Cocaine is a frequently used central nervous system (CNS) stimulant that enhances energy and mood. It is also a dangerous drug of abuse, the subject of much regulatory legislation, and a major target of the “war on drugs.”
Cocaine is a naturally occurring substance found in the shrub Erythroxylon coca that grows in the eastern highlands of the Andes in Bolivia, Peru, Ecuador, and Colombia. Native inhabitants of this region are known to have chewed coca leaves, usually in combination with lime, for at least 5,000 years. In 1551, the Spanish conquistadores condemned this practice as “an evil agent of the devil” but soon discovered that, without the drug, natives could barely work the fields or mine gold (at altitudes of more than 8,000 feet). Thus, crops were cultivated and leaves were distributed to workers three or four times a day in order to ward off hunger and fatigue.
In Western Europe and North America, significant use of cocaine did not emerge until the middle of the 19th century, when the pure alkaloid (cocaine) was isolated. Three men were particularly influential in increasing the popularity of the drug. The first of these, Angelo Mariani, was a French chemist who made and sold many products containing cocaine, including lozenges, tea, and, most notoriously, wine (Vin Mariani).
The second proponent was the “father of modern surgery,” Ward S. Halsted, who administered cocaine to his patients via the newly invented hypodermic syringe to induce local (topical) anesthesia. According to the Controlled Substances Act of 1970, which regulates the supply and distribution of drugs in the United States, this is currently the only legitimate medical use of cocaine.
Finally, Sigmund Freud, another father (of psychoanalysis), advocated the use of small doses of cocaine to combat alcoholism, depression (or, like Sherlock Holmes, boredom), indigestion, and, perhaps most interestingly, to treat the withdrawal symptoms and “cravings” of people who were trying to stop using another addictive drug, morphine. In this respect, Freud resembles contemporary pharmacotherapists who promote the use of methadone, naloxone, or buprenorphine to treat heroin addiction. While such therapies have many benefits (at least in part because they are legal and heroin is not), we are now faced with a new problem—addiction to methadone. Interestingly, heroin was first synthesized (by Bayer, AG) as a potential, nonaddictive opiate, to be used as a substitute for morphine.
By 1885, one pharmaceutical company (Parke, Davis) had marketed 15 different products containing cocaine. These included cigarettes, cigars, and inhalants. One year later, a Georgia pharmacist, John Pemberton, invented a new beverage, Coca-Cola, that, from 1886 until 1906, contained both cocaine and another, less potent CNS stimulant, caffeine. Shortly thereafter, cocaine use spread across the United States to such an extent that, in 1910, President Taft declared the drug to be “public enemy number one.” In 1914, the Harrison Narcotic Act prohibited the inclusion of cocaine (as well as opium) in patent medicines.
The use of cocaine, which was relatively stable from the 1920s to the 1960s (with relatively benign effects), increased dramatically during the 1970s and 1980s (to more than 10 million individuals in 1984) despite additional efforts by the U.S. government to limit its use. Moreover, this increase was accompanied by reports of dependence liability and toxicity. One reason for these developments, although certainly not the only one, is related to the way in which cocaine is administered. South American Indians chewed coca leaves, which contain small amounts of cocaine in a form that is absorbed relatively slowly from the gastrointestinal tract into the bloodstream (and brain). In contemporary North America, however, cocaine is usually self-administered in more concentrated form, either intravenously or, most recently, by smoking “crack.” Each of these routes produces more rapid effects, including psychological and possibly physiological dependence.
Coca leaves typically contain between 0.5% and 2% cocaine. To extract the pure drug, the leaves are soaked and mashed to form a paste, which, after the solvent evaporates, contains 60% to 80% cocaine. The paste is converted to a water-soluble salt, cocaine hydrochloride, which is a pink to off-white powder that can be taken orally, intranasally (“snorting”), or by intravenous injection and is the form that is now exported around the world. While the salt is vulnerable to pyrolysis (heat-induced breakdown), which prevents it from being smoked, the drug can be transformed back into its free base form (“crack” or “rock”) by dissolving it in baking soda and water.
Different routes of administration produce different patterns and levels of cocaine concentration in the blood. Extremely rapid absorption occurs with both intravenous injection and smoking; absorption is slower following oral administration or snorting. Once in the body, cocaine is widely distributed and metabolized rapidly into two substances, ecgonine methyl ester and benzoylecgonine, both of which are excreted in the urine. However, because the acute effects of cocaine have a rapid onset and relatively brief duration, detection of measurable amounts of either cocaine or its metabolites (and, thus of cocaine use) is difficult.
