Methadone doses of 100 mg or greater are more effective than lower doses at suppressing heroin self-administration in opioid-dependent volunteers


Sharon L. Walsh, Center for Drug and Alcohol Research, University of Kentucky, 43 Maxwelton Court, Lexington, KY 40506-0350, USA, Tel: 859-323-6126, Fax: 859-323-1193, E-mail:


Aims  Methadone maintenance has been an effective pharmacotherapy for the treatment of heroin dependence for nearly four decades. Recent clinical research suggests that methadone doses larger than those used in most clinics are more effective at suppressing illicit heroin use. This greater efficacy may result from greater cross-tolerance to the reinforcing effects of heroin.

Design  The purpose of this double-blind, within-subject study was to examine the relationship between methadone maintenance dose and the reinforcing effects of heroin.

Setting  Participants were stabilized on 50, 100 and 150 mg methadone (ascending order) during separate outpatient periods before being admitted to an inpatient research unit for testing at each maintenance dose.

Participants  Five opiate-dependent volunteers completed the study.

Measurements  During each 4-week inpatient testing period, participants sampled three doses of heroin (0, 10, or 20 mg; random order; one dose per week) and were subsequently allowed seven opportunities to choose between another injection of that week's heroin dose and varying amounts of money ($2–38).

Findings  The number of heroin injections chosen decreased as methadone dose was increased. Larger alternative monetary reinforcers were required to suppress heroin self-administration during maintenance on 50 compared to 100 or 150 mg methadone. Larger methadone doses also completely blocked the subjective effects of heroin and produced greater withdrawal suppression during the outpatient periods.

Conclusions  These results support other clinical and laboratory-based research indicating that persistent heroin use may be reduced by providing larger methadone maintenance doses that produce more effective cross-tolerance to heroin.