Methamphetamine

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This article is about the free base and salts of methamphetamine. "Meth" redirects here. For other uses, see Meth (disambiguation)
Methamphetamine
An image of the methamphetamine compound
A 3d image of the methamphetamine compound
Systematic (IUPAC) name
N-methyl-1-phenylpropan-2-amine
Clinical data
Licence data US FDA:link
Pregnancy cat. C (US)
Legal status Controlled (S8) (AU) Schedule I (CA) Class A (UK) Schedule II (US) ℞ Prescription only
Dependence liability Very high
Routes Medical: Oral
Recreational: Oral, Intravenous, Insufflation, Inhalation, Suppository
Pharmacokinetic data
Bioavailability Oral:Varies widely;[1] Rectal:99%; IV:100%
Protein binding Varies widely[1]
Metabolism Hepatic: CYP2D6[2] and FMO[3]
Half-life 9–12 hours[4]
Excretion Renal
Identifiers
CAS number 537-46-2 YesY
ATC code N06BA03
PubChem CID 1206
DrugBank DB01577
ChemSpider 1169 YesY
UNII 44RAL3456C YesY
KEGG D08187 YesY
ChEBI CHEBI:6809 YesY
ChEMBL CHEMBL1201201 YesY
Synonyms N-methylamphetamine
Chemical data
Formula C10H15N 
Mol. mass 149.2337 g/mol
Physical data
Melt. point 3 °C (37 °F) [5]
Boiling point 212 °C (414 °F) [6] at 760 MM HG
 YesY (what is this?)  (verify)

Methamphetamine[note 1] (pronunciation: /ˌmɛθæmˈfɛtəmiːn/; contracted from N-methyl-alpha-methylphenethylamine) is a neurotoxin and potent psychostimulant of the phenethylamine and amphetamine classes that is used to treat attention deficit hyperactivity disorder (ADHD) and obesity. Methamphetamine exists as two enantiomers, dextrorotary and levorotary.[note 2] Dextromethamphetamine is a stronger central nervous system (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 name Desoxyn. 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.

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. Unlike amphetamine and cocaine, methamphetamine is neurotoxic to humans, damaging both dopamine and serotonin neurons in the CNS. Entirely opposite to the long-term use of amphetamine, there is evidence that methamphetamine causes brain damage from long-term use in humans; 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.

Uses

Medical

In the United States, methamphetamine hydrochloride, under the trade name Desoxyn, has been approved by the USFDA for treating ADHD and exogenous obesity (obesity originating from factors outside of the patient's control) in both adults and children;[7] however, the USFDA also indicates that the limited therapeutic usefulness of methamphetamine should be weighed against the inherent risks associated with its use.[7] 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.[7] Methamphetamine hydrochloride dispensed in the United States is required to include the following black box warning:[7]

“ Methamphetamine has a high potential for abuse and should be tried only in weight reduction programs where alternative therapy has been ineffective. Administration of Methamphetamine for prolonged periods may lead to drug dependence. The drug should be prescribed or dispensed sparingly. Misuse may cause sudden death and serious cardiovascular adverse events. ”

Recreational

See also: Party and play and the Recreational routes of methamphetamine administration

Methamphetamine is often used recreationally for its effects as a potent aphrodisiac, euphoriant, and stimulant.[8] According to a National Geographic TV documentary on methamphetamine, "an entire subculture known as party and play is based around methamphetamine use."[8] Members of this sub-culture, which is comprised almost entirely of homosexual male methamphetamine users, will typically meet up through internet dating sites and have sex.[8] 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.[8] The crash following the use of methamphetamine in this manner is very often severe, with marked hypersomnia.[8]

Desoxyn tablet
Desoxyn tablets – pharmaceutical methamphetamine hydrochloride
Crystal meth
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 experiencing arteriosclerosis, glaucoma, hyperthyroidism, or severe hypertension.[7] 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.[7] 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.[7] Due to the potential for stunted growth, the USFDA advises monitoring the height and weight of growing children and adolescents during treatment.[7]

