Editing Stimulant (section)

== Medical uses ==
Stimulants are widely used throughout the world as [[prescription medicine]]s as well as without a prescription (either legally or [[Prohibition (drugs)|illicitly]]) as [[performance-enhancing substance|performance-enhancing]] or [[recreational drug use|recreational]] drugs. Among narcotics, stimulants produce a noticeable crash or ''[[Comedown (drugs)|comedown]]'' at the end of their effects. In the US, the most frequently prescribed stimulants as of 2013 were [[lisdexamfetamine]] (Vyvanse), [[methylphenidate]] (Ritalin), and [[amphetamine]] (Adderall).<ref name="www.drugs.com-top-100-2013">{{cite web|title=Top 100 Drugs for Q4 2013 by Sales – U.S. Pharmaceutical Statistics|url=https://www.drugs.com/stats/top100/sales|website=www.drugs.com|url-status=live|archive-url=https://web.archive.org/web/20130814232045/http://www.drugs.com/stats/top100/sales|archive-date=14 August 2013}}</ref> It was estimated in 2015 that the percentage of the world population that had used [[cocaine]] during a year was 0.4%. For the category "amphetamines and prescription stimulants" (with "amphetamines" including [[amphetamine]] and [[methamphetamine]]) the value was 0.7%, and for [[MDMA]] 0.4%.<ref name="World-Drug-Report-2015">{{cite web|title=World Drug Report 2015|url=https://www.unodc.org/documents/wdr2015/World_Drug_Report_2015.pdf|url-status=live|archive-url=https://web.archive.org/web/20160215044543/https://www.unodc.org/documents/wdr2015/World_Drug_Report_2015.pdf|archive-date=15 February 2016|page=149}}</ref>

Stimulants have been used in medicine for many conditions including [[obesity]], [[sleep disorders]], [[mood disorders]], [[impulse control disorders]], [[asthma]], [[nasal congestion]] and, in case of cocaine, as [[local anesthetic]]s.<ref name="pmid16848922">{{cite journal|last1=Harper|first1=S. J.|last2=Jones|first2=N. S.|title=Cocaine: what role does it have in current ENT practice? A review of the current literature|journal=The Journal of Laryngology and Otology|date=1 October 2006|volume=120|issue=10|pages=808–811|doi=10.1017/S0022215106001459|pmid=16848922|s2cid=28169472|issn=1748-5460}}</ref>  Drugs used to treat obesity are called [[anorectic]]s and generally include drugs that follow the general definition of a stimulant, but other drugs such as [[cannabinoid receptor antagonist]]s also belong to this group.<ref name="pmid15823441">{{cite journal|last1=Kaplan|first1=Lee M.|title=Pharmacological therapies for obesity|journal=Gastroenterology Clinics of North America|date=1 March 2005|volume=34|issue=1|pages=91–104|doi=10.1016/j.gtc.2004.12.002|pmid=15823441|issn=0889-8553}}</ref><ref name="pmid16924165">{{cite journal|last1=Palamara|first1=Kerri L.|last2=Mogul|first2=Harriette R.|last3=Peterson|first3=Stephen J.|last4=Frishman|first4=William H.|title=Obesity: new perspectives and pharmacotherapies|journal=Cardiology in Review|date=1 October 2016|volume=14|issue=5|pages=238–258|doi=10.1097/01.crd.0000233903.57946.fd|pmid=16924165|issn=1538-4683}}</ref> [[Eugeroic]]s are used in management of sleep disorders characterized by [[excessive daytime sleepiness]], such as [[narcolepsy]], and include stimulants such as [[modafinil]] and [[pitolisant]].