methamphetamine n : amphetamine used in the form of a crystalline hydrochloride; used as a stimulant to the nervous system and as an appetite suppressant [syn: methamphetamine hydrochloride, Methedrine, meth, deoxyephedrine, chalk, chicken feed, crank, glass, ice, shabu, trash]

English

Noun

1. A highly addictive phenethylamine stimulant drug, (S)-N-methyl-1-phenylpropan-2-amine.

Synonyms

• ice
• crystal
• crystal meth
• glass
• meth
• methamphetamines
• tweak

Translations

External links

Methamphetamine (/mɛθæmfɛtəmiːn/, a.k.a.methylamphetamine or desoxyephedrine) is a psychostimulant and sympathomimetic drug. The dextrorotatory (S-isomer) dextromethamphetamine can be prescribed to treat attention-deficit hyperactivity disorder, though unmethylated amphetamine is more commonly prescribed. Narcolepsy and obesity can also be treated by the aforementioned isomer under the brand name Desoxyn. It is considered a second line of treatment, used when amphetamine and methylphenidate cause the patient too many side effects. It is only recommended for short term use (~6 weeks) in obesity patients because it is thought that the anorectic effects of the drug are short lived and produce tolerance quickly, whereas the effects on CNS stimulation are much less susceptable to tolerance. It is also used illegally for weight loss and to maintain alertness, focus, motivation, and mental clarity for extended periods of time, and for recreational purposes.

Methamphetamine enters the brain and triggers a cascading release of norepinephrine, dopamine and serotonin. To a lesser extent methamphetamine acts as a dopaminergic and adrenergic reuptake inhibitor and in high concentrations as a monamine oxidase inhibitor (MAOI). Since it stimulates the mesolimbic reward pathway, causing euphoria and excitement, it is prone to abuse and addiction. Users may become obsessed or perform repetitive tasks such as cleaning, hand-washing, or assembling and disassembling objects. Withdrawal is characterized by excessive sleeping, eating, and depression-like symptoms, often accompanied by anxiety and drug-craving. Users of methamphetamine sometimes take sedatives such as benzodiazepines as a means of easing their "come down".

Common nicknames for methamphetamine include "meth", "ice", "crystal", "tina", "p", and "glass". Methamphetamine is sometimes referred to as "speed", but this term is usually used for regular amphetamine or dextroamphetamine.

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 Lazăr Edeleanu.

World War II

One of the earliest uses of methamphetamine was during World War II when 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 ("flyer's chocolate") when given to pilots, or Panzerschokolade ("tanker's chocolate") when given to tank crews. From 1942 until his death in 1945, Adolf Hitler was given frequent intravenous injections of methamphetamine by his personal physician, Theodor Morell as a treatment for depression and fatigue. 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 were related to use of methamphetamine.

Post-war use

After World War II, a large 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, a tradename). The Japanese Ministry of Health banned it in 1951; and its prohibition is thought to have added to the growing yakuza-activities related to illicit drug production. Today, methamphetamine is still associated with the Japanese underworld, but its usage 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 peaked in the 1980s. The December 2, 1989 edition of The Economist described San Diego, California as the "methamphetamine capital of North America."

In 2000, The Economist again described San Diego, California as the methamphetamine capital of North America, and 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, or perhaps in part because of this, usage of methamphetamine expanded throughout rural United States, especially through the Midwest and South.

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, the active ingredients in over-the-counter drugs such as Sudafed and Contac. However, 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.

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 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.

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 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) http://jpet.aspetjournals.org/cgi/content/abstract/321/1/178, indicates that methamphetamine binds to a group of receptors called TAAR. TAAR is a newly discovered receptor system which seems to be affected by a range of amphetamine-like substances called trace amines.

