Methamphetamine

From Wikipedia, the free encyclopedia

This article is about the free base and salts of methamphetamine. "Meth" redirects here. For other
uses, see Meth (disambiguation)

Methamphetamine

Systematic (IUPAC) name

N-methyl-1-phenylpropan-2-amine

Clinical data

Trade names

Desoxyn

Licence data

US FDA:link

US: C

Pregnancy cat.

Legal status

Dependence
liability

AU: Controlled (S8)

CA: Schedule I
UK: Class A
US: Schedule II

Prescription only
Very high

Routes

Medical: Oral
Recreational: Oral, Intravenous, Insufflation,
Inhalation, Suppository
Pharmacokinetic data

Bioavailability Oral:Varies widely;[1]Rectal:99%; IV:100%

Protein

Varies widely[1]

binding
Metabolism

CYP2D6,[2] DBH,[3] FMO3,[4]XMligase,[5] and ACGNAT[6]

Half-life

912 hours[7]

Excretion

Renal
Identifiers

CAS number

537-46-2

ATC code

N06BA03

PubChem

CID 1206

DrugBank

DB01577

ChemSpider

1169

UNII

44RAL3456C

KEGG

D08187

ChEBI

CHEBI:6809

ChEMBL

CHEMBL1201201

Synonyms

N-methylamphetamine
Chemical data

Formula

C10H15N

Mol. mass

149.2337 g/mol

SMILES[show]
InChI[show]
Physical data
Melt. point

3 C (37 F) [8]

Boiling point

212 C (414 F) [9] at760 MM HG

(what is this?) (verify)

Methamphetamine[note 1] (pronunciation: /mmftmin/; contracted from N-methyl-alphamethylphenethylamine) is a neurotoxinand potent central nervous system (CNS) stimulant of
the phenethylamine and amphetamine classes that is used as a recreational drug and, rarely, to
treat attention deficit hyperactivity disorder (ADHD) and obesity. Methamphetamine exists as
two enantiomers,dextrorotary and levorotary.[note 2] Dextromethamphetamine is a stronger CNS
stimulant than levomethamphetamine; however, both are addictive and produce the same toxicity
symptoms at high doses. Although rarely prescribed due to the potential risks, methamphetamine
hydrochloride is approved by the United States Food and Drug Administration (USFDA) under the
trade nameDesoxyn. Recreationally, methamphetamine is used to increase sexual desire, lift the
mood, and increase energy, allowing some users to engage in sexual activity continuously for
several days straight.
Methamphetamine may be sold illegally, either as pure dextromethamphetamine or in an equal
parts mixture of the right and left handed molecules (i.e., 50% levomethamphetamine and
50% dextromethamphetamine). Both dextromethamphetamine and racemic methamphetamine
are schedule II controlled substances in the United States. Similarly, the production, distribution,
sale, and possession of methamphetamine is restricted or illegal in many other countries due to its
placement in schedule II of the United Nations Convention on Psychotropic Substances treaty. In
contrast, levomethamphetamine is an over-the-counter drug in the United States.[note 3]
In low doses, methamphetamine can cause an elevated mood and increase alertness,
concentration, and energy in fatigued individuals. At higher doses, it can
induce psychosis, rhabdomyolysis and cerebral hemorrhage. Methamphetamine is known to have a
high potential for abuse and addiction. Recreational use of methamphetamine may result in
psychosis or lead to post-withdrawal syndrome, a withdrawal syndrome that can persist for months
beyond the typical withdrawal period.[i] Unlike amphetamine, methamphetamine is neurotoxic to
humans, damaging both dopamine and serotonin neurons in the CNS.[i] Contrary to the long-term
use of amphetamine,[iii] there is evidence that methamphetamine causes brain damage from longterm use in humans;[ii] this damage includes adverse changes in brain structure and function, such
as reductions in gray matter volume in several brain regions and adverse changes in markers of
metabolic integrity.[ii]
Contents
[hide]

1 Uses
o 1.1 Medical
o 1.2 Recreational
2 Contraindications
3 Side effects
o 3.1 Physical
o 3.2 Psychological
o 3.3 Dependence, addiction, and withdrawal
o 3.4 Neurotoxicity
o 3.5 Sexually transmitted infection
4 Overdose
o 4.1 Emergency treatment
o 4.2 Psychosis
5 Interactions

