Cocaine (benzoylmethylecgonine) 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 a stimulant of the central nervous system and an appetite suppressant. Specifically, it is a serotonin-norepinephrine-dopamine reuptake inhibitor, which mediates functionality of such as an exogenous catecholamine transporter ligand. Because of the way it affects the mesolimbic reward pathway, cocaine is addictive.

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 over 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 communities—ancient 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.

When the Spaniards conquered South America, they at first ignored aboriginal claims that the leaf gave them strength and energy, and declared the practice of chewing it the work of the Devil. But after discovering that these claims were true, they legalized and taxed the leaf, taking 10% off the value of each crop. In 1569, Nicolás Monardes described the practice of the natives of chewing a mixture of tobacco and coca leaves to induce "great contentment":

In 1609, Padre Blas Valera wrote:

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. Various European scientists had attempted to isolate cocaine, but none had been successful for two reasons: the knowledge of chemistry required was insufficient at the time, and the cocaine was worsened because coca does not grow in the Eurasian region and ruined easily amidst transcontinental shipping.

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 Archiv der Pharmazie.

In 1856, Friedrich Wöhler 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 Wöhler received a trunk full of coca. Wöhler passed on the leaves to Albert Niemann, a Ph.D. student at the University of Göttingen in Germany, who then developed an improved purification process.

Niemann described every step he took to isolate cocaine in his dissertation titled Über eine neue organische Base in den Cocablättern (On a New Organic Base in the Coca Leaves), which was published in 1860—it 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 “cocaine”—as 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 Willstätter in 1898. The synthesis started from tropinone, a related natural product and took five steps.

Medicalization

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 Würzburg, 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 anesthesia.

Today, cocaine has very limited medical use. See the section Cocaine as a local anesthetic

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, [and] whitening of the teeth.”

A chemist named Angelo Mariani who read Mantegazza’s 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, to become cocawine. The ethanol in wine acted as a solvent and extracted the cocaine from the coca leaves, altering the drink’s 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 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 anesthetic in Germany in 1884, about the same time as Sigmund Freud published his work Über Coca, in which he wrote that cocaine causes

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 user’s 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, it was injected by Arthur Conan Doyle’s 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.

Prohibition

By the turn of the twentieth century, the addictive properties of cocaine had become clear, 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 Pennsylvania’s 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.

The estimated U.S. cocaine market exceeded $70 billion in street value for the year 2005, exceeding revenues by corporations such as 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. Cocaine’s 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 the risk of ill effects or damage 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 anesthaesia as many users believe a strong numbing effect is the result of strong and/or pure cocaine, ephedrine or similar stimulants that are to produce an increased heart rate. The normal adulterants for profit are inactive sugars, usually mannitol, creatine or glucose, so introducing active adulterants gives the illusion of purity and to 'stretch' or make it so a dealer can sell more product than without the adulterants. The adulterant of sugars therefore allows the dealer to sell the product for a higher price because of the illusion of purity and allows to sell more of the product at that higher price, enabling dealers to make a lot of revenue with little cost of the adulterants. Cocaine trading carries large penalties in most jurisdictions, so user deception about purity and consequent high profits for dealers are the norm. A study by the European Monitoring Centre for Drugs and Drug Addiction in 2007 showed that the purity levels for street purchased cocaine was often under 5% and on average under 50% pure.

Biosynthesis

The first synthesis and elucidation of the cocaine molecule was by Richard Willstätter in 1898. Willstätter's synthesis derived cocaine from tropinone. Since then, Robert Robinson and Edward Leete have made significant contributions to the mechanism of the synthesis.

Biosynthesis of N-methyl-pyrrolinium cation

The biosynthesis begins with L-Glutamine, which is derived to L-ornithine in plants. The major contribution of L-ornithine and L-arginine as a precursor to the tropane ring was confirmed by Edward Leete. Ornithine then undergoes a Pyridoxal phosphate-dependent decarboxylation to form putrescine. In animals, however, the urea cycle derives putrescine from ornithine. L-ornithine is converted to L-arginine, which is then decarboxylated via PLP to form agmatine. Hydrolysis of the imine derives N-carbamoylputrescine followed with hydrolysis of the urea to form putrescine. The separate pathways of converting ornithine to putrescine in plants and animals have converged. A SAM-dependent N-methylation of putrescine gives the N-methylputrescine product, which then undergoes oxidative deamination by the action of diamine oxidase to yield the aminoaldehyde. Schiff base formation confirms the biosynthesis of the N-methyl-Δ¹-pyrrolinium cation.

