Cocaine

Effects and Addictive Nature

Cocaine blocks pain sensation and stimulates the central nervous system, producing a sudden increase in heart rate, temperature, and blood pressure. In the brain, it blocks the synaptic reabsorption of certain neurotransmitters (in particular dopamine). The resultant buildup of neurotransmitters causes pleasurable sensations to be passed along the neural pathways over and over again, creating a feeling of profound well-being, self-confidence, and alertness. It is accompanied by lack of hunger. The effect lasts for 10 to 30 minutes, and the user begins to crave more immediately as the neurotransmitter supply is exhausted. This pattern has led to cocaine's being described as “neuropsychologically addicting” in recognition that traditional definitions of physical vs. psychological addiction do not neatly fit in this case. Most cocaine addicts in treatment report some control over their use for the first two to four years, giving them the illusion that addiction will not develop.

Addiction is characterized by binges (usually of 4 to 24 hours, one to seven times per week), movement to intravenous use or smoking, extreme euphoria, and disregard for anything other than the drug, including food, sleep, sex, family, and survival. The behavior is limited only by the high cost of the drug and its limited availability. Abstinence after a cocaine binge leads to crashing (anxiety, depression, suspiciousness, sleep craving) and withdrawal (absence of pleasure in all things, lack of motivation, and boredom). Many users take other drugs (alcohol, marijuana, heroin) to attenuate these effects. A dangerous combination of cocaine and heroin, known as a “speedball,” is used by some. Withdrawal usually results in further use, often spurred by a conditioned cue such as a specific smell or location linked with cocaine use. If the drug is not taken again there is a gradual lessening of the craving, although conditioned cues may exert an effect years afterward. Long-term use can result in digestive disorders, weight loss, general physical deterioration, and marked deterioration of the nervous system. Most drug-related emergency room visits are cocaine-related.

Modes of Administration; “Crack” Cocaine

Cocaine is either snorted (sniffed), swallowed, injected, or smoked. Habitual snorting can result in serious damage to the nasal mucous membranes; shared needles put the user at increased risk of HIV infection. The street drug comes in the form of a white powder, cocaine hydrochloride. The hydrochloride salt and the cutting agents are removed to create the pure base product “freebase.” Freebase is smoked and reaches the brain in seconds. “Crack” cocaine, also called “rock,” is a form of freebase that comes in small lumps and makes a crackling sound when heated. It is relatively inexpensive, but must be repeated often.

Crack cocaine magnifies the effects of cocaine and is considered to be more highly and more quickly addictive than snorted cocaine. It causes a very abrupt increase in heart rate and blood pressure that can lead to heart attack and stroke even in young people with no history of vascular disease, sometimes the first time the drug is used. It also crosses the placental barrier; babies born to crack-addicted mothers go through withdrawal and are at a higher risk of stroke, cerebral palsy, and other birth defects.

Treatment

Treatment focuses on disruption of the addict's pattern of binges, followed by prevention of relapses. Counseling combined with treatments such as acupuncture and administration of antidepressants (e.g., desipramine) has met with some success. Treatment is often complicated by underlying social problems, mental illness, and the use of multiple drugs.

Production and Distribution

Most coca is grown in Peru, Bolivia, and Colombia. The farmers, for whom it is a relatively well-paying crop, harvest and dry the leaves, which are then processed into coca paste. Cocaine base is extracted from the paste in informal laboratories, usually in Peru or Bolivia. Further processing continues in Colombia, where the white powder, cocaine hydrochloride, is produced for export. Once in the United States, the cocaine is cut (diluted) with ingredients such as lactose, and sold or further processed into crack.

Import and production have been controlled by enormously powerful cartels such as the Medellín and Cali cartels in Colombia; the highly armed cartels have infiltrated governments and corrupted officials and have been held responsible for assassinations of public officials. Drug trafficking reached the highest levels of government and was at least in part responsible for the U.S. invasion of Panama in 1989 and the arrest and subsequent conviction of Panama's de facto leader, Manuel Noriega.

History of Cocaine Use

Andean Indians have long chewed leaves of the coca plant to decrease hunger and increase their stamina for work. Chewing the leaves produces no “high.” Cocaine was first extracted from coca in the 19th cent. and was at first hailed as a miracle drug. By the 1880s in the United States it was freely prescribed by physicians for such maladies as exhaustion, depression, and morphine addiction and was available in many patent medicines. After users and physicians began to realize its dangers and various regulations were enacted, its use decreased, and by the 1920s the epidemic had abated.

