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Research
Animal models have shown that low-dose methamphetamine improves cognitive and behavioural functioning following TBI (traumatic brain injury). This is in contrast to high, repeated doses which cause neurotoxicity. These models demonstrate that low-dose methamphetamine increases neurogenesis and reduces apoptosis in the dentate gyrus of the hippocampus following TBI. It has also been found that TBI patients testing positive for methamphetamine at the time of emergency department admission have lower rates of mortality.
It has been suggested, based on animal research, that calcitriol, the active metabolite of vitamin D, can provide significant protection against the DA- and 5-HT-depleting effects of neurotoxic doses of methamphetamine. Protection against methamphetamine-induced neurotoxicity has also been observed following administration of ascorbic acid (vitamin C), cobalamin (vitamin B12), and vitamin E
Trafficking
The Golden Triangle (Southeast Asia), specifically Shan State, Myanmar, is the world’s leading producer of methamphetamine as production has shifted to ya ba and crystalline methamphetamine, including for export to the United States and across East and Southeast Asia and the Pacific.
Concerning the accelerating synthetic drug production in the region, the Cantonese Chinese syndicate Sam Gor, also known as The Company, is understood to be the main international crime syndicate responsible for this shift. It is made up of members of five different triads. Sam Gor is primarily involved in drug trafficking, earning at least $8 billion per year. Sam Gor is alleged to control 40% of the Asia-Pacific methamphetamine market, while also trafficking heroin and ketamine. The organization is active in a variety of countries, including Myanmar, Thailand, New Zealand, Australia, Japan, China, and Taiwan. Sam Gor previously produced meth in Southern China and is now believed to manufacture mainly in the Golden Triangle, specifically Shan State, Myanmar, responsible for much of the massive surge of crystal meth in circa 2019. The group is understood to be headed by Tse Chi Lop, a gangster born in Guangzhou, China who also holds a Canadian passport.
Liu Zhaohua was another individual involved in the production and trafficking of methamphetamine until his arrest in 2005. It was estimated over 18 tonnes of methamphetamine were produced under his watch
Synthesis
Further information on illicit amphetamine synthesis: History and culture of substituted amphetamines Illegal synthesis
Racemic methamphetamine may be prepared starting from phenylacetone by either the Leuckart or reductive amination methods. 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. In this reaction, an iminium cation is formed as an intermediate which is reduced by the second equivalent of N-methylformamide. The intermediate formyl amide is then hydrolyzed under acidic aqueous conditions to yield methamphetamine as the final product. Alternatively, phenylacetone can be reacted with methylamine under reducing conditions to yield methamphetamine
In addition to its effect on the plasma membrane monoamine transporters, methamphetamine inhibits synaptic vesicle function by inhibiting VMAT2, which prevents monoamine uptake into the vesicles and promotes their release.This results in the outflow of monoamines from synaptic vesicles into the cytosol (intracellular fluid) of the presynaptic neuron, and their subsequent release into the synaptic cleft by the phosphorylated transporters.[153] Other transporters that methamphetamine is known to inhibit are SLC22A3 and SLC22A5. SLC22A3 is an extraneuronal monoamine transporter that is present in astrocytes, and SLC22A5 is a high-affinity carnitine transporter.
Methamphetamine is also an agonist of the alpha-2 adrenergic receptors and sigma receptors with a greater affinity for σ1 than σ2, and inhibits monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). Sigma receptor activation by methamphetamine may facilitate its central nervous system stimulant effects and promote neurotoxicity within the brain.Dextromethamphetamine is a stronger psychostimulant, but levomethamphetamine has stronger peripheral effects, a longer half-life, and longer perceived effects among heavy substance users. At high doses, both enantiomers of methamphetamine can induce similar stereotypy and methamphetamine psychosis, but levomethamphetamine has shorter psychodynamic effects
