methamphetamine#Sexual behaviour

File:Desoxyn Package of 100 Pills.jpg

In the United States, methamphetamine hydrochloride, sold under the brand name Desoxyn, is FDA-approved for the treatment of attention deficit hyperactivity disorder (ADHD); however, the FDA notes that the limited therapeutic usefulness of methamphetamine should be weighed against the risks associated with its use. To avoid toxicity and risk of side effects, FDA guidelines recommend an initial dose of methamphetamine at doses 5–10 mg/day for ADHD in adults and children over six years of age, and may be increased at weekly intervals of 5 mg, up to 25 mg/day, until optimum clinical response is found; the usual effective dose is around 20–25 mg/day. Methamphetamine is sometimes prescribed off-label for obesity, narcolepsy, and idiopathic hypersomnia.{{cite journal |vauthors = Mitler MM, Hajdukovic R, Erman MK |title = Treatment of narcolepsy with methamphetamine |journal = Sleep |volume = 16 |issue = 4 |pages = 306–317 |year = 1993 |pmid = 8341891 |pmc = 2267865 }}{{cite journal |vauthors = Morgenthaler TI, Kapur VK, Brown T, Swick TJ, Alessi C, Aurora RN, Boehlecke B, ((Chesson AL Jr)), Friedman L, Maganti R, Owens J, Pancer J, Zak R, ((Standards of Practice Committee of the American Academy of Sleep Medicine)) |title = Practice parameters for the treatment of narcolepsy and other hypersomnias of central origin |journal = Sleep |volume = 30 |issue = 12|pages = 1705–11 |year = 2007 |pmid = 18246980 |pmc = 2276123 |doi = 10.1093/sleep/30.12.1705}} In the United States, methamphetamine's levorotary form is available in some over-the-counter (OTC) nasal decongestant products.

Although the pharmaceutical name "methamphetamine hydrochloride" may suggest a racemic mixture, Desoxyn contains enantiopure dextromethamphetamine, which is a more potent stimulant than both levomethamphetamine and racemic methamphetamine. This naming convention deviates from the standard practice observed with other stimulants, such as Adderall and dextroamphetamine, where the dextrorotary enantiomer is explicitly identified as an active ingredient in both generic and brand-name pharmaceuticals.{{cite book |url=https://archive.org/details/amphetaminemisus0000unse/page/2 |title=Amphetamine Misuse: International Perspectives on Current Trends |vauthors=Yoshida T |date=1997 |publisher=Harwood Academic Publishers |isbn=9789057020810 |veditors=Klee H |location=Amsterdam, Netherlands |page=[https://archive.org/details/amphetaminemisus0000unse/page/2 2] |chapter=Chapter 1: Use and Misuse of Amphetamines: An International Overview |quote=Methamphetamine (INN: metamfetamine) is the N-methyl derivative of amphetamine. Unlike amfetamine (INN) which corresponds to the racemic mixture, metamfetamine (INN) refers to the dextro-isomer of l-phenyl-2-methylaminopropane. |chapter-url=https://books.google.com/books?id=gVw_wzZU4x8C&pg=PA2}}{{cite web | title=Adderall- dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate, and amphetamine sulfate tablet | website=DailyMed | publisher = Teva Pharmaceuticals USA, Inc. | date=29 May 2024 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f22635fe-821d-4cde-aa12-419f8b53db81 | access-date=3 December 2024}}{{cite web | title=Dextroamphetamine sulfate tablet | website=DailyMed | date=10 July 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e05cf690-d45a-4696-a1bf-40c9350cc084 | access-date=3 December 2024}}

As methamphetamine is associated with a high potential for misuse, the drug is regulated under the Controlled Substances Act and is listed under Schedule II in the United States. Methamphetamine hydrochloride dispensed in the United States is required to include a boxed warning regarding its potential for recreational misuse and addiction liability.

Desoxyn and Desoxyn Gradumet are both pharmaceutical forms of the drug. The latter is no longer produced and is an extended-release form of the drug, flattening the curve of the effect of the drug while extending it.{{Cite web |date=19 March 2022 |title=Desoxyn Gradumet Side Effects |url=https://www.drugs.com/sfx/desoxyn-gradumet-side-effects.html |url-status=live |access-date=18 October 2022 |website=Drugs.com |archive-date=18 October 2022 |archive-url=https://web.archive.org/web/20221018043550/https://www.drugs.com/sfx/desoxyn-gradumet-side-effects.html }}

{{Hatnote|See also: Party and play and the Recreational routes of methamphetamine administration}}

Methamphetamine is often used recreationally for its effects as a potent euphoriant and stimulant as well as aphrodisiac qualities.{{cite AV media |date=August 2013 |title=San Francisco Meth Zombies |medium=TV documentary |url=http://channel.nationalgeographic.com/drugs-inc/episodes/san-francisco-meth-zombies/ |publisher=National Geographic Channel |asin=B00EHAOBAO |access-date=7 July 2016 |archive-url=https://web.archive.org/web/20160708142916/http://channel.nationalgeographic.com/drugs-inc/episodes/san-francisco-meth-zombies/ |archive-date=8 July 2016 |url-status=dead }}

According to a National Geographic TV documentary on methamphetamine, an entire subculture known as party and play is based around sexual activity and methamphetamine use. Participants in this subculture, which consists almost entirely of homosexual male methamphetamine users, will typically meet up through internet dating sites and have sex. Because of its strong stimulant and aphrodisiac effects and inhibitory effect on ejaculation, with repeated use, these sexual encounters will sometimes occur continuously for several days on end. The crash following the use of methamphetamine in this manner is very often severe, with marked hypersomnia (excessive daytime sleepiness). The party and play subculture is prevalent in major US cities such as San Francisco and New York City.{{cite book | vauthors = Nelson LS, Lewin NA, Howland MA, Hoffman RS, Goldfrank LR, Flomenbaum NE |title = Goldfrank's toxicologic emergencies |date = 2011 |publisher = McGraw-Hill Medical |location = New York |isbn = 978-0-07-160593-9 |edition = 9th |page = 1080 }}

{{multiple image

| align = center

| direction = horizontal

| width =

| header =

| header_align = center

| header_background =

| footer =

| footer_align =

| footer_background =

| background color =

|image1=Desoxyn (methamphetamine) 5 mg tablets.jpg

|image2=Blue Crystal Meth.jpg

|width1=260

|caption1=Desoxyn tablets – pharmaceutical methamphetamine hydrochloride

|alt1=Desoxyn tablet

|width2=236

|caption2=Crystal meth – illicit methamphetamine hydrochloride

|alt2=Crystal meth

}}

{{clear}}

Methamphetamine is contraindicated in individuals with a history of substance use disorder, heart disease, or severe agitation or anxiety, or in individuals currently experiencing arteriosclerosis, glaucoma, hyperthyroidism, or severe hypertension. The FDA states that individuals who have experienced hypersensitivity reactions to other stimulants in the past or are currently taking monoamine oxidase inhibitors should not take methamphetamine. The FDA also advises individuals with bipolar disorder, depression, elevated blood pressure, liver or kidney problems, mania, psychosis, Raynaud's phenomenon, seizures, thyroid problems, tics, or Tourette syndrome to monitor their symptoms while taking methamphetamine. Owing to the potential for stunted growth, the FDA advises monitoring the height and weight of growing children and adolescents during treatment.

File:HarmCausedByDrugsTable.svg

Methamphetamine is a sympathomimetic drug that causes vasoconstriction and tachycardia. Methamphetamine also promotes abnormal extra heart beats and irregular heart rhythms some of which may be life-threatening.

{{cite journal | vauthors = Kevil CG, Goeders NE, Woolard MD, Bhuiyan MS, Dominic P, Kolluru GK, Arnold CL, Traylor JG, Orr AW | title = Methamphetamine Use and Cardiovascular Disease | journal = Arteriosclerosis, Thrombosis, and Vascular Biology | volume = 39 | issue = 9 | pages = 1739–1746 | date = September 2019 | pmid = 31433698 | pmc = 6709697 | doi = 10.1161/ATVBAHA.119.312461 }}

The effects can also include loss of appetite, hyperactivity, dilated pupils, flushed skin, excessive sweating, increased movement, dry mouth and teeth grinding (potentially leading to condition informally known as meth mouth), headache, rapid breathing, high body temperature, diarrhea, constipation, blurred vision, dizziness, twitching, numbness, tremors, dry skin, acne, and pale appearance. Long-term meth users may have sores on their skin;{{cite web | url = https://www.drugabuse.gov/publications/research-reports/methamphetamine/what-are-long-term-effects-methamphetamine-misuse | title = What are the long-term effects of methamphetamine misuse? | date = October 2019 | work = National Institute on Drug Abuse | publisher = National Institutes of Health, U.S. Department of Health & Human Services | access-date = 15 March 2020 | archive-date = 29 March 2020 | archive-url = https://web.archive.org/web/20200329012502/https://www.drugabuse.gov/publications/research-reports/methamphetamine/what-are-long-term-effects-methamphetamine-misuse | url-status = live }} these may be caused by scratching due to itchiness or the belief that insects are crawling under their skin, and the damage is compounded by poor diet and hygiene.{{cite web | url = https://www.drugrehab.com/addiction/drugs/crystal-meth/sores/ | title = Meth Sores | vauthors = Elkins C | date = 27 February 2020 | work = DrugRehab.com | publisher = Advanced Recovery Systems | access-date = 15 March 2020 | archive-date = 14 August 2020 | archive-url = https://web.archive.org/web/20200814113224/https://www.drugrehab.com/addiction/drugs/crystal-meth/sores/ | url-status = live }} Numerous deaths related to methamphetamine overdoses have been reported.{{Cite web|url=https://www.bluecrestrc.com/can-you-overdose-on-meth/|title=Meth Overdose Symptoms, Effects & Treatment | BlueCrest|date=17 June 2019|website=Bluecrest Recovery Center|access-date=8 October 2020|archive-date=16 January 2021|archive-url=https://web.archive.org/web/20210116171406/https://www.bluecrestrc.com/can-you-overdose-on-meth/|url-status=live}}{{Cite web|url=https://www.drugabuse.gov/drug-topics/trends-statistics/overdose-death-rates|title=Overdose Death Rates|author=National Institute on Drug Abuse|date=29 January 2021|website=National Institute on Drug Abuse|access-date=8 October 2020|archive-date=25 January 2018|archive-url=https://web.archive.org/web/20180125182059/https://www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates|url-status=live}} Additionally, "[p]ostmortem examinations of human tissues have linked use of the drug to diseases associated with aging, such as coronary atherosclerosis and pulmonary fibrosis",{{cite web |url=https://www.sciencedaily.com/releases/2015/02/150211153838.htm |title=Accelerated cellular aging caused by methamphetamine use limited in lab |author= |date=11 February 2015 |website=ScienceDaily |access-date=29 July 2024 |archive-date=22 September 2024 |archive-url=https://web.archive.org/web/20240922021108/https://www.sciencedaily.com/releases/2015/02/150211153838.htm |url-status=live }} which may be caused "by a considerable rise in the formation of ceramides, pro-inflammatory molecules that can foster cell aging and death."

{{Main|Meth mouth}}

File:Suspectedmethmouth09-19-05.jpg]]

Methamphetamine users, particularly heavy users, may lose their teeth abnormally quickly, regardless of the route of administration, from a condition informally known as meth mouth. The condition is generally most severe in users who inject the drug, rather than swallow, smoke, or inhale it.{{cite journal |vauthors = Hussain F, Frare RW, Py Berrios KL |title = Drug abuse identification and pain management in dental patients: a case study and literature review |journal = Gen. Dent. |volume = 60 |issue = 4 |pages = 334–345 |year = 2012 |pmid = 22782046 }} 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)".{{cite web |url = http://www.ada.org/prof/resources/topics/methmouth.asp |title = Methamphetamine Use (Meth Mouth) |access-date = 15 December 2006 |publisher = American Dental Association |archive-url = https://web.archive.org/web/20080601035323/http://www.ada.org/prof/resources/topics/methmouth.asp |archive-date = 1 June 2008 }} As dry mouth is also a common side effect of other stimulants, which are not known to contribute severe tooth decay, many researchers suggest that methamphetamine-associated tooth decay is more due to users' other choices. They suggest the side effect has been exaggerated and stylized to create a stereotype of current users as a deterrence for new ones.{{cite journal |vauthors = Hart CL, Marvin CB, Silver R, Smith EE |title = Is cognitive functioning impaired in methamphetamine users? A critical review |journal = Neuropsychopharmacology |volume = 37 |issue = 3 |pages = 586–608 |date = February 2012 |pmid = 22089317 |pmc = 3260986 |doi = 10.1038/npp.2011.276 }}

Methamphetamine use was found to be related to higher frequencies of unprotected sexual intercourse in both HIV-positive and unknown casual partners, an association more pronounced in HIV-positive participants. These findings suggest that methamphetamine use and engagement in unprotected anal intercourse are co-occurring risk behaviors, behaviors that potentially heighten the risk of HIV transmission among gay and bisexual men.{{cite journal |vauthors = Halkitis PN, Pandey Mukherjee P, Palamar JJ |title = Longitudinal Modeling of Methamphetamine Use and Sexual Risk Behaviors in Gay and Bisexual Men |journal = AIDS and Behavior |volume = 13 |issue = 4 |pages = 783–791 |year = 2008 |pmid = 18661225 |doi = 10.1007/s10461-008-9432-y |pmc = 4669892 }} Methamphetamine use allows users of both sexes to engage in prolonged sexual activity, which may cause genital sores and abrasions as well as priapism in men.{{cite web | vauthors = Moore P |url = http://www.villagevoice.com/2005-06-14/people/we-are-not-ok/ |title = We Are Not OK |publisher = VillageVoice |date = June 2005 |access-date = 15 January 2011 |archive-url = https://web.archive.org/web/20110604154056/http://www.villagevoice.com/2005-06-14/people/we-are-not-ok/ |archive-date = 4 June 2011 |url-status = live }} Methamphetamine may also cause sores and abrasions in the mouth via bruxism, increasing the risk of sexually transmitted infection.

