Operant analysis of human heroin self-administration and the effects of naltrexone

The effects of maintenance on a narcotic antagonist, naltrexone (50 mg/day p.o.), or placebo on patterns of operant acquisition and use of heroin were studied under double-blind conditions. Twelve male heroin addict volunteers lived on a clinical research ward for 34 days. After a 9 day drug-free period, naltrexone or placebo were given and heroin) 40 mg/day) was available for 10 days. Subjects could earn money ($1.50) or heroin (10 mg i.v.) by responding on a second-order schedule of reinforcement [FR 300 (FI 1 sec: S)] for approximately 90 min. The three naltrexone-maintained subjects took only 2 to 7.5% of the total heroin available. Two naltrexone subjects stopped heroin self-administration after the 1st or 2nd heroin injection; the third subject took a 3rd heroin injection on the 8th day of heroin availability. Naltrexone maintenance for 25 consecutive days did not produce adverse side effects. In contrast, the nine placebo naltrexone subjects used 57.5 to 100% of the total heroin available. Five placebo subjects used all or all but one of the 40 injections available; four placebo subjects often used less heroin than was available each day. Heroin intoxication did not impair operant performance. Heroin users worked longer hours and earned more purchase points (P < .05) during heroin self-administration and subsequent methadone detoxification than during the drug-free period. Subjects precisely titrated operant work to acquire the desired amount of heroin, then resumed working for money. These data demonstrate the feasibility of using direct measures of drug self-administration behavior to evaluate new pharmacotherapies for heroin abuse and indicate the effectiveness of naltrexone in suppressing heroin self-administration.