Editing Stimulant (section)

=== Methamphetamine ===
{{Main|Methamphetamine}}

Methamphetamine (contracted from {{nowrap|[[Methyl group|''N''-'''meth'''yl]]-[[amphetamine|'''a'''lpha-'''m'''ethyl'''ph'''en'''et'''hyl'''amine''']]}}) is a potent psychostimulant of the [[phenethylamine]] and [[substituted amphetamine|amphetamine]] [[chemical classification|classes]] that is used to treat [[attention deficit hyperactivity disorder]] (ADHD) and [[obesity]].<ref name = "Malenka">{{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 |isbn=978-0-07-148127-4 |page=370 |edition=2nd |chapter=15 |quote=Unlike cocaine and amphetamine, methamphetamine is directly toxic to midbrain dopamine neurons.}}</ref><ref name="Desoxyn">{{cite web |title=Desoxyn Prescribing Information |url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/005378s028lbl.pdf |date=December 2013 |work=United States Food and Drug Administration |access-date=6 January 2014 |url-status=live |archive-url=https://web.archive.org/web/20140102192621/http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/005378s028lbl.pdf |archive-date=2 January 2014  }}</ref><ref name="pmid19328213">{{cite journal|vauthors=Krasnova IN, Cadet JL |title=Methamphetamine toxicity and messengers of death |journal=Brain Res. Rev. |volume=60 |issue=2 |pages=379–407 |date=May 2009 |pmid=19328213 |pmc=2731235 |doi=10.1016/j.brainresrev.2009.03.002 |quote=Neuroimaging studies have revealed that METH can indeed cause neurodegenerative changes in the brains of human addicts (Aron and Paulus, 2007; Chang et al., 2007). These abnormalities include persistent decreases in the levels of dopamine transporters (DAT) in the orbitofrontal cortex, dorsolateral prefrontal cortex, and the caudate-putamen (McCann et al., 1998, 2008; Sekine et al., 2003; Volkow et al., 2001a, 2001c). The density of serotonin transporters (5-HTT) is also decreased in the midbrain, caudate, putamen, hypothalamus, thalamus, the orbitofrontal, temporal, and cingulate cortices of METH-dependent individuals (Sekine et al., 2006)&nbsp;...<br />Neuropsychological studies have detected deficits in attention, working memory, and decision-making in chronic METH addicts&nbsp;...<br /> There is compelling evidence that the negative neuropsychiatric consequences of METH abuse are due, at least in part, to drug-induced neuropathological changes in the brains of these METH-exposed individuals&nbsp;...<br /> Structural magnetic resonance imaging (MRI) studies in METH addicts have revealed substantial morphological changes in their brains. These include loss of gray matter in the cingulate, limbic, and paralimbic cortices, significant shrinkage of hippocampi, and hypertrophy of white matter (Thompson et al., 2004). In addition, the brains of METH abusers show evidence of hyperintensities in white matter (Bae et al., 2006; Ernst et al., 2000), decreases in the neuronal marker, N-acetylaspartate (Ernst et al., 2000; Sung et al., 2007), reductions in a marker of metabolic integrity, creatine (Sekine et al., 2002) and increases in a marker of glial activation, myoinositol (Chang et al., 2002; Ernst et al., 2000; Sung et al., 2007; Yen et al., 1994). Elevated choline levels, which are indicative of increased cellular membrane synthesis and turnover are also evident in the frontal gray matter of METH abusers (Ernst et al., 2000; Salo et al., 2007; Taylor et al., 2007).}}</ref> Methamphetamine exists as two [[enantiomer]]s, [[dextrorotary]] and [[levorotary]].