Effects

Common immediate effects.:

• Euphoria
• Increased energy and attentiveness
• Diarrhea, nausea
• Excessive sweating
• Loss of appetite, insomnia, tremor, jaw-clenching (Bruxism)
• Agitation, compulsive fascination with repetitive tasks (Punding)
• Talkativeness, irritability, panic attacks
• Increased libido

Side effects associated with chronic use:

• Drug craving
• Weight loss
• Withdrawal-related depression and anhedonia
• Rapid tooth decay ("meth mouth")
• Amphetamine psychosis
• Dopamine receptor downregulation and hypersensitization
• Axonic degeneration of the dopamine axon terminals in the striatum, frontal cortex, nucleus accumbens, and amygdala

Side effects associated with overdose:

• Brain damage/ Meningitis (Neurotoxicity)
• Formication (sensation of flesh crawling with bugs, with possible associated compulsive picking and infecting sores)
• Paranoia, delusions, hallucinations, which may trigger a tension headache
• Rhabdomyolysis (Muscle breakdown) which leads to Kidney failure

Death from overdose is usually due to stroke, heart failure, but can also be caused by cardiac arrest (sudden death) or hyperthermia.

Buffenstein et al. (1997) showed through SPECT scanning of methamphetamine abusers in Hawaii that brain deterioration continues for months after abstinence, possibly suggesting another unique and pathological feature of methamphetamine.

Pharmacokinetics

The half life of methamphetamine is 9–15 hours. It is excreted by the kidneys and its half life depends on urinary pH. One of the metabolites of methamphetamine is amphetamine.

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 person 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 until neurotransmitter levels are fully replenished, because of the toxic effects on dopaminergic neurons, this can be greater than 2–3 days. 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.

Addiction

Methamphetamine is addictive, especially 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.

Methamphetamine-induced hyperstimulation of pleasure pathways leads to anhedonia. Former users have noted that they feel stupid or dull when they quit using methamphetamine. It is possible that daily administration of the amino acids L-Tyrosine and L-5HTP/Tryptophan can aid in the recovery process by making it easier for the body to reverse the depletion of Dopamine, Norepinephrine, and Serotonin. Although studies involving the use of these amino acids have shown some success, this method of recovery has not been shown to be consistently effective.

It is shown that taking ascorbic acid prior to using methamphetamine 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 methamphetamine dosage had toxicity mediated, yet this will likely be of little avail in solving the serious behavioral problems associated with methamphetamine use that create many of the problems the users experience. Large doses of ascorbic acid also lower urinary pH, reducing methamphetamine's elimination half-life.

To combat addiction, doctors are beginning to use other forms of amphetamine such as dextroamphetamine to break the addiction cycle in a method similar to methadone for heroin addicts. There are no publicly available drugs comparable to naloxone, which blocks opiate receptors and is therefore used in treating opiate dependence, for use with methamphetamine problems. However, experiments with some monoamine reuptake inhibitors such as indatraline have been successful in blocking the action of methamphetamine. There are studies indicating that fluoxetine, bupropion and imipramine may reduce craving and improve adherence to treatment. Research has also suggested that modafinil can help addicts quit methamphetamine use.

Since the phenethylamine phentermine is a constitutional isomer of methamphetamine, it has been speculated that it may be effective in treating methamphetamine addiction. Although phenteremine is a central nervous stimulant that acts on dopamine and norepinephrine, it has not been reported to cause the same degree of euphoria that is associated with other amphetamines.

Abrupt interruption of chronic methamphetamine use results in the withdrawal syndrome in almost 90% of the cases. Withdrawal of amphetamine often causes a depression which is longer and deeper than even the depression from cocaine withdrawal.

Natural occurrence

Methamphetamine occurs naturally in Acacia berlandieri and possibly Acacia rigidula, trees which grow in west Texas. Acacia trees contain numerous other psychoactive compounds (ex.amphetamine, mescaline, nicotine, DMT, ...), but scientific papers specifically mentioning the presence of methamphetamine did not exist until 1997 and 1998.

Medical use

d-Methamphetamine is used medically under the brand name Desoxyn for the following conditions:

• Attention deficit hyperactivity disorder;
• Extreme obesity;
• Narcolepsy

Because of its social stigma and toxicity, Desoxyn is not generally prescribed for ADHD unless other stimulants, such as methylphenidate (Ritalin), dextroamphetamine (Dexedrine) or mixed amphetamines (Adderall) have failed.