<ref name="FDA-2017">{{cite web|title=The Voice of the Patient A series of reports from the U.S. Food and Drug Administration's (FDA's) Patient-Focused Drug Development Initiative|url=https://www.fda.gov/downloads/ForIndustry/UserFees/PrescriptionDrugUserFee/UCM402907.pdf|publisher=Center for Drug Evaluation and Research (CDER) U.S. Food and Drug Administration (FDA)|url-status=live|archive-url=https://web.archive.org/web/20170505031213/https://www.fda.gov/downloads/ForIndustry/UserFees/PrescriptionDrugUserFee/UCM402907.pdf|archive-date=5 May 2017}}</ref><ref name="pmid23539642">{{cite journal|last1=Heal|first1=David J|last2=Smith|first2=Sharon L|last3=Gosden|first3=Jane|last4=Nutt|first4=David J|title=Amphetamine, past and present – a pharmacological and clinical perspective|journal=Journal of Psychopharmacology |date=7 January 2017|volume=27|issue=6|pages=479–496|doi=10.1177/0269881113482532|pmc=3666194|issn=0269-8811|pmid=23539642}}</ref> Stimulants are used in impulse control disorders such as [[ADHD]]<ref name="Research-Cf-2019">{{cite web|last1=Research|first1=Center for Drug Evaluation and|title=Drug Safety and Availability - FDA Drug Safety Communication: Safety Review Update of Medications used to treat Attention-Deficit/Hyperactivity Disorder (ADHD) in adults|url=https://www.fda.gov/Drugs/DrugSafety/ucm279858.htm|website=www.fda.gov|language=en|url-status=live|archive-url=https://web.archive.org/web/20131030064843/https://www.fda.gov/Drugs/DrugSafety/ucm279858.htm|archive-date=30 October 2013|date=26 June 2019}}</ref> and [[off-label use|off-label]] in [[mood disorder]]s such as [[major depressive disorder]] to increase [[mental energy|energy]], focus and elevate mood.<ref name="pmid22034135">{{cite journal|last1=Stotz|first1=Gabriele|last2=Woggon|first2=Brigitte|last3=Angst|first3=Jules|title=Psychostimulants in the therapy of treatment-resistant depression Review of the literature and findings from a retrospective study in 65 depressed patients|journal=Dialogues in Clinical Neuroscience|date=1 December 1999|volume=1|issue=3|pages=165–174|doi=10.31887/DCNS.1999.1.3/gstotz |pmc=3181580|issn=1294-8322|pmid=22034135}}</ref>  Stimulants such as [[epinephrine]],<ref name="pmid18733372">{{cite journal |author = Doig RL | title = Epinephrin; especially in asthma | journal = California State Journal of Medicine | volume = 3 | issue = 2 | pages = 54–5 |date=February 1905 | pmid = 18733372 | pmc = 1650334 }}</ref>  [[theophylline]] and [[salbutamol]]<ref name="pmid15778490">{{cite journal|last1=Chu|first1=Eric K.|last2=Drazen|first2=Jeffrey M.|title=Asthma|journal=American Journal of Respiratory and Critical Care Medicine|date=1 June 2005|volume=171|issue=11|pages=1202–1208|doi=10.1164/rccm.200502-257OE|pmid=15778490|issn=1073-449X}}</ref> orally have been used to treat asthma, but inhaled [[adrenergic drug]]s are now preferred due to less systemic side effects. [[Pseudoephedrine]] is used to relieve nasal or sinus congestion caused by the common cold, sinusitis, hay fever and other respiratory allergies; it is also used to relieve ear congestion caused by ear inflammation or infection.<ref name="Bicopoulos">Bicopoulos D, editor. AusDI: Drug information for the healthcare professional, 2nd edition. Castle Hill: Pharmaceutical Care Information Services; 2002.</ref><ref name="PubMed Health">{{cite web|title=Pseudoephedrine (By mouth) – National Library of Medicine|url=https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0011888/|website=PubMed Health|url-status=live|archive-url=https://web.archive.org/web/20140214034938/http://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0011888/|archive-date=14 February 2014}}</ref>

===Depression===
