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{{About|the [[psychostimulant]] drug, methamphetamine, in both [[racemic]] and [[dextrorotatory]] forms|the CNS inactive [[over-the-counter drug|OTC]] nasal decongestant|levomethamphetamine}}

{{Drugbox
| Watchedfields = changed
| verifiedrevid = 306452948
|IUPAC_name = ''N-methyl-1-phenyl-propan-2-amine''
| image = Methamphetamine.svg
| image2 = Methamphetamine-3d-CPK.png
| width=200
| CASNo_Ref = {{cascite}}
| CAS_number=537-46-2
| ATC_prefix=N06
| ATC_suffix=BA03
| ATC_supplemental=
| PubChem=1206
| ChemSpiderID = 1169
| DrugBank=DB01577
| C=10 | H=15 | N=1
| molecular_weight = 149.233 g/mol
| smiles = CC(CC1=CC=CC=C1)NC
| synonyms = Desoxyephedrine<br>Pervitin<br>Anadrex<br>Methedrine<br>Methylamphetamine<br>Syndrox<br>Desoxyn
| bioavailability= 62.7% oral; 79% nasal; 90.3% smoked; 99% rectally; 100% IV
| metabolism = [[Hepatic]]
| elimination_half-life= 9–15 hours<ref name="ncbi.nlm.nih.gov">[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=12507968&query_hl=4&itool=pubmed_docsum Methamphetamine and amphetamine pharmacokinetics in oral fluid and plasma after controlled oral methamphetamine administration to human volunteers.]</ref>
| excretion = [[Renal]]
| pregnancy_AU =
| pregnancy_US = C
| pregnancy_category =
| legal_AU = S8
| legal_CA = Schedule I
| legal_UK =
| legal_US = Schedule II
| legal_status = Class A<small>([[New Zealand|NZ]])</small><br>Schedule 5<small>([[South Africa|SA]])</small><br>Injectable:Class A, Oral: A<small>([[United Kingdom|UK]])</small>
| routes_of_administration= Medical: Oral<br>Recreational: Oral, [[Intravenous therapy|I.V.]], [[Intramuscular injection|I.M.]], Insufflation, Inhalation, Rectal
}}

'''Methamphetamine''' ({{pron-en|ˌmɛθæmˈfɛtəmiːn}} <small>[http://cougar.eb.com/soundc11/m/metham01.wav listen])</small> also known as '''metamfetamine''' ([[International Nonproprietary Name|INN]]), '''dextromethamphetamine''', '''methylamphetamine''', '''N-methylamphetamine''', and '''desoxyephedrine''') is a [[psychoactive]] [[stimulant]] [[drug]]. It increases [[alertness]] and energy, and in high doses, can induce [[euphoria]], enhance [[self-esteem]], and increase [[sexual pleasure]].<ref name="isbn1-59385-174-X">{{cite book |author=Mack, Avram H.; Frances, Richard J.; Miller, Sheldon I. |title=Clinical Textbook of Addictive Disorders, Third Edition |publisher=The Guilford Press |location=New York |year=2005 |pages= 207|isbn=1-59385-174-X}}</ref><ref name="Logan">B.K. Logan. ''Methamphetamine - Effects on Human Performance and Behavior''. Forensic Science Review, Vol. 14, no. 1/2 (2002), p. 142 [http://www.ndaa.org/pdf/ntlc_meth.pdf Full PDF]</ref>
Methamphetamine has high potential for [[abuse]], activating the psychological [[reward system]] by increasing levels of [[dopamine]], [[norepinephrine]] and [[serotonin]] in the brain. Methamphetamine is [[FDA|FDA approved]] in the United States for the treatment of [[ADHD]] and [[exogenous obesity]], under the trademark name [[Desoxyn]].<ref>[http://www.rxlist.com/desoxyn-drug.htm ''Desoxyn (Methamphetamine Hydrochloride) - RxList'']</ref>

==History==
Methamphetamine was first synthesized from [[ephedrine]] in Japan in January 1893 by chemist [[Nagayoshi Nagai]].<ref>{{cite journal | url = http://ci.nii.ac.jp/naid/110003609935/ | journal|author =Nagai N.|title = Kanyaku maou seibun kenkyuu seiseki (zoku)|journal= Yakugaku
Zasshi |year=1893|volume= 127|pages= 832–860}}</ref> In 1919, crystallized methamphetamine was synthesized by [[Akira Ogata]] via [[redox|reduction]] of [[ephedrine]] using red [[phosphorus]] and [[iodine]]. In 1943, [[Abbott Laboratories]] requested for its approval from the [[Food and Drug Administration (United States)|U.S. Food and Drug Administration]] (FDA) for the treatment of [[narcolepsy]], mild [[Depression (mood)|depression]], [[postencephalitic parkinsonism]], chronic [[alcoholism]], cerebral [[arteriosclerosis]], and [[Rhinitis#Hay fever|hay fever]]. Methamphetamine was approved for all of these indications in December, 1944.{{Fact|date=January 2010}} All of these indication approvals were eventually removed.{{Fact|date=January 2010}} The only two approved marketing indications remaining for methamphetamine are for ADHD and the short-term management of [[exogenous obesity]], although the drug is clinically established as effective in the treatment of [[narcolepsy]].

===Second World War===
One of the earliest uses of methamphetamine was during World War II when it was used by Allied and Axis forces.<ref>{{cite book | last = Grinspoon | first = | authorlink = | coauthors = Hedblom | title = Speed Culture: Amphetamine Use and Abuse in America | publisher = Harvard University Press | date = 1975-01-01 | location = | pages = 18 | url = http://books.google.com/books?id=LyStWcRD6QIC&lpg=PT1&pg=PA18 | doi = | id = | isbn = 978-0674831926 }}</ref> The German military dispensed it under the trade name '''Pervitin'''. It was widely distributed across rank and division, from elite forces to tank crews and aircraft personnel, with many millions of tablets being distributed throughout the war.<ref name=Pervitin>{{cite web|url=http://www.spiegel.de/international/0,1518,354606,00.html |title=The Nazi Death Machine: Hitler's Drugged Soldiers - SPIEGEL ONLINE - News - International |accessdate=2009-11-17 |last=Andreas Ulrich |first=Andreas |work=Spiegel Online }}</ref> From 1942 until his death in 1945, [[Adolf Hitler]] may have been given intravenous injections of methamphetamine by his personal physician [[Theodor Morell]]. It is possible that it was used to treat Hitler's speculated [[Parkinson's disease]], or that his Parkinson-like symptoms that developed from 1940 onwards resulted from using methamphetamine.<ref>{{cite journal | last= Doyle | first = D | year= 2005 | title= Hitler's Medical Care | url= http://www.rcpe.ac.uk/journal/issue/journal_35_1/Hitler%27s_medical_care.pdf | journal = Journal of the Royal College of Physicians of Edinburgh | volume=35 | pages=75–82 | format = PDF | accessdate=2006-12-28}}</ref>

===Post-war use===
After World War II, a large supply of amphetamine stockpiled by the Japanese military became available in Japan under the street name ''shabu'' (also Philopon, pronounced ''Hiropon'', a trade name).<ref name=Philopon>{{cite web | url = http://www.yama-arashi.com/medical/antidepressants.htm | title = 抗うつ薬いろいろ (Various Antidepressants) | accessdate = 2006-07-14 | author = Digital Creators Studio Yama-Arashi | date= 2006-04-16 | work = 医療情報提供サービス | language = Japanese}}</ref> The Japanese Ministry of Health banned it in 1951; since then it has been increasingly produced by the [[Yakuza]] criminal organization.<ref name=banning_in_1951>{{cite web | url = http://www.unodc.org/unodc/en/data-and-analysis/bulletin/bulletin_1989-01-01_1_page007.html | title = Japan: stimulant epidemics past and present | accessdate = 14 July 2006 | author = M. Tamura | date= 1989-01-01 | work = Bulletin on Narcotics | publisher = United Nations Office on Drugs and Crime | pages = 83–93}}</ref> Today methamphetamine is still associated with the Japanese underworld, and its use is discouraged by strong social taboos.{{Citation needed|April 2009|date=April 2009}}

In the 1950s, there was a rise in the legal prescription of methamphetamine to the American public. In the 1954 edition of ''Pharmacology and Therapeutics'', indications for methamphetamine included "[[narcolepsy]], [[Encephalitis|postencephalitic]] [[parkinsonism]], [[alcoholism]], ... certain depressive states ... and in the treatment of [[obesity]]."<ref>{{cite book | last = Grollman | first = Arthur | authorlink = | coauthors = | title = Pharmacology and Therapeutics: a Textbook for Students and Practitioners of Medicine | publisher = Lea & Febiger | date = 1954 | location = | pages = 209}}</ref>

