Cocaine

For other uses, see Cocaine (disambiguation).

Cocaine

Systematic (IUPAC) name

methyl (1R,2R,3S,5S)-3- (benzoyloxy)-8-methyl-8-azabicyclo[3.2.1] octane-2-carboxylate

Identifiers

CAS number
50-36-2

ATC code
N01BC01 R02AD03,S01HA01, S02DA02

PubChem
CID 5760

DrugBank
DB00907

ChemSpider
10194104

Chemical data

Formula
C17H21NO4

Mol. mass
303.353 g/mol

SMILES
eMolecules & PubChem

Synonyms
methylbenzoylecgonine, benzoylmethylecgonine

Physical data

Melt. point
98 °C (208 °F)

Solubility in water
1800 mg/mL (20 °C)

Pharmacokinetic data

Bioavailability
Oral: 33%[1]
Insufflated: 60[2]–80%[3]
Nasal Spray: 25[4]–43%[1]

Metabolism
Hepatic CYP3A4

Half-life
1 hour

Excretion
Renal (benzoylecgonine and ecgonine methyl ester)

Therapeutic considerations

Pregnancy cat.
C

Legal status
Controlled (S8) (AU)Schedule I (CA) ? (UK)Schedule II (US)

Dependence Liability
High

Routes
Topical, Oral,Insufflation, IV, PO

Yes(what is this?) (verify)

Cocaine (benzoylmethylecgonine) is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant.[5] 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[clarification needed] as anexogenous catecholamine transporter ligand. Because of the way it affects the mesolimbic reward pathway, cocaine is addictive.[6]

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

Coca leaf in Bolivia

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.[7] There is also evidence that these cultures used a mixture of coca leaves and saliva as an anesthetic for the performance oftrepanation.[8]

When the Spanish arrived in South America, most 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.[9] In 1569, Nicolás Monardes described the practice of the natives of chewing a mixture of tobacco and coca leaves to induce "great contentment":


[…when they wished to] make themselves drunk and […] out of judgment [they chewed a mixture of tobacco and coca leaves which …] make them go as they were out of their wittes […][10]

In 1609, Padre Blas Valera wrote:


Coca protects the body from many ailments, and our doctors use it in powdered form to reduce the swelling of wounds, to strengthen broken bones, to expel cold from the body or prevent it from entering, and to cure rotten wounds or sores that are full of maggots. And if it does so much for outward ailments, will not its singular virtue have even greater effect in the entrails of those who eat it?

Isolation and naming

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 in the plant was damaged 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.[11]

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.[12]

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 theBritish 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” from "coca" (from Quechua "cuca") + suffix "ine".[12][13] Because of its use as a local anesthetic, a suffix "-caine" was later extracted and used to form names of synthetic local anesthetics.

The first synthesis and elucidation of the structure of the cocaine molecule was by Richard Willstätter in 1898.[14] 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.[15]

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,[16] and James Corning demonstrated peridural anesthesia.[17] 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.”

Pope Leo XIII purportedly carried a hipflask of the coca-treated Vin Mariani [citation needed] with him, and awarded a Vatican gold medal to Angelo Mariani.

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.[citation needed]

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 Freudpublished his work Über Coca, in which he wrote that cocaine causes

exhilaration and lasting euphoria, which in no way differs from the normal euphoria of the healthy person…You perceive an increase of self-control and possess more vitality and capacity for work….In other words, you are simply normal, and it is soon hard to believe you are under the influence of any drug….Long intensive physical work is performed without any fatigue…This result is enjoyed without any of the unpleasant after-effects that follow exhilaration brought about by alcohol….Absolutely no craving for the further use of cocaine appears after the first, or even after repeated taking of the drug…

Cocaine was marketed as a fast-acting anesthetic.

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 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.[18]

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.[19]

During the mid 1940’s amidst WWII cocaine was considered for inclusion as an ingredient of a future generation of ‘pep pills’ for the German military code named D-IX.[20]

Prohibition

Question book-new.svg

This section needs additional citations for verification.
Please help improve this article by adding reliable references. Unsourced material may be challenged and removed. (April 2009)

By the turn of the twentieth century, the addictive properties of cocaine had become clear, and perceived problems with cocaine use began to capture public attention in the United States. The dangers of cocaine use 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, theHarrison 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.[21][22] 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 by an American representative in the World Health Assembly banned the publication of the study, because it seemed to make a case for the positive uses of cocaine. An excerpt of the report strongly conflicted with accepted paradigms, for example "that occasional cocaine use does not typically lead to severe or even minor physical or social problems." [23] 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 "stepping 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.[citation needed] 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.[original research?] 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.[24]

Biosynthesis

Main article: Biosynthesis of cocaine

The first synthesis and elucidation of the cocaine molecule was by Richard Willstätter in 1898.[25] 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

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.[26]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,[27] 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

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.[28] 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.[29] 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.[30] This is due to the extra chiral center at C-2.[31] 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. Thebenzoyl moiety required for the formation of the cocaine diester is synthesized from phenylalanine via cinnamic acid.[32] Benzoyl-CoA then combines the two units to form cocaine.

Robert Robinson’s acetonedicarboxylate

Robinson biosynthesis of tropane

The biosynthesis of the tropane alkaloid, however, is still uncertain. Hemscheidt proposes that Robinson’s acetonedicarboxylate emerges as a potential intermediate for this reaction.[33] Condensation of N-methylpyrrolinium and acetonedicarboxylate would generate the oxobutyrate. Decarboxylation leads to tropane alkaloid formation.

Reduction of tropinone

Reduction of tropinone

The reduction of tropinone is mediated by NADPH-dependent reductase enzymes, which have been characterized in multiple plant species.[34] 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.[35]

Pharmacology

Appearance

A pile of cocaine hydrochloride

A piece of compressed cocaine powder

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 orbenzocaine, which mimic or add to cocaine’s numbing effect on mucous membranes. Cocaine may also be "cut" with other stimulants such as methamphetamine.[36] 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

Main article: Freebase (chemistry)

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[37] because of methylecgonidine’s effects on lung tissue[38] and liver tissue.[39]

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

Main article: Crack cocaine

A woman smoking 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.[40] The origin of the name is from the crackling sound (hence the onomatopoeic “crack”) produced when cocaine containing impurities are heated.[41]

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.[42] 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

A spoon containing baking soda, cocaine, and a small amount of water. Used in a "poor-man’s" crack-cocaine production

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, maximumphysiological 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.[43]

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.”[44] 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 inHawaii, 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[45] 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.[46] As tolerance builds rapidly in the short-term (hours), many lines are often snorted to produce greater effects.

A study by Bonkovsky and Mehta[47] reported that, just like shared needles, the sharing of straws used to "snort" cocaine can spread blood diseases such as Hepatitis C.[48]

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 American; more Hispanics than non-Hispanic White and non-Hispanic Black people received sentences for crimes related to powder cocaine.[49]

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".[50] In a study[45] 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 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.[51]

Inhalation

See also: Crack cocaine

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.[52] 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.[45]

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.[53] 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 cannabis.

