title: Human abuse liability assessment of oxycodone combined with ultra-low-dose naltrexone.
abstract: BACKGROUND
  Prescription opioid abuse has risen dramatically in the United States as clinicians have increased opioid prescribing for alleviation of both acute and chronic pain. Opioid analgesics with decreased risk for abuse are needed.
  
  
  OBJECTIVE
  Preclinical and clinical studies have shown that opioids combined with ultra-low-dose naltrexone (NTX) may have increased analgesic potency and have suggested reduced abuse or dependence liability. This study addressed whether addition of ultra-low-dose naltrexone might decrease the abuse liability of oxycodone (OXY) in humans.
  
  
  METHODS
  This double-blind, placebo-controlled study systematically examined the subjective and physiological effects of combining oral OXY and ultra-low NTX doses in 14 experienced opioid abusers. Seven acute drug conditions given at least 5 days apart were compared in a within-subject crossover design: placebo, OXY 20 mg, OXY 40 mg, plus each of the active OXY doses combined with 0.0001 and 0.001 mg NTX.
  
  
  RESULTS
  The methods were sensitive to detecting opioid effects on abuse liability indices, with significant differences between all OXY conditions and placebo as well as between 20 and 40 mg OXY doses on positive subjective ratings (e.g., "I feel a good drug effect" or "I like the drug"), on observer- and participant-rated opioid agonist effects, and on a drug-versus-money value rating. There were no significant differences or evident trends associated with the addition of either NTX dose on any abuse liability indices.
  
  
  CONCLUSIONS
  The addition of ultra-low-dose NTX to OXY did not decrease abuse liability of acutely administered OXY in experienced opioid abusers.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA. dtompki1@jhmi.edu
authors.forename: David Andrew
authors.initials: DA
authors.lastname: Tompkins
authors.forename: Ryan K
authors.initials: RK
authors.lastname: Lanier
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Harrison
authors.forename: Eric C
authors.initials: EC
authors.lastname: Strain
authors.forename: George E
authors.initials: GE
authors.lastname: Bigelow
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects*; D016739:Behavior, Addictive / Q000517:prevention & control* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000008:administration & dosage / Q000009:adverse effects*; D009293:Opioid-Related Disorders / Q000517:prevention & control* / Q000523:psychology; D010098:Oxycodone / Q000008:administration & dosage / Q000009:adverse effects*; D010919:Placebos
chemical_list: D000701:Analgesics, Opioid; D010919:Placebos; D009271:Naltrexone; D010098:Oxycodone
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