Effects of d-amphetamine and caffeine in humans under a cocaine discrimination procedure

This study examined further the pharmacological specificity of an oral cocaine discriminative stimulus in humans. Five male cocaine-abusing volunteers (two African-American/three Caucasian) were trained to discriminate between a low dose of cocaine hydrochloride (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 the dopamine reuptake inhibitor cocaine (20, 40, 80, 120 mg/70 kg, p.o.), the indirect dopamine agonist d-amphetamine (5, 10, 20 mg/70 kg, p.o.) and the adenosine antagonist caffeine (150, 300, 600 mg/70 kg, p.o.). Cocaine, d-amphetamine and caffeine each produced dose-related increases in cocaine-appropriate responding. Each compound produced at least a trend towards increases in a few stimulant-like self-reports and vital signs. When the relationship between cocaine-appropriate responding and self-reports were examined, cocaine and d-amphetamine, but not caffeine, had a similar profile of significant associations between discriminative performance and stimulant-like self-reports. These results suggest that, although the cocaine discriminative stimulus (80 mg/70 kg) is not specific only to stimulants with primarily dopaminergic actions, its pharmacological specificity may be more clearly defined when the relationship between discrimination and self-reports is examined.