Question:

Which way could you clean your system the fastest for meth?

Answer:

It will be out of your urine in 3-4 days on its own. There really still isn't much info available on it because its a fairly "new" drug but i suggest drinking lots of water, lots of cranberry juice, and one of those readyclean drinks if possible

More Info:


Apple juice
Apple juice is a fruit juice made by the maceration and pressing of apples. The resulting expelled juice may be further treated by enzymatic and centrifugal clarification to remove the starch and pectin, which holds fine particulate in suspension, and then pasteurized for packaging in glass, metal or aseptic processing system containers, or further treated by dehydration processes to a concentrate. Due to the complex and costly equipment required to extract and clarify juice from apples in large volume, apple juice is normally commercially produced. In the United States, unfiltered fresh apple juice is made by smaller operations in areas of high apple production, in the form of unclarified apple cider. Apple juice is one of the most common fruit juices in the world, with world production led by China, Poland, the United States, and Germany. Vitamin C is sometimes added by fortification, because content is variable, and much of that is lost in processing.][ Vitamin C also helps to prevent oxidation of the product. Other vitamin concentrations are low, but apple juice does contain various mineral nutrients, including boron, which may promote healthy bones. Apple juice has a significant concentration of natural phenols of low molecular weight (including chlorogenic acid, flavan-3-ols, and flavonols) and procyanidins that may protect from diseases associated with aging due to the antioxidant effects which help reduce the likelihood of developing cancer and Alzheimer's disease. Research suggests that apple juice increases acetylcholine in the brain, possibly resulting in improved memory. Despite having some health benefits, apple juice is high in sugar. It has 28 g carbohydrates (24 g sugars) per 8 ounces. This results in 130 calories per 8 ounces (protein and fat are not significant). Also like most fruit juice, apple juice contains a similar amount of sugar as the raw fruit, but lacks the fiber content. While apple juice generally refers to the filtered, pasteurised product of apple pressing, an unfiltered and sometimes unpasteurised product commonly known as apple cider in the United States and parts of Canada may be packaged and sold as apple juice. In the U.S., there is an unclear distinction between filtered apple juice and natural apple cider. In other places such as New Zealand, Australia and the United Kingdom, apple cider is an alcoholic beverage. The alcoholic beverage referred to as cider in these areas is usually referred to as hard cider in the United States.

Orange juice
Orange juice refers to the juice of oranges. It is made by squeezing the fresh fruit, by drying and later rehydrating the juice, or by concentration of the juice and later adding water to the concentrate. It is known for its health benefits, particularly its high concentration of vitamin C. It comes in several different varieties, including blood orange. In American English, the slang term O.J. may also be used to refer to orange juice. Due to the importance of oranges to the economy of the state of Florida, "the juice obtained from mature oranges of the species Citrus sinensis and hybrids thereof" was adopted as the official beverage of Florida in 1967. A cup serving of raw, fresh orange juice, amounting to 248 g or 8 ounces, has 124 mg of vitamin C (>100% RDI). It has 20.8 g of sugars and has 112 Calories. It also supplies potassium, thiamin, and folate. Citrus juices contain flavonoids (especially in the pulp), that may have health benefits. Orange juice is also a source of the antioxidant hesperidin. Due to its citric acid content, orange juice is acidic, with a typical pH of around 3.5. Commercial squeezed orange juice is pasteurized and filtered before being evaporated under vacuum and heat. After removal of most of the water, this concentrated juice, about 65% sugar by weight, is then stored at about . Essences, Vitamin C, and oils extracted during the vacuum concentration process may be added back to restore flavor.(see additives, below) When water is added to freshly thawed concentrated orange juice, it is said to be reconstituted. The product was developed in 1948 at the University of Florida's Citrus Research and Education Center. Since, it has emerged as a commodity product, and futures contracts have traded in New York since 1966. Options on FCOJ were introduced in 1985. From the late 1950s to the mid-1980s, the product had the greatest orange juice market share, but not-from-concentrate juices surpassed FCOJ in the 1980s. Orange juice that is pasteurized and then sold to consumers without having been concentrated is labeled as "not from concentrate". Just as "from concentrate" processing, most "not from concentrate" processing reduces the natural flavor from the juice. The largest producers of "not from concentrate" use a production process where the juice is placed in aseptic storage, with the oxygen stripped from it, for up to a year. A flavor pack is added in the final step to give the juice flavor. According to the citrus industry, the Food and Drug Administration does not require the contents of flavor packs to be detailed on a product's packaging. A small fraction of fresh orange juice is canned. Canned orange juice retains Vitamin C much better than bottled juice. The canned product loses flavor, however, when stored at room temperature for more than 12 weeks. Fresh-squeezed, unpasteurized juice is the closest to consuming the orange itself. This version of the juice consists of oranges that are squeezed and then bottled without having any additives or flavor packs inserted. The juice is not subjected to pasteurization. Fresh squeezed orange juice has a typical shelf life of 12 days.][ In the U.S., the major orange juice brand is Tropicana Products (owned by PepsiCo Inc.), which possesses nearly 65%][ of the market share. Tropicana also has a large presence in Latin America, Europe, and Central Asia. Competing products include Minute Maid (of The Coca-Cola Company) and Florida's Natural (a Florida-based agricultural cooperative that differentiates itself from the competition by using only Florida grown oranges; Tropicana and Simply Orange use a mixture of domestic and foreign stock). In Australia, Daily Juice (owned by National Foods) is a major brand of partially fresh, partially preserved, orange juice. In the United Kingdom, major orange juice brands include Del Monte and Princes. Some producers add citric acid or ascorbic acid to juice beyond what is naturally found in the orange. Some also include other nutrients. Often, additional vitamin C is added to replace that destroyed in pasteurization. Additional calcium may be added. Vitamin D, not found naturally in oranges, may be added as well. Sometimes Omega-3 fatty acids from fish oils are added to orange juice. Low-acid varieties of orange juice also are available. Juice producers generally use evaporators to remove much of the water from the juice in order to decrease its weight and decrease transportation costs. Because the process removes the distinct aroma compounds that give it a fresh-squeezed taste, producers later add back these compounds in a proprietary mixture, called a "flavor pack", in order to improve the taste and to ensure a consistent year-round taste. The compounds in the flavor packs are derived from orange peels. Producers do not mention the addition of flavor packs on the label of the orange juice. Common orange juice is made from the sweet orange. Different cultivars (e.g. Valencia, Hamlin) have different properties, and a producer may mix cultivar juices to get a desired taste. Orange juice usually varies between shades of orange and yellow, although some ruby red or blood orange varieties are a reddish-orange or even pinkish. This is due to different pigmentation in ruby red oranges. The blood orange is a mutant of the sweet orange. Blood orange juice is popular in Italy, but may be hard to find elsewhere. The Mandarin orange and varieties clementine and tangerine, are good for juice, and are often used for sparkling juice drinks. Recently, many brands of organic orange juices have become available on the market.

Cranberry juice
Cranberry juice is the juice of the cranberry. As a pure juice, it is quite tart; as with lime juice, it is seldom drunk on its own. One solution is to combine it with sweeter juices, such as apple or grape. Another solution is to dilute it with water and add some sweetener, such as corn syrup or sugar, or artificial sweetener (sucralose or aspartame). The term, used on its own, almost always refers to a sweetened version. In fact, Cranberry Juice available at grocery stores is one of the highest sugar content items across all items carried in any grocery store. Cranberry Juice has more sugar than Coke or Pepsi. While tasty, cranberry juice has an unusually high sugar content due to the unique tartness of the cranberry. To offset the tartness of the cranberry, more sugar is added to improve the overall flavor. An 8-ounce glass of cranberry juice has more sugar than a can of soda at 33 grams. According to info gathered by HealthScience.net, new information and research on cranberry juice suggests the beverage is not as healthy as once considered, and in many cases may be worse for you than soft drinks and sodas considering cranberry juice is higher in sugar and calories. However, this is debatable considering soft drinks often contain caffeine, another controversial ingredient that has both positive and negative characteristics. Parents have long considered cranberry juice a healthy choice for their children, however new information about the high sugar content in cranberry juice is emerging and causing concern. A laboratory study found that when fructose is present as children’s fat cells mature, it makes more of these cells mature into fat cells in body fat, contributing to overweight, obesity and subsequently related health issues such as diabetes, higher cholesterol, and higher blood pressure. Further, new research on cranberry juice also points to cranberry juice drinks causing kidney stones, because of the oxalate in them, despite earlier claims that cranberry juice drink was good for the prevention of kidney stones. Cranberry juice cocktail is sometimes used as a mixer with alcoholic drinks such as a Cape Codder (1+1/2 ounces of vodka to 4 ounces cranberry juice) or non-alcoholic drinks such as the Bog Grog (2 parts Chelmsford ginger ale [or regular ginger ale] to 3 parts cranberry juice).][ Cranberry juice contains substances that may affect individual health. These substances include: Cranberry juice may help prevent and relieve the symptoms of urinary tract infections (UTIs) by primary and secondary means. The primary means works on the bacteria directly by altering the molecular structure of the fimbriae on the pathogenic strains of the bacteria that cause the infections. The properties of the proanthocyanidins in cranberries prevents the bacteria from adhering to the surface of the bladder and urinary tract. The secondary means works indirectly on the bacteria by changing the intravesical pH (the pH of the bladder's contents) making it more acidic.][ However, results from recent randomized controlled trials have been disappointing. A trial of 319 college women with an acute UTI, failed to show that drinking cranberry juice (8 oz of 27% twice daily) would reduce the incidence of a second UTI. Another study performed in the Netherlands randomised 221 women to receive either co-trimoxazole or cranberry capsules. That study found that the antibiotics were superior to cranberry capsules, but were associated with an increase in antibiotic resistance. However, in an accompanying editorial, the dose of cranberries used in the study was criticised for being too low. A more recent study led by the University of Sterling in the U.K., shows the UTI benefits have been overhyped, and suggests there may not be much benefit from cranberry juice at all.][ Results from a review of 24 studies with a research sample of nearly 5,000 people suggest that cranberry juice may only be helpful in a select few women.][ For those select few, cranberry extract pills are recommended in lieu of cranberry juice due to the high sugar content in cranberry juice.][ 1cup of cranberry juice (253 mL) contains the following nutritional information according to the USDA:

Juice