6 Pharmacology
o 6.1 Pharmacodynamics
o 6.2 Pharmacokinetics
7 Physical and chemical properties
o 7.1 Synthesis
o 7.2 Degradation
8 History, society, and culture
o 8.1 Present legal status
9 See also
10 Notes
o 10.1 Reference notes
11 References
12 External links

Uses
Medical
In the United States, methamphetamine hydrochloride, under the trade name Desoxyn, has been
approved by the FDA for treatingADHD and exogenous obesity (obesity originating from factors
outside of the patient's control) in both adults and children;[14]however, the FDA also indicates that
the limited therapeutic usefulness of methamphetamine should be weighed against the inherent risks
associated with its use.[14] In the United States, methamphetamine's levorotary form is available in
some over-the-counter nasal decongestant products, such as Vicks VapoInhaler.[note 3]
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.[14] Methamphetamine hydrochloride dispensed in the United States is required to include the
following black box warning:[14]

Methamphetamine has a high potential for abuse. It should thus be tried only in weight reduction
programs for patients in whom alternative therapy has been ineffective. Administration of
methamphetamine for prolonged periods of time in obesity may lead to drug dependence and
must be avoided. Particular attention should be paid to the possibility of subjects obtaining
methamphetamine for non-therapeutic use or distribution to others, and the drug should be
prescribed or dispensed sparingly. Misuse of methamphetamine may cause sudden death and
serious cardiovascular adverse effects.

Recreational
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.[17] According to a National Geographic TV documentary on
methamphetamine, "an entire subculture known as party and play is based around
methamphetamine use".[17] Members of this San Francisco sub-culture, which consists almost
entirely of homosexual male methamphetamine users, will typically meet up through internet dating
sites and have sex.[17] Due to its strong stimulant and aphrodisiac effects and inhibitory effect
on ejaculation, with repeated use, these sexual encounters will sometimes occur continuously for
several days.[17] The crash following the use of methamphetamine in this manner is very often
severe, with marked hypersomnia.[17]

Desoxyn tablets pharmaceutical methamphetamine hydrochloride

Crystal meth illicit methamphetamine hydrochloride

Contraindications
Methamphetamine is contraindicated in individuals with a history of drug abuse, heart disease, or
severe agitation or anxiety, or in individuals currently
experiencingarteriosclerosis, glaucoma, hyperthyroidism, or severe hypertension.[14] The USFDA
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.[14] The
USFDA 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.[14] Due to the
potential for stunted growth, the USFDA advises monitoring the height and weight of growing
children and adolescents during treatment.[14]

Side effects
Physical
The physical effects of methamphetamine can include anorexia, hyperactivity, dilated pupils, flushed
skin, excessive sweating, increased movement, dry mouth and bruxism(leading to "meth mouth"),
headache, irregular heartbeat (usually as accelerated heartbeat or slowed heartbeat), rapid

breathing, high blood pressure, low blood pressure, high body temperature, diarrhea,
constipation, blurred vision, dizziness, twitching, numbness, tremors, dry skin, acne,
and pallor.[14][18] Methamphetamine that is present in a mother'sbloodstream can pass through
the placenta to a fetus and is or be secreted into breast milk.[19] Infants born to methamphetamineabusing mothers were found to have a significantly smaller gestational age-adjusted head
circumference and birth weight measurements.[19] Methamphetamine exposure was also associated
with neonatal withdrawalsymptoms of agitation, vomiting and tachypnea.[19] This withdrawal
syndrome is relatively mild and only requires medical intervention in approximately 4% of cases.[20]
Meth mouth
Main article: Meth mouth
Methamphetamine users and addicts may lose their teeth abnormally quickly, regardless of the route
of administration, from a condition informally known as meth mouth.[21] The condition is generally
most severe in users who inject the drug, rather than those who smoke, ingest or inhale
it.[21] 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)".[21][22] Many researchers suggest that methinduced tooth decay is due to users' lifestyles, as dry mouth is also a side effect of prescription
stimulants, which aren't known to cause serious tooth decay. They suggest that the side effect has
been exaggerated and stylized to deter potential users and stereotype current users.[23]

