Methamphetamine

Methamphetamine (methylamphetamine or desoxyephedrine), popularly shortened to meth, is a psychostimulant drug used primarily for recreational purposes, but also prescribed for attention-deficit hyperactivity disorder or narcolepsy under the brand name Desoxyn.

The drug causes euphoria and excitement by acting directly on the brain's reward mechanisms, thus making it prone to abuse and addiction. Methamphetamine rapidly enters the brain and triggers a cascading release of norepinephrine and dopamine (and to a lesser extent, serotonin). Users may become obsessed or perform repetitive tasks such as cleaning, hand-washing or assembling and disassembling objects. Withdrawal is characterized by increased sleeping and eating, and depression-like symptoms, often accompanied by anxiety and drug-craving.

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. The related compound amphetamine was first synthesized in Germany in 1887 by Lazar Edeleanu.

One of the earliest uses of amphetamine occurred during World War II when the German military dispensed the stimulant under the trade name Pervitin to troops. The drug was widely distributed across rank and division, from elite forces to tank crews and aircraft personnel. Chocolates dosed with methamphetamine were known as Fliegerschokolade ("flyer's chocolate") when given to pilots, or Panzerschokolade ("tanker's chocolate") when distributed to tank crews. From 1942 until his death in 1945, Adolf Hitler was given daily intravenous injections of methamphetamine by his personal physician, Theodor Morell, as a treatment for depression and fatigue. It is possible that the Parkinsons-like symptoms which Hitler increasingly developed from 1940 onwards were related to his use of this drug.

After World War II, a massive supply of amphetamine, formerly stockpiled by the Japanese military, became available in Japan under the street name shabu (also Philopon (pronounced ヒロポン, or Hiropon), its tradename there. ) The Japanese Ministry of Health banned it in 1951, which is thought to have added to the growing yakuza activities related to illicit drug production. Today, the Japanese underworld is still associated with the drug, although its use is discouraged by strong social taboos.

With the 1950s came 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 the significant use of clandestine manufacture and people creating methamphetamine in their homes for personal use. The recreational use of methamphetamine sky-rocketed in the 1980s. The December 2, 1989 edition of The Economist described San Diego, California as the "methamphetamine capital of North America."

In 1983, U.S. laws prohibiting the possession of precursors and equipment for methamphetamine production were passed; Canada followed a month later by passing a similar bill. In 1986, the U.S. government passed the Federal Controlled Substance Analogue Enforcement Act in an attempt to combat the growing use of designer drugs. In spite of this, its use expanded throughout the rural United States, especially in the Midwest and South.

Since 1989, five Federal laws and dozens of state laws have been implemented to combat the production of methamphetamine. Methamphetamine is easily “cooked up” in home laboratories using pseudoephedrine and/or ephedrine, the active ingredients in over-the-counter drugs such as Sudafed and Contac. Thus, preventive legal strategies over the past 17 years have steadily strengthened restrictions on the distribution of pseudoephedrine/ephedrine-containing products. The current Federal standard, as of January 2006, restricts the amount of pseudoephedrine and ephedrine an individual may purchase in a designated time period, and it requires that such products are stored in such a way as to prevent theft.

On August 8, 2005, an issue of Newsweek devoted a cover story to methamphetamine and its abuse, including criticism of the Bush administration's policies regarding the drug. Newsweek blamed the administration for not devoting enough resources to education about and prevention of the drug's use. The Bush administration has countered with the position that cannabis is a dangerous "gateway drug," so prevention of cannabis use should prevent potential abusers from trying and becoming hooked on "hard" drugs such as methamphetamine.

Meanwhile, the online magazine Slate posted an article in reaction to the Newsweek article, attacking Newsweek for failing to appropriately cite sources and data to back up the claim that this is a "new" problem. The topic remains controversial. The most recent figures released by the Federal government indicate that, contrary to public perception, methamphetamine use has actually declined nationally in recent years.

Production
Methamphetamine is most structurally similar to methcathinone and amphetamine. In illicit production, it is commonly made by the reduction of ephedrine or pseudoephedrine. Most of the necessary chemicals are readily available in household products or over-the-counter medicines. Synthesis is relatively simple, but most methods involve flammable and corrosive chemicals, particularly the solvents used in extraction and purification. As a result, clandestine production is often discovered due to fires and/or explosions caused by improper handeling of volatile/flammable solvents.

