Cocaine

Cocaine
Cocaine's chemical structure
cocaine
chemical name: [1R-(exo,exo)]-3-(Benzoyloxy)-8-methyl-8-azabicyclo [3.2.1]octane-2-carboxylic acid methyl ester alternate chemical name: 3beta-hydroxy-1alphaH, 5alphaH-tropane-2beta-carboxylic acid methyl ester benzoate alternate chemical name: 2beta-carbomethyoxy-3beta-benzoxytropane, ecgonine methyl ester benzoate alternate chemical name: l-cocaine, beta-cocaine, benzoylmethyl-ecgonine
CAS number 50-36-2	ATC code S01HA02
Chemical formula	C17H21NO4
Molecular weight	303.36 amu
Bioavailability	?
Metabolism	Liver
Elimination half life	Up to 72 hours
Excretion	Urine
Pregnancy category	C
Legal status (US)	US Schedule II
Legal status (UK)	Class A
Delivery	Topical, Insufflation, IV, PO
Melting Point (monoclinic tablets)	98°C
Melting Point (hydrochloride)	195°C
Melting Point (nitrate dihydrate)	58-63°C

This article is about the drug Cocaine. For the blues song by J.J. Cale (later covered by Eric Clapton) see Cocaine (song).

Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. It is a stimulant of the central nervous system and an appetite suppressant, creating what has been described as a euphoric sense of happiness and increased energy. Though most often used recreationally for this effect, cocaine is also a topical anesthetic that was used in eye and throat surgery in the 19th and early 20th centuries. Cocaine is highly addictive, and its possession, cultivation, and distribution is illegal for non-medicinal / non-government sanctioned purposes in virtually all parts of the world.

History

The coca leaf

For thousands of years and still today, South American indigenous peoples have chewed the coca leaf (Erythroxylum 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, but there is no evidence that its habitual use ever led to any of the negative consequences generally associated with habitual cocaine use today.

File:Coca.jpg

The coca plant, Erythroxylum coca.

When the Spaniards conquered South America, they at first ignored Aboriginal claims that the leaf gave them strength and energy, and declared the practice of chewing it the work of the Devil. But after discovering that these claims were true, they legalized and taxed the leaf, taking 10 percent off the value of each crop. These taxes were for a time the main source of support for the Roman Catholic Church in the region.

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

Although the stimulant and hunger-suppressant properties of coca had been known for many centuries, the isolation of the cocaine alkaloid was not achieved until 1855. Many scientists had attempted to isolate cocaine, but none had been successful for two reasons: the knowledge of chemistry required was insufficient at the time, and coca does not grow in Europe and is easily ruined during travel.

The cocaine alkaloid was first isolated by the German chemist Friedrich Gaedcke in 1855. Gaedcke named the alkaloid “erythroxyline,” and published a description in the journal Archives de Pharmacie.

In 1856, Friederich Wöhler asked Dr. Carl Scherzer, a scientist aboard the Novara (an Austrian frigate sent by Emperor Franz Joseph to circle the globe), to bring him a large amount of coca leaves from South America. In 1859, the ship finished its travels and Wöhler received a trunk full of coca. Wöhler passed on the leaves to Albert Niemann, a Ph.D. student at the University of Göttingen in Germany, who then developed an improved purification process.

Niemann described every step he took to isolate cocaine in his dissertation titled On a New Organic Base in the Coca Leaves, which was published in 1860 — it also earned him his Ph.D. and is now in the British Library. He wrote of the alkaloid's “colourless transparent prisms” and said that, “Its solutions have an alkaline reaction, a bitter taste, promote the flow of saliva and leave a peculiar numbness, followed by a sense of cold when applied to the tongue.” Niemann named the alkaloid “cocaine” — as with other alkaloids its name carried the “-ine” suffix (from Latin -ina).

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 Vin Mariani 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. 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 only known measure of the amount of cocaine in Coca-Cola was determined in 1902 as being as little as 1/400 of a grain (0.2 mg) per ounce of syrup. (6 ppm.) The actual amount of cocaine that Coca-Cola contained during the first twenty years of its production is impossible to determine.

In 1879 cocaine began to be used to treat morphine addiction. Cocaine was introduced into clinical use as a local anaesthetic in Germany in 1884, about the same time as Sigmund Freud published his work 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...

File:Cocaine tooth drops.jpg

Cocaine, the 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 as the cucaine injected by Arthur Conan Doyle’s fictional Sherlock Holmes.

In 1909, Ernest Shackleton took “Forced March” brand cocaine tablets to Antarctica, as did Captain Scott a year later on his ill-fated journey to the South Pole.

Prohibition

By the turn of the twentieth century, the addictive properties of cocaine had become clear to many, and the problem of cocaine abuse began to capture public attention in the United States. The dangers of cocaine abuse became part of a moral panic that was tied to the dominant racial and social anxieties of the day. In 1903, the American Journal of Pharmacy stressed that most cocaine abusers were "bohemians, gamblers, high- and low-class prostitutes, night porters, bell boys, burglars, racketeers, pimps, and casual laborers." In 1914, Dr. Christopher Koch of Pennsylvania’s State Pharmacy Board made the racial innuendo explicit, testifying that, “Most of the attacks upon the white women of the South are the direct result of a cocaine-crazed Negro brain.” Mass media manufactured an epidemic of cocaine use among African Americans in the Southern United States to play upon racial prejudices of the era, though there is little evidence that such an epidemic actually took place. In the same year, the Harrison Narcotics Tax Act outlawed the use of cocaine in the United States.