The 1960s saw the start of significant use of clandestinely manufactured methamphetamine as well as methamphetamine created in users' own homes for personal use. The recreational use of methamphetamine continues to this day. [[San Diego, California]] was described as the "methamphetamine capital of North America" in the December 2, 1989 edition of ''[[The Economist]]''
{{Citation needed|April 2009|date=April 2009}} and again in 2000, with [[South Gate, California]] listed as the second largest meth capital.{{Citation needed|April 2009|date=April 2009}}

===Legal restrictions===
{{See also|#Legality}}
In 1983, laws were passed in the United States prohibiting possession of precursors and equipment for methamphetamine production. This was followed a month later by a bill passed in Canada enacting similar laws. In 1986, the U.S. government passed the Federal Controlled Substance Analogue Enforcement Act in an attempt to curb the growing use of [[designer drug]]s. Despite this, use of methamphetamine expanded throughout rural United States, especially through the Midwest and South.<ref>[http://www.ncjrs.gov/pdffiles1/nij/grants/209730.pdf Methamphetamine Use: Lessons Learned]</ref>

Since 1989, five U.S. federal laws and dozens of state laws have been imposed in an attempt to curb the production of methamphetamine. Methamphetamine can be produced in home laboratories using pseudoephedrine or ephedrine, which at the time were the active ingredients in over-the-counter drugs such as [[Sudafed]] and [[Contac]]. Preventative legal strategies of the past 17 years have steadily increased restrictions to the distribution of pseudoephedrine/ephedrine-containing products.{{Citation needed|April 2009|date=April 2009}}

As a result of the U.S. [[Combat Methamphetamine Epidemic Act of 2005]], a subsection of the [[PATRIOT Act]], there are restrictions on the amount of pseudoephedrine and ephedrine one may purchase in a specified time period, and further requirements that these products must be stored in order to prevent theft.<ref>Cunningham JK, Liu LM. (2003) Impacts of Federal ephedrine and pseudoephedrine regulations on methamphetamine-related hospital admissions. Addiction, 98, 1229–1237.</ref> Increasingly strict restrictions have resulted in the reformulation of many over-the-counter drugs, and some such as [[Actifed]] have been discontinued entirely in the United States.

==Pharmacology==
A member of the family of [[phenethylamine]]s, methamphetamine is [[Chirality (chemistry)|chiral]], with two [[isomer]]s, [[levorotary]] and [[dextrorotatory]]. The levorotary form, called [[levomethamphetamine]], is an [[over-the-counter drug]] used in [[inhaler]]s for nasal decongestion. Levomethamphetamine does not possess any significant [[central nervous system]] activity or addictive properties. This article deals only with the dextrorotatory form, called [[dextromethamphetamine (medical)|dextromethamphetamine]], and the [[racemic]] form.

Methamphetamine is a potent [[central nervous system]] [[stimulant]] that affects neurochemical mechanisms responsible for regulating heart rate, body temperature, blood pressure, appetite, attention, mood and responses associated with alertness or alarm conditions.
The acute physical effects of the drug closely resemble the physiological and psychological effects of an [[epinephrine]]-provoked [[fight-or-flight response]], including increased heart rate and blood pressure, [[vasoconstriction]] (constriction of the arterial walls), [[Bronchodilator|bronchodilation]], and [[hyperglycemia]] (increased blood sugar). Users experience an increase in focus, increased mental alertness, and the elimination of fatigue, as well as a decrease in appetite.

The [[methyl group]] is responsible for the potentiation of effects as compared to the related compound [[amphetamine]], rendering the substance on the one hand more lipid-soluble and easing transport across the [[blood-brain barrier]], and on the other hand more stable against enzymatic degradation by [[Monoamine oxidase|MAO]].
Methamphetamine causes the [[norepinephrine]], [[dopamine]], and [[serotonin]] (5HT) transporters to reverse their direction of flow. This inversion leads to a release of these transmitters from the vesicles to the cytoplasm and from the cytoplasm to the synapse (releasing monoamines in rats with ratios of about [[Norepinephrine|NE]]:[[Dopamine|DA]] = 1:2, NE:[[5HT]]= 1:60), causing increased stimulation of post-synaptic receptors. Methamphetamine also indirectly prevents the reuptake of these neurotransmitters, causing them to remain in the synaptic cleft for a prolonged period (inhibiting monoamine reuptake in rats with ratios of about: NE:DA = 1:2.35, NE:5HT = 1:44.5).<ref>Rothman, et al. "Amphetamine-Type Central Nervous System Potently than they Release Dopamine and Serotonin." (2001): Synapse ''39'', 32-41 (Table V. on page 37)</ref>

Methamphetamine is a potent neurotoxin, shown to cause dopaminergic degeneration.<ref>{{cite journal | author = Itzhak Y, Martin J, Ali S | title = Methamphetamine-induced dopaminergic neurotoxicity in mice: long-lasting sensitization to the locomotor stimulation and desensitization to the rewarding effects of methamphetamine | journal = Prog Neuropsychopharmacol Biol Psychiatry | volume = 26 | issue = 6 | pages = 1177–83 | year = 2002 | pmid = 12452543 | doi = 10.1016/S0278-5846(02)00257-9}}</ref><!-- This corresponds to a human equivalent dose of at least 100 mg! Even higher on a simple mg/kg basis, which is probably a better measure for acute toxicity. --><ref>{{cite journal | author = C. Davidson, A. J. Gow, T. H. Lee, E. H. Ellinwood | title = Methamphetamine neurotoxicity: necrotic and apoptotic mechanisms and relevance to human abuse and treatment | journal = Brain Research Reviews | volume = 36 | issue = 1 | pages = 1–22 | year = 2001 | doi = 10.1016/S0165-0173(01)00054-6}}</ref> High doses of methamphetamine produce losses in several markers of brain dopamine and serotonin neurons. Dopamine and serotonin concentrations, dopamine and 5HT uptake sites, and tyrosine and tryptophan hydroxylase activities are reduced after the administration of methamphetamine. It has been proposed that dopamine plays a role in methamphetamine-induced neurotoxicity because experiments that reduce dopamine production or block the release of dopamine decrease the toxic effects of methamphetamine administration. When dopamine breaks down it produces [[reactive oxygen species]] such as hydrogen peroxide.

It is likely that the approximate 1200% increase in dopamine levels and subsequent [[oxidative stress]] that occurs after taking methamphetamine mediates its [[neurotoxicity]].<ref>{{cite journal | url = http://jpet.aspetjournals.org/cgi/content/full/287/1/107 | author = Yamamoto, B. and Zhu, W. | title = The Effects of Methamphetamine on the Production of Free Radicals and Oxidative Stress | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 287 | issue = 1 | pages = 107–114 |date=1 October 1998| accessdate=2007-11-19 | pmid = 9765328 }}</ref>

Recent research published in the Journal of Pharmacology And Experimental Therapeutics (2007)<ref>{{cite journal | url = http://jpet.aspetjournals.org/cgi/content/abstract/321/1/178 | author = Reese EA, Bunzow JR, Arttamangkul S, Sonders MS, Grandy DK. | title = Trace Amine-Associated Receptor 1 Displays Species-Dependent Stereoselectivity for Isomers of Methamphetamine, Amphetamine, and Para-Hydroxyamphetamine | journal = J. Pharmacol. Exp. Ther. |volume = 321 | issue = 1 | pages = 178–186 |year = 2007 | doi = 10.1124/jpet.106.115402 | pmid = 17218486 | unused_data = |pmid17218486}}</ref> indicates that methamphetamine binds to and activates a [[G protein-coupled receptor]] called [[TAAR]]1.<ref name="pmid17888514">{{cite journal |author=Grandy DK. |title=Trace amine-associated receptor 1-Family archetype or iconoclast? |journal=Pharmacol. Ther. |volume=116 |issue=3 |pages=355–390 |year=2007 |pmid=17888514 |doi=10.1016/j.pharmthera.2007.06.007}}</ref> [[TAAR]]s are a newly discovered receptor family<ref name="pmid11459929">{{cite journal |author=Borowsky B, Adham N, Jones KA, Raddatz R, Artymyshyn R, Ogozalek KL, Durkin MM, Lakhlani PP, Bonini JA, Pathirana S, Boyle N, Pu X, Kouranova E, Lichtblau H, Ochoa FY, Branchek TA, Gerald C |title=Trace amines: identification of a family of mammalian G protein-coupled receptors |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=98 |issue=16 |pages=8966–71 |year=2001 |pmid=11459929 |doi=10.1073/pnas.151105198}}</ref><ref name="pmid11723224">{{cite journal |author=Bunzow JR, Sonders MS, Arttamangkul S, Harrison LM, Zhang G, Quigley DI, Darland T, Suchland KL, Pasumamula S, Kennedy JL, Olson SB, Magenis RE, Amara SG, Grandy DK |title=Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor |journal=Mol. Pharmacol. |volume=60 |issue=6 |pages=1181–8 |year=2001 |unused_data=|pmid11723224}}</ref> whose members are activated by a number of [[amphetamine]]-like molecules<ref name="pmid11723224"/> called [[trace amines]], [[thyronamine]]s,<ref name="pmid15146179">{{cite journal |author=Scanlan TS, Suchland KL, Hart ME, Chiellini G, Huang Y, Kruzich PJ, Frascarelli S, Crossley DA, Bunzow JR, Ronca-Testoni S, Lin ET, Hatton D, Zucchi R, Grandy DK |title=3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone |journal=Nat. Med. |volume=10 |issue=6 |pages=638–42 |year=2004 |pmid=15146179 |doi=10.1038/nm1051}}</ref> and certain volatile odorants.<ref name="pmid16878137">{{cite journal |author=Liberles SD, Buck LB |title=A second class of chemosensory receptors in the olfactory epithelium |journal=Nature |volume=442 |issue=7103 |pages=645–50 |year=2006 |pmid=16878137 |doi=10.1038/nature05066}}</ref>

