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.