Modern usage

In most Western countries, cocaine (known colloquially as "coke," "nose candy," "blow," "snow," etc.; see List of street names of drugs) is a popular recreational drug. In the United States, the development of "crack" cocaine introduced the substance to a generally poorer inner-city market. Use of the powder form has stayed relatively constant, experiencing a new height of use during the late 1990s and early 2000s in the U.S., and has become much more popular in the last few years in the UK.

Cocaine use is prevalent across all socioeconomic strata, including age, demographics, economic, social, political, religious, and livelihood. Cocaine in its various forms comes in second only to cannabis as the most popular illegal recreational drug in the United States, and is number one in street value sold each year.

The estimated U.S. cocaine market exceeded $35 billion in street value for the year 2003, exceeding revenues by corporations such as AT&T and Starbucks. There is a tremendous demand for cocaine in the U.S. market, particularly among those who are making incomes affording luxury spending, such as single adults and various professionals. Cocaine’s status as a club drug shows its immense popularity among the “party crowd.” Cocaine’s high revenues may be due to the drug’s psychologically addictive nature, which makes the cessation of use quite difficult. It has become much more popular as a middle class drug in the United Kingdom in recent years.

Pharmacology

Appearance

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). Cocaine is frequently adulterated or “cut” with various powdery fillers to increase its surface area; the substances most commonly used in this process are baking soda; sugars, such as lactose, inositol, and mannitol; and local anesthetics, such as lidocaine or benzocaine, which mimic or add to cocaine's numbing effect on mucous membranes. 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 sodium bicarbonate, and the presence of impurities, but will generally range from a light brown to a pale brown. Its texture will also depend on the factors that affect color, but will range from a crumbly texture, which is usually the lighter variety, to a hard, almost crystalline nature, which is usually the darker variety.

Forms of cocaine

Cocaine sulfate

Cocaine sulfate is produced by macerating coca leaves along with water that has been acidulated with sulfuric acid, or a naphtha-based solvent, like kerosene or benzene. This is often accomplished by putting the ingredients into a vat and stamping on it, in a manner similar to the traditional method for crushing grapes. After the cocaine is extracted, the water is evaporated to yield a pasty mass of impure cocaine sulfate.

The sulfate itself is an intermediate step to producing cocaine hydrochloride. In South America, it is commonly smoked along with tobacco, and is known as pasta, basuco, basa, pitillo, paco or simply paste. It is also gaining popularity as a cheap drug (.30-.70 U.S. cents per "hit" or dose) in Argentina.

Freebase

Main article: Freebase

As the name implies, “freebase” is the base form of cocaine, as opposed to the salt form of cocaine hydrochloride. Whereas cocaine hydrochloride is extremely soluble in water, cocaine base is insoluble in water and is therefore not suitable for drinking, snorting or injecting. Cocaine hydrochloride is not well-suited for smoking because the temperature at which it vaporizes is very high, and close to the temperature at which it burns; however, cocaine base vaporizes at a low temperature, which makes it suitable for inhalation.

Smoking freebase is preferred by many users because the cocaine is absorbed immediately into blood via the lungs, where it reaches the brain in about five seconds. The rush is much more intense than sniffing the same amount of cocaine nasally, but the effects do not last as long. The peak of the freebase rush is over almost as soon as the user exhales the vapor, but the high typically lasts 5–10 minutes afterward. What makes freebasing particularly dangerous is that users typically don't wait that long for their next hit and will continue to smoke freebase until none is left. These effects are similar to those that can be achieved by injecting or “slamming” cocaine hydrochloride, but without the risks associated with intravenous drug use (though there are other serious risks associated with smoking freebase).

Freebase cocaine is produced by first dissolving cocaine hydrochloride in water. Once dissolved in water, cocaine hydrochloride (Coc HCl) disassociates into protonated cocaine ion (CocH⁺) and chloride ion (Cl^-). Any solids that remain in the solution are not cocaine (they are part of the cut) and are removed by filtering. A base, typically ammonia (NH₃), is added to the solution to remove the extra proton from the cocaine. The following net chemical reaction takes place:

NH₃ + CocH⁺ + Cl^- → NH₄Cl + Coc

As freebase cocaine (Coc) is insoluble in water, it precipitates and the solution becomes cloudy. To recover the freebase, diethyl ether is added to the solution: Because freebase is highly soluble in ether, a vigorous shaking of the mixture results in the freebase being dissolved in the ether. As ether is insoluble in water, it can be siphoned off. The ether is then left to evaporate, leaving behind the nearly pure freebase.

This procedure is dangerous because of the hazards of handling diethyl ether: it is extremely flammable, its vapors are heavier than air and can “creep” from an open bottle, and in the presence of oxygen it can form peroxides, which can spontaneously combust. Demonstrative of the dangers of the practice, the famous comedian Richard Pryor used to perform a well known skit in which he poked fun at himself during a 1980 incident in which he caused an explosion and set himself on fire while attempting to smoke “freebase,” presumably still wet with ether.

