title: Intranasal buprenorphine alone and in combination with naloxone: Abuse liability and reinforcing efficacy in physically dependent opioid abusers.
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.
authors.affiliation: 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.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Walsh
authors.affiliation: 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.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Nuzzo
authors.affiliation: 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.
authors.forename: Shanna
authors.initials: S
authors.lastname: Babalonis
authors.affiliation: Center on Drug and Alcohol Research, University of Kentucky, 845 Angliana Avenue, Lexington, KY 40508, USA. Electronic address: victoria.casselton@uky.edu.
authors.forename: Victoria
authors.initials: V
authors.lastname: Casselton
authors.affiliation: 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.
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Lofwall
mesh_terms: D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid; D002047:Buprenorphine / Q000494:pharmacology*; D000069479:Buprenorphine, Naloxone Drug Combination / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009294:Narcotics; D058850:Opiate Substitution Treatment / Q000379:methods; D009293:Opioid-Related Disorders / Q000188:drug therapy*; D010098:Oxycodone / Q000494:pharmacology; D012054:Reinforcement, Psychology; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D000069479:Buprenorphine, Naloxone Drug Combination; D009292:Narcotic Antagonists; D009294:Narcotics; D009270:Naloxone; D002047:Buprenorphine; D010098:Oxycodone
keywords: Abuse; Buprenorphine; Misuse; Mu agonist; Opioid; Opioid withdrawal