Another epidemic began in the United States in the 1970s and peaked in the mid-1980s; again the drug was at first considered harmless. With the latter epidemic and its accompanying crack epidemic (beginning in 1985 and peaking in 1988) violence in crack-infested neighborhoods increased dramatically. Young people with few other opportunities were lured by the power and money of being crack dealers; most carried guns and many were murdered in drug-gang wars that ensued. By the late 1990s the cocaine and crack epidemic had subsided as heroin regained popularity among illicit drug users.

Bibliography

See publications of the Drugs & Crime Data Center and Clearinghouse, the Bureau of Justice Statistics Clearinghouse, and the National Clearinghouse for Alcohol and Drug Information.

Cocaine
Systematic (IUPAC) name
methyl (1R,2R,3S,5S)-3- (benzoyloxy)-8-methyl-8-azabicyclo[3.2.1] octane-2-carboxylate
Identifiers
CAS number	50-36-2
ATC code	N01BC01 R02AD03, S01HA01, S02DA02
PubChem	5760
DrugBank	APRD00080
Chemical data
Formula	C17H21NO4
Mol. mass	303.353 g/mol
Physical data
Melt. point	195 °C (383 °F)
Solubility in water	1800 mg/mL (20 °C)
Pharmacokinetic data
Bioavailability	Oral: 33% Nasal: 19% (11%–26%)[1]
Metabolism	Hepatic CYP3A4
Half life	1 hour
Excretion	Renal (benzoylecgonine and ecgonine methyl ester)
Therapeutic considerations
Pregnancy cat.	C
Legal status	Controlled (S8)(AU) Schedule I(CA) Class A(UK) Schedule II(US)
Dependence Liability	High
Routes	Topical, Oral, Insufflation, IV, PO

Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is both a stimulant of the central nervous system and an appetite suppressant, giving rise to what has been described as a euphoric sense of happiness and increased energy. It is most often used recreationally for this effect. Because of the way it effects the mesolimbic reward pathway, cocaine is addictive. Nevertheless, cocaine is formally used in medicine as a topical anesthetic, specifically in eye, nose and throat surgery.

Its possession, cultivation, and distribution are illegal for non-medicinal and non-government sanctioned purposes in virtually all parts of the world. Although its free commercialization is illegal and has been severely penalized in virtually all countries, its use worldwide remains widespread in many social, cultural, and personal settings.

History

Originally consumed without any processing, the chewing of coca leaves was popular among South American natives long before the arrival of the Spanish in the 16th century. The leaves were chewed in a manner consistent with modern use of coffee, chewed for a small burst of energy or stamina. The Spanish explorers noticed how the natives used the coca leaves and themselves partook in some cases, but the practice of chewing the raw leaves did not become especially popular among Europeans. Coca's turning point in Europe came in 1860 when Albert Niemann extracted pure cocaine powder from coca leaves. This refinement allowed the use of cocaine in many different medicinal products and beverages, most notably Coca-Cola and Vin Mariani. Freud began experimenting with cocaine around this time, consuming small quantities to combat depression, sharing his experience with other European physicians who also found cocaine to be an effective topical anesthetic. Freud became a fervent supporter of the use of cocaine as an anti-depressant, even publishing a manuscript detailing its virtues. Conan Doyle stood alone in the late 19th century depicting the destructive qualities of cocaine in his consulting detective, Sherlock Holmes.^[2] As cocaine's popularity increased, health risks were noted and seized upon by American legislators, who made the substance all but illegal in 1916.

Pharmacology

Appearance

A pile of cocaine hydrochloride

A piece of compressed cocaine powder

Cocaine in its purest form is a white, pearly product. Cocaine appearing in powder form is a salt, typically cocaine hydrochloride (CAS 53-21-4). Street market cocaine is frequently adulterated or “cut” with various powdery fillers to increase its weight; the substances most commonly used in this process are baking soda; sugars, such as lactose, dextrose, inositol, and mannitol; and local anesthetics, such as lidocaine 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.^[3] 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 white to a yellowish cream to a light brown. Its texture will also depend on the adulterants, origin and processing of the powdered cocaine, and the method of converting the base. It ranges from a crumbly texture, sometimes extremely oily, to a hard, almost crystalline nature.