Psychological
The psychological effects of methamphetamine can include euphoria, dysphoria, changes
in libido, alertness, apprehension, concentration, decreased sense of
fatigue, insomniaor wakefulness, self-confidence, sociability, irritability,
restlessness, grandiosity and repetitive and obsessive behaviors.[14][18][24] Methamphetamine use also
has a high association with anxiety, depression, methamphetamine psychosis, suicide, and violent
behaviors.[25] Methamphetamine also has a very high addiction risk.[14]

Dependence, addiction, and withdrawal

See also: FosB
Signaling cascade in the nucleus accumbens that results in psychostimulant addiction

Note: colored text contains article links.

Nuclear pore
Nuclear membrane
Plasma membrane
Cav1.2
NMDAR
AMPAR
DRD1
DRD5
DRD2
DRD3
DRD4
Gs
Gi/o
cAMP

cAMP

PKA
CaM
CaMKII
DARPP-32
PP1
PP2B
CREB
FosB
JunD
c-Fos
SIRT1
HDAC1
[Color legend 1]

This diagram depicts the signaling events in the brain's reward center that are induced by chronic high-dose exposure
to psychostimulants that increase the concentration of synaptic dopamine,
like amphetamine,methylphenidate, phenethylamine, and cocaine. Following
presynaptic dopamine and glutamate co-releaseby such psychostimulants, postsynaptic receptors for
these neurotransmitters trigger internal signaling events through a cAMP pathway and calcium-dependent pathway
that ultimately result in increased CREBphosphorylation.[26][27] Phosphorylated CREB increases levels of FosB, which
in turn represses the c-fos gene with the help of corepressors.[27] A highly stable (phosphorylated) form of FosB, one
that persists in neurons for one or two months, slowly accumulates following repeated exposure to stimulants through
this process.[28][29] FosB functions as "one of the master control proteins" that produces addiction-relatedstructural
changes in the brain, and upon sufficient accumulation, it leads to the production of enough of its downstream targets
like nuclear factor kappa B) to induce an addictive state.[28][29]

Tolerance is expected to develop with regular methamphetamine use and, when abused, this
tolerance develops rapidly.[30][31]
The evidence on effective treatments for amphetamine and methamphetamine dependence and
abuse is limited.[32] In light of this,fluoxetine[note 4] and imipramine[note 5] appear to have some limited
benefits in treating abuse and addiction, "no treatment has been demonstrated to be effective for the
treatment of [methamphetamine] dependence and abuse".[32]
In highly dependent amphetamine and methamphetamine abusers, "when chronic heavy users
abruptly discontinue [methamphetamine] use, many report a time-limited withdrawal syndrome that
occurs within 24 hours of their last dose".[33] 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.[33] 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.[33]Withdrawal symptoms are associated with the degree of dependence (i.e., the extent
of abuse).[33] The mental depression associated with methamphetamine withdrawal lasts longer and
is more severe than that ofcocaine withdrawal.[20]
Current models of addiction from chronic drug use involve alterations in gene expression in certain
parts of the brain.[34][35] The most important transcription factors that produce these alterations
are FosB, cyclic adenosine monophosphate (cAMP) response element binding protein (CREB),
and nuclear factor kappa B (NFB).[35] FosB is the most significant, since its overexpression in
the nucleus accumbens is necessary and sufficient for many of the neural adaptations seen in drug
addiction;[35] it has been implicated in addictions

to alcohol, cannabinoids, cocaine, nicotine,phencyclidine, and substituted

amphetamines.[34][35][36] JunD is the transcription factor which directly opposes FosB.[35] Increases in
nucleus accumbens JunD expression can reduce or, with a large increase, even block most of the
neural alterations seen in chronic drug abuse (i.e., the alterations mediated by FosB).[35] FosB
also plays an important role in regulating behavioral responses to natural rewards, such as palatable
food, sex, and exercise.[35][37] Since natural rewards, like drugs of abuse, induce FosB, chronic
acquisition of these rewards can result in a similar pathological addictive state.[35][37] Consequently,
FosB is the key transcription factor involved in methamphetamine addiction, especially
methamphetamine-induced sex addictions.[35][37][38] FosB inhibitors (drugs that oppose its action) may
be an effective treatment for addiction and addictive disorders.[39]

