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Methamphetamine causes the ], ] and ] (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 ]:] = 1:2, NE:]= 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<ref>Rothman, et al. "Amphetamine-Type Central Nervous System Potently than they Release Dopamine and Serotonin." (2001): Synapse ''39'', 32-41 (Table V. on page 37)</ref>). Methamphetamine causes the ], ] and ] (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 ]:] = 1:2, NE:]= 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<ref>Rothman, et al. "Amphetamine-Type Central Nervous System Potently than they Release Dopamine and Serotonin." (2001): Synapse ''39'', 32-41 (Table V. on page 37)</ref>).


Methamphetamine is a potent neurotoxin, shown to cause dopaminergic degeneration.<ref>{{cite journal | author = Itzhak Y, Martin J, Ali S | title = Methamphetamine-induced dopaminergic neurotoxicity in mice: long-lasting sensitization to the locomotor stimulation and desensitization to the rewarding effects of methamphetamine | journal = Prog Neuropsychopharmacol Biol Psychiatry | volume = 26 | issue = 6 | pages = 1177–83 | year = 2002 | pmid = 12452543 | doi = 10.1016/S0278-5846(02)00257-9}}</ref><!-- This corresponds to a human equivalent dose of at least 100 mg! Even higher on a simple mg/kg basis, which is probably a better measure for acute toxicity. --><ref>{{cite journal | author = C. Davidson, A. J. Gow, T. H. Lee, E. H. Ellinwood | title = Methamphetamine neurotoxicity: necrotic and apoptotic mechanisms and relevance to human abuse and treatment | journal = Brain Research Reviews | volume = 36 | issue = 1 | pages = 1–22 | year = 2001 | doi = 10.1016/S0165-0173(01)00054-6}}</ref> 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 ] such as hydrogen peroxide. It is likely that the approximate 1200% increase in dopamine (vs. 350% ], which is not considered neurotoxic)<ref></ref> and subsequent oxidative stress that occurs after taking methamphetamine mediates its neurotoxicity.<ref>{{cite journal | url = http://jpet.aspetjournals.org/cgi/content/full/287/1/107 | author = Yamamoto, B. and Zhu, W. | title = The Effects of Methamphetamine on the Production of Free Radicals and Oxidative Stress | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 287 | issue = 1 | pages = 107–114 | month= October | year= 1998 | accessdate=2007-11-19 | pmid = 9765328 | day = 01}}</ref> It has been demonstrated that a high ambient temperature increases the neurotoxic effects of methamphetamine.<ref>{{cite journal | url = http://jpet.aspetjournals.org/cgi/content/abstract/jpet.105.096503v1 | journal = The Journal of Pharmacology and Experimental Therapeutics | title = Relationship between Temperature, Dopaminergic Neurotoxicity, and Plasma Drug Concentrations in Methamphetamine-Treated Squirrel Monkeys | volume = 316 | issue = 3 | year= 2006 | pages = 1210–1218 | accessdate = 2007-11-20 | pmid = 16293712 | doi = 10.1124/jpet.105.096503 | author = Yuan, J. }}</ref> Methamphetamine is a potent neurotoxin, shown to cause dopaminergic degeneration.<ref>{{cite journal | author = Itzhak Y, Martin J, Ali S | title = Methamphetamine-induced dopaminergic neurotoxicity in mice: long-lasting sensitization to the locomotor stimulation and desensitization to the rewarding effects of methamphetamine | journal = Prog Neuropsychopharmacol Biol Psychiatry | volume = 26 | issue = 6 | pages = 1177–83 | year = 2002 | pmid = 12452543 | doi = 10.1016/S0278-5846(02)00257-9}}</ref><!-- This corresponds to a human equivalent dose of at least 100 mg! Even higher on a simple mg/kg basis, which is probably a better measure for acute toxicity. --><ref>{{cite journal | author = C. Davidson, A. J. Gow, T. H. Lee, E. H. Ellinwood | title = Methamphetamine neurotoxicity: necrotic and apoptotic mechanisms and relevance to human abuse and treatment | journal = Brain Research Reviews | volume = 36 | issue = 1 | pages = 1–22 | year = 2001 | doi = 10.1016/S0165-0173(01)00054-6}}</ref> 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 ] such as hydrogen peroxide. It is likely that the approximate 1200% increase in dopamine levels and subsequent ] that occurs after taking methamphetamine mediates its ].<ref>{{cite journal | url = http://jpet.aspetjournals.org/cgi/content/full/287/1/107 | author = Yamamoto, B. and Zhu, W. | title = The Effects of Methamphetamine on the Production of Free Radicals and Oxidative Stress | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 287 | issue = 1 | pages = 107–114 | month= October | year= 1998 | accessdate=2007-11-19 | pmid = 9765328 | day = 01}}</ref> It has been demonstrated that a high ambient temperature increases the neurotoxic effects of methamphetamine.<ref>{{cite journal | url = http://jpet.aspetjournals.org/cgi/content/abstract/jpet.105.096503v1 | journal = The Journal of Pharmacology and Experimental Therapeutics | title = Relationship between Temperature, Dopaminergic Neurotoxicity, and Plasma Drug Concentrations in Methamphetamine-Treated Squirrel Monkeys | volume = 316 | issue = 3 | year= 2006 | pages = 1210–1218 | accessdate = 2007-11-20 | pmid = 16293712 | doi = 10.1124/jpet.105.096503 | author = Yuan, J. }}</ref>


