Concurrent use of cocaine and alcohol is more potent and potentially more toxic than use of either alone—A multiple-dose study

Background: Simultaneous abuse of cocaine and alcohol is widespread and increasingly detected in patients seeking emergent care. This double-blind, randomized, within-subjects study used a paradigm more closely approximating practices of drug abusers to better understand the pathogenesis of cocaine–alcohol abuse. Methods: Subjects meeting DSM-IV criteria for cocaine dependence and alcohol abuse participated in three drug administration sessions: four doses of intranasal cocaine (1 mg/kg every 30 min) with oral alcohol (1 g/kg) administered following the initial cocaine dose and a second dose (120 mg/kg) at 60 min calculated to maintain plasma alcohol concentration at approximately 100 mg/dL during cocaine administration; four doses of cocaine/placebo alcohol; four doses of cocaine placebo/alcohol. Pharmacokinetic, physiological, and behavioral effects were followed over 8 hours. Results: Cocaine–alcohol produced greater euphoria and increased perception of well-being relative to cocaine. Heart rate significantly increased following cocaine–alcohol administration relative to either drug alone. Cocaine concentrations were greater following cocaine–alcohol administration. Cocaethylene had a longer half-life with increasing concentrations relative to cocaine at later time points. Conclusions: Enhanced psychological effects during cocaine–alcohol abuse may encourage ingestion of larger amounts of these substances over time placing users at heightened risk for greater toxicity than with either drug alone.