It has been demonstrated that a high ambient temperature increases the neurotoxic effects of methamphetamine.<ref>{{cite journal | url = http://jpet.aspetjournals.org/cgi/content/abstract/jpet.105.096503v1 | journal = The Journal of Pharmacology and Experimental Therapeutics | title = Relationship between Temperature, Dopaminergic Neurotoxicity, and Plasma Drug Concentrations in Methamphetamine-Treated Squirrel Monkeys | volume = 316 | issue = 3 | year= 2006 | pages = 1210–1218 | accessdate = 2007-11-20 | pmid = 16293712 | doi = 10.1124/jpet.105.096503 | author = Yuan, J. }}</ref>

==Effects==
[[File:Effects of metamphetamine.png|thumb|320px|Short- and long-term adverse (negative) physical and mental effects that may appear in methamphetamine use, including rare effects.<ref>[http://www.recoveryconnection.org/drug_index/methamphetamine.php Recovery Connection.org > Methamphetamine Effects] Retrieved on April 16, 2009</ref>]]

===Physical effects===

Physical effects can include [[Anorexia (symptom)|anorexia]],<ref name="Erowid">http://www.erowid.org/chemicals/meth/meth_effects.shtml Erowid Methamphetamines Vault : Effects</ref> [[hyperactivity]],<ref name="Erowid"/> [[dilated pupils]],<ref name="CenTF1">{{cite web| url=http://www.iir.com/centf/guide.htm#What%20are%20the%20signs%20that%20a%20person%20may%20be%20using%20methamphetamine |title=What are the signs that a person may be using methamphetamine?|date=2009|work=The Methamphetamine Problem: Question-and-Answer Guide|publisher=Institute for Intergovernmental Research|accessdate=2009-08-13 |location=Tallahassee}}</ref> [[Flushing (physiology)|flushing]],<ref name="kci">http://www.kci.org/meth_info/sites/meth_facts2.htm</ref> [[Psychomotor agitation|restlessness]],<ref name="Drugs.com">http://www.drugs.com/mtm/methamphetamine.html</ref> [[dry mouth]],<ref name="kci"/> [[headache]],<ref name="Drugs.com"/> [[tachycardia]],<ref name="kci"/> [[bradycardia]],<ref name="DartToxicology">{{cite book | last = Dart | first = Richard | title = Medical Toxicology | publisher = Lippincott Williams & Wilkins | pages = 1074 | url = http://books.google.com/books?id=BfdighlyGiwC&pg=PA1074&as_brr=3#v=onepage | isbn = 978-0781728454 }}</ref> [[tachypnea]],<ref name="kci"/> [[hypertension]],<ref name="kci"/> [[hypotension]],<ref name="DartToxicology"/> [[hyperthermia]],<ref name="cesar.umd.edu">http://www.cesar.umd.edu/cesar/drugs/meth.asp</ref> [[diaphoresis]],<ref name="Erowid"/> [[diarrhea]],<ref name="Erowid"/> [[constipation]],<ref name="Drugs.com"/> [[blurred vision]],<ref name="Drugs.com"/> [[dizziness]],<ref name="Drugs.com"/> [[twitching]],<ref name="Drugs.com"/> [[insomnia]],<ref name="Drugs.com"/> [[numbness]],<ref name="Drugs.com"/> [[palpitations]],<ref name="CenTF1"/> [[arrhythmias]],<ref>{{cite book | last = Mohler | coauthors = Townsend | title = Advanced Therapy In Hypertension And Vascular Disease | pages = 469 | url = http://books.google.com/books?id=sCgURxhCJ-8C&pg=PA469&as_brr=3#v=onepage | isbn = 978-1550093186 }}</ref> [[tremors]],<ref name="Drugs.com"/> dry and/or itchy skin,<ref name="Erowid"/> [[acne]],<ref name="cesar.umd.edu"/> [[pallor]],<ref name="kci"/> and with chronic and/or high doses, [[convulsions]],<ref name="CenTF2">{{cite web| url=http://www.iir.com/centf/guide.htm#Are%20there%20any%20effective%20treatments%20for%20methamphetamine%20abusers |title=Are there any effective treatments for methamphetamine abusers?|date=2009|work=The Methamphetamine Problem: Question-and-Answer Guide|publisher=Institute for Intergovernmental Research|accessdate=2009-08-13 |location=Tallahassee}}</ref> [[myocardial infarction|heart attack]],<ref>http://www.montana.edu/wwwai/imsd/rezmeth/effmethod.htm</ref> [[stroke]],<ref name="Erowid"/> and [[death]] can occur.<ref name="cesar.umd.edu"/>

===Psychological effects===
Psychological effects can include [[euphoria]], [[anxiety]], increased [[libido]], [[alertness]], [[concentration]], [[energy]], [[self-esteem]], [[self-confidence]], [[sociability]], [[irritability]], [[aggression]], [[psychosomatic disorders]], [[psychomotor agitation]], [[hubris]], excessive feelings of [[Power (philosophy)|power]] and [[Wiktionary:invincible|invincibility]], repetitive and [[obsessive]] behaviors, [[paranoia]], and with chronic and/or high doses, [[amphetamine psychosis]] can occur.<ref name="Erowid"/>

===Withdrawal effects===
Withdrawal is characterized by [[excessive sleeping]], [[increased appetite]] and [[depression (mood)|depression]], often accompanied by anxiety and drug-craving.

==Pharmacokinetics==
The half-life of methamphetamine is 9–15 hours. It is excreted by the kidneys, and its half-life depends on urinary pH. Main metabolites of methamphetamine are amphetamine<ref name="ncbi.nlm
'.nih.gov">[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=12507968&query_hl=4&itool=pubmed_docsum Methamphetamine and amphetamine pharmacokinetics in oral fluid and plasma after controlled oral methamphetamine administration to human volunteers.]</ref>, 4-hydroxymethamphetamine, [[norpholedrine|4-hydroxyamphetamine]] and some of the methamphetamine remains unchanged until excretion.<ref name="meth_metabolites_quant">[http://www.aapsj.org/view.asp?art=aapsj080480 Quantitative Determination of Total Methamphetamine and Active Metabolites in Rat Tissue by Liquid Chromatography With Tandem Mass Spec
trometric Detection]</ref>

==Tolerance==
As with other amphetamines, tolerance to methamphetamine is not completely understood, but known to be sufficiently complex that it cannot be explained by any single mechanism. The extent of tolerance and the rate at which it develops vary widely between individuals, and even within one person it is highly dependent on dosage, duration of use, and frequency of administration. Tolerance to the awakening effect of amphetamines does not readily develop, making them suitable for the treatment of [[narcolepsy]].<ref name="GhodseBehavior">{{cite book | last = Ghodse | first = Hamid | title = Drugs and Addictive Behaviour: A Guide to Treatment | publisher = Cambridge University Press | pages = 114 | url = http://books.google.com/books?id=3WF79shLxB4C&lpg=PA114&ots=O-zuh81KqG&pg=PA114#v=onepage | isbn = 978-0521000017 }}</ref>

Short-term tolerance can be caused by depleted levels of [[neurotransmitters]] within the [[synaptic vesicle]]s available for release into the [[synaptic cleft]] following subsequent reuse ([[tachyphylaxis]]). Short-term tolerance typically lasts until neurotransmitter levels are fully replenished; because of the toxic effects on dopaminergic neurons, this can be greater than 2–3 days. Prolonged overstimulation of [[dopamine receptors]] caused by methamphetamine may eventually cause the receptors to [[downregulation|downregulate]] in order to compensate for increased levels of [[dopamine]] within the synaptic cleft.<ref>{{cite journal | author = Bennett B, Hollingsworth C, Martin R, Harp J | title = Methamphetamine-induced alterations in dopamine transporter function | journal = Brain Res | volume = 782 | issue = 1-2 | pages = 219–27 | year = 1998 | pmid = 9519266 | doi = 10.1016/S0006-8993(97)01281-X}}</ref> To compensate, larger quantities of the drug are needed in order to achieve the same level of effects.

