Human methadone self-administration: Effects of dose and ratio requirement

The effects of response requirement and small doses of methadone on human oral self-administration of methadone were examined. Three methadone maintenance patients stabilized at a dose of 80 mg methadone per day were recruited as subjects. Completing a response requirement, fixed ratio (FR) of 32, 64 or 128 responses (FR32, FR64, FR128) on one button dispensed 10 ml of drug solution. Completing the equivalent response requirement on a second concurrently available response button dispensed 10 ml of vehicle. The opportunity to respond was unavailable until the drug or vehicle had been consumed. Each 10 ml of drug solution contained methadone doses of 0.027, 0.054 or 0.108 mg/ml. The frequency of deliveries was limited so that subjects could not ingest more than 54 mg of methadone; the difference between the 80 mg daily methadone dose and the methadone consumed in session was administered 30 min post-session. At FR64 and FR128 the frequency of deliveries decreased, at the 0.054 and 0.027 mg/ml doses, relative to the frequency of deliveries at FR32. The amount of methadone consumed increased with increases in methadone dose and decreased with increases in FR size. These results demonstrate the reinforcing effects of small unit doses of methadone. This procedure provides a sensitive baseline for examining effects of other pharmacological interventions on methadone ingestion in humans.