Editing Methylphenidate (section)

===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" />