The efficacy of methadone tapering plus amantadine to detoxify heroin-dependent patients with or without an active cocaine use disorder was studied in a closed unit with two successive double-blind, placebo-controlled, 14-day trials. In the first trial, 40 heroin-dependent inpatients with an active cocaine use disorder were treated using methadone tapering, as well as amantadine (200-300 mg per day) or placebo. In the second trial, 40 heroin-dependent inpatients without an active cocaine use disorder received the same treatment. In both the trials, amantadine did not have a statistically significant effect on treatment completion, nor did it contribute, in completers, to a more rapid reduction in craving and opiate withdrawal. In the first trial, women were six times more likely than men to be non-completers, and on the last day of treatment, the first trial's completers and non-completers presented a comparable clinical state.