[[Reverse tolerance]] or sensitization can also occur.<ref name="GhodseBehavior"/> The effect is well established but the mechanism is not well understood.

==Addiction==
Methamphetamine is [[addictive]].<ref>[http://www.camh.net/About_Addiction_Mental_Health/Drug_and_Addiction_Information/methamphetamine_dyk.html Do You Know... Methamphetamine]. Centre for Addiction and Mental Health.</ref> While not dangerous, [[withdrawal symptoms|withdrawal]] symptoms are common with heavy use and [[relapse]] is common. Various organizations, such as [[Crystal Meth Anonymous]], are available to combat relapse.

Methamphetamine-induced hyperstimulation of pleasure pathways leads to [[anhedonia]]. It is possible that daily administration of the amino acids L-[[Tyrosine]] and [[5-HTP|L-5HTP]]/[[Tryptophan]] can aid in the recovery process by making it easier for the body to reverse the depletion of [[dopamine]], [[norepinephrine]], and [[serotonin]]. Although studies involving the use of these amino acids have shown some success, this method of recovery has not been shown to be consistently effective. {{Citation needed|date=November 2008}}

It is shown that taking [[ascorbic acid]] prior to using methamphetamine may help reduce acute toxicity to the brain, as rats given the human equivalent of 5–10&nbsp;grams of ascorbic acid 30 minutes prior to methamphetamine dosage had toxicity mediated<ref>Wagner GC, Carelli RM, Jarvis MF. "Pretreatment with ascorbic acid attenuates the neurotoxic effects of methamphetamine in rats." ''Research Communications in Chemical Pathology and Pharmacology''. 1985 Feb;'''47'''(2):221–8. PMID 3992009</ref><ref>Wagner GC, Carelli RM, Jarvis MF. "Ascorbic acid reduces the dopamine depletion induced by methamphetamine and the 1-methyl-4-phenyl pyridinium ion." ''Neuropharmacology''. 1986 May;'''25'''(5):559–61. PMID 3488515</ref>, yet this will likely be of little avail in solving the other serious behavioral problems associated with methamphetamine use and addiction that many users experience. Large doses of ascorbic acid also lower urinary [[pH]], reducing methamphetamine's elimination [[half-life]] and thus decreasing the duration of its actions.<ref>Oyler JM, Cone EJ, Joseph RE Jr, Moolchan ET, Huestis MA. [http://www.clinchem.org/cgi/content/full/48/10/1703 "Duration of detectable methamphetamine and amphetamine excretion in urine after controlled oral administration of methamphetamine to humans."] ''Clinical Chemistry''. 2002 Oct;'''48'''(10):1703–14. PMID 12324487.</ref>

To combat addiction, doctors are beginning to use other forms of amphetamine such as [[dextroamphetamine]] to break the addiction cycle in a method similar to the use of [[methadone]] in the treatment of [[heroin]] addicts. There are no publicly available drugs comparable to [[naloxone]], which blocks opiate receptors and is therefore used in treating [[opiate]] dependence, for use with methamphetamine problems.<ref>The Ice Age (See Below)</ref> However, experiments with some monoamine reuptake inhibitors such as [[indatraline]] have been successful in blocking the action of methamphetamine.<ref>Rothman RB, Partilla JS, Baumann MH, Dersch CM, Carroll FI, Rice KC. "Neurochemical Neutralization of Methamphetamine With High-Affinity Nonselective Inhibitors of Biogenic Amine Transporters: A Pharmacological Strategy for Treating Stimulant Abuse." ''Synapse'' 2000 Mar 1;'''35'''(3):222–7. PMID 10657029</ref> There are studies indicating that [[fluoxetine]], bupropion and imipramine may reduce craving and improve adherence to treatment.<ref name="pmid17990840">{{cite journal |author=Winslow BT, Voorhees KI, Pehl KA |title=Methamphetamine abuse |journal=American family physician |volume=76 |issue=8 |pages=1169–74 |year=2007 |pmid=17990840 |doi=}}</ref> Research has also suggested that [[modafinil]] can help addicts quit methamphetamine use.<ref>{{cite journal | author = Grabowski, J. et al. | title = Agonist-like, replacement pharmacotherapy for stimulant abuse and dependence | journal = Addictive Behaviors | volume = 29 | issue = 7 | pages = 1439–1464 | year = 2004 | url = http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6VC9-4D7C8G6-4&_user=10&_coverDate=09%2F01%2F2004&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=7bc6e2c0a338da052c8ac605628cdfb7 |accessdate = 2007-12-02 | doi = 10.1016/j.addbeh.2004.06.018}}</ref><ref>{{cite web | title = Sleep medicine 'can help ice addicts quit' | url = http://www.abc.net.au/news/stories/2007/12/01/2107027.htm | accessdate = 2007-12-02}}</ref>

Methamphetamine addiction is one of the most difficult forms of addictions to treat. [[Bupropion]], [[aripiprazole]], and [[baclofen]] have been employed to treat post-withdrawal cravings, although the success rate is low. [[Modafinil]] is somewhat more successful, but this is a Class IV scheduled drug. [[Ibogaine]] has been used with success in Europe, but is a Class I drug{{Where}} and available only for research use. [[Mirtazapine]] has been reported useful in some small-population studies.<ref>AJ Giannini. ''Drugs of Abuse—Second Edition''. Los Angeles, Practice Management Information Company, 1997.</ref>

Since the [[phenethylamine]] [[phentermine]] is a constitutional isomer of methamphetamine, it has been speculated that it may be effective in treating methamphetamine addiction. [[Phentermine]] is a [[central nervous system]] stimulant that acts on [[dopamine]] and [[norepinephrine]], it has not been reported to cause the same degree of euphoria that is associated with other amphetamines.{{Citation needed|June 2009|date=June 2009}}

Abrupt interruption of chronic methamphetamine use results in the withdrawal syndrome in almost 90% of the cases.

The mental depression associated with methamphetamine withdrawal is longer lasting and more severe than that of [[cocaine]] withdrawal.<ref name="pmid17990840" />

==Medical use==
[[Image:Deux pilules de Desoxyn Gradumet 10mg.jpg|thumb|right|100px|10 mg Desoxyn tablets]]
{{Main|Methamphetamine (medical)}}
Methamphetamine is FDA approved under the trademark name '''Desoxyn''', for the treatment of [[ADHD]] and [[exogenous obesity]], and is prescribed [[off-label]] for the treatment of [[narcolepsy]] and [[treatment-resistant depression]].<ref>{{cite journal|title=Treatment of Narcolepsy with Methamphetamine|journal=Sleep|date=|first=|last=Miller|coauthors=Hajdukovic, Erman|url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2267865|format=|accessdate=2009-08-26 }}</ref> Methamphetamine is known to produce central effects similar to other stimulants, but at smaller doses, with fewer peripheral effects.<ref>Properties and effects of methamphetamine http://www.turningpoint.org.au/library/cg_14.pdf</ref>

===Other uses===
A study by a group of [[University of Montana]] scientists showed that methamphetamine appears to lessen damage to the brains of rats and gerbils that have suffered strokes. The researchers found that small amounts of methamphetamine created a protective effect, while higher doses increased damage. The work is preliminary, and more research is needed to confirm and expand the findings; however, U.M. research assistant professor Dave Poulsen said someday humans may use methamphetamine to lessen stroke damage.<ref>{{cite news |url=http://www.boston.com/news/education/higher/articles/2006/10/12/um_study_meth_may_lessen_stroke_damage/ |title=UM study: Meth may lessen stroke damage |publisher=AP |date=2006-10-12 |archiveurl=http://www.webcitation.org/5drWLLkEb |archivedate=2009-01-15 |accessdate=2008-06-29 }}</ref>

==Health issues==
===Meth mouth===
{{Main|Meth mouth}}
Methamphetamine users and addicts may lose their teeth abnormally quickly, a condition known as "[[meth mouth]]". This effect is not caused by any corrosive effects of the drug itself, which is a common myth. According to the [[American Dental Association]], meth mouth "is probably caused by a combination of drug-induced psychological and physiological changes resulting in [[xerostomia]] (dry mouth), extended periods of poor [[oral hygiene]], frequent consumption of high-calorie, carbonated beverages and [[bruxism]] (teeth grinding and clenching)."<ref name="ADA">{{cite web |url=http://www.ada.org/prof/resources/topics/methmouth.asp |title=Methamphetamine Use (Meth Mouth) |accessdate=2006-12-16 |publisher=American Dental Association }}</ref> Similar, though far less severe symptoms have been reported in clinical use of other amphetamines, where effects are not exacerbated by a lack of oral hygiene for extended periods.<ref>[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15460293&query_hl=5&itool=pubmed_docsum Relationship between amphetamine ingestion and gingival enlargement]</ref>

Like other substances that stimulate the [[sympathetic nervous system]], methamphetamine causes decreased production of acid-fighting saliva and increased thirst, resulting in increased risk for tooth decay, especially when thirst is quenched by high-sugar drinks.<ref>[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12271905 Shaner JW, Caries associated with methamphetamine abuse]</ref>

===Hygiene===
Serious health and appearance problems can be caused by unsterilized needles, lack or ignoring of hygiene needs (more typical on chronic use), and obsessive skin-picking, which may lead to [[abscess]]es.<ref name="pmid17990840"/>

===Sexual behavior{{anchor|Sexual behavior}}=== <!-- anchor referred to by Methamphetamine and sex -->
{{See also|Sex and drugs}}
{{See also|Party and play}}
Users may exhibit sexually compulsive behavior while under the influence of methamphetamine. This disregard for the potential dangers of unprotected sex or other reckless sexual behavior may contribute to the spread of sexually transmitted infections ([[STIs]]) or sexually transmitted diseases ([[STDs]]). Among the effects reported by methamphetamine users are increased libido and sexual pleasure, the ability to have sex for extended periods of time, and an inability to [[ejaculate]] or reach [[orgasm]]. In addition to increasing the need for sex and enabling the user to engage in prolonged sexual activity, methamphetamine lowers inhibitions and may cause users to behave recklessly or to become forgetful.