Neurotoxicity
Unlike amphetamine, methamphetamine is directly neurotoxic to dopamine neurons.[40] Moreover,
methamphetamine abuse is associated with an increased risk of Parkinson's disease due to
excessive pre-synaptic dopamine autoxidation, a mechanism of neurotoxicity.[41][42][43][44] Similar to the
neurotoxic effects on the dopamine system, methamphetamine can also result in neurotoxicity
to serotonin neurons.[45] It has been demonstrated that a high core temperature is correlated with an
increase in the neurotoxic effects of methamphetamine.[46] As a result of methamphetamineinduced neurotoxicity to dopamine neurons, chronic use may also lead to post acute
withdrawals which persist beyond the withdrawal period for months, and even up to a year.[41]

Sexually transmitted infection

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.[47] 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.[47] 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.[14][48] Methamphetamine may also cause sores and abrasions in the mouth
via bruxism, increasing the risk of sexually transmitted infection.[14][48]
Besides the sexual transmission of HIV, it may also be transmitted between users who share a
common needle.[49] The level of needle sharing among methamphetamine users is similar to that
among other drug injection users.[49]

Overdose
A methamphetamine overdose may result in a wide range of symptoms.[7][14] 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 overresponsive reflexes, muscle aches, severe agitation, rapid breathing, tremor, urinary hesitancy,
and an inability to pass urine.[7][18] An extremely large overdose may produce symptoms such
as adrenergic storm, methamphetamine psychosis, substantially reduced or nil urine
output, cardiogenic shock, brain bleed, circulatory collapse, dangerously high body
temperature, pulmonary hypertension, kidney failure, rhabdomyolysis, serotonin syndrome, and a
form of stereotypy ("tweaking").[Refnote 1] A methamphetamine overdose will likely also result in
mild brain damage due todopaminergic and serotonergic neurotoxicity.[40][45] Death from
methamphetamine poisoning is typically preceded by convulsions and coma.[14]

Emergency treatment
The USFDA states[note 6] that acute methamphetamine intoxication is largely managed by treating the
symptoms and includes may initially include administration of activated

charcoal and sedation.[7] There is not enough evidence on hemodialysis or peritoneal dialysis in
cases of methamphetamine intoxication to determine their usefulness.[14] 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.[7] Hypertension presents a risk
for intracranial hemorrhage and, if severe, is typically treated with Intravenous
(IV) phentolamine or nitroprusside.[7] Blood pressure often drops gradually following sufficient
sedation with a benzodiazepine and providing a calming environment.[7] Chlorpromazine may be
useful in decreasing the stimulant and CNS effects of a methamphetamine overdose.[14] The use of a
nonselective beta blocker may be required to control increased heart rate.[7]

Psychosis
The main section for this topic is on the page Stimulant psychosis, in the section Substituted
amphetamines.
Abuse of methamphetamine can result in a stimulant psychosis which may present with a variety of
symptoms (e.g. paranoia, hallucinations, delirium, delusions).[7][53] ACochrane Collaboration review on
treatment for amphetamine, dextroamphetamine, and methamphetamine abuse-induced psychosis
states that about 515% of users fail to recover completely.[53][54] The same review asserts that,
based upon at least one trial, antipsychotic medications effectively resolve the symptoms of acute
amphetamine psychosis.[53] Methamphetamine psychosis may also develop occasionally as a
treatment-emergent side effect.[55]

Interactions
Methamphetamine is metabolized by the liver enzyme CYP2D6, so CYP2D6 inhibitors
(e.g., selective serotonin reuptake inhibitors (SSRIs)) will prolong the elimination half-life of
methamphetamine.[56] Methamphetamine also interacts with monoamine oxidase inhibitors (MAOIs),
since both MAOIs and methamphetamine increase plasma catecholamines; therefore, concurrent
use of both is dangerous.[14] Methamphetamine may decrease the effects
of sedatives and depressants and increase the effects of stimulants andantidepressants as
well.[14] Methamphetamine may counteract the effects of antihypertensives and antipsychotics due to
its effects on the cardiovascular system and cognition respectively.[14] The pH of gastrointestinal
content and urine affects the absorption and excretion of methamphetamine.[14] Specifically, acidic
substances will reduce the absorption of methamphetamine and increase urinary excretion, while
alkaline substances do the opposite.[14] Due to the effect pH has on absorption, proton pump
inhibitors, which reduce gastric acid, are known to interact with methamphetamine.[14]