Stimulants were one of the first classes of drugs to be used in the treatment of [[Major depressive disorder|depression]], beginning after the introduction of the amphetamines in the 1930s.<ref name="pmid18321627">{{cite journal | vauthors = Moncrieff J | title = The creation of the concept of an antidepressant: an historical analysis | journal = Soc Sci Med | volume = 66 | issue = 11 | pages = 2346–55 | date = June 2008 | pmid = 18321627 | doi = 10.1016/j.socscimed.2008.01.047 | url = https://discovery.ucl.ac.uk/id/eprint/10193706/1/Moncrieff_1-s2.0-S0277953608000129-main.pdf | access-date = 3 July 2024 | archive-date = 20 June 2024 | archive-url = https://web.archive.org/web/20240620144633/https://discovery.ucl.ac.uk/id/eprint/10193706/1/Moncrieff_1-s2.0-S0277953608000129-main.pdf | url-status = live }}</ref><ref name="Moncrieff2016">{{cite book | author = J. Moncrieff | date = 13 April 2016 | title = The Myth of the Chemical Cure: A Critique of Psychiatric Drug Treatment | publisher = Springer | pages = 121– | isbn = 978-0-230-58944-5 | oclc = 1047624331 | url = https://books.google.com/books?id=2tD7CwAAQBAJ&pg=PA121 | quote = A well-known textbook of physical treatments described stimulants as having 'limited value in depression' because the euphoria they induce quickly wears off and 'the patient slips back' (Sargant & Slater 1944). | access-date = 29 August 2022 | archive-date = 29 August 2022 | archive-url = https://web.archive.org/web/20220829225107/https://books.google.com/books?id=2tD7CwAAQBAJ&pg=PA121 | url-status = live }}</ref><ref name="pmid34000249">{{cite journal | vauthors = Morelli M, Tognotti E | title = Brief history of the medical and non-medical use of amphetamine-like psychostimulants | journal = Exp Neurol | volume = 342 | issue = | page = 113754 | date = August 2021 | pmid = 34000249 | doi = 10.1016/j.expneurol.2021.113754 | s2cid = 234768496 | url = }}</ref> However, they were largely abandoned for treatment of depression following the introduction of conventional [[antidepressant]]s in the 1950s.<ref name="pmid18321627"/><ref name="Moncrieff2016"/> Subsequent to this, there has been a resurgence in interest in stimulants for depression in recent years.<ref name="pmid26906078">{{cite journal | vauthors = Malhi GS, Byrow Y, Bassett D, Boyce P, Hopwood M, Lyndon W, Mulder R, Porter R, Singh A, Murray G | title = Stimulants for depression: On the up and up? | journal = Aust N Z J Psychiatry | volume = 50 | issue = 3 | pages = 203–7 | date = March 2016 | pmid = 26906078 | doi = 10.1177/0004867416634208 | s2cid = 45341424 | url = }}</ref><ref name="pmid17338594">{{cite journal | vauthors = Orr K, Taylor D | title = Psychostimulants in the treatment of depression: a review of the evidence | journal = CNS Drugs | volume = 21 | issue = 3 | pages = 239–57 | date = 2007 | pmid = 17338594 | doi = 10.2165/00023210-200721030-00004 | s2cid = 35761979 | url = }}</ref>

Stimulants produce a fast-acting and pronounced but transient and short-lived [[mood lift]].<ref name="pmid36009115">{{cite journal | vauthors = Pallikaras V, Shizgal P | title = Dopamine and Beyond: Implications of Psychophysical Studies of Intracranial Self-Stimulation for the Treatment of Depression | journal = Brain Sci | volume = 12 | issue = 8 | date = August 2022 | page = 1052 | pmid = 36009115 | doi = 10.3390/brainsci12081052 | pmc = 9406029 | url = | doi-access = free }}</ref><ref name="pmid35431828">{{cite journal | vauthors = Pallikaras V, Shizgal P | title = The Convergence Model of Brain Reward Circuitry: Implications for Relief of Treatment-Resistant Depression by Deep-Brain Stimulation of the Medial Forebrain Bundle | journal = Front Behav Neurosci | volume = 16 | issue = | page = 851067 | date = 2022 | pmid = 35431828 | pmc = 9011331 | doi = 10.3389/fnbeh.2022.851067 | url = | doi-access = free }}</ref><ref name="pmid26906078" /><ref name="Moncrieff2016" /> In relation to this, they are minimally effective in the treatment of depression when administered continuously.<ref name="pmid36009115" /><ref name="pmid35431828" /> In addition, tolerance to the mood-lifting effects of amphetamine has led to dose escalation and [[drug dependence|dependence]].