Forms of cocaine

Cocaine sulfate

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

Freebase

Main article: Freebase (chemistry)

As the name implies, “freebase” is the base form of cocaine, as opposed to the salt form of cocaine hydrochloride. Whereas cocaine hydrochloride is extremely soluble in water, cocaine base is insoluble in water and is therefore not suitable for drinking, snorting or injecting. Whereas cocaine hydrochloride is not well-suited for smoking because the temperature at which it vaporizes is very high, and close to the temperature at which it burns; however, cocaine base vaporizes at a much lower 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, reaching the brain in about five seconds. The rush is much more intense than snorting the same amount of cocaine nasally, but the effects do not last as long. The peak of the freebase rush is over almost as soon as the user exhales the vapor, but the high typically lasts 5–10 minutes afterward. What makes freebasing particularly dangerous is that users typically do not wait that long for their next hit and will continue to smoke freebase until none is left. These effects are similar to those that can be achieved by injecting or “slamming” cocaine hydrochloride, but without the risks associated with intravenous drug use (though there are other serious risks associated with smoking freebase).

Freebase cocaine is produced by first dissolving cocaine hydrochloride in water. Once dissolved in water, cocaine hydrochloride (Coc HCl) dissociates into protonated cocaine ion (Coc-H⁺) 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. The following net chemical reaction takes place:

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

Handling diethyl ether is dangerous because ether is extremely flammable, its vapors are heavier than air and can "creep" from an open bottle, and in the presence of oxygen it can form peroxides, which can spontaneously combust. Demonstrative of the dangers of the practice, comedian Richard Pryor used to perform a skit in which he poked fun at himself over a 1980 incident in which he caused an explosion and ignited himself attempting to smoke "freebase", presumably while still wet with ether (though his ex wife Jennifer Lee Pryor said that he poured high-proof rum over his body and torched himself in a drug psychosis).

Crack cocaine

Main article: Crack cocaine

Due to the dangers of using ether to produce pure freebase cocaine, cocaine producers began to omit the step of removing the freebase cocaine precipitate from the ammonia mixture. Typically, filtration processes are also omitted. The end result of this process is that the cut, in addition to the ammonium salt (NH₄Cl), remains in the freebase cocaine after the mixture is evaporated. The “rock” that is thus formed also contains a small amount of water. Sodium bicarbonate (baking soda) is also preferred in preparing the freebase, for when commonly "cooked" the ratio is 50/50 to 40/60% cocaine/bicarbonate. This acts as a filler which extends the overall profitability of illicit sales. Crack cocaine may be reprocessed in small quantities with water (users refer to the resultant product as "cookback"). This removes the residual bicarbonate, and any adulterants or cuts that have been used in the previous handling of the cocaine and leaves a relatively pure, anhydrous cocaine base.

When the rock is heated, this water boils, making a crackling sound (hence the onomatopoetic “crack”). Baking soda is now most often used as a base rather than ammonia for reasons of lowered stench and toxicity; however, any weak base can be used to make crack cocaine. Strong bases, such as sodium hydroxide, tend to hydrolyze some of the cocaine into non-psychoactive ecgonine.

Chewed/eaten

Coca leaves are typically mixed with an alkaline substance (such as lime) and chewed into a wad that is retained in the mouth between gum and cheek (much in the same as chewing tobacco is chewed) and sucked of its juices. The juices are absorbed slowly by the mucous membrane of the inner cheek and by the gastro-intestinal 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.^[4]

Mate de coca or coca-leaf infusion is also a traditional method of consumption and is often recommended in coca producing countries, like Peru and Bolivia, to ameliorate some symptoms of altitude sickness. This method of consumption has been practiced for many centuries by the native tribes of South America. One specific purpose of ancient coca leaf consumption was to increase energy and reduce fatigue in messengers who made multi-day quests to other settlements.

In 1986 an article in the Journal of the American Medical Association revealed that U.S. health food stores were selling dried coca leaves to be prepared as an infusion as “Health Inca Tea.”^[5] 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.^[6] Nevertheless, today coca leaf teabags (named "mate de coca") illegally smuggled into the U.S. can be readily purchased online via Internet stores and even eBay.