The language referring to paraphernalia and practices of smoking cocaine vary, as do the packaging methods in the street level sale.

Physical mechanisms

Cocaine binds directly to the DAT1 transporter, inhibiting reuptake with more efficacy than amphetamines which phosphorylate it causing internalization; instead primarily releasing DAT (which cocaine does not do) and only inhibiting its reuptake as a secondary, and much more minor, mode of action than cocaine and in another manner: from the opposite conformation/orientation to DAT.

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[54]) The most extensively studied effect of cocaine on the central nervous system is the blockade of the dopamine transporter protein. Dopaminetransmitter 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 thepresynaptic 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.[55] 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.[56] 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.[57]

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.[58]

Sigma receptors are effected by cocaine, as cocaine functions as a sigma ligand agonist.[59] Further specific receptors it has been demonstrated to function on are NMDA and the D1 dopamine receptor.[60]

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.[61] 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[62] and clock genes[63] 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.[64]

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 majormetabolite, 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.[65] 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.[66][67][68]

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.[69][70]

Detection in biological fluids

Cocaine and its major metabolites may be quantitated in blood, plasma or urine to monitor for abuse, confirm a diagnosis of poisoning or assist in the forensic investigation of a traffic or other criminal violation or a sudden death. Most commercial cocaine immunoassay screening tests cross-react appreciably with the major cocaine metabolites, but chromatographic techniques can easily distinguish and separately measure each of these substances. When interpreting the results of a test, it is important to consider the cocaine usage history of the individual, since a chronic user can develop tolerance to doses that would incapacitate a cocaine-naive individual, and the chronic user often has high baseline values of the metabolites in his system. Cautious interpretation of testing results may allow a distinction between passive or active usage, and between smoking versus other routes of administration.[71]

Effects and health issues

Cocaine is a powerful nervous system stimulant.[72] Its effects can last from 15–30 minutes to an hour, depending upon the method of ingestion.[73]

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.[72]

Health problems from the use of legal substances, particularly alcohol and tobacco, are greater than health problems from cocaine use. Occasional cocaine use does not typically lead to severe or even minor physical or social problems.[74][75]

Acute

Data from The Lancet suggests Cocaine as the 2nd most dependent and 2nd most harmful of 20 drugs.[76] Some experts however rate nicotine dependency higher than cocaine.[77]

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.[citation needed]

Chronic

Main effects of chronic cocaine use.

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.[78] 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.[citation needed]

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.[citation needed]

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 causestooth decay. However, cocaine does often cause involuntary tooth grinding, known as bruxism, which can deteriorate tooth enamel and lead to gingivitis.[79]

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.[80]

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 syndromeand other diseases.[81][82][83][84] It can also cause a wide array of kidney diseases and renal failure.[85][86]

Cocaine abuse doubles both the risks of hemorrhagic and ischemic strokes,[87] as well as increases the risk of other infarctions, such as myocardial infarction.[88]

Addiction

Main article: Cocaine dependence

Cocaine dependence (or addiction) is 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 hydrochloride for medical use.

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.[89]

Current prohibition

Main article: Legal status of cocaine

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.[90]

Illicit trade

Bricks of cocaine, a form in which it is commonly transported.

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.[citation needed]

Production

Colombia is the world’s leading producer of cocaine.[91] 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.

Estimated Andean region coca cultivation and potential pure cocaine production, 2000–2004.[92]

2000
2001
2002
2003
2004

Net cultivation (km2)
1875
2218
2007.5
1663
1662

Potential pure cocaine production (tonnes)
770
925
830
680
645

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

Cocaine smuggled in a charango, 2008.

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, the United States being the worlds largest consumer of Cocaine,[93] 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, southernFlorida, 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.[94]

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 through Chile, this route is primarily used for cocaine produced in Bolivia since the nearest seaports lie in northern Chile. The arid Bolivia-Chile border is easily crossed by 4×4 vehicles that then head to the seaports ofIquique and Antofagasta. While the price of cocaine is higher in Chile than in Peru and Bolivia, the final destination is usually Europe, especially Spain where drug dealing networks exist 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 CaribbeanGulf 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 subs 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.[95]

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, more powerful 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.[96]

The European Monitoring Centre for Drugs and Drug Addiction reports 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.[97]

Bags of cocaine, adulterated with fruit flavoring.

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%.[98]

Cocaine adulterants

Question book-new.svg

This section needs additional citations for verification.
Please help improve this article by adding reliable references. Unsourced material may be challenged and removed. (June 2009)

Cocaine is "cut" with many substances such as:

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).[99] 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%).[99]

In the United States
General usage

Cocaine is the second most popular illegal recreational drug in the U.S. (behind marijuana)[100] and the U.S. is the world’s largest consumer of cocaine.[93] 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. In 2001, more Hispanics received sentences for crimes relating to powder cocaine than any other ethnicity while more African Americans were convicted of crimes relating to crack cocaine in the United States.[101]

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, its use was significantly less prevalent than 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.[102]