Juice is a liquid that is naturally contained in fruit and vegetables. It can also refer to liquids that are flavored with these or other biological food sources such as meat and seafood. It is commonly consumed as a beverage or used as an ingredient or flavoring in foods. Juice is prepared by mechanically squeezing or macerating fruit or vegetable flesh without the application of heat or solvents. For example, orange juice is the liquid extract of the fruit of the orange tree, and tomato juice is the liquid that results from pressing the fruit of the tomato plant. Juice may be prepared in the home from fresh fruit and vegetables using a variety of hand or electric juicers. Juice is one of the most popular drinks to go with breakfast in the morning. Many commercial juices are filtered to remove fiber or pulp, but high-pulp fresh orange juice is a popular beverage. Common methods for preservation and processing of fruit juices include canning, pasteurization, concentrating, freezing, evaporation and spray drying. In the United Kingdom the name or names of the fruit followed by juice can only legally be used to describe a product which is 100% fruit juice, as required by the Fruit Juices and Fruit Nectars (England) Regulations and the Fruit Juices & Fruit Nectars (Scotland) Regulations 2003. However, a juice made by reconstituting concentrate can be called juice. A product described as fruit "nectar" must contain at least 25% to 50% juice, depending on the fruit. A juice or nectar including concentrate must state that it does. The term "juice drink" is not defined in the Regulations and can be used to describe any drink which includes juice, however little. Comparable rules apply in all EU member states in their respective languages. In the US fruit juice can only legally be used to describe a product which is 100% fruit juice. A blend of fruit juice(s) with other ingredients, such as high-fructose corn syrup, is called a juice cocktail or juice drink. According to the Food and Drug Administration (FDA), the term "nectar" is generally accepted in the US and in international trade for a diluted juice to denote a beverage that contains fruit juice or puree, water, and which may contain artificial sweeteners. "No added sugar" is commonly printed on labels of juice containers, but the products may contain large amounts of naturally occurring sugars; however, sugar content is listed with other carbohydrates on labels in many countries. Some carbonated beverages, not described as fruit juice, contain fruit juice (such as Mountain Dew or Orangina, which contain orange juice). Juices are often consumed for their perceived health benefits. For example, orange juice is rich in vitamin C, folic acid, potassium, is an excellent source of bioavailable antioxidant phytochemicals and significantly improves blood lipid profiles in people affected with hypercholesterolemia. Prune juice is associated with a digestive health benefit. Cranberry juice has long been known to help prevent or even treat bladder infections, and it is now known that a substance in cranberries prevents bacteria from binding to the bladder. Many fruit juices have a higher sugar (fructose) content than sweetened soft drinks; e.g., typical grape juice has 50% more sugar than Coca-Cola. While soft drinks (e.g. Coca-Cola) cause oxidative stress when ingested and may even lead to insulin resistance in the long term, the same thing cannot be attributed to fruit juices. On the contrary, fruit juices are actually known for their ability to raise serum antioxidant capacity and even offset the oxidative stress and inflammation normally caused by high-fat and high-sugar meals. Fruit juice consumption overall in Europe, Australia, New Zealand and the US has increased in recent years, probably due to public perception of juices as a healthy natural source of nutrients and increased public interest in health issues. Indeed, fruit juice intake has been consistently associated with reduced risk of many cancer types, might be protective against stroke and delay the onset of Alzheimer's disease. The perception of commercial fruit juice as equal in health benefit to fresh fruit has been questioned, mainly because it lacks fiber and has often been highly processed. High-fructose corn syrup, an ingredient of many juice cocktails, has been linked to the increased incidence of type II diabetes. High consumption of juice is also linked to weight gain in some studies, but not in others. In a controlled clinical study, regular consumption of grape juice for 12 weeks did not cause any weight gain in volunteers, but consumption of a soft drink did. Fruit juice in moderate amounts can help children and adults meet daily recommendations for fruit consumption, nutrient intake and calories. The American Academy of Pediatrics says that fruit juice should not be given to infants before 6 months of age. For children ages 1 to 6, intake of fruit juice should be limited to 4 to 6 ounces per day (about a half to three-quarters of a cup). Giving children excessive juice can lead to poor nutrition, diarrhea, gas, abdominal pain, bloating, and tooth decay. A juice bar is an establishment that primarily serves prepared juice beverages such as freshly squeezed or extracted fruit juices, juice blends, fruit smoothies (a thick fruit drink, often iced), or other juices such as fresh wheatgrass juice. Sometimes other solid ingredients or nutritional supplements may be added as boosters, such as fresh bananas, eggs, nuts or nut butter, bodybuilding supplements, soy protein powder or others such as whey or hemp protein powders, wheat germ, or Spirulina (dietary supplement) or Chlorella. Also if less juice is used with these same ingredients drinks called health shakes may be produced. Juice bars share some of the characteristics of a coffeehouse, a soda fountain, a café, and a snack bar. Juice bars may be stand alone businesses in cities, or located at gyms, along commuter areas, near lunch time areas, at beaches, and at tourist attractions. Media related to Juices at Wikimedia Commons

Soft drink
A soft drink (also called soda, pop, coke, soda pop, fizzy drink, tonic, seltzer, mineral, sparkling water, lolly water, or carbonated beverage) is a beverage that typically contains water (often, but not always, carbonated water), usually a sweetener, and usually a flavoring agent. The sweetener may be sugar, high-fructose corn syrup, fruit juice, sugar substitutes (in the case of diet drinks) or some combination of these. Soft drinks may also contain caffeine, colorings, preservatives and other ingredients. Soft drinks are called "soft" in contrast to "hard drinks" (alcoholic beverages). Small amounts of alcohol may be present in a soft drink, but the alcohol content must be less than 0.5% of the total volume if the drink is to be considered non-alcoholic. Fruit juice, tea, and other such non-alcoholic beverages are technically soft drinks by this definition but are not generally referred to as such. Soft drinks may be served chilled or at room temperature, and some, such as Dr Pepper, can be served warm. The first marketed soft drinks in the Western world appeared in the 17th century. They were made of water and lemon juice sweetened with honey. In 1676, the Compagnie des Limonadiers of Paris was granted a monopoly for the sale of lemonade soft drinks. Vendors carried tanks of lemonade on their backs and dispensed cups of the soft drink to thirsty Parisians. In the late 18th century, scientists made important progress in replicating naturally carbonated mineral waters. In 1767, Englishman Joseph Priestley first discovered a method of infusing water with carbon dioxide to make carbonated water when he suspended a bowl of distilled water above a beer vat at a local brewery in Leeds, England. His invention of carbonated water (also known as soda water) is the major and defining component of most soft drinks. Priestley found that water treated in this manner had a pleasant taste, and he offered it to friends as a refreshing drink. In 1772, Priestley published a paper entitled Impregnating Water with Fixed Air in which he describes dripping oil of vitriol (or sulfuric acid as it is now called) onto chalk to produce carbon dioxide gas, and encouraging the gas to dissolve into an agitated bowl of water. Another Englishman, John Mervin Nooth, improved Priestley's design and sold his apparatus for commercial use in pharmacies. Swedish chemist Torbern Bergman invented a generating apparatus that made carbonated water from chalk by the use of sulfuric acid. Bergman's apparatus allowed imitation mineral water to be produced in large amounts. Swedish chemist Jöns Jacob Berzelius started to add flavors (spices, juices, and wine) to carbonated water in the late eighteenth century. A variant of soda in the United States called "phosphate soda" appeared in the late 1870s. It became one of the most popular soda fountain drinks from 1900 through the 1930s, with the lemon or orange phosphate being the most basic. The drink consists of 1 US fl oz (30 ml) fruit syrup, 1/2 teaspoon of phosphoric acid, and enough carbonated water and ice to fill a glass. This drink was commonly served in pharmacies. Artificial mineral waters, usually called "soda water", and the soda fountain were mostly popular in the United States.][ Beginning in 1806, Yale University chemistry professor Benjamin Silliman sold soda waters in New Haven, Connecticut. He used a Nooth apparatus to produce his waters. Businessmen in Philadelphia and New York City also began selling soda water in the early 19th century. In the 1830s, John Matthews of New York City and John Lippincott of Philadelphia began manufacturing soda fountains. Both men were successful and built large factories for fabricating fountains. In 19th century America, the drinking of either natural or artificial mineral water was considered a healthy practice. The American pharmacists selling mineral waters began to add herbs and chemicals to unflavored mineral water. They used birch bark (see birch beer), dandelion, sarsaparilla, fruit extracts, and other substances. Flavorings were also added to improve the taste. Pharmacies with soda fountains became a popular part of American culture. Many Americans frequented the soda fountain on a daily basis. Due to problems in the U.S. glass industry, bottled drinks were a small portion of the market in the 19th century. (However, they were known in England. In The Tenant of Wildfell Hall, published in 1848, the caddish Huntingdon, recovering from months of debauchery, wakes at noon and gulps a bottle of soda-water.) In America, most soft drinks were dispensed and consumed at a soda fountain, usually in a drugstore or ice cream parlor. In the early 20th century, sales of bottled soda increased exponentially. In the second half of the 20th century, canned soft drinks became an important share of the market. Over 1,500 U.S. patents were filed for either a cork, cap, or lid for the carbonated drink bottle tops during the early days of the bottling industry. Carbonated drink bottles are under great pressure from the gas. Inventors were trying to find the best way to prevent the carbon dioxide or bubbles from escaping. In 1892, the "Crown Cork Bottle Seal" was patented by William Painter, a Baltimore, Maryland machine shop operator. It was the first very successful method of keeping the bubbles in the bottle. In 1899, the first patent was issued for a glass-blowing machine for the automatic production of glass bottles. Earlier glass bottles had all been hand-blown. Four years later, the new bottle-blowing machine was in operation. It was first operated by the inventor, Michael Owens, an employee of Libby Glass Company. Within a few years, glass bottle production increased from 1,400 bottles a day to about 58,000 bottles a day. During the 1920s, "Home-Paks" were invented. "Home-Paks" are the familiar six-pack cartons made from cardboard. Vending machines also began to appear in the 1920s. Since then, soft drink vending machines have become increasingly popular. Both hot and cold drinks are sold in these self-service machines throughout the world. Soft drinks are made by mixing dry ingredients and/or fresh ingredients (for example, lemons, oranges, etc.) with water. Production of soft drinks can be done at factories or at home. Soft drinks can be made at home by mixing either a syrup or dry ingredients with carbonated water. Carbonated water is made using a soda siphon or a home carbonation system or by dropping dry ice into water. Syrups are commercially sold by companies such as Soda-Club; dry ingredients are often sold in pouches, in the style of the popular U.S. drink mix Kool-Aid. Drinks like ginger ale and root beer are often brewed using yeast to cause carbonation. Of most importance is that the ingredient meets the agreed specification on all major parameters. This is not only the functional parameter (in other words, the level of the major constituent), but the level of impurities, the microbiological status, and physical parameters such as color, particle size, etc. A report in October 2006 demonstrated that some soft drinks contain measurable amounts of alcohol. In some older preparations, this resulted from natural fermentation used to build the carbonation. In the United States, soft drinks (as well as other beverages such as non-alcoholic beer) are allowed by law to contain up to 0.5% alcohol by volume. Modern drinks introduce carbon dioxide for carbonation, but there is some speculation that alcohol might result from fermentation of sugars in an unsterile environment. A small amount of alcohol is introduced in some soft drinks where alcohol is used in the preparation of the flavoring extracts such as vanilla extract. The consumption of sugar-sweetened soft drinks is associated with obesity, type 2 diabetes, dental caries, and low nutrient levels. Experimental studies tend to support a causal role for sugar-sweetened soft drinks in these ailments, though this is challenged by other researchers. "Sugar-sweetened" includes drinks that use high-fructose corn syrup, as well as those using sucrose. Many soft drinks contain ingredients that are themselves sources of concern: caffeine is linked to anxiety and sleep disruption when consumed in excess, and some critics question the health effects of added sugars and artificial sweeteners Sodium benzoate has been investigated by researchers at University of Sheffield as a possible cause of DNA damage and hyperactivity. Other substances have negative health effects, but are present in such small quantities that they are unlikely to pose any substantial health risk provided that the beverages are consumed only in moderation. In 1998, the Center for Science in the Public Interest published a report titled Liquid Candy: How Soft Drinks are Harming Americans' Health. The report examined statistics relating to the increase in soft drink consumption and claimed that consumption is "likely contributing to health problems." It also criticized marketing efforts by soft drink companies. From 1977 to 2002, Americans doubled their consumption of sweetened beverages—a trend that was paralleled by doubling the prevalence of obesity. The consumption of sugar-sweetened beverages is associated with weight and obesity, and changes in consumption can help predict changes in weight. One study followed 548 schoolchildren over 19 months and found that changes in soft drink consumption were associated with changes in body mass index (BMI). Each soft drink that a child added to his or her daily consumption was accompanied by an increase in BMI of 0.24 kg/m2. Similarly, an 8-year study of 50,000 female nurses compared women who went from drinking almost no soft drinks to drinking more than one a day to women who went from drinking more than one soft drink a day to drinking almost no soft drinks. The women who increased their consumption of soft drinks gained 8.0 kg over the course of the study while the women who decreased their consumption gained only 2.8 kg. In each of these studies, the absolute number of soft drinks consumed per day was also positively associated with weight gain. It remains possible that the correlation is due to a third factor: people who lead unhealthy lifestyles might consume more soft drinks. If so, then the association between soft drink consumption and weight gain could reflect the consequences of an unhealthy lifestyle rather than the consequences