Low-dose oral cocaine in humans: Acquisition of discrimination and time-course of effects

Seven cocaine-abusing volunteers were trained to discriminate 50 mg oral cocaine vs placebo across 50 2-h sessions. Discriminative, subjective and autonomic effects were assessed with a procedure developed for precise characterization of their acute time-course. Subjective effects of oral cocaine began 10-15 min post-drug, peaked at 40-50 min and took up to 100 min post-drug to return nearly to baseline. Autonomic effects also began 10-15 min post drug, peaked at 40-50 min and typically returned to baseline by 120 min post-drug; for most participants, peak heart rate and blood pressure remained within the range seen with placebo. Six out of seven participants acquired the discrimination (although this typically required 15-30 sessions, and there were some intriguing dissociations between the ability to discriminate oral cocaine from placebo and the ability to identify it as a stimulant). In most participants, oral cocaine produced increases in ratings of 'liking', 'alertness' and 'good effects', and in motor performance. Overall, the results support the sensitivity of the behavioral-testing procedure used, and show that 50 mg oral cocaine can serve as a discriminative stimulus in adult humans.