Cocaine/Crack
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 a stimulant of the central nervous system and an appetite suppressant. Specifically, it is a serotonin-norepinephrine-dopamine reuptake inhibitor, which mediates functionality of such as an exogenous catecholamine transporter ligand. Because of the way it affects the mesolimbic reward pathway, cocaine is addictive.
Its possession, cultivation, and distribution are illegal for non-medicinal and non-government sanctioned purposes in virtually all parts of the world. Although its free commercialization is illegal and has been severely penalized in virtually all countries, its use worldwide remains widespread in many social, cultural, and personal settings.
Coca leaf
For over a thousand years South American indigenous peoples have chewed the coca leaf, a plant that contains vital nutrients as well as numerous alkaloids, including cocaine. The leaf was, and is, chewed almost universally by some indigenous communities—ancient Peruvian mummies have been found with the remains of coca leaves and pottery from the time period depicts humans, cheeks bulged with the presence of something on which they are chewing.
The coca plant, Erythroxylon coca
When the Spaniards conquered South America, they at first ignored aboriginal claims that the leaf gave them strength and energy, and declared the practice of chewing it the work of the Devil. But after discovering that these claims were true, they legalized and taxed the leaf, taking 10% off the value of each crop. In 1569, Nicolás Monardes described the practice of the natives of chewing a mixture of tobacco and coca leaves to induce “great contentment”:
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In 1609, Padre Blas Valera wrote: “Coca protects the body from many ailments, and our doctors use it in powdered form to reduce the swelling of wounds, to strengthen broken bones, to expel cold from the body or prevent it from entering, and to cure rotten wounds or sores that are full of maggots. And if it does so much for outward ailments, will not its singular virtue have even greater effect in the entrails of those who eat it? ”
Although the stimulant and hunger-suppressant properties of coca had been known for many centuries, the isolation of the cocaine alkaloid was not achieved until 1855. Various European scientists had attempted to isolate cocaine, but none had been successful for two reasons: the knowledge of chemistry required was insufficient at the time, and the cocaine was worsened because coca does not grow in the Eurasian region and ruined easily amidst transcontinental shipping.
Niemann described every step he took to isolate cocaine in his dissertation titled Über eine neue organische Base in den Cocablättern (On a New Organic Base in the Coca Leaves), which was published in 1860—it earned him his Ph.D. and is now in the British Library. He wrote of the alkaloid’s “colourless transparent prisms” and said that, “Its solutions have an alkaline reaction, a bitter taste, promote the flow of saliva and leave a peculiar numbness, followed by a sense of cold when applied to the tongue.” Niemann named the alkaloid “cocaine”—as with other alkaloids its name carried the “-ine” suffix (from Latin -ina). The first synthesis and elucidation of the structure of the cocaine molecule was by Richard Willstätter in 1898.
Medicalization
With the discovery of this new alkaloid, Western medicine was quick to exploit the possible uses of this plant. In 1879, Vassili von Anrep, of the University of Würzburg, devised an experiment to demonstrate the analgesic properties of the newly-discovered alkaloid. Carl Koller (a close associate of Sigmund Freud, who would write about cocaine later) experimented with cocaine for ophthalmic usage. In an infamous experiment in 1884, he experimented upon himself by applying a cocaine solution to his own eye and then pricking it with pins. His findings were presented to the Heidelberg Ophthalmological Society. Also in 1884, Jellinek demonstrated the effects of cocaine as a respiratory system anesthetic. In 1885, William Halsted demonstrated nerve-block anesthesia, and James Corning demonstrated peridural anesthesia. 1898 saw Heinrich Quincke use cocaine for spinal anaesthesia. Today, cocaine has very limited medical use. See the section Cocaine as a local anesthetic.
Popularization
In 1859, an Italian doctor, Paolo Mantegazza, returned from Peru, where he had witnessed first-hand the use of coca by the natives. He proceeded to experiment on himself and upon his return to Milan he wrote a paper in which he described the effects. In this paper he declared coca and cocaine (at the time they were assumed to be the same) as being useful medicinally, in the treatment of “a furred tongue in the morning, flatulence, [and] whitening of the teeth.”