<ref name="Kuczenski">{{cite journal|vauthors=Kuczenski R, Segal DS, Cho AK, Melega W |title=Hippocampus norepinephrine, caudate dopamine and serotonin, and behavioral responses to the stereoisomers of amphetamine and methamphetamine |journal=J. Neurosci. |volume=15 |issue=2 |pages=1308–1317 |date=February 1995 |pmid=7869099 |doi=10.1523/JNEUROSCI.15-02-01308.1995|pmc=6577819 }}</ref><ref name="Mendelson">{{cite journal|vauthors=Mendelson J, Uemura N, Harris D, Nath RP, Fernandez E, Jacob P, Everhart ET, Jones RT |title=Human pharmacology of the methamphetamine stereoisomers |journal=Clin. Pharmacol. Ther. |volume=80 |issue=4 |pages=403–420 |date=October 2006 |pmid=17015058 |doi=10.1016/j.clpt.2006.06.013|s2cid=19072636 }}</ref> Dextromethamphetamine is a stronger CNS stimulant than [[levomethamphetamine]];<ref name="Westfall-2010" /><ref name="Kuczenski" /><ref name="Mendelson" /> however, both are addictive and produce the same toxicity symptoms at high doses.<ref name="Mendelson" /> Although rarely prescribed due to the potential risks, methamphetamine hydrochloride is approved by the [[United States Food and Drug Administration]] (USFDA) under the trade name ''Desoxyn''.<ref name="Desoxyn" /> Recreationally, methamphetamine is used to [[aphrodisiac|increase sexual desire]], [[euphoriant|lift the mood]], and increase [[mental energy|energy]], allowing some users to engage in sexual activity continuously for several days straight.<ref name="Desoxyn" />{{failed verification|date=December 2021}}<ref name="SF Meth" />{{unreliable source?|date=December 2021}}

Methamphetamine may be sold illicitly, either as pure dextromethamphetamine or in an [[racemate|equal parts]] mixture of the right- and left-handed molecules (i.e., 50%&nbsp;levomethamphetamine and 50%&nbsp;dextromethamphetamine).<ref name="SF Meth">{{cite episode |date=11 August 2013 |title=San Francisco Meth Zombies |url=http://channel.nationalgeographic.com/drugs-inc/episodes/san-francisco-meth-zombies/ |series=Drugs, Inc. |series-link=Drugs, Inc. |season=4 |number=1 |network=National Geographic Channel |minutes=43 |asin=B00EHAOBAO |archive-url=https://web.archive.org/web/20160708142916/http://channel.nationalgeographic.com/drugs-inc/episodes/san-francisco-meth-zombies/ |archive-date=8 July 2016  }}</ref> Both dextromethamphetamine and racemic methamphetamine are [[Schedule II Controlled Substance|schedule II]] controlled substances in the United States.<ref name="Desoxyn" /> Also, the production, distribution, sale, and possession of methamphetamine is restricted or illegal in many other countries due to its placement in schedule II of the [[Convention on Psychotropic Substances|United Nations Convention on Psychotropic Substances]] treaty.<ref name="United Nations-2007">{{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=11 November 2013 |url-status=live |archive-url=https://web.archive.org/web/20131016082310/http://www.unodc.org/pdf/youthnet/ATS.pdf |archive-date=16 October 2013  }}</ref><ref name="incb">{{cite web|title=List of psychotropic substances under international control |work=International Narcotics Control Board |publisher=United Nations |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 |date=August 2003}}</ref>  In contrast, [[levomethamphetamine]] is an [[over-the-counter drug]] in the United States.{{#tag:ref|The active ingredient in some OTC inhalers in the United States is listed as ''levmetamfetamine'', the [[International Nonproprietary Name|INN]] and [[United States Adopted Name|USAN]] of levomethamphetamine.<ref name="FDA levmetamfetamine">{{cite web|title=CFR TITLE 21: DRUGS FOR HUMAN USE: PART 341 – COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE|url=https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=341.80|website=United States Food and Drug Administration|access-date=7 March 2016|date=April 2015|quote=Topical nasal decongestants --(i) For products containing levmetamfetamine identified in 341.20(b)(1) when used in an inhalant dosage form. The product delivers in each 800 milliliters of air 0.04 to 0.150 milligrams of levmetamfetamine.|url-status=live|archive-url=https://web.archive.org/web/20150918190451/http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=341.80|archive-date=18 September 2015}}</ref><ref name="National Center for Biotechnology Information">{{cite web |title=Levomethamphetamine |url=https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=36604#section=Identification |website=PubChem |access-date=15 September 2017 |archive-date=6 October 2014 |archive-url=https://web.archive.org/web/20141006215922/http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=36604#section=Identification |url-status=live }}</ref>|name="OTC levmetamfetamine"|group = "note"}}