See also

Rod of asclepius.png
Medicine portal

References

  1. ^ a b Fattinger K, Benowitz NL, Jones RT, Verotta D (2000). "Nasal mucosal versus gastrointestinal absorption of nasally administered cocaine". Eur. J. Clin. Pharmacol. 56 (4): 305–10. doi:10.1007/s002280000147. PMID 10954344.
  2. ^ Barnett G, Hawks R, Resnick R (1981). "Cocaine pharmacokinetics in humans". J Ethnopharmacol 3 (2-3): 353–66. doi:10.1016/0378-8741(81)90063-5. PMID 7242115.
  3. ^ Jeffcoat AR, Perez-Reyes M, Hill JM, Sadler BM, Cook CE (1989). "Cocaine disposition in humans after intravenous injection, nasal insufflation (snorting), or smoking". Drug Metab. Dispos. 17 (2): 153–9. PMID 2565204.
  4. ^ Wilkinson P, Van Dyke C, Jatlow P, Barash P, Byck R (1980). "Intranasal and oral cocaine kinetics". Clin. Pharmacol. Ther. 27 (3): 386–94. PMID 7357795.
  5. ^ Aggrawal, Anil. Narcotic Drugs. National Book Trust, India (1995), p. 52-3. ISBN 81-237-1383-5.
  6. ^ Fattore L, Piras G, Corda MG, Giorgi O (2009). "The Roman high- and low-avoidance rat lines differ in the acquisition, maintenance, extinction, and reinstatement of intravenous cocaine self-administration". Neuropsychopharmacology 34 (5): 1091–101.doi:10.1038/npp.2008.43. PMID 18418365.
  7. ^ Altman AJ, Albert DM, Fournier GA (1985). "Cocaine’s use in ophthalmology: our 100-year heritage". Surv Ophthalmol 29 (4): 300–6. doi:10.1016/0039-6257(85)90153-5. PMID 3885453.
  8. ^ Gay GR, Inaba DS, Sheppard CW, Newmeyer JA (1975). "Cocaine: history, epidemiology, human pharmacology, and treatment. a perspective on a new debut for an old girl". Clin. Toxicol. 8 (2): 149–78. doi:10.1080/088506099304990. PMID 1097168.
  9. ^ "Drug that spans the ages: The history of cocaine". London: The Independent (UK). 2006. Retrieved 2010-04-30.
  10. ^ Monardes, Nicholas; Translated into English by J. Frampton (1925). Joyfull Newes out of the Newe Founde Worlde. New York, NY: Alfred Knopf.
  11. ^ F. Gaedcke (1855). "Ueber das Erythroxylin, dargestellt aus den Blättern des in Südamerika cultivirten Strauches Erythroxylon Coca". Archiv der Pharmazie 132 (2): 141–150. doi:10.1002/ardp.18551320208.
  12. ^ a b Albert Niemann (1860). "Ueber eine neue organische Base in den Cocablättern". Archiv der Pharmazie 153 (2): 129–256. doi:10.1002/ardp.18601530202.
  13. ^ Harper, Douglas. "Cocaine". Online Etymology Dictionary.
  14. ^ Humphrey AJ, O’Hagan D (2001). "Tropane alkaloid biosynthesis. A century old problem unresolved". Nat Prod Rep 18 (5): 494–502. doi:10.1039/b001713m. PMID 11699882.
  15. ^ Yentis SM, Vlassakov KV (1999). "Vassily von Anrep, forgotten pioneer of regional anesthesia". Anesthesiology 90 (3): 890–5. doi:10.1097/00000542-199903000-00033. PMID 10078692.
  16. ^ Halsted W (1885). "Practical comments on the use and abuse of cocaine". New York Medical Journal 42: 294–295.
  17. ^ Corning JL (1885). "An experimental study". New York Medical Journal 42: 483.
  18. ^ Barlow, William. "Looking Up At Down": The Emergence of Blues Culture. Temple University Press (1989), p. 207. ISBN 0-87722-583-4.
  19. ^ Streatfeild, Dominic (2003). Cocaine: An Unauthorized Biography. Picador. ISBN 0312422261.
  20. ^ Jeevan Vasagar: cocaine-based "wonder drug" tested on concentration camp inmates
  21. ^ Apple Sanity – Fetish – Blow: War on Drugs VS. Cocaine[dead link]
  22. ^ "Cocaine Market". Havocscope.com. Retrieved 2010-03-09.
  23. ^ WHO/UNICRI (1995). "WHO Cocaine Project".
  24. ^ EMCDDA (2007). "EMCDDA Retail Cocaine Purity Study".
  25. ^ Humphrey AJ, O’Hagan D (2001). "Tropane alkaloid biosynthesis. A century old problem unresolved". Nat Prod Rep 18 (5): 494–502. doi:10.1039/b001713m. PMID 11699882.
  26. ^ Leete E, Marion L, Sspenser ID (1954). "Biogenesis of hyoscyamine". Nature 174 (4431): 650–1. doi:10.1038/174650a0. PMID 13203600.
  27. ^ Robins RJ, Waltons NJ, Hamill JD, Parr AJ, Rhodes MJ (1991). "Strategies for the genetic manipulation of alkaloid-producing pathways in plants". Planta Med. 57 (7 Suppl): S27–35. doi:10.1055/s-2006-960226. PMID 17226220.
  28. ^ Dewick, P. M. (2009). Medicinal Natural Products. Chicester: Wiley-Blackwell. ISBN 978-0-4707-4276-1.
  29. ^ R. J. Robins, T. W. Abraham, A. J. Parr, J. Eagles and N. J. Walton (1997). "The Biosynthesis of Tropane Alkaloids in Datura stramonium: The Identity of the Intermediates between N-Methylpyrrolinium Salt and Tropinone". J. Am. Chem. Soc. 119: 10929.doi:10.1021/ja964461p.
  30. ^ Hoye TR, Bjorklund JA, Koltun DO, Renner MK (2000). "N-methylputrescine oxidation during cocaine biosynthesis: study of prochiral methylene hydrogen discrimination using the remote isotope method". Org. Lett. 2 (1): 3–5. doi:10.1021/ol990940s.PMID 10814231.
  31. ^ E. Leete, J. A. Bjorklund, M. M. Couladis and S. H. Kim (1991). "Late intermediates in the biosynthesis of cocaine: 4-(1-methyl-2-pyrrolidinyl)-3-oxobutanoate and methyl ecgonine". J. Am. Chem. Soc. 113: 9286. doi:10.1021/ja00024a039.
  32. ^ E. Leete, J. A. Bjorklund and S. H. Kim (1988). "The biosynthesis of the benzoyl moiety of cocaine". Phytochemistry 27: 2553. doi:10.1016/0031-9422(88)87026-2.
  33. ^ T. Hemscheidt; Vederas, John C. (2000). "Tropane and Related Alkaloids". Top. Curr. Chem. 209: 175. doi:10.1007/3-540-48146-X.
  34. ^ A. Portsteffen, B. Draeger and A. Nahrstedt (1992). "Two tropinone reducing enzymes from Datura stramonium transformed root cultures". Phytochemistry 31: 1135. doi:10.1016/0031-9422(92)80247-C.
