The drug discrimination assay: Interpretative value of partial generalization for drug schedule control actions.

The U.S. Food & Drug Administration (FDA) has issued a final guidance document on the preclinical determination of abuse potential that must be conducted in animals for all new molecular entities (NMEs) submitted for a new drug application (NDA). Under statutory restrictions government guidance documents serve only as a guide or an expression of the agency's current thinking on the topic. Guidelines do not legally bind the agency or its registrants to any content in the guidance. There are no statutory (legal) descriptions of what study designs or methodology must be submitted to the Drug Enforcement Administration with respect to drug scheduling review. This paper describes the utility of an alternate method used, worldwide, to assess the internal subjective effects of drugs to predict the abuse liability that provides additional information to address the relative aspects of that liability.

Abuse liability assessment of hydrocodone under current draft regulatory guidelines.

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.