of consuming soft drinks. Experimental evidence is needed to definitively establish the causal role of soft drink consumption. Reviews of the experimental evidence suggest that soft drink consumption does cause weight gain, but the effect is often small except for overweight individuals. Many of these experiments examined the influence of sugar-sweetened soft drinks on weight gain in children and adolescents. In one experiment, adolescents replaced sugar-sweetened soft drinks in their diet with artificially sweetened soft drinks that were sent to their homes over 25 weeks. Compared with children in a control group, children who received the artificially sweetened drinks saw a smaller increase in their BMI (by −.14 kg/m2), but this effect was only statistically significant among the heaviest children (who saw a benefit of −.75 kg/m2). In another study, an educational program encouraged schoolchildren to consume fewer soft drinks. During the school year, the prevalence of obesity decreased among children in the program by 0.2%, compared to a 7.5% increase among children in the control group. Sugar-sweetened drinks have also been speculated to cause weight gain in adults. In one study, overweight individuals consumed a daily supplement of sucrose-sweetened or artificially sweetened drinks or foods for a 10 week period. Most of the supplement was in the form of soft drinks. Individuals in the sucrose group gained 1.6 kg, and individuals in the artificial-sweetener group lost 1.0 kg. A two week study had participants supplement their diet with sugar-sweetened soft drinks, artificially sweetened soft drinks, or neither. Although the participants gained the most weight when consuming the sugar-sweetened drinks, some of the differences were unreliable: the differences between men who consumed sugar-sweetened drinks or no drinks was not statistically significant. Other research suggests that soft drinks could play a special role in weight gain. One four-week experiment compared a 450 calorie/day supplement of sugar-sweetened soft drinks to a 450 calorie/day supplement of jelly beans. The jelly bean supplement did not lead to weight gain, but the soft drink supplement did. The likely reason for the difference in weight gain is that people who consumed the jelly beans lowered their caloric intake at subsequent meals, while people who consumed soft drinks did not. Thus, the low levels of satiety provided by sugar-sweetened soft drinks may explain their association with obesity. That is, people who consume calories in sugar-sweetened beverages may fail to adequately reduce their intake of calories from other sources. Indeed, people consume more total calories in meals and on days when they are given sugar-sweetened beverages than when they are given artificially sweetened beverages or water. However, these results are contradicted by a study by Adam Drewnowski published in 2004, in which "32 subjects consumed a 300-calorie snack of fat-free raspberry cookies or regular cola on two occasions each – either two hours (“early”) or 20 minutes (“late”) before lunch." It found that "...the calories eaten at lunch were not affected by whether the snack was cookies or cola." A study by Purdue University reported that no-calorie sweeteners were linked to an increase in body weight. The experiment compared rats who were fed saccharin-sweetened yogurt and glucose-sweetened yogurt. The saccharin group eventually consumed more calories, gained more weight and more body fat, and did not compensate later by cutting back. The consumption of sugar-sweetened soft drinks can also be associated with many weight-related diseases, including diabetes, metabolic syndrome and cardiovascular risk factors, and elevated blood pressure. According to research presented at the American Heart Association's Epidemiology and Prevention/Nutrition, Physical Activity and Metabolism 2013 Scientific Sessions by researchers at the Harvard School of Public Health, sugar-sweetened beverages may be responsible for 180,000 deaths every year worldwide. Most soft drinks contain high concentration of simple carbohydrates: glucose, fructose, sucrose and other simple sugars. Oral bacteria ferment carbohydrates and produce acid, which dissolves tooth enamel during the dental decay process; thus, sweetened drinks are likely to increase risk of dental caries. The risk is greater if the frequency of consumption is high. This has led to dentists referring to soft drinks as "liquid chainsaws". A large number of soft drinks are acidic, and some may have a pH of 3.0 or even lower. Drinking acidic drinks over a long period of time and continuous sipping can therefore erode the tooth enamel. However, under normal conditions, scientific evidence indicates Coca-Cola's acidity causes no immediate harm. Using a drinking straw is often advised by dentists as the drink does not come into as much contact with the teeth. It has also been suggested that brushing teeth right after drinking soft drinks should be avoided as this can result in additional erosion to the teeth due to the presence of acid. There have been a handful of published reports describing individuals with severe hypokalemia (low potassium levels) related to chronic extreme consumption (4-10 L/day) of colas. In a meta-analysis of 88 studies, drinking soda correlates with a decrease in milk consumption along with the vitamin D, vitamin B6, vitamin B12, calcium, protein and other micronutrients. Phosphorus, a micronutrient, can be found in cola-type beverages, but there may be a risk in consuming too much. Phosphorus and calcium are used in the body to create calcium-phosphate, which is the main component of bone. However, the combination of too much phosphorus with too little calcium in the body can lead to a degeneration of bone mass. Research suggests a statistically significant inverse relationship between consumption of carbonated beverages and bone mineral density in young girls, which places them at increased risk of suffering fractures in the future. One hypothesis to explain this relationship is that the phosphoric acid contained in some soft drinks (colas) displaces calcium from the bones, lowering bone density of the skeleton and leading to weakened bones, or osteoporosis. However, calcium metabolism studies by Dr. Robert Heaney suggested that the net effect of carbonated soft drinks, (including colas, which use phosphoric acid as the acidulent) on calcium excretion in urine was negligible. Heaney concluded that carbonated soft drinks, which do not contain the nutrients needed for bone health, may displace other foods which do, and that the real issue is that people who drink a lot of soft drinks also tend to have an overall diet that is low in calcium. In the 1950s and 1960s there were attempts in France and Japan to ban the sale of Coca-Cola as dangerous since phosphates can block calcium absorption. However, these were unsuccessful as the amounts of phosphate were shown to be too small to have a significant effect. The USDA's recommended daily intake (RDI) of added sugars is less than 10 teaspoons per day for a 2,000-calorie diet. High caloric intake contributes to obesity if not balanced with exercise, with a large amount of exercise being required to offset even small but calorie-rich food and drinks. Until 1985, most of the calories in soft drinks came from sugar or corn syrup. As of 2010, in the United States high-fructose corn syrup (HFCS) is used nearly exclusively as a sweetener because of its lower cost, while in Europe, sucrose dominates, because EU agricultural policies favor production of sugar beets in Europe proper and sugarcane in the former colonies over the production of corn. HFCS has been criticized as having a number of detrimental effects on human health, such as promoting diabetes, hyperactivity, hypertension, and a host of other problems. Although anecdotal evidence has been presented to support such claims, it is well known that the human body breaks sucrose down into glucose and fructose before it is absorbed by the intestines. Simple sugars such as fructose are converted into the same intermediates as in glucose metabolism. However, metabolism of fructose is extremely rapid and is initiated by fructokinase. Fructokinase activity is not regulated by metabolism or hormones and proceeds rapidly after intake of fructose. While the intermediates of fructose metabolism are similar to those of glucose, the rates of formation are excessive. This fact promotes fatty acid and triglyceride synthesis in the liver, leading to accumulation of fat throughout the body and possibly non-alcoholic fatty liver disease. Increased blood lipid levels also seem to follow fructose ingestion over time. A sugar drink or high-sugar drink may refer to any beverage consisting primarily of water and sugar (often cane sugar or high-fructose corn syrup), including some soft drinks, some fruit juices, and energy drinks. In 2006, the United Kingdom Food Standards Agency published the results of its survey of benzene levels in soft drinks, which tested 150 products and found that four contained benzene levels above the World Health Organization (WHO) guidelines for drinking water. The United States Food and Drug Administration released its own test results of several soft drinks containing benzoates and ascorbic or erythorbic acid. Five tested drinks contained benzene levels above the Environmental Protection Agency's recommended standard of 5 ppb. The Environmental Working Group has uncovered additional FDA test results that showed the following results: Of 24 samples of diet soda tested between 1995 and 2001 for the presence of benzene, 19 (79%) had amounts of benzene in excess of the federal tap water standard of 5 ppb. Average benzene levels were 19 ppb, about four times tap water standard. One sample contained 55 ppb of benzene, 11 fold tap water standards. Despite these findings, as of 2006, the FDA stated its belief that "the levels of benzene found in soft drinks and other beverages to date do not pose a safety concern for consumers". In 2003, the Delhi non-profit Centre for Science and Environment published a disputed report finding pesticide levels in Coke and Pepsi soft drinks sold in India at levels 30 times that considered safe by the European Economic Commission. This was found in primarily 12 cold drink brands sold in and around New Delhi. The Indian Health Minister said the CSE tests were inaccurate, and said that the government's tests found pesticide levels within India's standards but above EU standards. A similar CSE report in August 2006 prompted many state governments to have issued a ban of the sale of soft drinks in schools. Kerala issued a complete ban on the sale or manufacture of soft drinks altogether. (These were later struck down in court.) In return, the soft drink companies like Coca-Cola and Pepsi have issued ads in the media regarding the safety of consumption of the drinks. The UK-based Central Science Laboratory, commissioned by Coke, found its products met EU standards in 2006. Coke and the University of Michigan commissioned an independent study of its bottling plants by The Energy and Resources Institute (TERI), which reported in 2008 no unsafe chemicals in the water supply used. In recent years, debate on whether high-calorie soft drink vending machines should be allowed in schools has been on the rise. Opponents of the (soft drink) vending machines believe that soft drinks are a significant contributor to childhood obesity and tooth decay, and that allowing soft drink sales in schools encourages children to believe they are safe to consume in moderate to large quantities. Opponents argue that schools have a responsibility to look after the health of the children in their care, and that allowing children easy access to soft drinks violates that responsibility. Vending machine proponents believe that obesity is a complex issue and soft drinks are not the only cause. They also note the immense amount of funding that soft drink sales bring to schools. Some people][ take a more moderate stance, saying that soft drink machines should be allowed in schools, but that they should not be the only option available. They propose that when soft drink vending machines are made available on school grounds, the schools should be required to provide children with a choice of alternative drinks (such as fruit juice, flavored water and milk) at a comparable price. Some lawmakers debating the issue in different states have argued that parents—not the government—should be responsible for children's beverage choices. On May 3, 2006, the Alliance for a Healthier Generation, Cadbury Schweppes, Coca-Cola, PepsiCo, and the American Beverage Association announced new School Beverage Guidelines that will voluntarily remove high-calorie soft drinks from all U.S. schools. On 19 May 2006, the British Education Secretary, Alan Johnson, announced new minimum nutrition standards for school food. Amongst a wide range of measures, from September 2006, school lunches will be free from carbonated drinks. Schools will also end the sale of junk food (including carbonated drinks) in vending machines and tuck shops. In the United States and elsewhere, legislators, health experts and consumer advocates are considering levying higher taxes on the sale of soft drinks and other sweetened beverages to help curb the epidemic of obesity among Americans, and its harmful impact on overall health. Some speculate that higher taxes could help reduce soda consumption. Others say that taxes could help fund education to increase consumer awareness of the unhealthy effects of excessive soft drink consumption, and also help cover costs of caring for conditions resulting from overconsumption. The food and beverage industry holds considerable clout in Washington, DC, as it has contributed more than $50 million to legislators since 2000. In January 2013, a British lobby group called for the price of sugary fizzy drinks to be increased, with the money raised (an estimated £1 billion at 20p per litre) to be put towards a "Children's Future Fund", overseen by an independent body, which would encourage children to eat healthily in school. In March 2013, New York City's mayor Michael Bloomberg proposed to ban the sale of non-diet soft drinks larger than 16 ounces, except in convenience stores and supermarkets. A lawsuit against the ban was upheld by a state judge, who voiced concerns that the ban was "fraught with arbitrary and capricious consequences". Bloomberg announced that he would be appealing the verdict.

