Cocaine detailed information

# Overview
Cocaine (benzoylmethyl ecgonine) is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is both a stimulant of the central nervous system and an appetite suppressant. Specifically, it is a dopamine reuptake inhibitor, a noradrenaline reuptake inhibitor and a serotonin reuptake inhibitor. Because of the way it affects the mesolimbic reward pathway, cocaine is addictive. Nevertheless, cocaine is used in medicine as a topical anesthetic, even in children, specifically in eye, nose and throat surgery.
Its possession, cultivation, and distribution are illegal for non-medicinal and non-government sanctioned purposes in virtually all parts of the world. Although its free commercialization is illegal and has been severely penalized in virtually all countries, its use worldwide remains widespread in many social, cultural, and personal settings.

# History

## Coca leaf
For a thousand years South American indigenous peoples have chewed the coca leaf (Erythroxylon coca), a plant that contains vital nutrients as well as numerous alkaloids, including cocaine. The leaf was, and is, chewed almost universally by some indigenous communitiesancient Peruvian mummies have been found with the remains of coca leaves, and pottery from the time period depicts humans, cheeks bulged with the presence of something on which they are chewing. There is also evidence that these cultures used a mixture of coca leaves and saliva as an anesthetic for the performance of trepanation.

## Isolation
Although the stimulant and hunger-suppressant properties of coca had been known for many centuries, the isolation of the cocaine alkaloid was not achieved until 1855 . Many scientists had attempted to isolate cocaine, but none had been successful for two reasons: the knowledge of chemistry required was insufficient at the time, worsened because coca does not grow in Europe and ruins easily during travel.
The cocaine alkaloid was first isolated by the German chemist Friedrich Gaedcke in 1855 . Gaedcke named the alkaloid "erythroxyline", and published a description in the journal Archives de Pharmacie.
In 1856, Friedrich Wohler asked Dr. Carl Scherzer, a scientist aboard the Novara (an Austrian frigate sent by Emperor Franz Joseph to circle the globe), to bring him a large amount of coca leaves from South America. In 1859, the ship finished its travels and Wohler received a trunk full of coca. Wohler passed on the leaves to Albert Niemann, a Ph.D. student at the University of Gottingen in Germany, who then developed an improved purification process.
Niemann described every step he took to isolate cocaine in his dissertation titled Uber eine neue organische Base in den Cocablattern (On a New Organic Base in the Coca Leaves), which was published in 1860it earned him his Ph.D. and is now in the British Library. He wrote of the alkaloid's colourless transparent prisms and said that, Its solutions have an alkaline reaction, a bitter taste, promote the flow of saliva and leave a peculiar numbness, followed by a sense of cold when applied to the tongue. Niemann named the alkaloid cocaineas with other alkaloids its name carried the -ine suffix (from Latin -ina).
The first synthesis and elucidation of the structure of the cocaine molecule was by Richard Willstatter in 1898. The synthesis started from tropinone, a related natural product and took five steps.

## Medicalisation
With the discovery of this new alkaloid, Western medicine was quick to exploit the possible uses of this plant.
In 1879, Vassili von Anrep, of the University of Wurzburg, devised an experiment to demonstrate the analgesic properties of the newly-discovered alkaloid. He prepared two separate jars, one containing a cocaine-salt solution, with the other containing merely salt water. He then submerged a frog's legs into the two jars, one leg in the treatment and one in the control solution, and proceeded to stimulate the legs in several different ways. The leg that had been immersed in the cocaine solution reacted very differently than the leg that had been immersed in salt water.
Carl Koller (a close associate of Sigmund Freud, who would write about cocaine later) experimented with cocaine for ophthalmic usage. In an infamous experiment in 1884, he experimented upon himself by applying a cocaine solution to his own eye and then pricking it with pins. His findings were presented to the Heidelberg Ophthalmological Society. Also in 1884, Jellinek demonstrated the effects of cocaine as a respiratory system anesthetic. In 1885, William Halsted demonstrated nerve-block anesthesia, and James Corning demonstrated peridural anesthesia. 1898 saw Heinrich Quincke use cocaine for Spinal anaesthesia.

## Popularization
In 1859, an Italian doctor, Paolo Mantegazza, returned from Peru, where he had witnessed first-hand the use of coca by the natives. He proceeded to experiment on himself and upon his return to Milan he wrote a paper in which he described the effects. In this paper he declared coca and cocaine (at the time they were assumed to be the same) as being useful medicinally, in the treatment of a furred tongue in the morning, flatulence,  whitening of the teeth.
A chemist named Angelo Mariani who read Mantegazzas paper became immediately intrigued with coca and its economic potential. In 1863, Mariani started marketing a wine called Vin Mariani, which had been treated with coca leaves. The ethanol in wine acted as a solvent and extracted the cocaine from the coca leaves, altering the drinks effect. It contained 6 mg cocaine per ounce of wine, but Vin Mariani, which was to be exported, contained 7.2 mg per ounce to compete with the higher cocaine content of similar drinks in the United States. A pinch of coca leaves was included in John Styth Pemberton's original 1886 recipe for Coca-Cola, though the company began using decocainized leaves in 1906 when the Pure Food and Drug Act was passed. The only known measure of the amount of cocaine in Coca-Cola was determined in 1902 as being as little as 1/400 of a grain (0.2 mg) per ounce of syrup (6 ppm). The actual amount of cocaine that Coca-Cola contained during the first twenty years of its production is practically impossible to determine.
In 1879 cocaine began to be used to treat morphine addiction. Cocaine was introduced into clinical use as a local anaesthetic in Germany in 1884, about the same time as Sigmund Freud published his work Uber Coca, in which he wrote that cocaine causes:
In 1885 the U.S. manufacturer Parke-Davis sold cocaine in various forms, including cigarettes, powder, and even a cocaine mixture that could be injected directly into the users veins with the included needle. The company promised that its cocaine products would supply the place of food, make the coward brave, the silent eloquent and ... render the sufferer insensitive to pain.
By the late Victorian era cocaine use had appeared as a vice in literature, for example as the cucaine injected by Arthur Conan Doyles fictional Sherlock Holmes.
In early 20th-century Memphis, Tennessee, cocaine was sold in neighborhood drugstores on Beale Street, costing five or ten cents for a small boxful.  Stevedores along the Mississippi River used the drug as a stimulant, and white employers encouraged its use by black laborers.
In 1909, Ernest Shackleton took Forced March brand cocaine tablets to Antarctica, as did Captain Scott a year later on his ill-fated journey to the South Pole. Even as late as 1938 , the Larousse Gastronomique was published carrying a recipe for cocaine pudding.