Most production methods involve hydrogenation of the hydroxyl group on the ephedrine or pseudoephedrine molecule. The most common method for small-scale methamphetamine labs in the United States is primarily called the "Red, White, and Blue Process", which involves red phosphorus, Pseudoephedrine or Ephedrine(white), and blue iodine which forms hydroiodic acid. This is a fairly dangerous process for amateur chemists. The red phosphorus production method can create phosphine gas, which is extremely toxic when inhaled. An increasingly common method utilizes a Birch reduction process, where metallic lithium is substituted for metallic sodium (due to the difficulty in obtaining metallic sodium). The Birch reduction is dangerous since the alkali metal and liquid anhydrous ammonia are both extremely reactive, and because the temperature of liquid ammonia makes it susceptible to explosive boiling when reactants are added. PS. Anhydrous Ammonia and Lithium/Sodium aka Birch Reduction has surpassed the 57-55% Hydriotic Acid (Catalytic Hydrogenation) as the most common method of manufacturing methamphetamine in the USA, and many believe this is the case in Mexico as well. You see the pictures of RP+I2=HI super labs that have been busted because they require much more complex of equipment thus breakdown time, exposure, etc. than a jar with LI + Nh3 incurs.

A completely different synthesis procedure involves creating methamphetamine by the reductive amination of phenylacetone with methylamine, both of which are currently DEA list I chemicals (as are pseudoephedrine and ephedrine). The reaction requires a catalyst that acts as a reducing agent, such as mercury-aluminum amalgam or platinum dioxide, also known as Adams' catalyst. This was once the preferred method of production by motorcycle gangs in California, but DEA restrictions on the chemicals have made this an uncommon way to produce the drug today.

Other less-common methods use other means of hydrogenation, such as hydrogen gas in the presence of a catalyst.

One of the more obvious signs of a production lab of methamphetamine in operation is an odor similar to that of cat urine. Meth labs can also give off noxious fumes, such as phosphine gas, mercury vapors, lead, methylamine gas, solvent fumes; such as acetone or chloroform, iodine vapors, white phosphorus, anhydrous ammonia, hydrogen chloride/muriatic acid, hydrogen iodide, lithium/sodium metal, ether, or methamphetamine vapors.

When performed by individuals who are not trained chemists, methamphetamine manufacture can lead to extremely dangerous situations. For example, if an amateur chemist allows the red phosphorus to overheat, due to lack of proper ventilation, phosphine gas can be produced. When produced in large quantities, the gas usually explodes, due to autoignition from diphosphine formation caused by overheating phosphorus.

Until the early 1990s, methamphetamine for the US market was made mostly in labs run by drug traffickers in Mexico and California. Since then, however, authorities have discovered increasing numbers of small-scale methamphetamine labs all over the United States, mostly located in rural, suburban, or low-income areas. The Indiana state police found 1,260 labs in 2003, compared to just 6 in 1995, although this may be a result of increased police activity rather than more manufacturing of the drug. Recently, mobile and motel-based methamphetamine labs have caught the attention of both the US news media and law enforcement agencies. The labs can cause explosions and fires, as well as expose the public to hazardous chemicals. Individuals who manufacture methamphetamine are often harmed by toxic gases. Many police departments have responded by creating specialized task forces with specialized training to respond to methamphetamine production scenarios. However, the National Drug Threat Assessment 2006, produced by the Department of Justice, found "decreased domestic methamphetamine production in both small and large-scale laboratories" but also stated that "decreases in domestic methamphetamine production have been offset by increased production in Mexico." They concluded that "methamphetamine availability is not likely to decline in the near term."

Since the passage of the methamphetamine act into law and therefore the increased difficulty of finding precursors, there have been manufacturing operations involving the extraction of methamphetamine from the urine of heavy users.

Distribution
A wide variety of groups are involved in the distribution of methamphetamine, from prison gangs and motorcycle gangs to street gangs, traditional organized crime operations, and impromptu small networks made up of users. Because of the ease of synthesis from over-the-counter medicines, clandestine manufacture is very common. The government of North Korea has supposedly been linked to the manufacture and distribution of methamphetamine, and allegedly plays a role in distribution networks throughout Asia as well as those in Australia and even in North America.