Health issues

In an article about his son's addiction to methamphetamine, California writer and former methamphetamine user David Schiff said "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.

Meth mouth

Methamphetamine addicts may lose their teeth abnormally quickly, a condition known as "meth mouth". This effect is not caused by any corrosive effects of the drug itself, which is a common 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.

Hygiene

Serious health and appearance problems are caused by unsterilized needles, lack of hygiene, and especially pollutants in street-grade methamphetamine. The use of methamphetamine may lead to hypertension, damage to heart valves, vastly deteriorated dental health, and increased risk of strokes. Obsessive skin-picking by chronic methamphetamine users may lead to abscesses.

Sexual behaviour

Users may exhibit sexually compulsive behaviour while under the influence. This disregard for the potential dangers of unprotected sex or other reckless sexual behavior may contribute to the spread of sexually transmitted infections (STIs) or sexually transmitted diseases (STDs).

Among the effects reported by methamphetamine users are increased libido and sexual pleasure, the ability to have sex for extended periods of time, 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 prolonged sexual activity, methamphetamine lowers inhibitions and may cause users to behave recklessly or to become forgetful. Users may even report negative experiences after prolonged use, which contradict reported feelings, thoughts, and attitudes achieved at similar dosages under similar circumstances but at earlier periods of an extended or prolonged cycle.

Additionally, many chronic users find themselves engaging in excessive and repeated masturbation. 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 six times less 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 due to vasoconstriction.

Epidemiology of methamphetamine abuse

In the US methamphetamine use is the highest in Native Hawaiians and Pacific islanders (2.2%) and Native Americans (1.7%), lower among whites (0.7%) and Hispanics (0.5%), and much lower in Asians (0.2%) and blacks (0.1%). According to one study in large cities, 13% of men having sex with men used methamphetamine in the previous 6 months.

Use in pregnancy and breastfeeding

Methamphetamine passes through the placenta and is secreted in the breast milk. Half of the newborns whose mothers used methamphetamine during pregnancy experience withdrawal syndrome; this syndrome is relatively mild and required medication in only 4% of the cases. 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.

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

"Smoking" amphetamines 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

Injection is a popular method for use, also known as slamming, but 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, 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.

Other methods

Very little research has focused on suppository or 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 methamphetamine for sexual stimulation as a "butt rocket," "booty bump," "keistering,", "plugging," "shelving," or "bumming" 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 membranes lining its walls. Another way of ingesting methamphetamine is to crush the crystals up and insufflate (snort) them. This also bypasses first pass metabolism and goes straight into the bloodstream.

Illicit production

• Party and Play
• Phenethylamines
• Clandestine chemistry
• Amphetamine
• Propylhexedrine
• Illegal drug trade
• Entomotoxicology

References

• Poison Information Monograph (PIM 334: Methamphetamine)
• Chronic Amphetamine Use and Abuse A very thorough review on the effects of chronic use (American College of Neuropsychopharmacology)
• Methamphetamine Use: Clinical and Forensic Aspects, by Errol Yudko, Harold V. Hall, and Sandra B. McPherson. CRC Press, Boca Raton, Fl, 2003.

Footnotes

Documentaries

• The Ice Age - ABC Australia - 4 Corners - Australian methamphetamine use.
• Frontline - The Meth Epidemic - PBS United States - Frontline - The Meth Epidemic

External links

• NLM Hazardous Substances Data Bank - Entry for d-methamphetamine
• Erowid Methamphetamine Vault
• [http://www.emcdda.europa.eu?nnodeid=25480 EMCDDA drugs profiles: Methamphetamine (2007)]
• A Key to Methamphetamine-Related Literature - A comprehensive thematic index of methamphetamine research published in academic and scientific journals with links from citations to the PubMed abstracts.
  • Meth FAQ - More detailed synthesis and synthesis from other sources.
• DEA's Methamphetamine News Releases