M, Dreisbach A, Lertora JJ, Kahn MJ | title = Palliative uses of methylphenidate in patients with cancer: a review | journal = Journal of Clinical Oncology | volume = 20 | issue = 1 | pages = 335–339 | date = January 2002 | pmid = 11773187 | doi = 10.1200/JCO.20.1.335 }}</ref> A 2021 systematic review and meta-analysis found that all studies on geriatric depression reported positive results of methylphenidate use; the review recommended short-term use in combination with [[citalopram]].<ref>{{cite journal | vauthors = Smith KR, Kahlon CH, Brown JN, Britt RB | title = Methylphenidate use in geriatric depression: A systematic review | journal = International Journal of Geriatric Psychiatry | volume = 36 | issue = 9 | pages = 1304–1312 | date = September 2021 | pmid = 33829530 | doi = 10.1002/gps.5536 | s2cid = 233184870 }}</ref> A 2018 review found low-quality evidence supporting its use to treat apathy as seen in [[Alzheimer's disease]], in addition to slight benefits for cognition and cognitive performance.<ref>{{cite journal | vauthors = Ruthirakuhan MT, Herrmann N, Abraham EH, Chan S, Lanctôt KL | title = Pharmacological interventions for apathy in Alzheimer's disease | journal = The Cochrane Database of Systematic Reviews | volume = 5 | issue = 6 | page = CD012197 | date = May 2018 | pmid = 29727467 | pmc = 6494556 | doi = 10.1002/14651858.CD012197.pub2 }}</ref>

===Enhancing performance===

Methylphenidate's efficacy as an [[Performance-enhancing substance|athletic performance enhancer]], [[Nootropic|cognitive enhancer]], [[aphrodisiac]], and [[euphoriant]] is supported by research.<ref>{{cite web |date=1 June 2018 |series=Attention deficit hyperactivity disorder (ADHD) |title=Treatment |url=https://www.nhs.uk/conditions/attention-deficit-hyperactivity-disorder-adhd/treatment/ |access-date=24 October 2022 |website=nhs.uk |language=en}}</ref><ref>{{cite journal | vauthors = Robison LS, Ananth M, Hadjiargyrou M, Komatsu DE, Thanos PK | title = Chronic oral methylphenidate treatment reversibly increases striatal dopamine transporter and dopamine type&nbsp;1 receptor binding in rats | journal = Journal of Neural Transmission | volume = 124 | issue = 5 | pages = 655–667 | date = May 2017 | pmid = 28116523 | pmc = 5400672 | doi = 10.1007/s00702-017-1680-4 }}</ref><ref name="Unambiguous">{{cite journal | vauthors = Spencer RC, Devilbiss DM, Berridge CW | title = The cognition-enhancing effects of psychostimulants involve direct action in the prefrontal cortex | journal = Biological Psychiatry | volume = 77 | issue = 11 | pages = 940–950 | date = June 2015 | pmid = 25499957 | pmc = 4377121 | doi = 10.1016/j.biopsych.2014.09.013 }}</ref><ref name="Cognitive & motivational effects">{{cite journal | vauthors = Ilieva IP, Hook CJ, Farah MJ | title = Prescription Stimulants' Effects on Healthy Inhibitory Control, Working Memory, and Episodic Memory: A Meta-analysis | journal = Journal of Cognitive Neuroscience | volume = 27 | issue = 6 | pages = 1069–1089 | date = June 2015 | pmid = 25591060 | doi = 10.1162/jocn_a_00776 | s2cid = 15788121 | url = https://repository.upenn.edu/cgi/viewcontent.cgi?article=1141&context=neuroethics_pubs | access-date = 12 June 2022 | archive-date = 26 May 2022 | archive-url = https://web.archive.org/web/20220526103820/https://repository.upenn.edu/cgi/viewcontent.cgi?article=1141&context=neuroethics_pubs | url-status = live | url-access = subscription }}</ref><ref name="pmid26813119">{{cite journal | vauthors = Busardò FP, Kyriakou C, Cipolloni L, Zaami S, Frati P | title = From Clinical Application to Cognitive Enhancement: The Example of Methylphenidate | journal = Current Neuropharmacology | volume = 14 | issue = 1 | pages = 17–27 | date = 2016 | pmid = 26813119 | pmc = 4787280 | doi = 10.2174/1570159x13666150407225902 }}</ref><ref name="pmid30657540">{{cite journal | vauthors = Carlier J, Giorgetti R, Varì MR, Pirani F, Ricci G, Busardò FP | title = Use of cognitive enhancers: methylphenidate and analogs | journal = European Review for Medical and Pharmacological Sciences | volume = 23 | issue = 1 | pages = 3–15 | date = January 2019 | pmid = 30657540 | doi = 10.26355/eurrev_201901_16741 | s2cid = 58643522 }}</ref><ref name="pmid33201262">{{cite journal | vauthors = Repantis D, Bovy L, Ohla K, Kühn S, Dresler M | title = Cognitive enhancement effects of stimulants: a randomized controlled trial testing methylphenidate, modafinil, and caffeine | journal = Psychopharmacology | volume = 238 | issue = 2 | pages = 441–451 | date = February 2021 | pmid = 33201262 | pmc = 7826302 | doi = 10.1007/s00213-020-05691-w }}</ref><ref name="Libido2008">{{cite journal | vauthors = Montgomery KA | title = Sexual desire disorders | journal = Psychiatry | volume = 5 | issue = 6 | pages = 50–55 | date = June 2008 | pmid = 19727285 | pmc = 2695750 }}</ref><ref name="Berezanskaya_2022">{{cite journal | vauthors = Berezanskaya J, Cade W, Best TM, Paultre K, Kienstra C | title = ADHD Prescription Medications and Their Effect on Athletic Performance: A Systematic Review and Meta-analysis | journal = Sports Medicine - Open | volume = 8 | issue = 1 | pages = 5 | date = January 2022 | pmid = 35022919 | pmc = 8755863 | doi = 10.1186/s40798-021-00374-y | doi-access = free }}</ref> However, the manner in which methylphenidate is used for these purposes (high dosages, alternate routes of administration, during sleep deprivation, etc.) can result in severe unintended side effects.<ref>{{cite journal | vauthors = Thoenes MM | title = Heat-related illness risk with methylphenidate use | language = English | journal = Journal of Pediatric Health Care | volume = 25 | issue = 2 | pages = 127–132 | date = 1 March 2011 | pmid = 21320685 | doi = 10.1016/j.pedhc.2010.07.006 }}</ref><ref>{{cite journal | vauthors = Docherty JR, Alsufyani HA | title = Cardiovascular and temperature adverse actions of stimulants | journal = British Journal of Pharmacology | volume = 178 | issue = 13 | pages = 2551–2568 | date = July 2021 | pmid = 33786822 | doi = 10.1111/bph.15465 | s2cid = 232431910 | doi-access = free }}</ref><ref name="Berezanskaya_2022" />
A 2015 review found that therapeutic doses of [[amphetamine]] and methylphenidate result in modest improvements in [[cognition]], including [[working memory]], [[episodic memory]], and [[inhibitory control]], in normal healthy adults;<ref name="Spencer-Devilbiss-Berridge-2015">{{cite journal | vauthors = Spencer RC, Devilbiss DM, Berridge CW | title = The cognition-enhancing effects of psychostimulants involve direct action in the prefrontal cortex | journal = Biological Psychiatry | volume = 77 | issue = 11 | pages = 940–950 | date = June 2015 | pmid = 25499957 | pmc = 4377121 | doi = 10.1016/j.biopsych.2014.09.013}}</ref>{{efn|
The procognitive actions of psychostimulants are only associated with low doses ... cognition-enhancing effects of psychostimulants involve the preferential elevation of catecholamines in the PFC and the subsequent activation of norepinephrine α2 and dopamine D1 receptors. ... This differential modulation of PFC-dependent processes across dose appears to be associated with the differential involvement of noradrenergic α2 versus α1 receptors.<ref name=Spencer-Devilbiss-Berridge-2015/>
}}<ref name="Ilieva-Hook-Farah-2015">{{cite journal | vauthors = Ilieva IP, Hook CJ, Farah MJ | title = Prescription Stimulants' Effects on Healthy Inhibitory Control, Working Memory, and Episodic Memory: A Meta-analysis | journal = Journal of Cognitive Neuroscience | volume = 27 | issue = 6 | pages = 1069–1089 | date = June 2015 | pmid = 25591060 | doi = 10.1162/jocn_a_00776 | url = https://repository.upenn.edu/neuroethics_pubs/130 | access-date = 14 November 2018 | url-status = live | s2cid = 15788121 | archive-url = https://web.archive.org/web/20180919111616/https://repository.upenn.edu/neuroethics_pubs/130/ | archive-date = 19 September 2018 | url-access = subscription }}</ref>{{efn|
The results of this meta-analysis ... do confirm the reality of cognitive enhancing effects for normal healthy adults in general, while also indicating that these effects are modest in size.<ref name=Ilieva-Hook-Farah-2015/>
}}
the cognition-enhancing effects of these drugs are known to occur through the [[indirect agonist|indirect activation]] of both [[dopamine receptor D1|dopamine receptor&nbsp;D<sub>1</sub>]] and [[Alpha-2 adrenergic receptor|adrenoceptor&nbsp;α<sub>2</sub>]] in the [[prefrontal cortex]].<ref name="Spencer-Devilbiss-Berridge-2015" /> Methylphenidate and other ADHD stimulants also improve task [[Salience (neuroscience)|saliency]] and increase arousal.<ref name="Malenka_2009" /><ref name="Continuum">{{cite journal | vauthors = Wood S, Sage JR, Shuman T, Anagnostaras SG | title = Psychostimulants and cognition: a continuum of behavioral and cognitive activation | journal = Pharmacological Reviews | volume = 66 | issue = 1 | pages = 193–221 | date = January 2014 | pmid = 24344115 | pmc = 3880463 | doi = 10.1124/pr.112.007054 }}</ref> Stimulants such as amphetamine and methylphenidate can improve performance on difficult and boring tasks,<ref name="Malenka_2009">{{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY | year = 2009 | chapter = Higher cognitive function and behavioral control | title = Molecular Neuropharmacology: A foundation for clinical neuroscience | publisher = McGraw-Hill Medical | location = New York, NY | isbn = 978-0-07-148127-4 | page = 318 | edition = 2nd}}</ref>{{efn|
