Cocaine (benzoylmethylecgonine) (INN) is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant.<ref name= aggrawal1>Aggrawal, Anil. Narcotic Drugs. National Book Trust, India (1995), p. 52-3. ISBN 978-81-237-1383-0.</ref> The name comes from "coca" and the alkaloid suffix -ine, forming cocaine. It is a stimulant, an appetite suppressant, and a topical anesthetic. Biologically, cocaine acts as a serotonin–norepinephrine–dopamine reuptake inhibitor, also known as a triple reuptake inhibitor (TRI). It is addictive because of its effect on the mesolimbic reward pathway.<ref>Template:Cite journal</ref>
Unlike most molecules, cocaine has pocketsTemplate:Clarify with both high hydrophilic and lipophilic efficiency, violating the rule of hydrophilic-lipophilic balance. This causes it to cross the blood–brain barrier far better than other psychoactive chemicals.Template:Citation needed
It is illegal to possess, produce, or distribute cocaine for non-medicinal and non-government-sanctioned purposes in almost every country.
Cocaine is a powerful nervous system stimulant.<ref name=WHO2004>World Health Organization (2004). Neuroscience of psychoactive substance use and dependence</ref> Its effects can last from 15–30 minutes to an hour, depending on the route of administration.<ref name=WHO2007>World Health Organization (2007). International medical guide for ships</ref>
Cocaine increases alertness, feelings of well-being and euphoria, energy and motor activity, feelings of competence and sexuality. Athletic performance may be enhanced in sports where sustained attention and endurance is required. Anxiety, paranoia and restlessness are also frequent. With excessive dosage, tremors, convulsions and increased body temperature are observed.<ref name=WHO2004/>
Occasional cocaine use does not typically lead to severe or even minor physical or social problems.<ref>Template:Cite news – re. International study on cocaine executed by the World Health Organization. </ref><ref>Cohen, Peter; Sas, Arjan (1994). Cocaine use in Amsterdam in non deviant subcultures. Addiction Research, Vol. 2, No. 1, pp. 71–94.</ref>
Template:Main With excessive or prolonged use, the drug can cause itching, tachycardia, hallucinations, and paranoid delusions.<ref name="weizhao2008">Template:Cite book</ref> Overdoses cause hyperthermia and a marked elevation of blood pressure, which can be life-threatening.<ref name="weizhao2008" />
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)Template:Spaced ndashmechanisms called down-/upregulation. However, studies suggest cocaine abusers do not show normal age-related loss of striatal dopamine transporter (DAT) sites, suggesting cocaine has neuroprotective properties for dopamine neurons.<ref>Template:Cite book</ref> 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.<ref>Template:Cite book</ref>
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. Physiological changes caused by cocaine withdrawal include vivid and unpleasant dreams, insomnia or hypersomnia, increased appetite and psychomotor retardation or agitation.<ref>Template:Cite book</ref>
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. Cocaine constricts blood vessels, dilates pupils, and increases body temperature, heart rate, and blood pressure. It can also cause headaches and gastrointestinal complications such as abdominal pain and nausea. A common but untrue belief is that the smoking of cocaine chemically breaks down tooth enamel and causes tooth decay. However, cocaine does often cause involuntary tooth grinding, known as bruxism, which can deteriorate tooth enamel and lead to gingivitis.<ref>Template:Cite journal</ref> Additionally, stimulants like cocaine, methamphetamine, and even caffeine cause dehydration and dry mouth. Since saliva is an important mechanism in maintaining one's oral pH level, chronic stimulant abusers who do not hydrate sufficiently may experience demineralization of their teeth due to the pH of the tooth surface dropping too low (below 5.5).
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.<ref name="pagliaros">Template:Cite book</ref>
Cocaine may also greatly increase this risk of developing rare autoimmune or connective tissue diseases such as lupus, Goodpasture's disease, vasculitis, glomerulonephritis, Stevens–Johnson syndrome and other diseases.<ref>Template:Cite web</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> It can also cause a wide array of kidney diseases and renal failure.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>
Cocaine misuse doubles both the risks of hemorrhagic and ischemic strokes,<ref>Template:Cite web</ref> as well as increases the risk of other infarctions, such as myocardial infarction.<ref>Template:Cite journal</ref>
Template:Main Cocaine dependence (or addiction) is psychological dependency on the regular use of cocaine. Cocaine dependency may result in physiological damage, lethargy, psychosis, depression, akathisia, and fatal overdose.
