Pharmacologic Effects and Mechanisms of Abuse and Dependence

Cocaine is a stimulant as well as a local anesthetic with potent vasoconstrictor properties. It induces a complex pattern of subjective effects that have been described as intense euphoria and alertness, increased confidence and strength, heightened sexual feelings, and indifference to concerns and cares. Yet these sensations rapidly change to their antithesis, so that despondency, dejection, and despair prevail. Euphoria is restored by the next dose of the drug, and it is this rapid alternation between ecstasy and dejection that purportedly leads to the "binge" pattern of cocaine use, in which the drug is used repeatedly at short intervals until either the supply or the user is exhausted. Cocaine, like many drugs, produces both pleasure and dysphoria, so the simplistic notion of "reward" does not accurately describe its effects. Instead, cocaine has reinforcing effects, which may be defined as any effect, positive, negative, or both, that maintains the behavior that leads to the continued administration of the drug. The reinforcing properties of cocaine appear to be related to the rapid onset and brief duration of its stimulant effects.

Cocaine can be used orally, intranasally (by insufflation), by inhalation, by intravenous injection, or by the smoking or inhalation of coca paste, cocaine freebase, or "crack" cocaine (freebase prepared with sodium bicarbonate). The onset of salient subjective effects is determined in part by the route of administration and frequency of use. Mood enhancement occurs very rapidly after smoking crack cocaine and after intravenous use, but less rapidly after intranasal administration. Cocaine rapidly increases the heart rate and blood pressure in a dose-related manner. These subjective and physiologic effects are not sustained, however, and cocaine abusers report using the drug repeatedly and frequently during a binge.

Cocaine has a relatively short plasma half-life (approximately 60 minutes) and is metabolized primarily by plasma esterases; its metabolites are excreted in urine. It is often used sequentially or simultaneously with other abused drugs. Combinations of cocaine and alcohol produce a metabolite, cocaethylene, that has cardiovascular effects similar to those of cocaine alone. Cocaethylene may also lengthen cocaine-induced euphoria and reduce the unpleasant symptoms of withdrawal.

The accelerating frequency of cocaine abuse has economic and social consequences that are well documented. The seemingly evanescent pleasures of using the drug are accompanied by the risk of death from cardiac arrhythmia, respiratory depression, and convulsions. Disorders of cerebral blood flow and perfusion defects due to the potent vasoconstrictive effects of the drug on cerebral arteries are also associated with chronic cocaine abuse.

The medical sequelae of cocaine use, including addiction, now challenge health professionals in nearly every major specialty. There is a growing consensus that much can be done in the primary care setting to facilitate public health efforts to reduce the prevalence of cocaine use and to treat those with cocaine-related disorders. Thus, there is a strong need for an authoritative work on the topic. Unfortunately, clinicians may be disappointed if they expect Cocaine to be useful as either a clinical handbook or a bibliographic resource.