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Meth Drug - Methamphetamine Information, Use, Testing and Treatment

Methamphetamine (/mɛθmfɛtəmiːn/, also known as methylamphetamine, N-methylamphetamine or desoxyephedrine) is a powerful 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. 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 treatment-resistant 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 susceptible to tolerance. It is primarily used illegally for recreational purposes, weight loss and to maintain alertness, focus, motivation, with mental clarity for extended periods of time.

Methamphetamine enters the brain and triggers a cascading release of norepinephrine, dopamine and serotonin. It is highly active in the mesolimbic reward pathway of the brain, inducing intense euphoria, with high-risk for abuse and powerful addiction. Methamphetamine, to a lesser extent, 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.  Users of methamphetamine often take sedatives such as benzodiazepines as a means of easing their "come down" and 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 without the drug than they did before. Many users report becoming an addict from their first "shot", or just one intravenous injection of crystal methamphetamine, marking its high affinity for a spiral of debilitating addiction and labelling as a "hard drug".

Common nicknames for methamphetamine include "crank", "meth", "ice", "snappy", "crystal", "tina", "glass", "P", "shabu" or "syabu" (Philippines), "tik" (South Africa), and "yaa baa" (Thailand). Methamphetamine is sometimes referred to as "speed", but this term is generally reserved for regular amphetamine and dextroamphetamine.

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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 ("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 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 ヒロポン, or 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 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.

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Effects

Physical effects

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

Psychological effects

Psychological effects can include euphoria, anxiety, increased libido, increased self-awareness, 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 dosages, amphetamine psychosis can occur.

Withdrawal effects

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

Pharmacokinetics

The half life of methamphetamine is 915 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 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 23 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

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

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

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

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 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 behavior

Users may exhibit sexually compulsive behavior 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.

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 aluminum 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

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.

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.

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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 Lzaro Crdenas, 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

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.

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One Step Single/Multi-Drug Screen Test Panel
Package Insert for 1 to 10 Drug Screen Panel Dip
Instruction Sheet for testing of any combination of the following drugs:
AMP, BAR, BZO, COC,THC, MTD , mAMP, OPI, PCP AND TCA

Amphetamine (AMP)
Barbiturates (BAR)
Benzodiazepines (BZO)
Cocaine (COC)
Marijuana (THC)
Methadone (MTD)
Methamphetamine (mAMP)
Opiate (300 ng/ml) (OPI 300 or MOP 300)
Opiate (OPI) (2000 ng/ml)
Phencyclidine
Tricyclic Antidepressant (TCA)
Non Cross-Reacting Compounds

A rapid, one step screening test for the simultaneous, qualitative detection of multiple drugs and drug metabolites in human urine. For healthcare professionals and professionals at point of care sites. For professional in vitro diagnostic use.
INTENDED USE
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The One Step Multi-Drug Screen Test Panel is a lateral flow chromatographic immunoassay for the qualitative detection of multiple drugs and drug metabolites in urine at the following cut-off concentrations: 300 ng/mL Benzoylecgonine (Cocaine metabolite), 1,000 ng/mL Amphetamine, 1,000 ng/mL Methamphetamine, 50 ng/mL 11-nor-.9 -THC-9- COOH (THC), 2,000 ng/mL Opiate, 25 ng/mL Phencyclidine, in urine.