Biosynthesis of cocaine

The additional carbon atoms required for the synthesis of cocaine are derived from acetyl-CoA, by addition of two acetyl-CoA units to the N-methyl-Δ¹-pyrrolinium cation . The first addition is a Mannich-like reaction with the enolate anion from acetyl-CoA acting as a nucleophile towards the pyrrolinium cation. The second addition occurs through a Claisen condensation. This produces a racemic mixture of the 2-substituted pyrrolidine, with the retention of the thioester from the Claisen condensation. In formation of tropinone from racemic ethyl [2,3-13C2]4(Nmethyl-2-pyrrolidinyl)-3-oxobutanoate there is no preference for either stereoisomer . In the biosynthesis of cocaine, however, only the (S)-enantiomer can cyclize to form the tropane ring system of cocaine. The stereoselectivity of this reaction was further investigated through study of prochiral methylene hydrogen discrimination . This is due to the extra chiral center at C-2 . This process occurs through an oxidation, which regenerates the pyrrolinium cation and formation of an enolate anion, and an intramolecular Mannich reaction. The tropane ring system undergoes hydrolysis, SAM-dependent methylation, and reduction via NADPH for the formation of methylecgonine. The benzoyl moiety required for the formation of the cocaine diester is synthesized from phenylalanine via cinnamic acid . Benzoyl-CoA then combines the two units to form cocaine.

Robert Robinson's acetonedicarboxylate

The biosynthesis of the tropane alkaloid, however, is still uncertain. Hemscheidt proposes that Robinson's acetonedicarboxylate emerges as a potential intermediate for this reaction . Condensation of N-methylpyrrolinium and acetonedicarboxylate would generate the oxobutyrate. Decarboxylation leads to tropane alkaloid formation.

Reduction of tropinone

The reduction of tropinone is mediated by NADPH-dependent reductase enzymes, which have been characterized in multiple plant species . These plant species all contain two types of the reductase enzymes, tropinone reductase I and tropinone reductase II. TRI produces tropine and TRII produces pseudotropine. Due to differing kinetic and pH/activity characteristics of the enzymes and by the 25-fold higher activity of TRI over TRII, the majority of the tropinone reduction is from TRI to form tropine .

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

Salts

Cocaine, like many alkaloids can form many different salts, such as hydrochloride (HCl) and sulfate (-SO4). Different salts have different solvency in solvents. Its hydrochloride, like many alkaloid hydrochloride is polar and is soluble in water.

Basic

As the name implies, “freebase” is the base form of cocaine, as opposed to the salt form. It is practically insoluble in water whereas hydrochloride salt is water soluble.

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.

Pure cocaine is prepared by neutralizing its compounding salt with an alkaline solution which will precipitate to non-polar basic cocaine. It is further refined through aqueous-solvent Liquid-liquid extraction.

Crack cocaine

Crack is a lower purity form of free-base cocaine and contains sodium bicarbonate as impurity. Freebase and crack are often administered by smoking. The origin of the name is from the crackling sound (hence the onomatopoeic “crack”) produced when cocaine containing impurities are heated.

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.

Routes of administration

Oral

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", "gummers" 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."

Coca leaf

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. The drug coats and is absorbed through the mucous membranes lining the sinuses. When insufflating cocaine, absorption through the nasal membranes is approximately 30–60%, 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, CD case or book) and divided into "bumps", "lines" or "rails", and then insufflated. As tolerance builds rapidly in the short-term (hours), many lines are often snorted to produce greater effects.

A study by Bonkovsky and Mehta reported that, just like shared needles, the sharing of straws used to "snort" cocaine can spread blood diseases such as Hepatitis C.

In the United States, as far back as 1992 many of the people sentenced by federal authorities for charges related to powder cocaine were Hispanic; more Hispanics than non-Hispanic White and non-Hispanic Black people received sentences for crimes related to powder cocaine.