Energy drink
An energy drink is a type of beverage containing stimulant drugs, chiefly caffeine, which is marketed as providing mental or physical stimulation. They may or may not be carbonated, and generally contain large amounts of caffeine and other stimulants, and many also contain sugar or other sweeteners, herbal extracts and amino acids. They are a subset of the larger group of energy products, which includes bars and gels. There are many brands and varieties of energy drinks. Coffee, tea and other naturally caffeinated beverages are usually not considered energy drinks. Soft drinks such as cola, may contain caffeine, but are also not energy drinks. Some alcoholic beverages, such as Four Loko, contain caffeine and other stimulants and are marketed as energy drinks, although such drinks are banned in some American states. Energy drinks were an active subset of the early soft drink industry, which was originally dominated by pharmacists and less scrupulous patent medicine salesmen. Coca-Cola, for instance, was originally marketed as an energy booster; its name was derived from its two active ingredients, both known stimulants: Coca leaves and kola nuts (a source of caffeine). Fresh coca leaves were replaced by "spent" ones in 1904 because of concerns over the use of cocaine in food products. In the UK, Lucozade Energy was originally introduced in 1929 as a hospital drink for "aiding the recovery;" in the early 1980s, it was promoted as an energy drink for "replenishing lost energy." One of the first energy drinks introduced in America was Dr. Enuf. Its origins date back to 1949, when a Chicago businessman named William Mark Swartz was urged by coworkers to formulate a soft drink fortified with vitamins as an alternative to sugar sodas full of empty calories. He developed an "energy booster" drink containing B vitamins, caffeine and cane sugar. After placing a notice in a trade magazine seeking a bottler, he formed a partnership with Charles Gordon of Tri-City Beverage to produce and distribute the soda. Dr. Enuf is still being manufactured in Johnson City, TN and sold sparsely throughout the nation. In Japan, the energy drink dates at least as far back as the early 1960s, with the release of the Lipovitan. However, most such products in Japan bear little resemblance to soft drinks, and are sold instead in small brown glass medicine bottles or cans styled to resemble such containers. These "eiyō dorinku" (literally, "nutritional drinks") are marketed primarily to salaryman. Bacchus-F, a South Korean drink closely modeled after Lipovitan, also appeared in the early 1960s, and targets a similar demographic. In 1985, Jolt Cola was introduced in the United States. Its marketing strategy centered on the drink's caffeine content, billing it as a means to promote wakefulness. The initial slogan was, "All the sugar and twice the caffeine." In 1995, PepsiCo launched Josta, the first energy drink introduced by a major US beverage company (one that had interests outside energy drinks), but Pepsi discontinued the product in 1999.][ Pepsi would later return to the energy drink market with the AMP brand. In Europe, energy drinks were pioneered by the Lisa and a product named Power Horse, before the business savvy of Dietrich Mateschitz, an Austrian entrepreneur, ensured his Red Bull product became far better known, and a worldwide best seller. Mateschitz developed Red Bull based on the Thai drink Krating Daeng, itself based on Lipovitan. Red Bull is the dominant brand in the US after its introduction in 1997, with a market share of approximately 47%. In New Zealand and Australia, the current leading energy drinks product in those markets V was introduced by Frucor Beverages It is now serves over 60% of market in New Zealand and Australia]. By 2001, the US energy drink market had grown to nearly 8 million per year in retail sales. Over the next 5 years, it grew an average of over 50% per year, totaling over $3 billion in 2005. Diet energy drinks are growing at nearly twice that rate within the category, as are 16-ounce (470 ml) sized energy drinks. The energy drink market became a $5.4 billion dollar market in 2007, and both Goldman Sachs and Mintel predicted that it would hit $10 billion by 2010. The market is currently estimated at over $12.5 Billion, having grown 60% between 2008-2012. Major companies such as Pepsi, Coca-Cola, Molson, and Labatt have tried to match smaller companies' innovative and different approach, with marginal success.][ Energy drinks are typically attractive to young people. Approximately 66% percent of its drinkers are between the ages of 13 and 35 years old, with males being approximately 65% of the market. A 2008 statewide Patient Poll conducted by the Pennsylvania Medical Society's Institute for Good Medicine found that: 20% of respondents ages 21–30 had used energy drinks in high school or college to stay awake longer to study or write a paper; 70% of respondents knew someone who had used an energy drink to stay awake longer to study or work. Energy drinks are also popular as drink mixers. UK supermarkets have launched their own brands of energy drinks at lower prices than the major soft drink manufacturers. These are mostly produced by Canadian beverage maker Cott. Tesco supermarkets sell 'Kx"'(used to be known as 'Kick') in 250 mL cans and 1 L bottles, Sainsbury's sell 'Blue Bolt' in similar packaging, Asda sell 'Blue Charge' in similar packaging and Morrison's sell 'Source' in 250 mL cans. Cott sells a variety of other branded energy drinks to independent retailers in various containers.][ Since 2002, there has been a growing trend for packaging energy drink in bigger cans.][ Since in many countries, including the US and Canada, there is a limitation on the maximum caffeine per serving in energy drinks, this allows manufacturers to include a greater amount of caffeine by including multiple servings per container. Popular brands such as Red Bull, Hype Energy Drinks and Monster have increased the amount of ounces per can. (For example, when Red Bull first came on the U.S. market, it was primarily in 250 mL (8.4 oz.) cans; it now sells cans as big as 600 mL (20 oz.), and Monster now sells a can as big as 32 oz. (946 mL).) Most energy drinks in the United States, with a few exceptions, primarily sell their drinks in 16 oz. (473 mL) cans, a trend provoked in part by companies such as Rockstar Energy promoting the 16-ounce cans over Red Bull's smaller ones in the mid-2000s. Conversely, the emergence of energy shots has gone the opposite way with much smaller packaging.][ In 2007, energy drink powders and effervescent tablets were introduced, in the form of a tablet or powder that can be added to water to create an energy drink. These can offer a more portable option to cans and shots.][ As of 2009, the industry has moved towards the use of natural stimulants and reduced sugar.][ On August 14, 2012, the word "energy drink" was listed for the first time in the mainstream Merriam-Webster's Collegiate Dictionary. Energy drinks generally contain methylxanthines (including caffeine), B vitamins, and herbs. Other commonly used ingredients are carbonated water, guarana, yerba mate, açaí, and taurine, plus various forms of ginseng, maltodextrin, inositol, carnitine, creatine, glucuronolactone, and ginkgo biloba. Some contain high levels of sugar, and many brands offer artificially sweetened 'diet' versions. A common ingredient in most energy drinks is caffeine (often in the form of guarana or yerba mate). Caffeine is the stimulant that is found in coffee and tea. There is little or no evidence that any of the ingredients found in energy drinks other than caffeine or sugar have a significant physiological effect. Energy drinks contain about three times the amount of caffeine as cola. Twelve ounces of Coca-Cola Classic contains 35 mg of caffeine, whereas a Monster Energy Drink contains 120 mg of caffeine. Energy drinks have the effects caffeine and sugar provide, but there is little or no evidence that the wide variety of other ingredients have any effect. However, a variety of physiological and psychological effects have been attributed to energy drinks and their ingredients. Two studies reported significant improvements in mental and cognitive performances as well as increased subjective alertness. Excess consumption of energy drinks may induce mild to moderate euphoria primarily caused by stimulant properties of caffeine and may also induce agitation, anxiety, irritability and insomnia. During repeated cycling tests in young healthy adults an energy drink significantly increased upper body muscle endurance. It has been suggested that reversal of caffeine withdrawal is a major component of the effects of caffeine on mood and performance. Restorative properties were shown by a combination of caffeine and the sugar glucose in an energy drink, and some degree of synergy between the cognition-modulating effects of glucose and caffeine was also suggested. In one experiment, a glucose-based energy drink (containing caffeine, taurine and glucuronolactone) was given to eleven tired participants being tested in a driving simulator. Lane drifting and reaction times were measured for two hours post-treatment and showed significant improvement. Two articles concluded that the improved information processing and other effects could not be explained in terms of the restoration of plasma caffeine levels to normal following caffeine withdrawal. Consumption of a single energy drink will not lead to excessive caffeine intake, but consumption of two or more drinks in a single day can. Other stimulants such as ginseng are often added to energy drinks and may enhance the effects of caffeine, and ingredients such as guarana themselves contain caffeine. Adverse effects associated with caffeine consumption in amounts greater than 400 mg include nervousness, irritability, sleeplessness, increased urination, abnormal heart rhythms (arrhythmia), and dyspepsia. Consumption also has been known to cause pupil dilation when taken with certain antidepressants or SSRIs. Most mainstream energy drinks do not provide electrolytes, and have a higher likelihood of an energy "crash-and-burn" effect. Caffeine in energy drinks can cause the excretion of water from the body to dilute high concentrations of sugar entering the blood stream, leading to dehydration. If the body is dehydrated by 1%, performance is decreased by up to 10%. In the US, energy drinks have been linked with reports of nausea, abnormal heart rhythms and emergency room visits. The drinks may cause seizures due to the "crash" following the energy high that occurs after consumption. Caffeine dosage is not required to be on the product label for food in the United States, unlike drugs, but some advocates are urging the FDA to change this practice. In November 2010, the University of Texas Medical School at Houston reported that energy drinks contain more caffeine than a strong cup of coffee][, and that the caffeine combined with other ingredients (sometimes not reported correctly on labels) such as guarana, taurine, other herbs, vitamins and minerals may interact. Energy drinks consumed with alcohol may affect heart rates, blood pressure and even mental states. The caffeine content of energy drinks range from 80–300 mg per 16-oz serving whereas a 16-oz cup of coffee can contain 70–200 mg.][ Health experts say caffeine prevents sleepiness and delays the feeling of drunkenness normally experienced when drinking alcohol, causing some people to continue drinking after they normally would have stopped. Caffeine is a very mild diuretic in comparison with alcohol, but some experts believe that mixing energy drinks with alcohol can cause greater dehydration than alcohol alone. The energy drink Red Bull did not get market approval in France after the death of an 18-year-old Irish athlete, Ross Cooney, who died within hours after playing a basketball game and consuming four cans of the product. This market approval was challenged in the European Court of Justice in 2004, and consequently lifted. Norway did not allow Red Bull for a while, although this has recently been revoked.][ The United Kingdom investigated the drink, but only issued a warning against its consumption by children and pregnant women. In November 2012, President Ramzan Kadyrov of Chechnya (Russian Federation) ordered