Pharmacology

This illustration depicts the normal operation of thedopaminergic terminal to the left, and the dopaminergic terminal in
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).

Pharmacodynamics
Like amphetamine, methamphetamine has been identified as a potent full agonist of trace amineassociated receptor 1(TAAR1), a G protein-coupled receptor (GPCR) that regulates
brain catecholamine systems.[57][58] Activation of TAAR1, viaadenylyl cyclase, 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).[57][59] 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.[57][60] Other transporters that methamphetamine is known to inhibit are vesicular
monoamine transporter 1(VMAT1), vesicular monoamine transporter 2 (VMAT2), SLC22A3,
and SLC22A5.[61] SLC22A3 is an extraneuronal monoamine transporter that is present
in astrocytes and SLC22A5 is a high-affinity carnitine transporter.[58][62] When methamphetamine
interacts with VMAT2, it induces a release of monoamines from the synaptic vesicles (vesicles that
stores monoamines) into the cytosol (intracellular fluid) of the presynaptic neuron.[63]
Methamphetamine is also an agonist of the alpha-2 adrenergic receptors and sigma receptors, and
inhibits vesicular monoamine transporter 1 (VMAT1), monoamine oxidase B (MAO-B),
and monoamine oxidase A (MAO-A).[58][64][65]Methamphetamine is known to inhibit the CYP2D6 liver
enzyme as well.[56] Dextromethamphetamine is a strongerpsychostimulant, but
levomethamphetamine has a longer half-life and is CNS-active with weaker effects (approximately
one-tenth) on striatal dopamine and shorter perceived effects among addicts.[66][67][68] At high doses,
both enantiomers of methamphetamine can induce stereotypy and methamphetamine
psychosis,[67] but levomethamphetamine is less desired by drug abusers because of its weaker
pharmacodynamic profile.[68]
Although all of the mechanisms are not fully understood, methamphetamine is a known neurotoxin in
both lab animals and humans.[40][45][69][70] Beyond neurotoxicity, magnetic resonance imaging studies
on human methamphetamine addicts and abusers indicate adverse neuroplastic changes, such as
significant abnormalities in various brain structures.[45] In particular, methamphetamine appears to
cause white matter hyperintensity and hypertrophy, marked shrinkage of hippocampi, and a
reduction in gray matter in the cingulate cortex, limbic cortex, and paralimbic cortex.[45] Moreover,
there are adverse changes in various metabolic markers of metabolic integrity or synthesis in
methamphetamine abusers, such as reductions in N-acetylaspartate and creatine as well as
elevated choline and myoinositol levels.[45]
Comparison to amphetamine pharmacodynamics
Both amphetamine and methamphetamine are potent CNS stimulants with a few biomolecular
targets and affected transporters in common; however, there are
importantpharmacodynamic differences between the two compounds.[Refnote 2] Both compounds are
potent trace amine-associated receptor 1 (TAAR1) agonists (causing non-competitive inhibition
of DAT, NET, and SERT) and inhibitors of VMAT2, SLC22A3, and SLC22A5.[Refnote 3] However,
methamphetamine appears to bind at a different site at VMAT2 than
amphetamine.[74] Methamphetamine also inhibits VMAT1, has agonist activity at all alpha-2
adrenergic receptor and sigma receptor subtypes, and is directly toxic to dopamine neurons in
humans, whereas there is no evidence of acute amphetamine toxicity in humans.[40][45][58][64] Sigma
receptor activity is known to potentiate the stimulant and neurotoxic effects of
methamphetamine.[64][65]