## Prohibition
By the turn of the twentieth century, the addictive properties of cocaine had become clear to many, and the problem of cocaine abuse began to capture public attention in the United States. The dangers of cocaine abuse became part of a moral panic that was tied to the dominant racial and social anxieties of the day. In 1903, the American Journal of Pharmacy stressed that most cocaine abusers were bohemians, gamblers, high- and low-class prostitutes, night porters, bell boys, burglars, racketeers, pimps, and casual laborers. In 1914, Dr. Christopher Koch of Pennsylvanias State Pharmacy Board made the racial innuendo explicit, testifying that, Most of the attacks upon the white women of the South are the direct result of a cocaine-crazed Negro brain. Mass media manufactured an epidemic of cocaine use among African Americans in the Southern United States to play upon racial prejudices of the era, though there is little evidence that such an epidemic actually took place. In the same year, the Harrison Narcotics Tax Act outlawed the sale and distribution of cocaine in the United States. This law incorrectly referred to cocaine as a narcotic, and the misclassification passed into popular culture. As stated above, cocaine is a stimulant, not a narcotic. Although technically illegal for purposes of distribution and use, the distribution, sale and use of cocaine was still legal for registered companies and individuals. Because of the misclassification of cocaine as a narcotic, the debate is still open on whether the government actually enforced these laws strictly. Cocaine was not considered a controlled substance until 1970, when the United States listed it as such in the Controlled Substances Act.  Until that point, the use of cocaine was open and rarely prosecuted in the US due to the moral and physical debates commonly discussed.

## Modern usage
In many countries, cocaine is a popular recreational drug. In the United States, the development of "crack" cocaine introduced the substance to a generally poorer inner-city market. Use of the powder form has stayed relatively constant, experiencing a new height of use during the late 1990s and early 2000s in the U.S., and has become much more popular in the last few years in the UK.
Cocaine use is prevalent across all socioeconomic strata, including age, demographics, economic, social, political, religious, and livelihood. Cocaine in its various forms comes in second only to cannabis as the most popular illegal recreational drug in the United States, and is number one in street value sold each year.
The estimated U.S. cocaine market exceeded $35 billion in street value for the year 2003, exceeding revenues by corporations such as AT&T and Starbucks. There is a tremendous demand for cocaine in the U.S. market, particularly among those who are making incomes affording luxury spending, such as single adults and professionals with discretionary income. Cocaines status as a club drug shows its immense popularity among the party crowd.
In 1995 the World Health Organization (WHO) and the United Nations Interregional Crime and Justice Research Institute (UNICRI) announced in a press release the publication of the results of the largest global study on cocaine use ever undertaken. However, a decision in the World Health Assembly banned the publication of the study. In the sixth meeting of the B committee the US representative threatened that "If WHO activities relating to drugs failed to reinforce proven drug control approaches, funds for the relevant programs should be curtailed". This led to the decision to discontinue publication. A part of the study has been recuperated. Available are profiles of cocaine use in 20 countries.
A problem with illegal cocaine use, especially in the higher volumes used to combat fatigue (rather than increase euphoria) by long-term users is trauma caused by the compounds used in adulteration. Cutting or "stamping on" the drug is commonplace, using compounds which simulate ingestion effects, such as Novocain (procaine) producing temporary anaesthaesia, ephedrine producing an increased heart rate, or more dangerously, strong toxins to produce vasodilatory effects. For example a nosebleed is incorrectly regarded by heavy users as a sign of purity. The normal adulterants for profit are inactive sugars, usually mannitol, creatine or glucose, so introducing active adulterants gives the illusion of purity. Cocaine trading carries large penalties in most jurisdictions, so user deception about purity and consequent high profits for dealers are the norm.

# Pharmacology

## Appearance
Cocaine in its purest form is a white, pearly product. Cocaine appearing in powder form is a salt, typically cocaine hydrochloride (CAS 53-21-4). Street market cocaine is frequently adulterated or cut with various powdery fillers to increase its weight; the substances most commonly used in this process are baking soda; sugars, such as lactose, dextrose, inositol, and mannitol; and local anesthetics, such as lidocaine or benzocaine, which mimic or add to cocaine's numbing effect on mucous membranes. Cocaine may also be "cut" with other stimulants such as methamphetamine. Adulterated cocaine is often a white, off-white or pinkish powder.
The color of crack cocaine depends upon several factors including the origin of the cocaine used, the method of preparation  with ammonia or baking soda  and the presence of impurities, but will generally range from white to a yellowish cream to a light brown. Its texture will also depend on the adulterants, origin and processing of the powdered cocaine, and the method of converting the base. It ranges from a crumbly texture, sometimes extremely oily, to a hard, almost crystalline nature.

## Forms of cocaine

### Cocaine sulfate
Cocaine sulfate is produced by macerating coca leaves along with water that has been acidulated with sulfuric acid, or an aromatic-based solvent, like kerosene or benzene. This is often accomplished by placing the ingredients into a vat and stomping on them, in a manner similar to the traditional method for crushing grapes. A more popular method in modern times is to form a makeshift "vat" by spreading a heavy nylon tarp on the floor of an enclosed area and shred the leaves with a gas-powered weed trimmer. This method is fast, and not only shreds the leaves, but results in bruising and fragmenting of the remaining pieces, aiding the extraction process. After the maceration is completed, the water is evaporated to yield a pasty mass of impure cocaine sulfate. The sulfate salt itself is an intermediate step to producing cocaine hydrochloride.