This assay provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used.
SUMMARY
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AMPHETAMINE (AMP)
Amphetamine is a Schedule II controlled substance available by prescription (Dexedrine) and is also available on the illicit market. Amphetamines are a class of potent sympathomimetic agents with therapeutic applications. They are chemically related to the human bodys natural catecholamines: epinephrine and norepinephrine. Acute higher does lead to enhanced stimulation of the central nervous system and induce euphoria, alertness, reduced appetite, and a sense of increased energy and power. Cardiovascular responses to Amphetamines include increased blood pressure and cardiac arrhythmias. More acute responses produce anxiety, paranoia, hallucinations, and psychotic behavior. The effects of Amphetamines generally last 2-4 hours following use, and the drug has a halflife of 4-24 hours in the body. About 30% of Amphetamines are excreted in the urine in unchanged form, with the remainder as hydroxylated and deaminated derivatives.
The AMP One Step Amphetamine Test Strip is a rapid urine screening test that can be performed without the use of an instrument. The test utilizes a monoclonal antibody to selectively detect elevated levels of Amphetamine in urine. The AMP One Step Amphetamine Test Strip yields a positive result when Amphetamines in urine exceed 1,000 ng/mL.
BARBITURATES (BAR)
Barbiturates are central nervous system depressants. They are used therapeutically as sedatives, hypnotics, and anticonvulsants. Barbiturates are almost always taken orally as capsules or tablets. The effects resemble those of intoxication with alcohol. Chronic use of barbiturates leads to tolerance and physical dependence.
Short acting Barbiturates taken at 400mg/day for 2-3 months produces a clinically significant degree of physical dependence. Withdrawal symptoms experienced during periods of drug abstinence can be severe enough to cause death.
Only a small amount (less than 5%) of most Barbiturates are excreted unaltered in urine. The approximate detection time limits for Barbiturates are:
Short Acting (e.g. Secobarbital) 100 mg PO (oral) 4 5 days
Long Acting (e.g. Phenobarbital 400 mg PO (oral) 7 days1
The One Step Drug Screen Test yields a positive result when the Barbiturates in urine exceeds 300ng/ml.
BENZODIAZEPINES (BZO)
Benzodiazepines are medications that are frequently prescribed for symptomatic treatment of anxiety and sleep disorders. They produce their effects via specific receptors involving a neurochemical called gamma aminobutyric acid (GABA). Because they are safer and more effective, Benzodiazepines have replaced barbiturates in the treatment of both anxiety and insomnia. Benzodiazepines are also used as sedatives before some surgical and medical procedures, and for the treatment of seizure disorders and alcohol withdrawal.
Risk of physical dependence increases if Benzodiazepines are taken regularly (e.g., daily) for more than a few months, especially at higher than normal doses. Stopping abruptly can bring on such symptoms trouble sleeping, gastrointestinal upset, feeling unwell, loss of appetite, sweating and trembling, weakness, anxiety and changes in perception.
Only trace amounts (less than 1%) of most Benzodiazepines are excreted unaltered in urine; most of the concentration in urine is conjugated drug. The detection period for the Benzodiazepines in urine is 3 7 days.
The One Step Drug screen Test Card yields a positive result when the Benzodiazepines in urine exceeds 300 ng/ml.
COCAINE (COC)
Cocaine is a potent central nervous system (CNS) stimulant and a local anesthetic. Initially, it brings about extreme energy and restlessness while gradually resulting in tremors, over-sensitivity and spasms. In large amounts, cocaine causes fever, unresponsiveness, and difficulty in breathing and unconsciousness.
Cocaine is often self-administered by nasal inhalation, intravenous injection and free-base smoking. It is excreted in the urine in a short time primarily as Benzoylecgonine1,2. Benzoylecgonine, a major metabolite of cocaine, has a longer biological half-life (5-8 hours) than cocaine (0.5-1.5 hours), and can generally be detected for 24-48 hours after cocaine exposure2.
The COC One Step Cocaine Test Strip is a rapid urine screening test that can be performed without the use of an instrument. The test utilizes a monoclonal antibody to selectively detect elevated levels of cocaine metabolite in urine. The COC One Step Cocaine Test Strip yields a positive result when the cocaine metabolite in urine exceeds 300 ng/mL. This is the suggested screening cut-off for positive specimens set by the Substance Abuse and Mental Health Services Administration (SAMHSA, USA).
MARIJUANA (THC)
