Methamphetamine drug profile
A synthetic substance. Normally seen as a white powder, it acts as a stimulant of the central nervous system (CNS). First manufactured in Japan in 1919, methamphetamine has some limited therapeutic use, but most is manufactured in clandestine laboratories, particularly in the USA and the Far East. It is under international control and closely related to amphetamine.
Methamphetamine (CAS-537-46-2) is a member of the phenethylamine family, which includes a range of substances that may be stimulants, entactogens or hallucinogens. Thus, methamphetamine is N,α-dimethylphenethylamine.
According to IUPAC, the fully systematic name is N,α-dimethylbenzeneethanamine. The asymmetric α-carbon atom gives rise to two enantiomers. These two forms were previously called the [–]- or l-stereoisomer and the [+]- or d-stereoisomer, but in modern usage are defined as the R- and S-stereoisomers.
Molecular formula: C10H15N
Molecular weight: 149.2 g/mol
Methamphetamine base is a colourless volatile oil insoluble in water. The most common salt is the hydrochloride (CAS-51-57-0), which occurs as a white or off-white powder or as crystals soluble in water. Illicit products mostly consist of powders, but the pure crystalline hydrochloride is known as 'ice'. Tablets containing methamphetamine may carry logos similar to those seen on MDMA and other ecstasy tablets.
Methamphetamine is a CNS stimulant that causes hypertension and tachycardia with feelings of increased confidence, sociability and energy. It suppresses appetite and fatigue and leads to insomnia. Following oral use, the effects usually start within 30 minutes and last for many hours. Later, users may feel irritable, restless, anxious, depressed and lethargic. It increases the activity of the noradrenergic and dopamine neurotransmitter systems. Methamphetamine has higher potency than amphetamine, but in uncontrolled situations the effects are almost indistinguishable. The S-isomer has greater activity than the R-isomer. The therapeutic dose of the S-isomer is up to 25 mg orally. It is rapidly absorbed after oral administration, and maximum plasma levels are in the range 0.001–0.005 mg/L. The plasma half-life is about nine hours. The major metabolites include 4-hydroxymethamphetamine and amphetamine. Fatalities directly attributed to methamphetamine are rare. In most fatal poisonings the blood concentration is above 0.5 mg/L. Analysis of methamphetamine in urine is confounded because it is a metabolite of certain medicinal products (e.g. selegiline). Acute intoxication causes serious cardiovascular disturbances as well as behavioural problems that include agitation, confusion, paranoia, impulsivity and violence. Chronic use of methamphetamine causes neurochemical and neuroanatomical changes. Dependence — as shown by increased tolerance — results in deficits in memory and in decision-making and verbal reasoning. Some of the symptoms resemble those of paranoid schizophrenia. These effects may outlast drug use, although often they resolve eventually. Injection of methamphetamine carries the same viral infection hazards (e.g. HIV and hepatitis) as are found with other injectable drugs such as heroin. When methamphetamine is smoked it reaches the brain much more quickly. Drugs which are smokable (e.g. methamphetamine, crack cocaine) are much more addictive and more likely to cause problems when consumed in this way than when taken orally.
Synthesis and precursors
The S-enantiomer is most commonly produced by reduction of l-ephedrine, i.e. (1R,2S)-2-methylamino-1-phenylpropan-1-ol, or by reduction of d-pseudoephedrine, i.e. (1S,2S)-2-methylamino-1-phenylpropan-1-ol. Both ephedrine and pseudoephedrine are commercially available and are used in certain medicinal products. Ephedrine may also be extracted from the plant Ephedra vulgaris L. (used in Chinese medicine as Ma Huang). Both the Leuckart route and reductive amination (e.g. the aluminium foil method) of 1-phenyl-2-propanone (P2P, BMK, phenylacetone) yield a racemic mixture of the R- and S-enantiomers. The synthetic route used may be identified by impurity profiling. Ephedrine, pseudoephedrine and 1-phenyl-2-propanone are listed in Table I of the United Nations 1988 Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances. The corresponding EU legislation is set out in Council Regulation (EEC) No 3677/90 (as later amended), which governs trade between the EU and third countries.
Mode of use
Methamphetamine may be ingested, snorted and, less commonly, injected or smoked. Unlike the sulfate salt of amphetamine, methamphetamine hydrochloride, particularly the crystalline form (ice), is sufficiently volatile to be smoked. When ingested, a dose may vary from several tens to several hundreds of milligrams depending on the purity and the isomeric composition.
