Cocaine: Encyclopedia II - Cocaine - Pharmacology

Cocaine - Pharmacology

Cocaine - Appearance

Cocaine in its purest form is an off-white or pink chunky product. Cocaine appearing in powder form is a salt, typically cocaine hydrochloride (CAS 53-21-4). Cocaine is frequently adulterated or “cut” with various powdery fillers to increase its surface area; the substances most commonly used in this process are baking soda, sugars, such as lactose, inositol, and mannitol, and local anesthetics, such as lidocaine. Adulterated cocaine is often a white or off-white powder.

The color of “crack” cocaine depends upon several factors including the origin of the cocaine used, the method of preparation — with ammonia or sodium bicarbonate, and the presence of impurities, but will generally range from a light brown to a pale brown. Its texture will also depend on the factors which affect color, but will range from a crumbly texture, which is usually the lighter variety, to hard, almost crystalline nature, which is usually the darker variety.

Cocaine - Forms of cocaine

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

The sulfate itself is an intermediate step to producing cocaine hydrochloride. In South America it is commonly smoked along with tobacco, and is known as pasta, basuco, basa, pitillo, or simply paste.

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

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

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

As freebase cocaine (Coc) is insoluble in water, it precipitates and the solution becomes cloudy. To recover the freebase, diethyl ether is added to the solution: 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 insoluble in water, it can be siphoned off. The ether is then left to evaporate, leaving behind the nearly pure freebase.

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

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

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

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

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

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

Cocaine - Methods of administration

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

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

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

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

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

The intravenous route of administration provides the highest blood levels of drug in the shortest time. It can get to the brain within 15 seconds. Injection of cocaine produces an exhilarating rush so intense that often the user may vomit uncontrollably, although the euphoria passes quickly as the liver rapidly metabolizes the drug. Aside from the toxic effects of cocaine, there is also danger of circulatory emboli from the insoluble substances that may be used to cut the drug. Obviously, there is also a risk of serious infection associated with the use of contaminated needles.

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

(see also: Crack cocaine above)

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

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

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

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

When smoked, cocaine is sometimes combined with other drugs, such as cannabis; often rolled into a joint or blunt. This combination is known as “primo”, “hype”, B-151er or a “woo”. Crack smokers who are being drug tested may also make their “primo” with cigarette tobacco instead of cannabis, since a crack smoker can test clean within 2 to 3 days of use, if only urine (and not hair) is being tested.

Cocaine - Mechanism of action

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

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

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

Cocaine is also a less potent blocker of the norepinephrine transporter (NET) and serotonin transporter (SERT). Cocaine also blocks sodium channels, thereby interfering with the propagation of action potentials; thus, like lidocaine and novocaine, it acts as a local anesthetic. The locomotor enhancing properties of cocaine may be attributable to its enhancement of dopaminergic transmission from the substantia nigra. Recent research points to an important role of circadian mechanisms [2] and clock genes [3] in behavioral actions of cocaine.

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

Cocaine - Metabolism and excretion

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

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

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

Cocaine - Effects and health issues

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

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

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

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

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

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

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

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

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

Cocaine - Cocaine as a local anesthetic

Cocaine was historically useful as a topical anesthetic in eye and nasal surgery. The major disadvantages of this use are cocaine's intense vasoconstrictor activity and potential for cardiovascular toxicity. Cocaine has since been replaced in Western medicine by synthetic local anaesthetics such as benzocaine, proparacaine, and tetracaine. If vasoconstriction is desired for a procedure (as it reduces bleeding), the anesthetic is combined with a vasoconstrictor such as phenylephrine or epinephrine. In Australia it is currently prescribed for use as a local anesthetic for conditions such as mouth and lung ulcers. Some Australian ENT specialists occasionally use cocaine within the practice when performing procedures such as nasal cauterization. In this scenario dissolved cocaine is soaked into a ball of cotton wool, which is placed in the nostril for the 10-15 minutes immediately prior to the procedure, thus performing the dual role of both numbing the area to be cauterized and also vasoconstriction.

Adapted from the Wikipedia article "Pharmacology", under the G.N U Free Docmentation License. Please also see http://en.wikipedia.org/wiki