Besides the sexual transmission of HIV, it may also be transmitted between users who share a common needle. The level of needle sharing among methamphetamine users is similar to that among other drug injection users.{{cite web |url = http://www.med.unsw.edu.au/NDARCWeb.nsf/resources/NDLERF_Methamphetamine/$file/NDLERF+USE+AND+HEALTH.pdf |archive-url = https://web.archive.org/web/20080816134234/http://www.med.unsw.edu.au/NDARCWeb.nsf/resources/NDLERF_Methamphetamine/%24file/NDLERF%2BUSE%2BAND%2BHEALTH.pdf |archive-date = 16 August 2008 |title = Methamphetamine Use and Health {{pipe}} UNSW: The University of New South Wales – Faculty of Medicine |access-date = 15 January 2011 |url-status=dead }}

The psychological effects of methamphetamine can include euphoria, dysphoria, changes in libido, alertness, apprehension and concentration, decreased sense of fatigue, insomnia or wakefulness, self-confidence, sociability, irritability, restlessness, grandiosity and repetitive and obsessive behaviors.{{cite web | title=Desoxyn- methamphetamine hydrochloride tablet | website=DailyMed | date=8 September 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=81bfc45f-c345-47d0-9fc9-77abe553b541 | access-date=20 June 2024 | archive-date=22 September 2024 | archive-url=https://web.archive.org/web/20240922021215/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=81bfc45f-c345-47d0-9fc9-77abe553b541 | url-status=live }}{{cite book |veditors = Brunton LL, Chabner BA, Knollmann BC |title = Goodman & Gilman's Pharmacological Basis of Therapeutics |year = 2010 |publisher = McGraw-Hill |location = New York |isbn = 978-0-07-162442-8 |vauthors = Westfall DP, Westfall TC | chapter = Miscellaneous Sympathomimetic Agonists | chapter-url = http://www.accessmedicine.com/content.aspx?aID=16661601 |edition = 12th |access-date = 1 January 2014 |archive-date = 10 November 2013 |archive-url = https://web.archive.org/web/20131110094145/http://www.accessmedicine.com/content.aspx?aID=16661601 }}{{cite web |url = http://www.merckmanuals.com/professional/special_subjects/drug_use_and_dependence/amphetamines.html | vauthors = O'Connor PG |title = Amphetamines |website = Merck Manual for Health Care Professionals |publisher = Merck |date = February 2012 |access-date = 8 May 2012 |archive-url = https://web.archive.org/web/20120506232123/http://www.merckmanuals.com/professional/special_subjects/drug_use_and_dependence/amphetamines.html |archive-date = 6 May 2012 |url-status = live }} Peculiar to methamphetamine and related stimulants is "punding", persistent non-goal-directed repetitive activity.{{cite journal | vauthors = Rusinyak DE |title = Neurologic manifestations of chronic methamphetamine abuse |journal = Neurologic Clinics |date = 2011 |volume = 29 |issue = 3 |pages = 641–655 |doi = 10.1016/j.ncl.2011.05.004 |pmc = 3148451 |pmid = 21803215 }} Methamphetamine use also has a high association with anxiety, depression, amphetamine psychosis, suicide, and violent behaviors.{{cite journal |vauthors = Darke S, Kaye S, McKetin R, Duflou J |title = Major physical and psychological harms of methamphetamine use |journal = Drug Alcohol Rev. |volume = 27 |issue = 3 |pages = 253–262 |date = May 2008 |pmid = 18368606 |doi = 10.1080/09595230801923702 }}{{cite news |vauthors=Raskin S |title=Missouri sword slay suspect smiles for mug shot after allegedly killing beau |url=https://nypost.com/2021/12/26/missouri-woman-grins-for-mug-shot-after-alleged-sword-slay/ |access-date=26 December 2021 |agency=New York Post |date=26 December 2021 |archive-date=26 December 2021 |archive-url=https://web.archive.org/web/20211226192534/https://nypost.com/2021/12/26/missouri-woman-grins-for-mug-shot-after-alleged-sword-slay/ |url-status=live }}

File:Glial ntox review.jpg that mediate methamphetamine-induced neurodegeneration in the human brain. The NF-κB-mediated neuroimmune response to methamphetamine use which results in the increased permeability of the blood–brain barrier arises through its binding at and activation of sigma receptors, the increased production of reactive oxygen species (ROS), reactive nitrogen species (RNS), and damage-associated molecular pattern molecules (DAMPs), the dysregulation of glutamate transporters (specifically, EAAT1 and EAAT2) and glucose metabolism, and excessive Ca²⁺ ion influx in glial cells and dopamine neurons.{{Cite book |vauthors = Beardsley PM, Hauser KF |chapter = Glial Modulators as Potential Treatments of Psychostimulant Abuse |title = Emerging Targets & Therapeutics in the Treatment of Psychostimulant Abuse |volume = 69 |pages = 1–69 |year = 2014 |pmid = 24484974 |pmc = 4103010 |doi = 10.1016/B978-0-12-420118-7.00001-9 |quote = Glia (including astrocytes, microglia, and oligodendrocytes), which constitute the majority of cells in the brain, have many of the same receptors as neurons, secrete neurotransmitters and neurotrophic and neuroinflammatory factors, control clearance of neurotransmitters from synaptic clefts, and are intimately involved in synaptic plasticity. Despite their prevalence and spectrum of functions, appreciation of their potential general importance has been elusive since their identification in the mid-1800s, and only relatively recently have they been gaining their due respect. This development of appreciation has been nurtured by the growing awareness that drugs of abuse, including the psychostimulants, affect glial activity, and glial activity, in turn, has been found to modulate the effects of the psychostimulants |series = Advances in Pharmacology |publisher = Academic Press |isbn = 978-0-12-420118-7 }}{{cite book | vauthors = Loftis JM, Janowsky A | title = Neuroimmune Signaling in Drug Actions and Addictions | chapter = Neuroimmune basis of methamphetamine toxicity | volume = 118 | pages = 165–197 | year = 2014 | pmid = 25175865 | pmc = 4418472 | doi = 10.1016/B978-0-12-801284-0.00007-5 | isbn = 978-0-12-801284-0 | series = International Review of Neurobiology | publisher = Academic Press | quote = Collectively, these pathological processes contribute to neurotoxicity (e.g., increased BBB permeability, inflammation, neuronal degeneration, cell death) and neuropsychiatric impairments (e.g., cognitive deficits, mood disorders) }}
{{cite journal | title = Figure 7.1: Neuroimmune mechanisms of methamphetamine-induced CNS toxicity | date = 2014 | pmc = 4418472 | journal = International Review of Neurobiology | volume = 118 | pages = 165–197 | doi = 10.1016/B978-0-12-801284-0.00007-5 | pmid = 25175865 | vauthors = Loftis JM, Janowsky A }}"]]

Methamphetamine is directly neurotoxic to dopaminergic neurons in both lab animals and humans. Excitotoxicity, oxidative stress, metabolic compromise, UPS dysfunction, protein nitration, endoplasmic reticulum stress, p53 expression and other processes contributed to this neurotoxicity.{{cite journal |vauthors = Carvalho M, Carmo H, Costa VM, Capela JP, Pontes H, Remião F, Carvalho F, Bastos Mde L |title = Toxicity of amphetamines: an update |journal = Arch. Toxicol. |volume = 86 |issue = 8 |pages = 1167–1231 |date = August 2012 |pmid = 22392347 |doi = 10.1007/s00204-012-0815-5 |bibcode = 2012ArTox..86.1167C |s2cid = 2873101 }} In line with its dopaminergic neurotoxicity, methamphetamine use is associated with a higher risk of Parkinson's disease. In addition to its dopaminergic neurotoxicity, a review of evidence in humans indicated that high-dose methamphetamine use can also be neurotoxic to serotonergic neurons.{{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) ...
Neuropsychological studies have detected deficits in attention, working memory, and decision-making in chronic METH addicts ...
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 ...
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). }} It has been demonstrated that a high core temperature is correlated with an increase in the neurotoxic effects of methamphetamine.{{cite journal |vauthors = Yuan J, Hatzidimitriou G, Suthar P, Mueller M, McCann U, Ricaurte G |title = Relationship between temperature, dopaminergic neurotoxicity, and plasma drug concentrations in methamphetamine-treated squirrel monkeys |journal = The Journal of Pharmacology and Experimental Therapeutics |volume = 316 |issue = 3 |pages = 1210–1218 |date = March 2006 |pmid = 16293712 |doi = 10.1124/jpet.105.096503 |s2cid = 11909155 }} Withdrawal of methamphetamine in dependent persons may lead to post-acute withdrawal which persists months beyond the typical withdrawal period.

Magnetic resonance imaging studies on human methamphetamine users have also found evidence of neurodegeneration, or adverse neuroplastic changes in brain structure and function. In particular, methamphetamine appears to cause hyperintensity and hypertrophy of white matter, marked shrinkage of hippocampi, and reduced gray matter in the cingulate cortex, limbic cortex, and paralimbic cortex in recreational methamphetamine users. Moreover, evidence suggests that adverse changes in the level of biomarkers of metabolic integrity and synthesis occur in recreational users, such as a reduction in N-acetylaspartate and creatine levels and elevated levels of choline and myoinositol.

Methamphetamine has been shown to activate TAAR1 in human astrocytes and generate cAMP as a result. Activation of astrocyte-localized TAAR1 appears to function as a mechanism by which methamphetamine attenuates membrane-bound EAAT2 (SLC1A2) levels and function in these cells.{{bull}}{{cite journal |vauthors = Cisneros IE, Ghorpade A |title = Methamphetamine and HIV-1-induced neurotoxicity: role of trace amine associated receptor 1 cAMP signaling in astrocytes |journal = Neuropharmacology |volume = 85 |pages = 499–507 |date = October 2014 |pmid = 24950453 |doi = 10.1016/j.neuropharm.2014.06.011 |quote = TAAR1 overexpression significantly decreased EAAT-2 levels and glutamate clearance ... METH treatment activated TAAR1 leading to intracellular cAMP in human astrocytes and modulated glutamate clearance abilities. Furthermore, molecular alterations in astrocyte TAAR1 levels correspond to changes in astrocyte EAAT-2 levels and function. |pmc = 4315503 }}
{{bull}}{{cite journal |vauthors = Jing L, Li JX |title = Trace amine-associated receptor 1: A promising target for the treatment of psychostimulant addiction |journal = Eur. J. Pharmacol. |volume = 761 |pages = 345–352 |date = August 2015 |pmid = 26092759 |doi = 10.1016/j.ejphar.2015.06.019 |quote = TAAR1 is largely located in the intracellular compartments both in neurons (Miller, 2011), in glial cells (Cisneros and Ghorpade, 2014) and in peripheral tissues (Grandy, 2007) |pmc = 4532615 }}

Methamphetamine binds to and activates both sigma receptor subtypes, σ₁ and σ₂, with micromolar affinity. Sigma receptor activation may promote methamphetamine-induced neurotoxicity by facilitating hyperthermia, increasing dopamine synthesis and release, influencing microglial activation, and modulating apoptotic signaling cascades and the formation of reactive oxygen species.

{{Addiction glossary|collapse=yes|width=610px}}

{{Psychostimulant addiction|align=right}}

Current models of addiction from chronic drug use involve alterations in gene expression in certain parts of the brain, particularly the nucleus accumbens.{{cite journal |vauthors = Hyman SE, Malenka RC, Nestler EJ |title = Neural mechanisms of addiction: the role of reward-related learning and memory |journal = Annu. Rev. Neurosci. |volume = 29 |pages = 565–598 |date = July 2006 |pmid = 16776597 |doi = 10.1146/annurev.neuro.29.051605.113009 |s2cid = 15139406 |url = https://pdfs.semanticscholar.org/fc1e/144037cd3c08aaf32d0a92b8c55a6ae451a5.pdf |archive-url = https://web.archive.org/web/20180919115435/https://pdfs.semanticscholar.org/fc1e/144037cd3c08aaf32d0a92b8c55a6ae451a5.pdf |archive-date = 19 September 2018 }} The most important transcription factors{{#tag:ref|Transcription factors are proteins that increase or decrease the expression of specific genes.{{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, USA |isbn = 978-0-07-148127-4 |page = 94 |edition = 2nd |chapter = Chapter 4: Signal Transduction in the Brain |quote = }}|group="note"}} that produce these alterations are ΔFosB, cAMP response element binding protein (CREB), and nuclear factor kappa B (NFκB). ΔFosB plays a crucial role in the development of drug addictions, since its overexpression in D1-type medium spiny neurons in the nucleus accumbens is necessary and sufficient{{#tag:ref|In simpler terms, this necessary and sufficient relationship means that ΔFosB overexpression in the nucleus accumbens and addiction-related behavioral and neural adaptations always occur together and never occur alone.|group="note"}} for most of the behavioral and neural adaptations that arise from addiction. Once ΔFosB is sufficiently overexpressed, it induces an addictive state that becomes increasingly more severe with further increases in ΔFosB expression. It has been implicated in addictions to alcohol, cannabinoids, cocaine, methylphenidate, nicotine, opioids, phencyclidine, propofol, and substituted amphetamines, among others.{{cite journal | vauthors = Ruffle JK |title = Molecular neurobiology of addiction: what's all the (Δ)FosB about? |journal = Am. J. Drug Alcohol Abuse |volume = 40 |issue = 6 |pages = 428–437 |date = November 2014 |pmid = 25083822 |doi = 10.3109/00952990.2014.933840 |s2cid = 19157711 |quote = ΔFosB is an essential transcription factor implicated in the molecular and behavioral pathways of addiction following repeated drug exposure. }}{{cite journal | vauthors = Olsen CM |title = Natural rewards, neuroplasticity, and non-drug addictions |journal = Neuropharmacology |volume = 61 |issue = 7 |pages = 1109–1122 |date = December 2011 |pmid = 21459101 |pmc = 3139704 |doi = 10.1016/j.neuropharm.2011.03.010 |quote = Similar to environmental enrichment, studies have found that exercise reduces self-administration and relapse to drugs of abuse (Cosgrove et al., 2002; Zlebnik et al., 2010). There is also some evidence that these preclinical findings translate to human populations, as exercise reduces withdrawal symptoms and relapse in abstinent smokers (Daniel et al., 2006; Prochaska et al., 2008), and one drug recovery program has seen success in participants that train for and compete in a marathon as part of the program (Butler, 2005). ... In humans, the role of dopamine signaling in incentive-sensitization processes has recently been highlighted by the observation of a dopamine dysregulation syndrome in some patients taking dopaminergic drugs. This syndrome is characterized by a medication-induced increase in (or compulsive) engagement in non-drug rewards such as gambling, shopping, or sex (Evans et al., 2006; Aiken, 2007; Lader, 2008). }}{{cite web |title = Alcoholism – Homo sapiens (human) |url = http://www.genome.jp/kegg-bin/show_pathway?hsa05034+2354 |website = KEGG Pathway |access-date = 31 October 2014 |author = Kanehisa Laboratories |date = 29 October 2014 |archive-url = https://web.archive.org/web/20141013072800/http://www.genome.jp/kegg-bin/show_pathway?hsa05034+2354 |archive-date = 13 October 2014 |url-status = live }}{{cite journal |vauthors = Kim Y, Teylan MA, Baron M, Sands A, Nairn AC, Greengard P |title = Methylphenidate-induced dendritic spine formation and DeltaFosB expression in nucleus accumbens |journal = Proc. Natl. Acad. Sci. U.S.A. |volume = 106 |issue = 8 |pages = 2915–2920 |date = February 2009 |pmid = 19202072 |pmc = 2650365 |doi = 10.1073/pnas.0813179106 |quote = |bibcode = 2009PNAS..106.2915K |doi-access = free }}