his government to develop a bill banning the sale of energy drinks, arguing that as a form of "intoxicating drug", such drinks were "unacceptable in a Muslim society". Kadyrov cited reports of one death and 530 hospital admissions in 2012 due to "poisoning" from the consumption of such drinks. A similar view was expressed by Gennady Onishchenko, Chief Sanitary Inspector of Russia. In 2009, a school in Hove, England requested that local shops refrain from selling energy drinks to students. Headteacher Malvina Sanders added that "This was a preventative measure, as all research shows that consuming high-energy drinks can have a detrimental impact on the ability of young people to concentrate in class." The school negotiated for their local branch of the Tesco supermarket to display posters asking students not to purchase the products. Similar measures were taken by a school in Oxted, England, which banned students from consuming drinks and sent letters to parents. Some countries have certain restrictions on the sale and/or manufacture of energy drinks for example; in Australia and New Zealand, energy drinks are regulated under the Australia New Zealand Food Standards Code; limiting the caffeine content of 'formulated caffeinated beverages' (energy drinks) at 320 mg/L (9.46 mg/oz) and soft-drinks at 145 mg/L (4.29 mg/oz). Mandatory caffeine labeling is issued for all food products containing guarana. On June 7, 2012, the parliament of Latvia approved changes in the legislation of sale of consumable goods, to prohibit sale of energy drinks to persons under the age of 18. As of 2013 in the United States some energy drinks, including Monster Energy and Rockstar Energy, were reported to be rebranding their products as beverages rather than as dietary supplements. As beverages they would be relieved of F.D.A. reporting requirements with respect to deaths and injuries and can be purchased with food stamps, but must list ingredients on the can. Energy shots are a specialized kind of energy drink. Whereas most energy drinks are sold in cans or bottles, energy shots are usually sold in smaller 50ml bottles. Energy shots can contain the same total amount of caffeine, vitamins or other functional ingredients as their larger versions, and may be considered concentrated forms of energy drinks. The marketing of energy shots generally focuses on their convenience and availability as a low-calorie "instant" energy drink that can be taken in one swallow (or "shot"), as opposed to energy drinks that encourage users to drink an entire can, which may contain 250 calories or more. Energy drinks such as Red Bull are often used as mixers with alcoholic beverages, producing mixed drinks such as Vodka Red Bull which are similar to but stronger than rum and coke with respect to the amount of caffeine that they contain. They are also sold in a wide variety of formulations such as Four Loko and Joose which combine caffeine and alcohol. Four Loko, a product of Phusion Projects, was originally promoted through young employees who were hired to introduce the product to their peer group. Through separate mechanisms, energy drinks act as stimulants, and alcohol as depressants. Mixing a depressant with a stimulant sends mixed signals to the nervous system and can cause cardiac problems such as heart arrhythmia. In addition, energy drinks can lessen some of the subjective effects of alcohol while making the drinker feel more stimulated and less fatigued. However, they may be unable to counteract some of the psychomotor impairments of alcohol intoxication. Consequently, the mix can be particularly hazardous as energy drinks can mask the influence of alcohol and a person may misinterpret their actual level of intoxication. In fact, people who drink mixers are more likely than non-mixers to drink more alcohol, and are also more likely to suffer alcohol-related consequences such as injury or being an intoxicated driver, even after adjusting for the number of drinks. Although people decide to drink energy drinks with alcohol with the intent of counteracting alcohol intoxication, another large majority do so to hide the taste of alcohol. Researchers at the Human Performance Laboratory have suggested people refrain from mixing such powerful stimulants with alcohol, they believe it might cause cardiopulmonary or cardiovascular failures. As of November 10, 2010 caffeinated alcoholic energy drinks had been banned in Washington and Michigan in the United States. The bans followed a widely publicized incident which resulted in hospitalization in the Fall of 2010 of college students who had consumed several cans of Four Loko caffeinated alcoholic beverage. Utah, which has state controlled liquor retail outlets, after studying them, never permitted the sale of caffeinated alcoholic energy drinks. The products will no longer be delivered to Oklahoma after December 3, 2010 and delivery to retailers has been suspended in New York. On November 17, 2010, the US Food and Drug Administration warned four companies, Charge Beverages Corp., New Century Brewing Co., Phusion Projects, and United Brands Company Inc, that the caffeine added to their malt alcoholic beverages is an "unsafe food additive" and said that further action, including seizure of their products, may occur under federal law. In a press release, the FDA states "there is evidence that the combinations of caffeine and alcohol in these products pose a public health concern." They also state that concerns have been raised that caffeine can mask some of the sensory cues individuals might normally rely on to determine their level of intoxication. Warning letters were issued to each of the four companies requiring them to provide to the FDA in writing within 15 days of the specific steps the firms will be taking. Manufacturers have argued that drinking a caffeinated alcoholic energy drink is indistinguishable from drinking a couple of glasses of wine followed by a couple of cups of coffee. Several beverages have been marketed in the 2000s as "anti-energy", "chill out", or "relaxation" drinks, including Lava Cola, Slow Cow, Drank, Marley's Mellow Mood, Mary Jane's Relaxing Soda, Chill, Calm, Malava Kava, V.i.B., Relax by Rockstar and Jones Gaba. They are growing in popularity, with sales doubling from 2008 to 2010, and expected to more than double again by 2014. They contain ingredients such as theanine and melatonin.

Methamphetamine
InChI=1S/C10H15N/c1-9(11-2)8-10-6-4-3-5-7-10/h3-7,9,11H,8H2,1-2H3 
Key:MYWUZJCMWCOHBA-UHFFFAOYSA-N  Methamphetamine (USAN) , also known as metamfetamine (INN), meth, ice, clouds crystal, glass, tik, N-methylamphetamine, methylamphetamine, and desoxyephedrine, is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs. Methamphetamine occurs in two enantiomers, dextrorotary and levorotary. Dextromethamphetamine is a stronger psychostimulant, but levomethamphetamine has a longer half-life and is CNS-active with weaker (approx. one-tenth) effects on striatal dopamine and shorter psychodynamic effects. At high doses, both enantiomers of methamphetamine can induce stereotypy and psychosis, but levomethamphetamine is less desired by drug abusers because of its weaker pharmacodynamic profile. Although rarely prescribed, methamphetamine hydrochloride is approved by the U.S. Food and Drug Administration (FDA) for the treatment of attention deficit hyperactivity disorder and obesity under the trade name Desoxyn. Illicitly, methamphetamine may be sold either as pure dextromethamphetamine or in a racemic mixture. Both dextromethamphetamine and racemic methamphetamine are Schedule II controlled substances in the United States, and similarly the production, distribution, sale, and possession of methamphetamine is restricted or illegal in many jurisdictions. Internationally, methamphetamine has been placed in Schedule II of the United Nations Convention on Psychotropic Substances treaty. Contrary to popular misconception, methamphetamine in both powder and crystal form is a hydrochloride salt. The freebase form of methamphetamine (as well as amphetamine) is an oily liquid. The misconception started with the fact that heroin and cocaine are injected or snorted as salts, but they are smoked in freebase form. See also: crack cocaine. In low dosages, methamphetamine can increase alertness, concentration, and energy in fatigued individuals. In higher doses, it can induce mania with accompanying euphoria, feelings of self-esteem and increased libido. Methamphetamine has a high potential for abuse and addiction, activating the psychological reward system by triggering a cascading release of dopamine in the brain characterized as Amphetamine/Stimulant psychosis. Chronic abuse may also lead to post-withdrawal syndrome, a result of methamphetamine-induced neurotoxicity to dopaminergic neurons. Post-withdrawal syndrome can persist beyond the withdrawal period for months, and sometimes up to a year. In addition to psychological harm, physical harm – primarily consisting of cardiovascular damage – may occur with chronic use or acute overdose. Methamphetamine has found use as both a medicinal and recreational drug. In United States, Methamphetamine has been approved by the Food and Drug Administration (FDA) in treating ADHD and exogenous obesity (obesity originating from factors outside of the patient's control) in both adults and children. Methamphetamine is a drug that is under the Controlled Substances Act which is listed under Schedule II in the United States and is sold under the name Desoxyn trademarked by the Danish pharmaceutical company Lundbeck. Because methamphetamine is highly abused for negative purposes such as selling the prescription to others, or overdosing (which contributes to very dangerous side effects) than using the medication medically, it is a tightly controlled substance under federal law. The minimum dosage prescribed is 5 milligrams. Desoxyn may be prescribed off-label for the treatment of narcolepsy and treatment-resistant depression. Methamphetamine's levorotary form is available in many over-the-counter nasal decongestant products. Methamphetamine is used as a recreational drug for its euphoric and stimulant properties. Physical effects can include anorexia, hyperactivity, dilated pupils, flushed skin, excessive sweating, restlessness, dry mouth and bruxism (leading to "meth mouth"), headache, accelerated heartbeat, slowed heartbeat, irregular heartbeat, rapid breathing, high blood pressure, low blood pressure, high body temperature, diarrhea, constipation, blurred vision, dizziness, twitching, insomnia, numbness, palpitations, tremors, dry and/or itchy skin, acne, pallor, and – with chronic and/or high doses – convulsions, heart attack, stroke, and death. Psychological effects can include euphoria, anxiety, increased libido, alertness, concentration, increased energy, increased self-esteem, self-confidence, sociability, irritability, aggressiveness, psychosomatic disorders, psychomotor agitation, dermatillomania (compulsive skin picking), hair pulling, delusions of grandiosity, hallucinations, excessive feelings of power and invincibility, repetitive and obsessive behaviors, paranoia, and – with chronic use and/or high doses – amphetamine psychosis. Withdrawal symptoms of methamphetamine primarily consist of fatigue, depression, and increased appetite. Symptoms may last for days with occasional use and weeks or months with chronic use, with severity dependent on the length of time and the amount of methamphetamine used. Withdrawal symptoms may also include anxiety, irritability, headaches, agitation, restlessness, excessive sleeping, vivid or lucid dreams, deep REM sleep, and suicidal ideation. Methamphetamine use has a high association with depression and suicide as well as serious heart disease, amphetamine psychosis, anxiety, and violent behaviors. Methamphetamine also has a very high addiction risk. Methamphetamine is not directly neurotoxic but long-term use can have neurotoxic side-effects. Its use is associated with an increased risk of Parkinson's disease due to the fact that uncontrolled dopamine release is neurotoxic. Long-term dopamine upregulation occurring as a result of Methamphetamine abuse can cause neurotoxicity, which is believed to be responsible for causing persisting cognitive deficits, such as memory loss, impaired attention, and decreased executive