Template:Main The first synthesis and elucidation of the cocaine molecule was by Richard Willstätter in 1898.<ref name="Humphrey2001">Template:Cite journal</ref> Willstätter's synthesis derived cocaine from tropinone. Since then, Robert Robinson and Edward Leete have made significant contributions to the mechanism of the synthesis.
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.<ref>Template:Cite book</ref> 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.<ref>Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref> This is due to the extra chiral center at C-2.<ref>Template:Cite journal</ref> This process occurs through an oxidation, which regenerates the pyrrolinium cation and formation of an enolate anion, and an intramolecular Mannich reaction. The tropane ring system undergoes hydrolysis, SAM-dependent methylation, and reduction via NADPH for the formation of methylecgonine. The benzoyl moiety required for the formation of the cocaine diester is synthesized from phenylalanine via cinnamic acid.<ref>Template:Cite journal</ref> Benzoyl-CoA then combines the two units to form cocaine.
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.<ref>Template:Cite journal</ref> 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,<ref>Template:Cite journal</ref> 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.
Robert Robinson's acetonedicarboxylate
The biosynthesis of the tropane alkaloid, however, is still uncertain. Hemscheidt proposes that Robinson's acetonedicarboxylate emerges as a potential intermediate for this reaction.<ref>Template:Cite journal</ref> Condensation of N-methylpyrrolinium and acetonedicarboxylate would generate the oxobutyrate. Decarboxylation leads to tropane alkaloid formation.
Reduction of tropinone
The reduction of tropinone is mediated by NADPH-dependent reductase enzymes, which have been characterized in multiple plant species.<ref>Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref>
Cocaine in its purest form is a white, pearly product. Cocaine appearing in powder form is a salt, typically cocaine hydrochloride (CAS 53-21-4). Street market cocaine is frequently adulterated or “cut” with various powdery fillers to increase its weight; the substances most commonly used in this process are baking soda; sugars, such as lactose, dextrose, inositol, and mannitol; and local anesthetics, such as lidocaine or benzocaine, which mimic or add to cocaine's numbing effect on mucous membranes. Cocaine may also be "cut" with other stimulants such as methamphetamine.<ref>Template:Cite web</ref> 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.
Cocaine is a weakly alkaline compound (an "alkaloid"), and can therefore combine with acidic compounds to form various salts. The hydrochloride (HCl) salt of cocaine is by far the most commonly encountered, although the sulfate (-SO4) and the nitrate (-NO3) are occasionally seen. Different salts dissolve to a greater or lesser extent in various solvents – the hydrochloride salt is polar in character and is quite soluble in water.
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<ref>Template:Cite journal</ref> because of methylecgonidine's effects on lung tissue<ref>Template:Cite journal</ref> and liver tissue.<ref>Template:Cite journal</ref>
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 is a lower purity form of free-base cocaine that is usually produced by neutralization of cocaine hydrochloride with a solution of baking soda (sodium bicarbonate, NaHCO3) and water, producing a very hard/brittle, off-white-to-brown colored, amorphous material that contains sodium carbonate, entrapped water, and other by-products as the main impurities.
The "freebase" and "crack" forms of cocaine are usually administered by vaporization of the powdered substance into smoke, which is then inhaled.<ref>"Substances – Cocaine" The Steinhardt School of Culture, Education, and Human Development. Retrieved August 2009.</ref> The origin of the name "crack" comes from the "crackling" sound (and hence the onomatopoeic moniker “crack”) that is produced when the cocaine and its impurities (i.e. water, sodium bicarbonate) are heated past the point of vaporization.<ref>George, Nelson. "Hip Hop America". 1998. Viking Penguin.(Page 40)</ref> Pure cocaine base/crack is easy to smoke because it vaporizes smoothly, with little or no decomposition at around 98°C,Template:Citation neededTemplate:Dubious which is below the boiling point of water. The smoke produced from cocaine base is usually described as having a very distinctive, pleasant taste.
