Smoking and insufflation

Glass pipe ("globe") used for smoking

methamphetamine.
Smoking refers to vaporizing a drug and inhaling the resulting fumes; crystal
methamphetamine (methamphetamine hydrochloride) and the free bases of
amphetamine and methamphetamine are sufficiently volatile substances to allow them
to be smoked. Crystal methamphetamine is commonly smoked in glass pipes, known
as "bubbles", "globes", and "stems" (rose-stem water containers are often used as a
makeshift pipe in urban populations). Lung disease has been reported in long-term
methamphetamine smokers.[77] Ya ba (a pill containing caffeine and
methamphetamine) smokers often use a technique in which a ya ba pill is placed on
aluminium foil that is heated underneath with a lighter, in turn vaporizing the pill so that
it can be inhaled through a heat-resistant pipe.[70] This method of administration is
sometimes referred to as "chasing the dragon".
Crystal methamphetamine and salts of amphetamine are sometimes powdered
and insufflated by recreational users, which results in a fairly rapid uptake of the drug
through the nasal epithelium; with regular use, amphetamine or methamphetamine
insufflation slowly damages and eventually destroys the nasal septum due to
their causticity and vasoconstrictive effects.
Rectal and vaginal
Rectal administration and intravaginal administration are less-popular drug routes in
the community with comparatively little research into their effects.[78] Information on
their use is largely anecdotal with reports of increased sexual pleasure and the effects
of the drug lasting longer,[79] though as methamphetamine is centrally active in the
brain, these effects are likely experienced through the higher bioavailability of the drug
in the bloodstream and the faster onset of action than many other routes of
administration.[80] Nicknames for the routes of administration within some
methamphetamine communities include a "butt rocket", a "booty bump", "potato
thumping", "turkey basting", "plugging", "boofing", "suitcasing", "hooping", "keistering",
"shafting", "bumming", and "shelving" (vaginal).[78]
Illegal synthesis
Illicitly synthesized crystal methamphetamine
Illicit industrial-scale methamphetamine and MDMA chemical factory (Cikande, Indonesia)
1 pound (0.45 kg) of methamphetamine found on a passenger at LA International
Airport (LAX)
Methamphetamine is most structurally similar to amphetamine. Synthesis is relatively
simple, but entails risk with flammable and corrosive chemicals, particularly the
solvents used in extraction and purification. The six major routes of production begin
with either phenyl-2-propanone (P2P) or with one of the isomeric
compounds pseudoephedrine and ephedrine. [81]

One procedure uses the reductive

amination of phenylacetone with methylamine,[82] P2P was usually obtained
from phenylacetic acid and acetic anhydride,[83] and phenylacetic acid might arise
from benzaldehyde, benzylcyanide, or benzylchloride.[84] Methylamine is crucial to all
such methods, and is produced from the model airplane fuel nitromethane,
or formaldehyde and ammonium chloride, or methyl iodide with hexamine.[85] This was
once the preferred method of production by motorcycle gangs in California,[86] until
DEA restrictions on the chemicals made the process difficult. Pseudoephedrine,
ephedrine, phenylacetone, and phenylacetic acid are currently DEA list I and acetic
anhydride is list II on the DEA list of chemicals subject to regulation and control
measures. This method can involve the use of mercuric chloride and leaves
behind mercury and lead environmental wastes.[87] The methamphetamine produced
by this method is racemic, consisting partly of the less-
desired levomethamphetamine isomer, though separation of the two enantiomeric
[88]