The local anesthetic properties of cocaine (above) are the result of the drug’s ability to block the conduction of nerve impulses within neurons by preventing the influx of sodium (Na+) ions, which are necessary for the generation of action potentials (neuronal firing). However, the mechanism that underlies most other effects of cocaine, including its stimulant and addictive properties, involves the enhancement of the actions of neurotransmitters (intercellular messengers), such as dopamine (DA), norepinephrine (NE), and serotonin (5-HT), by blocking their cellular reuptake by plasma membrane transport proteins. The mesocorticolimbic or limbic-extrapyramidal DA system appears to play a particularly important role in the acute, CNS effects of cocaine and other reinforcing drugs. The neurons of this system arise from cell bodies in the ventral tegmental area (VTA) of the midbrain and innervate the nucleus accumbens (NAc), ventral caudate-putamen, and the prefrontal cortex (PFC). Other neuronal systems, including those involving both excitatory (glutamate) and inhibitory (γ-amino butyric acid, GABA) amino acid neurotransmitters, might be involved in some of the chronic behavioral effects of the drug, including cocaine “craving.”
The effects of cocaine are similar but not identical to those of other stimulants such as d-amphetamine and methamphetamine (“speed”). In humans, they include mood amplification (both euphoria and dysphoria), heightened energy, sleep disturbances, insomnia, motor excitation, restlessness, talkativeness, hyperactive ideation, increased sexual interest, anger, verbal aggressiveness, mild to moderate anorexia (loss of appetite), and inflated self-esteem. When administered intravenously or smoked, the drug can also produce a “rush” that is sometimes described as being even more intense than an orgasm. Cocaine also has a variety of physiological (sympathomimetic) effects, including increasing heart rate, blood pressure, locomotor activation, and, at higher doses, stereotyped behavior.
Humans and other animals (rats, pigeons, monkeys) can be taught to discriminate between the effects of cocaine (the cocaine state) and the absence of these effects (or the presence of other drug states). These effects generalize readily to other stimulants such as d-amphetamine, methamphetamine, and methylphenidate (Ritalin), suggesting that these compounds have similar mechanisms of action.
When humans or other animals are given the opportunity to self-administer cocaine either intravenously or through surgically implanted cannulae directly into regions of the brain such as the VTA, NAc, or PFC, even naïve (nondependent) subjects do so quite readily. This suggests that cocaine is reinforcing and therefore has a high potential for abuse. Unlimited access to the drug may lead to compulsive use accompanied by weight loss, convulsions, and even death.
While cocaine use seems to have “leveled” off in the 1990s and continues to this day at an estimated 1.5 million individuals in the United States, reports of cocaine dependency (addiction) and toxicity continue to increase. In addition, many cocaine users and former users have turned to even more potent and more toxic substances, including methamphetamine (“ice”), mixtures of amphetamines and heroin, and methylphenidate (Ritalin).
As mentioned previously, cocaine users feel an initial “rush” or sense of well-being, of having more energy, and being more alert. However, this effect quickly wears off, leaving the user feeling more “down” or depressed than before he or she took the drug. This feeling leads to more cocaine use, sometimes just to feel “normal.” Over a period of time, both the amount of cocaine needed and the frequency of use have to be increased to maintain the “high” (tolerance). When more cocaine is not available, users frequently turn to other drugs such as alcohol; such combinations or synergisms (e.g., alcohol and cocaine) can be more deadly than either drug alone.
Despite a popular myth, cocaine does not enhance performance on the job, in sports, at school, or with a sexual partner. Long-term use can lead to loss of concentration, irritability, loss of memory, paranoia (cocaine psychosis), loss of energy, anxiety, and a loss of interest in sex. Breaking a cocaine habit, which can cost an addict thousands of dollars a week, is not easy. How long and how difficult a task it may be varies from person to person. Treatment can be costly, and the craving for cocaine may persist for long periods of time.
An alarming statistic that was first reported during the late 1980s and early 1990s was that at least 10% to 15% of infants born in public hospitals had been exposed to cocaine prenatally. While the effects of such exposure are controversial and may have been overestimated by both the press and the scientific community, cocaine-exposed neonates are frequently smaller and have smaller brains than normal babies, perhaps because they are more often born prematurely. The long-term consequences of exposure to cocaine in utero have not yet been fully determined.
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- U.S. Drug Enforcement Administration, http://www.usdoj.gov/dea/