Crack cocaine

A pile of crack cocaine "rocks."

Because of the dangers of using ether to produce pure freebase cocaine, cocaine producers began to omit the step of removing the freebase cocaine precipitate from the ammonia mixture. Typically, filtration processes are also omitted. The end result of this process is that the cut, in addition to the ammonium salt (NH₄Cl), remains in the freebase cocaine after the mixture is evaporated. The “rock” that is thus formed also contains a small amount of water. When the rock is heated, this water boils, making a crackling sound (hence the name “crack”). Baking soda is now most often used as a base rather than ammonia for reasons of lowered stench and toxicity; however, any weak base can be used to make crack cocaine. Strong bases, such as sodium hydroxide, tend to hydrolyze some of the cocaine into non-psychoactive ecgonine.

The net reaction when using baking soda (also called sodium bicarbonate, with a chemical formula of NaHCO₃) is:

CocH⁺ + Cl^- + NaHCO₃ → Coc + H₂O + CO₂ + NaCl

Crack is unique because it offers a strong cocaine experience in small, low-priced packages. In the United States, crack cocaine is often sold in small, inexpensive dosage units frequently known as “nickels” or “nickel rocks” (referring to the price of $5.00), and also “dimes” or “dime rocks” ($10.00) and sometimes as “twenties” or “solids,” and “forties.” The quantity provided by such a purchase varies depending upon many factors, such as local availability, which is affected by geographic location. A twenty may yield a quarter gram or half gram on average, yielding 30 minutes to an hour of effect if hits are taken every few minutes. After the $20 or $40 mark, crack and powder cocaine are sold in grams or fractions of ounces. Many inner-city addicts with a regular dealer will “work a corner,” taking money from anyone who wants crack, making a buy from the dealer, then delivering part of the product while keeping some for themselves.

Although consisting of the same active drug as powder cocaine, crack cocaine in the United States is seen as a drug primarily by and for the inner-city poor — the stereotypical "crack head" is a poor, urban, usually homeless person. While insufflated powder cocaine has an associated glamour attributed to its popularity among mostly middle and upper class whites (as well as musicians and entertainers), crack is perceived as a skid row drug of squalor and desperation. In many U.S. jurisdictions, possession or sale of crack cocaine carries a harsher penalty than an equivalent amount of powder cocaine.

Street names for crack include “bones,” "candy," "cheese," "devil's dick" (in which smoking crack using a pipe becomes "sucking the devil's dick"), “devil’s dandruff,” "devil's candy," “devil drug,” “devilsmoke,” “dope,” "food,” "girl," “hard,” "hobart," "juice," "krills," “lle" (Spanish), “llello" (Spanish), “matter,” “smoke,” "white bitch," “work,” "yay,” "yayo,” "yeyo," "yoyo," “yoda,” “yola,” "Sos," or "Sosa" (Dutch); but most commonly, it is simply called “rock.” Crack cocaine was extremely popular in the mid- and late 1980s, especially in inner cities, though its popularity declined through the 1990s. In 1998, Gary Webb's book Dark Alliance: The CIA, the Contras, and the Crack Cocaine Explosion linked the “crack explosion” to the CIA funding of the anti-Communism Contras fighting against Sandinistas in Nicaragua.

Methods of administration

Chewed/eaten

The simplest way to administer cocaine is to chew on the leaves of the plant. Because of physical restrictions of this modality, only small amounts of cocaine make it into the bloodstream and the effect is that of a mild stimulant. Mate de coca or coca-leaf tea is also a traditional method of consumption and is often recommended to treat altitude sickness.

In 1986 an article in the Journal of the American Medical Association revealed that health food stores were selling coca-leaf tea as “Health Inca Tea.” While the packaging claimed it had been “decocainized,” no such process had taken place—they were selling a controlled substance off the shelves. The article stated that drinking two cups of the tea per day gave a mild stimulation, increased heart rate, and mood elevation, and the tea was essentially harmless. Despite this, the DEA seized several shipments in Hawaii, Chicago, Illinois, Georgia, and several locations on the East Coast of the United States, and the product was removed from the shelves.

Insufflation

Insufflation (known colloquially as “snorting," “sniffing," or "blowing") is the most common method of ingestion of recreational powder cocaine in the Western world. Contrary to widespread belief, cocaine is not actually inhaled using this method; rather the drug coats and is absorbed through the mucous membranes lining the sinuses. When insufflating cocaine, absorption through the nasal membranes is approximately 80 percent. 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). Chronic use results in ongoing rhinitis and necrosis of the nasal membranes. Cellulose granulomas from adulterants have also been found in the lungs of recreational “sniffers.”

Prior to insufflation, cocaine powder must be divided into very fine particles. Cocaine of high purity breaks into smallest dust very easily, except when it's moist (not well stored) and forms “chunks,” which reduce the efficiency of nasal absorption.