Black market
In the U.S., illicit methamphetamine comes in a variety of forms, with an average price of $150 per gram of pure substance. Most commonly it is found as a colorless crystalline solid, sold on the street under the name crystal meth and a variety of other names. It is also sold as a less pure crystalline powder called crank, or in crystalline rock form. Colourful flavored pills containing methamphetamine and caffeine are known as yaba (Thai for "crazy medicine"). At its most impure, it is sold as a crumbly brown or off-white rock commonly referred to as "peanut butter crank." Methamphetamine found on the street is rarely pure, but adulterated with chemicals that were used to synthesize it. It may be diluted or "cut" with non-psychoactive substances like inositol.

d-Methamphetamine
d-Methamphetamine is used medically under the brand name Desoxyn for the following conditions: Because of its social stigma, Desoxyn is not generally prescribed for ADHD unless other stimulants, such as methylphenidate (Ritalin®), dextroamphetamine (Dexedrine®) or mixed amphetamines (Adderall®) have failed.
 * Attention deficit hyperactivity disorder
 * Extreme obesity
 * Narcolepsy
 * Decongestant

l-Methamphetamine
l-Methamphetamine is available over the counter as Vicks inhaler as a nasal decongestant. l-Methamphetamine alone can raise blood pressure and cause the heart to beat rapidly due to its effects mimicking the sympathetic nervous system, but is not thought to be nearly as addictive or centrally active as the d- isomer of methamphetamine. Its common side effects include muscle tremors and stomach cramps.

Pharmacology
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 methyl group is responsible for the potentiation of effects as compared to the related compound amphetamine, rendering the substance more lipid soluble and easing transport across the blood brain barrier.

Methamphetamine causes the norepinephrine and dopamine 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, 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. Serotonin levels are only weakly affected (ratio NE: DA = 2:1, NE:5HT = 60:1). It is a potent neurotoxin, shown to cause dopaminergic degeneration.

The acute 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.

Tolerance
As with other amphetamines, tolerance to methamphetamine is not completely understood, but known to be sufficiently complex that it cannot be explained by any single mechanism. The extent of tolerance and the rate at which it develops varies widely between individuals, and even within one individual it is highly dependent on dosage, duration of use and frequency of administration. Many cases of narcolepsy are treated with methamphetamine for years without escalating doses or any apparent loss of effect.

Short term tolerance can be caused by depleted levels of neurotransmitters within the vesicles available for release into the synaptic cleft following subsequent reuse (tachyphylaxis). Short term tolerance typically lasts 2-3 days, until neurotransmitter levels are fully replenished. Prolonged overstimulation of dopamine receptors caused by methamphetamine may eventually cause the receptors to downregulate in order to compensate for increased levels of dopamine within the synaptic cleft. To compensate, larger quantities of the drug are needed in order to achieve the same level of effects.

Immediate and Chronic Effects
Common immediate side effects:
 * Euphoria
 * Increased energy and attentiveness
 * Diarrhea, nausea
 * Loss of appetite, insomnia, tremor, jaw-clenching (Bruxism)
 * Agitation, compulsive fascination with repetitive tasks (Punding)
 * Talkativeness, irritability, panic attacks
 * Increased libido
 * Dilated pupils

Side effects associated with chronic use: Side effects associated with overdose:
 * Drug craving
 * Weight loss
 * Withdrawal-related depression and anhedonia
 * Rapid tooth decay ("meth mouth")
 * Amphetamine psychosis
 * Brain damage (Neurotoxicity)
 * Formication (sensation of flesh crawling with bugs, with possible associated compulsive picking and infecting sores)
 * Paranoia, delusions, hallucinations
 * Kidney damage (from Hyperkalemia)

Overdose fatalities are usually due to stroke or heart failure, but can also be caused by hyperthermia or kidney failure.

Meth Mouth
Methamphetamine addicts may lose their teeth abnormally quickly, a condition known as "meth mouth". This effect is not caused by "corrosive" effects that meth itself has on teeth as per commonly repeated myth. According to the American Dental Association, meth mouth "is probably caused by a combination of drug-induced psychological and physiological changes resulting in xerostomia (dry mouth), extended periods of poor oral hygiene, frequent consumption of high calorie, carbonated beverages and tooth grinding and clenching." Similar, though far less severe symptoms have been reported in clinical use of other amphetamines, where effects are not exacerbated by a lack of oral hygiene for extended periods. Like other substances which stimulate the sympathetic nervous system, methamphetamine causes decreased production of acid-fighting saliva and increased thirst, resulting in increased risk for tooth decay, especially when thirst is quenched by high-sugar drinks.

Sexual Behavior
Users may exhibit sexually compulsive behavior and may engage in sexual acts with one or more individuals. This sexual behavior is believed to have created a link between meth use and sexually transmitted disease (STD) transmission, especially HIV and syphilis.

Among the effects reported by methamphetamine users (known as "tweakers") is an increase in the need and urgency for sex, the ability to have sex for extended periods (hours or even days), and an inability to ejaculate or reach orgasm or physical release.