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.[7][9] Methamphetamine that is present in a mother's bloodstream can pass through the placenta to a fetus and is or be secreted into breast milk.[10] Infants born to methamphetamine-abusing mothers were found to have a significantly smaller gestational age-adjusted head circumference and birth weight measurements.[10] Methamphetamine exposure was also associated with neonatal withdrawal symptoms of agitation, vomiting and tachypnea.[10] This withdrawal syndrome is relatively mild and only requires medical intervention in approximately 4% of cases.[11]

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.[12] The condition is generally most severe in users who inject the drug, rather than those who smoke, ingest or inhale it.[12] 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)."[12][13]

Psychological

The psychological effects of methamphetamine can include euphoria, dysphoria, changes in libido, alertness, apprehension, concentration, decreased sense of fatigue, insomnia or wakefulness, self-confidence, sociability, irritability, restlessness, grandiosity and repetitive and obsessive behaviors.[7][9][14] Methamphetamine use also has a high association with anxiety, depression, methamphetamine psychosis, suicide, and violent behaviors.[15] Methamphetamine also has a very high addiction risk.[7]

Neurotoxicity

Unlike amphetamine, methamphetamine is directly neurotoxic to dopamine neurons.[16] Moreover, methamphetamine abuse is associated with an increased risk of Parkinson's disease due to excessive pre-synaptic dopamine autoxidation, a mechanism of neurotoxicity.[17][18][19][20] Similar to the neurotoxic effects on the dopamine system, methamphetamine can also result in neurotoxicity to serotonin neurons.[21] It has been demonstrated that a high core temperature is correlated with an increase in the neurotoxic effects of methamphetamine.[22] As a result of methamphetamine-induced 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.[17]

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.[23] 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.[23] 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.[7][24] Methamphetamine may also cause sores and abrasions in the mouth via bruxism, increasing the risk of sexually transmitted infection.[7][24]

Besides the sexual transmission of HIV, it may also be transmitted between users who share a common needle.[25] The level of needle sharing among methamphetamine users is similar to that among other drug injection users.[25]

Dependence, addiction, and withdrawal

See also: Amphetamine dependence

Tolerance is expected to develop with regular methamphetamine use and, when abused, this tolerance develops rapidly.[26][27]

The evidence on effective treatments for amphetamine and methamphetamine dependence and abuse is limited.[28] 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."[28]

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."[29] 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.[29] 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.[29] Withdrawal symptoms are associated with the degree of dependence (i.e., the extent of abuse).[29] The mental depression associated with methamphetamine withdrawal lasts longer and is more severe than that of cocaine withdrawal.[11]

Overdose

A methamphetamine overdose may result in a wide range of symptoms.[7] A moderate overdose of methamphetamine may induce symptoms such as: abnormal heart rhythm, confusion, dysuria, high or low blood pressure, hyperthermia, hyperreflexia, myalgia, severe agitation, tachypnea, tremor, urinary hesitancy, and urinary retention.[9] An extremely large overdose may produce symptoms such as adrenergic storm, methamphetamine psychosis, anuria, cardiogenic shock, cerebral hemorrhage, circulatory collapse, hyperpyrexia, pulmonary hypertension, renal failure, rhabdomyolysis, serotonin syndrome, and a form of stereotypy ("tweaking").[Refnote 1] A methamphetamine overdose will likely also result in mild brain damage due to dopaminergic and serotonergic neurotoxicity.[16][21] Death from fatal methamphetamine poisoning is typically preceded by convulsions and coma.[7]