A chemist named Angelo Mariani who read Mantegazza’s paper became immediately intrigued with coca and its economic potential. In 1863, Mariani started marketing a wine called Vin Mariani, which had been treated with coca leaves, to become cocawine. The ethanol in wine acted as a solvent and extracted the cocaine from the coca leaves, altering the drink’s effect. It contained 6 mg cocaine per ounce of wine, but Vin Mariani which was to be exported contained 7.2 mg per ounce, to compete with the higher cocaine content of similar drinks in the United States. A “pinch of coca leaves” was included in John Styth Pemberton’s original 1886 recipe for Coca-Cola, though the company began using decocainized leaves in 1906 when the Pure Food and Drug Act was passed. The actual amount of cocaine that Coca-Cola contained during the first twenty years of its production is practically impossible to determine.
In 1879 cocaine began to be used to treat morphine addiction. Cocaine was introduced into clinical use as a local anaesthetic in Germany in 1884, about the same time as Sigmund Freud published his work Über Coca, in which he wrote that cocaine causes exhilaration and lasting euphoria, which in no way differs from the normal euphoria of the healthy person…You perceive an increase of self-control and possess more vitality and capacity for work….In other words, you are simply normal, and it is soon hard to believe you are under the influence of any drug….Long intensive physical work is performed without any fatigue…This result is enjoyed without any of the unpleasant after-effects that follow exhilaration brought about by alcohol….Absolutely no craving for the further use of cocaine appears after the first, or even after repeated taking of the drug…
Cocaine was marketed as a fast-acting anesthetic
In 1885 the U.S. manufacturer Parke-Davis sold cocaine in various forms, including cigarettes, powder, and even a cocaine mixture that could be injected directly into the user’s veins with the included needle. The company promised that its cocaine products would “supply the place of food, make the coward brave, the silent eloquent and … render the sufferer insensitive to pain.”
By the late Victorian era cocaine use had appeared as a vice in literature. For example, it was injected by Arthur Conan Doyle’s fictional Sherlock Holmes. In early 20th-century Memphis, Tennessee, cocaine was sold in neighborhood drugstores on Beale Street, costing five or ten cents for a small boxful. Stevedores along the Mississippi River used the drug as a stimulant, and white employers encouraged its use by black laborers. In 1909, Ernest Shackleton took “Forced March” brand cocaine tablets to Antarctica, as did Captain Scott a year later on his ill-fated journey to the South Pole.
Prohibition
By the turn of the twentieth century, the addictive properties of cocaine had become clear, and the problem of cocaine abuse began to capture public attention in the United States. The dangers of cocaine abuse became part of a moral panic that was tied to the dominant racial and social anxieties of the day. In 1903, the American Journal of Pharmacy stressed that most cocaine abusers were “bohemians, gamblers, high- and low-class prostitutes, night porters, bell boys, burglars, racketeers, pimps, and casual laborers.” In 1914, Dr. Christopher Koch of Pennsylvania’s State Pharmacy Board made the racial innuendo explicit, testifying that, “Most of the attacks upon the white women of the South are the direct result of a cocaine-crazed Negro brain.” Mass media manufactured an epidemic of cocaine use among African Americans in the Southern United States to play upon racial prejudices of the era, though there is little evidence that such an epidemic actually took place. In the same year, the Harrison Narcotics Tax Act outlawed the sale and distribution of cocaine in the United States. This law incorrectly referred to cocaine as a narcotic, and the misclassification passed into popular culture. As stated above, cocaine is a stimulant, not a narcotic. Although technically illegal for purposes of distribution and use, the distribution, sale and use of cocaine was still legal for registered companies and individuals. Because of the misclassification of cocaine as a narcotic, the debate is still open on whether the government actually enforced these laws strictly. Cocaine was not considered a controlled substance until 1970, when the United States listed it as such in the Controlled Substances Act. Until that point, the use of cocaine was open and rarely prosecuted in the US due to the moral and physical debates commonly discussed.