According to a recent San Diego study, methamphetamine users often engage in [[safe sex|unsafe sexual activities]], and forget or choose not to use condoms. The study found that methamphetamine users were six times less likely to use condoms. The urgency for sex combined with the inability to achieve physical release (ejaculation) can result in tearing, chafing, and trauma (such as rawness and friction sores) to the [[sex organs]], the [[rectum]] and mouth, dramatically increasing the risk of infectious transmission. Methamphetamine also causes [[erectile dysfunction]] due to vasoconstriction.<ref>[http://www.drug-rehabs.org/iarticles/34/Meth_And_Sexual_Behavior ''Meth and Sexual Behavior - Drug-Rehabs.org'']</ref>

===Use in pregnancy and breastfeeding===
Methamphetamine passes through the placenta and is secreted in the breast milk. Half of the newborns whose mothers used methamphetamine during pregnancy experience [[withdrawal syndrome]]; this syndrome is relatively mild and requires medication in only 4% of the cases.<ref name="pmid17990840"/>
===Public Health Issues===
It has been found that the volatile remain products and even the methamphetamine itself can contaminate the "home" methamphetamine labs, thus becoming these places a public health hazard due to the possible consequences for new inhabitants, especially through the respiratory and conjunctiva mucosa, blood stream and Central Nervous System.<ref>http://www.cdc.gov/search.do?q=methamphetamine+labs&btnG.x=29&btnG.y=6&sort=date%3AD%3AL%3Ad1&oe=UTF-8&ie=UTF-8&ud=1&site=default_collection</ref>

==Routes of administration==
Studies have shown that the subjective pleasure of drug use (the reinforcing component of addiction) is proportional to the rate at which the blood level of the drug increases.<ref>Onset of Action and Drug Reinforcement http://jpet.aspetjournals.org/content/301/2/690.full.pdf</ref> In general, intravenous injection is the fastest mechanism (i.e., it causes blood concentrations to rise the most quickly), followed by smoking, [[suppository]] (anal insertion), [[Insufflation (medicine)|insufflation]] (snorting), and [[ingestion]] (swallowing). Ingestion does not produce a [[Rush (psychology)|rush]], which is the most [[Wiktionary:transcendent|transcendent]] state of euphoria experienced with the use of methamphetamine, and is the most prominent with intravenous use. While the onset of the rush produced by injection or smoking can occur in as little as a few seconds, the oral route of administration usually requires approximately half an hour before the high sets in. Thus, oral routes of administration are generally used by recreational or medicinal consumers of the drug, while other more fast-acting routes of administration are used by addicts.

===Injection===
[[Drug injection|Injection]] is a popular method for use, also known as "slamming" and "mainlining", but carries quite a few serious risks. The hydrochloride salt of methamphetamine is soluble in water; intravenous users may use any dose range from less than 100 [[milligram]]s to over one [[gram]] using a [[hypodermic]] needle (although it should be noted that typically street methamphetamine is "cut" with a water-soluble cutting material, which constitutes a significant portion of a given street methamphetamine dose). Intravenous users often experience skin rashes (sometimes called "speed bumps") and infections at the site of injection. As with the injection of any drug, if a group of users [[needle sharing|share a common needle]] or any type of injecting equipment without sterilization procedures, blood-borne diseases such as [[HIV]] or [[hepatitis]] can be transmitted.

===Smoking===
"Smoking" amphetamines refers to vaporizing it to inhale the resulting fumes, not burning it to inhale the resulting smoke. It is commonly smoked in glass pipes made from [[glass blowing|blown]] [[Pyrex]] tubes, light bulbs, or on aluminium foil heated underneath by a flame. This method is also known as "chasing the ''white'' dragon" (whereas smoking [[heroin]] is known as "[[chasing the dragon]]"). There is little evidence that methamphetamine inhalation results in greater toxicity than any other route of administration. Lung damage has been reported with long-term use, but manifests in forms independent of route (pulmonary hypertension and associated complications), or limited to injection users (pulmonary emboli).

===Insufflation===
Another popular route to intake methamphetamine is insufflation (snorting), where a user crushes the methamphetamine into a fine powder and then sharply inhales it (sometimes with a straw or a rolled up [[banknote]], similar to [[cocaine]]) into the nose where methamphetamine is absorbed through the soft tissue in the [[mucous membrane]] of the [[sinus cavity]] and straight into the bloodstream. This method bypasses first pass metabolism and has a quicker onset with a higher [[bioavailability]], though the duration of action is shorter than oral administration. This method is sometimes preferred by users who do not want to prepare and administer methamphetamine for injection or smoking, but still experience a fast onset with a rush.

===Other methods===
<!-- Deleted image removed: [[Image:lineofmeth.jpg|right|thumb|200px|A line of methamphetamine]] -->
Very little research has focused on [[suppository]] or anal insertion as a method, and anecdotal evidence of its effects is infrequently discussed, possibly due to social taboos in many cultures regarding the anus. This method is often known within methamphetamine communities as a "butt rocket", "potato thumping", "turkey basting", a "booty bump", "keistering", "plugging", "shafting", "bumming", or "shelving" (vaginal) and is anecdotally reported to increase sexual pleasure while the effects of the drug last longer.<ref>[http://www.citypages.com/databank/24/1171/article11254.asp Meth Myths, Meth Realities]{{Dead link|date=July 2009}}</ref> The rectum is where the majority of the drug would likely be taken up, through the membranes lining its walls.

==Illicit production==
[[Image:Méthamphétamine pure.jpg|left|thumb|200px|Crystal methamphetamine]]

===Synthesis===
Methamphetamine is most structurally similar to [[methcathinone]] and [[amphetamine]]. When illicitly produced, it is commonly made by the [[Redox|reduction]] of [[ephedrine]] or [[pseudoephedrine]]. Most of the necessary chemicals are readily available in household products or [[over-the-counter drug|over-the-counter]] cold or allergy medicines. Synthesis is relatively simple, but entails risk with flammable and corrosive chemicals, particularly the solvents used in extraction and purification. Clandestine production is therefore often discovered by fires and explosions caused by the improper handling of volatile or flammable solvents.
Most methods of illicit production involve [[hydrogenation]] of the [[hydroxyl]] group on the [[ephedrine]] or [[pseudoephedrine]] molecule. The most common method for small-scale methamphetamine labs in the United States is primarily called the "Red, White, and Blue Process", which involves red [[phosphorus]], [[pseudoephedrine]] or [[ephedrine]] (white), and blue [[iodine]] (which is technically a purple color in elemental form), from which [[Hydrogen iodide|hydroiodic acid]] is formed. In Australia, criminal groups have been known to substitute "red" phosphorus with either hypophosphorous acid or phosphorous acid.<ref>[http://pacia.org.au/_uploaditems/docs/2.code_illicitdrugmanufsept05.pdf]{{Dead link|date=August 2009}}</ref> This is a fairly dangerous process for amateur chemists, because [[phosphine]] gas, a side-product from [[in situ#Chemistry and chemical engineering|in situ]] hydroiodic acid production, is extremely toxic to inhale.

Another common method uses the [[Birch reduction]] (also called the "Nagai method"),<ref>http://www.illinoisattorneygeneral.gov/methnet/understandingmeth/basics.html</ref> in which metallic [[lithium]], commonly extracted from non-rechargeable [[Lithium battery|lithium batteries]], is substituted for difficult-to-find metallic [[sodium]]. However, the Birch reduction is dangerous because the alkali metal and liquid [[anhydrous ammonia]] are both extremely reactive, and the temperature of liquid ammonia makes it susceptible to explosive boiling when reactants are added. Anhydrous ammonia and lithium or sodium (Birch reduction) may be surpassing hydroiodic acid ([[catalytic hydrogenation]])<!-- huh? --> as the most common method of manufacturing methamphetamine in the U.S. and possibly in Mexico. New Jersey as well as Maine both rank in the top illegal underground methamphetamine producing states.