THC (.9--tetrahydrocannabinol) is the primary active ingredient in cannabinoids (marijuana). When smoked or orally administered, it produces euphoric effects. Users have impaired short term memory and slowed learning. They may also experience transient episodes of confusion and anxiety. Long term relatively heavy use may be associated with behavioral disorders. The peak effect of smoking marijuana occurs in 20-30 minutes and the duration is 90-120 minutes after one cigarette. Elevated levels of urinary metabolites are found within hours of exposure and remain detectable for 3-10 days after smoking. The main metabolite excreted in the urine is 11-nor-.9-tetrahydrocannabinol-9-carboxylic acid (.9-THC-COOH).
The THC One Step Marijuana Test Strip is a rapid urine screening test that can be performed without the use of an instrument. The test utilizes a monoclonal antibody to selectively detect elevated levels of marijuana in urine. The THC One Step Marijuana Test Strip yields a positive result when the concentration of marijuana in urine exceeds 50 ng/mL. This is the suggested screening cut-off for positive specimens set by the Substance Abuse and Mental Health Services Administration (SAMHSA, USA). 3
METHADONE (MTD)
Methadone is a narcotic pain reliever for medium to severe pain. It is also used in the treatment of heroin (opiate dependence: Vicodin, Percocet, Morphine, etc.) addiction. Oral Methadone is very different than IV Methadone. Oral Methadone is partially stored in the liver for late use. IV Methadone acts more like heroin. In most states you must go to a pain clinic or a Methadone maintenance clinic to be prescribed Methadone.
Methadone is a long acting pain reliever producing effects that last from twelve to forth-eight hours. Ideally, Methadone frees the client from the pressures of obtaining illegal heroin, from the dangers of injection and from the emotional roller coaster that most opiates produce. Methadone, if taken for long periods and at large doses, can lead to a very long withdrawal period. The withdrawals from Methadone are more prolonged and troublesome than those provoked by heroin cessation, yet the substitution and phased removal of methadone is an acceptable method of detoxification for patients and therapists.1
The MTD One step Methadone test yields a positive result when Methadone in urine exceeds 300 ng/ml.
METHAMPHETAMINE (mAMP)
Methamphetamine is an addictive stimulant drug that strongly activates certain systems in the brain. Methamphetamine is closely related chemically to amphetamine, but the central nervous system effects of Methamphetamine are greater. Methamphetamine is made in illegal laboratories and has a high potential for abuse and dependence. The drug can be taken orally, injected, or inhaled. Acute higher does lead to enhanced stimulation of the central nervous system and induce euphoria, alertness, reduced appetite, and a sense of increased energy and power. Cardiovascular responses to Methamphetamine include increased blood pressure and cardiac arrhythmias. More acute responses produce anxiety, paranoia, hallucinations, psychotic behavior, and eventually, depression and exhaustion.
The effects of Methamphetamine generally last 2-4 hours and the drug has a half-life of 9-24 hours in the body. Methamphetamine is excreted in the urine primarily as amphetamine and oxidized and deaminated derivatives. However, 10-20% of Methamphetamine is excreted unchanged. Thus, the presence of the parent compound in the urine indicates Methamphetamine use. Methamphetamine is generally detectable in the urine for 3-5 days, depending on urine pH level.
The mAMP One Step Methamphetamine Test Strip is a rapid urine screening test that can be performed without the use of an instrument. The test utilizes a monoclonal antibody to selectively detect elevated levels of Methamphetamine in urine. The mAMP One Step Methamphetamine Test Strip yields a positive result when the Methamphetamine in urine exceeds 1,000 ng/mL.
OPIATE (300 ng/ml) (OPI 300 or MOP 300)
Opiate refers to any drug that is derived from the opium poppy, including the natural products, morphine and codeine, and the semi-synthetic drugs such as heroin. Opioid is more general, referring to any drug that acts on the opioid receptor.
Opioid analgesics comprise a large group of substances which control pain by depressing the central nervous system. Large dose of morphine can produce higher tolerance levels, physiological dependency in users, and may lead to substance abuse. Morphine is excreted unmetabolized, and is also the major metabolic product of codeine and heroin. Morphine is detectable in the urine for several days after an opiate dose.4 The OPI One Step Opiate Test Strip is a rapid urine screening test that can be performed without the use of an instrument. The test utilizes a monoclonal antibody to selectively detect elevated levels of morphine in urine. The OPI One Step Opiate Test Strip yields a positive result when the morphine in urine exceeds 300 ng/mL.
OPIATE (OPI) (2000 ng/ml)
Opiate refers to any drug that is derived from the opium poppy, including the natural products, morphine and codeine, and the semi-synthetic drugs such as heroin. Opioid is more general, referring to any drug that acts on the opioid receptor.