Emergency treatment

The USFDA states[note 6] that acute methamphetamine intoxication is largely managed by treating the symptoms and includes gastric evacuation, 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.[7] Forced acid diuresis (e.g., with vitamin C) will increase methamphetamine excretion, but increases the risk of renal failure in the presence of myoglobinuria.[7] Intravenous (IV) phentolamine may be useful for acute cases of severe hypertension if the condition complicates methamphetamine overdose.[7] Blood pressure often drops gradually following sufficient sedation.[7] Chlorpromazine may be useful in decreasing the stimulant and CNS effects of a methamphetamine overdose.[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, delusions).[30] A Cochrane Collaboration review on treatment for amphetamine, dextroamphetamine, and methamphetamine abuse-induced psychosis states that about 5–15% of users fail to recover completely.[30][31] The same review asserts that, based upon at least one trial, antipsychotic medications effectively resolve the symptoms of acute amphetamine psychosis.[30] Methamphetamine psychosis may also develop occasionally as a treatment-emergent side effect.[32]

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.[2] Methmphetamine also interacts with monoamine oxidase inhibitors (MAOIs), since both MAOIs and methamphetamine increase plasma catecholamines; therefore, concurrent use of both is dangerous.[7] Methamphetamine may decrease the effects of sedatives and depressants and increase the effects of stimulants and antidepressants as well.[7] Methamphetamine may counteract the effects of antihypertensives and antipsychotics due to its effects on the cardiovascular system and cognition respectively.[7] The pH of gastrointestinal content and urine affects the absorption and excretion of methamphetamine.[7] Specifically, acidic substances will reduce the absorption of methamphetamine and increase urinary excretion, while alkaline substances do the opposite.[7] Due to the effect pH has on absorption, proton pump inhibitors, which reduce gastric acid, are known to interact with methamphetamine.[7]

Pharmacology

An image of methamphetamine pharmacodynamics
This illustration depicts the normal operation of the dopaminergic 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 amine-associated receptor 1 (TAAR1), a G protein-coupled receptor (GPCR) that regulates brain catecholamine systems.[33][34] Activation of TAAR1, via adenylyl 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).[33][35] 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.[33][36] Other transporters that methamphetamine is known to inhibit are vesicular monoamine transporter 1 (VMAT1), vesicular monoamine transporter 2 (VMAT2), SLC22A3, and SLC22A5.[37] SLC22A3 is an extraneuronal monoamine transporter that is present in astrocytes and SLC22A5 is a high-affinity carnitine transporter.[34][38] 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.[39]

Methamphetamine is also an agonist of the alpha-2 adrenergic receptors and inhibits vesicular monoamine transporter 1 (VMAT1), monoamine oxidase B (MAO-B), and monoamine oxidase A (MAO-A).[34] Methamphetamine is known to inhibit the CYP2D6 liver enzyme as well.[2] Dextromethamphetamine is a stronger psychostimulant, 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.[40][41][42] At high doses, both enantiomers of methamphetamine can induce stereotypy and methamphetamine psychosis,[41] but levomethamphetamine is less desired by drug abusers because of its weaker pharmacodynamic profile.[42]

Although all of the mechanisms are not fully understood, methamphetamine is a known neurotoxin in both lab animals and humans.[16][21][43][44] Beyond neurotoxicity, magnetic resonance imaging studies on human methamphetamine addicts and abusers indicate adverse neuroplastic changes, such as significant abnormalities in various brain structures.[21] 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.[21] 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.[21]

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 important pharmacodynamic 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.[45] Methamphetamine also inhibits VMAT1, has agonist activity at all alpha-2 adrenergic receptor subtypes, and is a neurotoxin in humans, whereas there is no evidence of amphetamine neurotoxicity in humans.[16][21][34] Amphetamine is an agonist of cocaine and amphetamine regulated transcript (CART), a psychostimulant neuropeptide with neurogenerative and neuroprotective effects in vitro;[46][47] in contrast, the limited available research on the association between methamphetamine and CART in humans suggests methamphetamine has no significant effects on the neuropeptide.[34][48]

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.[49][50]