### Freebase
As the name implies, freebase is the base form of cocaine, as opposed to the salt form of cocaine hydrochloride. Whereas cocaine hydrochloride is extremely soluble in water, cocaine base is insoluble in water and is therefore not suitable for drinking, snorting or injecting. Whereas cocaine hydrochloride is not well-suited for smoking because the temperature at which it vaporizes is very high and close to the temperature at which it burns, cocaine base vaporizes at a much lower temperature, which makes it suitable for inhalation.
Smoking freebase cocaine has the additional effect of releasing methylecgonidine into the user's system due to the pyrolysis of the substance (a side effect which insufflating or injecting powder cocaine does not create). Some research suggests that smoking freebase cocaine can be even more cardiotoxic than other routes of administration  because of methylecgonidine's effects on lung tissue  and liver tissue. 
Smoking freebase is preferred by many users because the cocaine is absorbed immediately into blood via the lungs, reaching the brain in about five seconds. The rush is much more intense than snorting the same amount of cocaine nasally, but the effects do not last as long. The peak of the freebase rush is over almost as soon as the user exhales the vapor, but the high typically lasts 510 minutes afterward. What makes freebasing particularly dangerous is that users typically do not wait that long for their next hit and will continue to smoke freebase until none is left. These effects are similar to those that can be achieved by injecting or slamming cocaine hydrochloride, but without the risks associated with intravenous drug use (though there are other serious risks associated with smoking freebase).
Freebase cocaine is produced by first dissolving cocaine hydrochloride in water. Once dissolved in water, cocaine hydrochloride (Coc-HCl) dissociates into the protonated cocaine ion (Coc-H+) and the chloride ion (Cl). Any solids that remain suspended in the solution are impurities from the cut and are removed by filtration. A base, typically ammonia (NH3), is added to the solution. The following net acid-base reaction takes place:
As freebase cocaine (Coc) is insoluble in water, it precipitates and the solution becomes cloudy. To recover the freebase in the "traditional" manner, diethyl ether is added to the solution. Since freebase is highly soluble in ether, a vigorous shaking of the mixture results in the freebase being dissolved in the ether. As ether is practically insoluble in water, it can be siphoned off. The ether is then left to evaporate, leaving behind the nearly pure freebase.
Handling diethyl ether is dangerous because ether is extremely flammable; its vapors are heavier than air and can "creep" from an open bottle, and in the presence of oxygen it can form peroxides, which can spontaneously combust. Comedian Richard Pryor has performed a skit poking fun at himself for a 1980 incident in which he caused an explosion and ignited himself attempting to smoke "freebase", presumably while still wet with ether (though his ex-wife Jennifer Lee Pryor said that he poured high-proof rum over his body and torched himself in a drug psychosis).

### Crack cocaine
In its creation process, due to the dangers of using ether to produce pure freebase cocaine, cocaine producers began to omit the step of removing the freebase cocaine precipitate from the ammonia mixture. Typically, filtration processes are also omitted. The end result of this process is that the cut, in addition to the ammonium salt (NH4Cl), remains in the freebase cocaine after the mixture is evaporated. The rock that is thus formed also contains a small amount of water. Sodium bicarbonate (baking soda) is also preferred in preparing the freebase, for when commonly "cooked" the ratio is 50/50 to 40/60% cocaine/bicarbonate. This acts as a filler which extends the overall profitability of illicit sales. Crack cocaine may be reprocessed in small quantities with water (users refer to the resultant product as "cookback"). This removes the residual bicarbonate, and any adulterants or cuts that have been used in the previous handling of the cocaine and leaves a relatively pure, anhydrous cocaine base.
When the rock is heated, this water boils, making a crackling sound (hence the onomatopoeic crack). Baking soda is now most often used as a base rather than ammonia for reasons of lowered stench and toxicity; however, any weak base can be used to make crack cocaine. Strong bases, such as sodium hydroxide, tend to hydrolyze some of the cocaine into non-psychoactive ecgonine.

### Chewed/eaten
Coca leaves are typically mixed with an alkaline substance (such as lime) and chewed into a wad that is retained in the mouth between gum and cheek (much in the same as chewing tobacco is chewed) and sucked of its juices. The juices are absorbed slowly by the mucous membrane of the inner cheek and by the gastrointestinal tract when swallowed. Alternatively, coca leaves can be infused in liquid and consumed like tea. Ingesting coca leaves generally is an inefficient means of administering cocaine. Advocates of the consumption of the coca leaf state that coca leaf consumption should not be criminalized as it is not actual cocaine, and consequently it is not properly the illicit drug. Because cocaine is hydrolyzed and rendered inactive in the acidic stomach, it is not readily absorbed when ingested alone. Only when mixed with a highly alkaline substance (such as lime) can it be absorbed into the bloodstream through the stomach. The efficiency of absorption of orally administered cocaine is limited by two additional factors. First, the drug is partly catabolized by the liver. Second, capillaries in the mouth and esophagus constrict after contact with the drug, reducing the surface area over which the drug can be absorbed. Nevertheless, cocaine metabolites can be detected in the urine of subjects that have sipped even one cup of coca leaf infusion. Therefore, this is an actual additional form of administration of cocaine, albeit an inefficient one.
Orally administered cocaine takes approximately 30 minutes to enter the bloodstream. Typically, only a third of an oral dose is absorbed, although absorption has been shown to reach 60% in controlled settings. Given the slow rate of absorption, maximum physiological and psychotropic effects are attained approximately 60 minutes after cocaine is administered by ingestion. While the onset of these effects is slow, the effects are sustained for approximately 60 minutes after their peak is attained.
Contrary to popular belief, both ingestion and insufflation result in approximately the same proportion of the drug being absorbed: 30 to 60%. Compared to ingestion, the faster absorption of insufflated cocaine results in quicker attainment of maximum drug effects. Snorting cocaine produces maximum physiological effects within 40 minutes and maximum psychotropic effects within 20 minutes, however, a more realistic activation period is closer to 5 to 10 minutes, which is similar to ingestion of cocaine. Physiological and psychotropic effects from nasally insufflated cocaine are sustained for approximately 40 - 60 minutes after the peak effects are attained.
Mate de coca or coca-leaf infusion is also a traditional method of consumption and is often recommended in coca producing countries, like Peru and Bolivia, to ameliorate some symptoms of altitude sickness. This method of consumption has been practiced for many centuries by the native tribes of South America. One specific purpose of ancient coca leaf consumption was to increase energy and reduce fatigue in messengers who made multi-day quests to other settlements.
In 1986 an article in the Journal of the American Medical Association revealed that U.S. health food stores were selling dried coca leaves to be prepared as an infusion as Health Inca Tea. While the packaging claimed it had been decocainized, no such process had actually taken place. The article stated that drinking two cups of the tea per day gave a mild stimulation, increased heart rate, and mood elevation, and the tea was essentially harmless. Despite this, the DEA seized several shipments in Hawaii, Chicago, Illinois, Georgia, and several locations on the East Coast of the United States, and the product was removed from the shelves.