  35. ^ Boswell HD, Dräger B, McLauchlan WR (1999). "Specificities of the enzymes of N-alkyltropane biosynthesis in Brugmansia and Datura". Phytochemistry 52 (5): 871–8. doi:10.1016/S0031-9422(99)00293-9. PMID 10626376.
  36. ^ "Psychedelic Chemistry: Cocaine". Retrieved 2007-07-10.
  37. ^ "Pharmacokinetics and Pharmacodynamics of Methylecgonidine, a Crack Cocaine Pyrolyzate – Scheidweiler et al. 307 (3): 1179 Figure IG6 – Journal of Pharmacology And Experimental". Jpet.aspetjournals.org. 2003-10-15. doi:10.1124/jpet.103.055434. Retrieved 2010-03-09.
  38. ^ Yang Y, Ke Q, Cai J, Xiao YF, Morgan JP (2001). "Evidence for cocaine and methylecgonidine stimulation of M(2) muscarinic receptors in cultured human embryonic lung cells". Br. J. Pharmacol. 132 (2): 451–60. doi:10.1038/sj.bjp.0703819.PMID 11159694.
  39. ^ Fandiño AS, Toennes SW, Kauert GF (2002). "Studies on hydrolytic and oxidative metabolic pathways of anhydroecgonine methyl ester (methylecgonidine) using microsomal preparations from rat organs". Chem. Res. Toxicol. 15 (12): 1543–8.doi:10.1021/tx0255828. PMID 12482236.
  40. ^ "Substances – Cocaine" The Steinhardt School of Culture, Education, and Human Development. Retrieved August 2009.
  41. ^ George, Nelson. "Hip Hop America". 1998. Viking Penguin.(Page 40)
  42. ^ Teobaldo, Llosa (1994). "The Standard Low Dose of Oral Cocaine: Used for Treatment of Cocaine Dependence". Substance Abuse 15 (4): 215–220.
  43. ^ 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.
  44. ^ Siegel RK, Elsohly MA, Plowman T, Rury PM, Jones RT (January 3, 1986). "Cocaine in herbal tea". Journal of the American Medical Association 255 (1): 40. doi:10.1001/jama.255.1.40. PMID 3940302.
  45. ^ a b c Nora D. Volkow; Wang, GJ; Fischman, MW; Foltin, R; Fowler, JS; Franceschi, D; Franceschi, M; Logan, J et al. (2000). "Effects of route of administration on cocaine induced dopamine transporter blockade in the human brain". Life Sciences 67 (12): 1507–1515. doi:10.1016/S0024-3205(00)00731-1. PMID 10983846.
  46. ^ cesar.umd.edu – Cocaine terminology
  47. ^ Bonkovsky HL, Mehta S (2001). "Hepatitis C: a review and update". J. Am. Acad. Dermatol. 44 (2): 159–82. doi:10.1067/mjd.2001.109311. PMID 11174373.
  48. ^ Erowid.org – Cocaine, Bits & Pieces
  49. ^ "White powder cocaine no longer just for yuppies." CNN.
  50. ^ "Bell ringer". Urban Dictionary. Retrieved 2010-03-09.
  51. ^ Dimitrijevic N, Dzitoyeva S, Manev H (2004). "An automated assay of the behavioral effects of cocaine injections in adult Drosophila". J Neurosci Methods 137 (2): 181–184. doi:10.1016/j.jneumeth.2004.02.023. PMID 15262059.
  52. ^ Appendix B: Production of Cocaine Hydrochloride and Cocaine Base, US Justice Dep.
  53. ^ Margaret Reist (January 16, 2005). "A rose by another name: crack pipe". Lincoln Journal Star. Retrieved 2009-08-21.
  54. ^ 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)
  55. ^ Spanagel R, Weiss F (1999). "The dopamine hypothesis of reward: past and current status". Trends Neurosci. 22 (11): 521–7. doi:10.1016/S0166-2236(99)01447-2. PMID 10529820.
  56. ^ Carta M, Allan AM, Partridge LD, Valenzuela CF (2003). "Cocaine inhibits 5-HT3 receptor function in neurons from transgenic mice overexpressing the receptor". Eur. J. Pharmacol. 459 (2-3): 167–9. doi:10.1016/S0014-2999(02)02867-4. PMID 12524142.
  57. ^ Filip M, Bubar MJ, Cunningham KA (2004). "Contribution of serotonin (5-hydroxytryptamine; 5-HT) 5-HT2 receptor subtypes to the hyperlocomotor effects of cocaine: acute and chronic pharmacological analyses". J. Pharmacol. Exp. Ther. 310 (3): 1246–54.doi:10.1124/jpet.104.068841. PMID 15131246.
  58. ^ Nature Neuroscience; Kniazeff, J; Bergmann, ML; Shi, L; Gracia, L; Raniszewska, K; Newman, AH; Javitch, JA et al. (2008). "The binding sites for cocaine and dopamine in the dopamine transporter overlap". Nature Neuroscience 11 (7): 780.doi:10.1038/nn.2146. PMID 18568020. PMC 2692229.
  59. ^ "Sigma Receptors Play Role In Cocaine-induced Suppression Of Immune System". Sciencedaily.com. 2003-05-06. Retrieved 2010-03-09.
  60. ^ Lluch J, Rodríguez-Arias M, Aguilar MA, Miñarro J (2005). "Role of dopamine and glutamate receptors in cocaine-induced social effects in isolated and grouped male OF1 mice". Pharmacol. Biochem. Behav. 82 (3): 478–87. doi:10.1016/j.pbb.2005.10.003.PMID 16313950.
  61. ^ "Drugbank website "drug card", "(DB00907)" for Cocaine: Giving ten targets of the molecule in vivo, including dopamine/serotonin sodium channel affinity & K-opioid affinity". Drugbank.ca. Retrieved 2010-03-09.
  62. ^ Uz T, Akhisaroglu M, Ahmed R, Manev H (2003). "The pineal gland is critical for circadian Period1 expression in the striatum and for circadian cocaine sensitization in mice". Neuropsychopharmacology 28 (12): 2117–23. doi:10.1038/sj.npp.1300254.PMID 12865893.
  63. ^ McClung C, Sidiropoulou K, Vitaterna M, Takahashi J, White F, Cooper D, Nestler E (2005). "Regulation of dopaminergic transmission and cocaine reward by the Clock gene". Proc Natl Acad Sci USA 102 (26): 9377–81. doi:10.1073/pnas.0503584102.PMID 15967985.
  64. ^ Carey RJ, Damianopoulos EN, Shanahan AB (2008). "Cocaine effects on behavioral responding to a novel object placed in a familiar environment". Pharmacol. Biochem. Behav. 88 (3): 265–71. doi:10.1016/j.pbb.2007.08.010. PMID 17897705.
