HUMAN METHADONE SELF-ADMINISTRATION - EFFECTS OF DOSE AND RATIO REQUIREMENT

The effects of response requirement and small doses of methadone on hu man oral self-administration of methadone were examined. Three methado ne maintenance patients stabilized at a dose of 80 mg methadone per da y were recruited as subjects, Completing a response requirement, fixed ratio (FR) of 32, 64 or 128 responses (FR32, FR64, FR128) on one butt on dispensed 10 ml Of drug solution. Completing the equivalent respons e requirement on a second concurrently available response button dispe nsed 10 mi of vehicle. The opportunity to respond was unavailable unti l the drug or vehicle had been consumed. Each 10 ml of drug solution c ontained 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 pos t-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 deliver ies at FR32. The amount of methadone consumed increased with increases in methadone dose and decreased with increases in FR size. These resu lts demonstrate the reinforcing effects of small unit doses of methado ne. This procedure provides a sensitive baseline for examining effects of other pharmacological interventions on methadone ingestion in huma ns.