Effect of intravenous injection speed on responses to cocaine and hydromorphone in humans

Rationale: It is commonly accepted that the relative abuse liability of dru gs is positively related to the rate of delivery to the central nervous sys tem; however, few controlled studies have tested this hypothesis in humans. Objectives: The aims of this study were to evaluate systematically the eff ects of modifying intravenous infusion speed on the pharmacodynamic respons es related to abuse liability and toxicity of intravenous cocaine and hydro morphone. Methods: Twelve experienced opiate and cocaine users completed th is 3-week inpatient study. After completing a safety session, participants were tested on 9 separate test days with intravenous cocaine (30 mg/70 kg), hydromorphone (3 mg/70 kg), and placebo, each administered under double-bl ind and randomized conditions at infusion rates of 2, 15, and 60 s. Depende nt outcome measures included a range of physiological, subjective, and obse rver-rated measures, and continuous electrocardiographic monitoring was con ducted for safety monitoring. Results: Subjective responses to cocaine (for example, "high," "liking") were significantly greater when cocaine was inf used more rapidly. Physiological responses to cocaine were largely unaltere d with no evidence of increased toxicity with faster infusion speeds. None of the effects of hydromorphone were altered by varying the speed of infusi on. Conclusions: This study provides empirical evidence for the commonly ac cepted belief that the abuse liability of cocaine can be enhanced by increa sing the rate of the intravenous infusion; this principal may not hold true for opioids but further work would be required to rule this out. The data also indicate that moderate doses of cocaine can be administered over a ran ge of infusion speeds commonly used in experimental settings without apprec iably altering the apparent medical risks.