The problems associated with chronic cocaine and amphetamine use and withdrawal are much more serious than those associated with caffeine. By the mid-1980s, more than 20 million people had used cocaine in the United States. With the recent introduction of cocaine in the free alkaloid base ("FREEBASE" or "CRACK") form, there has been a significant increase in cocaine-related medical, economic, social, and legal problems. In the free-base form, cocaine can be smoked, resulting in blood levels and brain concentrations of the drug that compare to those observed when the drug is injected intravenously. In non-user subjects in a laboratory setting, the administration of cocaine or amphetamine produces an elevation of mood, an increase in energy and alertness, and a decrease in fatigue and boredom. In some individuals, how ever, anxiety, irritability, and insomnia may be observed.
In nonlaboratory settings, heavy users of cocaine often take the drug in bouts or binges, only stopping when their supply runs out or they collapse from exhaustion. Immediately following the intravenous administration or inhalation of cocaine, the individual experiences an intense pleasurable sensation known as a "rush" or "flash," followed by euphoria. Cocaine rapidly penetrates into the brain to produce these effects, but then is rapidly redistributed to other tissues. In many cases, the intense pleasure followed by the rapid decline in the cocaine-induced elevation of mood is sufficient for the individual to begin to immediately seek out and use more of the drug to prolong these pleasurable effects. Following the intranasal administration of cocaine, the pleasure is less intense and the decline in brain concentrations of the drug progresses much more slowly, so that the craving for more of the drug is less pronounced. Cocaine and amphetamine appear to produce their reinforcing or pleasurable effects through interactions with the neurotransmitter dopamine, especially in limbic and cortical regions of the brain (i.e., within the mesocorticolimbic dopaminergic system). Both cocaine and amphetamine block the reabsorption of dopamine into the NEURONS, where it was released, thereby prolonging the action of dopamine in the synapse—the space between nerve cells. Amphetamine can also cause the direct release of dopamine from nerve cells and can inhibit the metabolism of the neurotransmitter. It is important to note, however, that every drug that augments the action of dopamine does not produce pleasurable or rewarding subjective effects.
The toxicity associated with cocaine or amphetamine use can be quite severe; it is often unrelated to the duration of use or to preexisting medical conditions in the individual. This potential for serious toxic side effects is amplified by the fact that tolerance usually develops to the subjective feelings of the cocaine-induced rush and euphoria, but not to some of the other central nervous system effects of the drug (especially seizure susceptibility). Some of the more minor toxic reactions include dizziness, confusion, nausea, headache, sweating, and mild tremors. These symptoms are experienced by virtually all cocaine and amphetamine users to some degree, as a result of stimulation of the sympathetic nervous system. More serious reactions are also fre quently observed. These serious toxic effects can include irregular heartbeats, convulsions and seizures, heart attacks, liver failure, kidney failure, heart failure, respiratory depression, stroke, coma, and death. The effects on the heart and cardiovascular system can sometimes be treated with alpha and beta noradrenergic-receptor antagonists or calcium channel blockers, although even prompt medical attention is not always successful. The convulsions can sometimes be controlled with diazepam (Valium); ventilation (oxygen) may be required for the respiratory depression. In addition to the effects described above for cocaine, amphetamine has been reported to produce direct and irreversible neuronal damage to dopaminergic neurons. A similar effect for cocaine has not yet been identified.
Psychiatric abnormalities resulting from chronic central nervous system stimulant abuse can include anxiety, DEPRESSION, HALLUCINATIONS, and, in some cases, a paranoid psychosis that is virtually indistinguishable from a paranoid SCHIZOPHRENIC psychosis. A withdrawal syndrome is also observed following the abrupt cessation of chronic cocaine or amphetamine use. This syndrome begins with exhaustion during the "crash" phase and is followed by prolonged periods of anxiety, depression, an-hedonia (loss of pleasure), hyperphagia (gluttony), and high craving for the drug. This craving may persist for several weeks, depending on the individual. The administration of dopaminergic agonists or tricyclic ANTIDEPRESSANTS may have some utility in decreasing the severity of the withdrawal symptoms.
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