### Insufflation
Insufflation (known colloquially as "snorting," "sniffing," or "blowing") is the most common method of ingestion of recreational powdered cocaine in the Western world. Cocaine is not inhaled using this method. The drug coats and is absorbed through the mucous membranes lining the sinuses. When insufflating cocaine, absorption through the nasal membranes is approximately 3060%, with higher doses leading to increased absorption efficiency. Any material not directly absorbed through the mucous membranes is collected in mucus and swallowed (this "drip" is considered pleasant by some and unpleasant by others). In a study of cocaine users, the average time taken to reach peak subjective effects was 14.6 minutes.  Any damage to the inside of the nose is because cocaine highly constricts blood vessels and therefore blood and oxygen/nutrient flow to that area.
Prior to insufflation, cocaine powder must be divided into very fine particles. Cocaine of high purity breaks into fine dust very easily, except when it is moist (not well stored) and forms "chunks," which reduces the efficiency of nasal absorption.
Rolled up banknotes, hollowed-out pens, cut straws, pointed ends of keys, specialized spoons, long fingernails, and (clean) tampon applicators are often used to insufflate cocaine. Such devices are often called "tooters" by users. The cocaine typically is poured onto a flat, hard surface (such as a mirror) and divided into "bumps", "lines" or "rails", and then insufflated. The amount of cocaine in a line varies widely from person to person and occasion to occasion (the purity of the cocaine is also a factor), but one line is generally considered to be a single dose and is typically 35 mg (a "bump") to 100 mg (a "rail"). As tolerance builds rapidly in the short-term (hours), many lines are often snorted to produce greater effects.
A study by Bonkovsky and Mehta published in Am Acad Dermatol (2001 Feb;44(2):159-82) reported that, just like shared needles, the sharing of straws used to "snort" cocaine can spread blood diseases such as Hepatitis C.

### Injected
Drug injection provides the highest blood levels of drug in the shortest amount of time. Upon injection, cocaine reaches the brain in a matter of seconds, and the exhilarating rush that follows can be so intense that it induces some users to vomit uncontrollably. In a study of cocaine users, the average time taken to reach peak subjective effects was 3.1 minutes. The euphoria passes quickly. Aside from the toxic effects of cocaine, there is also danger of circulatory emboli from the insoluble substances that may be used to cut the drug. As with all injected illicit substances, there is a risk of the user contracting blood-borne infections if sterile injecting equipment is not available or used.
An injected mixture of cocaine and heroin, known as speedball is a particularly popular and dangerous combination, as the converse effects of the drugs actually complement each other, but may also mask the symptoms of an overdose. It has been responsible for numerous deaths, particularly in and around Los Angeles, including celebrities such as John Belushi, Chris Farley (in Chicago), Mitch Hedberg (in North NJ) River Phoenix and Layne Staley (in Seattle).
Experimentally, cocaine injections can be delivered to animals such as fruit flies to study the mechanisms of cocaine addiction.

### Smoked
Smoking freebase or crack cocaine is most often accomplished using a pipe made from a small glass tube, often taken from "Love roses," small glass tubes with a paper rose that are promoted as romantic gifts. These are sometimes called "stems", "horns", "blasters" and "straight shooters". A small piece of clean heavy copper or occasionally stainless steel scouring pad often called a "brillo" (actual Brillo pads contain soap, and are not used), or "chore", named for Chore Boy brand copper scouring pads, serves as a reduction base and flow modulator in which the "rock" can be melted and boiled to vapor. In a pinch, crack smokers sometimes smoke though a soda can with small holes in the bottom instead of a crack pipe. Also, the bottoms of small glass liquor bottles can be removed, and the bottles neck can then be stuffed with chore to use as a makeshift crack pipe.
Crack is smoked by placing it at the end of the pipe; a flame held close to it produces vapor, which is then inhaled by the smoker. The effects, felt almost immediately after smoking, are very intense and do not last long usually five to fifteen minutes. In a study performed on crack cocaine users, the average time taken for them to reach their peak subjective "high" was 1.4 minutes. Most (especially frequent) users crave more immediately after the peak. "Crack houses" depend on these cravings by providing a place for smoking crack to its users, and a ready supply of small bags for sale.
When smoked, cocaine is sometimes combined with other drugs, such as cannabis, often rolled into a joint or blunt. Powdered cocaine is also sometimes smoked, though heat destroys much of the chemical; smokers often sprinkle it on marijuana.
The language referring to paraphernalia and practices of smoking cocaine vary across the United States, as do the packaging methods in the street level sale.

### Coca leaf infusions
Coca herbal infusion (also referred to as Coca tea) is used in coca-leaf producing countries much as any herbal medicinal infusion would elsewhere in the world. The free and legal commercialization of dried coca leaves under the form of filtration bags to be used as "coca tea" has been actively promoted by the governments of Peru and Bolivia for many years as a drink having medicinal powers. Visitors to the city of Cuzco in Peru, and La Paz in Bolivia are greeted with the offering of coca leaf infusions (prepared in tea pots with whole coca leaves) purportedly to help the newly-arrived traveler overcome the malaise of high altitude sickness. The effects of drinking coca tea are a mild stimulation and mood lift. It does not produce any significant numbing of the mouth nor does it give a rush like snorting cocaine. In order to prevent the demonization of this product, its promoters publicize the unproven concept that much of the effect of the ingestion of coca leaf infusion would come from the secondary alkaloids, as being not only quantitatively different from pure cocaine but also qualitatively different.
It has been promoted as an adjuvant for the treatment of cocaine dependence. In one controversial study, coca leaf infusion was used -in addition to counseling- to treat 23 addicted coca-paste smokers in Lima, Peru. Relapses fell from an average of four times per month before treatment with coca tea to one during the treatment. The duration of abstinence increased from an average of 32 days prior to treatment to 217 days during treatment. These results suggest that the administration of coca leaf infusion plus counseling would be an effective method for preventing relapse during treatment for cocaine addiction. Importantly, these results also suggest strongly that the primary pharmacologically active metabolite in coca leaf infusions is actually cocaine and not the secondary alkaloids.
The cocaine metabolite benzoylecgonine can be detected in the urine of people a few hours after drinking one cup of coca leaf infusion.

