The abuse of cocaine has become a major public-health problem in the United States since the 1970s. During that period it emerged from relative obscurity, described by experts as a harmless recreational drug with minimal toxicity. By the mid-1980s, cocaine use had increased substantially and its ability to lead to drug taking at levels that caused severe medical and psychological problems was obvious. Cocaine (also known as "coke," "snow," "lady," "CRACK" and "ready rock"), is an ALKALOID with both local anesthetic and PSYCHOMOTOR STIMULANT properties. It is generally taken in binge cycles, with periods of hours to days in which users take the drug repeatedly, alternating with periods of days to weeks when no cocaine is used. Many users are recalcitrant to treatment, and the introduction of substantial criminal penalties associated with its possession and sale have not yet been effective in reducing its prevalence of heavy use. In fact, although occasional use of cocaine diminished somewhat by the early 1990s, heavier use did not.
Cocaine is extracted from the COCA PLANT (Erythroxylon coca), a shrub now found mainly in the Andean highlands and the northwestern parts of the Amazon in South America. The history of coca plant use by the cultures and civilizations who lived in these areas (including the Inca) goes back more than a thousand years, with evidence of use found archeologically in their burial sites. The Inca called the plant a "gift of the Sun god" and believed that the leaf had supernatural powers. They used the leaves much as the highland Indians of South America do today. A wad of leaves, along with some ash, is placed in the mouth and both chewed and sucked. The ash helps in the extraction of the cocaine from the coca leafnd the cocaine is efficiently absorbed through the mucous membranes of the mouth.
During the height of the Inca Empire (11th-15th centuries) coca leaves were reserved for the nobility and for religious ceremonies, since it was believed that coca was of divine origin. With the conquest of the Inca Empire by the Spanish in the 1500s, coca use was banned. The Conquistadors soon discovered, however, that their Indian slaves worked harder and required less food if they were allowed to chew coca. The Catholic church began to cultivate coca plants, and in many cases the Indians were paid in coca leaves.
Although glowing reports of the stimulant effects of coca reached Europe, coca use did not achieve popularity. This was no doubt related to the fact that coca plants could not be grown in Europe and the active ingredient in the coca leaves did not survive the long ocean voyage from South America. After the isolation of cocaine from coca leaves by the German chemist Albert Niemann in 1860 and the subsequent purification of the drug, it became more popular. It was aided in this regard by commercial endeavors in which cocaine was combined with wine (e.g., Vin de Coca), products for which there appeared many enthusiastic and uncritical endorsements by notables of the time.
Both interest in and use of cocaine spread to the United States, where extracts of coca leaves were added to many patent medicines. Physicians began prescribing it for a variety of ills including dyspepsia, gastrointestinal disorders, headache, neuralgia, toothache, and morend use increased dramatically. By the beginning of the twentieth century, cocaine's harmful effects were noted and caused a reassessment of its utility. As part of a broader regulatory effort, the U.S. government began to control its manufacture and sale. In 1914, the HARRISON NARCOTIC ACT forbade use of cocaine in over-the-counter medications and required the registration of those involved in the importation, manufacture, and sale of either coca or opium products. This had the effect of substantially reducing cocaine use in the United States, which remained relatively low until the late 1960s, when it moved into the spotlight once again.
Cocaine is a drug with both anesthetic and stimulant properties. Its local anesthetic and vasoconstriction effects remain its major medical use. The local anesthetic effect was established by Carl Koller in the mid-1880s, in experiments on the eye, but because it has been found to cause sloughing of the cornea, it is no longer used in eye surgery. Because it is the only local anesthetic capable of causing intense vasoconstriction, cocaine is beneficial in surgeries where shrinking of the mucous membranes and the associated increased visualization and decreased bleeding are necessary. Therefore, it remains useful for topical administration in the upper respiratory tract. When used in clinically appropriate doses, and with medical safeguards in place, cocaine appears to be a useful and safe local anesthetic.
