Discriminative stimulus, self-reported and cardiovascular effects of orally administered cocaine in humans

This study evaluated whether an oral dose of cocaine can serve as a discriminative stimulus in humans. Four male and one female cocaine-abusing volunteers (ages 26-41 years) were trained to discriminate between cocaine HCl (80 mg/70 kg p.o.) and placebo. Once the criterion for discrimination was met (i.e., > or = 80% correct responding for four consecutive sessions), dose-effect curves were determined for orally administered cocaine (20, 40, 80 and 120 mg/70 kg), intranasally administered cocaine (20, 40, 80 and 120 mg/70 kg) and the benzodiazepine triazolam (0.25 and 0.50 mg/70 kg p.o.). All five subjects met the criterion for the cocaine-placebo discrimination within four to seven sessions. Novel cocaine doses by either the oral or intranasal route of administration generally produced dose-related increases in cocaine-appropriate responding, whereas triazolam produced predominantly placebo-appropriate responding. Cocaine by both routes produced qualitatively similar increases in stimulant-like self-reports, blood pressure and heart rate, whereas triazolam produced increases in sedative-like ratings and no changes in cardiovascular measures. Throughout dose-effect curve determinations, the training dose of cocaine and placebo continued to be identified correctly in four of five subjects (range, 75-100% correct responding). These results suggest that orally administered cocaine (80 mg/70 kg) is discriminable from placebo, has behavioral effects that are qualitatively similar to intranasal cocaine and does not show cross-generalization to a pharmacologically dissimilar compound.