Comparison of intravenous cocaethylene and cocaine in humans

Rationale: Cocaethylene is a pharmacologically active homolog and metabolit e of cocaine, formed by transesterification of cocaine in the presence of e thanol. Here we relate findings from a randomized, placebo-controlled, doub le-blind study in which we examined the physiological and subjective effect s and pharmacokinetics of IV administered cocaethylene in human volunteers using cocaine as a comparator. Methods: Cocaine-dependent participants rand omly received one study drug, cocaethylene (0.25 or 0.5 mg/kg), cocaine (0. 25 or 0.5 mg/kg), or placebo, during each experimental session which occurr ed on separate days. Results: Cocaethylene was less potent in elevating hea rt rate than equivalent doses of cocaine. Similar differences between cocai ne and cocaethylene were found for subjective measures ("Cocaine High", "Ru sh", "Stimulated" and "Good Drug Effects"). All active drug conditions prod uced significant increases in systolic blood pressure relative to placebo, but no significant effect on diastolic blood pressure was observed. Cocaeth ylene demonstrated a slower clearance, larger volume of distribution and co rrespondingly longer elimination half-life than cocaine. Conclusion: The fi ndings from this study confirm those of previous studies that show that coc aethylene has pharmacological properties in common with cocaine, but is les s potent.