ΔJunD, a transcription factor, and G9a, a histone methyltransferase enzyme, both directly oppose the induction of ΔFosB in the nucleus accumbens (i.e., they oppose increases in its expression).{{cite journal |vauthors = Nestler EJ |title = Epigenetic mechanisms of drug addiction |journal = Neuropharmacology |volume = 76 | issue = Pt B |pages = 259–268 |date = January 2014 |pmid = 23643695 |pmc = 3766384 |doi = 10.1016/j.neuropharm.2013.04.004 |quote = }} Sufficiently overexpressing ΔJunD in the nucleus accumbens with viral vectors can completely block many of the neural and behavioral alterations seen in chronic drug use (i.e., the alterations mediated by ΔFosB). ΔFosB also plays an important role in regulating behavioral responses to natural rewards, such as palatable food, sex, and exercise.{{cite journal |vauthors = Blum K, Werner T, Carnes S, Carnes P, Bowirrat A, Giordano J, Oscar-Berman M, Gold M |title = Sex, drugs, and rock 'n' roll: hypothesizing common mesolimbic activation as a function of reward gene polymorphisms |journal = Journal of Psychoactive Drugs |volume = 44 |issue = 1 |pages = 38–55 |date = March 2012 |pmid = 22641964 |pmc = 4040958 |doi = 10.1080/02791072.2012.662112 |quote = It has been found that deltaFosB gene in the NAc is critical for reinforcing effects of sexual reward. Pitchers and colleagues (2010) reported that sexual experience was shown to cause DeltaFosB accumulation in several limbic brain regions including the NAc, medial pre-frontal cortex, VTA, caudate, and putamen, but not the medial preoptic nucleus. ... these findings support a critical role for DeltaFosB expression in the NAc in the reinforcing effects of sexual behavior and sexual experience-induced facilitation of sexual performance. ... both drug addiction and sexual addiction represent pathological forms of neuroplasticity along with the emergence of aberrant behaviors involving a cascade of neurochemical changes mainly in the brain's rewarding circuitry. }} Since both natural rewards and addictive drugs induce expression of ΔFosB (i.e., they cause the brain to produce more of it), chronic acquisition of these rewards can result in a similar pathological state of addiction.{{cite journal |vauthors = Robison AJ, Nestler EJ |title = Transcriptional and epigenetic mechanisms of addiction |journal = Nat. Rev. Neurosci. |volume = 12 |issue = 11 |pages = 623–637 |date = November 2011 |pmid = 21989194 |pmc = 3272277 |doi = 10.1038/nrn3111 |quote = ΔFosB has been linked directly to several addiction-related behaviors ... Importantly, genetic or viral overexpression of ΔJunD, a dominant-negative mutant of JunD which antagonizes ΔFosB- and other AP-1-mediated transcriptional activity, in the NAc or OFC blocks these key effects of drug exposure^14,22–24. This indicates that ΔFosB is both necessary and sufficient for many of the changes wrought in the brain by chronic drug exposure. ΔFosB is also induced in D1-type NAc MSNs by chronic consumption of several natural rewards, including sucrose, high-fat food, sex, wheel running, where it promotes that consumption^14,26–30. This implicates ΔFosB in the regulation of natural rewards under normal conditions and perhaps during pathological addictive-like states. }} ΔFosB is the most significant factor involved in both amphetamine addiction and amphetamine-induced sex addictions, which are compulsive sexual behaviors that result from excessive sexual activity and amphetamine use.{{#tag:ref|The associated research only involved amphetamine, not methamphetamine; however, this statement is included here due to the similarity between the pharmacodynamics and aphrodisiac effects of amphetamine and methamphetamine.|group="note"}} These sex addictions (i.e., drug-induced compulsive sexual behaviors) are associated with a dopamine dysregulation syndrome which occurs in some patients taking dopaminergic drugs, such as amphetamine or methamphetamine.{{cite journal |vauthors = Pitchers KK, Vialou V, Nestler EJ, Laviolette SR, Lehman MN, Coolen LM |title = Natural and drug rewards act on common neural plasticity mechanisms with ΔFosB as a key mediator |journal = J. Neurosci. |volume = 33 |issue = 8 |pages = 3434–3442 |date = February 2013 |pmid = 23426671 |pmc = 3865508 |doi = 10.1523/JNEUROSCI.4881-12.2013 |quote = Drugs of abuse induce neuroplasticity in the natural reward pathway, specifically the nucleus accumbens (NAc), thereby causing development and expression of addictive behavior. ... Together, these findings demonstrate that drugs of abuse and natural reward behaviors act on common molecular and cellular mechanisms of plasticity that control vulnerability to drug addiction, and that this increased vulnerability is mediated by ΔFosB and its downstream transcriptional targets. ... Sexual behavior is highly rewarding (Tenk et al., 2009), and sexual experience causes sensitized drug-related behaviors, including cross-sensitization to amphetamine (Amph)-induced locomotor activity (Bradley and Meisel, 2001; Pitchers et al., 2010a) and enhanced Amph reward (Pitchers et al., 2010a). Moreover, sexual experience induces neural plasticity in the NAc similar to that induced by psychostimulant exposure, including increased dendritic spine density (Meisel and Mullins, 2006; Pitchers et al., 2010a), altered glutamate receptor trafficking, and decreased synaptic strength in prefrontal cortex-responding NAc shell neurons (Pitchers et al., 2012). Finally, periods of abstinence from sexual experience were found to be critical for enhanced Amph reward, NAc spinogenesis (Pitchers et al., 2010a), and glutamate receptor trafficking (Pitchers et al., 2012). These findings suggest that natural and drug reward experiences share common mechanisms of neural plasticity }}

Methamphetamine addiction is persistent for many individuals, with 61% of individuals treated for addiction relapsing within one year.{{cite journal |vauthors=Brecht ML, Herbeck D |title=Time to relapse following treatment for methamphetamine use: a long-term perspective on patterns and predictors |journal=Drug Alcohol Depend |volume=139 |pages=18–25 |date=June 2014 |pmid=24685563 |pmc=4550209 |doi=10.1016/j.drugalcdep.2014.02.702 }} About half of those with methamphetamine addiction continue with use over a ten-year period, while the other half reduce use starting at about one to four years after initial use.{{cite journal |vauthors=Brecht ML, Lovinger K, Herbeck DM, Urada D |title=Patterns of treatment utilization and methamphetamine use during first 10 years after methamphetamine initiation |journal=J Subst Abuse Treat |volume=44 |issue=5 |pages=548–56 |date=2013 |pmid=23313146 |pmc=3602162 |doi=10.1016/j.jsat.2012.12.006 }}

The frequent persistence of addiction suggests that long-lasting changes in gene expression may occur in particular regions of the brain, and may contribute importantly to the addiction phenotype. In 2014, a crucial role was found for epigenetic mechanisms in driving lasting changes in gene expression in the brain.

A review in 2015{{cite journal |vauthors=Godino A, Jayanthi S, Cadet JL |title=Epigenetic landscape of amphetamine and methamphetamine addiction in rodents |journal=Epigenetics |volume=10 |issue=7 |pages=574–80 |date=2015 |pmid=26023847 |pmc=4622560 |doi=10.1080/15592294.2015.1055441 }} summarized a number of studies involving chronic methamphetamine use in rodents. Epigenetic alterations were observed in the brain reward pathways, including areas like ventral tegmental area, nucleus accumbens, and dorsal striatum, the hippocampus, and the prefrontal cortex. Chronic methamphetamine use caused gene-specific histone acetylations, deacetylations and methylations. Gene-specific DNA methylations in particular regions of the brain were also observed. The various epigenetic alterations caused downregulations or upregulations of specific genes important in addiction. For instance, chronic methamphetamine use caused methylation of the lysine in position 4 of histone 3 located at the promoters of the c-fos and the C-C chemokine receptor 2 (ccr2) genes, activating those genes in the nucleus accumbens (NAc). c-fos is well known to be important in addiction.{{cite journal |vauthors=Cruz FC, Javier Rubio F, Hope BT |title=Using c-fos to study neuronal ensembles in corticostriatal circuitry of addiction |journal=Brain Res. |volume=1628 |issue=Pt A |pages=157–73 |date=December 2015 |pmid=25446457 |pmc=4427550 |doi=10.1016/j.brainres.2014.11.005 }} The ccr2 gene is also important in addiction, since mutational inactivation of this gene impairs addiction.

In methamphetamine addicted rats, epigenetic regulation through reduced acetylation of histones, in brain striatal neurons, caused reduced transcription of glutamate receptors.{{cite journal |vauthors=Jayanthi S, McCoy MT, Chen B, Britt JP, Kourrich S, Yau HJ, Ladenheim B, Krasnova IN, Bonci A, Cadet JL |title=Methamphetamine downregulates striatal glutamate receptors via diverse epigenetic mechanisms |journal=Biol. Psychiatry |volume=76 |issue=1 |pages=47–56 |date=July 2014 |pmid=24239129 |pmc=3989474 |doi=10.1016/j.biopsych.2013.09.034 }} Glutamate receptors play an important role in regulating the reinforcing effects of addictive drugs.{{cite journal |vauthors=Kenny PJ, Markou A |title=The ups and downs of addiction: role of metabotropic glutamate receptors |journal=Trends Pharmacol. Sci. |volume=25 |issue=5 |pages=265–72 |date=May 2004 |pmid=15120493 |doi=10.1016/j.tips.2004.03.009 }}

Administration of methamphetamine to rodents causes DNA damage in their brain, particularly in the nucleus accumbens region.{{cite journal | vauthors = Tokunaga I, Ishigami A, Kubo S, Gotohda T, Kitamura O | title = The peroxidative DNA damage and apoptosis in methamphetamine-treated rat brain | journal = The Journal of Medical Investigation | volume = 55 | issue = 3–4 | pages = 241–245 | date = August 2008 | pmid = 18797138 | doi = 10.2152/jmi.55.241 | doi-access = free }}{{cite journal | vauthors = Johnson Z, Venters J, Guarraci FA, Zewail-Foote M | title = Methamphetamine induces DNA damage in specific regions of the female rat brain | journal = Clinical and Experimental Pharmacology & Physiology | volume = 42 | issue = 6 | pages = 570–575 | date = June 2015 | pmid = 25867833 | doi = 10.1111/1440-1681.12404 | s2cid = 24182756 }} During repair of such DNA damages, persistent chromatin alterations may occur such as in the methylation of DNA or the acetylation or methylation of histones at the sites of repair.{{cite journal | vauthors = Dabin J, Fortuny A, Polo SE | title = Epigenome Maintenance in Response to DNA Damage | journal = Molecular Cell | volume = 62 | issue = 5 | pages = 712–727 | date = June 2016 | pmid = 27259203 | pmc = 5476208 | doi = 10.1016/j.molcel.2016.04.006 }} These alterations can be epigenetic scars in the chromatin that contribute to the persistent epigenetic changes found in methamphetamine addiction.

{{Further|Addiction#Research}}

A 2018 systematic review and network meta-analysis of 50 trials involving 12 different psychosocial interventions for amphetamine, methamphetamine, or cocaine addiction found that combination therapy with both contingency management and community reinforcement approach had the highest efficacy (i.e., abstinence rate) and acceptability (i.e., lowest dropout rate).{{cite journal | vauthors = De Crescenzo F, Ciabattini M, D'Alò GL, De Giorgi R, Del Giovane C, Cassar C, Janiri L, Clark N, Ostacher MJ, Cipriani A | title = Comparative efficacy and acceptability of psychosocial interventions for individuals with cocaine and amphetamine addiction: A systematic review and network meta-analysis | journal = PLOS Medicine | volume = 15 | issue = 12 | pages = e1002715 | date = December 2018 | pmid = 30586362 | pmc = 6306153 | doi = 10.1371/journal.pmed.1002715 | doi-access = free }} Other treatment modalities examined in the analysis included monotherapy with contingency management or community reinforcement approach, cognitive behavioral therapy, 12-step programs, non-contingent reward-based therapies, psychodynamic therapy, and other combination therapies involving these.

{{As of|December 2019}}, there is no effective pharmacotherapy for methamphetamine addiction.{{cite journal |vauthors = Stoops WW, Rush CR |title = Combination pharmacotherapies for stimulant use disorder: a review of clinical findings and recommendations for future research |journal = Expert Rev Clin Pharmacol |volume = 7 |issue = 3 |pages = 363–374 |date = May 2014 |pmid = 24716825 |doi = 10.1586/17512433.2014.909283 |quote = Despite concerted efforts to identify a pharmacotherapy for managing stimulant use disorders, no widely effective medications have been approved. |pmc = 4017926 }}{{cite journal |vauthors = Forray A, Sofuoglu M |title = Future pharmacological treatments for substance use disorders |journal = Br. J. Clin. Pharmacol. |volume = 77 |issue = 2 |pages = 382–400 |date = February 2014 |pmid = 23039267 |pmc = 4014020 |doi = 10.1111/j.1365-2125.2012.04474.x }} A systematic review and meta-analysis from 2019 assessed the efficacy of 17 different pharmacotherapies used in randomized controlled trials (RCTs) for amphetamine and methamphetamine addiction; it found only low-strength evidence that methylphenidate might reduce amphetamine or methamphetamine self-administration.{{cite journal | vauthors = Chan B, Freeman M, Kondo K, Ayers C, Montgomery J, Paynter R, Kansagara D | title = Pharmacotherapy for methamphetamine/amphetamine use disorder-a systematic review and meta-analysis | journal = Addiction | volume = 114 | issue = 12 | pages = 2122–2136 | date = December 2019 | pmid = 31328345 | doi = 10.1111/add.14755 | s2cid = 198136436 }} There was low- to moderate-strength evidence of no benefit for most of the other medications used in RCTs, which included antidepressants (bupropion, mirtazapine, sertraline), antipsychotics (aripiprazole), anticonvulsants (topiramate, baclofen, gabapentin), naltrexone, varenicline, citicoline, ondansetron, prometa, riluzole, atomoxetine, dextroamphetamine, and modafinil.{{Cite web |title=Pharmacotherapy for methamphetamine/amphetamine use disorder—a systematic review and meta-analysis |url=https://www.issup.net/files/2019-09/add.14755.pdf |website=issup.net}}

Medication-Assisted Treatment (MAT) combines FDA-approved medications with behavioral therapies to address substance use disorders. This approach aims to reduce cravings and withdrawal symptoms, supporting individuals in their recovery process.{{Cite web |title=Crystal Meth Addiction |url=https://redemptionrecoverygroup.com/addiction-recovery-resources/crystal-meth-addiction/ |access-date=22 March 2025 |website=Redemption Recovery |language=en-US}}