The term metamfetamine (the International Non-Proprietary Name: INN) strictly relates to the specific enantiomer(S)-N,α-dimethylbenzeneethanamine. Metamfetamine is also the name required by Directives 65/65/EECand 92/27/EEC for the labelling of medicinal products within the EU. In the United Kingdom and some other countries, the name used in drugs legislation is methylamphetamine. Other commonly used chemical names include N-methylamphetamine, 1-phenyl-2-methylaminopropane, phenyliospropylmethylamine and desoxyephedrine. Methamphetamine, as the N-methyl derivative of amphetamine, is sometimes included with amphetamine and other less common substances (e.g. benzphetamine) under the generic heading of ‘amphetamines’.
Hundreds of other synonyms and proprietary names exist (see, for example, http://www.chemindustry.com/chemicals/55866.html). ‘Street’ terms include speed, crank, meth, crystal meth, pervitin (particularly in eastern Europe; a name derived from an earlier medicinal product), yaba and shabu (certain countries in the Far East).
The Marquis field test produces an orange/brown coloration. The Simon test (for secondary amines) produces a blue coloration that will distinguish methamphetamine from primary amine such as amphetamine (red coloration). In the mass spectrum, the major ions are m/z = 58, 91, 59, 134, 65, 56, 42 and 57. Identification by gas chromatography–mass spectrometry can be improved by N-derivatisation. Using gas chromatography, the limit of detection in urine is <10 μg/L.
The S-enantiomer is listed in Schedule II of the United Nations 1971 Convention on Psychotropic Substances. The racemate (a 50:50 mixture of the R- and S-stereoisomers) is also listed in the same Schedule, but the R-enantiomer is not separately identified in the Convention.
Methamphetamine has occasional therapeutic use in the treatment of narcolepsy and attention deficit hyperactivity disorder (ADHD).
Wastewater analysis and drugs — a European study (March 2023)
European Web Survey on Drugs 2021: Ukraine (July 2022)
Utilising an online survey to monitor methamphetamine availability, prices and supply: involvement of organised crime in New Zealand (June 2022)
European Drug Report 2022: Trends and Developments (June 2022)
Europe’s emergence as a globally important producer of methamphetamine (May 2022)
EU Drug Markets: Main methamphetamine production methods used in Europe (May 2022)
EU Drug Markets: Methamphetamine and criminal networks in Europe (May 2022)
Infographics and media
Advisory Council on the Misuse of Drugs (2005), Methylamphetamine Review (report), Advisory Council on the Misuse of Drugs, London (http://www.drugs.gov.uk/publication-search/acmd/ACMD-Meth-Report-November-2005?view=Binary).
Cook, C. E., Jeffcoat, A. R., Hill, J. M., et al. (1993),‘Pharmacokinetics of methamphetamine self-administered to human subjects by smoking S-(+)-methamphetamine hydrochloride’, Drug Metabolism and Disposition 21, pp. 717–23.
Hammer, M. R. (2006), A Key to Methamphetamine-Related Literature, New York State Department of Health, New York (http://www.nyhealth.gov/diseases/aids/harm_reduction/crystalmeth/docs/meth_literature_index.pdf).
Iversen, L. (2006), Speed, Ecstasy, Ritalin: the science of amphetamines, Oxford University Press, Oxford.
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Moffat, A. C., Osselton, M, D. and Widdop, B, (eds.) (2004), Clarke's Analysis of Drugs and Poisons, 3rd edn, Vol. 2, Pharmaceutical Press, London.
Remberg, B. and Stead, A. H. (1999), ‘Drug characterization/impurity profiling, with special focus on methylamphetamine: recent work of the United Nations International Drug Control Programme’, Bulletin on Narcotics 11(1 and 2), pp. 97–117.
United Nations (2006), Multilingual Dictionary of Narcotic Drugs and Psychotropic Substances under International Control, United Nations, New York.
United Nations (2006), Recommended methods for the identification and analysis of amphetamine, methamphetamine and their ring-substituted analogues in seized materials (revised and updated), Manual for Use by National Drug Testing Laboratories, United Nations, New York.
United Nations Office on Drugs and Crime (2003), Ecstasy and Amphetamines Global Survey 2003, United Nations Office on Drugs and Crime, Vienna (http://www.unodc.org/pdf/publications/report_ats_2003-09-23_1.pdf).
United Nations Office on Drugs and Crime (2004), World Drug Report 2004, Vol. 1: Analysis, United Nations Office on Drugs and Crime, Vienna (http://www.unodc.org/pdf/WDR_2004/volume_1.pdf).