Recent research published in the Journal of Pharmacology And Experimental Therapeutics (2007),<ref></ref> indicates that methamphetamine binds to a group of receptors called ]. TAAR is a newly discovered receptor system which seems to be affected by a range of amphetamine-like substances called ]. Recent research published in the Journal of Pharmacology And Experimental Therapeutics (2007),<ref></ref> indicates that methamphetamine binds to a group of receptors called ]. TAAR is a newly discovered receptor system which seems to be affected by a range of amphetamine-like substances called ].

Revision as of 19:28, 27 May 2009

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This article is about the psychostimulant drug, methamphetamine, in both racemic and dextrorotatory forms. For the CNS inactive OTC nasal decongestant, see levomethamphetamine.

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Pharmaceutical compound
Methamphetamine
Clinical data
Other namesDesoxyephedrine
Pervitin
Anadrex
Methedrine
Methylamphetamine
Syndrox
Desoxyn
Routes of
administration
Medical: Oral
Recreational: Oral, I.V., I.M., Insufflation, Inhalation, Suppository
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability62.7% oral; 79% nasal; 90.3% smoked; 99% rectally; 100% IV
MetabolismHepatic
Elimination half-life9–15 hours
ExcretionRenal
Identifiers
IUPAC name
  • (2S)-N-methyl-1-phenyl-propan-2-amine
CAS Number
PubChem CID
ChemSpider
CompTox Dashboard (EPA)
ECHA InfoCard100.007.882 Edit this at Wikidata
Chemical and physical data
FormulaC10H15N
Molar mass149.233 g/mol g·mol
3D model (JSmol)
SMILES
  • CC(CC1=CC=CC=C1)NC

Methamphetamine (/mɛθæm'fɛtəmiːn/, also known as, methylamphetamine, N-methylamphetamine, desoxyephedrine, crystalline methamphetamine hydrochloride) is a psychostimulant and sympathomimetic drug. It is a member of the family of phenylethylamines. The levorotary (R-isomer) levomethamphetamine is an over-the-counter drug and used in inhalers for nasal decongestion and does not possess the CNS activity of dextro or racemic methamphetamine. 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.

Methamphetamine enters the brain and triggers a cascading release of dopamine, serotonin and norepinephrine. It is highly active in the mesolimbic reward pathways of the brain, inducing intense euphoria, with high risks for addiction. To a lesser extent, methamphetamine acts as a dopaminergic and adrenergic reuptake inhibitor with high 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 major depression, often accompanied by anxiety and drug-craving. Methamphetamine users may take sedatives such as benzodiazepines as a means of easing their "come down", anxiety or enable them to sleep.

Methamphetamine addiction typically occurs when a person begins to use it because of its powerful enhancing effects on mood and energy, weight loss and appetite suppression, among its other psychological and physical effects. Over time effectiveness decreases, and users find that they need to take higher doses to get the same results and have far greater difficulty functioning and experiencing pleasure than they did before, which unlike cocaine persists indefinitely due to neurotoxicity produced by methamphetamine in long-term recovered addicts. Many users report having become an addict from their first "shot", or just one intravenous injection of crystal methamphetamine, marking its high affinity for a spiral of debilitating addiction. Methamphetamine's predominance as an addictive drug was the motivation behind several anti-drug advertisements and slogans. Nicknames for methamphetamine are numerous and vary significantly from region to region, some common nicknames for methamphetamine include "crank", "meth", "ice", "crystal", "glass", "shabu" or "syabu" (Philippines), "tik" (South Africa), "P" (New Zealand), "piko" (Slovakia), and "yaa baa" (Thailand). Methamphetamine is sometimes referred to as "speed", but this term is generally reserved for regular amphetamine and dextroamphetamine.

