title: Abuse liability assessment of hydrocodone under current draft regulatory guidelines.
abstract: BACKGROUND
  The abuse liability of hydrocodone was assessed in male Sprague-Dawley rats under the European Medicines Agency, the International Commission on Harmonisation, and the U.S. Food & Drug Administration draft guidelines for the non-clinical investigation of the dependence potential of medicinal products.
  
  
  METHODS
  Self-administration, drug discrimination, and repeat-dose two week dependence liability studies were conducted to compare hydrocodone to the prototypical opiates, morphine and oxycodone.
  
  
  RESULTS
  Hydrocodone was self-administered, produced an opiate-like subjective discriminative generalization profile and produced a significant discontinuation syndrome following abrupt treatment cessation that was quantitatively and qualitatively similar to morphine and/or oxycodone.
  
  
  CONCLUSIONS
  Hydrocodone has abuse liability more similar to Schedule II opiates than other Schedule III compounds currently controlled under the U.S. Controlled Substance Act.
authors.affiliation: Department of Safety Pharmacology and Neurobehavioral Sciences, MPI Research Inc., Mattawan, MI, United States. Electronic address: david.gauvin@mpiresearch.com.
authors.forename: David V
authors.initials: DV
authors.lastname: Gauvin
authors.affiliation: Department of Safety Pharmacology and Neurobehavioral Sciences, MPI Research Inc., Mattawan, MI, United States.
authors.forename: Margaret
authors.initials: M
authors.lastname: McComb
authors.affiliation: Department of Safety Pharmacology and Neurobehavioral Sciences, MPI Research Inc., Mattawan, MI, United States.
authors.forename: Robert
authors.initials: R
authors.lastname: Code
authors.affiliation: Department of Safety Pharmacology and Neurobehavioral Sciences, MPI Research Inc., Mattawan, MI, United States.
authors.forename: Jill A
authors.initials: JA
authors.lastname: Dalton
authors.affiliation: Department of Safety Pharmacology and Neurobehavioral Sciences, MPI Research Inc., Mattawan, MI, United States.
authors.forename: Theodore J
authors.initials: TJ
authors.lastname: Baird
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D004192:Discrimination, Psychological; D017408:Guidelines as Topic; D006853:Hydrocodone / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology; D009293:Opioid-Related Disorders / Q000503:physiopathology*; D010098:Oxycodone / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
chemical_list: D000701:Analgesics, Opioid; D006853:Hydrocodone; D009020:Morphine; D010098:Oxycodone
keywords: Abuse liability; Discontinuation syndrome; Drug dependence; Drug discrimination; Hydrocodone; Methods; Morphine; Oxycodone; Self administration; Withdrawal