Opioid analgesics comprise a large group of substances which control pain by depressing the central nervous system. Large dose of morphine can produce higher tolerance levels, physiological dependency in users, and may lead to substance abuse. Morphine is excreted unmetabolized, and is also the major metabolic product of codeine and heroin. Morphine is detectable in the urine for several days after an opiate dose.4
The OPI One Step Opiate Test Strip is a rapid urine screening test that can be performed without the use of an instrument. The test utilizes a monoclonal antibody to selectively detect elevated levels of morphine in urine. The OPI One Step Opiate Test Strip yields a positive result when the morphine in urine exceeds 2,000 ng/mL. This is the suggested screening cut-off for positive specimens set by the Substance Abuse and Mental Health Services Administration (SAMHSA, USA).
PHENCYCLIDINE
Phencyclidine, also known as PCP or Angel Dust, is a hallucinogen that was first marketed as a surgical anesthetic in the 1950s. It was removed from the market because patients receiving it became delirious and experienced hallucinations.
Phencyclidine is used in powder, capsule, and tablet form. The powder is either snorted or smoked after mixing it with marijuana or vegetable matter. Phencyclidine is most commonly administered by inhalation but can be used intravenously, intra-nasally, and orally. After low doses, the user thinks and acts swiftly and experiences mood swings from euphoria to depression. Self-injurious behavior is one of the devastating effects of Phencyclidine.
PCP can be found in urine within 4 to 6 hours after use and will remain in urine for 7 to 14 days, depending on factors such as metabolic rate, users age, weight, activity, and diet.5 Phencyclidine is excreted in the urine as an unchanged drug (4% to 19%) and conjugated metabolites (25% to 30%).6
The PCP One Step Phencyclidine Test Strip is a rapid urine screening test that can be performed without the use of an instrument. The test utilizes a monoclonal antibody to selectively detect elevated levels of phencyclidine metabolite in urine. The PCP One Step Phencyclidine Test Strip yields a positive result when the phencyclidine metabolite in urine exceeds 25 ng/mL. This is the suggested screening cut-off for positive specimens set by the Substance Abuse and Mental Health Services Administration (SAMHSA, USA).
TRICYCLIC ANTIDEPRESSANT (TCA)
TCA (Tricyclic Antidepressants) are commonly used for the treatment of depressive disorders. TCA overdoses can result in profound central nervous system depression, cardiotoxicity and anticholinergic effects. TCA overdose is the most common cause of death from prescription drugs. TCAs are taken orally or sometimes by injection. TCAs are metabolized in the liver. Both TCAs and their metabolites are excreted in urine mostly in the form of metabolites for up to ten days.
The One Step Drug Screen Tests yields a positive result when the Tricyclic Antidepressant in urine exceeds 1,000 ng/ml.
PRINCIPLE
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The One Step Multi-Drug Screen Test Panel is an immunoassay based on the principle of competitive binding. Drugs which may be present in the urine specimen compete against their respective drug conjugate for binding sites on their specific antibody.
During testing, a urine specimen migrates upward by capillary action. A drug, if present in the urine specimen below its cut-off concentration, will not saturate the binding sites of its specific antibody. The antibody will then react with the drug-protein conjugate and a visible colored line will show up in the test line region of the specific drug strip. The presence of drug above the cut-off concentration will saturate all the binding sites of the antibody. Therefore, the colored line will not form in the test line region.
A drug-positive urine specimen will not generate a colored line in the specific test line region of the strip because of drug competition, while a drug-negative urine specimen will generate a line in the test line region because of the absence of drug competition.
To serve as a procedural control, a colored line will always appear at the control line region, indicating that proper volume of specimen has been added and membrane wicking has occurred.
REAGENTS
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The test panel contains specific mouse monoclonal antibody, goat polyclonal antibody and drug protein conjugates.
PRECAUTIONS
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For healthcare professionals and professionals at point of care sites.
For in vitro diagnostic use only. Do not use after the expiration date.
The test panel should remain in the sealed pouch until use.
All specimens should be considered potentially hazardous and handled in the same manner as an infectious agent.
The used test panel should be discarded according to federal, state and local regulations