### Oral
Cocaine has been used medically and informally as an oral anesthetic. Many users rub the powder along the gum line, or onto a cigarette filter which is then smoked, which numbs the gums and teeth - hence the colloquial names of "numbies", "gummies" or "cocoa puffs" for this type of administration. This is mostly done with the small amounts of cocaine remaining on a surface after insufflation. Another oral method is to wrap up some cocaine in rolling paper and swallow it. This is sometimes called a "snow bomb."

## Physical mechanisms
The pharmacodynamics of cocaine involve the complex relationships of neurotransmitters (inhibiting monoamine uptake in rats with ratios of about: serotonin:dopamine = 2:3, serotonin:norepinephrine = 2:5) The most extensively studied effect of cocaine on the central nervous system is the blockade of the dopamine transporter protein. Dopamine transmitter released during neural signaling is normally recycled via the transporter; i.e., the transporter binds the transmitter and pumps it out of the synaptic cleft back into the pre-synaptic neuron, where it is taken up into storage vesicles. Cocaine binds tightly at the dopamine transporter forming a complex that blocks the transporter's function. The dopamine transporter can no longer perform its reuptake function, and thus dopamine accumulates in the extracellular space (synaptic cleft). This results in an enhanced and prolonged post-synaptic effect of dopaminergic signaling at dopamine receptors on the receiving neuron. Prolonged exposure to cocaine, as occurs with habitual use, leads to homeostatic dysregulation of normal (i.e. without cocaine) dopaminergic signaling via down-regulation of dopamine receptors and enhanced signal transduction. The decreased dopaminergic signaling after chronic cocaine use may contribute to depressive mood disorders and sensitize this important brain reward circuit to the reinforcing effects of cocaine (e.g. enhanced dopaminergic signalling only when cocaine is self-administered). This sensitization contributes to the intractable nature of addiction and relapse.
Dopamine-rich brain regions such as the ventral tegmental area, nucleus accumbens, and prefrontal cortex are frequent targets of cocaine addiction research. Of particular interest is the pathway consisting of dopaminergic neurons originating in the ventral tegmental area that terminate in the nucleus accumbens. This projection may function as a "reward center", in that it seems to show activation in response to drugs of abuse like cocaine in addition to natural rewards like food or sex. While the precise role of dopamine in the subjective experience of reward is highly controversial among neuroscientists, the release of dopamine in the nucleus accumbens is widely considered to be at least partially responsible for cocaine's rewarding effects. This hypothesis is largely based on laboratory data involving rats that are trained to self-administer cocaine. If dopamine antagonists are infused directly into the nucleus accumbens, well-trained rats self-administering cocaine will undergo extinction (i.e. initially increase responding only to stop completely) thereby indicating that cocaine is no longer reinforcing (i.e. rewarding) the drug-seeking behavior.
Cocaine's effects on serotonin (5-hydroxytryptamine, 5-HT) show across multiple serotonin receptors, and is shown to inhibit the re-uptake of 5-HT3 specifically as an important contributor to the effects of cocaine. The overabundance of 5-HT3 receptors in cocaine conditioned rats display this trait, however the exact effect of 5-HT3 in this process is unclear. The 5-HT2 receptor (particularly the subtypes 5-HT2AR, 5-HT2BR and 5-HT2CR) show influence in the evocation of hyperactivity displayed in cocaine use.
Sigma receptors are effected by cocaine, as cocaine functions as a sigma ligand agonist. Further specific receptors it has been demonstrated to function on are NMDA and the D1 dopamine receptor.
Cocaine also blocks sodium channels, thereby interfering with the propagation of action potentials; thus, like lignocaine and novocaine, it acts as a local anesthetic. Cocaine also causes vasoconstriction, thus reducing bleeding during minor surgical procedures. The locomotor enhancing properties of cocaine may be attributable to its enhancement of dopaminergic transmission from the substantia nigra. Recent research points to an important role of circadian mechanisms and clock genes in behavioral actions of cocaine.
Because nicotine increases the levels of dopamine in the brain, many cocaine users find that consumption of tobacco products during cocaine use enhances the euphoria. This, however, may have undesirable consequences, such as uncontrollable chain smoking during cocaine use (even users who do not normally smoke cigarettes have been known to chain smoke when using cocaine), in addition to the detrimental health effects and the additional strain on the cardiovascular system caused by tobacco.
In addition to irritability, mood disturbances, restlessness, paranoia, and auditory hallucinations, crack can cause several dangerous physical conditions. It can lead to disturbances in heart rhythm and heart attacks, as well as chest pains or even respiratory failure. In addition, strokes, seizures and headaches are common in heavy users.
Cocaine can often cause reduced food intake, many chronic users lose their appetite and can experience severe malnutrition and significant weight loss.

## Metabolism and excretion
Cocaine is extensively metabolized, primarily in the liver, with only about 1% excreted unchanged in the urine. The metabolism is dominated by hydrolytic ester cleavage, so the eliminated metabolites consist mostly of benzoylecgonine, the major metabolite, and in lesser amounts ecgonine methyl ester and ecgonine.
If taken with alcohol, cocaine combines with the ethanol in the liver to form cocaethylene, which is both more euphorigenic and some studies suggest a higher cardiovascular toxicity than cocaine by itself. It is precisely this characteristic that has prompted heavily inebriated persons, since the early 20th century, to snort cocaine to relieve them of the depressive effects of alcohol abuse.
Depending on liver and kidney function, cocaine metabolites are detectable in urine. Benzoylecgonine can be detected in urine within four hours after cocaine intake and remains detectable in concentrations greater than 150 ng/ml typically for up to eight days after cocaine is used. Detection of accumulation of cocaine metabolites in hair is possible in regular users until the sections of hair grown during use are cut or fall out.

