Abuse liability of prescription opioids compared to heroin in morphine-maintained heroin abusers

Abstract

Abuse of prescription opioid medications has increased dramatically in the United States during the past decade, as indicated by a variety of epidemiological sources. However, few studies have systematically examined the relative reinforcing effects of commonly abused opioid medications. The current double-blind, placebo-controlled in-patient study was designed to compare the effects of intravenously delivered fentanyl (0, 0.0625, 0.125, 0.187, and 0.250 mg/70 kg), oxycodone (0, 6.25, 12.5, 25, and 50 mg/70 kg), morphine (0, 6.25, 12.5, 25, and 50 mg/70 kg), buprenorphine (0, 0.125, 0.5, 2, and 8 mg/70 kg), and heroin (0, 3.125, 6.25, 12.5, and 25 mg/70 kg) in morphine-maintained heroin abusers (N=8 completers maintained on 120 mg per day oral morphine in divided doses (30 mg q.i.d.)). All of the participants received all of the drugs tested; drugs and doses were administered in non-systematic order. All of the drugs produced statistically significant, dose-related increases in positive subjective ratings, such as 'I feel a good drug effect' and 'I like the drug.' In general, the order of potency in producing these effects, from most to least potent, was fentanyl>buprenorphine>or=heroin >morphine=oxycodone. In contrast, buprenorphine was the only drug that produced statistically significant increases in ratings of 'I feel a bad drug effect' and it was the only drug that was not self-administered above placebo levels at any dose tested. These data suggest that the abuse liability of buprenorphine in heroin-dependent individuals may be low, despite the fact that it produces increases in positive subjective ratings. The abuse liabilities of fentanyl, morphine, oxycodone, and heroin, however, appear to be similar under these experimental conditions.

Figure 1

Selected visual analog scale ratings completed during sample sessions as a function of drug and dose. Data points represent the mean peak ratings ± 1 standard error of the mean (SEM). Filled symbols indicate significant differences from the placebo dose for that drug. (N=8)

Figure 2

Selected drug effects questionnaire ratings completed during sample sessions as a function of drug and dose. Data points represent the mean peak ratings ± 1 standard error of the mean (SEM). Filled symbols indicate significant differences from the placebo dose for that drug. (N=8)

Figure 3

Progressive ratio break point values for drug (left panel) and money (right panel) during choice sessions as a function of dose and drug. Data points represent the mean values ± 1 standard error of the mean (SEM). Filled symbols indicate significant differences from the placebo dose for that drug. (N=8)

Figure 4

Selected physiological responses collected during sample sessions as a function of dose and drug. Data points represent mean trough pupil size (top left panel) and mean respiratory effects (all other panels). The lowest (trough) pupil diameter after drug administration was obtained for each participant and then these values were averaged across participants. For the respiratory measures, the average value across the session after drug administration was obtained for each participant and then these values were averaged across participants. Filled symbols indicate significant differences from the placebo dose for that drug. (N=8)