Rolled up banknotes, hollowed-out pens, cut straws and specialized spoons are often used to insufflate cocaine. Such devices are often referred to as "tooters" by users. The cocaine typically is poured onto a flat, hard surface (such as a mirror) and divided into "lines" (usually with a razor blade or credit card), which are then insufflated. The amount of cocaine in a line varies widely from person to person and occasion to occasion (the purity of the cocaine is also a factor), but one line is generally considered to be a single dose.

Insufflating can cause coughs and nosebleeds.

Injected

The intravenous route of administration provides the highest blood levels of drug in the shortest amount of time. Upon injection, cocaine reaches the brain in a matter of seconds, and the exhilarating rush that follows can be so intense that it induces some users to vomit uncontrollably. The euphoria passes quickly due to neural upregulation, but the drug continues to affect the body until the liver metabolizes it. 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. Obviously, there is also a risk of serious infection associated with the use of contaminated needles.

An injected mixture of cocaine and heroin, known as “speedball” or “moonrock”, is a particularly popular and dangerous combination, as the converse effects of the drugs actually complement each other, but may also mask the symptoms of an overdose. It has been responsible for numerous deaths, particularly in and around Los Angeles, including celebrities such as John Belushi, Chris Farley and Layne Staley. Experimentally, cocaine injections can be delivered to animals such as fruit flies [1] to study the mechanisms of cocaine addiction.

Smoked

File:Leslie-crack.jpg

A woman smoking crack from a glass pipe

(see also: Crack cocaine above)

Smoking freebase or crack cocaine is most often accomplished using a pipe made from a small glass tube about one quarter-inch (about 6 mm) in diameter and up to several inches long. These are sometimes called "straight shooters," readily available in convenience stores or smoke shops. They will sometimes contain a small paper flower and are promoted as a romantic gift. Buyers usually ask for a "rose" or a "flower." An alternate method is to use a small length of a radio antenna or similar metal tube. To avoid burning the user’s fingers and lips on the metal pipe, a small piece of paper or cardboard (such as a piece torn from a matchbook cover) is wrapped around one end of the pipe and held in place with either a rubber band or a piece of adhesive tape.

A small piece of steel or copper scouring pad — often called a "brillo" or "chore", from the scouring pads of the same name — is placed into one end of the tube after having the soapy cleanser coating burned off the metal. It then serves as a crude filter in which the "rock" can melt and boil to vapor. The use of steel wool also acts as a reducing agent, preventing the oxidation of the cocaine.

The "rock" is placed at the end of the pipe closest to the filter and the other end of the pipe is placed in the mouth. A flame from a cigarette lighter or handheld torch is then held under the rock. As the rock is heated, it melts and burns away to vapor, which the user inhales as smoke. The effects are felt almost immediately after smoking, are very intense, and do not last long — usually five to fifteen minutes. Most users will want more after this time, especially frequent users. "Crack houses" depend on these cravings by providing users a place to smoke, and a ready supply of small bags for sale.

A heavily used crackpipe tends to fracture at the end from overheating with the flame used to heat the crack as the user obsessively attempts to inhale every bit of the drug on the metal wool filter. The end is often broken further as the user "pushes" the pipe. "Pushing" is a technique used to partially recover crack that hardens on the inside wall of the pipe as the pipe cools. The user pushes the metal wool filter through the pipe from one end to the other to collect the build-up inside the pipe. The ends of the pipe can be broken by the object used to push the filter, frequently a small screwdriver or stiff piece of wire. The user will often remove the most jagged edges and continue using the pipe until it becomes so short that it burns the lips and fingers. To continue using the pipe, the user will sometimes wrap a small piece of paper or cardboard around one end and hold it in place with a rubber band or adhesive tape. Of course, not all people who smoke crack cocaine will let it get that short, and will get a new or different pipe. The tell-tale signs of a used crack pipe are a glass tube with burn marks at one or both ends and a clump of metal wool inside.

When smoked, cocaine is sometimes combined with other drugs, such as cannabis; often rolled into a joint or blunt. This combination is known as "primo", "hype", "B-151er", a "cocoapuff", a "dirty" or a "woo". Crack smokers who are being drug tested may also make their "primo" with cigarette tobacco instead of cannabis, since a crack smoker can test clean within two to three days of use, if only urine (and not hair) is being tested.

Powder cocaine is sometimes smoked, but it is inefficient as the heat involved destroys much of the chemical. One way of smoking powder is to put a "bump" into the end of an unlit cigarette, smoking it in one go as the user lights the cigarette normally.

Mechanism of action

Once cocaine is introduced into the bloodstream, its acute clinical effects can be observed once the drug crosses the blood-brain barrier. This process can occur within seconds following administration, but can also last upward of a half an hour. The delay in the onset of effects is largely determined by the method of administration.

The primary mechanism of cocaine within the central nervous system is the blockage of the dopamine transporter (DAT). DAT is a protein that functions as a "clean-up" mechanism for the neurotransmitter dopamine once it is no longer needed for inter-cell signalling. The extra dopamine within the synaptic cleft binds to the DAT and is then carried back to the pre-synaptic neuron for repackaging and re-release at a future date. Because cocaine's chemical structure allows it to bind to the DAT it interferes with this re-uptake process.