[[Image:methjakarta.jpg|right|250px|thumb|Industrial scale methamphetamine factory in Cikande, [[Indonesia]].]]
A completely different procedure of synthesis uses the [[reductive amination]] of [[phenylacetone]] with [[methylamine]],<ref>[http://www.erowid.org/archive/rhodium/chemistry/amph.alhg.html A Synthesis of Amphetamine. J. Chem. Educ. 51, 671 (1974)]</ref> both of which are currently [[Drug Enforcement Administration|DEA]] [[DEA list I chemicals|list I]] chemicals (as are pseudoephedrine and ephedrine). The reaction requires a catalyst that acts as a reducing agent, such as [[mercury-aluminum amalgam]] or platinum dioxide, also known as [[Adams' catalyst]]. This was once the preferred method of production by [[motorcycle gangs]] in [[California]],<ref>{{cite book |url=http://books.google.com/books?id=8lWBixJv0QAC |title=No Speed Limit: The Highs and Lows of Meth |first=Frank |last=Owen |publisher=Macmillan |year=2007 |isbn=9780312356163 |chapter=Chapter 1: The Rise of Nazi Dope |pages=17–18}}</ref> until DEA restrictions on the chemicals made the process difficult. Other less common methods use other means of hydrogenation, such as [[hydrogen]] [[gas]] in the presence of a [[catalyst]].{{Citation needed|date=June 2009}}

Methamphetamine labs can give off noxious fumes, such as [[phosphine]] gas, [[methylamine]] gas, solvent vapors; such as [[acetone]] or [[chloroform]], [[iodine]] vapors, white [[phosphorus]], anhydrous [[ammonia]], [[hydrogen chloride]]/[[muriatic acid]], [[hydrogen iodide]], [[lithium]]/[[sodium]] metal, [[ether]], or methamphetamine vapors. If performed by amateurs, manufacturing methamphetamine can be extremely dangerous. If the red [[phosphorus]] overheats, because of a lack of ventilation, phosphine gas can be produced. This gas is highly toxic and if present in large quantities is likely to explode upon autoignition from [[diphosphine]], which is formed by overheating [[phosphorus]].{{Citation needed|date=June 2009}}

In recent years, reports of a simplified "Shake 'n Bake" synthesis have surfaced. The method is suitable for such small batches that pseudoephedrine restrictions are less effective, it uses chemicals that are easier to obtain (though no less dangerous than traditional methods), and it is so easy to carry out that some addicts have made the drug while driving.<ref>{{cite news|url=http://www.nydailynews.com/lifestyle/health/2009/08/25/2009-08-25_new_method_for_making_crystal_meth_gets_around_drug_laws.html |title=New 'shake-and-bake' method for making crystal meth gets around drug laws but is no less dangerous |author=Associated Press |publisher=New York Daily News |date=August 25, 2009}}</ref> Producing meth in this fashion can be extremely dangerous and has been linked to several fatalities.<ref>{{cite web|url=http://alcoholism.about.com/od/meth/a/shake_and_bake.htm |title=Shake and Bake Meth - New 'Shake and Bake' Meth Method Explodes |accessdate=2009-12-01 }}</ref>

===Production and distribution===
Until the early 1990s, methamphetamine for the US market was made mostly in labs run by drug traffickers in [[Mexico]] and [[California]]. Since then, authorities{{Which?|date=July 2009}} have discovered increasing numbers of small-scale methamphetamine labs all over the United States, mostly in rural, suburban, or low-income areas.{{Citation needed|date=July 2009}} [[Indiana]] [[state police]] found 1,260 labs in 2003, compared to just 6 in 1995, although this may be partly a result of increased police activity.<ref>[http://web.archive.org/web/20070926225227/http://www.in.gov/cji/methfreeindiana/enforce.html Law Enforcement Facts, 2007]</ref> As of 2007, drug and lab seizure data suggests that approximately 80 percent of the methamphetamine used in the United States originates from larger laboratories operated by Mexican-based syndicates on both sides of the border, and that approximately 20 percent comes from small toxic labs (STLs) in the United States.<ref>{{Cite book
|url=http://www.usdoj.gov/dea/pubs/cngrtest/ct032207attach.html
|title=DEA Congressional Testimony, "Drug Threats And Enforcement Challenges"
|publisher=U.S. Drug Enforcement Administration
|date=March 22, 2007
|accessdate=2008-05-03}}</ref>

Mobile and motel-based methamphetamine labs have caught the attention of both the US news media and the police. Such labs can cause explosions and fires, and expose the public to hazardous chemicals. Those who manufacture methamphetamine are often harmed by toxic gases. Many police departments have specialized task forces with training to respond to cases of methamphetamine production. The National Drug Threat Assessment 2006, produced by the [[United States Department of Justice|Department of Justice]], found "decreased domestic methamphetamine production in both small and large-scale laboratories", but also that "decreases in domestic methamphetamine production have been offset by increased production in Mexico." They concluded that "methamphetamine availability is not likely to decline in the near term."<ref>{{cite web|url=http://www.usdoj.gov/ndic/pubs11/18862/meth.htm |title=Methamphetamine - National Drug Threat Assessment 2006 |accessdate=2009-08-25 |date=January 2006 |publisher=National Drug Intelligence Center }}</ref>

In July 2007, a ship was caught by Mexican officials at the port of [[Lázaro Cárdenas, Michoacán|Lázaro Cárdenas]], originating in [[Hong Kong]], after traveling through the port of [[Long Beach, California|Long Beach]] with 19 tons of [[pseudoephedrine]], a raw material needed for meth.<ref>[http://www.thetelegram.com/index.cfm?pid=1154&cpcat=world&stry=59519030 Mexico says pseudoephedrine case signals breakdown in port security in U.S., China] AP, The Telegram (The Canadian Press), July 26, 2007. Olga R. Rodriguez</ref>

Methamphetamine is distributed by prison gangs, [[Outlaw motorcycle club|outlaw motorcycle gangs]], street gangs, traditional [[organized crime]] operations, and impromptu small networks.{{Citation needed|May 2009|date=May 2009}} In the United States illicit methamphetamine comes in a variety of forms with prices varying widely over time.<ref>[http://www.whitehousedrugpolicy.gov/publications/price_purity/ The Price and Purity of Illicit Drugs: 1981 Through the Second Quarter of 2003]</ref> Most commonly it is found as a colorless [[crystalline]] solid. Impurities may result in a brownish or tan color. Colourful flavored pills containing methamphetamine and [[caffeine]] are known as [[yaba (drug)|yaa baa]] (Thai for "crazy medicine").

An impure form of methamphetamine is sold as a crumbly brown or off-white rock, commonly referred to as "peanut butter crank".<ref>The Ice Epidemic http://www.wctu.com.au/pages/education_papers/Education%20Paper%202007-09.pdf</ref> Methamphetamine found on the street is rarely pure, but adulterated with chemicals that were used to synthesize it.{{Citation needed|date=November 2009}} It may be diluted or "[[cutting agent|cut]]" with non-psychoactive substances like [[inositol]], [[isopropylbenzylamine]] or [[dimethylsulfone]]. Another popular method is to combine methamphetamine with other stimulant substances such as [[caffeine]] or [[cathine]] into a pill known as a "Kamikaze", which can be particularly dangerous due to the [[synergistic]] effects of multiple stimulants. It may also be flavored with high-sugar candies, drinks, or drink mixes to mask the bitter taste of the drug. Coloring may be added to the meth, as is the case with "Strawberry Quick."<ref>[http://www.cbsnews.com/stories/2007/05/02/health/main2752266.shtml Candy Flavored Meth Targets New Users] CBS News, May 2, 2007. Lloyd De Vries. Accessed 2009-12-29.</ref><ref>{{cite web|url=http://www.snopes.com/horrors/drugs/candymeth.asp |title=snopes.com: Strawberry Meth |accessdate=2009-08-25 |last=Mikkelson |first=Barbara }}</ref>

==Natural occurrence==
Methamphetamine has been reported to occur naturally in ''[[Acacia berlandieri]]'' and possibly ''[[Acacia rigidula]]'', trees that grow in west [[Texas]].<ref>BA Clement, CM Goff, TDA Forbes, Phytochemistry Vol.49, No 5, pp1377–1380 (1998)
"Toxic amines and alkaloids from Acacia rigidula"</ref> Methamphetamine and other amphetamines were long thought to be strictly human-synthesized,<ref>[http://www.cognitiveliberty.org/shulgin/adsarchive/acacia.htm Ask Dr. Shulgin Online: Acacias and Natural Amphetamine]</ref> but acacia trees contain numerous other psychoactive compounds (e.g. [[amphetamine]], [[mescaline]], [[nicotine]], [[dimethyltryptamine]]), and the related compound β-phenethylamine is known from numerous ''Acacia'' species.<ref>{{cite journal |author= Siegler, D.S.|title=Phytochemistry of ''Acacia—sensu lato'' |journal= Biochemical Systematics and Ecology |volume=31 |issue=8 |pages=845–873 |year=2003 |month=August |doi=10.1016/S0305-1978(03)00082-6 |url=}}</ref>