History

Methamphetamine was first synthesized from ephedrine in Japan in 1894 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 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 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 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 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, use 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. 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 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 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

Main short and long term adverse (negative) physical and mental effects that may appear in methamphetamine use.

Physical effects

Physical effects can include anorexia, hyperactivity, dilated pupils, flushing, restlessness, dry mouth, headache, tachycardia, bradycardia, tachypnea, hypertension, hypotension, hyperthermia, diaphoresis, diarrhea, constipation, blurred vision, aphasia, dizziness, muscle twitches, insomnia, numbness, palpitations, arrhythmias, tremors, dry and/or itchy skin, acne, pallor, and with chronic and/or high dosages, convulsions, heart attack, stroke and death can occur.

Psychological effects

Psychological effects can include euphoria, anxiety, increased libido, increased alertness, increased concentration, increased energy, increased self-esteem, increased self-confidence, increased excitation, increased orgasmic intensity, increased sociability, increased irritability, increased aggression, psychomotor agitation, hubris, excessive feelings of power and/or superiority, repetitive and/or obsessive behaviors, paranoia, and with chronic and/or high doses, amphetamine psychosis can occur.

Withdrawal effects

Withdrawal is characterized by excessive sleeping, excessive eating, and depression, often accompanied by anxiety and drug-craving.

Pharmacokinetics

The half life of methamphetamine is 9–15 hours. It is excreted by the kidneys and its half life depends on urinary pH. Main metabolites of methamphetamine are amphetamine, 4-hydroxymethamphetamine, 4-hydroxyamphetamine and some of the methamphetamine remains unchanged until excretion.

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 were 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. 12 Step meetings, such as Crystal Meth Anonymous are available to combat relapse.

Methamphetamine-induced hyperstimulation of pleasure pathways leads to anhedonia. 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 other serious behavioral problems associated with methamphetamine use and addiction that many users experience. Large doses of ascorbic acid also lower urinary pH, reducing methamphetamine's elimination half-life and thus decreasing the duration of its actions.

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 the use of methadone in the treatment of 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.

Methamphetamine addiction is one of the most difficult forms of addictions to treat. Although Wellbutrin, Abilify, and Baclofen have been employed to treat post-withdrawal cravings the success rate is low. Modafinil is somewhat more successful, but this is a Class IV scheduled drug. Ibogaine has been used with success in Europe, but is a Class I drug and available only for research use. Remeron has been reported useful in some small-population studies.

Since the phenethylamine phentermine is a constitutional isomer of methamphetamine, it has been speculated that it may be effective in treating methamphetamine addiction. Although phentermine 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

Acacia berlandieri Tree

Methamphetamine has been reported to occur 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

Main article: Desoxyn

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

10 mg Desoxyn

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

Other uses

A new study by a group of University of Montana scientists showed that methamphetamine appears to lessen damage to the brains of rats and gerbils that have suffered strokes. The researchers found that small amounts of methamphetamine created a protective effect, while higher doses increased damage. The work is preliminary, and more research is needed to confirm and expand the findings; however, U.M. research assistant professor Dave Poulsen said someday humans may use methamphetamine to lessen stroke damage.

Health issues

Meth mouth

Suspected case of meth mouth
Main article: 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 bruxism (teeth 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 can be caused by unsterilized needles, lack or ignoring of hygiene needs (more typical on chronic use), increase in acne on high doses, and obsessive skin-picking which may lead to abscesses.

Sexual behaviour

See also: sex and drugs

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) (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.

According to a recent San Diego study , methamphetamine users often engage in unsafe sexual activities, and forget to 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.

See also: Party and play

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.

Routes of administration

Studies have shown that the subjective pleasure of drug use (the reinforcing component of addiction) is proportional to the rate at which the blood level of the drug increases. In general, intravenous injection is the fastest mechanism (i.e., it causes blood concentrations to rise the most quickly), followed by smoking, anal insertion (suppository), insufflation, and ingestion (swallowing). Ingestion does not produce a "rush", which is the most transcendent state of euphoria experienced with the use of methamphetamine and is the most prominent with intravenous use. While the onset of the "rush" produced by injection or smoking can occur in as little as two minutes, the oral route of administration usually requires approximately half an hour before the "high" kicks in. Thus, oral routes of administration are generally used by recreational or medicinal consumers of the drug, while other more fast-acting routes of administration are used by addicts.