In low doses, methamphetamine can cause an [[euphoria|elevated mood]] and increase alertness, concentration, and energy in fatigued individuals.<ref name="Westfall-2010" /><ref name="Desoxyn" /> At higher doses, it can induce [[methamphetamine psychosis|psychosis]], [[rhabdomyolysis]], and [[cerebral hemorrhage]].<ref name="Westfall-2010" /><ref name="Desoxyn" /> Methamphetamine is known to have a high potential for [[substance abuse|abuse]] and [[substance dependence|addiction]].<ref name="Westfall-2010" /><ref name="Desoxyn" /> Recreational use of methamphetamine may result in psychosis or lead to [[post-withdrawal syndrome]], a withdrawal syndrome that can persist for months beyond the typical withdrawal period.<ref name="Cruickshank-2009">{{cite journal|vauthors=Cruickshank CC, Dyer KR |title=A review of the clinical pharmacology of methamphetamine |journal=Addiction |volume=104 |issue=7 |pages=1085–1099 |date=July 2009 |pmid=19426289 |doi=10.1111/j.1360-0443.2009.02564.x|s2cid=37079117 |doi-access=free }}</ref> Unlike [[amphetamine]] and [[cocaine]], methamphetamine is [[neurotoxic]] to humans, damaging both [[dopamine]] and [[serotonin]] neurons in the [[central nervous system]] (CNS).<ref name = "Malenka" /><ref name="pmid19328213" /> Unlike the long-term use of amphetamine in prescription doses, which may improve certain brain regions in individuals with ADHD, there is evidence that methamphetamine causes brain damage from long-term use in humans;<ref name = "Malenka" /><ref name="pmid19328213" /> this damage includes adverse changes in brain structure and function, such as reductions in [[gray matter]] volume in several brain regions and adverse changes in markers of metabolic integrity.<ref name="Neuroplasticity 1">{{cite journal|vauthors=Hart H, Radua J, Nakao T, Mataix-Cols D, Rubia K |title=Meta-analysis of functional magnetic resonance imaging studies of inhibition and attention in attention-deficit/hyperactivity disorder: exploring task-specific, stimulant medication, and age effects |journal=JAMA Psychiatry |volume=70 |issue=2 |pages=185–198 |date=February 2013 |pmid=23247506 |doi=10.1001/jamapsychiatry.2013.277 }}</ref><ref name="Neuroplasticity 2">{{cite journal|vauthors=Spencer TJ, Brown A, Seidman LJ, Valera EM, Makris N, Lomedico A, Faraone SV, Biederman J |title=Effect of psychostimulants on brain structure and function in ADHD: a qualitative literature review of magnetic resonance imaging-based neuroimaging studies |journal=J. Clin. Psychiatry |volume=74 |issue=9 |pages=902–917 |date=September 2013 |pmid=24107764 |doi=10.4088/JCP.12r08287 |pmc=3801446}}</ref><ref name="pmid19328213" /> However, recreational amphetamine doses may also be neurotoxic.<ref name="pmid6320247">{{cite journal|url=https://www.cambridge.org/core/journals/psychological-medicine/article/abs/continuous-amphetamine-intoxication-an-animal-model-of-the-acute-psychotic-episode/7DEB3BCC38395608F1C4FE87529D4C8F|doi=10.1017/S003329170005145X|title=Continuous amphetamine intoxication: An animal model of the acute psychotic episode|year=1983|last1=Ellison|first1=Gaylord D.|last2=Eison|first2=Michael S.|journal=Psychological Medicine|volume=13|issue=4|pages=751–761|pmid=6320247|s2cid=2337423|url-access=subscription|access-date=23 July 2021|archive-date=3 June 2020|archive-url=https://web.archive.org/web/20200603170616/https://www.cambridge.org/core/journals/psychological-medicine/article/continuous-amphetamine-intoxication-an-animal-model-of-the-acute-psychotic-episode/7DEB3BCC38395608F1C4FE87529D4C8F|url-status=live}}</ref>