Cocaine can be taken by a number of routes of administrationral, intranasal, intravenous, and smoked. Although the effects of cocaine are similar no matter what the route, route clearly contributes to the likelihood that the drug will be abused. The likelihood that cocaine will be taken for nonmedical purposes is assumed to be related to the rate of increase in cocaine brain level (as measured by blood levels) associated with those routes that provide the largest and most rapid changes in brain level being associated with greater self-administration. The oral route of administration, not a route used by cocaine abusers, is characterized by relatively slow absorption and peak levels that do not appear until approximately an hour after ingestion. Cocaine, however, is quickly absorbed from the nasal mucosa when it is inhaled into the nose as a powder (cocaine hydrochloride). Because of its local anesthetic properties, cocaine numbs or "freezes" the mucous membranes, a quality used by those purchasing the drug on the street to test for purity. When cocaine is used intranasally ("snorting"), cocaine blood levels, as well as subjective and physiological effects, peak at about 20 to 30 minutes, and reports of a "rush" are minimal. Intranasal users report that they are ready to take a second dose of the drug within 30 to 40 minutes after the first dose. Although this route was the most common way for people to use cocaine in the mid-1980s, it is not as efficient in getting the drug to the brain as either smoking or intravenous injection, and it has declined in popularity.
When taken intravenously, venous blood levels peak virtually immediately and subjects report a substantial, dose-related rush. This route was, until the mid-1980s, traditionally the choice of the experienced user, since it provided a rapid increase in brain levels of cocaine with a parallel increase in subjective effects. Blood levels of cocaine dissipate in parallel with subjective effects, and subjects report that they are ready for another intravenous dose within about 30 to 40 minutes. Users of intravenous cocaine are also more likely to combine their cocaine with HEROIN (e.g., a "speedball") than are users by other routes.
In the mid-1980s, smoked cocaine began to achieve popularity. FREEBASE, or "crack," is cocaine base, which is not destroyed at temperatures required to volatilize it. As with intravenous cocaine, blood levels peak almost immediately and, as with intravenous cocaine, a substantial rush ensues after smoking it. Users can prepare their own free-base from the powdered form they purchase on the street, or they can purchase it in the form of crack, or "ready-rock." The development of a smokable form of cocaine provided a more socially acceptable route of drug administration (both NICOTINE and MARIJUANA cigarettes provided the model for smoking cocaine), resulting in a drug that was both easy to use and highly toxic, since the route allowed for frequent repeated dosing with a readily available and relatively inexpensive drug. The use of intravenous
Cocaine is frequently taken in combination with other drugs such as alcohol, marijuana, and OPIATES. In fact, almost 75 percent of cocaine deaths reported in 1989 involved co-ingestion of other drugs. When taken in combination with alcohol, a metaboliteOCAETHYLENEs formed, which appears to be only slightly less potent than cocaine in its behavioral effects. It is possible that some of the toxicity reported after relatively low doses of cocaine might well be due to the combination of cocaine and alcohol.
Cocaine is broken down rapidly by enzymes (esterases) in the blood and liver. The major metabolites of this action (all relatively inactive) are BENZOYLECGONINE, ecgonine, and ecgonine methyl ester, all of which are excreted in the urine. Cocaethylene is an additional metabolite when cocaine and alcohol are ingested in combination. People with deficient plasma cholinesterase activityetuses, infants, pregnant women, patients with liver disease, and the elderlyre all likely to be sensitive to cocaine and therefore at higher risk for adverse effects than are others.
Research has been focused on the neurochemical and neuroanatomical substrates that mediate cocaine's reinforcing effects. Although a number of NEUROTRANSMITTER systems are involved, there is growing evidence that cocaine's effects on dopaminergic neurons in the mesolimbic and/or mesocortical neuronal systems of the brain are most closely associated with its reinforcing and other behavioral effects. The initial site of action in the brain for its reinforcing effects has been hypothesized to be the dopamine transporter of mesolimbocortical neurons. Cocaine action at the DOPAMINE transporter has the effect of inhibiting dopamine re-uptake, resulting in higher levels of dopamine at the synapse. These dopaminergic pathways may mediate the reinforcing effects of other stimulants and opiates as well. A substantial body of evidence suggests that dopamine plays a major role in mediating cocaine's reinforcing effects, although it is clear that cocaine affects not only the dopamine but also the SEROTONIN and noradrenaline systems.