Tolerance is expected to develop with regular methamphetamine use and, when used recreationally, this tolerance develops rapidly.{{cite web | vauthors = O'Connor P |title = Amphetamines: Drug Use and Abuse |url = http://www.merckmanuals.com/home/special_subjects/drug_use_and_abuse/amphetamines.html |website = Merck Manual Home Health Handbook |publisher = Merck |access-date = 26 September 2013 |archive-url = https://web.archive.org/web/20070217053619/http://www.merck.com/mmhe/sec07/ch108/ch108g.html |archive-date = 17 February 2007 |url-status = live }}{{cite journal |vauthors=Pérez-Mañá C, Castells X, Torrens M, Capellà D, Farre M |title = Efficacy of psychostimulant drugs for amphetamine abuse or dependence |journal = Cochrane Database Syst. Rev. |volume = 2013 |issue = 9 |pages = CD009695 |year = 2013 |pmid = 23996457 |doi = 10.1002/14651858.CD009695.pub2 | veditors = Pérez-Mañá C |doi-access = free |pmc = 11521360 }} In dependent users, withdrawal symptoms are positively correlated with the level of drug tolerance. Depression from methamphetamine withdrawal lasts longer and is more severe than that of cocaine withdrawal.{{cite journal |vauthors = Winslow BT, Voorhees KI, Pehl KA |title = Methamphetamine abuse |journal = American Family Physician |volume = 76 |issue = 8 |pages = 1169–1174 |year = 2007 |pmid = 17990840 }}

According to the current Cochrane review on drug dependence and withdrawal in recreational users of methamphetamine, "when chronic heavy users abruptly discontinue [methamphetamine] use, many report a time-limited withdrawal syndrome that occurs within 24 hours of their last dose".{{cite journal |vauthors = Shoptaw SJ, Kao U, Heinzerling K, Ling W |title = Treatment for amphetamine withdrawal |journal = Cochrane Database Syst. Rev. |issue = 2 |pages = CD003021 |year = 2009 |volume = 2009 |pmid = 19370579 |doi = 10.1002/14651858.CD003021.pub2 |editor = Shoptaw SJ |quote = The prevalence of this withdrawal syndrome is extremely common (Cantwell 1998; Gossop 1982) with 87.6% of 647 individuals with amphetamine dependence reporting six or more signs of amphetamine withdrawal listed in the DSM when the drug is not available (Schuckit 1999) ... Withdrawal symptoms typically present within 24 hours of the last use of amphetamine, with a withdrawal syndrome involving two general phases that can last 3 weeks or more. The first phase of this syndrome is the initial "crash" that resolves within about a week (Gossop 1982;McGregor 2005) |pmc = 7138250 }} Withdrawal symptoms in chronic, high-dose users are frequent, occurring in up to 87.6% of cases, and persist for three to four weeks with a marked "crash" phase occurring during the first week. Methamphetamine withdrawal symptoms can include anxiety, drug craving, dysphoric mood, fatigue, increased appetite, increased movement or decreased movement, lack of motivation, sleeplessness or sleepiness, and vivid or lucid dreams.

Methamphetamine that is present in a mother's bloodstream can pass through the placenta to a fetus and be secreted into breast milk. Infants born to methamphetamine-abusing mothers may experience a neonatal withdrawal syndrome, with symptoms involving of abnormal sleep patterns, poor feeding, tremors, and hypertonia. This withdrawal syndrome is relatively mild and only requires medical intervention in approximately 4% of cases.

{{clear right}}

{{Addiction-related plasticity|Table title=Summary of addiction-related plasticity}}

Unlike other drugs, babies with prenatal exposure to methamphetamine do not show immediate signs of withdrawal. Instead, cognitive and behavioral problems start emerging when the children reach school age.{{cite web | url = https://www.abc.net.au/news/2020-01-03/the-hidden-problem-of-babies-born-to-meth-affected-mothers/11829668 | title = Babies born to meth-affected mothers seem well behaved, but their passive nature masks a serious problem | archive-url = https://web.archive.org/web/20211024113948/https://www.abc.net.au/news/2020-01-03/the-hidden-problem-of-babies-born-to-meth-affected-mothers/11829668 | archive-date = 24 October 2021 | vauthors = Kennedy E | work = ABC News Online | date = 3 January 2020 }}

A prospective cohort study of 330 children showed that at the age of 3, children with methamphetamine exposure showed increased emotional reactivity, as well as more signs of anxiety and depression; and at the age of 5, children showed higher rates of externalizing disorders and attention deficit hyperactivity disorder (ADHD).{{cite journal | vauthors = LaGasse LL, Derauf C, Smith LM, Newman E, Shah R, Neal C, Arria A, Huestis MA, DellaGrotta S, Lin H, Dansereau LM, Lester BM | title = Prenatal methamphetamine exposure and childhood behavior problems at 3 and 5 years of age | journal = Pediatrics | volume = 129 | issue = 4 | pages = 681–8 | date = April 2012 | pmid = 22430455 | pmc = 3313637 | doi = 10.1542/peds.2011-2209 | publisher=American Academy of Pediatrics }}

Methamphetamine overdose is a diverse term. It frequently refers to the exaggeration of the unusual effects with features such as irritability, agitation, hallucinations and paranoia. The cardiovascular effects are typically not noticed in young healthy people. Hypertension and tachycardia are not apparent unless measured. A moderate overdose of methamphetamine may induce symptoms such as: abnormal heart rhythm, confusion, difficult and/or painful urination, high or low blood pressure, high body temperature, over-active and/or over-responsive reflexes, muscle aches, severe agitation, rapid breathing, tremor, urinary hesitancy, and an inability to pass urine. An extremely large overdose may produce symptoms such as adrenergic storm, methamphetamine psychosis, substantially reduced or no urine output, cardiogenic shock, bleeding in the brain, circulatory collapse, hyperpy rexia (i.e., dangerously high body temperature), pulmonary hypertension, kidney failure, rapid muscle breakdown, serotonin syndrome, and a form of stereotypy ("tweaking").{{#tag:ref|{{cite book |veditors = Olson KR, Anderson IB, Benowitz NL, Blanc PD, Kearney TE, Kim-Katz SY, Wu AH |title = Poisoning & Drug Overdose | vauthors = Albertson TE |year = 2011 |publisher = McGraw-Hill Medical |location = New York |isbn = 978-0-07-166833-0 |chapter = Amphetamines |pages = 77–79 |edition = 6th }}{{cite web |title = Amphetamine Poisoning |url = http://emergency.unboundmedicine.com/emergency/ub/view/5-Minute_Emergency_Consult/307063/all/Amphetamine_Poisoning |website = Emergency Central |publisher = Unbound Medicine |date = 11 February 2011 |access-date = 11 June 2013 |vauthors = Oskie SM, Rhee JW |archive-url = https://web.archive.org/web/20130926150016/http://emergency.unboundmedicine.com/emergency/ub/view/5-Minute_Emergency_Consult/307063/all/Amphetamine_Poisoning |archive-date = 26 September 2013 |url-status = live }}{{cite journal |vauthors = Isbister GK, Buckley NA, Whyte IM |title = Serotonin toxicity: a practical approach to diagnosis and treatment |journal = Med. J. Aust. |volume = 187 |issue = 6 |pages = 361–365 |date = September 2007 |pmid = 17874986 |doi = 10.5694/j.1326-5377.2007.tb01282.x|s2cid = 13108173 |url = https://www.mja.com.au/system/files/issues/187_06_170907/isb10375_fm.pdf |access-date = 2 January 2014 |archive-url = https://web.archive.org/web/20140704062057/https://www.mja.com.au/system/files/issues/187_06_170907/isb10375_fm.pdf |archive-date = 4 July 2014 |url-status = live }}| group="sources" }} A methamphetamine overdose will likely also result in mild brain damage owing to dopaminergic and serotonergic neurotoxicity.{{cite book |title=Molecular Neuropharmacology: A Foundation for Clinical Neuroscience |vauthors=Malenka RC, Nestler EJ, Hyman SE, Holtzman DM |publisher=McGraw-Hill Medical |year=2015 |isbn=9780071827706 |edition=3rd |location=New York |chapter=Chapter 16: Reinforcement and Addictive Disorders |quote=Unlike cocaine and amphetamine, methamphetamine is directly toxic at higher doses to midbrain dopamine neurons}} Death from methamphetamine poisoning is typically preceded by convulsions and coma.

{{hatnote|Main section: {{section link|Stimulant psychosis|Substituted amphetamines}}}}

Use of methamphetamine can result in a stimulant psychosis which may present with a variety of symptoms (e.g., paranoia, hallucinations, delirium, and delusions). A Cochrane Collaboration review on treatment for amphetamine, dextroamphetamine, and methamphetamine use-induced psychosis states that about 5–15% of users fail to recover completely.{{cite journal |veditors = Shoptaw SJ, Ali R |vauthors = Shoptaw SJ, Kao U, Ling W |title = Treatment for amphetamine psychosis |journal = Cochrane Database Syst. Rev. |issue = 1 |pages = CD003026 |year = 2009 |volume = 2009 |pmid = 19160215 |doi = 10.1002/14651858.CD003026.pub3 |pmc = 7004251 |quote = A minority of individuals who use amphetamines develop full-blown psychosis requiring care at emergency departments or psychiatric hospitals. In such cases, symptoms of amphetamine psychosis commonly include paranoid and persecutory delusions as well as auditory and visual hallucinations in the presence of extreme agitation. More common (about 18%) is for frequent amphetamine users to report psychotic symptoms that are sub-clinical and that do not require high-intensity intervention ...
About 5–15% of the users who develop an amphetamine psychosis fail to recover completely (Hofmann 1983) ...
Findings from one trial indicate use of antipsychotic medications effectively resolves symptoms of acute amphetamine psychosis. }}{{cite book | vauthors = Hofmann FG |title = A Handbook on Drug and Alcohol Abuse: The Biomedical Aspects |publisher = Oxford University Press |isbn = 978-0-19-503057-0 |location = New York |year = 1983 |page = [https://archive.org/details/handbookondrugal0002hofm/page/329 329] |edition = 2nd |url = https://archive.org/details/handbookondrugal0002hofm/page/329 }} The same review asserts that, based upon at least one trial, antipsychotic medications effectively resolve the symptoms of acute amphetamine psychosis. Amphetamine psychosis may also develop occasionally as a treatment-emergent side effect.{{cite journal |vauthors = Berman SM, Kuczenski R, McCracken JT, London ED |title = Potential adverse effects of amphetamine treatment on brain and behavior: a review |journal = Mol. Psychiatry |volume = 14 |issue = 2 |pages = 123–142 |date = February 2009 |pmid = 18698321 |pmc = 2670101 |doi = 10.1038/mp.2008.90 }}

The CDC reported that the number of deaths in the United States involving psychostimulants with abuse potential to be 23,837 in 2020 and 32,537 in 2021.{{cite journal | vauthors = Spencer MR, Miniño AM, Warner M | title = Drug Overdose Deaths in the United States, 2001–2021 | journal = NCHS Data Brief | issue = 457 | pages = 1–8 | date = December 2022 | pmid = 36598401 | doi = 10.15620/cdc:122556 | publisher = National Center for Health Statistics (U.S.) | s2cid = 254388862 | doi-access = free }} This category code (ICD–10 of T43.6) includes primarily methamphetamine but also other stimulants such as amphetamine, and methylphenidate. The mechanism of death in these cases is not reported in these statistics and is difficult to know.{{cite journal | vauthors = Parish DC, Goyal H, Dane FC | title = Mechanism of death: there's more to it than sudden cardiac arrest | journal = Journal of Thoracic Disease | volume = 10 | issue = 5 | pages = 3081–3087 | date = May 2018 | pmid = 29997977 | pmc = 6006107 | doi = 10.21037/jtd.2018.04.113 | doi-access = free }} Unlike fentanyl which causes respiratory depression, methamphetamine is not a respiratory depressant. Some deaths are as a result of intracranial hemorrhage{{cite journal | vauthors = Noblett D, Hacein-Bey L, Waldau B, Ziegler J, Dahlin B, Chang J | title = Increased rupture risk in small intracranial aneurysms associated with methamphetamine use | journal = Interventional Neuroradiology | volume = 27 | issue = 1 | pages = 75–80 | date = February 2021 | pmid = 32967503 | pmc = 7903554 | doi = 10.1177/1591019920959534 }} and some deaths are cardiovascular in nature including flash pulmonary edema{{cite journal | vauthors = Paone S, Clarkson L, Sin B, Punnapuzha S | title = Recognition of Sympathetic Crashing Acute Pulmonary Edema (SCAPE) and use of high-dose nitroglycerin infusion | journal = The American Journal of Emergency Medicine | volume = 36 | issue = 8 | pages = 1526.e5–1526.e7 | date = August 2018 | pmid = 29776826 | doi = 10.1016/j.ajem.2018.05.013 | s2cid = 21698404 }} and ventricular fibrillation.{{Cite journal |vauthors=Gholami F, Hosseini SH, Ahmadi A, Nabati M |date=15 October 2019 |title=A Case report of hemodynamic instability, cardiac arrest, and acute severe dyspnea subsequent to inhalation of crystal methamphetamine |url=https://publish.kne-publishing.com/index.php/PBR/article/view/1585 |journal=Pharmaceutical and Biomedical Research |doi=10.18502/pbr.v5i2.1585 |issn=2423-4494 |doi-access=free |access-date=26 December 2023 |archive-date=26 December 2023 |archive-url=https://web.archive.org/web/20231226003031/https://publish.kne-publishing.com/index.php/PBR/article/view/1585 |url-status=live }}{{cite journal | vauthors = De Letter EA, Piette MH, Lambert WE, Cordonnier JA | title = Amphetamines as potential inducers of fatalities: a review in the district of Ghent from 1976-2004 | journal = Medicine, Science, and the Law | volume = 46 | issue = 1 | pages = 37–65 | date = January 2006 | pmid = 16454462 | doi = 10.1258/rsmmsl.46.1.37 }}

Acute methamphetamine intoxication is largely managed by treating the symptoms and treatments may initially include administration of activated charcoal and sedation. There is not enough evidence on hemodialysis or peritoneal dialysis in cases of methamphetamine intoxication to determine their usefulness. Forced acid diuresis (e.g., with vitamin C) will increase methamphetamine excretion but is not recommended as it may increase the risk of aggravating acidosis, or cause seizures or rhabdomyolysis. Hypertension presents a risk for intracranial hemorrhage (i.e., bleeding in the brain) and, if severe, is typically treated with intravenous phentolamine or nitroprusside. Blood pressure often drops gradually following sufficient sedation with a benzodiazepine and providing a calming environment.