Smoking

"Smoking" amphetamines actually refers to vaporizing it to inhale fumes, rather than burning and inhaling the resulting smoke, as with tobacco. It is commonly smoked in glass pipes made from blown Pyrex tubes, light bulbs, or on aluminium foil heated underneath by a flame. This method is also known as "chasing the white dragon" (derived from 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 milligrams to over one gram using a hypodermic needle (Although it should be noted that typically street methamphetamine is "cut" with a water-soluble cutting material which constitutes a significant portion of that street methamphetamine dose). 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.

Insufflation

Another popular method for recreational use of methamphetamine is to insufflate (sometimes called snorting). This is done by crushing the methamphetamine crystals up into a fine powder and then sharply inhaling it (sometimes with a straw or a rolled up bill) into the nose where the methamphetamine is absorbed through the soft tissue in the mucous membrane of the sinus cavity straight into the bloodstream. This method bypasses first pass metabolism and has a faster onset with a higher bioavailability, although duration is shorter than oral administration. This method is sometimes preferred by users who do not want to use needles for injection or do not want to have to smoke the methamphetamine.

Other methods

File:Lineofmeth.jpg
A line of methamphetamine.

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 method is often known within methamphetamine communities as a "butt rocket", "potato thumping", "turkey basting", a "booty bump", "keistering", "plugging", "shafting", "shelving" (vaginal), or "bumming" and is anecdotally reported to increase sexual pleasure while the effects of the drug last longer. The rectum is where the majority of the drug would likely be taken up, through the membranes lining its walls.

Illicit production

Methamphetamine crystals

Synthesis

Methamphetamine is most structurally similar to methcathinone and amphetamine. When illicitly produced, 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 cold or allergy medicines. Synthesis is relatively simple, but entails risk with flammable and corrosive chemicals, particularly the solvents used in extraction and purification. Clandestine production is therefore often discovered by fires and explosions caused by the improper handling of volatile or flammable solvents.

Most methods of illicit production 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 is technically a purple color in elemental form), from which hydroiodic acid is formed. In Australia, criminal groups have been known to substitute "red" phosphorus with either hypophosphorus acid or phosphorus acid.

This is a fairly dangerous process for amateur chemists, because phosphine gas, a side-product from in situ hydroiodic acid production, is extremely toxic to inhale. An increasingly common method uses the process of Birch reduction, in which metallic lithium, commonly extracted from non-rechargeable lithium batteries, is substituted for difficult-to-find metallic sodium.

However, the Birch reduction is dangerous because the alkali metal and liquid anhydrous ammonia are both extremely reactive, and the temperature of liquid ammonia makes it susceptible to explosive boiling when reactants are added. Anhydrous ammonia and lithium or sodium (Birch reduction) may be surpassing hydroiodic acid (catalytic hydrogenation) as the most common method of manufacturing methamphetamine in the U.S. and possibly in Mexico. Hydroiodic acid "super lab" busts receive more media attention because the equipment employed is much more complex and visible than the glass jars or coffee carafes commonly used to produce methamphetamine with Birch reduction.

Industrial scale methamphetamine factory in Cikande, Indonesia.

A completely different procedure of synthesis uses 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, until DEA restrictions on the chemicals made the process difficult. Other less common methods use other means of hydrogenation, such as hydrogen gas in the presence of a catalyst.

Methamphetamine labs can give off noxious fumes, such as phosphine gas, methylamine gas, solvent vapors; such as acetone or chloroform, iodine vapors, white phosphorus, anhydrous ammonia, hydrogen chloride/muriatic acid, hydrogen iodide, lithium/sodium metal, ether, or methamphetamine vapors. If performed by amateurs, manufacturing methamphetamine can be extremely dangerous. If the red phosphorus overheats, because of a lack of ventilation, phosphine gas can be produced. This gas, if present in large quantities, is likely to explode upon autoignition from diphosphine, which is formed by overheating phosphorus.

Production and distribution

Until the early 1990s, methamphetamine for the US market was made mostly in labs run by drug traffickers in Mexico and California. Since then, authorities have discovered increasing numbers of small-scale methamphetamine labs all over the United States, mostly in rural, suburban, or low-income areas. Indiana state police found 1,260 labs in 2003, compared to just 6 in 1995, although this may be partly a result of increased police activity. As of 2007, drug and lab seizure data suggests that approximately 80 percent of the methamphetamine used in the United States originates from larger laboratories operated by Mexican-based syndicates on both sides of the border, and that approximately 20 percent comes from small toxic labs (STLs) in the United States.