  65. ^ Kolbrich EA, Barnes AJ, Gorelick DA, Boyd SJ, Cone EJ, Huestis MA (2006). "Major and minor metabolites of cocaine in human plasma following controlled subcutaneous cocaine administration". J Anal Toxicol 30 (8): 501–10. PMID 17132243.
  66. ^ Wilson LD, Jeromin J, Garvey L, Dorbandt A (2001). "Cocaine, ethanol, and cocaethylene cardiotoxity in an animal model of cocaine and ethanol abuse". Acad Emerg Med 8 (3): 211–22. doi:10.1111/j.1553-2712.2001.tb01296.x. PMID 11229942.
  67. ^ Pan WJ, Hedaya MA (1999). "Cocaine and alcohol interactions in the rat: effect of cocaine and alcohol pretreatments on cocaine pharmacokinetics and pharmacodynamics". J Pharm Sci 88 (12): 1266–74. doi:10.1021/js990184j. PMID 10585221.
  68. ^ Hayase T, Yamamoto Y, Yamamoto K (1999). "Role of cocaethylene in toxic symptoms due to repeated subcutaneous cocaine administration modified by oral doses of ethanol". J Toxicol Sci 24 (3): 227–35. PMID 10478337.
  69. ^ Barley, Shanta (13 November 2009). "Cocaine and pepper spray – a lethal mix?". New Scientist. Retrieved 2009-11-14.
  70. ^ Mendelson, John E. (October 2, 2009). "Capsaicin, an active ingredient in pepper sprays, increases the lethality of cocaine". Forensic Toxicology. ISSN 1860-8973.
  71. ^ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 349-355.
  72. ^ a b World Health Organization (2004). Neuroscience of psychoactive substance use and dependence
  73. ^ World Health Organization (2007). International medical guide for ships
  74. ^ Goldacre, Ben (June 2008). "Cocaine study that got up the nose of the US". Bad Science (London: The Guardian). – re. International study on cocaine executed by the World Health Organization.
  75. ^ Cohen, Peter; Sas, Arjan (1994). Cocaine use in Amsterdam in non deviant subcultures. Addiction Research, Vol. 2, No. 1, pp. 71-94.
  76. ^ Nutt, D.; King, L. A.; Saulsbury, W.; Blakemore, C. (2007). "Development of a rational scale to assess the harm of drugs of potential misuse". The Lancet 369: 1047. doi:10.1016/S0140-6736(07)60464-4. PMID 17382831. edit
  77. ^ Hilts, Philip J. (1994). Relative Addictiveness of Drugs. New York Times.
  78. ^ Biological Psychiatry By H. A. H. D’haenen, Johan A. den Boer, Paul Willner. Books.google.com. Retrieved 2010-03-09.
  79. ^ Baigent, Michael (2003). "Physical complications of substance abuse: what the psychiatrist needs to know". Curr Opin Psychiatry 16 (3): 291–296. doi:10.1097/00001504-200305000-00004.
  80. ^ Pagliaro, Louis; Ann Marie Pagliaro (2004). Pagliaros’ Comprehensive Guide to Drugs and Substances of Abuse. Washington, D.C.: American Pharmacists Association. ISBN 1582120668.
  81. ^ "scienceblog.com". Retrieved 2007-07-10.
  82. ^ Trozak D, Gould W (1984). "Cocaine abuse and connective tissue disease". J Am Acad Dermatol 10 (3): 525. doi:10.1016/S0190-9622(84)80112-7. PMID 6725666.
  83. ^ Ramón Peces; Navascués, RA; Baltar, J; Seco, M; Alvarez, J (1999). "Antiglomerular Basement Membrane Antibody-Mediated Glomerulonephritis after Intranasal Cocaine Use". Nephron 81 (4): 434–438. doi:10.1159/000045328. PMID 10095180.
  84. ^ Moore PM, Richardson B (1998). "Neurology of the vasculitides and connective tissue diseases". J. Neurol. Neurosurg. Psychiatr. 65 (1): 10–22. doi:10.1136/jnnp.65.1.10. PMID 9667555. PMC 2170162.
  85. ^ Jared A. Jaffe; Kimmel, PL (2006). "Chronic Nephropathies of Cocaine and Heroin Abuse: A Critical Review". Clinical Journal of the American Society of Nephrology (American Society of Nephrology) 1 (4): 655. doi:10.2215/CJN.00300106. PMID 17699270.
  86. ^ Fokko J. van der Woude (2000). "Cocaine use and kidney damage". Nephrology Dialysis Transplantation (Oxford University Press) 15 (3): 299–301. doi:10.1093/ndt/15.3.299. PMID 10692510.
  87. ^ "MedlinePlus: Stroke a risk for cocaine, amphetamine abusers". Retrieved 2007-07-10.[dead link]
  88. ^ Vasica G, Tennant CC (2002). "Cocaine use and cardiovascular complications". Med. J. Aust. 177 (5): 260–2. PMID 12197823.
  89. ^ Sawada, H.; Yamakawa, K; Yamakado, H; Hosokawa, R; Ohba, M; Miyamoto, K; Kawamura, T; Shimohama, S (2005-02-23). "Cocaine and Phenylephrine Eye Drop Test for Parkinson Disease". JAMA the Journal of the American Medical Association (Journal of the American Medical Association) 293 (8): 932. doi:10.1001/jama.293.8.932-c. PMID 15728162.
  90. ^ "Cocaine: Seizures, 1998–2003" (PDF). World Drug Report 2006. 2. New York: United Nations. 2006.
  91. ^ CIA.gov
  92. ^ NDIC (2006). National Drug Threat Assessment 2006.
  93. ^ a b Field Listing – Illicit drugs (by country)
  94. ^ Jacobson, Robert. "Illegal Drugs: America’s Anguish". Farmington Hills, MI: Thomson Gale, 2006
  95. ^ "Coast Guard hunts drug-running semi-subs". CNN. 2008-03-20. Retrieved 2008-03-20.
  96. ^ "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.
  97. ^ European Monitoring Centre for Drugs and Drug Addiction (2008). Annual report: the state of the drugs problem in Europe. Luxembourg: Office for Official Publications of the European Communities. p. 59. ISBN 978-92-9168-324-6.
  98. ^ (PDF) The Cocaine Threat: A Hemispheric Perspective. United States Department of Defense.
  99. ^ a b (PDF) World Drug Report 2007. New York: United Nations. 2007., p243.
  100. ^ "erowid.org". Retrieved 2007-07-10.
  101. ^ RJHresearch.com
  102. ^ (PDF) The State of the Drugs Problem in Europe 2008. Luxembourg: European Monitoring Centre for Drugs and Drug Addiction. 2008., p58-62.