In contrast, cocaine hydrochloride does not vaporize until heated to a much higher temperature (about 197°C), and considerable decomposition/burning occurs at these high temperatures. This effectively destroys some of the cocaine, and yields a sharp, acrid, and foul-tasting smoke.
Smoking or vaporizing cocaine and inhaling it into the lungs produces an almost immediate "high" that can be very powerful (and addicting) quite rapidly – this initial crescendo of stimulation is known as a "rush". While the stimulating effects may last for hours, the euphoric sensation is very brief, prompting the user to smoke more immediately.
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.<ref>Template:Cite journalTemplate:Dead link</ref> 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
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 (parachute) it. This is sometimes called a "snow bomb."
Coca leaves are typically mixed with an alkaline substance (such as lime) and chewed into a wad that is retained in the mouth between gum and cheek (much in the same as chewing tobacco is chewed) and sucked of its juices. The juices are absorbed slowly by the mucous membrane of the inner cheek and by the gastrointestinal tract when swallowed. Alternatively, coca leaves can be infused in liquid and consumed like tea. Ingesting coca leaves generally is an inefficient means of administering cocaine. Advocates of the consumption of the coca leaf state that coca leaf consumption should not be criminalized as it is not actual cocaine, and consequently it is not properly the illicit drug. Because cocaine is hydrolyzed and rendered inactive in the acidic stomach, it is not readily absorbed when ingested alone. Only when mixed with a highly alkaline substance (such as lime) can it be absorbed into the bloodstream through the stomach. The efficiency of absorption of orally administered cocaine is limited by two additional factors. First, the drug is partly catabolized by the liver. Second, capillaries in the mouth and esophagus constrict after contact with the drug, reducing the surface area over which the drug can be absorbed. Nevertheless, cocaine metabolites can be detected in the urine of subjects that have sipped even one cup of coca leaf infusion. Therefore, this is an actual additional form of administration of cocaine, albeit an inefficient one.
Orally administered cocaine takes approximately 30 minutes to enter the bloodstream. Typically, only a third of an oral dose is absorbed, although absorption has been shown to reach 60% in controlled settings. Given the slow rate of absorption, maximum physiological and psychotropic effects are attained approximately 60 minutes after cocaine is administered by ingestion. While the onset of these effects is slow, the effects are sustained for approximately 60 minutes after their peak is attained.
Contrary to popular belief, both ingestion and insufflation result in approximately the same proportion of the drug being absorbed: 30 to 60%. Compared to ingestion, the faster absorption of insufflated cocaine results in quicker attainment of maximum drug effects. Snorting cocaine produces maximum physiological effects within 40 minutes and maximum psychotropic effects within 20 minutes, however, a more realistic activation period is closer to 5 to 10 minutes, which is similar to ingestion of cocaine. Physiological and psychotropic effects from nasally insufflated cocaine are sustained for approximately 40–60 minutes after the peak effects are attained.<ref>Template:Cite journal; Jones, supra note 19; Wilkinson et al., Van Dyke et al.</ref>
Coca tea, an infusion of coca leaves, is also a traditional method of consumption. The tea has often been recommended for travelers in the Andes to prevent altitude sickness.<ref name=luks>Andrew M. Luks, et al. "Wilderness Medical Society Consensus Guidelines for the Prevention and Treatment of Acute Altitude Illness". Wilderness & Environmental Medicine, 21, 146–155 (2010).</ref> However, its actual effectiveness has never been systematically studied.<ref name=luks/> 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.”<ref>Template:Cite journal</ref> While the packaging claimed it had been "decocainized," no such process had actually taken place. The article stated that drinking two cups of the tea per day gave a mild stimulation, increased heart rate, and mood elevation, and the tea was essentially harmless. Despite this, the DEA seized several shipments in Hawaii, Chicago, Illinois, Georgia, and several locations on the East Coast of the United States, and the product was removed from the shelves.