The ventral tegmental area (VTA), the nucleus accumbens and the prefrontal cortex are regions of the brain that are rich with dopamine receptors and dopamine-releasing neurons. Hence they are often the focus of research into the addictive and rewarding properties of cocaine use.

Cocaine is also a less potent blocker of the norepinephrine transporter (NET) and serotonin transporter (SERT). Cocaine also blocks sodium channels, thereby interfering with the propagation of action potentials; thus, like lidocaine and novocaine, it acts as a local anesthetic. 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 [2] and clock genes [3] 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 don't 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.

Metabolism and excretion

Cocaine is extensively metabolized, primarily in the liver, with only about 1% excreted unchanged in the urine. It is mostly eliminated as benzoylecgonine, the major metabolite of cocaine, and is also excreted in lesser amounts as ecgonine methyl ester and ecgonine.

If taken with alcohol, cocaine combines with the ethanol in the liver to form cocaethylene, which is both more euphorigenic and has higher cardiovascular toxicity than cocaine by itself.

Cocaine metabolites are detectable in urine for up to four days after cocaine is used. Benzoylecgonine can be detected in urine within four hours after cocaine inhalation and remains detectable in concentrations greater than 1000 ng/ml for as long as 48 hours. Detection in hair is possible in regular users until the sections of hair grown during use are cut or fall out.

Effects and health issues

Cocaine is a potent central nervous system stimulant. Its effects can last from 20 minutes to several hours, depending upon the dosage of cocaine taken, purity, and method of administration.

The initial signs of stimulation are hyperactivity, restlessness, increased blood pressure, increased heart rate and euphoria. The euphoria is sometimes followed by feelings of discomfort and depression and a craving to re-experience the drug. Side effects can include twitching and paranoia, which usually increase with frequent usage.

With excessive dosage the drug can produce hallucinations, paranoid delusions, tachycardia, itching, and formication.

Overdose causes tachyarrhythmias and a marked elevation of blood pressure. These can be life-threatening, especially if the user has existing cardiac problems.

Cocaine raises the amount of dopamine and serotonin in the nucleus accumbens; the "crash" experienced after the initial high is marked by an undershooting of normal levels afterward. This is because neurons run out of dopamine and serotonin neurotransmitters. Receptors disappear as a response mechanism to too much neurotransmitter. This contributes to the rise in an abuser's tolerance thus requiring a larger dosage to achieve the same effect. The lack of normal amounts of serotonin and dopamine in the brain is the cause of the dysphoria and depression felt after the initial high. The diagnostic criteria for cocaine withdrawal is characterized by a dysphoric mood, fatigue, unpleasant dreams, insomnia or hypersomnia, increased appetite, psychomotor retardation or agitation, and anxiety.

The LD₅₀ of cocaine when administered to mice is 95.1 mg/kg. Toxicity results in seizures, followed by respiratory and circulatory depression of medullar origin. This may lead to death from respiratory failure, stroke, cerebral hemorrhage, or heart-failure. Cocaine is also highly pyrogenic, because the stimulation and increased muscular activity cause greater heat production. Heat loss is inhibited by the intense vasoconstriction. Cocaine-induced hyperthermia may cause muscle cell destruction and myoglobinuria resulting in renal failure. There is no specific antidote for cocaine overdose.

Cocaine abuse is associated with a lifetime risk of heart attack that is seven times that of non-users. During the hour after cocaine is used, heart attack risk rises 24-fold. It accounts for 25% of the heart attacks in the 18–45-year-old age group. [4]

Side effects from chronic smoking of cocaine include chest pain, lung trauma, shortness of breath, sore throat, hoarse voice, dyspnea, and an aching, flu-like syndrome. A common misconception is that the smoking of cocaine breaks down tooth enamel and causes tooth decay. Although this is not true, the lifestyle of frequent cocaine users may include poor dental hygiene, which often results in tooth decay. In addition, cocaine often causes involuntary tooth grinding, known as bruxism, which can deteriorate tooth enamel and lead to gingivitis.

Chronic intranasal usage can degrade the cartilage separating the nostrils (the Septum nasi), leading eventually to its complete disappearance.

Cocaine as a local anesthetic

Cocaine was historically useful as a topical anesthetic in eye and nasal surgery. The major disadvantages of this use are cocaine's intense vasoconstrictor activity and potential for cardiovascular toxicity. Cocaine has since been largely replaced in Western medicine by synthetic local anaesthetics such as benzocaine, proparacaine, 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 Australian 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.

Cocaine trade

File:Cocaine bricks scorpion logo.jpg

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

Because of the extensive processing it undergoes during preparation and its highly addictive nature, 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, is occasionally bought and sold, but this is exceedingly rare as it is much easier and more profitable to conceal and smuggle it in powdered form.

Production

The following table is based upon information provided by the CIA's Crime and Narcotics Center. [5]

Estimated Andean Region Coca Cultivation and Potential Pure Cocaine Production, 2000–2004.