External links

Recreational drug use

Anesthetics: Local anesthetics – primarily sodium channel blockers (N01B)

Esters

Esters of aminobenzoic acid

AmylocaineBenzocaineButacaineButambenChloroprocaineDimethocaineMeprylcaineMetabutoxycaineOrthocainePropoxycaineProcaine (Novocaine) • ProxymetacaineRisocaineTetracaine

Esters of benzoic acid

3-(p-Fluorobenzoyloxy)tropaneCocaineCyclomethycaineHexylcainePiperocaine

Amides

ArticaineBupivacaine # /Levobupivacaine/RopivacaineCarticaineCinchocaineEtidocaineLidocaine #  • MepivacainePrilocaineTrimecaine

Combinations

IontocaineLidocaine/prilocaine

#WHO-EM. Withdrawn from market. CLINICAL TRIALS: Phase III. §Never to phase III

M: PNS

anat(h, r, t, c, b, l, s)/phys/devp

noco/auto/cong/tumr, sysi/epon, injr

proc, drug(N1B)

 

Crack cocaine

A pile of crack cocaine ‘rocks’.

Crack cocaine is the freebase form of cocaine that can be smoked. It may also be termed rock or just crack. [1][2][3]

Appearance and characteristics

In purer forms, crack rocks appear as off-white nuggets with jagged edges,[2] with a slightly higher density than candle wax. Purer forms of crack resemble a hard brittle plastic, in crystalline form[2] (snaps when broken). A crack rock acts as a local anesthetic (see: Cocaine), numbing the tongue or mouth only where directly placed. When smoked, crack can leave the tongue numb where the smoke enters the mouth.[citation needed] Purer forms of crack will sink in water or melt at the edges when near a flame (crack vaporizes at 90 °C, 194 °F).[1]

Crack cocaine as sold on the streets may be adulterated or "buffed" to increase bulk. According to Cpl. Kent Dahl, with Red Deer RCMP Federal Drugs, Canada, white substances mimicking the appearance of cocaine are added to increase bulk. Use of toxic adulterants such as levamisole[4] has been documented.[3]

Chemistry

Possible reagents and equipment needed to convert cocaine into crack

This section may contain original research. Please improve it by verifying the claims made and adding references. Statements consisting only of original research may be removed. More details may be available on the talk page. (August 2009)

Crack cocaine, often nicknamed "crack" after the sound made during its manufacture, appeared primarily in impoverished inner-city neighborhoods in New York, Los Angeles, and Miami in late 1984 and 1985.[5]Because of the dangers for manufacturers of using ether to produce pure freebase cocaine, producers began to omit the step of removing the freebase precipitate from the ammonia mixture. Typically, filtration processes are also omitted. The end result is that the cut, in addition to the ammonium salt (NH4Cl), remains in the freebase cocaine after the mixture has evaporated. The "rock" that is thus formed also contains a small amount of water. [original research?]

Crack being made in a spoon

Baking soda is a base used in preparation of crack, although other weak bases may substitute for it. The net reaction when using sodium bicarbonate (NaHCO3, common baking soda) is

Coc-H+Cl + NaHCO3 → Coc + H2O + CO2 + NaCl

[citation needed]

Crack cocaine is usually purchased already in rock form,[2] although it is not uncommon for some users to "wash up" or "cook" the cocaine into crack themselves. This process is done with baking soda (sodium bicarbonate), water, and a spoon. Once mixed and heated, the bicarbonate breaks down into carbon dioxide and sodium carbonate, which then reacts with the hydrochloride of the cocaine molecule, leaving cocaine as an oily free base. Once separated from the hydrochloride, the cocaine alkaloid floats to the top of the now leftover liquid. It is at this point that the oil is picked up rapidly, usually with a pin or long thin object. This pulls the oil up and spins it, allowing air to set and dry the oil, and allows the user and/or maker to roll the oil into the rock-like shape.

Crack vaporizes near temperature 90 °C (194 °F),[1] much lower than the cocaine hydrochloride melting point of 190 °C (374 °F).[1] Whereas cocaine hydrochloride cannot be smoked (burns with no effect),[1] crack cocaine when smoked allows for quick absorption into the blood stream, and reaches the brain in 8 seconds.[1] Coupled with the fact that crack is considered more potent than cocaine hydrochloride, users obtain an intense high much more quickly than with the normal method of insufflating[citation needed] ("sniffing" or "snorting") the powdered cocaine.

Psychological effects

Crack cocaine is a substance that affects the brain chemistry of the user: causing euphoria,[6] supreme confidence,[7] loss of appetite,[6] insomnia,[6] alertness,[6] increased energy,[6] a craving for more cocaine,[7]and potential paranoia (ending after use).[6][8] Its initial effect is to release a large amount of dopamine,[2] a brain chemical inducing feelings of euphoria. The high usually lasts from 5–10 minutes,[2][6] after which time dopamine levels in the brain plummet, leaving the user feeling depressed and low.[2] When cocaine is dissolved and injected, the absorption into the bloodstream is at least as rapid as the absorption of the drug which occurs when crack cocaine is smoked,[6] and similar euphoria may be experienced.

A typical response among users is to have another hit of the drug; however, the levels of dopamine in the brain take a long time to replenish themselves, and each hit taken in rapid succession leads to increasingly less intense highs.[2] However, a person might binge for 3 or more days without sleep, while partying with hits from the pipe.[8]

Use of cocaine in a binge, during which the drug is taken repeatedly and at increasingly high doses, leads to a state of increasing irritability, restlessness, and paranoia.[6] This may result in a full-blown paranoid psychosis, in which the individual loses touch with reality and experiences auditory hallucinations.[6]

Stimulant drug abuse (particularly amphetamine and cocaine) can lead to delusional parasitosis (aka Ekbom’s Syndrome: a mistaken belief they are infested with parasites).[9] For example, excessive cocaine use can lead to formication, nicknamed "cocaine bugs" or "coke bugs," where the affected people believe they have, or feel, parasites crawling under their skin.[9] These delusions are also associated with high fevers or extreme alcohol withdrawal, often together with visual hallucinations about insects.[9]

People experiencing these hallucinations might scratch themselves to the extent of serious skin damage and bleeding, especially when they are delirious.[8][9]

Physiological effects

Main physiological effects of Crack cocaine.

The short-term physiological effects of cocaine include:[6] constricted blood vessels; dilated pupils; and increased temperature, heart rate, and blood pressure. Large amounts (several hundred milligrams or more) intensify the user’s high, but may also lead to bizarre, erratic, and violent behavior.[6] Large amounts can induce tremors, vertigo, muscle twitches, paranoia, or, with repeated doses, a toxic reaction closely resembling amphetamine poisoning.[6] Some users of cocaine report feelings of restlessness, irritability, and anxiety. In rare instances, sudden death can occur on the first use of cocaine or unexpectedly thereafter.[6] Cocaine-related deaths are often a result of cardiac arrest or seizures followed by respiratory arrest.

An appreciable tolerance to cocaine’s high may develop, with many addicts reporting that they seek but fail to achieve as much pleasure as they did from their first experience.[6] Some users will frequently increase their doses to intensify and prolong the euphoric effects. While tolerance to the high can occur, users might also become more sensitive (sensitization) to cocaine’s anesthetic and convulsant effects, without increasing the dose taken: this increased sensitivity may explain some deaths occurring after apparently low doses of cocaine.[6]

Addiction

Main article: Substance dependence

Crack cocaine is popularly thought to be the most addictive form of cocaine,[1] and one of the most addictive forms of any drug.[1] However, this claim has been contested: Morgan and Zimmer wrote that available data indicated that "…smoking cocaine by itself does not increase markedly the likelihood of dependence…. The claim that cocaine is much more addictive when smoked must be reexamined."[10]They argued that cocaine users who are already prone to abuse are most likely to "move toward a more efficient mode of ingestion" (that is, smoking).

The intense desire to recapture the initial high is what is so addictive for many users.[2] Purer forms of crack cocaine will produce the feeling of euphoria:[2] even after smoking diluted or fake crack for hours, one hit of real crack will produce euphoria. Hours of misery or tweaking can be reversed with one single hit of real crack. The memory of that type of high can cause addicts to buy large amounts of street crack, hoping for the real thing.[7]

On the other hand, Reinarman et al. wrote that the nature of crack addiction depends on the social context in which it is used and the psychological characteristics of users, pointing out that many heavy crack users go for days or weeks without using the drugs.[11]

Health issues

Smoking crack cocaine.

Because crack also refers to non-pure (or fake) versions of rock cocaine,[3] the health issues also include risks beyond smoking cocaine. However, crack usage is less dangerous than speedballing or "snowballing" (mixing cocaine with heroin), which can lead to more fatalities than either drug used on its own.