## Effects and health issues

### Acute
Cocaine is a potent central nervous system stimulant. Its effects can last from 20 minutes to several hours, depending upon the dosage of cocaine taken, purity, and method of administration.
The initial signs of stimulation are hyperactivity, restlessness, increased blood pressure, increased heart rate and euphoria. The euphoria is sometimes followed by feelings of discomfort and depression and a craving to experience the drug again. Sexual interest and pleasure can be amplified. Side effects can include twitching, paranoia, and impotence, which usually increases with frequent usage.
With excessive dosage the drug can produce itching, tachycardia, hallucinations, and paranoid delusions. Overdoses cause tachyarrhythmias and a marked elevation of blood pressure. These can be life-threatening, especially if the user has existing cardiac problems. The LD50 of cocaine when administered to mice is 95.1 mg/kg. Toxicity results in seizures, followed by respiratory and circulatory depression of medullar origin. This may lead to death from respiratory failure, stroke, cerebral hemorrhage, or heart-failure. Cocaine is also highly pyrogenic, because the stimulation and increased muscular activity cause greater heat production. Heat loss is inhibited by the intense vasoconstriction. Cocaine-induced hyperthermia may cause muscle cell destruction and myoglobinuria resulting in renal failure. Emergency treatment often consists of administering a benzodiazepine sedation agent, such as diazepam (Valium) to decrease the elevated heart rate and blood pressure. Physical cooling (ice, cold blankets, etc...) and paracetamol(acetaminophen) may be used to treat hyperthermia, while specific treatments are then developed for any further complications. There is no officially approved specific antidote for cocaine overdose, and although some drugs such as dexmedetomidine and rimcazole have been found to be useful for treating cocaine overdose in animal studies, no formal human trials have been carried out.
In cases where a patient is unable or unwilling to seek medical attention, cocaine overdoses resulting in mild-moderate tachycardia (i.e.: a resting pulse greater than 120 bpm), may be initially treated with 20 mg of orally administered diazepam or equivalent benzodiazepine (eg: 2mg lorazepam). Acetaminophen and physical cooling may likewise be used to reduce mild hyperthermia (<39 C). However, a history of high blood pressure or cardiac problems puts the patient at high risk of cardiac arrest or stroke, and requires immediate medical treatment. Similarly, if benzodiazepine sedation fails to reduce heart rate or body temperatures fails to lower, professional intervention is necessary.
Cocaine's primary acute effect on brain chemistry is to raise the amount of dopamine and serotonin in the nucleus accumbens (the pleasure center in the brain); this effect ceases, due to metabolism of cocaine to inactive compounds and particularly due to the depletion of the transmitter resources (tachyphylaxis). This can be experienced acutely as feelings of depression, as a "crash" after the initial high. Further mechanisms occur in chronic cocaine use. The "crash" is accompanied with muscle spasms throughout the body, also known as the "jitters", muscle weakness, headaches, dizziness, and suicidal thoughts. Not all users will experience these, but most tend to experience some or all of these symptoms.
Studies have shown that cocaine usage during pregnancy triggers premature labor and may lead to abruptio placentae.
Cocaine can cause coronary artery spasms which lead to a myocardial infarction.  This effect can happen randomly to any user.  The coronary artery spasms can occur on the users first usage or any other usage after.  The coronary spasms cause the ectopic ventricular foci of the heart to become hypoxic and the extreme irritability can trigger life-threatening ventricular arrhythmias.

### Chronic
Chronic cocaine intake causes brain cells to adapt functionally  to strong imbalances of transmitter levels in order to compensate extremes. Thus, receptors disappear from the cell surface or reappear on it, resulting more or less in an "off" or "working mode" respectively, or they change their susceptibility for binding partners (ligands) mechanisms called down-/upregulation. Chronic cocaine use leads to a DATS upregulation, further contributing to depressed mood states. However, studies suggest cocaine abusers do not show normal age-related loss of striatal DAT sites, suggesting cocaine has neuroprotective properties for dopamine neurons. Physical withdrawal is not dangerous, and is in fact restorative. The experience of insatiable hunger, aches, insomnia/oversleeping, lethargy, and persistent runny nose are often described as very unpleasant. Depression with suicidal ideation may develop in very heavy users. Finally, a loss of vesicular monoamine transporters, neurofilament proteins, and other morphological changes appear to indicate a long term damage of dopamine neurons.
All these effects contribute a rise in tolerance thus requiring a larger dosage to achieve the same effect. The lack of normal amounts of serotonin and dopamine in the brain is the cause of the dysphoria and depression felt after the initial high. The diagnostic criteria for cocaine withdrawal are characterized by a dysphoric mood, fatigue, unpleasant dreams, insomnia or hypersomnia, erectile dysfunction, increased appetite, psychomotor retardation or agitation, and anxiety.
Cocaine abuse also has multiple physical health consequences. It is associated with a lifetime risk of heart attack that is 6% higher than that of non-users. During the hour after cocaine is used, heart attack risk rises 24-fold.
Side effects from chronic smoking of cocaine include hemoptysis, bronchospasm, pruritus, fever, diffuse alveolar infiltrates without effusions, pulmonary and systemic eosinophiliachest, pain, lung trauma, shortness of breath, sore throat, asthma, hoarse voice, dyspnea, and an aching, flu-like syndrome. A common but untrue belief is that the smoking of cocaine chemically breaks down tooth enamel and causes tooth decay. However, cocaine does often cause involuntary tooth grinding, known as bruxism, which can deteriorate tooth enamel and lead to gingivitis.
Chronic intranasal usage can degrade the cartilage separating the nostrils (the septum nasi), leading eventually to its complete disappearance. Due to the absorption of the cocaine from cocaine hydrochloride, the remaining hydrochloride forms a dilute hydrochloric acid.
Cocaine may also greatly increase this risk of developing rare autoimmune or connective tissue diseases such as lupus, Goodpasture's disease, vasculitis, glomerulonephritis, Stevens-Johnson syndrome and other diseases. It can also cause a wide array of kidney diseases and renal failure. While these conditions are normally found in chronic use they can also be caused by short term exposure in susceptible individuals.
Cocaine abuse doubles both the risks of hemorrhagic and ischemic strokes.
Years after the abuse has ended, many ex-abusers report a noticeably reduced attention span.