In contrast to the adverse neuroplastic effects evident in methamphetamine addicts and abusers,
long-term use of amphetamine or methylphenidate at therapeutic doses appears to produce
beneficial changes in brain function and structure, such as normalization of the right caudate
nucleus.[75][76]

Pharmacokinetics
Following oral administration, methamphetamine is well-absorbed into the bloodstream, with peak
plasma methamphetamine concentrations achieved in approximately 3.136.3 hours post
ingestion.[77] Methamphetamine is also well absorbed following inhalation and following intranasal
administration.[7] Due to the high lipophilicity of methamphetamine, it can readily move through
the blood brain barrier faster than other stimulants, where it is more resistant to degradation
by monoamine oxidase.[7][77] The amphetamine metabolite peaks at 1024 hours.[7] It is excreted by
the kidneys, with the rate of excretion into the urine heavily influenced by urinary pH.[14][77] When
taken orally, 3054% of the dose is excreted in urine as methamphetamine and 1023% as
amphetamine.[77] Following IV doses, about 45% is excreted as methamphetamine and 7% as
amphetamine.[77] The half-life of methamphetamine is variable with a mean value of between 5
12 hours.[7][77]
CYP2D6, dopamine -hydroxylase, flavin-containing monooxygenase, butyrate-CoA ligase,
and glycine N-acyltransferase are the enzymes known to metabolize methamphetamine or its
metabolites in humans.[3][4][5][6][56] The primary metabolites are amphetamine and 4hydroxymethamphetamine; other minor metabolites include:4-hydroxyamphetamine, 4hydroxynorephedrine, 4-hydroxyphenylacetone, benzoic acid, hippuric acid, norephedrine,
and phenylacetone, the metabolites of amphetamine.[2][77][78][79] Among these metabolites, the
active sympathomimetics are amphetamine, 4-hydroxyamphetamine,[80] 4-hydroxynorephedrine,[81]4hydroxymethamphetamine,[77] and norephedrine.[82]
The main metabolic pathways involve aromatic para-hydroxylation, aliphatic alpha- and betahydroxylation, N-oxidation, N-dealkylation, and deamination.[2][77][78] The known metabolic pathways
include:[2][77][79]
Metabolic pathways of methamphetamine

Methamphetamine
4-Hydroxymethamphetamine
4-Hydroxyphenylacetone
Phenylacetone
Benzoic acid
Hippuric acid
Amphetamine
Norephedrine
4-Hydroxyamphetamine
4-Hydroxynorephedrine
The primary metabolites of methamphetamine are amphetamine and 4-hydroxymethamphetamine.[77]

Detection in biological fluids

Methamphetamine and amphetamine are often measured in urine or blood as part of a drug test for
sports, employment, poisoning diagnostics, and forensics.[83][84][85][86] Chiral techniques may be
employed to help distinguish the source the drug to determine whether it was obtained illicitly or
legally via prescription or prodrug.[87] Chiral separation is needed to assess the possible contribution
of levomethamphetamine (e.g., Vicks Vapoinhaler) toward a positive test result.[87][88][89] Dietary zinc
supplements can mask the presence of methamphetamine and other drugs in urine.[90]

Physical and chemical properties

Pure shards of 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.[9] It is soluble in diethyl
ether and ethanol as well as miscible with chloroform.[9] In contrast, the methampetamine
hydrochloride salt is odorless with a bitter taste.[9] It has a melting point between 170 to 175 C (338
to 347 F) and, at room temperature, occurs as white crystals or a white crystalline powder.[9] The
hydrochloride salt is also freely soluble in alcohol and water.[9]

Synthesis
For more details on illicit amphetamine synthesis, see Illegal synthesis of substituted amphetamines.
Racemic methamphetamine may be prepared starting from phenylacetone by either
the Leuckart[91] or reductive amination methods.[92] In the Leuckart reaction, one equivalent of
phenylacetone is reacted with two equivalents of N-methylformamide to produce the formyl amideof
methamphetamine plus carbon dioxide and methylamine as side products.[92] In this reaction,
an iminium cation is formed as an intermediate which is reduced by the second equivalent of Nmethylformamide.[92] The intermediate formyl amide is then hydrolyzedunder acidic aqueous
conditions to yield methamphetamine as the final product.[92] Alternatively, phenylacetone can be
reacted with methylamine under reducing conditions to yield methamphetamine.[92]
Methamphetamine synthesis