Modern usage
In many countries, cocaine is a popular recreational drug. In the United States, the development of “crack” cocaine introduced the substance to a generally poorer inner-city market. Use of the powder form has stayed relatively constant, experiencing a new height of use during the late 1990s and early 2000s in the U.S., and has become much more popular in the last few years in the UK. Cocaine use is prevalent across all socioeconomic strata, including age, demographics, economic, social, political, religious, and livelihood.
The estimated U.S. cocaine market exceeded $70 billion in street value for the year 2005, exceeding revenues by corporations such as Starbucks. There is a tremendous demand for cocaine in the U.S. market, particularly among those who are making incomes affording luxury spending, such as single adults and professionals with discretionary income. Cocaine’s status as a club drug shows its immense popularity among the “party crowd”.
In 1995 the World Health Organization (WHO) and the United Nations Interregional Crime and Justice Research Institute (UNICRI) announced in a press release the publication of the results of the largest global study on cocaine use ever undertaken. However, a decision in the World Health Assembly banned the publication of the study. In the sixth meeting of the B committee the US representative threatened that “If WHO activities relating to drugs failed to reinforce proven drug control approaches, funds for the relevant programs should be curtailed”. This led to the decision to discontinue publication. A part of the study has been recuperated.[20] Available are profiles of cocaine use in 20 countries.
A problem with illegal cocaine use, especially in the higher volumes used to combat fatigue (rather than increase euphoria) by long-term users, is the risk of ill effects or damage caused by the compounds used in adulteration. Cutting or “stamping on” the drug is commonplace, using compounds which simulate ingestion effects, such as Novocain (procaine) producing temporary anaesthaesia as many users believe a strong numbing effect is the result of strong and/or pure cocaine, ephedrine or similar stimulants that are to produce an increased heart rate. The normal adulterants for profit are inactive sugars, usually mannitol, creatine or glucose, so introducing active adulterants gives the illusion of purity and to ’stretch’ or make it so a dealer can sell more product than without the adulterants. The adulterant of sugars therefore allows the dealer to sell the product for a higher price
because of the illusion of purity and allows to sell more of the product at that higher price, enabling dealers to make a lot of revenue with little cost of the adulterants. Cocaine trading carries large penalties in most jurisdictions, so user deception about purity and consequent high profits for dealers are the norm.
A 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. Street market cocaine is frequently adulterated or “cut” with various powdery fillers to increase its weight; the substances most commonly used in this process are baking soda; sugars, such as lactose, dextrose, inositol, and mannitol; and local anesthetics, such as lidocaine or benzocaine, which mimic or add to cocaine’s numbing effect on mucous membranes. Cocaine may also be “cut” with other stimulants such as methamphetamine. Adulterated cocaine is often a white, off-white or pinkish powder.
The color of “crack” cocaine depends upon several factors including the origin of the cocaine used, the method of preparation – with ammonia or baking soda – and the presence of impurities, but will generally range from white to a yellowish cream to a light brown. Its texture will also depend on the adulterants, origin and processing of the powdered cocaine, and the method of converting the base. It ranges from a crumbly texture, sometimes extremely oily, to a hard, almost crystalline nature.
Forms of Cocaine
Salts
Cocaine, like many alkaloids can form many different salts, such as hydrochloride (HCl) and sulfate (-SO4). Different salts have different solvency in solvents. Its hydrochloride, like many alkaloid hydrochloride is polar and is soluble in water.
