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.
|Number of pages||9|
|Journal||Drug and Alcohol Dependence|
|State||Published - May 1 2016|
Bibliographical noteFunding Information:
This study was supported by a grant from the National Institute on Drug Abuse, R01 DA016718-04 (SLW) and the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, UL1TR000117. Reckitt Benckiser and the National Institute on Drug Abuse provided the drug supply at no cost. None of these agencies had any role in the study design; in the collection, analysis and interpretation of the data; in writing of the report; and in the decision to submit the article for publication.
The authors would like to thank the nursing staff at the Center for Clinical and Translational Research, the research staff at the Center on Drug and Alcohol Research, the pharmacy staff at the Investigational Drug Services Pharmacy at the University of Kentucky for support of this project, and Lisa Middleton, Ph.D. for work on an early draft of the protocol. The authors also thank Reckitt Benckiser Pharmaceuticals, especially Dr. Neil Hyde and Dr. Chris Chapleo, for assistance in obtaining the EU buprenorphine/naloxone supply at no cost through the NIDA Research Triangle Institute drug supply program.
© 2016 Elsevier Ireland Ltd.
- Mu agonist
- Opioid withdrawal
ASJC Scopus subject areas
- Psychiatry and Mental health
- Pharmacology (medical)