function. Similar to the neurotoxic effects on the dopamine system, methamphetamine can also result in neurotoxicity to the serotonin system. As a result of methamphetamine-induced neurotoxicity to dopaminergic neurons, chronic abuse may also lead to post acute withdrawals which persist beyond the withdrawal period for months, and even up to a year. A study performed on female Japanese prison inmates suffering from methamphetamine addiction showed that 49% experienced "flashbacks" afterward and 21% experienced a psychosis resembling schizophrenia which persisted for longer than six months post-methamphetamine use; this amphetamine psychosis could be resistant to traditional treatment. Other studies in Japan show that those who experience methamphetamine-induced psychosis are much more likely to experience psychotic symptoms again if they use methamphetamine.][ In addition to psychological harm, physical harm – primarily consisting of cardiovascular damage – may occur with chronic use or acute overdose. As with other amphetamines, tolerance to methamphetamine is not completely understood but is 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 vary widely between individuals, and even within one person. It is highly dependent on dosage, duration of use, and frequency of administration. Tolerance to the awakening effect of amphetamines does not readily develop, making them suitable for the treatment of narcolepsy. Short-term tolerance can be caused by depleted levels of neurotransmitters within the synaptic 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. Reverse tolerance or sensitization can also occur. The effect is well established, but the mechanism is not well understood. Methamphetamine is highly addictive. While the withdrawal itself may not be dangerous, withdrawal symptoms are common with heavy use and relapse is common. Methamphetamine-induced hyperstimulation of pleasure pathways can lead to anhedonia months after use has been discontinued. Investigation of treatments targeting dopamine signalling such as bupropion, or psychological treatments that raise hedonic tone, such as behavioral activation therapy, have been suggested. It is possible that daily administration of the amino acids L-tyrosine and -5HTPL/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 stimulants such as dextroamphetamine, the dextrorotatory (right-handed) isomer of the amphetamine molecule, 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, as can Topiramate. Methamphetamine addiction is one of the most difficult forms of addictions to treat. Bupropion, aripiprazole, and baclofen have been employed to treat post-withdrawal cravings, although the success rate is low. Modafinil is somewhat more successful, but this is a Class IV scheduled drug. Adrafinil is the prodrug of Modafinil, being metabolized by the body to Modafinil in 45–60 minutes, and is not a controlled substance.][ Ibogaine has been used with success in Europe, where it is a Class I drug and available only for scientific research. Mirtazapine has been reported useful in some small-population studies. As the phenethylamine phentermine is a constitutional isomer of methamphetamine, it has been suggested that it may be effective in treating methamphetamine addiction. Phentermine is a central nervous system stimulant that acts on dopamine and norepinephrine. When comparing (+)-amphetamine, (+/-)-ephedrine, and phentermine, one key difference among the three drugs is their selectivity for norepinephrine (NE) release vs. dopamine (DA) release. The NE/DA selectivity ratios for these drugs as determined in vitro [(EC(50) NE(-1))/(EC(50) DA(-1))] are (+/-)-ephedrine (18.6) > phentermine (6.7) > (+)-amphetamine (3.5). Abrupt interruption of chronic methamphetamine use results in the withdrawal syndrome in almost 90% of the cases.][ The mental depression associated with methamphetamine withdrawal lasts longer and is more severe than that of cocaine withdrawal. Methamphetamine users and addicts may lose their teeth abnormally quickly, a condition informally known as meth mouth. 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)". Some reports have also speculated that the caustic nature of the drug is a contributing factor. Methamphetamine also has the potential to cause excessive cigarette smoking for users already smoking. This combined with the methamphetamine can perpetuate the "meth mouth". Similar, though far less severe, symptoms have been reported in clinical use of regular amphetamine, where effects are not exacerbated by extended periods of poor oral hygiene. Short-term exposure to high concentrations of chemical vapors that may exist in black market methamphetamine laboratories can cause severe health problems or even result in death. Exposure to these substances can occur from volatile air emissions, spills, fires, and explosions. Such methamphetamine labs are often discovered when fire fighters respond to a blaze. Methamphetamine cooks, their families, and first responders are at highest risk of acute health effects from chemical exposure, including lung damage and chemical burns to the body. Following a seizure of a methamphetamine lab, there is often a low exposure risk to chemical residues, however this contamination should be sanitized. Chemical residues and lab wastes that are left behind at a former methamphetamine lab can result in severe health problems for people who use the property, therefore local health departments should thoroughly assess the property for hazards prior to allowing it to be reinhabited, especially by children. Those seeking home ownership in heavy meth use areas should be especially careful while house hunting and be sure to have properties inspected before purchasing. Methamphetamine present in a mother's bloodstream passes through the placenta to a fetus, and is also secreted into breast milk. Infants born to methamphetamine-abusing mothers were found to have a significantly smaller gestational age-adjusted head circumference and birth weight measurements. Methamphetamine exposure was also associated with neonatal withdrawal symptoms of agitation, vomiting and tachypnea. This withdrawal syndrome is relatively mild and only requires medical intervention in approximately 4% of cases. Men who use methamphetamine, cocaine, MDMA, and ketamine, are twice as likely to have unprotected sex than those who do not use such drugs, according to British research. American psychologist Perry N. Halkitis performed an analysis using data collected from community-based participants among gay and bisexual men to examine the associations between their methamphetamine use and sexual risk taking behaviors. Methamphetamine use was found to be related to higher frequencies of unprotected sexual intercourse in both HIV-positive and unknown casual partners in the study population. The association between methamphetamine use and unprotected acts were also more pronounced in HIV-positive participants. These findings suggested that methamphetamine use and engagement in unprotected anal intercourse are co-occurring risk behaviors that potentially heighten the risk of HIV transmission among gay and bisexual men. Methamphetamine allows users of both sexes to engage in prolonged sexual activity, which may cause genital sores and abrasions. Methamphetamine can also cause sores and abrasions in the mouth via bruxism (teeth clenching and grinding), which can turn typically low-risk sex acts, such as oral sex, into high-risk sexual activity. As with the injection of any drug, if a group of users share a common needle, blood-borne diseases, such as HIV or hepatitis, can be transmitted. The level of needle sharing among methamphetamine users is similar to that among other drug injection users. Following oral administration, methamphetamine is readily absorbed into the bloodstream, with peak plasma concentrations achieved in approximately 3.13 to 6.3 hours post ingestion. The amphetamine metabolite peaks at 10 to 24 hours. Methamphetamine is also well absorbed following inhalation and following intranasal administration. It is distributed to most parts of the body. Methamphetamine is known to produce central effects similar to the other stimulants, but at smaller doses, with fewer peripheral effects. Methamphetamine's high lipophilicity also allows it to cross the blood brain barrier faster than other stimulants, where it is more stable against degradation by monoamine oxidase (MAO). Methamphetamine is metabolized in the liver with the main metabolites being amphetamine (active) and 4-hydroxymethamphetamine (pholedrine); other minor metabolites include 4-hydroxyamphetamine, norephedrine, and 4-hydroxynorephedrine. Other drugs metabolized to amphetamine and methamphetamine include benzphetamine, furfenorex, and famprofazone. Selegiline (marketed as Deprenyl, EMSAM, and others) is metabolized into levomethamphetamine which in turn is metabolized into levoamphetamine. Although only the D-Isomer of selegiline will metabolize into active metabolites, both isomers may cause a positive result for methamphetamine and amphetamine on a drug test, in certain cases. It is excreted by the kidneys, with the rate of excretion into the urine heavily influenced by urinary pH. Between 30-54% of an oral dose is excreted in urine as unchanged methamphetamine and 10-23% as unchanged amphetamine. Following an intravenous dose, 45% is excreted as unchanged parent drug and 7% amphetamine. The half-life of methamphetamine is variable with a mean value of between 9 and 12 hours. Methamphetamine and amphetamine are often measured in urine, sweat or saliva as part of a drug-abuse testing program, in plasma or serum to confirm a diagnosis of poisoning in hospitalized victims, or in whole blood to assist in a forensic investigation of a traffic or other criminal violation or a case of sudden death. Chiral techniques may be employed to help distinguish the source of the drug, whether obtained legally (via prescription) or illicitly, or possibly as a result of formation from a prodrug such as famprofazone or selegiline. Chiral separation is needed to assess the possible contribution of l-methamphetamine (Vicks Inhaler) toward a positive test result. In 2011, researchers at John Jay College of Criminal Justice reported that dietary zinc supplements can mask the presence of methamphetamine and other drugs in urine.][ Similar claims have been made in web forums on that topic. A member of the family of phenethylamines, methamphetamine is chiral, with two isomers, levorotatory and dextrorotatory. The levorotatory form, called levomethamphetamine, is an over-the-counter drug used in inhalers for nasal decongestion. Methamphetamine is a potent central nervous system stimulant that affects neurochemical mechanisms responsible for regulating heart rate, body temperature, blood pressure, appetite, attention, mood and emotional responses associated with alertness or alarming 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. It is known to produce central effects similar to the other stimulants, but at smaller doses, with fewer peripheral effects. Methamphetamine's fat solubility also allows it to enter the brain faster than other stimulants, where it is more stable against degradation by monoamine oxidase (MAO). The methyl group is responsible for the potentiation of effects as compared to the related compound amphetamine, rendering the substance more lipid-soluble, enhancing transport across the blood–brain barrier, and more stable against enzymatic degradation by monoamine oxidase (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 also interacts with TAAR1 to trigger phosphorylation of PKA and PKC, ultimately resulting in the internalization of dopamine transporters. The presynaptic cell is less able to effectively remove dopamine from the synapse. The binding of methamphetamine to TAAR1 also activates adenylyl cyclase, which allows for increased intracellular cAMP. Taken together, the binding of methamphetamine to TAAR1 results in a massive efflux of neurogenic monoamines with a sustained synaptic presence. 