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 morphinemaintained heroin abusers (N ¼ 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 fentanyl4buprenorphineXheroin 4morphine ¼ 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.

The Subjective, Reinforcing, and Analgesic Effects of Oxycodone in Patients with Chronic, Non-Malignant Pain who are Maintained on Sublingual Buprenorphine/Naloxone

“…These results are in marked contrast with previous reports observed with heroin-dependent participants and prescription opioid abusers who self-administered similar oxycodone doses at significantly higher levels (Comer et al, 2008(Comer et al, , 2009Comer et al, 2010). The Bup/Nx dosing regimen used in this study was most likely responsible for the marked differences in outcomes between prescription opioid-abusing pain patients and heroin abusers.…”

“…When compared with Bup/Nx, oxycodone had similar effects on experimentally induced pain and clinical pain assessments, yet with minimal aversive effects and a number of positive subjective effects. This observation is consistent with recent reports of an overall positive subjective profile of oxycodone among opioid abusers and non-abusers (Comer et al, 2008;Walsh et al, 2008;Zacny and Lichtor, 2008). Yet, in comparison to other investigations noting the positive subjective effects of similar oxycodone doses, those reported in this study were relatively small.…”

“…The use of opioids for the treatment of chronic, non-cancer pain has escalated in recent years, and it is estimated that opioids are used to manage a significant percentage of cases involving moderate to severe persistent pain (Ballantyne and Mao, 2003;Trescot et al, 2006). Despite their medical utility, many opioid analgesics including morphine, hydrocodone, hydromorphone, fentanyl, and oxycodone have significant abuse liability (Comer et al, 2008;Walsh et al, 2008;Zacny and Lichtor, 2008). Aberrant opioid use behaviors among patients with pain include: obtaining prescriptions from multiple prescribers, forging prescriptions, 'borrowing' or stealing opioids, aggressively seeking more medication from physicians, and escalating doses without the physician's knowledge (Cowan et al, 2001;Martell et al, 2007;Passik et al, 2006).…”

“…Multiple laboratories have consistently shown that oxycodone produces dose-related increases in positive subjective effects among heroin abusers, prescription opioid abusers, and non-drug abusers (Comer et al, 2008(Comer et al, , 2009(Comer et al, , 2010bWalsh et al, 2008;Zacny and Gutierrez, 2009;Zacny and Lichtor, 2008). Oxycodone serves as a robust reinforcer among participants who abuse heroin or prescription opioids (Comer et al, 2008;Comer et al, 2009), yet non-drug-abusing volunteers only selfadminister oxycodone when they are exposed to experimentally induced pain (Comer et al, 2010). These data suggest that although subjective response to oxycodone (eg, greater drug liking and/or lesser adverse effects) may predispose individuals to abuse it, this factor alone is not sufficient to motivate abuse.…”

Likeability and Abuse Liability of Commonly Prescribed Opioids

“…Some studies included questionnaires involving reinforcement data including drug effect, liking, and take again [6][7][8][9]. One study directly assessed breakpoint values of participants' desire for drug vs. money [10]. Additionally, studies included objective physiologic data and performance batteries to assess timing of onset, duration, and extent of opioid affects (Table 1).…”