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 abusedopioid 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 0.250mg/70kg), oxycodone (0, 6.25, 12.5, 25, and 50mg/70kg), morphine (0, 6.25, 12.5,25, and 50mg/70kg), buprenorphine (0, 0.125, 0.5, 2, and 8mg/70kg), and heroin (0, 3.125, 6.25, 12.5, and 25mg/70kg) in morphine-maintained heroin abusers (N = 8 completers maintained on 120mg per day oral morphine in divided doses (30mg q.i.d.)). All of theparticipants received all of the drugs tested; drugs and doses were administered in non-systematic order. All of the drugs producedstatistically 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>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 abuseliability 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.
Generally, mean peak ratings of good effect, drug liking, and desire to take the drug again were similar to the VAS ratings. That is ratings were generally highest for heroin, morphine, followed by oxycodone, and lower for fentanyl and buprenorphine across the range of doses tested. Participants reported ‘a little’ good effect, ‘likebut not very much,’ and ‘a little’, or ‘moderately’ interested in taking the drug again for fentanyl and buprenorphine,while they reported ‘moderately’ good effects, ‘like some-what,’ and ‘quite a bit’ interested in taking the drug again for heroin, morphine, and oxycodone. Consistent with the majority of positive subjective-effects ratings, the average progressive ratio break point for 25mg/70kg morphine was slightly lower, but not significantly so, than 12.5mg/70kg heroin.
IV heroin and morphine, at their higher dose levels (25mg and 50mg/70kg morphine or 12.5mg and 25mg /70kg heroin) produced the highest subjective ratings and highest self-administration and reinforcing effect, albeit with some “bad effects” (defined as effects which were noted to be "unpleasant" such as excessive sedation, respiratory depression, nausea, and histamine-related effects such as pruritus. Heroin acts as a morphine prodrug and this accounts for this). Oxycodone produced virtually no “bad effects”. although it failed to achieve the reinforcing effect of higher heroin and morphine doses.
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