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.