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: Sharon L Walsh, Paul A Nuzzo, Shanna Babalonis, Victoria Casselton, Michelle R Lofwall
• Journal: Drug and alcohol dependence (Drug Alcohol Depend) Vol. 162 Pg. 190-8 (May 01 2016) ISSN: 1879-0046 [Electronic] Ireland
• PMID: 27012435 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Analgesics, Opioid
• Buprenorphine, Naloxone Drug Combination
• Narcotic Antagonists
• Narcotics
• Naloxone
• Buprenorphine
• Oxycodone

Topics

• Administration, Intranasal
• Adolescent
• Adult
• Analgesics, Opioid
• Buprenorphine (pharmacology)
• Buprenorphine, Naloxone Drug Combination (pharmacology)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Humans
• Male
• Middle Aged
• Naloxone (pharmacology)
• Narcotic Antagonists (pharmacology)
• Narcotics
• Opiate Substitution Treatment (methods)
• Opioid-Related Disorders (drug therapy)
• Oxycodone (pharmacology)
• Reinforcement, Psychology
• Self Administration
• Substance Withdrawal Syndrome (drug therapy)
• Young Adult