forms through selective recrystallization of the tartrate salt can occur in order to isolate
the more active dextromethamphetamine.[89]
The alternative Leuckart route also relies on P2P to produce a racemic product, but
proceeds via methylformamide in formic acid to an intermediate N-formyl-
methamphetamine, which is then decarboxylated with hydrochloric acid.[81][84]
Illicit methamphetamine is more commonly made by
the reduction of ephedrine or pseudoephedrine, which produces the more active d-
methamphetamine isomer. The maximum conversion rate for ephedrine and
pseudoephedrine is 92%, although typically, illicit methamphetamine laboratories
convert at a rate of 50% to 75%.[90] Most methods of illicit production
involve protonation of the hydroxyl group on the ephedrine or pseudoephedrine
molecule.
Though dating back to the discovery of the drug, the Nagai route[91] did not become
popular among illicit manufacturers until c.1982, and comprised 20% of production in
Michigan in 2002.[92] It involves red phosphorus and hydrogen iodide (also known as
hydroiodic acid or iohydroic acid). (The hydrogen iodide is replaced by iodine and
water in the "Moscow route".)[93] The hydrogen iodide is used to reduce either
ephedrine or pseudoephedrine to methamphetamine.[87] On heating, the precursor is
rapidly iodinated by the hydrogen iodide to form iodoephedrine. The phosphorus
assists in the second step, by consuming iodine to form phosphorus triiodide (which
decomposes in water to phosphorous acid, regenerating hydrogen iodide). Because
hydrogen iodide exists in a chemical equilibrium with iodine and hydrogen, the
phosphorus reaction shifts the balance toward hydrogen production when iodine is
consumed (see Le Châtelier's principle).[94] In Australia, criminal groups have been
known to substitute "red" phosphorus with either hypophosphorous
acid or phosphorous acid (the "Hypo route"). [93][95][96] This is a hazardous process for
amateur chemists because phosphine gas, a side-product from in situ hydrogen iodide
production,[97] is extremely toxic to inhale. The reaction can also create toxic,
flammable white phosphorus waste.[87] Methamphetamine produced in this way is
usually more than 95% pure.[98]
The conceptually similar Emde route involves reduction of ephedrine to
chloroephedrine using thionyl chloride (SOCl2), followed by catalytic hydrogenation.
The catalysts for this reaction are palladium or platinum.[81][99] The Rosenmund route
also uses hydrogen gas and a palladium catalyst poisoned with barium
sulfate (Rosenmund reduction), but uses perchloric acid instead of thionyl chloride.[84]
The Birch reduction, also called the "Nazi method", became popular in the mid-to-late
1990s and comprised the bulk of methamphetamine production in Michigan in
2002.[92] It reacts pseudoephedrine with liquid anhydrous ammonia and an alkali metal
such as sodium or lithium. The reaction is allowed to stand until the ammonia
evaporates.[100] However, the Birch reduction is dangerous because the alkali metal
and ammonia are both extremely reactive, and the temperature of liquid ammonia
makes it susceptible to explosive boiling when reactants are added. It has been the
most popular method in Midwestern states of the U.S. because of the ready availability
of liquid ammonia fertilizer in farming regions.[87][101]
In recent years, a simplified "Shake 'n Bake" one-pot synthesis has become more
popular. The method is suitable for such small batches that pseudoephedrine
restrictions are less effective, it uses chemicals that are easier to obtain (though no
less dangerous than traditional methods), and it is so easy to carry out that some
addicts have made the drug while driving.[102] It involves placing crushed
pseudoephedrine tablets into a nonpressurized container containing ammonium
nitrate, water, and a hydrophobic solvent such as Coleman fuel[103] or
automotive starting fluid, to which lye and lithium (from lithium batteries) is
added. Hydrogen chloride gas produced by a reaction of salt with sulfuric acid is then
used to recover crystals for purification. The container needs to be "burped"
periodically to prevent failure under accumulating pressure, as exposure of the lithium
to the air can spark a flash fire.[103] The battery lithium can react with water to shatter a
container and potentially start a fire or explosion.[103]
Illegal laboratories
Waste left behind from a methamphetamine lab
Short-term exposure to high concentrations of chemical vapors that exist in black-
market methamphetamine laboratories can cause severe health problems and
death.[104] Exposure to these substances can occur from volatile air emissions, spills,
fires, and explosions.[104] Such methamphetamine labs are sometimes discovered
when emergency personnel respond to fires due to improper handling of volatile or
flammable materials.[104][105] Single-pot "shake and bake" syntheses are particularly
prone to explode and ignite, and, when abandoned, still pose a severe hazard to
firefighters.[105]
Methamphetamine cooks, their families, and first responders are at high risk of
experiencing acute health effects from chemical exposure, including lung damage and
chemical burns to the body.[104][106] After the seizure of a methamphetamine lab, a low
exposure risk to chemical residues often exists, but this contamination can be
sanitized.[106] Chemical residues and lab wastes that are left behind at a former
methamphetamine lab can cause severe health problems for people who use the
property.[106]
Impurities and adulterants
In Japan, methamphetamine seizures are usually white crystals of high purity, but
contain impurities that vary according to the means of production, and are sometimes
adulterated.
Diagnostic impurities are the naphthalenes 1-benzyl-methylnaphthalene and 1,3-
dimethyl-2-phenylnaphthalene,[94] arising in the Nagai and Leuckart routes,
and cis- or trans- 1,2-dimethyl-3-phenylaziridine, ephedrine, or erythro-3,4-dimethyl-
5-phenyloxazolidine, arising in the Nagai and Emde routes; these are absent in the
reductive amination route.[84] Characteristic impurities of the Birch route include N-
methyl-1-(1-(1,4-cyclohexadienyl))-2-propanamine.[100] Methamphetamine produced
by the Birch route contains phenyl-2-propanone, the precursor for the reductive
amination route, as a degradation product.[94] However, specific diagnostic impurities
are not very reliable in practice, and it is generally preferable for forensic technicians
to evaluate a larger profile of trace compounds.[81]
A common adulterant is dimethyl sulfone, a solvent and cosmetic base without known
effect on the nervous system; other adulterants include dimethylamphetamine HCl,
ephedrine HCl, sodium thiosulfate, sodium chloride, sodium glutamate, and a mixture
of caffeine with sodium benzoate.[93]
In the United States, illicit methamphetamine comes in a variety of forms with prices
varying widely over time.[107] Most commonly, it is found as a colorless crystalline solid.
Impurities may result in a brownish or tan color. Colorful flavored pills containing
methamphetamine and caffeine are known as ya ba (Thai for "crazy medicine").
An impure form of methamphetamine is sold as a crumbly brown or off-white rock,
commonly referred to as "peanut butter crank".[108] It may be diluted or cut with non-
psychoactive substances like inositol, isopropylbenzylamine or dimethylsulfone.
Another popular method is to combine methamphetamine with other stimulant
substances, such as caffeine or cathine, into a pill known as a "Kamikaze", which can
be particularly dangerous due to the synergistic effects of multiple stimulants. Reports
in 2007 of the appearance of flavored "Strawberry Quik meth" circulated in the media
and local law enforcement,[109] but were debunked in 2010 by the DEA, although meth
of varying colors has been seized.[110]
Rarely, the impure reaction mixture from the hydrogen iodide/red phosphorus route is
used without further modification, usually by injection; it is called "ox blood".[100] "Meth
oil" refers to the crude methamphetamine base produced by several synthesis
procedures. Ordinarily it is purified by exposure to hydrogen chloride, as a solution or
as a bubbled gas, and extraction of the resulting salt occurs by precipitation and/or
recrystallization with ether/acetone.[100]