STORAGE AND STABILITY
Kit can be stored at room temperature or refrigerated at 2-30C. The test panel is stable through the expiration date printed on the sealed pouch. The test panel must remain in the sealed pouch until use. DO NOT FREEZE. Do not use beyond the expiration date.
MATERIALS PROVIDED
Test panels
Package insert
MATERIALS REQUIRED BUT NOT PROVIDED
Specimen collection container
External controls
Timer
PREPARATION URINE ASSAY
The urine specimen must be collected in a clean and dry container. Urine collected at any time of the day may be used. Urine specimens exhibiting visible precipitates should be centrifuged, filtered, or allowed to settle to obtain a clear supernatant for testing.
SPECIMEN STORAGE
Urine specimens may be stored at 2-8C for up to 48 hours prior to testing. For prolonged storage, specimens may be frozen and stored below -20C. Frozen specimens should be thawed and mixed well before testing.
QUALITY CONTROL
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A procedural control is included in the test. A colored line appearing in the control region (C) is considered an internal procedural control. It confirms sufficient specimen volume, adequate membrane wicking and correct procedural technique.
Control standards are not supplied with this kit. However, it is recommended that positive and negative controls be tested as good laboratory practice to confirm the test procedure and to verify proper test performance.
LIMITATIONS
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1. The One Step Multi-Drug Screen Test Panel provides only a qualitative, preliminary analytical result. A secondary analytical method must be used to obtain a confirmed result. Gas chromatography and mass spectrometry (GC/MS) is the preferred confirmatory method. 3,4,7
2. There is a possibility that technical or procedural errors, as well as other interfering substances in the urine specimen may cause erroneous results.
3. Adulterants, such as bleach and/or alum, in urine specimens may produce erroneous results regardless of the analytical method used. If adulteration is suspected, the test should be repeated with another urine specimen.
4. A Positive result does not indicate level or intoxication, administration route or concentration in urine.
5. A Negative result may not necessarily indicate drug-free urine. Negative results can be obtained when drug is present but below the cut-off level of the test.
6. Test does not distinguish between drugs of abuse and certain medications.
PERFORMANCE CHARACTERISTICS - ACCURACY
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A side-by-side comparison was conducted using The One Step Single Drug Test and commercially available drug rapid tests. Testing was performed on approximately 300 specimens previously collected from subjects presenting for Drug Screen Testing. Presumptive positive results were confirmed by GC/MS. The following compounds were quantified by GC/MS and contributed to the total amount of drugs found in presumptive positive urine samples tested.
TEST Compounds Contributed to the Totals of GC/MS