Nasal 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<ref name="Volkow">Template:Cite journal</ref> 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 vesselsTemplate:Spaced ndashand therefore blood and oxygen/nutrient flowTemplate:Spaced ndashto that area. Nosebleeds after cocaine insufflation are due to irritation and damage of mucus membranes by foreign particles and adulterants and not the cocaine itself; as a vasoconstrictor, cocaine acts to reduce bleeding.
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.<ref>cesar.umd.edu – Cocaine terminology</ref> The amount of cocaine in a line varies widely from person to person and occasion to occasion (the purity of the cocaine is also a factor), but one line is generally considered to be a single dose and is typically 35 mg (a "bump") to 100 mg (a "rail")Template:Dubious. As tolerance builds rapidly in the short-term (hours), many lines are often snorted to produce greater effects.
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.<ref>Template:Cite web</ref>
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".<ref>Template:Cite web</ref> In a study<ref name="Volkow" /> 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. Additionally, because cocaine is a vasoconstrictor, and usage often entails multiple injections within several hours or less, subsequent injections are progressively more difficult to administer, which in turn may lead to more injection attempts and more sequelae from improperly performed injection.
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.
Template:See also 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.<ref>Appendix B: Production of Cocaine Hydrochloride and Cocaine Base, US Justice Dep.</ref> 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.<ref name="Volkow" />
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.<ref>Template:Cite news</ref> These are sometimes called "stems", "horns", "blasters" and "straight shooters". A small piece of clean heavy copper or occasionally stainless steel scouring padTemplate:Spaced ndashoften called a "brillo" (actual Brillo pads contain soap, and are not used), or "chore", named for Chore Boy brand copper scouring pads,Template:Spaced ndashserves 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 longTemplate:Spaced ndashusually 5 to 15 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.
Little research has been focused on the suppository (anal or vaginal insertion) method of administration, also known as "plugging". This method of administration is commonly administered using an oral syringe. Cocaine can be dissolved in water and withdrawn into an oral syringe which may then be lubricated and inserted into the anus or vagina before the plunger is pushed. Anecdotal evidence of its effects are infrequently discussed, possibly due to social taboos in many cultures. The rectum and the vaginal canal is where the majority of the drug would likely be taken up, through the membranes lining its walls.Template:Citation needed
Mechanism of action
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<ref>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)</ref>) The most extensively studied effect of cocaine on the central nervous system is the blockade of the dopamine transporter protein. Dopamine transmitter released during neural signaling is normally recycled via the transporter; i.e., the transporter binds the transmitter and pumps it out of the synaptic cleft back into the presynaptic neuron, where it is taken up into storage vesicles. Cocaine binds tightly at the dopamine transporter forming a complex that blocks the transporter's function. The dopamine transporter can no longer perform its reuptake function, and thus dopamine accumulates in the synaptic cleft. This results in an enhanced and prolonged postsynaptic effect of dopaminergic signaling at dopamine receptors on the receiving neuron. Prolonged exposure to cocaine, as occurs with habitual use, leads to homeostatic dysregulation of normal (i.e. without cocaine) dopaminergic signaling via down-regulation of dopamine receptors and enhanced signal transduction. The decreased dopaminergic signaling after chronic cocaine use may contribute to depressive mood disorders and sensitize this important brain reward circuit to the reinforcing effects of cocaine (for example, 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.<ref name="pmid10529820">Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref>
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.<ref>Template:Cite journal</ref>
Sigma receptors are affected by cocaine, as cocaine functions as a sigma ligand agonist.<ref>Template:Cite web</ref> Further specific receptors it has been demonstrated to function on are NMDA and the D1 dopamine receptor.<ref>Template:Cite journal</ref>
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 and 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.<ref>Template:Cite web</ref> 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<ref>Template:Cite journal</ref> and clock genes<ref>Template:Cite journal</ref> 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.
