This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Epidemiological studies report increasing non-medical use and diversion of prescription opioid analgesics. Oxycodone is marketed in an array of formulations and used for the treatment of acute and chronic pain. Oxycontin is a sustained-release formulation which is marketed in higher dosage formulations compared to immediate release products; both formulations have received substantial negative publicity due to reports of increased frequency of unintentional addiction, fatal overdose and criminal diversion. Hydrocodone, a related semi-synthetic opioid, is the most widely prescribed opioid analgesic in the United States and the most frequently mentioned prescription opioid in emergency room admissions. Despite their widespread clinical use, few studies have evaluated the abuse liability and clinical pharmacology of these commonly used opioids. This project will employ controlled laboratory procedures to evaluate and characterize the effects of oxycodone and hydrocodone in volunteers with histories of opioid abuse under an array of conditions. This study will use a randomized, placebo-controlled, double-blind, within-subject design. Dose rising pilot evaluations will precede randomized testing for safety purposes. Experiment 1 will compare the effects of oral oxycodone and hydrocodone to those of hydromorphone, a mu opioid agonist with known high abuse potential, and placebo over a broad range of doses. Physiological, subjective and behavioral measures will be collected to assess safety and abuse liability, respectively, and a battery of psychomotor and cognitive tasks will assess the impairing effects of these agents. This study will contribute substantial new knowledge about the relative abuse potential and safety of these widely available agents at therapeutic and supratherapeutic doses in a population of subjects who are likely to abuse them. Information relevant to the public health will include the relative potency and tolerability of these compounds, and empirical information relevant to safety, scheduling and marketing of these agent
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