AMP Amphetamine

BAR Secobarbital, Butalbital, Phenobarbital, Pentobarbital

BZO Oxazepam, Nordiazepam, a-OH-Alprazolam, Desalklflurazepam

COC Benzoylecgonine

THC 11-nor-.9-tetrahydrocannabinol-carboxylic acid

TEST Compounds Contributed to the Totals of GC/MS

MTD Methadone

mAMP Methamphetamine

OPI Morphine, Codeine

PCP Phencyclidine

TCA Nortriptyline

Forty (40) clinical samples for each drug were run using each of the One Step Single Drug tests by an untrained operator at a Professional Point of Care site. Based on GC/MS data, the operator obtained statistically similar Positive Agreement, Negative Agreement and Overall Agreement rates as trained Laboratory personnel.
*Note: TCA was based on HPLC data.
Precision
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A study was conducted at three physician offices by untrained operators using three different lots of product to demonstrate the within run, between run and between operator precision. An identical panel of coded specimens, containing drugs at the concentration of 50% and 25% cut-off level, was labeled as a blind and tested at each site. The results are given below:









Analytical Sensitivityty
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A drug-free urine pool was spiked with drugs to the concentrations at 50% cut-off and 25% cut-off. The results are summarized below.
Drug conc. (Cut-off range) n AMP BAR BZO COC THC MTD mAMP OPI PCP TCA
- + - + - + - + - + - + - + - + - + - +
0% Cut-off 30 30 0 30 0 30 0 30 0 30 0 30 1 30 0 30 0 30 0 30 0
-50% Cut-off 30 30 0 30 0 30 0 30 0 30 0 29 1 30 0 30 0 30 0 30 0
-25% Cut-off 30 30 0 27 3 26 4 30 0 12 1 24 6 30 0 30 0 19 11 22 8
Cut-off 30 18 12 22 8 12 18 4 26 1 29 21 9 18 12 30 17 16 14 12 18
+25% Cut-off 30 1 29 7 23 3 27 0 30 1 29 2 28 1 29 30 26 6 24 7 23
+50% Cut-off 30 0 30 2 28 0 30 0 30 0 30 0 30 0 30 0 30 0 30 0 30
Analytical Specificity
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The following table lists the concentration of compounds (ng/mL) that are detected positive in urine by The One Step Multi-Drug Screen Test Panel at 5 minutes.
AMPHETAMINE
D-Amphetamine 1,000
D,L-Amphetamine sulfate 3,000
L-Amphetamine 50,000
()3,4-Methylenedioxyamphetamine 2,000
Phentermine 3,000
Secobarbital 300
Amobarbital 300
Alphenol 150
Aprobarbital 200
Butalbital 75
Butethal 2500
Cyclopentobarbital 100
Pentobarbital 600
Phenobarbital 300
Benzodiazepines
Oxazepam 300
Alprazolam 196
a-Hydroxyalprazolam 1262
Bromazepam 1562
Chlordiazepoxide 1562
Chlordiazepoxide HCI 781
Clobazam 98
Clonazepam 781
Clorazepate dipotassium 195
Delorazepam 1562
Desalkyflurazepam 390
Diazepam 195
Estazolam 2500
Flunitrazepam 390
( + ) Lorazepam 1562
RS-Lorazepam glucuronide 156
Midazolam 12500
Nitrazepam 98
Norchlordiazepoxide 195
Nordiazepam 390
Temazepam 98
Triazolam 2500
COCAINE ng/ml
Benzoylecgonine 300
Cocaine HCl 780
Cocaethylene 12,500
Ecgonine HCl 32,000
MARIJUANA (THC)
11-nor-.9 -THC-9 COOH 50
Cannabinol 20,000
11-nor-.8-THC-9 COOH 30
.8 -THC 15,000
.9 -THC 15,000
Methadone
Methadone 300
Doxylamine 50000
METHAMPHETAMINE
D-Methamphetamine 1,000
-Hydroxymethamphetamine 30,000
L-Methamphetamine 8,000
()-3,4-Methylenedioxymethamphetamine 2,000
Mephentermine 50,000
OPIATES ng/ml
Morphine 2,000
Codeine 2,000
Ethylmorphine 5,000
Hydrocodone 12,500
Hydromorphone 5,000
Levophanol 75,000
6-Monoacetylmorphine 5,000
Morphine 3--D-glucuronide 2,000
Norcodeine 12,500
Normorphone 50,000
Oxycodone 25,000
Oxymorphone 25,000
Procaine 150,000
Thebaine 100,000
PCP
Phencyclidine 25
4-Hydroxyphencyclidine 12,500
TCA
Nortriptyline 1,000
Nordoxepine 1,000
Trimipramine 3,000
Amitriptyline 1,500
Promazine 1,500
Desipramine 200
Imipramine 400
Clomipramine 12,500
Doxepin 2,000
Maprotiline 2,000
Promethazine 25,000
Effect of Urinary Specific Gravity