Freebase
As the name implies, “freebase” is the base form of cocaine, as opposed to the salt form. It is practically insoluble in water whereas hydrochloride salt is water soluble. Smoking freebase cocaine has the additional effect of releasing methylecgonidine into the user’s system due to the pyrolysis of the substance (a side effect which insufflating or injecting powder cocaine does not create). Some research suggests that smoking freebase cocaine can be even more cardiotoxic than other routes of administration because of methylecgonidine’s effects on lung tissue and liver tissue. Pure cocaine is prepared by neutralizing its compounding salt with an alkaline solution which will precipitate to non-polar basic cocaine. It is further refined through aqueous-solvent Liquid-liquid extraction.
Crack cocaine
Crack is a lower purity form of free-base cocaine and contains sodium bicarbonate as impurity. Freebase and crack are often administered by smoking. The origin of the name is from the crackling sound (hence the onomatopoeic “crack”) produced when cocaine containing impurities are heated.
Coca leaf infusions
Coca herbal infusion (also referred to as Coca tea) is used in coca-leaf producing countries much as any herbal medicinal infusion would elsewhere in the world. The free and legal commercialization of dried coca leaves under the form of filtration bags to be used as “coca tea” has been actively promoted by the governments of Peru and Bolivia for many years as a drink having medicinal powers. Visitors to the city of Cuzco in Peru, and La Paz in Bolivia are greeted with the offering of coca leaf infusions (prepared in tea pots with whole coca leaves) purportedly to help the newly-arrived traveler overcome the malaise of high altitude sickness. The effects of drinking coca tea are a mild stimulation and mood lift. It does not produce any significant numbing of the mouth nor does it give a rush like snorting cocaine. In order to prevent the demonization of this product, its promoters publicize the unproven concept that much of the effect of the ingestion of coca leaf infusion would come from the secondary alkaloids, as being not only quantitatively different from pure cocaine but also qualitatively different.
It has been promoted as an adjuvant for the treatment of cocaine dependence. In one controversial study, coca leaf infusion was used -in addition to counseling- to treat 23 addicted coca-paste smokers in Lima, Peru. Relapses fell from an average of four times per month before treatment with coca tea to one during the treatment. The duration of abstinence increased from an average of 32 days prior to treatment to 217 days during treatment. These results suggest that the administration of coca leaf infusion plus counseling would be an effective method for preventing relapse during treatment for cocaine addiction. Importantly, these results also suggest strongly that the primary pharmacologically active metabolite in coca leaf infusions is actually cocaine and not the secondary alkaloids. The cocaine metabolite benzoylecgonine can be detected in the urine of people a few hours after drinking one cup of coca leaf infusion.
Routes of Administration
Oral
A spoon containing baking soda, cocaine, and a small amount of water. Used in a “poor-man’s” crack-cocaine production. Many users rub the powder along the gum line, or onto a cigarette filter which is then smoked, which numbs the gums and teeth – hence the colloquial names of “numbies”, “gummers” or “cocoa puffs” for this type of administration. This is mostly done with the small amounts of cocaine remaining on a surface after insufflation. Another oral method is to wrap up some cocaine in rolling paper and swallow it. This is sometimes called a “snow bomb.”
Coca leaf
Coca leaves are typically mixed with an alkaline substance (such as lime) and chewed into a wad that is retained in the mouth between gum and cheek (much in the same as chewing tobacco is chewed) and sucked of its juices. The juices are absorbed slowly by the mucous membrane of the inner cheek and by the gastrointestinal tract when swallowed. Alternatively, coca leaves can be infused in liquid and consumed like tea. Ingesting coca leaves generally is an inefficient means of administering cocaine. Advocates of the consumption of the coca leaf state that coca leaf consumption should not be criminalized as it is not actual cocaine, and consequently it is not properly the illicit drug. Because cocaine is hydrolyzed and rendered inactive in the acidic stomach, it is not readily absorbed when ingested alone. Only when mixed with a highly alkaline substance (such as lime) can it be absorbed into the bloodstream through the stomach. The efficiency of absorption of orally administered cocaine is limited by two additional factors. First, the drug is partly catabolized by the liver. Second, capillaries in the mouth and esophagus constrict after contact with the drug, reducing the surface area over which the drug can be absorbed. Nevertheless, cocaine metabolites can be detected in the urine of subjects that have sipped even one cup of coca leaf infusion. Therefore, this is an actual additional form of administration of cocaine, albeit an inefficient one.