Mobile and motel-based methamphetamine labs have caught the attention of both the US news media and the police. Such labs can cause explosions and fires, and expose the public to hazardous chemicals. Those who manufacture methamphetamine are often harmed by toxic gases. Many police departments have specialized task forces with training to respond to cases of methamphetamine production. 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 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."

In July 2007, a ship was caught by Mexican officials at the port of Lázaro Cárdenas, originating in Hong Kong, after traveling through the port of Long Beach with 19 tons of pseudoephedrine, a raw material needed for meth. The Chinese owner Zhenli Ye Gon was found to have $206 million at his Mexico City mansion. The load went undetected at Long Beach.

Methamphetamine is distributed by prison gangs, outlaw motorcycle gangs, street gangs, traditional organized crime operations, and impromptu small networks. In the U.S. illicit methamphetamine comes in a variety of forms, at an average price of $150 per gram for pure substance. Most commonly it is found as a colorless crystalline solid. Impurities may result in a brownish or tan color. Colourful flavored pills containing methamphetamine and caffeine are known as yaa baa (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, 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 is particularly dangerous due to the synergistic effects of multiple stimulants on the heart. It may also be flavored with high-sugar candies, drinks, or drink mixes to mask the bitter taste of the drug. Coloring may be added to the meth, as is the case with "Strawberry Quick."

Legality

Australia

Strictly speaking, as a Schedule 9 drug, the medical use of methamphetamine is recognized in Australia, however in practice this is not the case.

Some forms of Methamphetamine are known or Ice and has become the focus of a nation-wide crackdown.

Canada

Methamphetamine is not approved for medical use in Canada. As of 2005, methamphetamine has been moved to Schedule I of the Controlled Drugs and Substances Act, which provides access to the highest maximum penalties. The maximum penalty for production and distribution of methamphetamine has increased from 10 years to life in prison.

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 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.

Italy

Methamphetamine is not approved for medical use in Italy, except for an extremely small number of case-approved, strictly controlled experimental therapies, and it is inscribed in the Tabella 1 ("Schedule One") of the Psychotropic Substances List of the Italian Ministry of Health, which lists all illegal drugs (while the Tabella 2, or "Schedule Two", lists psychotropic substances that can be used as prescription drugs). Methamphetamine is thus regulated like any other "heavy drug" (Italian law makes distinction between "Light Drugs", such as marijuana, and "heavy drugs", such as heroin, cocaine or MDMA). Production, traffic and/or sale of methamphetamine can be punished with a sentence of imprisonment ranging from six to twenty years, and with a fine ranging from 26.000 to 260.000 Euros, according to the severity of the felony. As for any other drugs, the consumption of methamphetamine and the possession of the substance for "personal use" (under a certain quantity) is not illegal in Italy, although law enforcement and health authorities keep files on known users and addicts, which are often forced to undergo treatment. However, methamphetamine is not a particularly common or popular substance in Italy, surclassed by the above-mentioned cocaine, heroin, and by Ecstasy.

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 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 unique street name P.

Singapore

Under the Misuse of Drugs Act in Singapore, methamphetamine is a Class A — Schedule I controlled drug. Under the Section 17 of the Misuse of Drugs Act, any person who carries 25 or more grammes of the drug shall be presumed to possess them for the purpose of drug trafficking, which is punishable by death. Unless authorized by the government, the possession, consumption, manufacturing, import, export, or trafficking of methamphetamine in any amount are illegal.

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 18 January 2007, methamphetamine is classified as a Class A drug in the UK 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 Lab Seizures in the US
Year Seizures
1999 7,438
2000 9,902
2001 13,357
2002 16,212
2003 17,356
2004 17,710
2005 12,484
2006 6,435

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, some 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 2,148.6 kg 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.

DEA El Paso Intelligence Center EPIC data is showing a distinct downward trend in the seizure of clandestine drug labs for the illicit manufacture of methampetamine from a high of 17,710 in 2004. Lab seizure data for the United States is available from EPIC beginning in 1999 when 7,438 labs were reported to have been seized during that calendar year.

Legality of similar chemicals

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

See also

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Footnotes

  1. Nicknames for methamphetamine are varied and differ from region to region, some less known and less notable nicknames for methamphetamine include "jib", "batu", "meth amps", "poof", "rail", "tina", and "tweak". For additional drug slang and terminology for numerous recreational drug please see the Erowid Drug Slang & Terminology.

Further reading

  • Poison Information Monograph (PIM 334: Methamphetamine)
  • Chronic Amphetamine Use and Abuse - a 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.

Documentaries

External links

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