Antipsychotics such as haloperidol are useful in treating agitation and psychosis from methamphetamine overdose.{{cite journal |vauthors = Richards JR, Derlet RW, Duncan DR |title = Methamphetamine toxicity: treatment with a benzodiazepine versus a butyrophenone |journal = Eur. J. Emerg. Med. |date = September 1997 |volume = 4 |issue = 3 |pages = 130–135 |pmid = 9426992 |doi = 10.1097/00063110-199709000-00003 }} Beta blockers with lipophilic properties and CNS penetration such as metoprolol and labetalol may be useful for treating CNS and cardiovascular toxicity.{{cite web | title = Methamphetamine Toxicity: Treatment & Management | url = http://emedicine.medscape.com/article/820918-treatment#showall |vauthors = Richards JR, Derlet RW, Albertson TE | work = Medscape |publisher = WebMD |access-date = 20 April 2016 |archive-url = https://web.archive.org/web/20160409114830/http://emedicine.medscape.com/article/820918-overview#showall |archive-date = 9 April 2016 |url-status = live }}{{Citation | vauthors = Farzam K, Jan A |title=Beta Blockers |date=2025 |work=StatPearls |url=https://www.ncbi.nlm.nih.gov/books/NBK532906/ |access-date=22 March 2025 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=30422501 }} The mixed alpha- and beta-blocker labetalol is especially useful for treatment of concomitant tachycardia and hypertension induced by methamphetamine.{{cite journal |vauthors = Richards JR, Albertson TE, Derlet RW, Lange RA, Olson KR, Horowitz BZ |title = Treatment of toxicity from amphetamines, related derivatives, and analogues: a systematic clinical review |journal = Drug Alcohol Depend. |date = May 2015 |volume = 150 |pages = 1–13 |doi = 10.1016/j.drugalcdep.2015.01.040 |pmid = 25724076 }} The phenomenon of "unopposed alpha stimulation" has not been reported with the use of beta-blockers for treatment of methamphetamine toxicity.

Methamphetamine is metabolized by the liver enzyme CYP2D6, so CYP2D6 inhibitors will prolong the elimination half-life of methamphetamine.{{cite web |title = Methamphetamine: Enzymes | url = http://www.drugbank.ca/drugs/DB01577#enzymes |work = DrugBank |publisher = University of Alberta |date = 8 February 2013 |access-date = 2 January 2014 |archive-date = 28 December 2015 |archive-url = https://web.archive.org/web/20151228164940/http://www.drugbank.ca/drugs/DB01577#enzymes |url-status = live }} Methamphetamine also interacts with monoamine oxidase inhibitors (MAOIs), since both MAOIs and methamphetamine increase plasma catecholamines; therefore, concurrent use of both is dangerous. Methamphetamine may decrease the effects of sedatives and depressants and increase the effects of antidepressants and other stimulants as well. Methamphetamine may counteract the effects of antihypertensives and antipsychotics owing to its effects on the cardiovascular system and cognition respectively. The pH of gastrointestinal content and urine affects the absorption and excretion of methamphetamine. Specifically, acidic substances will reduce the absorption of methamphetamine and increase urinary excretion, while alkaline substances do the opposite. Owing to the effect pH has on absorption, proton pump inhibitors, which reduce gastric acid, are known to interact with methamphetamine. Norepinephrine reuptake inhibitors (NRIs) like atomoxetine prevent norepinephrine release induced by amphetamines and have been found to reduce the stimulant, euphoriant, and sympathomimetic effects of dextroamphetamine in humans.{{cite journal | vauthors = Treuer T, Gau SS, Méndez L, Montgomery W, Monk JA, Altin M, Wu S, Lin CC, Dueñas HJ | title = A systematic review of combination therapy with stimulants and atomoxetine for attention-deficit/hyperactivity disorder, including patient characteristics, treatment strategies, effectiveness, and tolerability | journal = J Child Adolesc Psychopharmacol | volume = 23 | issue = 3 | pages = 179–193 | date = April 2013 | pmid = 23560600 | pmc = 3696926 | doi = 10.1089/cap.2012.0093 | url = }}{{cite book | vauthors = Heal DJ, Smith SL, Findling RL | title = Behavioral Neuroscience of Attention Deficit Hyperactivity Disorder and Its Treatment | chapter = ADHD: current and future therapeutics | series = Current Topics in Behavioral Neurosciences | volume = 9 | pages = 361–390 | date = 2012 | pmid = 21487953 | doi = 10.1007/7854_2011_125 | isbn = 978-3-642-24611-1 | chapter-url = | quote = Adjunctive therapy with DL-methylphenidate in atomoxetine partial responders has been successful (Wilens et al. 2009), but this also increases the rates of insomnia, irritability and loss of appetite (Hammerness et al. 2009). This combination therapy has not included amphetamine because blockade of NET by atomoxetine prevents entry of amphetamine into presynaptic noradrenergic terminals (Sofuoglu et al. 2009). }}{{cite journal | vauthors = Sofuoglu M, Poling J, Hill K, Kosten T | title = Atomoxetine attenuates dextroamphetamine effects in humans | journal = Am J Drug Alcohol Abuse | volume = 35 | issue = 6 | pages = 412–416 | date = 2009 | pmid = 20014909 | pmc = 2796580 | doi = 10.3109/00952990903383961 | url = }} Similarly, norepinephrine–dopamine reuptake inhibitors (NRIs) like methylphenidate and bupropion prevent norepinephrine and dopamine release induced by amphetamines and bupropion has been found to reduce the subjective and sympathomimetic effects of methamphetamine in humans.{{cite journal | vauthors = Elkashef A, Vocci F, Hanson G, White J, Wickes W, Tiihonen J | title = Pharmacotherapy of methamphetamine addiction: an update | journal = Subst Abus | volume = 29 | issue = 3 | pages = 31–49 | date = 2008 | pmid = 19042205 | pmc = 2597382 | doi = 10.1080/08897070802218554 | bibcode = 2008JPkR...29...31E | url = }}{{cite journal | vauthors = Simmler LD, Wandeler R, Liechti ME | title = Bupropion, methylphenidate, and 3,4-methylenedioxypyrovalerone antagonize methamphetamine-induced efflux of dopamine according to their potencies as dopamine uptake inhibitors: implications for the treatment of methamphetamine dependence | journal = BMC Res Notes | volume = 6 | issue = | pages = 220 | date = June 2013 | pmid = 23734766 | pmc = 3679734 | doi = 10.1186/1756-0500-6-220 | doi-access = free | url = }}{{cite journal | vauthors = Newton TF, Roache JD, De La Garza R, Fong T, Wallace CL, Li SH, Elkashef A, Chiang N, Kahn R | title = Bupropion reduces methamphetamine-induced subjective effects and cue-induced craving | journal = Neuropsychopharmacology | volume = 31 | issue = 7 | pages = 1537–1544 | date = July 2006 | pmid = 16319910 | doi = 10.1038/sj.npp.1300979 | url = }}

File:Amphetamine mechanism of action.svg terminal to the left, and the dopaminergic terminal in the presence of methamphetamine to the right. Methamphetamine reverses the action of the dopamine transporter (DAT) by activating TAAR1 (not shown). TAAR1 activation also causes some of the dopamine transporters to move into the presynaptic neuron and cease transport (not shown). At VMAT2 (labeled VMAT), methamphetamine causes dopamine efflux (release).|alt=An image of methamphetamine pharmacodynamics]]

Methamphetamine has been identified as a potent full agonist of trace amine-associated receptor 1 (TAAR1), a G protein-coupled receptor (GPCR) that regulates brain catecholamine systems.{{cite journal | vauthors = Miller GM |title = The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity |journal = J. Neurochem. |volume = 116 |issue = 2 |pages = 164–176 |date = January 2011 |pmid = 21073468 |pmc = 3005101 |doi = 10.1111/j.1471-4159.2010.07109.x }}{{cite web |title = Methamphetamine: Targets | url = http://www.drugbank.ca/drugs/DB01577#targets |work = DrugBank |publisher = University of Alberta |date = 8 February 2013 |access-date = 4 January 2014 |archive-date = 28 December 2015 |archive-url = https://web.archive.org/web/20151228164940/http://www.drugbank.ca/drugs/DB01577#targets |url-status = live }} Activation of TAAR1 increases cyclic adenosine monophosphate (cAMP) production and either completely inhibits or reverses the transport direction of the dopamine transporter (DAT), norepinephrine transporter (NET), and serotonin transporter (SERT).{{cite journal |vauthors = 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 = 8966–8971 |date = July 2001 |pmid = 11459929 |pmc = 55357 |doi = 10.1073/pnas.151105198 |bibcode = 2001PNAS...98.8966B |doi-access = free }} When methamphetamine binds to TAAR1, it triggers transporter phosphorylation via protein kinase A (PKA) and protein kinase C (PKC) signaling, ultimately resulting in the internalization or reverse function of monoamine transporters.{{cite journal |vauthors = Xie Z, Miller GM |title = A receptor mechanism for methamphetamine action in dopamine transporter regulation in brain |journal = J. Pharmacol. Exp. Ther. |volume = 330 |issue = 1 |pages = 316–325 |date = July 2009 |pmid = 19364908 |pmc = 2700171 |doi = 10.1124/jpet.109.153775 }} Methamphetamine is also known to increase intracellular calcium, an effect which is associated with DAT phosphorylation through a Ca2+/calmodulin-dependent protein kinase (CAMK)-dependent signaling pathway, in turn producing dopamine efflux.{{cite web |title = TA₁ receptor |url = http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=364 |website = IUPHAR database |publisher = International Union of Basic and Clinical Pharmacology |access-date = 8 December 2014 |vauthors = Maguire JJ, Davenport AP |date = 2 December 2014 |quote = |archive-url = https://web.archive.org/web/20150629065449/http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=364 |archive-date = 29 June 2015 |url-status = live }}{{cite journal |vauthors = Underhill SM, Wheeler DS, Li M, Watts SD, Ingram SL, Amara SG |title = Amphetamine modulates excitatory neurotransmission through endocytosis of the glutamate transporter EAAT3 in dopamine neurons |journal = Neuron |volume = 83 |issue = 2 |pages = 404–416 |date = July 2014 |pmid = 25033183 |pmc = 4159050 |doi = 10.1016/j.neuron.2014.05.043 |quote = AMPH also increases intracellular calcium (Gnegy et al., 2004) that is associated with calmodulin/CamKII activation (Wei et al., 2007) and modulation and trafficking of the DAT (Fog et al., 2006; Sakrikar et al., 2012). }}{{cite journal |vauthors = Vaughan RA, Foster JD |title = Mechanisms of dopamine transporter regulation in normal and disease states |journal = Trends Pharmacol. Sci. |volume = 34 |issue = 9 |pages = 489–496 |date = September 2013 |pmid = 23968642 |pmc = 3831354 |doi = 10.1016/j.tips.2013.07.005 |quote = AMPH and METH also stimulate DA efflux, which is thought to be a crucial element in their addictive properties [80], although the mechanisms do not appear to be identical for each drug [81]. These processes are PKCβ– and CaMK–dependent [72, 82], and PKCβ knock-out mice display decreased AMPH-induced efflux that correlates with reduced AMPH-induced locomotion [72]. }} TAAR1 has been shown to reduce the firing rate of neurons through direct activation of G protein-coupled inwardly-rectifying potassium channels.{{cite journal |vauthors = Ledonne A, Berretta N, Davoli A, Rizzo GR, Bernardi G, Mercuri NB |title = Electrophysiological effects of trace amines on mesencephalic dopaminergic neurons |journal = Front. Syst. Neurosci. |volume = 5 |pages = 56 |date = July 2011 |pmid = 21772817 |pmc = 3131148 |doi = 10.3389/fnsys.2011.00056 |quote = inhibition of firing due to increased release of dopamine; (b) reduction of D2 and GABAB receptor-mediated inhibitory responses (excitatory effects due to disinhibition); and (c) a direct TA1 receptor-mediated activation of GIRK channels which produce cell membrane hyperpolarization. |doi-access = free }}{{cite web | url = http://genatlas.medecine.univ-paris5.fr/fiche.php?symbol=TAAR1 | title = TAAR1 | author = mct | date = 28 January 2012 | website = GenAtlas | publisher = University of Paris | access-date = 29 May 2014 | quote =
{{bull}} tonically activates inwardly rectifying K(+) channels, which reduces the basal firing frequency of dopamine (DA) neurons of the ventral tegmental area (VTA) | archive-url = https://web.archive.org/web/20140529150342/http://genatlas.medecine.univ-paris5.fr/fiche.php?symbol=TAAR1 | archive-date = 29 May 2014 | url-status = live }}{{cite journal |vauthors = Revel FG, Moreau JL, Gainetdinov RR, Bradaia A, Sotnikova TD, Mory R, Durkin S, Zbinden KG, Norcross R, Meyer CA, Metzler V, Chaboz S, Ozmen L, Trube G, Pouzet B, Bettler B, Caron MG, Wettstein JG, Hoener MC |title = TAAR1 activation modulates monoaminergic neurotransmission, preventing hyperdopaminergic and hypoglutamatergic activity |journal = Proc. Natl. Acad. Sci. U.S.A. |volume = 108 |issue = 20 |pages = 8485–8490 |date = May 2011 |pmid = 21525407 |pmc = 3101002 |doi = 10.1073/pnas.1103029108 |bibcode = 2011PNAS..108.8485R |doi-access = free }} TAAR1 activation by methamphetamine in astrocytes appears to negatively modulate the membrane expression and function of EAAT2, a type of glutamate transporter.

