RESUMEN
RATIONALE: We recently conducted a pilot study supporting the feasibility, safety, and validity of a human laboratory model of ad libitum cocaine administration in which subjects self-selected the timing of infusions. The current study extends this work to include a randomized design with a test-retest component in a larger sample. OBJECTIVES: To investigate the regulation of cocaine intake by humans and its effects on subjective and cardiovascular responses. MATERIALS AND METHODS: Subjects were 14 non-treatment seeking volunteers (10 M, 4 F) with cocaine abuse/dependence. Subjects self-administered cocaine infusions (0, 8, 16, and 32 mg/70 kg) over a 2-h period under a fixed ratio 1, 5-min time-out schedule on 4 consecutive days. A fifth session was conducted at 16-mg dose to assess the paradigm's test-retest reliability. RESULTS: Subjects regulated their cocaine intake in a dose-dependent fashion. Self-reports of cocaine-related subjective effects (e.g., "high" and "stimulated") also varied in a dose-dependent way. Test-retest data and the randomized design support the conclusion that such effects are not due to tolerance or other experimental artifacts. CONCLUSION: The current study replicates prior work demonstrating the feasibility, safety, and validity of our human laboratory paradigm of cocaine administration in a larger sample using a randomized design. The current study also shows the test-retest reliability of these methods, establishing its utility for comparisons of experimental interventions (e.g., pharmacological treatments). Finally, the current study suggests that factors other than drug-induced euphoria (i.e., "high") contribute to the regulation of cocaine-taking behaviors in humans.