==Terminology==
[[Slang|Nicknames]] for methamphetamine are numerous and vary significantly from region to region. Some common nicknames for methamphetamine include "ice", "meth", "crystal", "crystal meth", "crank", "glass", "nazi dope", "shabu" ([[Japan]], [[Philippines]]), "tik" ([[South Africa]]),<ref>http://www.whitehousedrugpolicy.gov/DrugFact/methamphetamine/methamphetamine_ff.html</ref><ref name="UCT">{{cite news|work=UCT|accessdate=2009-08-13 |last=Plüddemann|first=Andreas| date=2005-06|title=Tik, memory loss and stroke|journal=Science in Africa|publisher=Science magazine for Africa CC|location=South Africa|url=http://www.scienceinafrica.co.za/2005/june/tik.htm}}</ref> "[[ya ba]]" ([[Thailand]]), and "P" ([[New Zealand]]).<ref>[http://www.police.govt.nz/safety/meth.html ''What is methamphetamine? - New Zealand Police'']</ref> Methamphetamine may also be referred to as "speed", although this street term is officially reserved for regular [[amphetamine]], without the [[methyl group]].<ref>[http://wordnetweb.princeton.edu/perl/webwn?s=speed ''speed - WordNet'']</ref>

==Legality==
===Australia===
As a Schedule 8 drug, the medical use of methamphetamine is recognized in Australia.<ref>{{cite web|url=http://www.comlaw.gov.au/ComLaw/Legislation/LegislativeInstrument1.nsf/previewlodgmentattachments/FDEA253A6FEDDFC9CA257608007EB777/$file/PoisonsStandard2009SUSDP24.htm |title=Poisons Standard 2009 |accessdate=2009-08-17 |date=2009-08-03 }}</ref>
It is not, however, available for medicinal use.

===Canada===
Methamphetamine is not approved for medical use in Canada. As of 2005, methamphetamine has been moved to Schedule I of the Controlled Drugs and Substances Act, which provides access to the highest maximum penalties. The maximum penalty for production and distribution of methamphetamine has increased from 10 years to [[Life in prison#Canada|life in prison]].<ref>{{cite web
|url=http://www.kcd.gc.ca/ev.php?ID=6493_201&ID2=DO_TOPIC
|title=Government of Canada increases maximum penalties for Methamphetamine offences
|work=Health Canada News Release
|publisher=Health Canada
|date=2005-08-11
|accessdate=2008-09-01 }}{{Dead link|date=August 2009}}</ref>

===Hong Kong===
Methamphetamine is regulated under Schedule 1 of Hong Kong's ''Dangerous Drugs Ordinance''.<ref>{{cite web|url=http://www.hklii.org/hk/legis/en/ord/134/sch1.html |title=DANGEROUS DRUGS ORDINANCE - SCHEDULE 1 |accessdate=2009-08-25 }}</ref> It can only be used legally by health professionals and for university research purposes. The substance can be given by pharmacists under a prescription. Anyone who supplies the substance without prescription can be punished with 15 years imprisonment and a fine of $100,000 ([[Hong Kong dollar|HKD]]).<ref>{{cite web|url=http://www.hklii.org/hk/legis/en/ord/134/s5.html |title=DANGEROUS DRUGS ORDINANCE - SECT 5 |accessdate=2009-08-25 }}</ref> The penalty for trafficking or manufacturing the substance is a $5,000,000 (HKD) fine and life imprisonment.<ref>{{cite web|url=http://www.hklii.org/hk/legis/en/ord/134/s4.html |title=DANGEROUS DRUGS ORDINANCE - SECT 4 |accessdate=2009-08-25 }}</ref> Possession or use of the substance without license from the Department of Health is liable to a $1,000,000 (HKD) fine and/or 7 years of imprisonment.<ref>{{cite web|url=http://www.hklii.org/hk/legis/en/ord/134/s8.html |title=DANGEROUS DRUGS ORDINANCE - SECT 8 |accessdate=2009-08-25 }}</ref>

===Italy===
Methamphetamine is not approved for medical use in Italy, except for an extremely small number of case-approved, strictly controlled experimental therapies, and it is listed in the ''Tabella 1'' ("Schedule One") of the Psychotropic Substances List of the Italian Ministry of Health.<ref>{{cite web|url=http://www.ministerosalute.it/imgs/C_17_FarmaciAree_7_listaFile_itemName_1_file.pdf |title=TABELLA I |accessdate=2009-08-25 |format=PDF |language=Italian }}</ref> Methamphetamine is thus regulated like any other "heavy drug" (Italian law makes distinction between "light drugs", such as [[marijuana]], and "heavy drugs", such as [[heroin]], [[cocaine]] or [[MDMA]]). Production, traffic and/or sale of methamphetamine can be punished with a sentence of imprisonment ranging from six to twenty years, and with a fine ranging from 26,000 to 260,000 [[Euro]]s, according to the severity of the felony. As for any other drugs, the consumption of methamphetamine and the possession of the substance for "personal use" (under a certain quantity) is not illegal in Italy, although law enforcement and health authorities keep files on known users and addicts, which are often forced to undergo treatment.<ref>http://www.altalex.com/index.php?idnot=33849 ''Testo Unico sulla Droga'' Italian drugs law</ref> However, methamphetamine is not a particularly common or popular substance in Italy, surclassed by the above-mentioned [[cocaine]], [[heroin]], and by [[MDMA|ecstasy]], even if its popularity it's growing <ref>{{it}}http://www.repubblica.it/2009/11/sezioni/cronaca/rapporto-droga/rapporto-droga/rapporto-droga.html?ref=rephpnews}</ref>

===The Netherlands===
Methamphetamine is not approved for medical use in The Netherlands. It falls under Schedule I of the Opium Act.<ref>{{cite web |url=http://www.douane.nl/bibliotheek/handboeken/vgem/hvgem_10-03-00-11.html |title=Bijlage 1 Lijst I Opiumwetmiddelen}}</ref> Although production and distribution of this drug are prohibited, few people who were caught with a small amount for personal use have been prosecuted.{{Citation needed|date=August 2009}}

===New Zealand===
Methamphetamine is a Class "A" or Schedule 1 controlled drug under the [[Misuse of Drugs Act (New Zealand)|Misuse of Drugs Act 1975]].<ref>{{cite web |url=http://legislation.govt.nz/act/public/1975/0116/latest/DLM436576.html |title=Misuse of Drugs Act 1975 No 116 (as at 01 October 2008), Public Act}}</ref> The maximum penalty for production and distribution is imprisonment for life. While in theory a doctor could prescribe it for an appropriate indication, this would require case-by-case approval by the director-general of public health. High purity methamphetamine is most commonly referred to by the uniquely New Zealand street name of ''P'', for "pure".<ref>{{cite web|url=http://www.chamberlain.net.nz/research/glossary.php|title=Glossary|last=Chamberlain|first=Simon|date=2005|work=Methamphetamine, ecstasy and BZP in New Zealand: An annotated bibliography|accessdate=2009-06-27}}</ref>

===Singapore===
Under the [[Misuse of Drugs Act (Singapore)|Misuse of Drugs Act]] in Singapore, methamphetamine is a Class A&nbsp;— Schedule I controlled drug.<ref>{{cite web |url=http://statutes.agc.gov.sg/non_version/cgi-bin/cgi_getdata.pl?actno=2008-REVED-185&segid=1207125305-001556 |title=First Schedule, Section 2, Controlled Druge, PART I, Class A Drugs | publisher=Attorney General's Chamber | work=Singapore Statutes Online | accessdate=2009-12-29}}</ref> Under the Section 17 of the Misuse of Drugs Act, any person who carries 25 or more grammes of the drug shall be presumed to possess them for the purpose of drug trafficking,<ref>{{cite web |url=http://statutes.agc.gov.sg/non_version/cgi-bin/cgi_getdata.pl?actno=2008-REVED-185&segid=1207125303-000331#1207125303-000370 |title=Part III, Evidence, Enforcement and Punishment, Presumption concerning trafficking| publisher=Attorney General's Chamber | work=Singapore Statutes Online | accessdate=2009-12-29}}</ref> which is punishable by death. Unless authorized by the government, the possession, consumption, manufacturing, import, export, or trafficking of methamphetamine in any amount are illegal.