In addition to blocking the re-uptake of several neurotransmitters, cocaine use results in central nervous system stimulation and local anesthesia. This latter effect may be responsible for the neural and myocardial depression seen after taking large doses. Cocaine use has been implicated in a broad range of medical complications covering virtually every one of the body's organ systems. At low doses, cocaine causes increases in heart rate, blood pressure, respiration, and body temperature. There have been suggestions that cocaine's cardiovascular effects can interact with ongoing behavior, resulting in increased toxicity. Cocaine intoxication has been associated with cardiovascular toxicity, related to both its local anesthetic effects and its inhibition of neuronal uptake of catecholamines, including heart attacks, stroke, vasospasm, and cardiac arrhythmias.
Cocaine is generally taken in binges, repeatedly, for several hours or days, followed by a period in which none is taken. When taken repeatedly, chronic cocaine intoxication can cause a psychosis, characterized by paranoia, anxiety, a stereotyped repetitive behavior pattern, and vivid visual, auditory, and tactile hallucinations. Less severe behavioral reactions to repeated cocaine use include irritability, hypervigilance, paranoid thinking, hyperactivity, and eating and sleep disturbances. In addition, when a cocaine binge ceases, there appears to be a crash response, characterized by depression, fatigue, and eating and sleep disturbances. Initially, the crash is accompanied by little cocaine craving, but as time increases since the last dose of cocaine, compulsive drug seeking can occur in which users think of little else but the next dose.
Nonhuman Research Subjects.
One of cocaine's characteristics, as a PSYCHOMOTOR STIMU-LANT, is its ability to elicit increases in the motor behavior of animals. Single low doses produce increases in exploration, locomotion, and grooming. With increasing doses, locomotor activity decreases and stereotyped behavior patterns emerge (continuous repetitious chains of behavior). When administered repeatedly, cocaine produces increased levels of locomotor activity, increases in stereotyped behavior, and increases in susceptibility to drug-induced seizures (i.e., "kindling"). This sensitization occurs in a number of different species and has been suggested as a model for psychosis or schizophrenia in humans. Although sensitization to cocaine's unconditioned behavioral effects generally occurs, such effects are related to dose, environmental context, and schedule of cocaine administration. For example, sensitization occurs more readily when dosing is intermittent rather than continuous and when dosing occurs in the same environment as testing.
Learned behaviors, typically generated in the laboratory using operant schedules of reinforcement in which animals make responses that have consequences (e.g., press a lever to get food), generally show a rate-dependent effect of cocaine. As with AMPHETAMINE, cocaine engenders increases in low rates of responding and decreases in high rates of responding. Environmental variables and behavioral context can modify this effect. For example, responding maintained by food delivery was decreased by doses of cocaine that either had no effect or increased comparable rates of responding maintained by shock avoidance. Cocaine's effects can also be modified by drug history. Although repeated administration can result in the development of sensitization to cocaine's effects on unlearned behaviors, repeated administration generally results in tolerance to cocaine's effects on schedule-controlled responding. This decrease in effect of the same dose after repeated dosing is influenced by behavioral as well as pharmacological factors.
Human Research Subjects.
A major behavioral effect of cocaine in humans is its mood-altering effect, generally believed related to its potential for abuse. Traditionally, subjective effects have provided the basis for classifying a substance as having abuse potentialnd the cocaine-engendered profile of subjective effects is prototypic of stimulant drugs of abuse. Thus, cocaine produces dose-related reports of "high," "liking," and "euphoria"; increases in stimulant-related factors, such as increases on Vigor and Friendliness scale scores; ratings of "stimulated"; and decreases in various sedation scores. Subjective effects correlate well with single intravenous or smoked doses of cocaine, peaking soon after administration and dissipating in parallel with decreasing plasma concentrations. When cocaine is administered repeatedly, tolerance develops rapidly to many of its subjective effects and the same dose no longer exerts much of an effect. This means that the user must take increasingly larger amounts of cocaine to achieve the same effect. Tolerance to the cardiovascular effects of cocaine is less complete; the result here is a potential for drug-induced toxicity, since more and more drug is taken when the subjective effects are not present but the disruptions in cardiovascular function are still present.