Injection

Drug injection provides the highest blood levels of drug in the shortest amount of time. Subjective effects not commonly shared with other methods of administration include a ringing in the ears moments after injection (usually when in excess of 120 milligrams) lasting 2 to 5 minutes including tinnitus & audio distortion. This is colloquially referred to as a "bell ringer". 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, including celebrities such as John Belushi, Chris Farley, Mitch Hedberg, River Phoenix and Layne Staley.

Experimentally, cocaine injections can be delivered to animals such as fruit flies to study the mechanisms of cocaine addiction.

Inhalation

Inhalation or smoking is one of the several means cocaine is administered. Cocaine is smoked by inhaling the vapor by sublimating solid cocaine by heating. In a 2000 Brookhaven National Laboratory medical department study, based on self reports of 32 abusers who participated in the study,"peak high" was found at mean of 1.4min +/- 0.5 minutes.

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. Crack smokers also sometimes smoke through a soda can with small holes in the bottom.

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.

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, as do the packaging methods in the street level sale.

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 presynaptic 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 synaptic cleft. This results in an enhanced and prolonged postsynaptic 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.

In addition to the mechanism shown on the above chart, cocaine has been demonstrated to bind as to directly stabilize the DAT transporter on the open outward-facing conformation whereas other stimulants (namely phenethylamines) stabilize the closed conformation. Further, cocaine binds in such a way as to inhibit a hydrogen bond innate to DAT that otherwise still forms when amphetamine and similar molecules are bound. Cocaine's binding properties are such that it attaches so this hydrogen bond will not form and is blocked from formation due to the tightly locked orientation of the cocaine molecule. Research studies have suggested that the affinity for the transporter is not what is involved in habituation of the substance so much as the conformation and binding properties to where & how on the transporter the molecule binds.

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. It also functions on the binding sites to the dopamine & serotonin sodium dependent transport area as targets as separate mechanisms from its reuptake of those transporters; unique to its local anesthetic value which makes it in a class of functionality different from both its own derived phenyltropanes analogues which have that removed and the amphetamine class of stimulants which as well altogether lack that. In addition to this cocaine has some target binding to the site of the Kappa-opioid receptor as well. 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, cocaine use 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. Cocaine effects, further, are shown to be potentiated for the user when used in conjunction with new surroundings and stimuli, and otherwise novel environs.

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 (BE), the major metabolite, and other significant metabolites in lesser amounts such as ecgonine methyl ester (EME) and ecgonine. Further minor metabolites of cocaine include norcocaine, p-hydroxycocaine, m-hydroxycocaine, p-hydroxybenzoylecgonine (pOHBE), and m-hydroxybenzoylecgonine. These do not include metabolites created beyond the standard metabolism of the drug in the human body, like for example by the process of pyrolysis such as is the case with methylecgonidine.

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.

If consumed with alcohol, cocaine combines with alcohol in the liver to form cocaethylene. Studies have suggested cocaethylene is both more euphorigenic, and has a higher cardiovascular toxicity than cocaine by itself.

A study in mice has suggested that capsaicin found in pepper spray may interact with cocaine with potentially fatal consequences. The method through which they would interact however, is not known.

Effects and health issues

Cocaine is a powerful nervous system stimulant. Its effects can last from 15-30 minutes to an hour, depending upon the method of ingestion.

Cocaine increases alertness, feelings of well-being and euphoria, energy and motor activity, feelings of competence and sexuality. Athletic performance may be enhanced. Anxiety, paranoia and restlessness are also frequent. With excessive dosage, tremors, convulsions and increased body temperature are observed.

Health problems from the use of legal substances, particularly alcohol and tobacco, are greater than health problems from cocaine use and occasional cocaine use does not typically lead to severe or even minor physical or social problems.

Acute

With excessive or prolonged use, the drug can cause 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 intraperitoneally 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: 2 mg 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="" risk="" 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.

Studies have shown that cocaine usage during pregnancy triggers premature labor and may lead to abruptio placentae.

