Methamphetamine (pronounced /ˌmɛθæmˈfɛtəmiːn/ also known as metamfetamine (INN), dextromethamphetamine , methylamphetamine , N-methylamphetamine , and desoxyephedrine ) is a psychostimulant and sympathomimetic drug. Methamphetamine enters the brain and triggers a cascading release of dopamine and norepinephrine. It is highly active in the mesolimbic reward pathways of the brain, inducing intense euphoria, with a high potential for addiction. To a lesser extent, methamphetamine releases serotonin and acts as a dopaminergic and adrenergic reuptake inhibitor with higher concentrations serving as a monoamine oxidase inhibitor. Users may become hypersexual or obsessed with a task, thought or activity. Withdrawal is characterized by excessive sleeping, eating, and depression, often accompanied by anxiety and drug-craving. Methamphetamine users may take sedatives such as benzodiazepines as a means of easing their comedown, anxiety, or difficulty sleeping.
Methamphetamine has medical uses as well as the potential to cause addiction. Methamphetamine addiction typically occurs when a person begins to use the drug illicitly, most often in its crystalline form (crystal methamphetamine) for its powerful enhancing effects on mood and energy. Tolerance quickly develops, and users have greater difficulty functioning and experiencing pleasure without the drug.
Nicknames for methamphetamine are numerous and vary significantly from region to region, some common nicknames for methamphetamine include "ice", "crystal", "meth", "crank", "glass", "speed" (USA & Canada), "shabu" or "syabu" (Japan and Philippines), "tik" (South Africa), and "ya ba" (Thailand).
History
Methamphetamine was first synthesized from ephedrine in Japan in 1893 by chemist Nagayoshi Nagai. In 1919, crystallized methamphetamine was synthesized by Akira Ogata via reduction of ephedrine using red phosphorus and iodine.
World War II
One of the earliest uses of methamphetamine was during World War II when it was used by various Allied and Axis forces. The German military dispensed it under the trade name Pervitin . It was widely distributed across rank and division, from elite forces to tank crews and aircraft personnel. Chocolates dosed with methamphetamine were known as Fliegerschokolade ("airmen's chocolate") when given to pilots, or Panzerschokolade ("tank chocolate") when given to tank crews. From 1942 until his death in 1945, Adolf Hitler may have been given intravenous injections of methamphetamine by his personal physician Theodor Morell. It is possible that it was used to treat Hitler's speculated Parkinson's disease, or that his Parkinson-like symptoms which developed from 1940 onwards resulted from using methamphetamine.
Post-war use
After World War II, a large supply of amphetamine stockpiled by the Japanese military became available in Japan under the street name shabu (also Philopon, pronounced Hiropon , a tradename). The Japanese Ministry of Health banned it in 1951; since then it has been increasingly produced by the yakuza criminal organization. Today methamphetamine is still associated with the Japanese underworld, and its use is discouraged by strong social taboos.
In the 1950s there was a rise in the legal prescription of methamphetamine to the American public. According to the 1951 edition of Pharmacology and Therapeutics by Arthur Grollman, it was to be prescribed for "narcolepsy, post-encephalitic Parkinsonism, alcoholism, ... in certain depressive states... and in the treatment of obesity."
The 1960s saw the start of significant use of clandestinely manufactured methamphetamine as well as methamphetamine created in users' own homes for personal use. The recreational use of methamphetamine continued into the 1980s. San Diego, California was described as the "methamphetamine capital of North America" in the December 2, 1989 edition of The Economist and again in 2000, also with South Gate, California as the second capital city.
Legal restrictions
In 1983 laws were passed in the United States prohibiting possession of precursors and equipment for methamphetamine production; this was followed a month later by a bill passed in Canada enacting similar laws. In 1986 the U.S. government passed the Federal Controlled Substance Analogue Enforcement Act in an attempt to curb the growing use of designer drugs. Despite this, use of methamphetamine expanded throughout rural United States, especially through the Midwest and South. Predictably, restrictions on laboratory equipment have caused clandestine laboratories to switch from flasks and beakers to mason jars and plastic kitchenware.