Although users of stimulant drugs claim that their performance of many activities is improved by cocaine use, the data do not support their assertions. In general, cocaine has little effect on performance except under conditions in which performance has deteriorated from fatigue. Under those conditions, cocaine can bring it back to nonfatigue levels. This effect, however, is relatively short-lived, since cocaine has a half-life of less than one hour.
Despite substantial efforts directed toward treatment of cocaine abuse, in the mid-1990s we are still unable to treat successfully many of the cocaine abusers who seek treatment. For many years the only approach to treating these people was psychological or behavioral. As of 1994, the most promising of these include behavioral therapy, relapse prevention, rehabilitation (e.g., vocational, educational, and social-skills training) and supportive psychotherapy. A major problem with these treatment approaches is related to their lack of selectivity. Rather than tailoring programs to an individual's background, drug-use history, psychiatric state, and socioeconomic level, individuals receive the treatment being delivered by the particular program they happen to attend. Treatment programs that focus on specific target populations will be far more successful than those which cover all who apply. For example, patients with relatively mild symptoms might do quite well in a behavioral intervention with some relapse-prevention instructions but those with more severe problems might require the addition of pharmacotherapy.
Pharmacological approaches to treating cocaine abusers have focused on potential neurophysiological changes related to chronic cocaine use. Thus, because dopamine appears to mediate cocaine's reinforcing effects, dopamine agonists such as AM-ANTADINE and bromocriptine have been tried. METHYLPHENIDATE, a stimulant, has been suggested as a possible substitution medication, and ANTIDEPRESSANTS such as desipramine have been studied because of their actions on the dopaminergic system. In addition, because cocaine blocks re-uptake of SEROTONIN at nerve terminals, serotonin-uptake blockers, such as fluoxetine, have also been tested. Although most of the potential medications have been shown to be successful in some patients under open label conditions, none have been clearly successful in double blind placebo-controlled clinical trials.
Clearly, no medication yet exists for the treatment of cocaine abuse. It may well be that different medications may be effective for the various target populations and that variations in dosages and durations of treatment might be required, depending on a variety of patient characteristics. In fact, several medications have been shown to be effective only for small and carefully delineated populations (e.g., lithium for cocaine abusers diagnosed with concurrent bipolar manic-depressive or cyclothymic disorders). An artificial enzyme has been developed that inactivates cocaine as soon as it enters the blood-stream by binding the cocaine and breaking it into two inactive metabolites, and this has the potential for destroying much of the cocaine before it reaches the brain. As of 1994, this technique is unavailable for human use. In addition, and most importantly, cocaine abuse (and drug abuse in general) is a behavioral problem, and it is unlikely that any medication will be effective unless it is combined with an appropriate behavioral intervention.
(SEE ALSO: ; Colombia As Drug Source; Epidemics of Drug Abuse; Epidemiology of Drug Abuse; National Household Survey on Drug Abuse; )
BOCK, G., & WHELAN, J. (1992). Cocaine: Scientific and social dimensions. Ciba Foundation Symposium 166. Chichester: Wiley.
JOHANSON, C. E., & FISCHMAN, M. W. (1989). Pharmacology of cocaine related to its abuse. Pharmacological Reviews, 41, 3-52.
KLEBER, H. D. (1989). Treatment of drug dependence: What works. International Review of Psychiatry, 1, 81-100.
LANDRY, D. W., ET AL. (1993). Antibody-catalyzed degradation of cocaine. Science, 259, 1899-1901.
MARIAN W. FISCHMAN
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