Insufflation

Cocaine lines on a mirror

Insufflation (known colloquially as "snorting," "sniffing," or "blowing") is the most common method of ingestion of recreational powdered cocaine in the Western world. Cocaine is not inhaled using this method. The drug coats and is absorbed through the mucous membranes lining the sinuses. When insufflating cocaine, absorption through the nasal membranes is approximately 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^[7] of cocaine users, the average time taken to reach peak subjective effects was 14.6 minutes. Chronic use can result in ongoing rhinitis and necrosis of the nasal membranes.^{[citation needed]} Any damage to the inside of the nose is because cocaine highly constricts blood vessels – and therefore blood and oxygen/nutrient flow – to that area. If this restriction of adequate blood supply is severe enough and, especially prolonged enough, the tissue there can die.^{[citation needed]}

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, and (clean) tampon applicators are often used to insufflate cocaine. Such devices are often called "tooters" by users. The cocaine typically is poured onto a flat, hard surface (such as a mirror) and divided into "bumps", "lines" or "rails", and then insufflated.^[8] The amount of cocaine in a line varies widely from person to person and occasion to occasion (the purity of the cocaine is also a factor), but one line is generally considered to be a single dose and is typically 35 mg (a "bump") to 100 mg (a "rail"). As tolerance builds rapidly in the short-term (hours), many lines are often snorted to produce greater effects.

A study by Bonkovsky and Mehta published in Am Acad Dermatol (2001 Feb;44(2):159-82) reported that, just like shared needles, the sharing of straws used to "snort" cocaine can spread blood diseases such as Hepatitis C.^[9]

Injected

Drug injection provides the highest blood levels of drug in the shortest amount of time. Upon injection, cocaine reaches the brain in a matter of seconds, and the exhilarating rush that follows can be so intense that it induces some users to vomit uncontrollably which causes bleeding of the esophagus.^{[citation needed]} In a study^[7] 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. 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 (in Chicago), River Phoenix and Layne Staley (in Seattle).

Experimentally, cocaine injections can be delivered to animals such as fruit flies to study the mechanisms of cocaine addiction.^[10]

Smoked

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 on the average, four inches long. These are sometimes called "stems", "horns", "blasters" and "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 popular (usually pejorative) term for crack pipes is "glass dick." Tire pressure gauges have also been used by breaking off their tops and removing their numbered sticks. These can be purchased at most convenience stores or gas stations.

A small piece (approximately one inch) of clean heavy copper or occasionally stainless steel scouring pad—often called a "brillo" or "chore", from the scouring pads of the same name—is placed into one end of the tube and carefully packed down to approximately three-quarters of an inch. Prior to insertion, the "brillo" is burnt off to remove any oily coatings that may be present. It then serves as a reduction base and flow modulator in which the "rock" can be melted and boiled to vapor.

Another method is to use a deep socket, typically 12 mm, wrapped with electrical tape. Instead of Chore Boy, users typically employ high grade (very fine) speaker wire rolled into a ball as the filter medium. A Zippo lighter is often used because of its stronger flame, but the taste of naphtha is quite noticeable. However, the socket is practically indestructible and inconspicuous.

A less sophisticated but common method is to use a discarded soda can and puncture several small holes on the side of the can near its bottom. Tobacco ash is then placed in the divot created with the drug placed on top. The mouthpiece is the original opening of the can, creating a cost-effective alternative to a proper crack pipe.

To smoke the "rock," it is placed at the end of the pipe, closest to the filter. The other end is then placed in the user's mouth and a flame from a cigarette lighter or hand-held torch is held under the "rock." As the "rock" is heated, it melts and heats into vapor, which the user inhales as smoke.

The effects, felt almost immediately after smoking, are very intense and do not last long — usually five to fifteen minutes. In a study^[7] performed on crack cocaine users, the average time taken for them to reach their peak subjective "high" was 1.4 minutes. Most (especially frequent) users crave more immediately after the peak. "Crack houses" depend on these cravings by providing a place for smoking crack to its users, and a ready supply of small bags for sale.

A heavily-used crack pipe tends to fracture at its end due to overheating from the flame used to heat the crack, typically because users attempt to inhale every last bit of the drug on the metal wool filter. The end is often broken further as users "push" the pipe. "Pushing" is a technique used to partially recover crack that hardens on the inside wall of the pipe as the pipe cools. This is accomplished by pushing the metal wool filter through the pipe from one end to the other in order to collect the build-up inside the pipe, which is a very pure and potent form of the base. 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. Users will often remove the most jagged edges and continue using the pipe until it becomes so short that it burns their lips and fingers. To continue using the pipe, users will sometimes wrap a small piece of paper or cardboard around its one end and hold it in place with a rubber band or adhesive tape. Of course, not all crack cocaine users will allow it to get that short, and will instead opt for a new or different pipe. The telltale 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. The language referring to paraphernalia and practices of smoking cocaine vary across the United States, as do the packaging methods in the street level sale.