Since 1989 five U.S. federal laws and dozens of state laws have been imposed in an attempt to curb the production of methamphetamine. Methamphetamine can be produced in home laboratories using pseudoephedrine or ephedrine, which at the time were the active ingredients in over-the-counter drugs such as Sudafed and Contac. Preventative legal strategies of the past 17 years have steadily increased restrictions to the distribution of pseudoephedrine/ephedrine-containing products.
As a result of the U.S. Combat Methamphetamine Epidemic Act of 2005, a subsection of the PATRIOT Act, there are restrictions on the amount of pseudoephedrine and ephedrine one may purchase in a specified time period, and further requirements that these products must be stored in order to prevent theft. Increasingly strict restrictions have resulted in the reformulation of many over-the-counter drugs, and some such as Actifed have been discontinued entirely in the United States.
Pharmacology
A member of the family of phenylethylamines, methamphetamine is chiral, with two isomers, levorotary and dextrorotatory. The levorotary form, called levomethamphetamine, is an over-the-counter drug used in inhalers for nasal decongestion. Levomethamphetamine does not possess any significant central nervous system activity or addictive properties. This article deals only with the dextrorotatory form, called dextromethamphetamine, and the racemic form.
Methamphetamine is a potent central nervous system stimulant which affects neurochemical mechanisms responsible for regulating heart rate, body temperature, blood pressure, appetite, attention, mood and responses associated with alertness or alarm conditions. The acute physical effects of the drug closely resemble the physiological and psychological effects of an epinephrine-provoked fight-or-flight response, including increased heart rate and blood pressure, vasoconstriction (constriction of the arterial walls), bronchodilation, and hyperglycemia (increased blood sugar). Users experience an increase in focus, increased mental alertness, and the elimination of fatigue, as well as a decrease in appetite.
The methyl group is responsible for the potentiation of effects as compared to the related compound amphetamine, rendering the substance on the one hand more lipid soluble and easing transport across the blood brain barrier, and on the other hand more stable against enzymatic degradation by MAO. Methamphetamine causes the norepinephrine, dopamine and serotonin (5HT) transporters to reverse their direction of flow. This inversion leads to a release of these transmitters from the vesicles to the cytoplasm and from the cytoplasm to the synapse (releasing monoamines in rats with ratios of about NE:DA = 1:2, NE:5HT= 1:60), causing increased stimulation of post-synaptic receptors. Methamphetamine also indirectly prevents the reuptake of these neurotransmitters, causing them to remain in the synaptic cleft for a prolonged period (inhibiting monoamine reuptake in rats with ratios of about: NE:DA = 1:2.35, NE:5HT = 1:44.5).
Methamphetamine is a potent neurotoxin, shown to cause dopaminergic degeneration. High doses of methamphetamine produce losses in several markers of brain dopamine and serotonin neurons. Dopamine and serotonin concentrations, dopamine and 5HT uptake sites, and tyrosine and tryptophan hydroxylase activities are reduced after the administration of methamphetamine. It has been proposed that dopamine plays a role in methamphetamine induced neurotoxicity because experiments which reduce dopamine production or block the release of dopamine decrease the toxic effects of methamphetamine administration. When dopamine breaks down it produces reactive oxygen species such as hydrogen peroxide. It is likely that the approximate 1200% increase in dopamine levels and subsequent oxidative stress that occurs after taking methamphetamine mediates its neurotoxicity. It has been demonstrated that a high ambient temperature increases the neurotoxic effects of methamphetamine.
Recent research published in the Journal of Pharmacology And Experimental Therapeutics (2007) indicates that methamphetamine binds to and activates a G protein-coupled receptor called TAAR1. TAARs are a newly discovered receptor family whose members are activated by a number of amphetamine-like molecules called trace amines, thyronamines and certain volatile odorants.
Effects
Physical effects
Physical effects can include anorexia, hyperactivity, dilated pupils, flushing, restlessness, dry mouth, headache
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