EVALUATION OF COCAINE-ETHANOL INTERACTION

By whatever criterion one uses- loss of life, loss of productivity, family
disintegration, mental anguish, health care costs, costs at all levels of
government- cocaine abuse has posed a significant problem. Adding further
to the dimension of this problem is the birth of "crack" cocaine babies
and the AIDS scourge. The cost of this multifaceted problem to this
nation, in human and economic terms, is almost beyond comprehension. One particularly important characteristic of drug dependence, regardless
of substance, is the pattern of multiple drug use. A consequence of that
practice is the potential for interactions among the abused substances
which can further exacerbate a toxic state or affect the dependence
liability of any or all of the abused substances. In the case of cocaine,
what is particularly remarkable is the degree of ethanol coingestion.
Several surveys have indicated a high incidence of co-use of these two
drugs. It is also clear that this coingestion results in increased
pharmacologic response and it results in far greater risk of death
compared to cocaine use alone. The reason(s) for these observations has not been firmly established but
at least two possibilities exist to explain the ethanol-enhanced response
to cocaine. The first involves the alteration in the disposition of
cocaine per se and, in concert with this, is the alteration of the profile
of active or toxic metabolites. One particularly interesting aspect of the
latter possibility is the recent recognition of the formation of an active
metabolite, cocaethylene (ethyl cocaine), resulting from the interaction
between ethanol and cocaine. The research program outlined here has been designed to quantitate the
disposition kinetics of cocaine in the absence and presence of ethanol.
This will be done in rats under acute and chronic dosing paradigms. In
addition, we propose to examine the response (locomotor activity) to
cocaine and metabolites in the absence and presence of ethanol. These data
will be used to develop a combined pharmacokinetic-pharmacodynamic model
to explore the cocaine-ethanol interaction.