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.<ref>Template:Cite journal</ref>
Metabolism and excretion
Cocaine is extensively metabolized, primarily in the liver, with only about 1% excreted unchanged in the urine. The metabolism is dominated by hydrolytic ester cleavage, so the eliminated metabolites consist mostly of benzoylecgonine (BE), the major metabolite, and other significant metabolites in lesser amounts such as ecgonine methyl ester (EME) and ecgonine. Further minor metabolites of cocaine include norcocaine, p-hydroxycocaine, m-hydroxycocaine, p-hydroxybenzoylecgonine (pOHBE), and m-hydroxybenzoylecgonine.<ref>Template:Cite journal</ref> 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; or the binding of other exogenous subsumed chemicals in administration concurrently with any constituent cocaine molecule conformation in vivo to be enumerated within the user as a conditionate dependant on tertiary measures to form as a novel metabolite too vast in potential instances to account for beyond the tertiary measure of their otherwise notability.
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.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>
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.<ref>Template:Cite news</ref><ref>Template:Cite journal</ref>
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.<ref>R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 9th edition, Biomedical Publications, Seal Beach, CA, 2011, pp. 390–394.</ref> In 2011, researchers at John Jay College of Criminal Justice reported that dietary zinc supplements can mask the presence of cocaine and other drugs in urine. Similar claims have been made in web forums on that topic.<ref>Template:Cite journal</ref>
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 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.<ref>Template:Cite journal</ref>
For over a thousand years South American indigenous peoples have chewed the leaves of Erythroxylon coca, a plant that contains vital nutrients as well as numerous alkaloids, including cocaine. The coca leaf was, and still is, chewed almost universally by some indigenous communities. The remains of coca leaves have been found with ancient Peruvian mummies, and pottery from the time period depicts humans with bulged cheeks, indicating the presence of something on which they are chewing.<ref name="mummies">Template:Cite journal</ref> There is also evidence that these cultures used a mixture of coca leaves and saliva as an anesthetic for the performance of trepanation.<ref name="trepanning">Template:Cite journal</ref>
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.Template:Citation needed But after discovering that these claims were true, they legalized and taxed the leaf, taking 10% off the value of each crop.<ref>Template:Cite news</ref> In 1569, Nicolás Monardes described the practice of the natives of chewing a mixture of tobacco and coca leaves to induce "great contentment": Template:Quote
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. Template:Citation needed Additionally contemporary conditions of sea-shipping from South America could degrade the cocaine in the plant samples available to Europeans. Template:Citation needed
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.<ref>Template:Cite journal</ref>
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.<ref name=nie1860>Template:Cite journal</ref>
Niemann described every step he took to isolate cocaine in his dissertation titled Über eine neue organische Base in den Cocablättern (On a New Organic Base in the Coca Leaves), which was published in 1860—it earned him his Ph.D. and is now in the British Library. He wrote of the alkaloid's "colourless transparent prisms" and said that, "Its solutions have an alkaline reaction, a bitter taste, promote the flow of saliva and leave a peculiar numbness, followed by a sense of cold when applied to the tongue." Niemann named the alkaloid "cocaine" from "coca" (from Quechua "cuca") + suffix "ine".<ref name=nie1860/><ref>Template:OEtymD</ref> 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.<ref name="Humphrey2001" /> The synthesis started from tropinone, a related natural product and took five steps.
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 from the leg that had been immersed in salt water.<ref name="anrep_frog">Template:Cite journal</ref>
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,<ref>Template:Cite journal</ref> and James Leonard Corning demonstrated peridural anesthesia.<ref>Template:Cite journal</ref> 1898 saw Heinrich Quincke use cocaine for spinal anesthesia.
Today, cocaine has very limited medical use. See the section Cocaine as a local anesthetic
In 1859, an Italian doctor, Paolo Mantegazza, returned from Peru, where he had witnessed first-hand the use of coca by the natives. He proceeded to experiment on himself and upon his return to Milan he wrote a paper in which he described the effects. In this paper he declared coca and cocaine (at the time they were assumed to be the same) as being useful medicinally, in the treatment of "a furred tongue in the morning, flatulence, and whitening of the teeth."