Pharmacokinetics

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.[51] Methamphetamine is also well absorbed following inhalation and following intranasal administration.[4] 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 against degradation by monoamine oxidase.[4][51] The amphetamine metabolite peaks at 10–24 hours.[4] It is excreted by the kidneys, with the rate of excretion into the urine heavily influenced by urinary pH.[7][51] When taken orally, 30–54% of the dose is excreted in urine as methamphetamine and 10–23% as amphetamine.[51] Following IV doses, about 45% is excreted as methamphetamine and 7% as amphetamine.[51] The half-life of methamphetamine is variable with a mean value of between 5–12 hours.[4][51]

Methamphetamine is metabolized in the liver by CYP2D6[2] and Flavin-containing monooxygenase[3] with the main metabolites being amphetamine and 4-hydroxymethamphetamine; other minor metabolites include: 4-hydroxyamfetamine, 4-hydroxynorephedrine, 4-hydroxyphenylacetone, benzoic acid, hippuric acid, norephedrine, and phenylacetone, the metabolites of amphetamine.[51][52][53][54] Among these metabolites, the active sympathomimetics are amphetamine, 4‑hydroxyamphetamine,[55] 4‑hydroxynorephedrine,[56] 4-hydroxymethamphetamine,[51] and norephedrine.[57]

The main metabolic pathways involve aromatic para-hydroxylation, aliphatic alpha- and beta-hydroxylation, N-oxidation, N-dealkylation, and deamination.[51][52][53] The known metabolic pathways include:[51][52][54]

Metabolic pathways of methamphetamine

The primary metabolites of methamphetamine are amphetamine and 4-hydroxymethamphetamine.[51]

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.[58][59][60][61] 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.[62] Chiral separation is needed to assess the possible contribution of levomethamphetamine (e.g., Vicks Vapoinhaler) toward a positive test result.[62][63][64] Dietary zinc supplements can mask the presence of methamphetamine and other drugs in urine.[65]

Physical and chemical properties

Methamphetamine hydrochloride
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.[6] It is soluble in diethyl ether and ethanol as well as miscible with chloroform.[6] In contrast, the methampetamine hydrochloride salt is odorless with a bitter taste.[6] 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.[6] The hydrochloride salt is also freely soluble in alcohol and water.[6]

Synthesis

Racemic methamphetamine may be prepared starting from phenylacetone by either the Leuckart[66] or reductive amination methods.[67] In the Leuckart reaction, one equivalent of phenylacetone is reacted with two equivalents of N-methylformamide to produce the formyl amide of methamphetamine plus carbon dioxide and methylamine as side products.[67] In this reaction, an iminium cation is formed as an intermediate which is reduced by the second equivalent of N-methylformamide.[67] The intermediate formyl amide is then hydrolyzed under acidic aqueous conditions to yield methamphetamine as the final product.[67] Alternatively, phenylacetone can be reacted with methylamine under reducing conditions to yield methamphetamine.[67]

Methamphetamine synthesis

Diagram of methamphetamine synthesis by reductive amination
Method of methamphetamine synthesis of methamphetamine via reductive amination
Diagram of methamphetamine synthesis by Leuckart reaction
Methods of methamphetamine synthesis via the Leuckart reaction

History, society, and culture

Main article: History and culture of substituted amphetamines

Amphetamine, discovered before methamphetamine, was first synthesized in 1887 in Germany by Romanian chemist Lazăr Edeleanu who named it phenylisopropylamine.[68][69] Shortly after, methamphetamine was synthesized from ephedrine in 1893 by Japanese chemist Nagai Nagayoshi.[70] Three decades later, in 1919, methamphetamine hydrochloride was synthesized by pharmacologist Akira Ogata via reduction of ephedrine using red phosphorus and iodine.[71] During World War II, methamphetamine was used extensively by the Axis forces for its stimulant effects.[69][72] Obetrol, patented by Obetrol Pharmaceuticals in the 1950s and indicated for treatment of obesity, was one of the first brands of pharmaceutical methamphetamine products.[73] Due to the psychological and stimulant effects of methamphetamine, Obetrol became a popular diet pill in America in the 1950s and 1960s.[73] Eventually, as the addictive properties of the drug became known, governments began to strictly regulate the production and distribution of methamphetamine.[69] For example, during the early 1970s in the United States, methamphetamine became a schedule II controlled substance under the Controlled Substances Act.[74] Currently, methamphetamine is sold under the trade name Desoxyn, trademarked by the Danish pharmaceutical company Lundbeck.[75] As of January 2013, the Desoxyn trademark had been sold to Italian pharmaceutical company Recordati.[76]

