Abuse liability assessment of hydrocodone under current draft regulatory guidelines

Abstract

Introduction: 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.

Conclusion: Hydrocodone has abuse liability more similar to Schedule II opiates than other Schedule III compounds currently controlled under the U.S. Controlled Substance Act.

Keywords: Abuse liability; Discontinuation syndrome; Drug dependence; Drug discrimination; Hydrocodone; Methods; Morphine; Oxycodone; Self administration; Withdrawal.