title: Abuse potential of intranasal buprenorphine versus buprenorphine/naloxone in buprenorphine-maintained heroin users.
abstract: In spite of the clinical utility of buprenorphine, parenteral abuse of this medication has been reported in several laboratory investigations and in the real world. Studies have demonstrated lower abuse liability of the buprenorphine/naloxone combination relative to buprenorphine alone. However, clinical research has not yet examined the utility of the combined formulation to deter intranasal use in a buprenorphine-maintained population. Heroin-using volunteers (n = 12) lived in the hospital for 8-9 weeks and were maintained on each of three sublingual buprenorphine doses (2, 8, 24 mg). Under each maintenance dose, participants completed laboratory sessions during which the reinforcing and subjective effects of intranasal doses of buprenorphine (8, 16 mg), buprenorphine/naloxone (8/2, 8/8, 8/16, 16/4 mg) and controls (placebo, heroin 100 mg, naloxone 4 mg) were assessed. Intranasal buprenorphine alone typically produced increases in positive subjective effects and the 8 mg dose was self-administered above the level of placebo. The addition of naloxone dose dependently reduced positive subjective effects and increased aversive effects. No buprenorphine/naloxone combination dose was self-administered significantly more than placebo. These data suggest that within a buprenorphine-dependent population, intranasal buprenorphine/naloxone has reduced abuse potential in comparison to buprenorphine alone. These data strongly argue in favor of buprenorphine/naloxone rather than buprenorphine alone as the more reasonable option for managing the risk of buprenorphine misuse.
authors: Division of Substance Abuse, New York Psychiatric Institute and Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
authors: Jermaine D
authors: JD
authors: Jones
authors: Division of Substance Abuse, New York Psychiatric Institute and Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
authors: Maria A
authors: MA
authors: Sullivan
authors: Division of Substance Abuse, New York Psychiatric Institute and Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
authors: Suzanne K
authors: SK
authors: Vosburg
authors: Division of Substance Abuse, New York Psychiatric Institute and Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
authors: Jeanne M
authors: JM
authors: Manubay
authors: Division of Substance Abuse, New York Psychiatric Institute and Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
authors: Shanthi
authors: S
authors: Mogali
authors: Division of Substance Abuse, New York Psychiatric Institute and Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
authors: Verena
authors: V
authors: Metz
authors: Division of Substance Abuse, New York Psychiatric Institute and Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
authors: Sandra D
authors: SD
authors: Comer
mesh_terms: D000281:Administration, Intranasal; D000286:Administration, Sublingual; D000328:Adult; D000704:Analysis of Variance; D002047:Buprenorphine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000069479:Buprenorphine, Naloxone Drug Combination / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006556:Heroin Dependence / Q000534:rehabilitation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009292:Narcotic Antagonists / Q000008:administration & dosage* / Q000493:pharmacokinetics; D009293:Opioid-Related Disorders / Q000517:prevention & control*; D011597:Psychomotor Performance / Q000187:drug effects; D012054:Reinforcement, Psychology; D012646:Self Administration; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000069479:Buprenorphine, Naloxone Drug Combination; D009292:Narcotic Antagonists; D002047:Buprenorphine
keywords: Abuse liability; buprenorphine; intranasal; opioids; self-administration