Therapeutic (relatively low) doses of psychostimulants, such as methylphenidate and amphetamine, improve performance on working memory tasks both in normal subjects and those with ADHD ... [It] is now believed that dopamine and norepinephrine, but not serotonin, produce the beneficial effects of stimulants on working memory. At abused (relatively high) doses, stimulants can interfere with working memory and cognitive control ... stimulants act not only on working memory function, but also on general levels of arousal and, within the nucleus accumbens, improve the saliency of tasks. Thus, stimulants improve performance on effortful but tedious tasks ... through indirect stimulation of dopamine and norepinephrine receptors.<ref name=Malenka_2009/>
}}<ref name="Continuum" /><ref>{{cite journal | vauthors = Agay N, Yechiam E, Carmel Z, Levkovitz Y | title = Non-specific effects of methylphenidate (Ritalin) on cognitive ability and decision-making of ADHD and healthy adults | journal = Psychopharmacology | volume = 210 | issue = 4 | pages = 511–519 | date = July 2010 | pmid = 20424828 | doi = 10.1007/s00213-010-1853-4 | s2cid = 17083986}}</ref> and are used by some students as a study and test-taking aid.<ref name="Abelman 68" /><ref>{{cite web | work = JS Online | vauthors = Twohey M | date = 26 March 2006 | title = Pills become an addictive study aid | access-date = 2 December 2007 | url = http://www.jsonline.com/story/index.aspx?id=410902 | archive-url = https://web.archive.org/web/20070815200239/http://www.jsonline.com/story/index.aspx?id=410902 | archive-date = 15 August 2007}}</ref> Based upon studies of self-reported illicit stimulant use, performance-enhancing use rather than use as a [[recreational drug]], is the primary reason that students use stimulants.<ref name="pmid16999660">{{cite journal | vauthors = Teter CJ, McCabe SE, LaGrange K, Cranford JA, Boyd CJ | title = Illicit use of specific prescription stimulants among college students: prevalence, motives, and routes of administration | journal = Pharmacotherapy | volume = 26 | issue = 10 | pages = 1501–1510 | date = October 2006 | pmid = 16999660 | pmc = 1794223 | doi = 10.1592/phco.26.10.1501}}</ref>

Excessive doses of methylphenidate, above the therapeutic range, can interfere with working memory and [[cognitive control]].<ref name="Malenka_2009" /><ref name="Continuum" /> Like amphetamine and [[bupropion]], methylphenidate increases stamina and [[endurance]] in humans primarily through [[reuptake inhibition]] of dopamine in the central nervous system.<ref name="Roelands_2013">{{cite journal | vauthors = Roelands B, de Koning J, Foster C, Hettinga F, Meeusen R | title = Neurophysiological determinants of theoretical concepts and mechanisms involved in pacing | journal = Sports Medicine | volume = 43 | issue = 5 | pages = 301–311 | date = May 2013 | pmid = 23456493 | doi = 10.1007/s40279-013-0030-4 | s2cid = 30392999 }}</ref> Similar to the loss of cognitive enhancement when using large amounts, large doses of methylphenidate can induce [[side effect]]s that impair athletic performance, such as [[rhabdomyolysis]] and [[hyperthermia]].<ref name="Daytrana FDA label">{{cite web |date=15 June 2021 |title=Daytrana- methylphenidate patch |url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2c312c31-3198-4775-91ab-294e0b4b9e7f |url-status=live |archive-url=https://web.archive.org/web/20220319232456/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2c312c31-3198-4775-91ab-294e0b4b9e7f |archive-date=19 March 2022 |access-date=26 March 2022 |website=DailyMed}}</ref> While literature suggests it might improve cognition, most authors agree that using the drug as a study aid when an ADHD diagnosis is not present does not actually improve [[GPA]].<ref name="Abelman 68" /> Moreover, it has been suggested that students who use the drug for studying may be self-medicating for potentially deeper underlying issues.<ref name="Abelman 68" />