A chemist named Angelo Mariani who read Mantegazza's paper became immediately intrigued with coca and its economic potential. In 1863, Mariani started marketing a wine called Vin Mariani, which had been treated with coca leaves, to become cocawine. The ethanol in wine acted as a solvent and extracted the cocaine from the coca leaves, altering the drink's effect. It contained 6 mg cocaine per ounce of wine, but Vin Mariani which was to be exported contained 7.2 mg per ounce, to compete with the higher cocaine content of similar drinks in the United States. A "pinch of coca leaves" was included in John Styth Pemberton's original 1886 recipe for Coca-Cola, though the company began using decocainized leaves in 1906 when the Pure Food and Drug Act was passed. The actual amount of cocaine that Coca-Cola contained during the first twenty years of its production is practically impossible to determine.Template: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 Freud published his work Über Coca, in which he wrote that cocaine causes:
In 1885 the U.S. manufacturer Parke-Davis sold cocaine in various forms, including cigarettes, powder, and even a cocaine mixture that could be injected directly into the 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."
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.<ref name= barlow>Barlow, William. "Looking Up At Down": The Emergence of Blues Culture. Temple University Press (1989), p. 207. ISBN 978-0-87722-583-6.</ref>
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.<ref name="dominic_streatfeild">Template:Cite book</ref>
Template:Globalize The gears of prohibition began churning long before the Harrison Act was passed by Congress in 1914 – a law requiring cocaine and narcotics to be dispensed only with a doctor's order.<ref name="Madge 2001 106">Template:Cite book</ref> Before this moment, various factors and groups acted on primarily a state level influencing a move towards prohibition and away from a laissez-faire attitude.<ref name="Spillane 2000 121">Template:Cite book</ref>
By 1903 cocaine consumption had grown to about five times that of 1890.<ref name="Spillane 2000 91">Template:Cite book</ref> Non-medical users accounted for almost the entire increase as cocaine-users extended outside the middle-aged, white, professional class.<ref name="Spillane 2000 91"/> Cocaine became associated with laborers, youths, blacks and the urban underworld.<ref name="Spillane 2000 91"/>
The popularization of cocaine first began with laborers who used cocaine as a stimulant to increase productivity.<ref name="Spillane 2000 91"/> Cocaine was often supplied by employers.<ref name="Madge 2001 84">Template:Cite book</ref> Cocaine was often supplied to African American workers, who many employers believed were better physical workers; cocaine was thought to provide added strength and constitution and according to the Medical News, made blacks “impervious to the extremes of heat and cold.”<ref name="Spillane 2000 91"/> However, users of cocaine quickly acquired a reputation as dangerous and in 1897, the first state bill of control for cocaine sales came from a mining county in Colorado.<ref>Template:Cite book</ref>
The popularization of cocaine use was not confined to African Americans or simple laborers. In Northern cities, cocaine use increased amongst poorer people – in fact, cocaine was often cheaper than alcohol.<ref name="Madge 2001 84"/> In the Northeast in particular, cocaine became popular amongst workers in factories, textile mills and on rail roads.<ref name="Spillane 2000 93">Template:Cite book</ref> In some instances, cocaine use supplemented or replaced caffeine as the drug-of-choice to keep workers awake and working overtime.<ref name="Spillane 2000 93"/>
This period of increasing cocaine use followed with increasing fears that young children were being preyed upon and forced into cocaine addiction.<ref name="Gootenberg 1999 33">Template:Cite book</ref> Indeed, it was even thought that cocaine was used to seduce young girls away from their homes and cause them to be addicted and dependent upon the substance and therefore fall prey to an inescapable cycle of prostitution.<ref>Template:Cite book</ref> Fears of the corruption of the youth by cocaine were popular and widespread but there is little evidence to support their veracity.<ref name="Gootenberg 1999 33"/>