Method of methamphetamine synthesis of methamphetamine via reductive amination

Methods of methamphetamine synthesis via the Leuckart reaction

Degradation
Bleach exposure time and concentration are correlated with destruction of
methamphetamine.[93] Methamphetamine in soils has shown to be a persistent pollutant.[94] Meth is
largely degraded within 30 days in a study of bioreactors under exposure to light in wastewater.[95]

History, society, and culture

Main article: History and culture of substituted amphetamines

A Pervitin tablet container, the methamphetamine brand used by German soldiers during World War II

A 1970 advertisement for Obetrol, a pharmaceutical mixture of amphetamine and methamphetamine salts

Amphetamine, discovered before methamphetamine, was first synthesized in 1887 in Germany by

Romanian chemist Lazr Edeleanu who named it phenylisopropylamine.[96][97] Shortly after,
methamphetamine was synthesized from ephedrine in 1893 by Japanese chemist Nagai
Nagayoshi.[98] Three decades later, in 1919, methamphetamine hydrochloride was synthesized by
pharmacologist Akira Ogata via reduction of ephedrine using red phosphorus and iodine.[99]
During World War II, Pervitin (methamphetamine) developed by Berlin
based Temmler pharmaceutical company was used extensively by all branches of the German
armed forces (Luftwaffe pilots, in particular) for its performance enhancing stimulant effects and to
induce extended wakefulness.[100][101] Pervitin became colloquially known among the German troops
as "Tank-Chocolates" (Panzerschokolade), "Stuka-Tablets" (Stuka-Tabletten) and "Herman-GringPills" (Hermann-Gring-Pillen).
Obetrol, patented by Obetrol Pharmaceuticals in the 1950s and indicated for treatment of obesity,
was one of the first brands of pharmaceutical methamphetamine products.[102] Due to the
psychological and stimulant effects of methamphetamine, Obetrol became a popular diet pill in
America in the 1950s and 1960s.[102] Eventually, as the addictive properties of the drug became
known, governments began to strictly regulate the production and distribution of
methamphetamine.[97] For example, during the early 1970s in the United States, methamphetamine
became a schedule II controlled substance under the Controlled Substances Act.[103]Currently,
methamphetamine is sold under the trade name Desoxyn, trademarked by the Danish
pharmaceutical companyLundbeck.[104] As of January 2013, the Desoxyn trademark had been sold to
Italian pharmaceutical company Recordati.[105]

Present legal status

Main article: Legal status of methamphetamine
The production, distribution, sale, and possession of methamphetamine is restricted or illegal in
many jurisdictions.[106][107]Methamphetamine has been placed in schedule II of the United
Nations Convention on Psychotropic Substances treaty.[107]

See also

Amphetamine
Breaking Bad A television series involving the criminal production of methamphetamine
Faces of Meth
Levomethamphetamine
Methamphetamine in the United States
Montana Meth Project
Phenelzine
Rolling meth lab
Ya ba

Notes
1. Jump up^ Synonyms and alternate spellings include: metamfetamine (International
Nonproprietary Name (INN)), N-methylamphetamine, desoxyephedrine, Syndrox, and
Desoxyn.[10][11] Common slang terms for methamphetamine include: speed, meth, crystal, crystal
meth, glass, shards, ice, and tic[12]and, in New Zealand, "P"[13].
2. Jump up^ Enantiomers are molecules that are mirror images of one another; they are
structurally identical, but of the opposite orientation.
3. ^ Jump up to:a b The active ingredient in Vicks Vapoinhaler is listed as levmetamfetamine,
the INN and USAN of levomethamphetamine.[15][16]
4. Jump up^ During short-term treatment, fluoxetine may decrease drug craving.[32]
5. Jump up^ During "medium-term treatment," imipramine may extend the duration of adherence to
addiction treatment.[32]
6. Jump up^ They suggest consulting with a Certified Poison Control Center on treatment for up-todate information, advice, and guidance.[14]

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1. Jump up^
Ion channel
G proteins & linked receptors
(Text color) Transcription factors