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. However, studies suggest cocaine abusers do not show normal age-related loss of striatal DAT sites, suggesting cocaine has neuroprotective properties for dopamine neurons. 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. Physical withdrawal is not dangerous, and is in fact restorative. 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.

Physical side effects from chronic smoking of cocaine include hemoptysis, bronchospasm, pruritus, fever, diffuse alveolar infiltrates without effusions, pulmonary and systemic eosinophilia, chest pain, lung trauma, sore throat, asthma, hoarse voice, dyspnea (shortness of breath), 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.

Cocaine abuse doubles both the risks of hemorrhagic and ischemic strokes, as well as increases the risk of other infarctions, such as myocardial infarction.

Addiction

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

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 anesthetics 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.

In 2005, researchers from Kyoto University Hospital proposed the use of cocaine in conjunction with phenylephrine administered in the form of an eye drop as a diagnostic test for Parkinson's disease.

Etymology

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

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. In addition, some parts of Europe and Australia allow processed cocaine for medicinal uses only.

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

Colombia is the world's leading producer of cocaine.Due to Colombia's 1994 legalization of small amounts of cocaine for personal use, while sale of cocaine was still prohibited, the result was the spread of local coca crops, partly justified by the local demand.

Three-quarters of the world's annual yield of cocaine has been produced in Colombia, 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. Although production fell temporarily, coca crops rebounded as numerous smaller fields in Colombia, rather than the larger plantations.

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.

2000

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(cocaine has 4 chiral centres - 1R,2R,3S,5S - hence a total potential of 16 possible enantiomers and disteroisomers) plus 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 criminalgangs 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, the United States being the worlds largest consumer of Cocaine, where it is sold at huge markups; usually in the US at $80–$120 for 1 gram, and $250–300 for 3.5 grams (1/8th of an ounce, or an "eight ball").

Caribbean and Mexican routes

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 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 500–700 kg in the Bahama Islands or off the coast of Puerto Rico, mid-ocean boat-to-boat transfers of 500–2,000 kg, and the commercial shipment of tonnes of cocaine through the port of Miami.

Chilean route

Another route of cocaine traffic goes trough Chile, this route is primarily used for cocaine produced in Bolivia since the nearest seaports lies in northern Chile. The arid Bolivia-Chile border is easily crossed by 4x4 vehicles that then heads to the seaports of Iquique and Antofagasta.While the prize of cocaine is higher in Chile than in Peru and Bolivia the final destination is usually Europe, specially Spain where drug dealing networks exists among South American immigrants.

Techniques

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 elsewhere. 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 alone.

Bulk cargo ships are also used to smuggle cocaine to staging sites in the western Caribbean–Gulf of Mexico area.These vessels are typically 150–250-foot (50–80 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.

Sophisticated drug subsare 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 methamphetamineamong 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 (0.1–0.15 g) of cocaine. Twenty dollars might purchase .15–.3 g. However, in lower Texas, it's sold cheaper due to it being easier to receive: a dime for $10 is .4g, a 20 is .8-1.0 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.

The European Monitoring Centre for Drugs and Drug Addictionreports that the typical retail price of cocaine varied between 50€ and 75€ per gram in most European countries, although Cyprus, Romania, Sweden and Turkey reported much higher values.

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%.

Cocaine adulterants

Cocaine is "cut" with many substances such as:

Anesthetics:

• Lidocaine
• Benzocaine
• Procaine

Other stimulants:

• Caffeine
• Ephedrine
• Methamphetamine

Inertpowder:

• Baking soda
• Inositol

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 is the second most popular illegal recreational drug in the U.S. (behind marijuana) and the U.S. is the world's largest consumer of cocaine. Cocaine is commonly used in middle to upper class communities. It is also popular amongst college students, 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.

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 18–25 at 1.7%, an increase from 1.2% in 1997. Rates declined between 1996 and 1998 for ages 26–34, while rates slightly increased for the 12–17 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.

In Europe

General usage

Cocaine is the second most popular illegal recreational drug in Europe (behind marijuana). Since the mid-1990s, overall cocaine usage in Europe has been on the rise, but usage rates and attitudes tend to vary between countries. Countries with the highest usage rates are: The United Kingdom, Spain, Italy, and Ireland.