In addition to its effect on the plasma membrane monoamine transporters, methamphetamine inhibits synaptic vesicle function by inhibiting VMAT2, which prevents monoamine uptake into the vesicles and promotes their release. This results in the outflow of monoamines from synaptic vesicles into the cytosol (intracellular fluid) of the presynaptic neuron, and their subsequent release into the synaptic cleft by the phosphorylated transporters.{{cite journal |vauthors = Eiden LE, Weihe E |title = VMAT2: a dynamic regulator of brain monoaminergic neuronal function interacting with drugs of abuse |journal = Ann. N. Y. Acad. Sci. |volume = 1216 |issue = 1|pages = 86–98 |date = January 2011 |pmid = 21272013 |doi = 10.1111/j.1749-6632.2010.05906.x |pmc = 4183197 |bibcode = 2011NYASA1216...86E }} Other transporters that methamphetamine is known to inhibit are SLC22A3 and SLC22A5.{{cite web |title = Methamphetamine: Transporters | url = http://www.drugbank.ca/drugs/DB01577#transporters |work = DrugBank |publisher = University of Alberta |date = 8 February 2013 |access-date = 4 January 2014 |archive-date = 28 December 2015 |archive-url = https://web.archive.org/web/20151228164940/http://www.drugbank.ca/drugs/DB01577#transporters |url-status = live }} SLC22A3 is an extraneuronal monoamine transporter that is present in astrocytes, and SLC22A5 is a high-affinity carnitine transporter.{{cite journal |vauthors = Inazu M, Takeda H, Matsumiya T |title = [The role of glial monoamine transporters in the central nervous system] |language = ja |journal = Nihon Shinkei Seishin Yakurigaku Zasshi |volume = 23 |issue = 4 |pages = 171–178 |date = August 2003 |pmid = 13677912 }}

Methamphetamine is also an agonist of the alpha-2 adrenergic receptors and sigma receptors with a greater affinity for σ₁ than σ₂, and inhibits monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B).{{cite journal |vauthors = Kaushal N, Matsumoto RR |title = Role of sigma receptors in methamphetamine-induced neurotoxicity |journal = Curr Neuropharmacol |volume = 9 |issue = 1 |pages = 54–57 |date = March 2011 |pmid = 21886562 |pmc = 3137201 |doi = 10.2174/157015911795016930 |quote = σ Receptors seem to play an important role in many of the effects of METH. They are present in the organs that mediate the actions of METH (e.g. brain, heart, lungs) [5]. In the brain, METH acts primarily on the dopaminergic system to cause acute locomotor stimulant, subchronic sensitized, and neurotoxic effects. σ Receptors are present on dopaminergic neurons and their activation stimulates dopamine synthesis and release [11–13]. σ-2 Receptors modulate DAT and the release of dopamine via protein kinase C (PKC) and Ca2+-calmodulin systems [14].
σ-1 Receptor antisense and antagonists have been shown to block the acute locomotor stimulant effects of METH [4]. Repeated administration or self administration of METH has been shown to upregulate σ-1 receptor protein and mRNA in various brain regions including the substantia nigra, frontal cortex, cerebellum, midbrain, and hippocampus [15, 16]. Additionally, σ receptor antagonists ... prevent the development of behavioral sensitization to METH [17, 18]. ...
σ Receptor agonists have been shown to facilitate dopamine release, through both σ-1 and σ-2 receptors [11–14]. }}{{cite journal |vauthors = Rodvelt KR, Miller DK |title = Could sigma receptor ligands be a treatment for methamphetamine addiction? |journal = Curr Drug Abuse Rev |volume = 3 |issue = 3 |pages = 156–162 |date = September 2010 |pmid = 21054260 |doi = 10.2174/1874473711003030156 }} Sigma receptor activation by methamphetamine may facilitate its central nervous system stimulant effects and promote neurotoxicity within the brain. Dextromethamphetamine is a stronger psychostimulant, but levomethamphetamine has stronger peripheral effects, a longer half-life, and longer perceived effects among heavy substance users.{{cite journal |vauthors = Melega WP, Cho AK, Schmitz D, Kuczenski R, Segal DS |title = l-methamphetamine pharmacokinetics and pharmacodynamics for assessment of in vivo deprenyl-derived l-methamphetamine |journal = J. Pharmacol. Exp. Ther. |volume = 288 |issue = 2 |pages = 752–758 |date = February 1999 |doi = 10.1016/S0022-3565(24)38016-4 |pmid = 9918585 }}{{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 |pmc = 6577819 |doi = 10.1523/jneurosci.15-02-01308.1995}}{{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 }} At high doses, both enantiomers of methamphetamine can induce similar stereotypy and methamphetamine psychosis, but levomethamphetamine has shorter psychodynamic effects.

The bioavailability of methamphetamine is 67% orally, 79% intranasally, 67 to 90% via inhalation (smoking), and 100% intravenously. Following oral administration, methamphetamine is well-absorbed into the bloodstream, with peak plasma methamphetamine concentrations achieved in approximately 3.13–6.3 hours post ingestion. Methamphetamine is also well absorbed following inhalation and following intranasal administration. Because of the high lipophilicity of methamphetamine due to its methyl group, it can readily move through the blood–brain barrier faster than other stimulants, where it is more resistant to degradation by monoamine oxidase.{{cite journal |vauthors=Xu J, Zhang Z, Liu R, Sun Y, Liu H, Nie Z, Zhao X, Pu X |title=Function of complement factor H and imaging of small molecules by MALDI-MSI in a methamphetamine behavioral sensitization model |journal=Behavioural Brain Research |volume=364 |issue= |pages=233–244 |date=May 2019 |pmid=30731099 |doi=10.1016/j.bbr.2019.02.002 |s2cid=72333584 |quote=Methamphetamine (METH) is a potent amphetamine-type stimulant that has high abuse potential and can be smoked, snorted, injected, or taken orally. The drug is high in lipid solubility and can cross the blood-brain barrier more readily than amphetamine due to the addition of an extra methyl group.}} The amphetamine metabolite peaks at 10–24 hours. Methamphetamine is excreted by the kidneys, with the rate of excretion into the urine heavily influenced by urinary pH. When taken orally, 30–54% of the dose is excreted in urine as methamphetamine and 10–23% as amphetamine. Following IV doses, about 45% is excreted as methamphetamine and 7% as amphetamine. The elimination half-life of methamphetamine varies with a range of 5–30{{nbsp}}hours, but it is on average 9 to 12{{nbsp}}hours in most studies.{{cite journal |vauthors = Schep LJ, Slaughter RJ, Beasley DM |title = The clinical toxicology of metamfetamine |journal = Clinical Toxicology |volume = 48 |issue = 7 |pages = 675–694 |date = August 2010 |pmid = 20849327 |doi = 10.3109/15563650.2010.516752 |s2cid = 42588722 |issn = 1556-3650 }} The elimination half-life of methamphetamine does not vary by route of administration, but is subject to substantial interindividual variability.{{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 }}

CYP2D6, dopamine β-hydroxylase, flavin-containing monooxygenase 3, butyrate-CoA ligase, and glycine N-acyltransferase are the enzymes known to metabolize methamphetamine or its metabolites in humans.{{#tag:ref|{{cite web |title = Adderall XR Prescribing Information |url = http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021303s026lbl.pdf |pages = 12–13 |publisher = Shire US Inc |website = United States Food and Drug Administration |date = December 2013 |access-date = 30 December 2013 |archive-url = https://web.archive.org/web/20131230233702/http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021303s026lbl.pdf |archive-date = 30 December 2013 |url-status = live }}{{cite journal |vauthors = Krueger SK, Williams DE |title = Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism |journal = Pharmacol. Ther. |volume = 106 |issue = 3 |pages = 357–387 |date = June 2005 |pmid = 15922018 |pmc = 1828602 |doi = 10.1016/j.pharmthera.2005.01.001 }}
{{cite journal | url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602/table/T5/ | title = Table 5: N-containing drugs and xenobiotics oxygenated by FMO | date = 2005 | pmc = 1828602 | archive-url = https://web.archive.org/web/20180916144516/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828602/table/T5/ | archive-date=16 September 2018 | journal = Pharmacology & Therapeutics | volume = 106 | issue = 3 | pages = 357–387 | doi = 10.1016/j.pharmthera.2005.01.001 | pmid = 15922018 | vauthors = Krueger SK, Williams DE }}{{cite journal |vauthors = Cashman JR, Xiong YN, Xu L, Janowsky A |title = N-oxygenation of amphetamine and methamphetamine by the human flavin-containing monooxygenase (form 3): role in bioactivation and detoxication |journal = J. Pharmacol. Exp. Ther. |volume = 288 |issue = 3 |pages = 1251–1260 |date = March 1999 |doi = 10.1016/S0022-3565(24)38081-4 |pmid = 10027866 }}{{cite journal |vauthors = Santagati NA, Ferrara G, Marrazzo A, Ronsisvalle G |title = Simultaneous determination of amphetamine and one of its metabolites by HPLC with electrochemical detection |journal = J. Pharm. Biomed. Anal. |volume = 30 |issue = 2 |pages = 247–255 |date = September 2002 |pmid = 12191709 |doi = 10.1016/S0731-7085(02)00330-8 }}{{cite book |vauthors = Glennon RA |veditors = Lemke TL, Williams DA, Roche VF, Zito W |title = Foye's principles of medicinal chemistry |date = 2013 |publisher = Wolters Kluwer Health/Lippincott Williams & Wilkins |location = Philadelphia, USA |isbn = 978-1-60913-345-0 |pages = 646–648 |edition = 7th | chapter-url = https://books.google.com/books?id=Sd6ot9ul-bUC&pg=PA646 | chapter = Phenylisopropylamine stimulants: amphetamine-related agents |quote = The simplest unsubstituted phenylisopropylamine, 1-phenyl-2-aminopropane, or amphetamine, serves as a common structural template for hallucinogens and psychostimulants. Amphetamine produces central stimulant, anorectic, and sympathomimetic actions, and it is the prototype member of this class (39). ... The phase 1 metabolism of amphetamine analogs is catalyzed by two systems: cytochrome P450 and flavin monooxygenase. ... Amphetamine can also undergo aromatic hydroxylation to p-hydroxyamphetamine. ... Subsequent oxidation at the benzylic position by DA β-hydroxylase affords p-hydroxynorephedrine. Alternatively, direct oxidation of amphetamine by DA β-hydroxylase can afford norephedrine. |access-date = 5 October 2017 |archive-date = 13 January 2023 |archive-url = https://web.archive.org/web/20230113011526/https://books.google.com/books?id=Sd6ot9ul-bUC&pg=PA646 |url-status = live }}{{cite journal | vauthors = Taylor KB |title = Dopamine-beta-hydroxylase. Stereochemical course of the reaction |journal = J. Biol. Chem. |volume = 249 |issue = 2 |pages = 454–458 |date = January 1974 |doi = 10.1016/S0021-9258(19)43051-2 |pmid = 4809526 |access-date = 6 November 2014 |url = http://www.jbc.org/content/249/2/454.full.pdf |quote = Dopamine-β-hydroxylase catalyzed the removal of the pro-R hydrogen atom and the production of 1-norephedrine, (2S,1R)-2-amino-1-hydroxyl-1-phenylpropane, from d-amphetamine. |archive-url = https://web.archive.org/web/20181007182156/http://www.jbc.org/content/249/2/454.full.pdf |archive-date = 7 October 2018 |url-status = live |doi-access = free }}{{cite journal |vauthors = Sjoerdsma A, von Studnitz W |title = Dopamine-beta-oxidase activity in man, using hydroxyamphetamine as substrate |journal = Br. J. Pharmacol. Chemother. |volume = 20 |issue = 2|pages = 278–284 |date = April 1963 |pmid = 13977820 |pmc = 1703637 |doi = 10.1111/j.1476-5381.1963.tb01467.x |quote = Hydroxyamphetamine was administered orally to five human subjects ... Since conversion of hydroxyamphetamine to hydroxynorephedrine occurs in vitro by the action of dopamine-β-oxidase, a simple method is suggested for measuring the activity of this enzyme and the effect of its inhibitors in man. ... The lack of effect of administration of neomycin to one patient indicates that the hydroxylation occurs in body tissues. ... a major portion of the β-hydroxylation of hydroxyamphetamine occurs in non-adrenal tissue. Unfortunately, at the present time one cannot be completely certain that the hydroxylation of hydroxyamphetamine in vivo is accomplished by the same enzyme which converts dopamine to noradrenaline. }}{{cite web |title = butyrate-CoA ligase: Substrate/Product | url = http://www.brenda-enzymes.info/enzyme.php?ecno=6.2.1.2&Suchword=&organism%5B%5D=Homo+sapiens&show_tm=0 |work = BRENDA |publisher = Technische Universität Braunschweig. |access-date = 5 October 2017 |archive-date = 22 June 2017 |archive-url = https://web.archive.org/web/20170622234353/http://www.brenda-enzymes.info/enzyme.php?ecno=6.2.1.2&Suchword=&organism%5B%5D=Homo+sapiens&show_tm=0 |url-status = live }}{{cite web |title = glycine N-acyltransferase: Substrate/Product | url = http://www.brenda-enzymes.info/enzyme.php?ecno=2.3.1.13&Suchword=&organism%5B%5D=Homo+sapiens&show_tm=0 |work = BRENDA |publisher = Technische Universität Braunschweig. |access-date = 5 October 2017 |archive-date = 23 June 2017 |archive-url = https://web.archive.org/web/20170623000309/http://www.brenda-enzymes.info/enzyme.php?ecno=2.3.1.13&Suchword=&organism%5B%5D=Homo+sapiens&show_tm=0 |url-status = live }}| name="methamphetamine metabolism" |group="sources" }} The primary metabolites are amphetamine and 4-hydroxymethamphetamine;{{cite web |title = Methamphetamine: Pharmacology | url = https://www.drugbank.ca/drugs/DB01577#pharmacology |work = DrugBank |publisher = University of Alberta |access-date = 5 October 2017 |date = 2 October 2017 |quote = Methamphetamine is rapidly absorbed from the gastrointestinal tract with peak methamphetamine concentrations occurring in 3.13 to 6.3 hours post ingestion. Methamphetamine is also well absorbed following inhalation and following intranasal administration. It is distributed to most parts of the body. Because methamphetamine has a high lipophilicity it is distributed across the blood brain barrier and crosses the placenta. ...
The primary site of metabolism is in the liver by aromatic hydroxylation, N-dealkylation and deamination. At least seven metabolites have been identified in the urine, with the main metabolites being amphetamine (active) and 4-hydroxymethamphetamine. Other minor metabolites include 4-hydroxyamphetamine, norephedrine, and 4-hydroxynorephedrine. |archive-date = 6 October 2017 |archive-url = https://web.archive.org/web/20171006012111/https://www.drugbank.ca/drugs/DB01577#pharmacology |url-status = live }} other minor metabolites include: {{nowrap|4-hydroxyamphetamine}}, {{nowrap|4-hydroxynorephedrine}}, {{nowrap|4-hydroxyphenylacetone}}, benzoic acid, hippuric acid, norephedrine, and phenylacetone, the metabolites of amphetamine. Among these metabolites, the active sympathomimetics are amphetamine, {{nowrap|4‑hydroxyamphetamine}},{{cite web |title = p-Hydroxyamphetamine: Compound Summary | url = https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3651 |work = PubChem Compound |publisher = National Center for Biotechnology Information |access-date = 4 September 2017 |archive-date = 7 June 2013 |archive-url = https://web.archive.org/web/20130607202440/http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3651 |url-status = live }} {{nowrap|4‑hydroxynorephedrine}},{{cite web |title = p-Hydroxynorephedrine: Compound Summary | url = https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=11099 |work = PubChem Compound |publisher = National Center for Biotechnology Information|access-date = 4 September 2017 |archive-date = 15 October 2013 |archive-url = https://web.archive.org/web/20131015073126/http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=11099 |url-status = live }} {{nowrap|4-hydroxymethamphetamine}}, and norephedrine.{{cite web |title = Phenylpropanolamine: Compound Summary | url = https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=26934 |work = PubChem Compound |publisher = National Center for Biotechnology Information |access-date = 4 September 2017 |archive-date = 29 September 2013 |archive-url = https://web.archive.org/web/20130929154657/http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=26934 |url-status = live }} Methamphetamine is a CYP2D6 inhibitor.

