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Cocaine can be taken by a number of routes of administration—oral, 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 intra-nasally ("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 freebase 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 intrave-

Figure 1

Chemical Structure of Cocaine

Figure 1

Chemical Structure of Cocaine nous cocaine, in contrast, was limited to those able to acquire the paraphernalia and willing to put a needle in a vein. The toxicity of the smoked route of administration is in part related to the fact that a potent dose of cocaine is available to anyone who can afford it.

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 metabolite—COCAETHYLENE—is 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 BEN-ZOYLECGONINE, 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 activity— fetuses, infants, pregnant women, patients with liver disease, and the elderly—are all likely to be sensitive to cocaine and therefore at higher risk for adverse effects than are others.

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