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Fifteen (15) urine samples of normal, high, and low specific gravity ranges (1.000-1.037) were spiked with drugs at 50% below and 50% above cut-off levels respectively. The Multi-Drug Screen Test was tested in duplicate using fifteen drug-free urine and spiked urine samples. The results demonstrate that varying ranges of urinary specific gravity does not affect the test results.
Effect of the Urinary pH
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The pH of an aliquoted negative urine pool was adjusted to a pH range of 5 to 9 in 1 pH unit increments and spiked with drugs at 50% below and 50% above cut-off levels. The spiked, pH-adjusted urine was tested with The One Step Multi-Drug Screen Test Panel. The results demonstrate that varying ranges of pH does not interfere with the performance of the test.
Cross-Reactivity
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A study was conducted to determine the cross-reactivity of the test with compounds in either drug-free urine or Cocaine, Amphetamine, Methamphetamine, Marijuana, Opiate or Phencyclidine positive urine. The following compounds show no cross-reactivity when tested with the One Step Multi-Drug Screen Test Panel at a concentration of 100 g/mL.
Non Cross-Reacting Compounds
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Acetaminophen Deoxycorticosterone Loperamide Promazine
Acetophenetidin Dextromethorphan Maprotiline Promethazine
N-Acetylprocainamide Diazepam MDE DL-Propranolol
Acetylsalicylic acid Diclofenac Meperidine D-Propoxyphene
Aminopyrine Diflunisal Meprobamate D-Pseudoephedrine
Amitryptyline Digoxin Methadone Quinacrine
Amoxicillin Diphenhydramine Methoxyphenamine Quinidine
Ampicillin Doxylamine Nalidixic acid Quinine
L-Ascorbic acid (-) --Ephedrine Naloxone Ranitidine
DL-Amphetamine sulfate -Estradiol Naltrexone Salicylic acid
Apomorphine Estrone-3-sulfate Naproxen Serotonin
Aspartame Ethyl-p-aminobenzoate Niacinamide Sulfamethazine
Atropine [1R,2S] (-) Ephedrine Nifedipine Sulindac
Benzilic acid (L) Epinephrine Norethindrone Temazepam
Benzoic acid Erythromycin D-Norpropoxyphene Tetracycline
Benzphetamine Fenoprofen Noscapine Tetrahydrocortisone, 3-acetate
Bilirubin Furosemide DL-Octopamine Tetrahydrocortisone 3-
() Brompheniramine Gentisic acid Oxalic acid (-D-glucuronide)
Caffeine Hemoglobin Oxazepam Tetrahydrozoline
Cannabidiol Hydralazine Oxolinic acid Thiamine
Chloralhydrate Hydrochlorothiazide Oxymetazoline Thioridazine
Chloramphenicol Hydrocortisone Papaverine DL-Tyrosine
Chlorothiazide O-Hydroxyhippuric acid Penicillin-G Tolbutamide
() Chlorpheniramine p-Hydroxyamphetamine Pentazocine hydrochloride Triamterene
Chlorpromazine 3-Hydroxytyramine Perphenazine Trifluoperazine
Chlorquine Ibuprofen Phenelzine Trimethoprim
Cholesterol Imipramine Trans-2-phenylcyclo-propylamine Trimipramine
Clomipramine Iproniazid hydrochloride Tryptamine
Clonidine () Isoproterenol L-Phenylephrine DL-Tryptophan
Cortisone Isoxsuprine -Phenylethylamine Tyramine
(-) Cotinine Ketamine Phenylpropanolamine Uric acid
Creatinine Ketoprofen Prednisolone Verapamil
  Labetalol Prednisone Zomepirac
BIBLIOGRAPHY
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1. Stewart DJ, Inaba T, Lucassen M, Kalow W. Clin Pharmacol. Ther, April 1979; 25 ed: 464, 264-8
2. Ambre J. J. Anal. Toxicol. 1985; 9:241
3. Hawks RL, CN Chiang. Urine Testing for Drugs of Abuse. National Institute for Drug Abuse (NIDA), Research Monograph 73, 01986; 1735.
4. Tietz NA. Textbook of Clinical Chemistry. W.B. Saunders Company. 1986; 1735.
5. FDA Guidance Document: Guidance for Premarket Submission for Kits for Screening Drugs of Abuse to be used by the Consumer, 199.
6. Robert DeCresce. Drug Testing in the workplace, 114.
7. Baselt RC. Disposition of Toxic Drugs and Chemicals in Man. 2nd ED. Biomedical Publ., Davis, CA 1982; 487.