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", "jay bomb", "shake and bake", a "turbo", a "yolabowla", "SnowCaps", "Canadian Health Care", "B-51er", a "cocoapuff", a "dirty", a "woo", or "geeking." 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.

Powdered 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. This cigarette is then referred to as a "Jimmy". Alternatively, cocaine powder may be sprinkled onto the marijuana in a blunt or possibly a joint and then smoked. This is known as a "Chewy" or may also be referred to by one of the names mentioned above for crack-laced marijuana. When a marijuana bowl is laced with cocaine powder, it is often referred to as a "SnowCap" which is a reference to snow capped mountains."

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.^[11] Importantly, these results also suggest strongly that the primary pharmacologically active metabolite in coca leaf infusions is actually cocaine and not the secondary alkaloids.

The cocaine metabolite benzoylecgonine can be detected in the urine of people a few hours after drinking one cup of coca leaf infusion.

Oral

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

Physical mechanisms

The pharmacodynamics of cocaine involve the complex relationships of neurotransmitters (inhibiting monoamine uptake in rats with ratios of about: Serotonin:Dopamine = 2:3, Serotonin:Norepinephrine = 2:5^[12]) The most extensively studied effect of cocaine on the central nervous system is the blockage of the dopamine transporter protein. Dopamine transmitter released during neural signaling is normally recycled via the transporter; i.e., the transporter binds the transmitter and pumps it out of the synaptic cleft back into the pre-synaptic neuron, where it is taken up into storage vesicles. Cocaine binds tightly at the dopamine transporter forming a complex that blocks the transporter's function. The dopamine transporter can no longer perform its reuptake function, and thus dopamine accumulates in the extracellular space (synaptic cleft). This results in an enhanced and prolonged post-synaptic effect of dopaminergic signalling 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 downregulation of dopamine receptors and enhanced signal transduction. The decreased dopaminergic signalling after chronic cocaine use may contribute to depressive mood disorders and sensitize this important brain reward circuit to the reinforcing effects of cocaine (e.g. enhanced dopaminergic signalling only when cocaine is self-administered). This sensitization contributes to the intractable nature of addiction and relapse.

Dopamine-rich brain regions such as the ventral tegmental area, nucleus accumbens, and prefrontal cortex are frequent targets of cocaine addiction research. Of particular interest is the pathway consisting of dopaminergic neurons originating in the ventral tegmental area that terminate in the nucleus accumbens. This projection may function as a "reward center", in that it seems to show activation is response to drugs of abuse like cocaine in addition to natural rewards like food or sex (R Spanagel and F Weiss, The dopamine hypothesis of reward: past and current status. Trends Neurosci 22 (1999), pp. 521–527). 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 also blocks sodium channels, thereby interfering with the propagation of action potentials; thus, like lignocaine and novocaine, it acts as a local anesthetic. Cocaine also causes vasoconstriction, thus reducing bleeding during minor surgical procedures. The locomotor enhancing properties of cocaine may be attributable to its enhancement of dopaminergic transmission from the substantia nigra. Recent research points to an important role of circadian mechanisms^[13] and clock genes^[14] in behavioral actions of cocaine.

Because nicotine increases the levels of dopamine in the brain, many cocaine users find that consumption of tobacco products during cocaine use enhances the euphoria. This, however, may have undesirable consequences, such as uncontrollable chain smoking during cocaine use (even users who do not normally smoke cigarettes have been known to chain smoke when using cocaine), in addition to the detrimental health effects and the additional strain on the cardiovascular system caused by tobacco.

In addition to irritability, mood disturbances, restlessness, paranoia, and auditory hallucinations, crack can cause several dangerous physical conditions. It can lead to disturbances in heart rhythm and heart attacks, as well as chest pains or even respiratory failure. In addition, strokes, seizures and headaches are common in heavy users.

Cocaine can often cause reduced food intake, many chronic users lose their appetite and can experience severe malnourishment and significant weight loss.

Metabolism and excretion