Mainstream media reported cocaine epidemics as early as 1894 in Dallas, Texas.<ref name="Spillane 2000 94">Template:Cite book</ref> Reports of the cocaine epidemic would foreshadow a familiar theme in later so-called epidemics, namely that cocaine presented a social threat more dangerous than simple health effects and had insidious results when used by blacks and members of the lower class.<ref name="Spillane 2000 94"/> Similar anxiety-ridden reports appeared throughout cities in the South leading some to declare that “the cocaine habit has assumed the proportions of an epidemic among the colored people.”<ref name="Spillane 2000 94"/> In 1900, state legislatures in Alabama, Georgia and Tennessee considered anti-cocaine bills for the first time.<ref name="Spillane 2000 94"/>
Hyperbolic reports of the effect of cocaine on African Americans went hand-in-hand with this hysteria. In 1901, the Atlanta Constitution reported that “Use of the drug [cocaine] among negroes is growing to an alarming extent.”<ref name="Madge 2001 85">Template:Cite book</ref> The New York Times reported that under the influence of cocaine, “sexual desires are increased and perverted … peaceful negroes become quarrelsome, and timid negroes develop a degree of 'Dutch courage' that is sometimes almost incredible.”<ref name="Madge 2001 89">Template:Cite book</ref> A medical doctor even wrote “cocaine is often the direct incentive to the crime of rape by the negroes.”<ref name="Madge 2001 89"/> To complete the characterization, a judge in Mississippi declared that supplying a “negro” with cocaine was more dangerous than injecting a dog with rabies.<ref>Template:Cite book</ref>
These attitudes not only influenced drug law and policy but also led to increased violence against African Americans. In 1906, a major race riot led by whites erupted; it was sparked by reports of crimes committed by black ‘cocaine fiends.’<ref name="Madge 2001 85"/> Indeed, white-led, race riots spawning from reports of blacks under the influence of cocaine were not uncommon.<ref>Template:Cite book</ref> Police in the South widely adopted the use of a heavier caliber handguns so as to better stop a cocaine-crazed black person – believed to be empowered with super-human strength.<ref>Template:Cite book</ref> Another dangerous myth perpetuated amongst police was that cocaine imbued African Americans with tremendous accuracy with firearms and therefore police were better advised to shoot first in questionable circumstances.<ref>Template:Cite book</ref>
Ultimately public opinion rested against the cocaine user. Criminality was commonly believed to be a natural result of cocaine use.<ref name="Spillane 2000 119">Template:Cite book</ref> Much of the influence for these kind of perceptions came from the widespread publicity given to notorious cases.<ref name="Spillane 2000 121"/> While the historical reality of cocaine’s effect on violence and crime is difficult to disentangle from inflamed perceptions, it does appear that public opinion was swayed by the image of the violent, cocaine-crazed fiend and pushed over the edge by a few violent episodes.<ref name="Spillane 2000 119"/> It was an image of the cocaine-user that carried acute racial overtones.<ref name="Spillane 2000 121"/>
Before any substantive federal regulation of cocaine, state and local municipalities evoked their own means to regulate cocaine. Because of the initial lack of targeted legislation, on both federal and state level, the most typical strategy by law enforcement was the application of nuisance laws pertaining to vagrancy and disturbing the peace.<ref>Template:Cite book</ref> Subsequent legislative actions aimed at controlling the distribution of cocaine rather than its manufacture.<ref name="Gootenberg 1999 35">Template:Cite book</ref> Reformers took this approach in part because of legal precedents which made it easier to control distributors such as pharmacies; state and local boards of hearth or boards of pharmacy often took the place of regulatory bodies for controlling the distribution of cocaine.<ref name="Gootenberg 1999 35"/>
Some states took the position of outright banning of all forms of cocaine sale; Georgia was the first to do this in 1902.<ref>Template:Cite book</ref> A New Orleans ordinance banned cocaine sales as well but left an ill-defined exception for therapeutic uses.<ref name="Gootenberg 1999 35"/> A more common requirement was to restrict the sale of cocaine or impose labeling requirements. A 1907 California law limiting sale of cocaine to only those with a physician’s prescription resulted in the arrest of over 50 store owners and clerks in the first year.<ref name="Gootenberg 1999 35"/> A 1913 New York state law limited druggists’ cocaine stocks to under 5 ounces. Labeling requirements initially operated on a state level with some states even going so far as to require that cocaine and cocaine-containing products be labeled as poison.<ref name="Gootenberg 1999 37">Template:Cite book</ref>