	2000	2001	2002	2003	2004
Net Cultivation (hectares)	187,500	221,800	200,750	166,300	166,200
Potential Pure Cocaine Production (metric tonnes)	770	925	830	680	645

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

Super Coca

The French news agency AFP recently reported the discovery of a new species of coca plant. According to the report, which was repeated by various media around the world, a coca plant was found in Colombia’s Sierra Nevada that had a high cocaine content and a higher level of purity, and which was also resistant to the effects of aerial spraying. We would like to respond to the confusion and false impressions that this report could cause.

The report apparently originated with the Colombian radio station, Radio Caracol, after an interview with medical toxicologist Camilo Uribe, an adviser to the Anti-Drug Police, on August 23. Dr. Uribe will soon join the International Narcotics Control Board (INCB), the U.N. organisation charged with overseeing proper implementation of international conventions on drugs. As a researcher, Dr. Uribe is known for his conclusions that the aerial spraying of illicit crops is harmless to the environment. According to the researcher, "The quality and percentage of hydrochloride obtained from each leaf is much greater, between 97 and 98 percent, when a normal plant — for example, the one used by the Caucano Indians — has no more than 25 percent." Drug traffickers supposedly had developed a variety that was resistant to glyphosate [the active ingredient in Monsanto's Roundup] spraying. These giant coca plants were allegedly the drug traffickers’ response to the intensive campaigns of crop- spraying and manual destruction of illicit crops being carried out by the Colombian government with strong support from the U.S. government.

A few scientific facts provide grounds for questioning the credibility of this report about the cocaine alkaloid content of the coca leaf. In establishing the presence of "toxic" alkaloids in the coca leaf, scientifically proven percentages vary between 0.25 percent and 2.25 percent. (1) According to other studies, the alkaloid content is probably between 0.1 percent and 0.8 percent, with some exceptions. (2) With Operation Breakthrough, the U.S. Drug Enforcement Administration (DEA) attempted to establish scientific grounds for a reliable calculation of cocaine production. According to the DEA, before the operation such calculations were based only on anecdotal data. Results from the operation, which was launched in Bolivia in 1993 and in Peru and Colombia in the following years, demonstrated an average cocaine alkaloid content of between 0.72 percent and 0.85 percent in Bolivia. (3) In Peru and Colombia, estimates of cocaine content were lower than for the Bolivian leaf, at least in studies by the U.S. State Department.

Trafficking and distribution

Organized criminal gangs operating on a large scale dominate the cocaine trade. Most cocaine is grown and processed in South America, particularly in Colombia and Peru, and smuggled into the United States and Europe, where it is sold at huge markups.

Cocaine shipments from South America transported through Mexico or Central America are generally moved over land or by air to staging sites in northern Mexico. The cocaine is then broken down into smaller loads for smuggling across the U.S.–Mexico border. The primary cocaine importation points in the United States are in Arizona, southern California, southern Florida, and Texas. Typically, land vehicles are driven across the U.S.-Mexico border.

Cocaine is also carried in small, concealed, kilogram quantities across the border by couriers known as “mules” (or “burros”), who enter the United States either legally through ports of entry or illegally through undesignated points along the border. Colombian traffickers have also started using a new concealment method whereby they add chemical compounds to cocaine hydrochloride to produce “black cocaine.” The cocaine in this substance is not detected by standard chemical tests or drug-sniffing canines.

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.

Bulk cargo ships are also used to smuggle cocaine to staging sites in the western Caribbean–Gulf of Mexico area. These vessels are typically 150–250 foot (50–80 m) coastal freighters that carry an average cocaine load of approximately 2.5 tonnes. Commercial fishing vessels are also used for smuggling operations. In areas with a high volume of recreational traffic, smugglers use the same types of vessels, such as go-fast boats, as those used by the local populations.

Most cocaine is smuggled in large quantities in trucks, boats, or small airplanes. Smaller gangs will often send out a drug mule, often a young woman, with kilos of cocaine strapped to her waist or legs or hidden in her bags. If she gets through without being caught, the gangs will reap most of the profits. If she is caught however, gangs will sever all links and she will usually stand trial for trafficking by herself.

Addiction

Cocaine addiction is the obsessive or uncontrollable abuse of cocaine, and can result in physiological damage, lethargy, depression, or a potentially fatal overdose. Many habitual abusers have been diagnosed with a manic condition similar to amphetamine psychosis and schizophrenia, whose symptoms include aggression, severe paranoia, and tactile hallucinations (including the feeling of insects under the skin, or "coke bugs").

Cocaine has positive reinforcement effects, which refers to the effect that certain stimuli have on behavior. Good feelings become associated with the drug, causing a frequent user to take the drug as a response to bad news or mild depression. This activation strengthens the response that was just made. If the drug was taken by a fast acting route such as injection or inhalation, the response will be the act of taking more cocaine, so the response will be reinforced. Powder cocaine, being a club drug is most commonly available in the evening and night hours. Because cocaine is a stimulant, a user will often drink large amounts of alcohol during and after usage or smoke marijuana to dull the effects to help one achieve slumber. These several hours of temporary relief and pleasure will further reinforce the positive response. Other downers such as heroin and various pharmaceuticals are often used for the same purpose, further increasing addiction potential and harmfulness.