Orally administered cocaine takes approximately 30 minutes to enter the bloodstream. Typically, only a third of an oral dose is absorbed, although absorption has been shown to reach 60% in controlled settings. Given the slow rate of absorption, maximum physiological and psychotropic effects are attained approximately 60 minutes after cocaine is administered by ingestion. While the onset of these effects is slow, the effects are sustained for approximately 60 minutes after their peak is attained.
Contrary to popular belief, both ingestion and insufflation result in approximately the same proportion of the drug being absorbed: 30 to 60%. Compared to ingestion, the faster absorption of insufflated cocaine results in quicker attainment of maximum drug effects. Snorting cocaine produces maximum physiological effects within 40 minutes and maximum psychotropic effects within 20 minutes, however, a more realistic activation period is closer to 5 to 10 minutes, which is similar to ingestion of cocaine. Physiological and psychotropic effects from nasally insufflated cocaine are sustained for approximately 40 – 60 minutes after the peak effects are attained.
Mate de coca or coca-leaf infusion is also a traditional method of consumption and is often recommended in coca producing countries, like Peru and Bolivia, to ameliorate some symptoms of altitude
sickness. This method of consumption has been practiced for many centuries by the native tribes of South America. One specific purpose of ancient coca leaf consumption was to increase energy and reduce fatigue in messengers who made multi-day quests to other settlements.
In 1986 an article in the Journal of the American Medical Association revealed that U.S. health food stores were selling dried coca leaves to be prepared as an infusion as “Health Inca Tea.” While the packaging claimed it had been “decocainized,” no such process had actually taken place. The article stated that drinking two cups of the tea per day gave a mild stimulation, increased heart rate, and mood elevation, and the tea was essentially harmless. Despite this, the DEA seized several shipments in Hawaii, Chicago, Illinois, Georgia, and several locations on the East Coast of the United States, and the product was removed from the shelves.
Insufflation
Insufflation (known colloquially as “snorting,” “sniffing,” or “blowing”) is the most common method of ingestion of recreational powdered cocaine in the Western world. The drug coats and is absorbed through the mucous membranes lining the sinuses. When insufflating cocaine, absorption through the nasal membranes is approximately 30–60%, with higher doses leading to increased absorption efficiency. Any material not directly absorbed through the mucous membranes is collected in mucus and swallowed (this “drip” is considered pleasant by some and unpleasant by others). In a study of cocaine users, the average time taken to reach peak subjective effects was 14.6 minutes. Any damage to the inside of the nose is because cocaine highly constricts blood vessels – and therefore blood and oxygen/nutrient flow – to that area.
Prior to insufflation, cocaine powder must be divided into very fine particles. Cocaine of high purity breaks into fine dust very easily, except when it is moist (not well stored) and forms “chunks,” which reduces the efficiency of nasal absorption. Rolled up banknotes, hollowed-out pens, cut straws, pointed ends of keys, specialized spoons, long fingernails, and (clean) tampon applicators are often used to insufflate cocaine. Such devices are often called “tooters” by users. The cocaine typically is poured onto a flat, hard surface (such as a mirror, CD case or book) and divided into “bumps”, “lines” or “rails”, and then insufflated. As tolerance builds rapidly in the short-term (hours), many lines are often snorted to produce greater effects.
A study by Bonkovsky and Mehta reported that, just like shared needles, the sharing of straws used to “snort” cocaine can spread blood diseases such as Hepatitis C.
In the United States, as far back as 1992 many of the people sentenced by federal authorities for charges related to powder cocaine were Hispanic; more Hispanics than non-Hispanic White and non-Hispanic Black people received sentences for crimes related to powder cocaine.
