Sharon L Walsh1, Paul A Nuzzo2, Shanna Babalonis3, Victoria Casselton4, Michelle R Lofwall5. 1. Center on Drug and Alcohol Research, University of Kentucky, 845 Angliana Avenue, Lexington, KY 40508, USA; Department of Behavioral Science, University of Kentucky, USA; Department of Psychiatry, University of Kentucky, USA; Department of Pharmacology, University of Kentucky, USA; Department of Pharmaceutical Sciences, University of Kentucky, USA. Electronic address: sharon.walsh@uky.edu. 2. Center on Drug and Alcohol Research, University of Kentucky, 845 Angliana Avenue, Lexington, KY 40508, USA; Department of Behavioral Science, University of Kentucky, USA. Electronic address: paul.nuzzo@uky.edu. 3. Center on Drug and Alcohol Research, University of Kentucky, 845 Angliana Avenue, Lexington, KY 40508, USA; Department of Behavioral Science, University of Kentucky, USA. Electronic address: shanna.babalonis@uky.edu. 4. Center on Drug and Alcohol Research, University of Kentucky, 845 Angliana Avenue, Lexington, KY 40508, USA. Electronic address: victoria.casselton@uky.edu. 5. Center on Drug and Alcohol Research, University of Kentucky, 845 Angliana Avenue, Lexington, KY 40508, USA; Department of Behavioral Science, University of Kentucky, USA; Department of Psychiatry, University of Kentucky, USA. Electronic address: michelle.lofwall@uky.edu.
Abstract
BACKGROUND:Buprenorphine can be abused by the intranasal route. This study sought to examine the relative abuse liability and reinforcing efficacy of intranasal buprenorphine compared to intranasal buprenorphine/naloxone in opioid-dependent individuals. METHODS:Eleven healthy male and female volunteers physically dependent on short-acting opioids resided as inpatients during participation in this double blind, within subject, placebo-controlled study. Participants were maintained on oxycodone (30 mg/q.i.d., p.o.) throughout the 6-week study. Eight pairs of experimental sessions were conducted at ≥48 h intervals to examine the pharmacodynamic profile (Sample) and reinforcing efficacy (Self-administration the following day) of intranasal placebo, oxycodone (60 mg), buprenorphine (2, 8 & 16 mg) and buprenorphine/naloxone (2/0.5, 8/2 & 16/4 mg). Subjective, observer-rated and physiological measures were collected to assess the magnitude of opioid agonist and antagonist effects. A progressive ratio self-administration procedure assessed choices for drug versus money. RESULTS: All active doses produced opioid agonist-like effects (e.g., increased ratings of "liking," and miosis) compared to placebo. The effects of buprenorphine and buprenorphine/naloxone were not reliably dose-dependent. Intranasal buprenorphine/naloxone elicited modest and transient opioid withdrawal-like effects in the first hour post-drug administration, while simultaneously blunting or blocking the early onset of agonist effects seen with buprenorphine alone. All active doses of buprenorphine were self-administered more than placebo, but buprenorphine/naloxone doses were not. CONCLUSIONS: These data confirm that intranasal buprenorphine/naloxone has deterrent properties related to transient withdrawal effects that likely decrease its desirability for misuse compared to buprenorphine in opioid-dependent individuals maintained on short-acting opioids.
RCT Entities:
BACKGROUND:Buprenorphine can be abused by the intranasal route. This study sought to examine the relative abuse liability and reinforcing efficacy of intranasal buprenorphine compared to intranasal buprenorphine/naloxone in opioid-dependent individuals. METHODS: Eleven healthy male and female volunteers physically dependent on short-acting opioids resided as inpatients during participation in this double blind, within subject, placebo-controlled study. Participants were maintained on oxycodone (30 mg/q.i.d., p.o.) throughout the 6-week study. Eight pairs of experimental sessions were conducted at ≥48 h intervals to examine the pharmacodynamic profile (Sample) and reinforcing efficacy (Self-administration the following day) of intranasal placebo, oxycodone (60 mg), buprenorphine (2, 8 & 16 mg) and buprenorphine/naloxone (2/0.5, 8/2 & 16/4 mg). Subjective, observer-rated and physiological measures were collected to assess the magnitude of opioid agonist and antagonist effects. A progressive ratio self-administration procedure assessed choices for drug versus money. RESULTS: All active doses produced opioid agonist-like effects (e.g., increased ratings of "liking," and miosis) compared to placebo. The effects of buprenorphine and buprenorphine/naloxone were not reliably dose-dependent. Intranasal buprenorphine/naloxone elicited modest and transient opioid withdrawal-like effects in the first hour post-drug administration, while simultaneously blunting or blocking the early onset of agonist effects seen with buprenorphine alone. All active doses of buprenorphine were self-administered more than placebo, but buprenorphine/naloxone doses were not. CONCLUSIONS: These data confirm that intranasal buprenorphine/naloxone has deterrent properties related to transient withdrawal effects that likely decrease its desirability for misuse compared to buprenorphine in opioid-dependent individuals maintained on short-acting opioids.
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