It is speculated that cocaine's addictive properties stem from its DAT-blocking effects (in particular, increasing the dopaminergic transmission from ventral tegmental area neurons). However, a study has shown that mice with no dopamine transporters still exhibit the rewarding effects of cocaine administration [6]. Later work demonstrated that a combined DAT/SERT knockout eliminated the rewarding effects [7]. The rewarding effects of cocaine are influenced by circadian rhythms [8], possibly by involving a set of genes termed "clock genes" [9].

Treatment

Cognitive Behavioral Therapy (CBT) shows promising results. Spiritual based Twelve-step programs such as Cocaine Anonymous (modeled on Alcoholics Anonymous) have some success combatting this problem. A cocaine vaccine is also being tested that may prevent the recipient from feeling the desirable effects of the drug, though a similar effort to develop a heroin vaccine was abandoned as ineffective in the 1970s.

GVG

File:Dopamine monkey.png

Positron Emission Tomography scans showing the average level of dopamine receptors in six primates' brains. Red is high- and blue is low-concentration of dopamine receptors. The higher the level of dopamine, the fewer receptors there will be.

Studies have shown that gamma vinyl-gamma-aminobutyric acid (gamma vinyl-GABA, or GVG), a drug normally used to treat epilepsy, blocks cocaine's action in the brains of primates. GVG increases the amount of the neurotransmitter GABA in the brain and reduces the level of dopamine in the region of the brain that is thought to be involved in addiction. In January 2005 the U.S. Food and Drug Administration gave permission for a Phase I clinical trial of GVG for the treatment of addiction. Another drug currently tested for anti-addictive properties is the cannabinoid antagonist rimonabant.

GBR 12909

GBR 12909 (Vanoxerine) is a selective dopamine uptake inhibitor. Because of this, it reduces cocaine's effect on the brain, and may help to treat cocaine addiction. Studies have shown that GBR, when given to primates, suppresses cocaine self-administration.

Venlafaxine

Venlafaxine (Effexor), although not a dopamine re-uptake inhibitor, is a potent serotonin-norepinephrine reuptake inhibitor that has been successfully used to combat the depression caused by cocaine and to a lesser extent, the addiction associated with the drug itself. Venlafaxine has been shown to have significant withdrawal problems itself, and can lead to lifetime use due to these withdrawal effects. A statistically significant number of people prescribed Effexor have committed suicide (2 attempts per 1000 patients, vs 1.56 suicides per 1,000 untreated depressives).

Coca Tea

Coca herbal tea has been used for the treatment of cocaine dependence. Two reports found that treatment that includes coca tea can be successful in controlling relapse to cocaine dependence. In one study, coca tea plus counseling was used to treat cocaine dependence in 23 cocaine-addicted coca paste smokers seeking treatment at an outpatient clinic in Lima, Peru. Cocaine lapses fell from 4.35 times a month prior to treatment to 1.22 during treatment. Mean abstinence increased from 32 days before treatment to 217.2 days during treatment. The results support the effectiveness of Coca herbal tea for preventing relapse in cocaine-addicted patients.

Legal status

The production, the distribution and the sale of cocaine products is restricted (and illegal in most contexts) in most countries. See legal status of cocaine for more information.

Usage

In the United States

Overall usage

The National Household Survey on Drug Abuse (NHSDA) reported in 1999 that cocaine was used by 3.7 million Americans, or 1.7 percent of the household population age 12 and older. Estimates of the current number of those who use cocaine regularly (at least once per month) vary, but 1.5 million is a widely accepted figure within the research community.

Although cocaine use had not significantly changed over the six years prior to 1999, the number of first-time users went from 574,000 in 1991, to 934,000 in 1998 — an increase of 63%. While these numbers indicated that cocaine is still widely present in the United States, cocaine use was significantly less prevalent than it was during the early 1980s. Cocaine use peaked in 1982 when 10.4 million Americans (5.6 percent of the population) reportedly used the drug.

Usage among youth

The 1999 Monitoring the Future (MTF) survey found the proportion of American students reporting use of powder cocaine rose during the 1990s. In 1991, 2.3 percent of eighth-graders stated that they had used cocaine in their lifetime. This figure rose to 4.7 percent 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 percent to 7.7 percent for tenth-graders and from 6.1 percent to 9.8 percent for twelfth-graders. Lifetime use of crack cocaine, according to MTF, also increased among eighth-, tenth-, and twelfth-graders, from an average of 2 percent in 1991 to 3.9 percent 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 percent, an increase from 1.2 percent 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.

Availability

Cocaine is readily available in all major U.S. 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 because some users were switching to methamphetamine, which was cheaper and provides a longer-lasting high. Numbers of cocaine users are still very large, with a concentration among city-dwelling youth.

