Rationale: The efficacy of methadone for treating heroin dependence derives, in part, from suppression of opiate withdrawal and attenuation of the effects of heroin. Objectives: The purpose of this double-blind, within-subject, inpatient study was to determine whether larger doses of methadone, which are more effective in the treatment of opioid dependence, produce greater or longer-lasting blockade of the effects of heroin in addition to adequate withdrawal suppression. Methods: Participants were maintained on 30, 60, and 120 mg methadone (ascending order) for approximately 3 weeks at each dose. During each maintenance period, heroin challenges were administered at 4, 28, and 52 h after the last methadone dose. Opioid agonist effects and opioid withdrawal symptoms were assessed prior to heroin challenge. Challenge sessions consisted of three doses of heroin (0, 10, and 20 mg/70 kg; ascending order) 45 min apart. Results: All three methadone maintenance doses produced similar agonist effects. Participants tested 4 h after receiving 120 mg methadone showed complete suppression of withdrawal symptoms and full attenuation of the effects of heroin. Thirty and 60 mg methadone suppressed withdrawal for up to 52 h, but failed to block completely the effects of heroin. The effects of heroin increased slightly at longer post-methadone intervals. Conclusions: Heroin use may persist during methadone treatment because low to moderate doses of methadone suppress withdrawal, but fail to eliminate the effects of heroin. These results provide a mechanism for the clinical observation that higher methadone doses are more effective at reducing heroin use.
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