COCAETHYLENE: IMMUNOLOGIC, HEPATIC, AND CARDIAC EFFECTS

Concomitant cocaine and ethanol use produce the compound cocaethylene. A 1995 study estimated that 60 to 80 percent of cocaine users consume ethanol simultaneously. Some users of cocaine mix it with ethanol together as they extend the euphoric sensation and lessen the dysphoria associated with a cessation of cocaine. Cocaethylene, a compound synthesized in vivo, was only identified in 1979. It also has been named in literature as ethylcocaine, ethylbenzoylecgonine, and benzoylecgonine ethyl ester. In 1990, an NIAAA Survey reported that 5.3 million Americans had used cocaine concurrently (during the same period of time) with alcohol, and 4.6 million simultaneously (on the same occasion) with ethanol.

Although the mechanism by which the combination of cocaine and ethanol may be particularly deleterious to the cardiovascular system is unknown, two hypotheses have been proposed:

1. It may markedly increase the determinants of myocardial oxygen demand and simultaneously diminish supply, leading to a marked supply:demand imbalance; in human volunteers, the use of both drugs produces a greater increase in heart rate than either substance alone.
2. The concomitant ingestion of cocaine and ethanol may lead to the production of a metabolite which induces marked coronary arterial vasoconstriction, leading to myocardial ischemia, infarction, and/or sudden death.

While formed when cocaine and ethanol were consumed simultaneously in humans, monkeys, and mice, formation of cocaethylene resulted through transesterification of cocaine by hepatic carboxylesterases in the liver. Further studies must be done in species that resemble humans to determine the pathways and significance of the cocaine and ethanol combination.

The toxicity that results from combined cocaine and ethanol use is not due to enhanced sensitivity to alcohol in cocaine abusers. In rats cocaethylene exposure during the brain growth spurt period causes teratogenic effects slowing brain growth. Cocaethylene is a neuroteratogen as indicated by altered concentrations of catecholamines and indoleamines in developing brains. There was a region-specific alteration in neurotransmitter levels in response to six days of cocaethylene exposure. It also appears that cocaethylene is more similar to ethanol than cocaine in terms of neuroteratogeneis. Measured cocaine and cocaethylene concentration in postmortem human cerebral cortex and that combined use of cocaine and ethanol increased the risk of death 18-fold.

In the first primate study the effects of intravenously administered cocaine on extracellular dopamine in the primate was compared to the effects of cocaethylene. There are numerous biochemical and pharmacological differences between primates, rodents and dogs that make it important to study primates if immediate extensions to clinical research studies in humans are to be made. Both cocaethylene and cocaine are equipotent and were found to increase extracellular dopamine in the caudate nucleus. Cocaethylene retains activity similar to cocaine including inhibition of dopamine transporter. In most case studies, the potentiality of cocaine and cocaethylene seem to point to equal potency in in vitro experiments. The organs of 60 percent of the addicts seeking medical attention in emergency rooms, or examined postmortem specimens, contain cocaethylene.

BIBLIOGRAPHY

Chen, W. J. A., & West, J. R.. (1997). Cocaethylene exposure during the brain growth spurt period: Brain growth restrictions and neurochemisty studies. Developmental Brain Research, 100 : 220-229.

Pirozhkov, S.V.& Watson, R. R. P.. (1993). Immunomodulalting and hepatotoxic effects of cocaine and coaerthylene: enhancement by simultaneous ethanol administration. Alcologia, 5 : 113-116.

Song, N., Parker, R. B., & Laizure, C. S. (1999). Cocaethylene formation in rat, dog, and human hepatic microsomes. Life Sciences, 64 : 2101-2108.

Albert D. Arvallo

Ronald Ross Watson