Present legal status

Main article: Legal status of methamphetamine

The production, distribution, sale, and possession of methamphetamine is restricted or illegal in many jurisdictions.[77][78] Methamphetamine has been placed in schedule II of the United Nations Convention on Psychotropic Substances treaty.[78]

See also

Notes

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

Reference notes

  1. ↑ [5][6][7][8][9][10]
  2. ↑ [11][12][13][14][15]
  3. ↑ [16][12][17][13]

References

  1. ↑ 1.0 1.1 Biomedical Effects and Toxicity. "Methamphetamine". PubChem Compound. National Center for Biotechnology Information. Retrieved 31 December 2013. 
  2. ↑ 2.0 2.1 2.2 2.3 Enzymes. "Methamphetamine". DrugBank. University of Alberta. 8 February 2013. Retrieved 31 December 2013. 
  3. ↑ 3.0 3.1 Krueger SK, Williams DE (June 2005). "Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism". Pharmacol. Ther. 106 (3): 357–387. doi:10.1016/j.pharmthera.2005.01.001. PMC 1828602. PMID 15922018. 
  4. ↑ 4.0 4.1 4.2 4.3 4.4 Schep LJ, Slaughter RJ, Beasley DM (August 2010). "The clinical toxicology of metamfetamine". Clinical Toxicology (Philadelphia, Pa.) 48 (7): 675–694. doi:10.3109/15563650.2010.516752. ISSN 1556-3650. PMID 20849327. 
  5. ↑ Properties: Predicted - EP|Suite. "Methmphetamine". Chemspider. Retrieved 3 January 2013. 
  6. ↑ 6.0 6.1 6.2 6.3 6.4 6.5 Chemical and Physical Properties. "Methamphetamine". PubChem Compound. National Center for Biotechnology Information. Retrieved 31 December 2013. 
  7. ↑ 7.0 7.1 7.2 7.3 7.4 7.5 7.6 7.7 7.8 7.9 7.10 7.11 7.12 7.13 7.14 7.15 7.16 7.17 7.18 7.19 7.20 7.21 7.22 7.23 7.24 7.25 7.26 7.27 "Desoxyn Prescribing Information". United States Food and Drug Administration. December 2013. Retrieved 6 January 2014. 
  8. ↑ 8.0 8.1 8.2 8.3 8.4 San Francisco Meth Zombies (TV documentary). National Geographic Channel. August 2013. ASIN B00EHAOBAO. 
  9. ↑ 9.0 9.1 9.2 Westfall DP, Westfall TC (2010). "Miscellaneous Sympathomimetic Agonists". In Brunton LL, Chabner BA, Knollmann BC. Goodman & Gilman's Pharmacological Basis of Therapeutics (12th ed.). New York: McGraw-Hill. ISBN 978-0-07-162442-8. 
  10. ↑ 10.0 10.1 10.2 Chomchai C, Na Manorom N, Watanarungsan P, Yossuck P, Chomchai S (December 2010). "Methamphetamine abuse during pregnancy and its health impact on neonates born at Siriraj Hospital, Bangkok, Thailand. | PubMed". Southeast Asian J. Trop. Med. Public Health 35 (1): 228–231. PMID 15272773. 
  11. ↑ 11.0 11.1 Winslow BT, Voorhees KI, Pehl KA (2007). "Methamphetamine abuse". American Family Physician 76 (8): 1169–1174. PMID 17990840. 
  12. ↑ 12.0 12.1 12.2 Hussain F, Frare RW, Py Berrios KL (2012). "Drug abuse identification and pain management in dental patients: a case study and literature review". Gen. Dent. 60 (4): 334–345. PMID 22782046. 
  13. ↑ "Methamphetamine Use (Meth Mouth)". American Dental Association. Archived from the original on June 2008. Retrieved December 2006. 
  14. ↑ O'Connor PG (February 2012). "Amphetamines". Merck Manual for Health Care Professionals. Merck. Retrieved 8 May 2012. 
