Cocaine choice in humans during D-amphetamine maintenance.

The results of preclinical laboratory experiments and clinical trials indicate that agonist replacements such as d-amphetamine may be a viable option for managing cocaine dependence. This study determined the effects of d-amphetamine maintenance on cocaine choice behavior in human participants. We predicted that d-amphetamine maintenance would reduce cocaine choice. Nine cocaine-dependent participants completed the study. Two d-amphetamine maintenance conditions were completed in a counterbalanced order (0 and 40 mg/d). After 3 to 5 days of placebo or d-amphetamine maintenance, the participants completed 5 experimental sessions. During these sessions, the participants first sampled the placebo (ie, 4 mg of intranasal cocaine) identified as drug A. The participants then sampled a second intranasal drug dose (4, 10, 20, or 30 mg of cocaine) identified as drug B. The participants then made 6 discrete choices between drugs A and B. Drug choices were separated by 45 minutes. The primary outcome measure was the number of cocaine choices. All doses of cocaine were chosen significantly more than placebo during both maintenance conditions (ie, placebo and d-amphetamine). Choice of the 20-mg dose of cocaine was significantly lower during d-amphetamine maintenance relative to when this cocaine dose was tested during placebo-d-amphetamine maintenance. Cocaine produced prototypical subject-rated drug effects (eg, good effects, like drug, willing to take again). These effects were not altered to a significant degree by d-amphetamine maintenance. Cocaine was well tolerated during D-amphetamine maintenance, and no unexpected or serious adverse events occurred. These results are concordant with those of previous preclinical experiments, human laboratory studies, and clinical trials that suggest that agonist replacement therapy may be a viable strategy for managing cocaine dependence.