This study assessed the subjective and cardiovascular effects of relevant doses of cocaine administration during steady-state treatment of the combination of amantadine and baclofen compared to placebo. Participants included 8 healthy, male, cocaine-dependent, non-treatment-seeking individuals (age=36.6 +/- 5.9; 75% African American, 25% Caucasian; using cocaine for an average of 15.3 +/- 6.5 years). Data were collected prior to and following double-blind intravenous administration of 0 mg, 20 mg, and 40 mg of cocaine. Data were collected at baseline, following 5 days of treatment with placebo, and again following 5 days of treatment with a combination of amantadine 100 mg t.i.d. and baclofen 30 mg t.i.d. counterbalanced for order of medication and placebo in a cross-over design. Results showed no significant alterations to cardiovascular variables (heart rate, systolic and diastolic blood pressure) from treatment using combination medication or placebo in the presence of cocaine. Self-rated "desire" for cocaine was significantly lower during cocaine administrations while participants were receiving treatment with amantadine-baclofen compared to infusions while taking placebo medication, although there was no difference in the intensity of cocaine-induced euphoria, or reduction in the likelihood to use cocaine if given access. Study findings support the safety of the amantadine-baclofen combination treatment for cocaine dependence. (c) 2006 Elsevier Ireland Ltd. All rights reserved.