## Cocaine as a local anesthetic
Cocaine was historically useful as a topical anesthetic in eye and nasal surgery, although it is now predominantly used for nasal and lacrimal duct surgery. The major disadvantages of this use are cocaine's intense vasoconstrictor activity and potential for cardiovascular toxicity. Cocaine has since been largely replaced in Western medicine by synthetic local anaesthetics such as benzocaine, proparacaine, lignocaine/xylocaine/lidocaine, and tetracaine though it remains available for use if specified. If vasoconstriction is desired for a procedure (as it reduces bleeding), the anesthetic is combined with a vasoconstrictor such as phenylephrine or epinephrine. In Australia it is currently prescribed for use as a local anesthetic for conditions such as mouth and lung ulcers. Some ENT specialists occasionally use cocaine within the practice when performing procedures such as nasal cauterization. In this scenario dissolved cocaine is soaked into a ball of cotton wool, which is placed in the nostril for the 10-15 minutes immediately prior to the procedure, thus performing the dual role of both numbing the area to be cauterized and also vasoconstriction. Even when used this way, some of the used cocaine may be absorbed through oral or nasal mucosa and give systemic effects.

## Etymology
The word "cocaine" was made from "coca" + the suffix "-ine"; from its use as a local anaesthetic a suffix "-caine" was extracted and used to form names of synthetic local anaesthetics.

# Current Prohibition
The production, distribution and sale of cocaine products is restricted (and illegal in most contexts) in most countries as regulated by the Single Convention on Narcotic Drugs, and the United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances. In the United States the manufacture, importation, possession, and distribution of cocaine is additionally regulated by the 1970 Controlled Substances Act.
Some countries, such as Peru and Bolivia permit the cultivation of coca leaf for traditional consumption by the local indigenous population, but nevertheless prohibit the production, sale and consumption of cocaine.
Some parts of Europe and Australia allow processed cocaine for medicinal uses only.
In certain countries in the Middle East and Asia, such as Singapore, Saudi Arabia and Indonesia, being in possession of cocaine can be punishable by death.

## Interdiction
In 2004, according to the United Nations, 589 metric tons of cocaine were seized globally by law enforcement authorities. Colombia seized 188 tons, the United States 166 tons, Europe 79 tons, Peru 14 tons, Bolivia 9 tons, and the rest of the world 133 tons.

# Illicit trade
Because of the extensive processing it undergoes during preparation, cocaine is generally treated as a 'hard drug', with severe penalties for possession and trafficking. Demand remains high, and consequently black market cocaine is quite expensive. Unprocessed cocaine, such as coca leaves, are occasionally purchased and sold, but this is exceedingly rare as it is much easier and more profitable to conceal and smuggle it in powdered form. The scale of the market is immense: 770 tonnes times $100 per gram retail = up to $77 billion.

## Production
By 1999, Colombia had become the world's leading producer of cocaine. Three-quarters of the world's annual yield of cocaine was produced there, both from cocaine base imported from Peru (primarily the Huallaga Valley) and Bolivia, and from locally grown coca. There was a 28% increase from the amount of potentially harvestable coca plants which were grown in Colombia in 1998 . This, combined with crop reductions in Bolivia and Peru, made Colombia the nation with the largest area of coca under cultivation after the mid-1990s. Coca grown for traditional purposes by indigenous communities, a use which is still present and is permitted by Colombian laws, only makes up a small fragment of total coca production, most of which is used for the illegal drug trade. Attempts to eradicate coca fields through the use of defoliants have devastated part of the farming economy in some coca growing regions of Colombia, and strains appear to have been developed that are more resistant or immune to their use. Whether these strains are natural mutations or the product of human tampering is unclear. These strains have also shown to be more potent than those previously grown, increasing profits for the drug cartels responsible for the exporting of cocaine. The cultivation of coca has become an attractive, and in some cases even necessary, economic decision on the part of many growers due to the combination of several factors, including the persistence of worldwide demand, the lack of other employment alternatives, the lower profitability of alternative crops in official crop substitution programs, the eradication-related damages to non-drug farms, and the spread of new strains of the coca plant.

## Synthesis
Synthetic cocaine would be highly desirable to the illegal drug industry, as it would eliminate the high visibility and low reliability of offshore sources and international smuggling, replacing them with clandestine domestic laboratories, as are common for illicit methamphetamine. However, natural cocaine remains the lowest cost and highest quality supply of cocaine.
Actual full synthesis of cocaine is rarely done. Formation of inactive enantiomers and synthetic by-products limits the yield and purity.
Note, names like 'synthetic cocaine' and 'new cocaine' have been misapplied to phencyclidine (PCP) and various designer drugs.