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 that 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 twelvefold increase in dopamine levels and subsequent oxidative stress that occurs after taking methamphetamine mediates its neurotoxicity. The lab of David Sulzer and colleagues at Columbia University developed a technique known as "intracellular patch electrochemistry" to measure concentrations of dopamine in the cytosol, and found massive increases following methamphetamine, leading to the "cytosolic dopamine hypothesis" of neurotoxicity, in which dopamine oxidation, particularly close to synaptic vesicles, produce oxidative stress that in turn leads to exacerbation of autophagy that can destroy axons and dendrites. Recent research published in the Journal of Pharmacology And Experimental Therapeutics (2007) indicates that methamphetamine binds to and activates a G protein-coupled receptor called TAAR1. TAARs are a newly discovered receptor family whose members are activated by a number of amphetamine-like molecules called trace amines, thyronamines, and certain volatile odorants. It has been demonstrated that a high core temperature is correlated with an increase in the neurotoxic effects of methamphetamine. Methamphetamine has been reported to occur naturally in Acacia berlandieri, and possibly Acacia rigidula, trees that grow in West Texas. Methamphetamine and amphetamine were long thought to be strictly human-synthesized, but Acacia trees contain these and numerous other psychoactive compounds (e. g., mescaline, nicotine, dimethyltryptamine), and the related compound β-phenethylamine is known to occur from numerous Acacia species. The findings, however, have never been confirmed or repeated, leading some researchers to believe the results were the result of cross-contamination.][ 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. These findings suggest the route of administration used affects the potential risk for psychological addiction independently of other risk factors, such as dosage and frequency of use. Intravenous injection is the fastest route of drug administration, causing blood concentrations to rise the most quickly, followed by smoking, suppository (anal or vaginal insertion), insufflation (snorting), and ingestion (swallowing). Ingestion does not produce a rush, an acute transcendent state of euphoria as forerunner to the high experienced with the use of methamphetamine, which is most pronounced with the intravenous route of administration. While the onset of the rush induced by injection can occur in as little as a few seconds, the oral route of administration requires approximately half an hour before the high sets in. Injection carries relatively greater risks than other methods of administration. The hydrochloride salt of methamphetamine is soluble in water. Intravenous users may use any dose range, from less than 100 milligrams to over one gram, using a hypodermic needle, although it should be noted that typically street methamphetamine is “cut,” or diluted, with a water-soluble cutting material, which constitutes a significant portion of a given street methamphetamine dose. Intravenous users risk developing pulmonary embolism (PE), a blockage of the main artery of the lung or one of its branches, and commonly develop skin rashes (also known as "speed bumps") or infections at the site of injection. As with the injection of any drug, if a group of users share a common needle without sterilization procedures, blood-borne diseases, such as HIV or hepatitis, can be transmitted. Smoking amphetamines refers to vaporizing it to inhale the resulting fumes, not burning it to inhale the resulting smoke. It is commonly smoked in glass pipes made from glassblown Pyrex tubes and light bulbs. It can also be smoked off aluminium foil, which is heated underneath by a flame. This method is also known as "chasing the white dragon" (whereas smoking heroin is 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 (PH)), or limited to injection users (pulmonary embolism (PE)). Another popular route of administration to intake methamphetamine is insufflation (snorting). This method allows methamphetamine to be absorbed through the soft tissue of the mucous membrane in the sinus cavity, and then directly into the bloodstream, bypassing first-pass metabolism. Suppository (anal or vaginal insertion) is a less popular method of administration used in the community with comparatively little research into its effects. Information on its use is largely anecdotal with reports of increased sexual pleasure and the effects of the drug lasting longer, though as methamphetamine is centrally active in the brain, these effects are likely experienced through the higher bioavailability of the drug in the bloodstream (second to injection) and the faster onset of action (than insufflation). Nicknames for the route of administration within some methamphetamine communities include a "butt rocket", a "booty bump", "potato thumping", "turkey basting", "plugging", "boofing", "suitcasing", "hooping", "keistering", "shafting", "bumming", and "shelving" (vaginal). Shortly after the first synthesis of amphetamine in 1887, methamphetamine was synthesized from ephedrine in 1893 by Japanese chemist Nagai Nagayoshi. The term "methamphetamine" was derived from elements of the chemical structure of this new compound: ylmeth lphaa-ethylm enylph hylet amine. In 1919, crystallized methamphetamine was synthesized by pharmacologist Akira Ogata via reduction of ephedrine using red phosphorus and iodine. One of the earliest uses of methamphetamine was during World War II, when it was used by Axis and Allied forces. The company Temmler produced methamphetamine under the trademark Pervitin and so did the German and Finnish militaries. It was also dubbed "Pilot's chocolate" or "Pilot's salt". It was widely distributed across rank and division, from elite forces to tank crews and aircraft personnel, with many millions of tablets being distributed throughout the war. Its use by German Panzer crews also led to it being known as "Panzerschokolade" ("Panzer chocolate" or "tankers' chocolate"). More than 35 million three-milligram doses of Pervitin were manufactured for the German army and air force between April and July 1940. From 1942 until his death in 1945, Adolf Hitler was given intravenous injections of methamphetamine by his personal physician Theodor Morell. It is possible that it was used to treat Hitler's speculated Parkinson's disease, or that his Parkinson-like symptoms that developed from 1940 onwards resulted from using methamphetamine. In Japan, methamphetamine was sold under the registered trademark of Philopon (ヒロポン hiropon) by Dainippon Pharmaceuticals (present-day Dainippon Sumitomo Pharma [DSP]) for civilian and military use. As with the rest of the world at the time, the side effects of methamphetamine were not well studied, and regulation was not seen as necessary. In the 1940s and 1950s the drug was widely administered to Japanese industrial workers to increase their productivity. Methamphetamine and amphetamine were given to Allied bomber pilots during World War II to sustain them by fighting off fatigue and enhancing focus during long flights. The experiment failed because soldiers became agitated, could not channel their aggression and showed impaired judgment. Rather, dextroamphetamine (Dexedrine) became the drug of choice for American bomber pilots, being used on a voluntary basis by roughly half of the U.S. Air Force pilots during the Persian Gulf War, a practice which came under some media scrutiny in 2003 after a mistaken attack on Canadian troops. Following the use of amphetamine (such as Benzedrine, introduced 1932) in the 1930s for asthma, narcolepsy, and symptoms of the common cold, in 1943, Abbott Laboratories requested U.S. FDA approval of methamphetamine for treatment of narcolepsy, mild depression, postencephalitic parkinsonism, chronic alcoholism, cerebral arteriosclerosis, and hay fever, which was granted in December 1944.][ Sale of the massive postwar surplus of methamphetamine in Europe, North America, and Japan stimulated civilian demand. After World War II, a large Japanese military stockpile of methamphetamine, known by its trademark Philopon, flooded the market. Post-war Japan experienced the first methamphetamine epidemic, which later spread to Guam, the U. S. Marshall Islands, and to the U. S. West Coast. In 1948, the Philopon trademark came under a well-publicized lawsuit by Philips Corporation. Philips, under its Koninklijke division, filed suit against Dainippon Pharmaceuticals to cease using Philipon as the commercial name for methamphetamine. Philips claimed the exclusive right to use the trademark as a portmanteau of Philips and Nippon, the Japanese name of the country. DSP's attorneys challenged Philips' standing to sue as a foreign (Dutch) corporation. The matter was ultimately settled out of court in 1952, with Dainippon Pharmaceuticals agreeing to pay Philips a 5% royalty on worldwide sales of methamphetamines sold by DSP under the Philopon label. The Japanese Ministry of Health banned production less than a year later. In the 1950s, there was a rise in the legal prescription of methamphetamine to the American public. In the 1954 edition of Pharmacology and Therapeutics, conditions treatable by methamphetamine included "narcolepsy, postencephalitic parkinsonism, alcoholism, certain depressive states, and in the treatment of obesity." Methamphetamine constituted half of the amphetamine salts for the original formulation for the diet drug Obetrol, which later became the ADHD drug Adderall. Methamphetamine was also marketed for sinus inflammation or for non-medicinal purposes as "pep pills" or "bennies". In 1950 the Japanese Ministry of Health banned stimulant production, but drug companies continued to produce stimulants and they wound up on the black market. From 1951 to 1954 a series of acts were passed by the Japanese government to try to stop production and sale of stimulants; however, the production and sale of stimulant drugs continued through criminal syndicates such as Yakuza criminal organizations. On the streets, it is also known as S, Shabu, and Speed, in addition to its old trademarked name. The 1960s saw the start of significant use of clandestinely manufactured methamphetamine, most of which was produced by motorcycle gangs. It was also prescribed by San Franciscan drug clinics to treat heroin addiction. Beginning in the 1990s, the production of methamphetamine in users' own homes for personal and recreational use became popular. In 1970, methamphetamine was regulated in the Controlled Substances Act in the U. S., and a public education campaign was mounted against it. By the 2000s, the only two FDA approved marketing indications remaining for methamphetamine were for attention-deficit hyperactivity disorder (ADHD) and the short-term management of exogenous obesity, although the drug is clinically established as effective in the treatment of narcolepsy. The production, distribution, sale, and possession of methamphetamine is restricted or illegal in many jurisdictions. Methamphetamine has been placed in Schedule II of the United Nations Convention on Psychotropic Substances treaty. North Korea might be facing one of the world's worst meth epidemics. Although the secrecy of the North Korean government means that any report may be only approximate, there have been an increasing number of signs that meth is very widespread throughout the country, used both recreationally and as medicine. Methamphetamine is called Bingdu (Hangul: ; Hanja: ; "ice poison") in the Korean language. 