Eventually the federal government stepped in and instituted a national labeling requirement for cocaine and cocaine-containing products through the Food and Drug Act of 1906.<ref name="Gootenberg 1999 37"/> The next impactful federal regulation was the Harrison Narcotics Tax Act of 1914. While this act is often seen as the start of prohibition, the act itself was not actually a prohibition on cocaine, but instead setup a regulatory and licensing regime.<ref name="Madge 2001 106"/> The Harrison Act did not recognize addiction as a treatable condition and therefore the therapeutic use of cocaine, heroin or morphine to such individuals was outlawed – leading the Journal of American Medicine to remark, “[the addict] is denied the medical care he urgently needs, open, above-board sources from which he formerly obtained his drug supply are closed to him, and he is driven to the underworld where he can get his drug, but of course, surreptitiously and in violation of the law.”<ref>Template:Cite book</ref> The Harrison Act left manufacturers of cocaine untouched so long as they met certain purity and labeling standards.<ref name="Gootenberg 1999 40">Template:Cite book</ref> Despite that cocaine was typically illegal to sell and legal outlets were more rare, the quantities of legal cocaine produced declined very little.<ref name="Gootenberg 1999 40"/> Legal cocaine quantities did not decrease until the Jones-Miller Act of 1922 put serious restrictions on cocaine manufactures.<ref name="Gootenberg 1999 40"/>
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. Template:Citation needed
Cocaine use is prevalent across all socioeconomic strata, including age, demographics, economic, social, political, religious, and livelihood. Template:Citation needed
The estimated U.S. cocaine market exceeded $70 billion in street value for the year 2005, exceeding revenues by corporations such as Starbucks.<ref>Template:Cite web</ref><ref>Template:Cite webTemplate:Dead link</ref> 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." <ref>Template:Cite web</ref> 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.
It was reported in October 2010 that the use of cocaine in Australia has doubled since monitoring began in 2003.<ref>Template:Cite news</ref>
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.Template: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.Template:Or 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.<ref>Template:Cite web</ref>
Society and culture
Template:Main 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.
In 2004, according to the United Nations, 589 tonnes of cocaine were seized globally by law enforcement authorities. Colombia seized 188 t, the United States 166 t, Europe 79 t, Peru 14 t, Bolivia 9 t, and the rest of the world 133 t.<ref name="un-wdr2006">Template:Cite book</ref>
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.Template:Citation needed
Colombia is the world's leading producer of cocaine.<ref name="CIA World Factbook">Colombia. CIA World Factbook</ref> 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.
An interview with a coca farmer published in 2003 described a mode of production by acid-base extraction that has changed little since 1905. Roughly 625 pounds of leaves were harvested per hectare, six times per year. The leaves were dried for half a day, then chopped into small pieces with a strimmer and sprinkled with a small amount of powdered cement (replacing sodium carbonate from former times). Several hundred pounds of this mixture was soaked in Template:Convert of gasoline for a day, then the gasoline was removed and the leaves were pressed for remaining liquid, after which they could be discarded. Then battery acid (weak sulfuric acid) was used, one bucket per 25 kilograms of leaves, to create a phase separation in which the cocaine free base in the gasoline was acidified and extracted into a few buckets of "murky-looking smelly liquid". Once powdered caustic soda was added to this, the cocaine precipitated and could be removed by filtration through a cloth. The resulting material, when dried, was termed pasta and sold by the farmer. The 3750 pound yearly harvest of leaves from a hectare produced Template:Convert of pasta, approximately 40–60% cocaine. Repeated recrystallization from solvents, producing pasta lavada and eventually crystalline cocaine, were performed at specialized laboratories after the sale.<ref>Template:Cite book</ref>
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.
|Net cultivation (km2)||1875||2218||2007.5||1663||1662|
|Potential pure cocaine production (tonnes)||770||925||830||680||645|