AIMS: Activation of PPARγ by pioglitazone (PIO) has shown some efficacy in attenuating addictive-like responses in laboratory animals. The ability of PIO to alter the effects of opioids in humans has not been characterized in a controlled laboratory setting. The proposed investigation sought to examine the effects of PIO on the subjective, analgesic, physiological and cognitive effects of oxycodone (OXY).METHODS: During this investigation, nondependent prescription opioid abusers (N=17 completers) were maintained for 2-3weeks on ascending daily doses of PIO (0mg, 15mg, 45mg) prior to completing a laboratory session assessing the aforementioned effects of OXY [using a within-session cumulative dosing procedure (0, 10, and 20mg, cumulative dose=30mg)].RESULTS: OXY produced typical mu opioid agonist effects: miosis, decreased pain perception, and decreased respiratory rate. OXY also produced dose-dependent increases in positive subjective responses. Yet, ratings such as: drug "liking," "high," and "good drug effect," were not significantly altered as a function of PIO maintenance dose.DISCUSSION: These data suggest that PIO may not be useful for reducing the abuse liability of OXY. These data were obtained with a sample of nondependent opioid users and therefore may not be applicable to dependent populations or to other opioids. Although PIO failed to alter the abuse liability of OXY, the interaction between glia and opioid receptors is not well understood so the possibility remains that medications that interact with glia in other ways may show more promise.