## Trafficking and distribution
Organized criminal gangs operating on a large scale dominate the cocaine trade. Most cocaine is grown and processed in South America, particularly in Colombia, Bolivia, Peru, and smuggled into the United States and Europe, where it is sold at huge markups; usually in the US at $50-$75 for 1 gram (or a "fitty rock"), and $125-200 for 3.5 grams (1/8th of an ounce, or an "eight ball").
Cocaine shipments from South America transported through Mexico or Central America are generally moved over land or by air to staging sites in northern Mexico. The cocaine is then broken down into smaller loads for smuggling across the U.S.Mexico border. The primary cocaine importation points in the United States are in Arizona, southern California, southern Florida, and Texas. Typically, land vehicles are driven across the U.S.-Mexico border. Sixty Five percent of cocaine enters the United States through Mexico, and the vast majority of the rest enters through Florida.
Cocaine is also carried in small, concealed, kilogram quantities across the border by couriers known as mules (or mulas), who cross a border either legally, e.g. through a port or airport, or illegally through undesignated points along the border. The drugs may be strapped to the waist or legs or hidden in bags, or hidden in the body. If the mule gets through without being caught, the gangs will reap most of the profits. If he or she is caught however, gangs will sever all links and the mule will usually stand trial for trafficking by him/herself.
Cocaine traffickers from Colombia, and recently Mexico, have also established a labyrinth of smuggling routes throughout the Caribbean, the Bahama Island chain, and South Florida. They often hire traffickers from Mexico or the Dominican Republic to transport the drug. The traffickers use a variety of smuggling techniques to transfer their drug to U.S. markets. These include airdrops of 500700 kg in the Bahama Islands or off the coast of Puerto Rico, mid-ocean boat-to-boat transfers of 5002,000 kg, and the commercial shipment of tonnes of cocaine through the port of Miami.
Bulk cargo ships are also used to smuggle cocaine to staging sites in the western CaribbeanGulf of Mexico area. These vessels are typically 150250-foot (5080 m) coastal freighters that carry an average cocaine load of approximately 2.5 tonnes. Commercial fishing vessels are also used for smuggling operations. In areas with a high volume of recreational traffic, smugglers use the same types of vessels, such as go-fast boats, as those used by the local populations.
Bales of cocaine washed up on the beaches of Cornwall February 28.
Sophisticated submarine-like boats are the latest tool drug runners are using to bring cocaine north from Colombia, it was reported on March 20 2008. Although the vessels were once viewed as a quirky sideshow in the drug war, they are becoming faster, more seaworthy, and capable of carrying bigger loads of drugs than earlier models, according to those charged with catching them.

## Sales to consumers
Cocaine is readily available in all major countries' metropolitan areas. According to the Summer 1998 Pulse Check, published by the U.S. Office of National Drug Control Policy, cocaine use had stabilized across the country, with a few increases reported in San Diego, Bridgeport, Miami, and Boston. In the West, cocaine usage was lower, which was thought to be due to a switch to methamphetamine among some users; methamphetamine is cheaper and provides a longer-lasting high. Numbers of cocaine users are still very large, with a concentration among urban youth.
In addition to the amounts previously mentioned, cocaine can be sold in "bill sizes": for example, $10 might purchase a "dime bag," a very small amount (0.10.15 g)  of cocaine. Twenty dollars might purchase .15.3 g. However, in lower Texas its sold cheaper due to it being easier to receive. A dime for $10 is .4g, a 20 is .8 or a gram and a 8-ball (3.5g) is sold for $60 to $80 dollars depending on the quality and dealer. These amounts and prices are very popular among young people because they are inexpensive and easily concealed on one's body. Quality and price can vary dramatically depending on supply and demand, and on geographic region.
However UK prices are astronomical compared to that of a USA with 40 (typically $80) getting 1 Gram of Cocaine.

## Consumption
World annual cocaine consumption currently stands at around 600 metric tons, with the United States consuming around 300 metric tons, 50% of the total, Europe about 150 metric tons, 25% of the total, and the rest of the world the remaining 150 metric tons or 25%.
According to the United Nations Office on Drugs and Crime 2006 World Drug Report, the United States has the world's greatest rate of cocaine consumption by people aged 15 to 64, 2.8%. It is closely followed by Spain with 2.7%, and England & Wales with 2.4%. Most Western European countries have a consumption rate between 1% and 2%.

# Usage
According to a 2007 United Nations report, Spain is the country with the highest rate of cocaine usage (3.0% of adults in the previous year).  Other countries where the usage rate meets or exceeds 1.5% are the United States (2.8%), England and Wales (2.4%), Canada (2.3%), Italy (2.1%), Bolivia (1.9%), Chile (1.8%), and Scotland (1.5%).

## In the United States

### General usage
Cocaine has become the second most popular illegal recreational drug in the U.S. (behind marijuana). Cocaine is commonly used in middle to upper class communities. It is also popular amongst college students, not just to aid in studying, but also as a party drug. Its users span over different ages, races, and professions. In the 1970s and 80's, the drug became particularly popular in the disco culture as cocaine usage was very common and popular in many discos such as Studio 54.
The National Household Survey on Drug Abuse (NHSDA) reported in 1999 that cocaine was used by 3.7 million Americans, or 1.7% of the household population age 12 and older. Estimates of the current number of those who use cocaine regularly (at least once per month) vary, but 1.5 million is a widely accepted figure within the research community.
Although cocaine use had not significantly changed over the six years prior to 1999, the number of first-time users went up from 574,000 in 1991, to 934,000 in 1998 an increase of 63%. While these numbers indicated that cocaine is still widely present in the United States, cocaine use was significantly less prevalent than it was during the early 1980s. Cocaine use peaked in 1982 when 10.4 million Americans (5.6% of the population) reportedly used the drug.

### Usage among youth
The 1999 Monitoring the Future (MTF) survey found the proportion of American students reporting use of powdered cocaine rose during the 1990s. In 1991, 2.3% of eighth-graders stated that they had used cocaine in their lifetime. This figure rose to 4.7% in 1999. For the older grades, increases began in 1992 and continued through the beginning of 1999. Between those years, lifetime use of cocaine went from 3.3% to 7.7% for tenth-graders and from 6.1% to 9.8% for high school seniors. Lifetime use of crack cocaine, according to MTF, also increased among eighth-, tenth-, and twelfth-graders, from an average of 2% in 1991 to 3.9% in 1999.
Perceived risk and disapproval of cocaine and crack use both decreased during the 1990s at all three grade levels. The 1999 NHSDA found the highest rate of monthly cocaine use was for those aged 1825 at 1.7%, an increase from 1.2% in 1997. Rates declined between 1996 and 1998 for ages 2634, while rates slightly increased for the 1217 and 35+ age groups. Studies also show people are experimenting with cocaine at younger ages. NHSDA found a steady decline in the mean age of first use from 23.6 years in 1992 to 20.6 years in 1998.

# Addiction
Cocaine dependence (or addiction) is physical and psychological dependency on the regular use of cocaine. It can result in physiological damage, lethargy, psychosis, depression, or a potentially fatal overdose.