<ref name="pmid17338594"/> Although the efficacy for depression with continuous administration is modest, it may still reach [[statistical significance]] over [[placebo]] and provide benefits similar in magnitude to those of conventional antidepressants.<ref name="pmid29028590">{{cite journal | vauthors = Giacobbe P, Rakita U, Lam R, Milev R, Kennedy SH, McIntyre RS | title = Efficacy and tolerability of lisdexamfetamine as an antidepressant augmentation strategy: A meta-analysis of randomized controlled trials | journal = J Affect Disord | volume = 226 | issue = | pages = 294–300 | date = January 2018 | pmid = 29028590 | doi = 10.1016/j.jad.2017.09.041 | url = }}</ref><ref name="pmid28590365">{{cite journal | vauthors = McIntyre RS, Lee Y, Zhou AJ, Rosenblat JD, Peters EM, Lam RW, Kennedy SH, Rong C, Jerrell JM | title = The Efficacy of Psychostimulants in Major Depressive Episodes: A Systematic Review and Meta-Analysis | journal = J Clin Psychopharmacol | volume = 37 | issue = 4 | pages = 412–418 | date = August 2017 | pmid = 28590365 | doi = 10.1097/JCP.0000000000000723 | s2cid = 27622964 | url = }}</ref><ref name="pmid34144366">{{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 = J Affect Disord | volume = 292 | issue = | pages = 416–423 | date = September 2021 | pmid = 34144366 | doi = 10.1016/j.jad.2021.05.119 | url = }}</ref><ref name="pmid34986373">{{cite journal | vauthors = Nuñez NA, Joseph B, Pahwa M, Kumar R, Resendez MG, Prokop LJ, Veldic M, Seshadri A, Biernacka JM, Frye MA, Wang Z, Singh B | title = Augmentation strategies for treatment resistant major depression: A systematic review and network meta-analysis | journal = J Affect Disord | volume = 302 | issue = | pages = 385–400 | date = April 2022 | pmid = 34986373 | pmc = 9328668 | doi = 10.1016/j.jad.2021.12.134 | url = }}</ref> The reasons for the short-term mood-improving effects of stimulants are unclear, but may relate to rapid [[drug tolerance|tolerance]].<ref name="pmid36009115" /><ref name="pmid35431828" /><ref name="Moncrieff2016" /><ref name="pmid15893821" /> Tolerance to the effects of stimulants has been studied and characterized both in animals<ref name="pmid15893821" /><ref name="pmid30768951">{{cite journal | vauthors = Folgering JH, Choi M, Schlumbohm C, van Gaalen MM, Stratford RE | title = Development of a non-human primate model to support CNS translational research: Demonstration with D-amphetamine exposure and dopamine response | journal = J Neurosci Methods | volume = 317 | issue = | pages = 71–81 | date = April 2019 | pmid = 30768951 | doi = 10.1016/j.jneumeth.2019.02.005 | s2cid = 72333922 | url = | doi-access = free }}</ref><ref name="pmid30733244">{{cite journal | vauthors = van Gaalen MM, Schlumbohm C, Folgering JH, Adhikari S, Bhattacharya C, Steinbach D, Stratford RE | title = Development of a Semimechanistic Pharmacokinetic-Pharmacodynamic Model Describing Dextroamphetamine Exposure and Striatal Dopamine Response in Rats and Nonhuman Primates following a Single Dose of Dextroamphetamine | journal = J Pharmacol Exp Ther | volume = 369 | issue = 1 | pages = 107–120 | date = April 2019 | pmid = 30733244 | doi = 10.1124/jpet.118.254508 | s2cid = 73441294 | url = | doi-access = free }}</ref><ref name="pmid30733244-2">{{cite journal | last1=van Gaalen | first1=Marcel M. | last2=Schlumbohm | first2=Christina | last3=Folgering | first3=Joost H. | last4=Adhikari | first4=Saugat | last5=Bhattacharya | first5=Chandrali | last6=Steinbach | first6=Douglas | last7=Stratford | first7=Robert E. | title=Development of a Semimechanistic Pharmacokinetic-Pharmacodynamic Model Describing Dextroamphetamine Exposure and Striatal Dopamine Response in Rats and Nonhuman Primates following a Single Dose of Dextroamphetamine | journal=Journal of Pharmacology and Experimental Therapeutics | publisher=American Society for Pharmacology & Experimental Therapeutics (ASPET) | volume=369 | issue=1 | date=7 February 2019 | issn=0022-3565 | doi=10.1124/jpet.118.254508 | pages=107–120| pmid=30733244 | s2cid=73441294 | doi-access=free }}</ref> and humans.