title: Abuse liability of intravenous buprenorphine/naloxone and buprenorphine alone in buprenorphine-maintained intravenous heroin abusers.
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.
authors.affiliation: Department of Psychiatry, Columbia University, New York State Psychiatric Institute, New York, NY 10032, USA. sdc10@columbia.edu
authors.forename: Sandra D
authors.initials: SD
authors.lastname: Comer
authors.forename: Maria A
authors.initials: MA
authors.lastname: Sullivan
authors.forename: Suzanne K
authors.initials: SK
authors.lastname: Vosburg
authors.forename: Jeanne
authors.initials: J
authors.lastname: Manubay
authors.forename: Leslie
authors.initials: L
authors.lastname: Amass
authors.forename: Ziva D
authors.initials: ZD
authors.lastname: Cooper
authors.forename: Phillip
authors.initials: P
authors.lastname: Saccone
authors.forename: Herbert D
authors.initials: HD
authors.lastname: Kleber
mesh_terms: D000286:Administration, Sublingual; D000328:Adult; D000704:Analysis of Variance; D016739:Behavior, Addictive; D002047:Buprenorphine / Q000008:administration & dosage* / Q000009:adverse effects; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006556:Heroin Dependence / Q000191:economics / Q000534:rehabilitation*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000008:administration & dosage* / Q000009:adverse effects; D009292:Narcotic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D009294:Narcotics / Q000008:administration & dosage* / Q000009:adverse effects; D057240:Patient Preference; D012646:Self Administration; D015819:Substance Abuse, Intravenous / Q000534:rehabilitation*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy; D055815:Young Adult
chemical_list: D004338:Drug Combinations; D009292:Narcotic Antagonists; D009294:Narcotics; D009270:Naloxone; D002047:Buprenorphine
references.citation: Am J Addict. 2008 Mar-Apr;17(2):116-20
references.pmid: 18393054
references.citation: Addiction. 2007 Dec;102(12):1899-907
references.pmid: 17784896
references.citation: Drug Alcohol Depend. 1998 Mar 1;50(1):1-8
references.pmid: 9589267
references.citation: Am J Addict. 2004;13 Suppl 1:S29-41
references.pmid: 15204674
references.citation: Psychopharmacology (Berl). 1988;94(4):484-90
references.pmid: 2453895
references.citation: Addiction. 2001 Feb;96(2):267-72
references.pmid: 11182872
references.citation: Drug Alcohol Depend. 1993 Sep;33(2):105-17
references.pmid: 8261875
references.citation: N Engl J Med. 2003 Sep 4;349(10):949-58
references.pmid: 12954743
references.citation: Psychopharmacology (Berl). 2001 Mar;154(3):230-42
references.pmid: 11351930
references.citation: Cochrane Database Syst Rev. 2008 Apr 16;(2):CD002207
references.pmid: 18425880
references.citation: Neuropsychobiology. 1988;19(2):90-6
references.pmid: 3226529
references.citation: Drug Alcohol Depend. 1997 Apr 14;45(1-2):81-91
references.pmid: 9179510
references.citation: Addiction. 2005 Feb;100(2):197-205
references.pmid: 15679749
references.citation: Addiction. 2003 Mar;98(3):291-303
references.pmid: 12603229
references.citation: Drug Alcohol Rev. 2008 Mar;27(2):197-9
references.pmid: 18264882
references.citation: AIDS Care. 2002 Feb;14(1):77-93
references.pmid: 11798407
references.citation: Addiction. 2008 Jan;103(1):80-8
references.pmid: 17995994
references.citation: Clin Pharmacol Ther. 1989 Jan;45(1):66-71
references.pmid: 2491980
references.citation: Drug Alcohol Depend. 2007 Apr 17;88(1):75-8
references.pmid: 17055191
references.citation: Drug Alcohol Depend. 2008 Jul 1;96(1-2):183-6
references.pmid: 18423901
references.citation: Singapore Med J. 2006 Nov;47(11):919-21
references.pmid: 17075655
references.citation: Lancet. 2008 Nov 15;372(9651):1733-45
references.pmid: 18817968
references.citation: Drug Alcohol Depend. 2008 Sep 1;97(1-2):105-13
references.pmid: 18479840
references.citation: Clin Infect Dis. 2006 Dec 15;43 Suppl 4:S197-215
references.pmid: 17109307
references.citation: Curr Psychiatry Rep. 2007 Oct;9(5):358-64
references.pmid: 17915074
references.citation: Drug Alcohol Depend. 2004 Jul 15;75(1):37-45
references.pmid: 15225887
references.citation: Psychopharmacology (Berl). 1999 Apr;143(4):327-38
references.pmid: 10367549
references.citation: Subst Abuse Treat Prev Policy. 2008 Jun 17;3:16
references.pmid: 18559110
references.citation: N Engl J Med. 2006 Jul 27;355(4):365-74
references.pmid: 16870915
references.citation: J Subst Abuse Treat. 2003 Oct;25(3):125-34
references.pmid: 14670518
references.citation: J Pharmacol Exp Ther. 2005 Dec;315(3):1320-30
references.pmid: 16144974
references.citation: Drug Alcohol Depend. 2008 Jul 1;96(1-2):1-15
references.pmid: 18436394
references.citation: N Engl J Med. 2000 Nov 2;343(18):1290-7
references.pmid: 11058673
references.citation: Ann Intern Med. 1993 Jul 1;119(1):23-7
references.pmid: 8498759
references.citation: Addiction. 2005 Feb;100(2):150-8
references.pmid: 15679744
references.citation: Drug Alcohol Depend. 2003 May 21;70(2 Suppl):S49-57
references.pmid: 12738350