===South Africa===

In South Africa, methamphetamine is classified as a Schedule 7 drug,<ref>{{cite web|url=http://www.info.gov.za/regulations/2003/24727a/24727ad.pdf |title=Medicines and Related Substances Act: Schedules |accessdate=2010-01-01 |date=2003-04-10 |format=PDF |publisher=Government Gazette }}</ref> and is listed as Undesirable Dependence-Producing Substances in Part III of Schedule 2 of the Drugs and Drug Trafficking Act, 1992.<ref>{{cite web|url=http://www.saps.gov.za/drugs/ats.htm |title=Drug Awareness -- ATS |accessdate=2010-01-01 |publisher=South African Police Service }}</ref> Commonly called '''tik''',<ref name="UCT" /> it is predominantly used by non-whites in the [[Cape Flats]] areas.<ref>{{cite web|url=http://www.guardian.co.uk/world/2007/sep/23/china.southafrica |title=Rare shellfish bartered for drugs |accessdate=2010-01-01 |last=Kiley |first=Sam |date=2007-09-23 |work=The Observer }}</ref>

===United Kingdom===
As of 18 January 2007,<ref>Misuse of Drugs Act 1971 (Amendment Order) SI 2006/3331</ref> methamphetamine is classified as a Class A drug in the UK under the [[Misuse of Drugs Act 1971]] following a recommendation made by the [[Advisory Council on the Misuse of Drugs]] in June 2006.<ref>[http://news.bbc.co.uk/1/hi/uk_politics/5079266.stm Crystal meth to be class A drug], BBC News, 14 June 2006</ref> It had previously been classified as a Class B drug, except when prepared for injection.

===United States===
{| class="wikitable" style="text-align:center" align="right"
|+ Methamphetamine Lab Seizures in the US
|-
! Year !! Seizures
|-
|1999 || 7,438
|-
|2000 || 9,902
|-
|2001 || 13,357
|-
|2002 || 16,212
|-
|2003 || 17,356
|-
|2004 || 17,170
|-
|2005 || 12,619
|-
|2006 || 7,347
|-
|2007 || 5,910
|-
|2008 || 6,783
|}
Methamphetamine is classified as a [[Controlled Substances Act#Schedule II drugs|Schedule II]] substance by the [[Drug Enforcement Administration]] under the [[Convention on Psychotropic Substances]].<ref>[http://www.incb.org/pdf/e/list/green.pdf List of psychotropic substances under international control]. International Narcotics Control Board.</ref> It is available by prescription under the trade name [[Desoxyn]], manufactured by [[Ovation Pharma]]. While there is technically no difference between the laws regarding methamphetamine and other controlled stimulants, most medical professionals are averse to prescribing it due to its notoriety.

Illicit methamphetamine has become a major focus of the '[[war on drugs]]' in the United States in recent years{{When|date=November 2009}}.{{Citation needed|date=November 2009}} In addition to federal laws, some states have placed additional restrictions on the sale of precursor chemicals commonly used to synthesize methamphetamine, particularly [[pseudoephedrine]], a common over-the-counter [[decongestant]]. In 2005, the [[Drug Enforcement Administration|DEA]] seized 2,148.6&nbsp;kg(4,736.8 lbs) of methamphetamine.<ref>[http://www.dea.gov/statistics.html#seizures Stats & Facts: 2006 Successes in the Fight Against Drugs]</ref> In 2005, the [[Combat Methamphetamine Epidemic Act of 2005]] was passed as part of the [[USA PATRIOT Act]], putting restrictions on the sale of methamphetamine precursors. Various state governments have passed even more stringent laws to regulate the sale of pseudoephedrine decongestants.

On November 7, 2006, the US Department of Justice declared that November 30, 2006 be Methamphetamine Awareness Day.<ref>{{cite web|url=http://www.usdoj.gov/dea/pubs/states/methawareness_news_releases.html|title=Meth Awareness News Releases|author=DEA|date=2007-01-01}}</ref>

[[Drug Enforcement Administration|DEA]] El Paso Intelligence Center data is showing a distinct downward trend in the seizure of clandestine drug labs for the illicit manufacture of methampetamine from a high of 17,356 in 2003. Lab seizure data for the United States is available from EPIC beginning in 1999 when 7,438 labs were reported to have been seized during that calendar year. These figures include methamphetamine lab, "dumpsite" and "chemical and glassware" seizures.<ref>{{cite web|url=http://www.usdoj.gov/dea/concern/map_lab_seizures.html|title=Maps of Methamphetamine Lab Incidents|author=DEA}}</ref>

===Legality of similar chemicals===
See [[pseudoephedrine]] and [[ephedrine]] for legal restrictions in place as a result of their use as precursors in the [[clandestine chemistry|clandestine manufacture]] of methamphetamine.

==See also==
* [[Amphetamine]]
* [[Childhelp Crystal Darkness]]
* [[Clandestine chemistry]]
* [[G protein-coupled receptor]]
* [[Methamphetamine (medical)]]
* [[Illegal drug trade#methamphetamine|Methamphetamine Drug Trade]]
* [[Levomethamphetamine]]
* [[Meth capital of the world]]
* [[Montana Meth Project]]
* [[Phenethylamine]]
* [[Propylhexedrine]]
* [[Releasing agent]]
* [[Rolling meth lab]]

==Footnotes==
<references group="Note" />

==References==
{{Reflist|2}}

==Further reading==

* {{cite book|last=Yudko|first=Errol|coauthors=McPherson, Sandra; Hall, Harold|title=Methamphetamine Use: Clinical and Forensic Aspects|publisher=CRC Press|location=Boca Raton, FL|date=2008-10-29|edition=2|series=408|isbn=978-0849372735|url=http://search.barnesandnoble.com/booksearch/isbninquiry.asp?ean=9780849372735&box=978-0849372735&pos=-1}}

==External links==
* [http://toxnet.nlm.nih.gov/cgi-bin/sis/search/r?dbs+hsdb:@term+@rn+@rel+537-46-2 NLM Hazardous Substances Data Bank] - Entry for d-methamphetamine
* [http://www.erowid.org/chemicals/meth/meth.shtml Erowid Methamphetamine Vault]
* [http://www.emcdda.europa.eu?nnodeid=25480 EMCDDA drugs profiles: Methamphetamine (2007)]
* [http://www.nyhealth.gov/diseases/aids/harm_reduction/crystalmeth/docs/meth_literature_index.pdf A Key to Methamphetamine-Related Literature] - A comprehensive thematic index of methamphetamine research published in academic and scientific journals with links from citations to the PubMed abstracts.
** [http://www.erowid.org/chemicals/meth/meth_faq.shtml#synthesis Meth FAQ] - More detailed synthesis and synthesis from other sources.
* [http://www.usdoj.gov/dea/pubs/pressrel/meth_index.html DEA's Methamphetamine News Releases]
* [http://www.inchem.org/documents/pims/pharm/pim334.htm Poison Information Monograph] (PIM 334: Methamphetamine)
* [http://www.acnp.org/g4/GN401000166/Default.htm Chronic Amphetamine Use and Abuse] - a thorough review on the effects of chronic use (American College of Neuropsychopharmacology)
* [http://methcoaster.yolasite.com/] - Self Help Guide for Family Members and Loved Ones of Meth Addicts
===Documentaries===
*[http://abc.net.au/4corners/special_eds/20060320/ The Ice Age] - ABC Australia - 4 Corners&nbsp;— Australian methamphetamine use.
*[http://www.pbs.org/wgbh/pages/frontline/meth/ Frontline - The Meth Epidemic] - PBS United States&nbsp;— Frontline.
*[http://shop.nationalgeographic.com/product/1167/3408/1074.html The World's Most Dangerous Drug] - National Geographic.
*[http://www.bbc.co.uk/iplayer/episode/b00m572d/Louis_Theroux_The_City_Addicted_to_Crystal_Meth The City Addicted to Crystal Meth - BBC (Louis Theroux)]
===Academic Sources===
*[http://books.google.com/books?hl=en&lr=&id=gVw_wzZU4x8C&oi=fnd&pg=PA113&dq=history+methamphetamine&ots=qAxtq4m1HZ&sig=najz_xcJJ782gsd41TEqXm40igo#v=onepage&q=history%20methamphetamine&f=false History and Epidemiology of Amphetamine Abuse in United States]
*[http://studentpulse.com/articles/77/the-methamphetamine-crisis-in-american-indian-and-native-alaskan-communities-toward-a-new-research-agenda The Methamphetamine Crisis in American Indian and Native Alaskan Communities]

{{Methamphetamine}}
{{Drug use}}
{{Stimulants}}
{{Antihyperkinetics}}
{{Anorectics}}
{{Adrenergics}}
{{Dopaminergics}}
{{Phenethylamines}}


[[Category:Anorectics]]
[[Category:Japanese inventions]]
[[Category:Methamphetamine]]
[[Category:Monoamine oxidase inhibitors]]
[[Category:Cardiac stimulants]]
[[Category:Dopamine agonists]]
[[Category:Serotonin receptor agonists]]
[[Category:Drugs]]
[[Category:Drugs acting on the nervous system]]
[[Category:Euphoriants]]
[[Category:Sympathomimetic amines]]

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Revision as of 16:13, 11 March 2010

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