In addition to increasing the need for sex and enabling the user to engage in marathon sex sessions, methamphetamine lowers inhibitions and causes users to behave recklessly or to become forgetful. According to a recent San Diego study, methamphetamine users often engage in unsafe sexual activities, and forget or choose not to use condoms. The study found that methamphetamine users were a sixth as likely to use condoms.

The urgency for sex combined with the inability to achieve release (ejaculation) can result in tearing, chafing, and trauma (such as rawness and friction sores) to the sex organs, the rectum, and mouth dramatically increasing the risk of transmission of HIV and other sexually transmitted diseases. Methamphetamine also causes erectile dysfunction (though the term has more rarely been used to describe the extreme urge for sex experienced by many methamphetamine users), which often leads people to decide to engage in receptive anal sex or fisting.

Addiction
Methamphetamine is highly addictive, particularly when injected or smoked. While not life-threatening, withdrawal is often intense and, as with all addictions, relapse is common. To combat relapse, many recovering addicts attend 12 Step meetings, such as Crystal Meth Anonymous.

In an article about his son's addiction to methamphetamine, a California writer who has also experimented with the drug put it this way: This drug has a unique, horrific quality. In an interview, Stephan Jenkins, the singer in the band Third Eye Blind, said that methamphetamine makes you feel 'bright and shiny.' It also makes you paranoid, incoherent and both destructive and pathetically and relentlessly self-destructive. Then you will do unconscionable things in order to feel bright and shiny again.

Former users have noted that they feel stupid or dull when they quit using methamphetamine. This is because the brain is adapting a need for methamphetamine to think faster, or at what seems to be a higher level. Individuals with ADHD may be at higher risk for addiction to methamphetamine, because the drug increases the user's ability to focus and reduces impulsivity. Because of its abuse potential, meth is not generally prescribed for ADHD unless other stimulants, such as methylphenidate (Ritalin®), dextroamphetamine (Dexedrine®) or mixed amphetamines (Adderall®) have failed.

With long-term use, abstinence often leads to slow thinking and depression, which in turn requires that the addict use more meth to 'fix' it. A chronic pattern of such behavior is known colloquially as "The Vampire Life." It is shown that taking ascorbic acid prior to using meth may help reduce acute toxicity to the brain, as rats given the human equivalent of 5-10 grams of ascorbic acid 30 minutes prior to meth dosage had toxicity mediated, yet this will likely be of little avail in solving the serious behavioral problems associated with meth use that create many of the problems the users experience.

Serious drug addiction correlates with poor hygiene and general self-care, and even minor health problems can lead to serious complications when left untreated. Striking health problems popularly associated with methamphetamine addiction, such as severe tooth decay or massive skin infections, are caused by unsterilized needles and a lack of hygiene. Even long-term use does not generally result in outward symptoms, but may lead to hypertension, damage to heart valves, and increased risk of strokes.

To combat addiction, doctors are beginning to use other, less volatile forms of amphetamine such as dexamphetamine to break the addiction cycle in a method similar to methadone for heroin addicts. There are no known drugs comparable to naloxone that blocks opiate poisoning, and is sometimes used in treating opiate addicts, for use with methamphetamine problems.

Routes of administration
The usual route for medical use is oral administration. In recreational use it can be swallowed, snorted, smoked, dissolved in water and injected (or even without water, in what is called a dry shot), inserted anally (with or without dissolution in water; also known as a booty bump), or into the urethra. As with all addictive drugs, the potential for addiction is greater when it is delivered by methods that cause the concentration in the blood to rise quickly, principally because the effects desired by the user are felt more quickly and with a higher intensity than through a moderated delivery mechanism. In fact, studies have shown that the subjective pleasure of drug use (the reinforcing component of addiction) is proportional to the rate that the blood level of the drug increases. In general, smoking is the fastest mechanism (i.e., it causes the blood concentration to rise the most quickly in the shortest period of time as it allows the substance to travel to the brain through a more direct route than intravenous injection), followed by injecting, anal insertion, insufflation and swallowing.

"Smoking" methamphetamine actually refers to vaporizing it to produce fumes, rather than burning and inhaling the resulting smoke, as with tobacco. It is commonly smoked in glass pipes, or in aluminum foil heated by a flame underneath. This method is also known as "chasing the white dragon" (as derived from the method of smoking heroin known as "chasing the dragon"). There is little evidence that methamphetamine inhalation results in greater toxicity than any other route of administration. Lung damage has been reported with long-term use, but manifests in forms independent of route (pulmonary hypertension and associated complications), or limited to injection users (pulmonary emboli).

