Abuse liability of intravenous buprenorphine/naloxone and buprenorphine alone in buprenorphine-maintained intravenous heroin abusers

Addiction. 2010 Apr;105(4):709-18. doi: 10.1111/j.1360-0443.2009.02843.x.

Abstract

Background: Sublingual buprenorphine is an effective maintenance treatment for opioid dependence, yet intravenous buprenorphine misuse occurs. A buprenorphine/naloxone formulation was developed to mitigate this misuse risk. This randomized, double-blind, cross-over study was conducted to assess the intravenous abuse potential of buprenorphine/naloxone compared with buprenorphine in buprenorphine-maintained injection drug users (IDUs).

Methods: Intravenous heroin users (n = 12) lived in the hospital for 8-9 weeks and were maintained on each of three different sublingual buprenorphine doses (2 mg, 8 mg, 24 mg). Under each maintenance dose, participants completed laboratory sessions during which the reinforcing and subjective effects of intravenous placebo, naloxone, heroin and low and high doses of buprenorphine and buprenorphine/naloxone were examined. Every participant received each test dose under the three buprenorphine maintenance dose conditions.

Results: Intravenous buprenorphine/naloxone was self-administered less frequently than buprenorphine or heroin (P < 0.0005). Participants were most likely to self-administer drug intravenously when maintained on the lowest sublingual buprenorphine dose. Subjective ratings of 'drug liking' and 'desire to take the drug again' were lower for buprenorphine/naloxone than for buprenorphine or heroin (P = 0.0001). Participants reported that they would pay significantly less money for buprenorphine/naloxone than for buprenorphine or heroin (P < 0.05). Seven adverse events were reported; most were mild and transient.

Conclusions: These data suggest that although the buprenorphine/naloxone combination has intravenous abuse potential, that potential is lower than it is for buprenorphine alone, particularly when participants received higher maintenance doses and lower buprenorphine/naloxone challenge doses. Buprenorphine/naloxone may be a reasonable option for managing the risk for buprenorphine misuse during opioid dependence treatment.

Trial registration: ClinicalTrials.gov NCT00710385.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Sublingual
  • Adult
  • Analysis of Variance
  • Behavior, Addictive
  • Buprenorphine / administration & dosage*
  • Buprenorphine / adverse effects
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Heroin Dependence / economics
  • Heroin Dependence / rehabilitation*
  • Humans
  • Male
  • Middle Aged
  • Naloxone / administration & dosage*
  • Naloxone / adverse effects
  • Narcotic Antagonists / administration & dosage*
  • Narcotic Antagonists / adverse effects
  • Narcotics / administration & dosage*
  • Narcotics / adverse effects
  • Patient Preference
  • Self Administration
  • Substance Abuse, Intravenous / rehabilitation*
  • Substance Withdrawal Syndrome / drug therapy
  • Young Adult

Substances

  • Drug Combinations
  • Narcotic Antagonists
  • Narcotics
  • Naloxone
  • Buprenorphine

Associated data

  • ClinicalTrials.gov/NCT00710385