  15. ↑ Darke S, Kaye S, McKetin R, Duflou J (May 2008). "Major physical and psychological harms of methamphetamine use". Drug Alcohol Rev. 27 (3): 253–262. doi:10.1080/09595230801923702. PMID 18368606. 
  16. ↑ 16.0 16.1 16.2 16.3 Malenka RC, Nestler EJ, Hyman SE (2009). "15". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. p. 370. ISBN 978-0-07-148127-4. "Unlike cocaine and amphetamine, methamphetamine is directly toxic to midbrain dopamine neurons." 
  17. ↑ 17.0 17.1 Cruickshank CC, Dyer KR (July 2009). "A review of the clinical pharmacology of methamphetamine". Addiction 104 (7): 1085–1099. doi:10.1111/j.1360-0443.2009.02564.x. PMID 19426289. 
  18. ↑ Thrash B, Thiruchelvan K, Ahuja M, Suppiramaniam V, Dhanasekaran M (2009). "Methamphetamine-induced neurotoxicity: the road to Parkinson's disease" (PDF). Pharmacol Rep 61 (6): 966–977. PMID 20081231. 
  19. ↑ Sulzer D, Zecca L (February 2000). "Intraneuronal dopamine-quinone synthesis: a review". Neurotox. Res. 1 (3): 181–195. doi:10.1007/BF03033289. PMID 12835101. 
  20. ↑ Miyazaki I, Asanuma M (June 2008). "Dopaminergic neuron-specific oxidative stress caused by dopamine itself". Acta Med. Okayama 62 (3): 141–150. PMID 18596830. 
  21. ↑ 21.0 21.1 21.2 21.3 21.4 21.5 21.6 Krasnova IN, Cadet JL (May 2009). "Methamphetamine toxicity and messengers of death". Brain Res. Rev. 60 (2): 379–407. doi:10.1016/j.brainresrev.2009.03.002. PMC 2731235. PMID 19328213. "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)."     
  22. ↑ Yuan J, Hatzidimitriou G, Suthar P, Mueller M, McCann U, Ricaurte G (March 2006). "Relationship between temperature, dopaminergic neurotoxicity, and plasma drug concentrations in methamphetamine-treated squirrel monkeys". The Journal of Pharmacology and Experimental Therapeutics 316 (3): 1210–1218. doi:10.1124/jpet.105.096503. PMID 16293712. 
  23. ↑ 23.0 23.1 Halkitis PN, Pandey Mukherjee P, Palamar JJ (2008). "Longitudinal Modeling of Methamphetamine Use and Sexual Risk Behaviors in Gay and Bisexual Men". AIDS and Behavior 13 (4): 783–791. doi:10.1007/s10461-008-9432-y. PMID 18661225. 
  24. ↑ 24.0 24.1 Patrick Moore (June 2005). "We Are Not OK". VillageVoice. Retrieved January 2011. 
  25. ↑ 25.0 25.1 "Methamphetamine Use and Health | UNSW: The University of New South Wales – Faculty of Medicine" (PDF). Archived from the original on August 2008. Retrieved January 2011. 
  26. ↑ O'Connor, Patrick. "Amphetamines: Drug Use and Abuse". Merck Manual Home Health Handbook. Merck. Retrieved 26 September 2013. 
  27. ↑ Pérez-Mañá C, Castells X, Torrens M, Capellà D, Farre M (2013). "Efficacy of psychostimulant drugs for amphetamine abuse or dependence". In Pérez-Mañá, Clara. Cochrane Database Syst. Rev. 9: CD009695. doi:10.1002/14651858.CD009695.pub2. PMID 23996457. 
  28. ↑ 28.0 28.1 Srisurapanont M, Jarusuraisin N, Kittirattanapaiboon P (2001). "Treatment for amphetamine dependence and abuse". In Srisurapanont, Manit. Cochrane Database Syst. Rev. (4): CD003022. doi:10.1002/14651858.CD003022. PMID 11687171. "Although there are a variety of amphetamines and amphetamine derivatives, the word "amphetamines" in this review stands for amphetamine, dextroamphetamine and methamphetamine only." 