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 from its initial base in California throughout the rural United States, especially through the Midwest and South. Government officials in many U.S. counties now report that meth is their most serious drug problem. Meth use is said to be particularly common in the American western states, where the substance is in high demand. States like Montana, South Dakota, Idaho, Colorado and Arizona have all launched extensive efforts – both private and public – to stop meth use. Methamphetamine is most structurally similar to methcathinone and amphetamine. Synthesis is relatively simple, but entails risk with flammable and corrosive chemicals, particularly the solvents used in extraction and purification; therefore, illicit production is often discovered by fires and explosions caused by the improper handling of volatile or flammable solvents. The six major routes of production begin with either phenyl-2-propanone (P2P) or with one of the isomeric compounds pseudoephedrine and ephedrine. One procedure uses the reductive amination of phenyl-2-propanone (phenylacetone) with methylamine, P2P was usually obtained from phenylacetic acid and acetic anhydride, though many other methods have been considered, and phenylacetic acid might arise from benzaldehyde, benzylcyanide, or benzylchloride. Methylamine is crucial to all such methods, and is produced from the model airplane fuel nitromethane, or formaldehyde and ammonium chloride, or methyl iodide with hexamine. This was once the preferred method of production by motorcycle gangs in California, until DEA restrictions on the chemicals made the process difficult. Pseudoephedrine, ephedrine, phenylacetone, and phenylacetic acid are currently DEA list I and acetic anhydride is list II on the DEA list of chemicals subject to regulation and control measures. This method can involve the use of mercuric chloride and leaves behind mercury and lead environmental wastes. The methamphetamine produced by this method is racemic, consisting partly of the less-desired levomethamphetamine isomer. The alternative Leuckart route also relies on P2P to produce a racemic product, but proceeds via methylformamide in formic acid to an intermediate N-formyl-methamphetamine, which is then decarboxylated with hydrochloric acid. Two infrequently used reductive amination routes have also been reported. The "nitropropene route", in which benzaldehyde is condensed with nitroethane to produce 1-phenyl-2-nitropropene, which is subsequently reduced by hydrogenation of the double bond and reduction of the nitro group using hydrogen over a palladium catalyst or lithium aluminum hydride. The "oxime route" reacts phenyl-2-propanol with hydroxylamine to produce an oxime intermediate which likewise is hydrogenated using hydrogen over a palladium catalyst or lithium aluminum hydride. Illicit methamphetamine is more commonly made by the reduction of ephedrine or pseudoephedrine, which produces the more active d-methamphetamine isomer. The maximum conversion rate for ephedrine and pseudoephedrine is 92%, although typically, illicit methamphetamine laboratories convert at a rate of 50% to 75%. Most methods of illicit production involve protonation of the hydroxyl group on the ephedrine or pseudoephedrine molecule. Though dating back to the discovery of the drug, the Nagai route did not become popular among illicit manufacturers until ca. 1982, and comprised 20% of production in Michigan in 2002 It involves red phosphorus and hydrogen iodide (also known as hydroiodic acid or iohydroic acid). (The hydrogen iodide is replaced by iodine and water in the "Moscow route") The hydrogen iodide is used to reduce either ephedrine or pseudoephedrine to methamphetamine. On heating the precursor is rapidly iodinated by the hydrogen iodide to form iodoephedrine. The phosphorus assists in the second step, by consuming iodine to form phosphorus triiodide (which decomposes in water to phosphorous acid, regenerating hydrogen iodide). Because hydrogen iodide exists in a chemical equilibrium with iodine and hydrogen, the phosphorus reaction shifts the balance toward hydrogen production when iodine is consumed. In Australia, criminal groups have been known to substitute "red" phosphorus with either hypophosphorous acid or phosphorous acid (the "Hypo route"). This is a hazardous process for amateur chemists because phosphine gas, a side-product from in situ hydrogen iodide production, is extremely toxic to inhale. The reaction can also create toxic, flammable white phosphorus waste. Methamphetamine produced in this way is usually more than 95% pure. The conceptually similar Emde route involves reduction of ephedrine to chloroephedrine using thionyl chloride (SOCl2), followed by catalytic hydrogenation. The catalysts for this reaction are palladium or platinum. The Rosenmund route also uses hydrogen gas and a palladium catalyst poisoned with barium sulfate (Rosenmund reduction), but uses perchloric acid instead of thionyl chloride. The Birch reduction, also called the "Nazi method", became popular in the mid-to-late 1990s and comprised the bulk of methamphetamine production in Michigan in 2002. It reacts pseudoephedrine with liquid anhydrous ammonia and an alkali metal such as sodium or lithium. The reaction is allowed to stand until the ammonia evaporates. However, the Birch reduction is dangerous because the alkali metal and ammonia are both extremely reactive, and the temperature of liquid ammonia makes it susceptible to explosive boiling when reactants are added. It has been the most popular method in Midwestern states of the U. S. because of the ready availability of liquid ammonia fertilizer in farming regions. In recent years, a simplified "Shake 'n Bake" one-pot synthesis has become more popular. The method is suitable for such small batches that pseudoephedrine restrictions are less effective, it uses chemicals that are easier to obtain (though no less dangerous than traditional methods), and it is so easy to carry out that some addicts have made the drug while driving. It involves placing crushed pseudoephedrine tablets into a nonpressurized container containing ammonium nitrate, water, and a hydrophobic solvent such as Coleman fuel or automotive starting fluid, to which lye and lithium (from lithium batteries) is added. Hydrogen chloride gas produced by a reaction of salt with sulfuric acid is then used to recover crystals for purification. The container needs to be "burped" periodically to prevent failure under accumulating pressure, as exposure of the lithium to the air can spark a flash fire; thus an abandoned reaction becomes a severe hazard to firefighters. The battery lithium can react with water to shatter a container and potentially start a fire or explosion. Producing methamphetamine in this fashion can be extremely dangerous and has been linked to several fatalities. Because users frequently carry out the reaction in a two-liter bottle held close to their bodies, which can explode if the cap is removed too soon or if it accidentally perforates, the procedure has led to a large number of severe burns — for example, approximately 70 in Indiana during 2010 and 2011. As 90% of these cases in the United States lack health insurance, and the average cost for their treatment is $130,000 (60% more than the average), which is only partially compensated by Medicaid, this method of synthesis has been blamed for the closure of hospital burn units and a cost to taxpayers of tens or hundreds of millions of dollars. Until the early 1990s, methamphetamine for the U.S. market was made mostly in labs run by drug traffickers in Mexico and California. 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 U.S. 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." The report concluded that "methamphetamine availability is not likely to decline in the near term. " Methamphetamine labs can give off noxious fumes, such as phosphine gas, methylamine gas, solvent vapors, acetone or chloroform, iodine vapors, white phosphorus, anhydrous ammonia, hydrogen chloride/muriatic acid, hydrogen iodide, lithium and sodium gases, 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 is highly toxic and, if present in large quantities, is likely to explode upon autoignition from diphosphine, which is formed by overheating phosphorus.][ In July 2007, Mexican officials at the port of Lázaro Cárdenas seized a ship carrying 19 tons of pseudoephedrine, a raw material needed for methamphetamine. The shipment originated in Hong Kong and passed through the United States at the port of Long Beach prior to its arrival in Mexico. The Australian Crime Commission's illicit drug data report for 2011–2012 was released in western Sydney, Australia on 20 May 2013 and revealed that the average strength of crystal methamphetamine doubled in most Australian jurisdictions within a 12-month period and the majority of domestic laboratory closures involved small "addict-based" operations. In Japan, methamphetamine seizures are usually white crystals of high purity, but contain impurities that vary according to the means of production, and are sometimes adulterated. Diagnostic impurities are the naphthalenes 1-benzyl-methylnaphthalene and 1,3-dimethyl-2-phenylnaphthalene, arising in the Nagai and Leuckart routes, and cis- or trans- 1,2-dimethyl-3-phenylaziridine, ephedrine, or erythro-3,4-dimethyl- 5-phenyloxazolidine, arising in the Nagai and Emde routes; these are absent in the reductive amination route. Characteristic impurities of the Birch route include N-methyl-1-(1-(1,4-cyclohexadienyl))-2-propanamine. Methamphetamine produced by the Birch route contains phenyl-2-propanone, the precursor for the reductive amination route, as a degradation product. However, specific diagnostic impurities are not very reliable in practice, and it is generally preferable for forensic technicians to evaluate a larger profile of trace compounds. A common adulterant is dimethyl sulfone, a solvent and cosmetic base without known effect on the nervous system; other adulterants include dimethylamphetamine HCl, ephedrine HCl, sodium thiosulfate, sodium chloride, sodium glutamate, and a mixture of caffeine with sodium benzoate. In the United States, illicit methamphetamine comes in a variety of forms with prices varying widely over time. Most commonly, it is found as a colorless crystalline solid. Impurities may result in a brownish or tan color. Colorful flavored pills containing methamphetamine and caffeine are known as yaa baa (Thai for "crazy medicine"). An impure form of methamphetamine is sold as a crumbly brown or off-white rock, commonly referred to as "peanut butter crank". 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 can be particularly dangerous due to the synergistic effects of multiple stimulants. Reports in 2007 of the appearance of flavored "Strawberry Quik meth" circulated in the media and local law enforcement, but were debunked in 2010 by the DEA, although meth of varying colors has been seized. Rarely, the impure reaction mixture from the hydrogen iodide/red phosphorus route is used without further modification, usually by injection; it is called "ox blood". "Meth oil" refers to the crude methamphetamine base produced by several synthesis procedures. Ordinarily it is purified by exposure to hydrogen chloride, as a solution or as a bubbled gas, and extraction of the resulting salt occurs by precipitation and/or recrystallization with ether/acetone. Slang terms for methamphetamine, especially common among illicit users, are numerous and vary from region to region. Some names are "crystal meth", "meth", "speed", "crystal", "clavo", "ice", "shards", "shabu/shaboo", "glass", "jib", "crank", "batu/batunas", "scanté", "schizznit", "gack", "tweak", "rizz", "rock", "tina" and "cold". Some terms vary by region or subculture. Some regional terms are based on the original trade names; thus "필로폰" ("Pilopon") in South Korea, "Пико" for pure methamphetamine in Bulgaria or "piko" in the Czech Republic, Slovakia, and Poland after the trade name "Pervitin". Also "peří" ("feathers", phonetically similar to "Pervitin") and "perník" ("gingerbread", phonetically similar to "Pervitin" in the Czech Republic. In New Zealand it is called "P". Other local names include “冰毒” (Bīng Dú, Chinese for "Ice drug") in China, "ya ba" (Thai for "Crazy Medicine", Thailand), "ya ice" (Thai for "Ice drug", Thailand), "đá" (Vietnamese for "ice", Vietnam), "batu kilat" (Malaysian for "shining rocks", Malaysia), "bato" (Filipino for "rock" or "stone", Philippines) "شیشه" (in translation "Glass", transliterate to "Shishe", Iran), "tik" (South Africa), "dimineata speciala aurie" ("Special golden morning", Romania), "bala" in Brazilian Portuguese, "tjäck" in Swedish, "ספיד" in Israel and "Teeft" United Kingdom. "Vint", Russian for "a screw", specifically refers to a very impure homemade form of methamphetamine in Russia. The name originally comes from "Pervitin," a pharmaceutical trademark. The DSM IV has amphetamine defined in two ways: Amphetamine dependence (304.40) and Amphetamine abuse (305.70) M: PSO/PSI mepr dsrd (o, p, m, p, a, d, s), sysi/epon, spvo proc (eval/thrp), drug (N5A/5B/5C/6A/6B/6D) M: NUT cof, enz, met noco, nuvi, sysi/epon, met drug (A8/11/12)
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