When large amounts of dopamine are released by crack consumption, it becomes easier for the brain to generate motivation for other activities. The activity also releases a large amount of adrenaline into the body, which tends to increase heart rate[12] and blood pressure, leading to long-term cardiovascular problems. It is suggested by research that smoking crack or freebase cocaine has additional health issues beyond other methods of taking cocaine. Many of these issues relate specifically to the release of methylecgonidine, and the specific effect of methylecgonidine on the heart,[12] lungs,[13] and liver.[14]

  • Toxic adulterants: As noted previously, virtually any substance may have been added in order to expand the volume of a batch, or appear to be pure crack. Occasionally, highly toxic substances are used, with an indefinite range of corresponding short and long-term health risks. For example, if candle wax or macadamia nuts are procured (as a form of fake crack) they will burn in a crack pipe producing a noxious smoke.
  • Smoking problems: The task of introducing the drug into the body further presents a series of health risks. Crack can not be snorted like regular cocaine, so smoking is the most common consumption method. Crack has a melting point of around 90 °C (194 °F),[1] and the smoke does not remain potent for long. Therefore, crack pipes are generally very short, to minimise the time between evaporating and losing strength. This often causes cracked and blistered lips, colloquially "crack lip", from having a very hot pipe pressed against the lips. The use of "convenience store crack pipes"[15] – glass tubes which originally contained small artificial roses – may also create this condition. These 4-inch (10-cm) pipes[15] are not durable and will quickly develop breaks; users will typically continue to use the pipe even though it has been broken to a shorter length. The hot pipe might burn the lips, tongue, or fingers, especially when shared with other people quickly taking another hit from the already hot short pipe.
  • Pure or large doses: Because the quality of crack can vary greatly, some people might smoke larger amounts of diluted crack, unaware that a similar hit of a new batch of purer crack could cause an overdose: triggering heart problems or rendering the user unconscious.
  • Pathogens on pipes: When pipes are shared, unless users rotate and push the pipe to the burnt, sterilized end, any bacteria or viruses from the previous user’s mouth can be transferred: tuberculosis can be spread by saliva. In terms of harm reduction, mouth pieces (lengths of tubing added to the end of the glass pipe) should be used and not shared.
  • Pathogens in needles/spoons: When crack is cooked down, as in a spoon with vinegar or lemon juice, for injecting with a syringe, diseases can be spread. Sexually transmitted infections such as HIV can be passed through a shared needle (or shared spoon if the needle is emptied into the spoon). From a harm reduction perspective, clean injection equipment should always be used and never shared. Ascorbic acid is safer for use than vinegar.

As a comparison, studies have shown that long-term insufflation (snorting) of cocaine in powder form can, after extensive use, destroy tissues in the nasal cavity,[16] and has been known to create deviated septa, potentially collapsing the nose.[16]

  • Addiction is widely considered a health issue. Many governments have made access to clean equipment and education regarding safer practices difficult, as the use of cocaine is illegal.
Effects in pregnancy and nursing

"Crack baby" is a term for a child born to a mother who used crack cocaine during her pregnancy. There remains some dispute as to whether cocaine use during pregnancy poses a threat to the fetus. One complicating factor is the smoking of cigarettes, because almost all crack users also smoke cigarettes.[17] The official opinion of the National Institute on Drug Abuse of the United States warns about health risks while cautioning against stereotyping:

Many recall that "crack babies," or babies born to mothers who used crack cocaine while pregnant, were at one time written off by many as a lost generation. They were predicted to suffer from severe, irreversible damage, including reduced intelligence and social skills. It was later found that this was a gross exaggeration. However, the fact that most of these children appear normal should not be overinterpreted as indicating that there is no cause for concern. Using sophisticated technologies, scientists are now finding that exposure to cocaine during fetal development may lead to subtle, yet significant, later deficits in some children, including deficits in some aspects of cognitive performance, information-processing, and attention to tasks—abilities that are important for success in school.[18]

Some people previously believed that crack cocaine caused infant death as SIDS, but when investigators began looking at the incidence of SIDS in the children of women who used crack cocaine, they found it to be no higher than in children of women who smoked cigarettes.[17]

There are also warnings about the threat of breastfeeding: "It is likely that cocaine will reach the baby through breast milk." The March of Dimes advises the following regarding cocaine use during pregnancy:

Cocaine use during pregnancy can affect a pregnant woman and her unborn baby in many ways. During the early months of pregnancy, it may increase the risk of miscarriage. Later in pregnancy, it can trigger preterm labor (labor that occurs before 37 weeks of pregnancy) or cause the baby to grow poorly. As a result, cocaine-exposed babies are more likely than unexposed babies to be born with low birthweight (less than 5.5 lb/2.5 kg). Low-birthweight babies are 20 times more likely to die in their first month of life than normal-weight babies, and face an increased risk of lifelong disabilities such as mental retardation and cerebral palsy. Cocaine-exposed babies also tend to have smaller heads, which generally reflect smaller brains. Some studies suggest that cocaine-exposed babies are at increased risk of birth defects, including urinary-tract defects and, possibly, heart defects. Cocaine also may cause an unborn baby to have a stroke, irreversible brain damage, or a heart attack.[19]

Legal status

Canada

As a Schedule I substance, crack is not differentiated from cocaine and other coca products in the Criminal Code of Canada. However, the court may weigh the socio-economic factors of crack usage in sentencing. As a guideline, Schedule I drugs carry a maximum 7 year prison sentence for possession for an indictable offense, up to life imprisonment for trafficking and production. For a summary conviction on possession; a $1000–$2000 fine and/or 6 months to a year imprisonment.

United States

Cocaine is listed as a Schedule I drug in the United Nations 1961 Single Convention on Narcotic Drugs, making it illegal for non-state-sanctioned production, manufacture, export, import, distribution, trade, use and possession.[20][21]

In the United States cocaine is a Schedule II drug under the Controlled Substances Act since it has high abuse potential but also carries a medicinal purpose.[22][23] Under the DEA listing of schedule I substances, crack is not considered separate from cocaine since they are essentially the same drug compound in different forms.

Law enforcement running drug stings to catch purchasers of crack cocaine often use macadamia nuts to simulate the drug.[24] When chopped, these nuts resemble crack cocaine in color.

There has been some controversy over the disproportionate sentences mandated by the Federal Sentencing Guidelines for crack cocaine (versus powder cocaine) since 1987. Whereas it is a 5-year minimum sentence for trafficking 500g of powdered cocaine, the same sentence can be imposed for mere possession of 5 grams of crack cocaine, a 100:1 ratio. There is no mandatory minimum sentence for mere possession of powder cocaine.[25] The United States Sentencing Commission has recommended that this disparity be rectified and existing sentences reduced.[26] Some claim that this disparity amounts to institutional racism, as crack cocaine is more common in inner-city black communities, and powder cocaine in white suburban communities.[27][28] The Supreme Court ruled in Kimbrough v. United States (2007) that the Guidelines for cocaine are advisory only, and that a judge may consider the disparity between the Guidelines’ treatment of crack and powder cocaine offenses when sentencing a defendant.