Approximately 12 million Europeans (3.6%) have used cocaine at least once, 4 million (1.2%) in the last year, and 2 million in the last month (0.5%).

Usage among young adults

About 3.5 million or 87.5% of those who have used the drug in the last year are young adults (15–34 years old). Usage is particularly prevalent among this demographic: 4% to 7% of males have used cocaine in the last year in Spain, Denmark, Ireland, Italy, and the United Kingdom. The ratio of male to female users is approximately 3.8:1, but this statistic varies from 1:1 to 13:1 depending on country.

See also

References

1. Aggrawal, Anil. Narcotic Drugs. National Book Trust, India (1995), p. 52-3. ISBN 81-237-1383-5.
2. Barlow, William. "Looking Up At Down": The Emergence of Blues Culture. Temple University Press (1989), p. 207. ISBN 0-87722-583-4.
3. Apple Sanity - Fetish - Blow: War on Drugs VS. Cocaine
4. Cocaine Market
5. Pharmacokinetics and Pharmacodynamics of Methylecgonidine, a Crack Cocaine Pyrolyzate - Scheidweiler et al. 307 (3): 1179 Figure IG6 - Journal of Pharmacology And Experimental...
6. "Substances - Cocaine" The Steinhardt School of Culture, Education, and Human Developmentaccessed August 2009
7. George, Nelson. "Hip Hop America". 1998. Viking Penguin.(Page 40)
8. G. Barnett, R. Hawks and R. Resnick, "Cocaine Pharmacokinetics in Humans," 3 Journal of Ethnopharmacology 353 (1981); Jones, supra note 19; Wilkinson et al., Van Dyke et al.
9. cesar.umd.edu - Cocaine terminology
10. www.erowid.org - Cocaine, Bits & Pieces
11. " White powder cocaine no longer just for yuppies." CNN.
12. Urban Dictionary: Bell ringer
13. Appendix B: Production of Cocaine Hydrochloride and Cocaine Base, US Justice Dep.
14. Rothman, et al. "Amphetamine-Type Central Nervous System Stimulants Release Norepinepehrine more Potently than they Release Dopamine and Serotonin." (2001): Synapse 39, 32-41 (Table V. on page 37)
15. The binding sites for cocaine and dopamine in the dopamine transporter overlap. Nature Neuroscience 11, 780 - 789 (2008) Published online: 22 June 2008
16. Sigma Receptors Play Role In Cocaine-induced Suppression Of Immune System
17. Drugbank website "drug card", "(DB00907)" for Cocaine: Giving ten targets of the molecule in vivo, including dopamine/serotonin sodium channel affinity & K-opioid affinity
18. World Health Organization (2004). Neuroscience of psychoactive substance use and dependence
19. World Health Organization (2007). International medical guide for ships
20. - re. International study on cocaine executed by the World Health Organization.
21. Biological Psychiatry By H. A. H. D'haenen, Johan A. den Boer, Paul Willner
22. https://www.cia.gov/library/publications/the-world-factbook/geos/co.html.
23. Field Listing - Illicit drugs (by country)
24. Jacobson, Robert. "Illegal Drugs: America's Anguish". Farmington Hills, MI: Thomson Gale, 2006
25. "Pricing powder", The Economist, June 28, 2007, Prices: USA around $110/g, Israel/ Germany/ Britain around $46/g, Colombia $2/g, New Zealand recordbreaking $714.30/g.
26. , p243.
27. , p58-62.

External links

• Cocaine in Egyptian Mummies
• EMCDDA drugs profile: Cocaine(2007)
• Erowid -> Cocaine Information — A collection of data about cocaine including dose, effects, chemistry, legal status, images and more.
• Slang Dictionary for Cocaine.
• Cocaine content of plants
• Cocaine - The History and the Risks at h2g2
• Cocaine Frequently Asked Questions
• Cocaine users are destroying the rainforest - at 4 square metres a gram|World news|The Guardian

Estimated Andean region coca cultivation and potential pure cocaine production, 2000–2004.

		2001	2002	2003	2004
Net cultivation (km2)	1875	2218	2007.5	1663	1662
Potential pure cocaine production (tonnes)	770	925	830	680	645