The main metabolic pathways involve aromatic para-hydroxylation, aliphatic alpha- and beta-hydroxylation, N-oxidation, N-dealkylation, and deamination.{{cite web |title = Amphetamine |url = https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3007 |work = Pubchem Compound |publisher = National Center for Biotechnology Information |access-date = 12 October 2013 |archive-url = https://web.archive.org/web/20131013122604/http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3007 |archive-date = 13 October 2013 |url-status = live }} The known metabolic pathways include:

{{Methamphetamine pharmacokinetics|header=Metabolic pathways of methamphetamine in humans|caption=The primary metabolites of methamphetamine are amphetamine and 4-hydroxymethamphetamine. Human microbiota, particularly Lactobacillus, Enterococcus, and Clostridium species, contribute to the metabolism of methamphetamine via an enzyme which N-demethylates methamphetamine and 4-hydroxymethamphetamine into amphetamine and 4-hydroxyamphetamine respectively.{{cite journal |vauthors = Haiser HJ, Turnbaugh PJ |title = Developing a metagenomic view of xenobiotic metabolism |journal = Pharmacol. Res. |volume = 69 |issue = 1 |pages = 21–31 |date = March 2013 |pmid = 22902524 |pmc = 3526672 |doi = 10.1016/j.phrs.2012.07.009 }}
{{cite journal | url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3526672/table/T2/ | title = Table 2: Xenobiotics metabolized by the human gut microbiota | journal = Pharmacological Research | date = March 2013 | volume = 69 | issue = 1 | doi = 10.1016/j.phrs.2012.07.009 | pmid = 22902524 | pmc = 3526672 | archive-url = https://web.archive.org/web/20211031105429/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3526672/table/T2/ | archive-date = 31 October 2021 | vauthors = Haiser HJ, Turnbaugh PJ | pages = 21–31 }}{{cite journal | vauthors = Caldwell J, Hawksworth GM | title = The demethylation of methamphetamine by intestinal microflora | journal = The Journal of Pharmacy and Pharmacology | volume = 25 | issue = 5 | pages = 422–424 | date = May 1973 | pmid = 4146404 | doi = 10.1111/j.2042-7158.1973.tb10043.x | s2cid = 34050001 }}}}

{{clear}}

Methamphetamine and amphetamine are often measured in urine or blood as part of a drug test for sports, employment, poisoning diagnostics, and forensics.{{cite journal |vauthors = Liddle DG, Connor DJ |title = Nutritional supplements and ergogenic AIDS |journal = Prim. Care |volume = 40 |issue = 2 |pages = 487–505 |date = June 2013 |pmid = 23668655 |doi = 10.1016/j.pop.2013.02.009 }}{{cite journal |vauthors = Kraemer T, Maurer HH |title = Determination of amphetamine, methamphetamine and amphetamine-derived designer drugs or medicaments in blood and urine |journal = J. Chromatogr. B |volume = 713 |issue = 1 |pages = 163–187 |date = August 1998 |pmid = 9700558 |doi = 10.1016/S0378-4347(97)00515-X }}{{cite journal |vauthors = Kraemer T, Paul LD |title = Bioanalytical procedures for determination of drugs of abuse in blood |journal = Anal. Bioanal. Chem. |volume = 388 |issue = 7 |pages = 1415–1435 |date = August 2007 |pmid = 17468860 |doi = 10.1007/s00216-007-1271-6 |s2cid = 32917584 }}{{cite journal |vauthors = Goldberger BA, Cone EJ |title = Confirmatory tests for drugs in the workplace by gas chromatography-mass spectrometry |journal = J. Chromatogr. A |volume = 674 |issue = 1–2 |pages = 73–86 |date = July 1994 |pmid = 8075776 |doi = 10.1016/0021-9673(94)85218-9 }} Chiral techniques may be employed to help distinguish the source of the drug to determine whether it was obtained illicitly or legally via prescription or prodrug. Chiral separation is needed to assess the possible contribution of levomethamphetamine, which is an active ingredients in some OTC nasal decongestants, toward a positive test result.{{cite journal |vauthors = Paul BD, Jemionek J, Lesser D, Jacobs A, Searles DA |title = Enantiomeric separation and quantitation of (+/-)-amphetamine, (+/-)-methamphetamine, (+/-)-MDA, (+/-)-MDMA, and (+/-)-MDEA in urine specimens by GC-EI-MS after derivatization with (R)-(−)- or (S)-(+)-alpha-methoxy-alpha-(trifluoromethy)phenylacetyl chloride (MTPA) |journal = J. Anal. Toxicol. |volume = 28 |issue = 6 |pages = 449–455 |date = September 2004 |pmid = 15516295 |doi = 10.1093/jat/28.6.449 |doi-access = free }}{{cite journal |vauthors = de la Torre R, Farré M, Navarro M, Pacifici R, Zuccaro P, Pichini S |title = Clinical pharmacokinetics of amfetamine and related substances: monitoring in conventional and non-conventional matrices |journal = Clin Pharmacokinet |volume = 43 |issue = 3 |pages = 157–185 |year = 2004 |pmid = 14871155 |doi = 10.2165/00003088-200443030-00002 |s2cid = 44731289 }}{{cite book | vauthors = Baselt RC |title = Disposition of toxic drugs and chemicals in man |year = 2020 |publisher = Biomedical Publications |location = Seal Beach, Ca. |isbn = 978-0-578-57749-4 |pages = 1277–1280}} Dietary zinc supplements can mask the presence of methamphetamine and other drugs in urine.{{cite journal |vauthors = Venkatratnam A, Lents NH |title = Zinc reduces the detection of cocaine, methamphetamine, and THC by ELISA urine testing |journal = J. Anal. Toxicol. |volume = 35 |issue = 6 |pages = 333–340 |date = July 2011 |pmid = 21740689 |doi = 10.1093/anatox/35.6.333 |doi-access = }}

{{multiple image|perrow = 1|total_width=300

| image1 = Crystal Meth.jpg

| image2 = Crystal methamphetamine Canadian quarter.jpg

| footer = Shards of pure methamphetamine hydrochloride, also known as crystal meth

}}

Methamphetamine is a chiral compound with two enantiomers, dextromethamphetamine and levomethamphetamine. At room temperature, the free base of methamphetamine is a clear and colorless liquid with an odor characteristic of geranium leaves. It is soluble in diethyl ether and ethanol as well as miscible with chloroform.

In contrast, the methamphetamine hydrochloride salt is odorless with a bitter taste. It has a melting point between {{convert|170|and|175|C|F}} and, at room temperature, occurs as white crystals or a white crystalline powder. The hydrochloride salt is also freely soluble in ethanol and water. The crystal structure of either enantiomer is monoclinic with P2₁ space group; at {{convert|90|K|C F}}, it has lattice parameters a = 7.10 Å, b = 7.29 Å, c = 10.81 Å, and β = 97.29°.{{cite journal | vauthors = Hakey P, Ouellette W, Zubieta J, Korter T | title = Redetermination of (+)-methamphetamine hydro-chloride at 90 K | journal = Acta Crystallographica Section E | volume = 64 | issue = Pt 5 | pages = o940 | date = April 2008 | pmid = 21202421 | pmc = 2961146 | doi = 10.1107/S1600536808011550 | bibcode = 2008AcCrE..64O.940H }}

A 2011 study into the destruction of methamphetamine using bleach showed that effectiveness is correlated with exposure time and concentration.{{cite web | vauthors = Nakayama MT |title = Chemical Interaction of Bleach and Methamphetamine: A Study of Degradation and Transformation Effects |url = http://gradworks.umi.com/14/93/1493688.html |website = gradworks |publisher = UNIVERSITY OF CALIFORNIA, DAVIS |access-date = 17 October 2014 |archive-url = https://web.archive.org/web/20141019005517/http://gradworks.umi.com/14/93/1493688.html |archive-date = 19 October 2014 |url-status = live }} A year-long study (also from 2011) showed that methamphetamine in soils is a persistent pollutant.{{cite journal |vauthors = Pal R, Megharaj M, Kirkbride KP, Heinrich T, Naidu R |title = Biotic and abiotic degradation of illicit drugs, their precursor, and by-products in soil |journal = Chemosphere |volume = 85 |issue = 6 |pages = 1002–9 |date = October 2011 |pmid = 21777940 |doi = 10.1016/j.chemosphere.2011.06.102 |bibcode = 2011Chmsp..85.1002P }} In a 2013 study of bioreactors in wastewater, methamphetamine was found to be largely degraded within 30 days under exposure to light.{{cite journal |vauthors = Bagnall J, Malia L, Lubben A, Kasprzyk-Hordern B |title = Stereoselective biodegradation of amphetamine and methamphetamine in river microcosms |journal = Water Res. |volume = 47 |issue = 15 |pages = 5708–18 |date = October 2013 |pmid = 23886544 |doi = 10.1016/j.watres.2013.06.057 |bibcode = 2013WatRe..47.5708B |doi-access = free }}

{{further|topic=illicit amphetamine synthesis|History and culture of substituted amphetamines#Illegal synthesis}}

Racemic methamphetamine may be prepared starting from phenylacetone by either the Leuckart{{cite journal |vauthors = Crossley FS, Moore ML |title = Studies on the Leuckart reaction |journal = The Journal of Organic Chemistry |date = November 1944 |volume = 9 |issue = 6 |pages = 529–536 |doi = 10.1021/jo01188a006 }} or reductive amination methods.{{cite journal |vauthors = Kunalan V, Nic Daéid N, Kerr WJ, Buchanan HA, McPherson AR |title = Characterization of route specific impurities found in methamphetamine synthesized by the Leuckart and reductive amination methods |journal = Anal. Chem. |volume = 81 |issue = 17 |pages = 7342–7348 |date = September 2009 |pmid = 19637924 |pmc = 3662403 |doi = 10.1021/ac9005588 }} In the Leuckart reaction, one equivalent of phenylacetone is reacted with two equivalents of {{nowrap|N-methylformamide}} to produce the formyl amide of methamphetamine plus carbon dioxide and methylamine as side products. In this reaction, an iminium cation is formed as an intermediate which is reduced by the second equivalent of {{nowrap|N-methylformamide}}. The intermediate formyl amide is then hydrolyzed under acidic aqueous conditions to yield methamphetamine as the final product. Alternatively, phenylacetone can be reacted with methylamine under reducing conditions to yield methamphetamine.

{{clear}}

{{Main|History and culture of substituted amphetamines}}

File:Pervitin (MMM Corones).jpg, was dispensed in various forms, including tablet containers.]]

File:US timeline. Drugs involved in overdose deaths.jpg related fatalities in 2017 were 70,200, including 10,333 of those related to psychostimulants (including methamphetamine).{{cite web | url = https://www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates | title = Overdose Death Rates | archive-url = https://web.archive.org/web/20171213234138/https://www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates | archive-date=13 December 2017 | work = National Institute on Drug Abuse (NIDA) }}{{cite news |title=US overdose deaths from fentanyl and synthetic opioids doubled in 2016 |url=https://www.theguardian.com/us-news/2017/sep/03/fentanyl-synthetic-opioids-deaths-doubled-us |work=The Guardian |date=3 September 2017 |access-date=17 August 2018 |archive-url=https://web.archive.org/web/20180817225855/https://www.theguardian.com/us-news/2017/sep/03/fentanyl-synthetic-opioids-deaths-doubled-us |archive-date=17 August 2018 |url-status=live }}]]

Amphetamine, discovered before methamphetamine, was first synthesized in 1887 in Germany by Romanian chemist Lazăr Edeleanu who named it phenylisopropylamine.{{cite book | vauthors = Rassool GH |title = Alcohol and Drug Misuse: A Handbook for Students and Health Professionals |year = 2009 |publisher = Routledge |location = London |isbn = 978-0-203-87117-1 |page = 113 }}{{cite web |url = http://healthvermont.gov/adap/meth/brief_history.aspx |title = Historical overview of methamphetamine |website = Vermont Department of Health |publisher = Government of Vermont |access-date = 29 January 2012 |archive-url = https://web.archive.org/web/20120620083221/http://healthvermont.gov/adap/meth/brief_history.aspx |archive-date = 20 June 2012 |url-status = live }} Shortly after, methamphetamine was synthesized from ephedrine in 1893 by Japanese chemist Nagai Nagayoshi.{{cite journal |vauthors = Grobler SR, Chikte U, Westraat J |title = The pH Levels of Different Methamphetamine Drug Samples on the Street Market in Cape Town |journal = ISRN Dentistry |volume = 2011 |pages = 1–4 |year = 2011 |pmid = 21991491 |pmc = 3189445 |doi = 10.5402/2011/974768 |doi-access = free }} Three decades later, in 1919, methamphetamine hydrochloride was synthesized by pharmacologist Akira Ogata via reduction of ephedrine using red phosphorus and iodine.{{cite web |url = http://healthvermont.gov/adap/meth/brief_history.aspx |title = Historical overview of methamphetamine |publisher = Vermont Department of Health |access-date = 15 January 2012 |archive-url = https://web.archive.org/web/20120620083221/http://healthvermont.gov/adap/meth/brief_history.aspx |archive-date = 20 June 2012 |url-status = live }}

From 1938, methamphetamine was marketed on a large scale in Germany as a nonprescription drug under the brand name Pervitin, produced by the Berlin-based Temmler pharmaceutical company.{{Citation|title=Pervitin|url=http://www.chemie.de/lexikon/Pervitin.html|publisher=CHEMIE.DE Information Service GmbH|location=Berlin|language=de|access-date=16 September 2015|archive-date=18 December 2019|archive-url=https://web.archive.org/web/20191218224238/https://www.chemie.de/lexikon/Pervitin.html|url-status=live}}{{cite book | vauthors = Freye E |title= Pharmacology and Abuse of Cocaine, Amphetamines, Ecstasy and Related Designer Drugs |year=2009 |publisher=Springer |location=University Düsseldorf, Germany |isbn=978-90-481-2447-3 |page=110 }} It was used by all branches of the combined armed forces of the Third Reich, for its stimulant effects and to induce extended wakefulness.{{Cite news |title = The Nazi Death Machine: Hitler's Drugged Soldiers |url = http://www.spiegel.de/international/the-nazi-death-machine-hitler-s-drugged-soldiers-a-354606.html |publisher = Der Spiegel, 6 May 2005 |newspaper = Spiegel Online |date = 6 May 2005 | vauthors = Ulrich A |access-date = 12 August 2014 |archive-url = https://web.archive.org/web/20171219062055/http://www.spiegel.de/international/the-nazi-death-machine-hitler-s-drugged-soldiers-a-354606.html |archive-date = 19 December 2017 |url-status = live }}{{cite journal |vauthors = Defalque RJ, Wright AJ |title = Methamphetamine for Hitler's Germany: 1937 to 1945 |journal = Bull. Anesth. Hist. |volume = 29 |issue = 2 |pages = 21–24, 32 |date = April 2011 |pmid = 22849208 |doi = 10.1016/s1522-8649(11)50016-2 }} Pervitin became colloquially known among the German troops as "Stuka-Tablets" (Stuka-Tabletten) and "Herman-Göring-Pills" (Hermann-Göring-Pillen), as a snide allusion to Göring's widely-known addiction to drugs. However, the side effects, particularly the withdrawal symptoms, were so serious that the army sharply cut back its usage in 1940.{{cite book | vauthors = Kamieński Ł |title = Shooting Up: A Short History of Drugs and War |url = https://books.google.com/books?id=NAVCCwAAQBAJ&pg=PA112 |year = 2016 |publisher = Oxford University Press |pages = 111–13 |isbn = 978-0-19-026347-8 |access-date = 23 October 2016 |archive-url = https://web.archive.org/web/20170323182238/https://books.google.com/books?id=NAVCCwAAQBAJ&pg=PA112 |archive-date = 23 March 2017 |url-status = live }} By 1941, usage was restricted to a doctor's prescription, and the military tightly controlled its distribution. Soldiers would only receive a couple of tablets at a time, and were discouraged from using them in combat. Historian Łukasz Kamieński says,

{{blockquote|A soldier going to battle on Pervitin usually found himself unable to perform effectively for the next day or two. Suffering from a drug hangover and looking more like a zombie than a great warrior, he had to recover from the side effects.}}

Some soldiers turned violent, committing war crimes against civilians; others attacked their own officers. At the end of the war, it was used as part of a new drug: D-IX.