  29. ↑ 29.0 29.1 29.2 29.3 Shoptaw SJ, Kao U, Heinzerling K, Ling W (2009). "Treatment for amphetamine withdrawal". In Shoptaw SJ. Cochrane Database Syst. Rev. (2): CD003021. doi:10.1002/14651858.CD003021.pub2. PMID 19370579. "
    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)"     
  30. ↑ 30.0 30.1 30.2 Shoptaw SJ, Kao U, Ling W (2009). "Treatment for amphetamine psychosis". In Shoptaw SJ, Ali R. Cochrane Database Syst. Rev. (1): CD003026. doi:10.1002/14651858.CD003026.pub3. PMID 19160215. "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."     
  31. ↑ Hofmann FG (1983). A Handbook on Drug and Alcohol Abuse: The Biomedical Aspects (2nd ed.). New York: Oxford University Press. p. 329. ISBN 978-0-19-503057-0. 
  32. ↑ Berman SM, Kuczenski R, McCracken JT, London ED (February 2009). "Potential adverse effects of amphetamine treatment on brain and behavior: a review". Mol. Psychiatry 14 (2): 123–142. doi:10.1038/mp.2008.90. PMC 2670101. PMID 18698321. 
  33. ↑ 33.0 33.1 33.2
  34. ↑ 34.0 34.1 34.2 34.3 34.4
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  36. ↑ Xie Z, Miller GM (July 2009). "A receptor mechanism for methamphetamine action in dopamine transporter regulation in brain". J. Pharmacol. Exp. Ther. 330 (1): 316–325. doi:10.1124/jpet.109.153775. PMC 2700171. PMID 19364908. 
  37. ↑ Transporters. "Methamphetamine". DrugBank. University of Alberta. 8 February 2013. Retrieved 31 December 2013. 
  38. ↑ Inazu M, Takeda H, Matsumiya T (August 2003). "[The role of glial monoamine transporters in the central nervous system]". Nihon Shinkei Seishin Yakurigaku Zasshi (in Japanese) 23 (4): 171–178. PMID 13677912. 
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  41. ↑ 41.0 41.1 Kuczenski R, Segal DS, Cho AK, Melega W (February 1995). "Hippocampus norepinephrine, caudate dopamine and serotonin, and behavioral responses to the stereoisomers of amphetamine and methamphetamine". J. Neurosci. 15 (2): 1308–1317. PMID 7869099. 
  42. ↑ 42.0 42.1 Mendelson J, Uemura N, Harris D, Nath RP, Fernandez E, Jacob P, Everhart ET, Jones RT (October 2006). "Human pharmacology of the methamphetamine stereoisomers". Clin. Pharmacol. Ther. 80 (4): 403–420. doi:10.1016/j.clpt.2006.06.013. PMID 17015058. 
  43. ↑ Itzhak Y, Martin JL, Ali SF (October 2002). "Methamphetamine-induced dopaminergic neurotoxicity in mice: long-lasting sensitization to the locomotor stimulation and desensitization to the rewarding effects of methamphetamine". Progress in Neuro-psychopharmacology & Biological Psychiatry 26 (6): 1177–1183. doi:10.1016/S0278-5846(02)00257-9. PMID 12452543. 
  44. ↑ Davidson C, Gow AJ, Lee TH, Ellinwood EH (August 2001). "Methamphetamine neurotoxicity: necrotic and apoptotic mechanisms and relevance to human abuse and treatment". Brain Research. Brain Research Reviews 36 (1): 1–22. doi:10.1016/S0165-0173(01)00054-6. PMID 11516769. 
