The effects of pioglitazone, a PPARγ receptor agonist, on the abuse liability of oxycodone among nondependent opioid users

Abstract

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 2–3 weeks on ascending daily doses of PIO (0 mg, 15 mg, 45 mg) prior to completing a laboratory session assessing the aforementioned effects of OXY [using a within-session cumulative dosing procedure (0, 10, and 20 mg, cumulative dose = 30 mg)]. 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.

Glial and neuroinflammatory targets for treating substance use disorders

“…The investigators found that OXY produced dose-dependent increases in positive subjective responses. PIO administration appeared not to alter OXY-induced increases in positive subjective effects as ratings on measures of drug “liking,” “high,” and “good drug effect” were not significantly altered as a function of PIO maintenance dose (Jones et al, 2016). The authors concluded that PIO may not be useful for reducing the abuse liability of OXY (Jones et al, 2016).…”

“…PIO administration appeared not to alter OXY-induced increases in positive subjective effects as ratings on measures of drug “liking,” “high,” and “good drug effect” were not significantly altered as a function of PIO maintenance dose (Jones et al, 2016). The authors concluded that PIO may not be useful for reducing the abuse liability of OXY (Jones et al, 2016). Yet among the study’s limitations the investigators note that results obtained from a non-dependent sample of opioid users, may not be generalizable to heavier, opioid-dependent users.…”

The exploration of pioglitazone’s potential as a pharmacotherapy option for drug addiction

“…15 Interestingly, pioglitazone did not have any significant effects on the abuse potential of the opioid oxycodone in nondependent users of prescription opioids. 16 It is important to note, however, that this may have been due to the fact that the sample population were not opioid-dependent. 16 This data may be inconsistent with previously mentioned preclinical studies with opioids because animal models are representations of stronger opioid dependence.…”

“…1 In addition to its uses as an anti-diabetic medication, evidence suggests that pioglitazone can cross the blood-brain barrier and improve various neurological conditions. [4][5][6][7] Current research suggests that PPARγ agonists may be a promising novel treatment option for drug addiction treatment. 8 Specifically, the therapeutic benefits of pioglitazone in drug addiction has been investigated in both preclinical and clinical experiments.…”

“…8 Specifically, the therapeutic benefits of pioglitazone in drug addiction has been investigated in both preclinical and clinical experiments. 2,[9][10][11][12][13][14][15][16] The present review will investigate the current preclinical and clinical evidence supporting the therapeutic potential of pioglitazone in the prevention of drug addiction development and relapse. This review will also explore the potential mechanisms underlying the anti-addictive properties of pioglitazone and its side effects.…”