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

Abstract.

Rationale: It is commonly accepted that the relative abuse liability of drugs is positively related to the rate of delivery to the central nervous system; however, few controlled studies have tested this hypothesis in humans. Objectives: The aims of this study were to evaluate systematically the effects of modifying intravenous infusion speed on the pharmacodynamic responses related to abuse liability and toxicity of intravenous cocaine and hydromorphone. Methods: Twelve experienced opiate and cocaine users completed this 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-blind and randomized conditions at infusion rates of 2, 15, and 60 s. Dependent outcome measures included a range of physiological, subjective, and observer-rated measures, and continuous electrocardiographic monitoring was conducted for safety monitoring. Results: Subjective responses to cocaine (for example, "high," "liking") were significantly greater when cocaine was infused more rapidly. Physiological responses to cocaine were largely unaltered with no evidence of increased toxicity with faster infusion speeds. None of the effects of hydromorphone were altered by varying the speed of infusion. Conclusions: This study provides empirical evidence for the commonly accepted belief that the abuse liability of cocaine can be enhanced by increasing 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 range of infusion speeds commonly used in experimental settings without appreciably altering the apparent medical risks.