Injection
Drug injection provides the highest blood levels of drug in the shortest amount of time. Subjective effects not commonly shared with other methods of administration include a ringing in the ears moments after injection (usually when in excess of 120 milligrams) lasting 2 to 5 minutes including tinnitus & audio distortion. This is colloquially referred to as a “bell ringer”.[46] In a study[41] of cocaine users, the average time taken to reach peak subjective effects was 3.1 minutes. The euphoria passes quickly. Aside from the toxic effects of cocaine, there is also danger of circulatory emboli from the insoluble substances that may be used to cut the drug. As with all injected illicit substances, there is a risk of the user contracting blood-borne infections if sterile injecting equipment is not available or used.
An injected mixture of cocaine and heroin, known as “speedball” is a particularly popular and dangerous combination, as the converse effects of the drugs actually complement each other, but may also mask the symptoms of an overdose. It has been responsible for numerous deaths, including celebrities such as John Belushi, Chris Farley, Mitch Hedberg, River Phoenix and Layne Staley.
Experimentally, cocaine injections can be delivered to animals such as fruit flies to study the mechanisms of cocaine addiction.
Inhalation
Inhalation or smoking is one of the several means cocaine is administered. Cocaine is smoked by inhaling the vapor by sublimating solid cocaine by heating. In a 2000 Brookhaven National Laboratory medical department study, based on self reports of 32 abusers who participated in the study,”peak high” was found at mean of 1.4min +/- 0.5 minutes.
Smoking freebase or crack cocaine is most often accomplished using a pipe made from a small glass tube, often taken from “Love roses,” small glass tubes with a paper rose that are promoted as romantic gifts. These are sometimes called “stems”, “horns”, “blasters” and “straight shooters”. A small piece of clean heavy copper or occasionally stainless steel scouring pad – often called a “brillo” (actual Brillo pads contain soap, and are not used), or “chore”, named for Chore Boy brand copper scouring pads, – serves as a reduction base and flow modulator in which the “rock” can be melted and boiled to vapor. Crack smokers also sometimes smoke through a soda can with small holes in the bottom.
Crack is smoked by placing it at the end of the pipe; a flame held close to it produces vapor, which is then inhaled by the smoker. The effects, felt almost immediately after smoking, are very intense and do not last long – usually five to fifteen minutes. When smoked, cocaine is sometimes combined with other drugs, such as cannabis, often rolled into a joint or blunt. Powdered cocaine is also sometimes smoked, though heat destroys much of the chemical; smokers often sprinkle it on marijuana.
The language referring to paraphernalia and practices of smoking cocaine vary, as do the packaging methods in the street level sale.
Physical mechanisms
Cocaine binds directly to the DAT1 transporter, inhibiting reuptake with more efficacy than amphetamines which phosphorylate it causing internalization; instead primarily releasing DAT (which cocaine does not do) and only inhibiting its reuptake as a secondary, and much more minor, mode of action than cocaine and in another manner: from the opposite conformation/orientation to DAT.
The pharmacodynamics of cocaine involve the complex relationships of neurotransmitters (inhibiting monoamine uptake in rats with ratios of about: serotonin:dopamine = 2:3, serotonin:norepinephrine = 2:5) The most extensively studied effect of cocaine on the central nervous system is the blockade of the dopamine transporter protein. Dopamine transmitter released during neural signaling is normally recycled via the transporter; i.e., the transporter binds the transmitter and pumps it out of the synaptic cleft back into the presynaptic neuron, where it is taken up into storage vesicles. Cocaine binds tightly at the dopamine transporter forming a complex that blocks the transporter’s function. The dopamine transporter can no longer perform its reuptake function, and thus dopamine accumulates in the synaptic cleft. This results in an enhanced and prolonged postsynaptic effect of dopaminergic signaling at dopamine receptors on the receiving neuron. Prolonged exposure to cocaine, as occurs with habitual use, leads to homeostatic dysregulation of normal (i.e. without cocaine) dopaminergic signaling via down-regulation of dopamine receptors and enhanced signal transduction. The decreased dopaminergic signaling after chronic cocaine use may contribute to depressive mood disorders and sensitize this important brain reward circuit to the reinforcing effects of cocaine (e.g. enhanced dopaminergic signalling only when cocaine is self-administered). This sensitization contributes to the intractable nature of addiction and relapse.
