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 are 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, Crystal meth for sale 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.
Methamphetamine base is a colorless 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 a 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 of 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 behavioral 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 that 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-phenyl propane-1-ol, or by reduction of d-pseudoephedrine, i.e. (1S,2S)-2-methylamino-1-phenyl propane-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 aluminum 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.