Injection is a popular method for use, but potentially carries quite serious risks. The hydrochloride salt of methamphetamine is soluble in water; injection users may use any dose from 125 mg to over a gram in one I.V. dose using a small needle. This dosage range may be fatal to non-addicts; addicts rapidly develop tolerance to the drug. Injection users often experience skin rashes (sometimes called "speed bumps") and infections at the site of injection. As with any injected drug, if a group of users shares a common needle or any type of injecting equipment without sterilization procedures, blood-borne diseases such as HIV or hepatitis can be transmitted as well.

Very little research has focused on anal insertion as a method, and anecdotal evidence of its effects is infrequently discussed, possibly due to social taboos in many cultures regarding the anus. This is often known within communities that use meth for sexual stimulation as a "booty bump," "keistering," or "plugging," and is anecdotally reported to increase sexual pleasure while the effects of the drug last. The rectum is where the majority of the drug would likely be taken up, through the mucous membranes lining its walls. (See Methamphetamine and sex for further information on other risk factors.)

Australia
The medical use of methamphetamine is not recognised in Australia.

Canada
Methamphetamine is not approved for medical use in Canada. As of 2005, it falls under Schedule I of the Controlled Drugs and Substances Act. The maximum penalty for the production and distribution is imprisonment for life.

Hong Kong
Methamphetamine is regulated under Schedule 1 of Hong Kong's Chapter 134 Dangerous Drugs Ordinance. It can only be used legally by health professionals and for university research purposes. The substance can be be given by pharmacists under a prescription. Anyone who supplies the substance without prescription can be fined $10000(HKD). The penalty for trafficking or manufacturing the substance is a $5,000,000 (HKD) fine and life imprisonment. Possession of the substance for consumption without license from the Department of Health is illegal with a $1,000,000 (HKD) fine and/or 7 years of jail time.

The Netherlands
Methamphetamine is not approved for medical use in The Netherlands. It falls under Schedule I of the Opium Act. Although production and distribution of this drug are prohibited, few people who were caught with a small amount for personal use have been prosecuted.

New Zealand
Methamphetamine is a Class A controlled drug under the New Zealand Misuse of Drugs Act 1975. The maximum penalty for production and distribution is imprisonment for life. While in theory a doctor could prescribe it for an appropriate indication, this would require case-by-case approval by the director-general of public health. In New Zealand, Methamphetamine is most commonly referred to by the street name P (short for "pure methamphetamine" ).

South Africa
In South Africa, methamphetamine is classified as a Schedule 5 drug, and is listed as Undesirable Dependence-Producing Substances in Part III of Schedule 2 of the Drugs and Drug Trafficking Act, 1992 (Act No 140 of 1992). Commonly called Tik, it is mostly abused by youths under the age of 20 in the Cape Flats areas.

United Kingdom
As of 18th January 2007, methamphetamine is classified as a Class A drug under the Misuse of Drugs Act 1971 following a recommendation made by the Advisory Council on the Misuse of Drugs in June 2006. It had previously been classified as a Class B drug, except when prepared for injection.

United States
Methamphetamine is classified as a Schedule II substance by the Drug Enforcement Administration under the Convention on Psychotropic Substances. It is available by prescription under the trade name Desoxyn, manufactured by Ovation Pharma. While there is technically no difference between the laws regarding methamphetamine and other controlled stimulants, most medical professionals are averse to prescribing it due to its notoriety.

Illicit methamphetamine has become a major focus of the 'war on drugs' in the United States in recent years. In addition to federal laws, somes states have placed additional restrictions on the sale of precursor chemicals commonly used to synthesize methamphetamine, particularly pseudoephedrine, a common over-the-counter decongestant. In 2005, the DEA seized 2,148.6kg of methamphetamine.

In 2005, the Combat Methamphetamine Epidemic Act of 2005 was passed as part of the USA PATRIOT Act, putting restrictions on the sale of methamphetamine precursors.

On November 7, 2006, the US Department of Justice declared that November 30, 2006 be Methamphetamine Awareness Day.

Legality of similar chemicals
See pseudoephedrine and ephedrine for legal restrictions in place as a result of their use as a precursors in the clandestine manufacture of methamphetamine.

Television

 * The Ice Age - ABC Australia - 4 Corners - Australia's Crystal Meth Abuse, Effects & Treatment (Dextroamphetamine)


 * Frontline - The Meth Epidemic - PBS United States - Frontline - The Meth Epidemic


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