The order of drug administration: its effects on the interaction between cocaine and ethanol

To investigate the pharmacologic effects of the interaction between cocaine and ethanol, six male, paid volunteers familiar with the use of both ethanol and cocaine were tested in a dose-response, placebo-controlled, single-blind, randomly-assigned, cross-over design. Cocaine HCl (1.25 and 1.9 mg/kg) or placebo (lidocaine and mannitol) was given by nasal insufflation (snorting). Thirty minutes after cocaine snorting, ethanol (0.85 g/kg) or placebo was administered in divided doses over a thirty minute period. Cocaine and cocaethylene plasma concentrations, blood ethanol levels, subjective ratings of drug effects, heart rate and blood pressure were measured. Statistical analysis of the effects of cocaine snorting before ethanol ingestion indicate that: 1) cocaine did not alter the blood ethanol levels or the ratings of ethanol intoxication; 2) cocaethylene was formed and appeared in plasma more slowly and in concentrations lower than those of its parent compound; 3) the appearance of cocaethylene in plasma did not alter the decline of cocaine's subjective and heart rate effects; and 4) cocaine plasma concentrations were not increased and no augmentation of the subjective and heart rate effects of cocaine occurred. This latter finding, is in sharp contrast to the significant increase in cocaine plasma concentration and augmentation of cocaine's subjective and heart rate effects produced when ethanol is ingested prior to cocaine snorting.