Obetrol, patented by Obetrol Pharmaceuticals in the 1950s and indicated for treatment of obesity, was one of the first brands of pharmaceutical methamphetamine products.{{cite book | vauthors = Rasmussen N |title = On Speed: The Many Lives of Amphetamine |date = March 2008 |publisher = New York University Press |edition = 1 |isbn = 978-0-8147-7601-8 |page = 148 }} Because of the psychological and stimulant effects of methamphetamine, Obetrol became a popular diet pill in America in the 1950s and 1960s. Eventually, as the addictive properties of the drug became known, governments began to strictly regulate the production and distribution of methamphetamine. For example, during the early 1970s in the United States, methamphetamine became a schedule II controlled substance under the Controlled Substances Act. Currently, methamphetamine is sold under the trade name Desoxyn, trademarked by the Danish pharmaceutical company Lundbeck.{{cite web |url = http://www.lundbeck.com/us/products/cns-products/desoxyn |title = Desoxyn |publisher = Lundbeck: Desoxyn |access-date = 15 December 2012 |archive-url = https://web.archive.org/web/20121130095007/http://www.lundbeck.com/us/products/cns-products/desoxyn |archive-date = 30 November 2012 |df = dmy-all }} As of January 2013, the Desoxyn trademark had been sold to Italian pharmaceutical company Recordati.{{cite web |url = http://www.recordatirarediseases.com/products/us-product/desoxyn%C2%AE-cii-methamphetamine-hydrochloride-tablets-usp |title = Recordati: Desoxyn |work = Recordati Rare Diseases |date = 2 May 2013 |publisher = Recordati SP |access-date = 15 May 2013 |archive-url = https://web.archive.org/web/20130707013757/http://www.recordatirarediseases.com/products/us-product/desoxyn%C2%AE-cii-methamphetamine-hydrochloride-tablets-usp |archive-date = 7 July 2013 |df = dmy-all |author1 = Admin }}

The Golden Triangle (Southeast Asia), specifically Shan State, Myanmar, is the world's leading producer of methamphetamine as production has shifted to Yaba and crystalline methamphetamine, including for export to the United States and across East and Southeast Asia and the Pacific.{{Cite web|url=https://www.unodc.org/documents/southeastasiaandpacific/Publications/2019/SEA_TOCTA_2019_web.pdf/|title=Transnational Organized Crime in Southeast Asia: Evolution, Growth and Challenges|date=June 2019|access-date=30 July 2020|archive-date=22 January 2021|archive-url=https://web.archive.org/web/20210122015018/https://www.unodc.org/documents/southeastasiaandpacific/Publications/2019/SEA_TOCTA_2019_web.pdf}}

Concerning the accelerating synthetic drug production in the region, the Cantonese Chinese syndicate Sam Gor, also known as {{not a typo|The Company}}, is understood to be the main international crime syndicate responsible for this shift.{{Cite web |url=https://edition.cnn.com/2019/10/23/opinions/tse-chi-lop-revealed-opinion-intl-hnk/index.html |title=The Man Accused of Running the Biggest Drug Trafficking Syndicate in Asia's History has Been Revealed: Here's What Needs To Happen Next |publisher=CNN |date=24 October 2019 |access-date=30 July 2020 |archive-date=22 October 2021 |archive-url=https://web.archive.org/web/20211022232716/https://edition.cnn.com/2019/10/23/opinions/tse-chi-lop-revealed-opinion-intl-hnk/index.html |url-status=live }} It is made up of members of five different triads. Sam Gor is primarily involved in drug trafficking, earning at least $8 billion per year.{{cite news | vauthors = Smith N |title=Drugs investigators close in on Asian 'El Chapo' at centre of vast meth ring |url=https://www.telegraph.co.uk/news/2019/10/14/drugs-investigators-close-asian-el-chapo-centre-vast-meth-ring/ |archive-url=https://ghostarchive.org/archive/20220110/https://www.telegraph.co.uk/news/2019/10/14/drugs-investigators-close-asian-el-chapo-centre-vast-meth-ring/ |archive-date=10 January 2022 |url-access=subscription |url-status=live |work=The Telegraph |date=14 October 2019}}{{cbignore}} Sam Gor is alleged to control 40% of the Asia-Pacific methamphetamine market, while also trafficking heroin and ketamine. The organization is active in a variety of countries, including Myanmar, Thailand, New Zealand, Australia, Japan, China, and Taiwan. Sam Gor previously produced meth in Southern China and is now believed to manufacture mainly in the Golden Triangle, specifically Shan State, Myanmar, responsible for much of the massive surge of crystal meth in circa 2019.{{Cite web|url=https://nypost.com/2019/10/14/inside-the-hunt-for-the-man-known-as-asias-el-chapo/|title=Inside the hunt for the man known as 'Asia's El Chapo'|work=New York Post|date=14 October 2019|access-date=30 July 2020|archive-date=19 January 2021|archive-url=https://web.archive.org/web/20210119003851/https://nypost.com/2019/10/14/inside-the-hunt-for-the-man-known-as-asias-el-chapo/|url-status=live}} The group is understood to be headed by Tse Chi Lop, a gangster born in Guangzhou, China who also holds a Canadian passport.

Liu Zhaohua was another individual involved in the production and trafficking of methamphetamine until his arrest in 2005.{{Cite web |date=16 September 2009 |title=Notorious drug kingpin executed for trafficking |url=https://www.scmp.com/article/692604/notorious-drug-kingpin-executed-trafficking |access-date=3 June 2022 |website=South China Morning Post |language=en |archive-date=3 June 2022 |archive-url=https://web.archive.org/web/20220603092530/https://www.scmp.com/article/692604/notorious-drug-kingpin-executed-trafficking |url-status=live }} It was estimated over 18 tonnes of methamphetamine were produced under his watch.

{{Main|Legal status of methamphetamine}}

The production, distribution, sale, and possession of methamphetamine is restricted or illegal in many jurisdictions.{{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 |archive-url = https://web.archive.org/web/20131016082310/http://www.unodc.org/pdf/youthnet/ATS.pdf |archive-date = 16 October 2013 |url-status = live }}{{cite web |title = List of psychotropic substances under international control |website = 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 }} In some jurisdictions, it is legally available as a prescription medication. Methamphetamine has been placed in schedule II of the United Nations Convention on Psychotropic Substances treaty, indicating that it has limited medical use.

Animal models have shown that low-dose methamphetamine improves cognitive and behavioural functioning following TBI (traumatic brain injury). This is in contrast to high, repeated doses which cause neurotoxicity. These models demonstrate that low-dose methamphetamine increases neurogenesis and reduces apoptosis in the dentate gyrus of the hippocampus following TBI.{{cite journal | vauthors = Rau TF, Kothiwal AS, Rova AR, Brooks DM, Poulsen DJ | title = Treatment with low-dose methamphetamine improves behavioral and cognitive function after severe traumatic brain injury | language = en-US | journal = The Journal of Trauma and Acute Care Surgery | volume = 73 | issue = 2 Suppl 1 | pages = S165–S172 | date = August 2012 | pmid = 22847088 | doi = 10.1097/TA.0b013e318260896a }} It has also been found that TBI patients testing positive for methamphetamine at the time of emergency department admission have lower rates of mortality.{{cite journal | vauthors = O'Phelan K, McArthur DL, Chang CW, Green D, Hovda DA | title = The impact of substance abuse on mortality in patients with severe traumatic brain injury | language = en-US | journal = The Journal of Trauma | volume = 65 | issue = 3 | pages = 674–677 | date = September 2008 | pmid = 18784583 | doi = 10.1097/TA.0b013e31817db0a5 }}

It has been suggested, based on animal research, that calcitriol, the active metabolite of vitamin D, can provide significant protection against the DA- and 5-HT-depleting effects of neurotoxic doses of methamphetamine.{{cite journal | vauthors = Cass WA, Smith MP, Peters LE | title = Calcitriol protects against the dopamine- and serotonin-depleting effects of neurotoxic doses of methamphetamine | journal = Annals of the New York Academy of Sciences | volume = 1074 | issue = 1 | pages = 261–271 | date = August 2006 | pmid = 17105922 | doi = 10.1196/annals.1369.023 | bibcode = 2006NYASA1074..261C | s2cid = 8537458 }} Protection against methamphetamine-induced neurotoxicity has also been observed following administration of ascorbic acid (vitamin C),{{cite journal | vauthors = Huang YN, Yang LY, Wang JY, Lai CC, Chiu CT, Wang JY | title = L-Ascorbate Protects Against Methamphetamine-Induced Neurotoxicity of Cortical Cells via Inhibiting Oxidative Stress, Autophagy, and Apoptosis | journal = Molecular Neurobiology | volume = 54 | issue = 1 | pages = 125–136 | date = January 2017 | pmid = 26732595 | doi = 10.1007/s12035-015-9561-z }} cobalamin (vitamin B₁₂),{{cite journal | vauthors = Moshiri M, Hosseiniyan SM, Moallem SA, Hadizadeh F, Jafarian AH, Ghadiri A, Hoseini T, Seifi M, Etemad L | title = The effects of vitamin B₁₂ on the brain damages caused by methamphetamine in mice | journal = Iranian Journal of Basic Medical Sciences | volume = 21 | issue = 4 | pages = 434–438 | date = April 2018 | pmid = 29796230 | pmc = 5960763 | doi = 10.22038/IJBMS.2018.23362.5897 }} and vitamin E.{{Cite journal | vauthors = Anazodo G |date=May 2024 |title=Protective effects of vitamin C and E on amygdala of methamphetamine-induced brain disorder on adult male Wistar rats |url=https://wjpr.s3.ap-south-1.amazonaws.com/article_issue/eefe2451ff2a6848f0249c533e1fc88d.pdf |journal=World Journal of Pharmaceutical Research |volume=13 |issue=9 |pages=2121–2170 |access-date=19 September 2024 |archive-date=22 September 2024 |archive-url=https://web.archive.org/web/20240922021107/https://wjpr.s3.ap-south-1.amazonaws.com/article_issue/eefe2451ff2a6848f0249c533e1fc88d.pdf |url-status=live }}

• 18-MC
• Breaking Bad, a TV drama series centered on illicit methamphetamine synthesis
• Drug checking
• Faces of Meth, a drug prevention project
• Famprofazone, a non-steroidal anti-inflammatory drug yielding methamphetamine as a major metabolite
• Harm reduction
• Methamphetamine and Native Americans
• Methamphetamine in Australia
• Methamphetamine in Bangladesh
• Methamphetamine in the Philippines
• Methamphetamine in the United States
• Montana Meth Project, a Montana-based organization aiming to reduce meth use among teenagers
• Recreational drug use
• Rolling meth lab, a transportable laboratory that is used to illegally produce methamphetamine
• Ya ba, Southeast Asian tablets containing a mixture of methamphetamine and caffeine

{{reflist|group=Color legend}}

{{reflist|group=note}}

{{clear}}

{{Reflist}}

{{refbegin}}

• {{cite journal|vauthors=Hart CL, Marvin CB, Silver R, Smith EE|title=Is cognitive functioning impaired in methamphetamine users? A critical review|journal=Neuropsychopharmacology|date=February 2012|volume=37|issue=3|pages=586–608|doi=10.1038/npp.2011.276|pmid=22089317|issn=0893-133X|pmc=3260986}}
• {{cite journal | vauthors = Rusyniak DE | title = Neurologic manifestations of chronic methamphetamine abuse | journal = Neurologic Clinics | volume = 29 | issue = 3 | pages = 641–655 | date = August 2011 | pmid = 21803215 | pmc = 3148451 | doi = 10.1016/j.ncl.2011.05.004 }}
• {{cite magazine |vauthors=Szalavitz M |date=21 November 2011 |title=Why the Myth of the Meth-Damaged Brain May Hinder Recovery |magazine=Time |url=https://healthland.time.com/2011/11/21/why-the-myth-of-the-meth-damaged-brain-may-hinder-recovery/ |access-date=22 September 2024 |archive-date=22 September 2024 |archive-url=https://web.archive.org/web/20240922021109/https://healthland.time.com/2011/11/21/why-the-myth-of-the-meth-damaged-brain-may-hinder-recovery/ |url-status=live }}

{{refend}}

{{sisterlinks|d=Q191924|c=Category:Dextromethamphetamine|n=Category:Methamphetamine|q=no|b=no|v=no|voy=no|m=no|mw=no|s=no|wikt=no|species=no}}

• [https://www.inchem.org/documents/pims/pharm/pim334.htm Methamphetamine Poison Information Monograph]
• [https://www.fbi.gov/news/stories/aryan-brotherhood-methamphetamine-operation-dismantled Drug Trafficking: Aryan Brotherhood Methamphetamine Operation Dismantled], FBI

{{Amphetamine}}

{{Methamphetamine}}

{{Drug use}}

{{Stimulants}}

{{ADHD pharmacotherapies}}

{{Navboxes

| title = Pharmacodynamics

| titlestyle = background:#ccccff

| list1 =

{{Monoamine releasing agents}}

{{TAAR ligands}}

{{Sigma receptor modulators}}

{{Monoamine neurotoxins}}

}}

{{Phenethylamines}}

{{Authority control}}

Category:1893 introductions

Category:Anorectics

Category:Anti-obesity drugs

Category:Aphrodisiacs

Category:Attention deficit hyperactivity disorder management

Category:Carbonic anhydrase activators

Category:Cardiac stimulants

Category:Euphoriants

Category:Excitatory amino acid reuptake inhibitors

Category:Human drug metabolites

Category:Japanese inventions

Category:Monoaminergic activity enhancers

Category:Norepinephrine-dopamine releasing agents

Category:Sigma agonists

Category:Stimulants

Category:Substituted amphetamines

Category:Sympathomimetics

Category:TAAR1 agonists

Category:VMAT inhibitors