Dopamine-rich brain regions such as the ventral tegmental area, nucleus accumbens, and prefrontal cortex are frequent targets of cocaine addiction research. Of particular interest is the pathway consisting of dopaminergic neurons originating in the ventral tegmental area that terminate in the nucleus accumbens. This projection may function as a “reward center”, in that it seems to show activation in response to drugs of abuse like cocaine in addition to natural rewards like food or sex.
While the precise role of dopamine in the subjective experience of reward is highly controversial among neuroscientists, the release of dopamine in the nucleus accumbens is widely considered to be at least partially responsible for cocaine’s rewarding effects. This hypothesis is largely based on laboratory data involving rats that are trained to self-administer cocaine. If dopamine antagonists are infused directly into the nucleus accumbens, well-trained rats self-administering cocaine will undergo extinction (i.e. initially increase responding only to stop completely) thereby indicating that cocaine is no longer reinforcing (i.e. rewarding) the drug-seeking behavior.
Cocaine’s effects on serotonin (5-hydroxytryptamine, 5-HT) show across multiple serotonin receptors, and is shown to inhibit the re-uptake of 5-HT3 specifically as an important contributor to the effects of cocaine. The overabundance of 5-HT3 receptors in cocaine conditioned rats display this trait, however the exact effect of 5-HT3 in this process is unclear. The 5-HT2 receptor (particularly the subtypes 5-HT2AR, 5-HT2BR and 5-HT2CR) show influence in the evocation of hyperactivity displayed in cocaine use.
Cocaine has been demonstrated to bind as to directly stabilize the DAT transporter on the open outward-facing conformation whereas other stimulants (namely phenethylamines) stabilize the closed conformation. Further, cocaine binds in such a way as to inhibit a hydrogen bond innate to DAT that otherwise still forms when amphetamine and similar molecules are bound. Cocaine’s binding properties are such that it attaches so this hydrogen bond will not form and is blocked from formation due to the tightly locked orientation of the cocaine molecule. Research studies have suggested that the affinity for the transporter is not what is involved in habituation of the substance so much as the conformation and binding properties to where & how on the transporter the molecule binds.
Sigma receptors are effected by cocaine, as cocaine functions as a sigma ligand agonist. Further specific receptors it has been demonstrated to function on are NMDA and the D1 dopamine receptor. Cocaine also blocks sodium channels, thereby interfering with the propagation of action potentials; thus, like lignocaine and novocaine, it acts as a local anesthetic. Cocaine also causes vasoconstriction, thus reducing bleeding during minor surgical procedures. The locomotor enhancing properties of cocaine may be attributable to its enhancement of dopaminergic transmission from the substantia nigra. Recent research points to an important role of circadian mechanisms and clock genes in behavioral actions of cocaine.
Because nicotine increases the levels of dopamine in the brain, many cocaine users find that consumption of tobacco products during cocaine use enhances the euphoria. This, however, may have undesirable consequences, such as uncontrollable chain smoking during cocaine use (even users who do not normally smoke cigarettes have been known to chain smoke when using cocaine), in addition to the detrimental health effects and the additional strain on the cardiovascular system caused by tobacco.
In addition to irritability, mood disturbances, restlessness, paranoia, and auditory hallucinations, cocaine use can cause several dangerous physical conditions. It can lead to disturbances in heart rhythm and heart attacks, as well as chest pains or even respiratory failure. In addition, strokes, seizures and headaches are common in heavy users. Cocaine can often cause reduced food intake, many chronic users lose their appetite and can experience severe malnutrition and significant weight loss. Cocaine effects, further, are shown t