<ref name="pmid27021968">{{cite journal | vauthors = Ermer JC, Pennick M, Frick G | title = Lisdexamfetamine Dimesylate: Prodrug Delivery, Amphetamine Exposure and Duration of Efficacy | journal = Clin Drug Investig | volume = 36 | issue = 5 | pages = 341–56 | date = May 2016 | pmid = 27021968 | pmc = 4823324 | doi = 10.1007/s40261-015-0354-y | url = }}</ref><ref name="pmid28936175">{{cite journal | vauthors = Dolder PC, Strajhar P, Vizeli P, Hammann F, Odermatt A, Liechti ME | title = Pharmacokinetics and Pharmacodynamics of Lisdexamfetamine Compared with D-Amphetamine in Healthy Subjects | journal = Front Pharmacol | volume = 8 | issue = | page = 617 | date = 2017 | pmid = 28936175 | pmc = 5594082 | doi = 10.3389/fphar.2017.00617 | url = | doi-access = free }}</ref><ref name="pmid8834422">{{cite journal | vauthors = Brauer LH, Ambre J, De Wit H | title = Acute tolerance to subjective but not cardiovascular effects of d-amphetamine in normal, healthy men | journal = J Clin Psychopharmacol | volume = 16 | issue = 1 | pages = 72–6 | date = February 1996 | pmid = 8834422 | doi = 10.1097/00004714-199602000-00012 | url = }}</ref><ref name="pmid11441429">{{cite journal | vauthors = Comer SD, Hart CL, Ward AS, Haney M, Foltin RW, Fischman MW | title = Effects of repeated oral methamphetamine administration in humans | journal = Psychopharmacology (Berl) | volume = 155 | issue = 4 | pages = 397–404 | date = June 2001 | pmid = 11441429 | doi = 10.1007/s002130100727 | s2cid = 19103494 | url = }}</ref> Stimulant [[drug withdrawal|withdrawal]] is remarkably similar in its symptoms to those of [[major depressive disorder]].<ref name="pmid12368072">{{cite journal | vauthors = Barr AM, Markou A, Phillips AG | title = A 'crash' course on psychostimulant withdrawal as a model of depression | journal = Trends Pharmacol Sci | volume = 23 | issue = 10 | pages = 475–82 | date = October 2002 | pmid = 12368072 | doi = 10.1016/s0165-6147(02)02086-2 | url = }}</ref><ref name="pmid15893821">{{cite journal | vauthors = Barr AM, Markou A | title = Psychostimulant withdrawal as an inducing condition in animal models of depression | journal = Neurosci Biobehav Rev | volume = 29 | issue = 4–5 | pages = 675–706 | date = 2005 | pmid = 15893821 | doi = 10.1016/j.neubiorev.2005.03.012 | s2cid = 23653608 | url = }}</ref><ref name="pmid21161752">{{cite book | vauthors = D'Souza MS, Markou A | title = Behavioral Neuroscience of Drug Addiction | chapter = Neural substrates of psychostimulant withdrawal-induced anhedonia | series = Current Topics in Behavioral Neurosciences | volume = 3 | pages = 119–78 | date = 2010 | location = Berlin, Heidelberg | pmid = 21161752 | doi = 10.1007/7854_2009_20 | isbn = 978-3-642-03000-0 | chapter-url = }}</ref><ref name="pmid16140055">{{cite journal | vauthors = Baicy K, Bearden CE, Monterosso J, Brody AL, Isaacson AJ, London ED | title = Common substrates of dysphoria in stimulant drug abuse and primary depression: therapeutic targets | journal = Int Rev Neurobiol | series = International Review of Neurobiology | volume = 65 | issue = | pages = 117–45 | date = 2005 | pmid = 16140055 | doi = 10.1016/S0074-7742(04)65005-7 | isbn = 978-0-12-366866-0 | url = }}</ref>