Works concerning cocaine

Books about cocaine

• Cocaine: an unauthorized biography by Dominic Streatfeild
• Novel, With Cocaine, by M. Ageyev
• Über Coca by Sigmund Freud
• The Triumph of Surgery by Jürgen Thorwald - Ch. 6 - The second battle against Pain (The early use of cocaine solution in eye surgery)
• More, Now, Again by Elizabeth Wurtzel
• Snowblind by Robert Sabbag
• Celerino III Castillo & Dave Harmon (1994). Powderburns: Cocaine, Contras & the Drug War, Sundial. ISBN 0889625786 (paperback) ISBN 0809548550 (hardcover; Borgo Pr; 3rd ed.; 1995).
• Alexander Cockburn & Jeffrey St. Clair (1999). Whiteout: The CIA, Drugs and the Press, Verso. ISBN 1859841392 (cloth), ISBN 1859842585 (paperback). Cites 116 books.
• Frederick P. Hitz (1999). Obscuring Propriety: The CIA and Drugs, International Journal of Intelligence and Counterintelligence, 12(4): 448-462 DOI:10.1080/088506099304990
• Robert Parry (1999). Lost History: Contras, Cocaine, the Press & “Project Truth”, Media Consortium. ISBN 1893517004.
• Richard Smart (Hard Cover 1985). The Snow Papers The Atlantic Monthly Press ISBN 0-87113-030-0
• Peter Dale Scott & Jonathan Marshall (1991). Cocaine Politics: Drugs, Armies, and the CIA in Central America, University of California Press. ISBN 0520214498 (paperback, 1998 reprint), ISBN 0520073126 (hardcover, 1991), ISBN 0520077814 (paperback, 1992 reprint).
• Gary Webb(1998). Dark Alliance: The CIA, the Contras, and the Crack Cocaine Explosion, Seven Stories Press. ISBN 1888363681 (hardcover, 1998), ISBN 1888363932 (paperback, 1999).
• Philippe Bourgois In Search of Respect: Selling Crack in El Barrio. New York: Cambridge University Press. 2003. Second Updated Edition.
• Otto Snow THC & Tropacocaine ISBN 0966312856 (paperback 2004)
• David Lee Cocaine Handbook ISBN 091590456X (paperback 1981)
• Adam Gottlieb Cocaine Tester's Handbook ASIN B0007C137A (paperback 1975)
• Adam Gottlieb Pleasures of Cocaine: If You Enjoy: This Book May Save Your Life ISBN 091417181X (paperback 1996)
• Carol Saline Doctor Snow: How the FBI Nailed a Ivy League Coke King ISBN 0-453-00593-4 (HardCover 1986)
• Mark Bowden Doctor Dealer: The Rise & Fall Of An All American Boy and his Multi-Million Dollar Cocaine Empire ISBN 0-446-51382-2 (HardCover 1987)
• Less Than Zero by Bret Easton Ellis (1985)

Movies about cocaine

The following films feature the use or trade of cocaine as a major plot element

• Bad Lieutenant directed by Abel Ferrara
• Blow directed by Ted Demme
• Boogie Nights directed by Paul Thomas Anderson
• Bright Lights, Big City directed by James Bridges
• Carlito's Way directed by Brian de Palma (the main drug in this film is actually heroin)]
• Clean and Sober directed by Glenn Gordon Carron
• Fear and Loathing in Las Vegas directed by Terry Gilliam (the centric drugs in this film are actually hallucinogens)]
• Federal Hill directed by Michael Corrente
• Goodfellas directed by Martin Scorsese
• Just Say Know directed by Tao Ruspoli
• Layer Cake directed by Matthew Vaughn
• Less Than Zero directed by Marek Kanievska
• Leon directed by Luc Besson
• Lord of War directed by Andrew Niccol
• Maria Full of Grace directed by Joshua Marston
• New Jack City directed by Mario Van Peebles
• Requiem for a Dream directed by Darren Aronofsky
• Scarface directed by Brian de Palma
• The Seven-Per-Cent Solution directed by Herbert Ross
• Starsky & Hutch directed by Todd Phillips
• Traffic directed by Steven Soderbergh
• True Romance directed by Tony Scott
• Big Money Hustlas directed by John Cafiero

See also

• List of songs about cocaine

See also

• Benzocaine
• Coca eradication
• Crack baby
• Coca tea
• Cuscohygrine
• Dihydrocuscohygrine
• Drug addiction
• Ecgonine benzoate
• Hydroxytropacocaine
• Hygrine
• Methylecgonine cinnamate
• Novocaine
• Tropacocaine
• Truxilline
• Psychoactive drug

References

• Nahas, Gabriel G.: The Experimental Use of Cocaine in Human Subjects, Bulletin on Narcotics, 1990.
• Siegel RK, Elsohly MA, Plowman T, Rury PM, Jones RT. (1986). "Cocaine in herbal tea." Journal of the American Medical Association 255, 40. PubMed unique identifier 3940302

External links

• Self-test — from Cocaine Addicts Anonymous
• Cocaine User Helping Hand — Internet Portal dedicated to help crack- and cocaine-addicted people. Contains wide variety of information on drug abuse, available treatment, and recovery issues.
• Good Drugs Guide
• The Erowid Cocaine Vault
• Urban Legends Reference Pages: Cokelore (Cocaine-Cola) — information about cocaine in Coke
• Addictive properties
• The Mystery of the Coca Plant that Wouldn't Die - Wired Magazine
• Shared Responsibility — Information about European cocaine use and drug trafficking in Colombia.
• Cocaine content of plants
• Cocaine.org — A very thorough information guide on Cocaine and its history, use/abuse, etc.