Europe

In the United Kingdom crack is a Class A drug. In the Netherlands it is a List 1 drug of the Opium Law.

See also

References

  1. ^ a b c d e f g h i Manual of Adolescent Substance Abuse Treatment, Todd Wilk Estroff, M.D., 2001 (306 pages), pp. 44-45, (describes cocaine/crack processing & melting points): p.44 has "cannot be smoked because…melting point of 190°C"; p.45 has "It is the most addictive form of cocaine", webpage: Google-Books-Estroff.
  2. ^ a b c d e f g h i j "Crack rocks offer a short but intense high to smokers" staff members, A.M. Costa Rica, July 2008, webpage: AMCosta-crack.
  3. ^ a b c "Officials warn of life-threatening cocaine in area", Stacy O’Brien, Red Deer Advocate, December 2008, webpage: reddeer-officials.
  4. ^ Kinzie, Erik (April 2009). "Levamisole Found in Patients Using Cocaine". Annals of Emergency Medicine 53 (4). Retrieved 2009-08-18.
  5. ^ Reinarman, Craig; Levine, Harry G. (1997). "Crack in Context: America’s Latest Demon Drug". in Reinarman, Craig; Levine, Harry G.. Crack in America: Demon Drugs and Social Justice. Berkeley, Ca.: University of California Press.
  6. ^ a b c d e f g h i j k l m n o p "DEA, Drug Information, Cocaine", United States DOJ Drug Enforcement Agency, 2008, webpage: DEA-cocaine.
  7. ^ a b c White Mischief: A Cultural History of Cocaine, Tim Madge, 2004, ISBN 1560253703, Google Books link: books-google-PT18.
  8. ^ a b c "Life or Meth – CRACK OF THE 90’S", Salt Lake City Police Department, Utah, 2008, PDF file: Methlife-PDF.
  9. ^ a b c d "Delusional Parasitosis", The Bohart Museum of Entomology, 2005, webpage: UCDavis-delusional.
  10. ^ Morgan, John P.; Zimmer, Lynn (1997). "Social Pharmacology of Smokeable Cocaine". in Reinarman, Craig; Levine, Harry G.. Crack in America: Demon Drugs and Social Justice. Berkeley, Ca.: University of California Press.
  11. ^ Reinarman, Craig; Waldorf, Dan; Murphy, Sheigla B.; Levine, Harry G. (1997). "The Contingent Call of the Pipe: Bingeing and Addiction Among Heavy Cocaine Smokers". in Reinarman, Craig; Levine, Harry G.. Crack in America: Demon Drugs and Social Justice. Berkeley, Ca.: University of California Press.
  12. ^ a b Scheidweiler KB, Plessinger MA, Shojaie J, Wood RW, Kwong TC (2003). "Pharmacokinetics and pharmacodynamics of methylecgonidine, a crack cocaine pyrolyzate". J. Pharmacol. Exp. Ther. 307 (3): 1179–87. doi:10.1124/jpet.103.055434.PMID 14561847. Retrieved 2008-02-24.
  13. ^ Yang Y, Ke Q, Cai J, Xiao YF, Morgan JP (2001). "Evidence for cocaine and methylecgonidine stimulation of M(2) muscarinic receptors in cultured human embryonic lung cells". Br. J. Pharmacol. 132 (2): 451–60. doi:10.1038/sj.bjp.0703819.PMID 11159694.
  14. ^ Fandiño AS, Toennes SW, Kauert GF (2002). "Studies on hydrolytic and oxidative metabolic pathways of anhydroecgonine methyl ester (methylecgonidine) using microsomal preparations from rat organs". Chem. Res. Toxicol. 15 (12): 1543–8.doi:10.1021/tx0255828. PMID 12482236.
  15. ^ a b "A Rose With Another Name: Crack Pipe", Allan Lengel, The Washington Post, April 5, 2006, webpage: highbeam-576: states "four-inch-long tube that holds the flower" and "Convenience stores, liquor stores and gas stations…sell what the street calls ‘rosebuds’ or ‘stems’ for $1 to $2".
  16. ^ a b Kaplan & Sadock’s Synopsis of Psychiatry: Behavioral, Benjamin J. Sadock, Harold I. Kaplan, 2007, page 426, Google-Books webpage: books-google-KS426.
  17. ^ a b "Preventing Poisoned Minds", Dennis Meredith, Duke Magazine, July/August 2007, webpage: DM-17.
  18. ^ NIDA – Research Report Series – Cocaine Abuse and Addiction
  19. ^ "Illicit Drug Use During Pregnancy". March of Dimes. Retrieved 2009-05-26.
  20. ^ "Cocaine and Crack". European Monitoring Centre for Drugs and Drug Addiction. Retrieved 2008-05-01.
  21. ^ "Single Convention on Narcotic Drugs, 1961". International Narcotics Control Board. Retrieved 2008-05-01.
  22. ^ "DEA, Title 21, Section 812". Usdoj.gov. Retrieved 2008-09-05.
  23. ^ 21 U.S.C. § 812(b)(2) Retrieved on 2008-05-01.
  24. ^ "Nuts! Cops use holiday treat in drug sting", Chicago Sun Times, December 24, 2004. Accessed November 21, 2007.
  25. ^ Sabet, Kevin A. Making it Happen: The Case for Compromise in the Federal Cocaine Law Debate
  26. ^ U.S. Sentencing Commission, U.S. Sentencing Commission Votes To Amend Guidelines For Terrorism, Firearms, And Steroids, news release, April 27, 2007.
  27. ^ Lynn Eberhardt, Jennifer; Fiske, Susan T. (1998). Confronting racism: the problem and the response. Thousand Oaks, Calif.: Sage Publications. ISBN 0-7619-0368-2.
  28. ^ Angeli, David H. (1997). "A "Second Look" at Crack Cocaine Sentencing Policies: One More Try for Federal Equal Protection". American Criminal Law Review 34. Retrieved 2008-04-12..

External links

Search Wiktionary
Look up crack cocaine inWiktionary, the free dictionary.

Search Wikimedia Commons
Wikimedia Commons has media related to: Crack cocaine

 

Black cocaine

 

Black cocaine, also known as Coca Negra, is a combination of regular cocaine hydrochloride and various chemicals, such as potassium thiocyanate, usually added at 40% admixture. This renders it undetectable to drug sniffing dogs and the regular chemical tests. Since the result is usually black, it is generally smuggled in as toner in fake IBM or HP brand toner cartridges, fingerprint powder, fertilizer or pigment. The potassium thiocyanate substance is separated out after delivery with a solvent such asacetone and discarded.

The Securtec "Drugwipe test" has been one of a few that have worked in detecting the mixture.

This is not a new process, Black cocaine was detected for the first time in Germany in February 1998.

Advertisements