  45. ↑ Sulzer D, Sonders MS, Poulsen NW, Galli A (April 2005). "Mechanisms of neurotransmitter release by amphetamines: a review". Prog. Neurobiol. 75 (6): 406–433. doi:10.1016/j.pneurobio.2005.04.003. PMID 15955613. "They also demonstrated competition for binding between METH and reserpine, suggesting they might bind to the same site on VMAT. George Uhl's laboratory similarly reported that AMPH displaced the VMAT2 blocker tetrabenazine (Gonzalez et al., 1994). It should be noted that tetrabenazine and reserpine are thought to bind to different sites on VMAT (Schuldiner et al., 1993a)" 
  46. ↑
  47. ↑
  48. ↑ Morio A, Ujike H, Nomura A, Tanaka Y, Morita Y, Otani K, Kishimoto M, Harano M, Inada T, Komiyama T, Yamada M, Sekine Y, Iwata N, Iyo M, Sora I, Ozaki N, Kuroda S (August 2006). "No association between CART (cocaine- and amphetamine-regulated transcript) gene and methamphetamine dependence". Ann. N. Y. Acad. Sci. 1074: 411–417. doi:10.1196/annals.1369.041. PMID 17105939. 
  49. ↑ Hart H, Radua J, Nakao T, Mataix-Cols D, Rubia K (February 2013). "Meta-analysis of functional magnetic resonance imaging studies of inhibition and attention in attention-deficit/hyperactivity disorder: exploring task-specific, stimulant medication, and age effects". JAMA Psychiatry 70 (2): 185–198. doi:10.1001/jamapsychiatry.2013.277. PMID 23247506. 
  50. ↑ Spencer TJ, Brown A, Seidman LJ, Valera EM, Makris N, Lomedico A, Faraone SV, Biederman J (September 2013). "Effect of psychostimulants on brain structure and function in ADHD: a qualitative literature review of magnetic resonance imaging-based neuroimaging studies". J. Clin. Psychiatry 74 (9): 902–917. doi:10.4088/JCP.12r08287. PMC 3801446. PMID 24107764. 
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  52. ↑ 52.0 52.1 52.2 "Adderall XR Prescribing Information". United States Food and Drug Administration. December 2013. pp. 12–13. Retrieved 30 December 2013. 
  53. ↑ 53.0 53.1 Biomedical Effects and Toxicity. "Amphetamine". Pubchem Compound. National Center for Biotechnology Information. Retrieved 12 October 2013. 
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  56. ↑ Compound Summary. "p-Hydroxynorephedrine". PubChem Compound. National Center for Biotechnology Information. Retrieved 15 October 2013. 
  57. ↑ Compound Summary. "Phenylpropanolamine". PubChem Compound. National Center for Biotechnology Information. Retrieved 15 October 2013. 
  58. ↑ Liddle DG, Connor DJ (June 2013). "Nutritional supplements and ergogenic AIDS". Prim. Care 40 (2): 487–505. doi:10.1016/j.pop.2013.02.009. PMID 23668655. 
  59. ↑ Kraemer T, Maurer HH (August 1998). "Determination of amphetamine, methamphetamine and amphetamine-derived designer drugs or medicaments in blood and urine". J. Chromatogr. B Biomed. Sci. Appl. 713 (1): 163–187. doi:10.1016/S0378-4347(97)00515-X. PMID 9700558. 
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  77. ↑ United Nations Office on Drugs and Crime (2007). Preventing Amphetamine-type Stimulant Use Among Young People: A Policy and Programming Guide. New York: United Nations. ISBN 978-92-1-148223-2. Retrieved 11 November 2013. 
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