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Effects of the NK1 antagonist, aprepitant, on response to oral and intranasal oxycodone in prescription opioid abusers

Authors

  • Sharon L. Walsh,

    Corresponding author
    1. Center on Drug and Alcohol Research, University of Kentucky, Lexington, KY, USA
    2. Department of Behavioral Science, University of Kentucky, Lexington, KY, USA
    3. Department of Psychiatry, University of Kentucky, Lexington, KY, USA
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  • Markus Heilig,

    1. National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA
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  • Paul A. Nuzzo,

    1. Center on Drug and Alcohol Research, University of Kentucky, Lexington, KY, USA
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  • Pam Henderson,

    1. Center on Drug and Alcohol Research, University of Kentucky, Lexington, KY, USA
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  • Michelle R. Lofwall

    1. Center on Drug and Alcohol Research, University of Kentucky, Lexington, KY, USA
    2. Department of Behavioral Science, University of Kentucky, Lexington, KY, USA
    3. Department of Psychiatry, University of Kentucky, Lexington, KY, USA
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  • This work was carried out at the Straus Behavioral Science Research Building, University of Kentucky, Center on Drug and Alcohol Research, 515 Oldham Court, Lexington, KY 40503.

Sharon L. Walsh, Center on Drug and Alcohol Research, 515 Oldham Court, Lexington, KY 40503, USA. E-mail: sharon.walsh@uky.edu

ABSTRACT

Pre-clinical studies suggest that the neurokinin-1 (NK1) receptor may modulate the response to opioids, with NK1 inactivation leading to decreased opioid reinforcement, tolerance and withdrawal. Aprepitant is a selective NK1 antagonist currently marketed for clinical use as an anti-emetic. This 6-week in-patient study used a randomized, double-blind, double-dummy, within-subject, crossover design. Subjects (n = 8; 6 male/2 female) were healthy, adult volunteers who provided subjective and objective evidence of current prescription opioid abuse (without physical dependence) and underwent careful medical and psychiatric screening. Fifteen experimental conditions, consisting of one aprepitant dose (0, 40 and 200 mg, p.o. given as a 2-hour pre-treatment) in combination with one oxycodone dose [placebo, oral (20 and 40 mg/70 kg) and intranasal (15 and 30 mg/70 kg)], were examined. Sessions were conducted at least 48-hour apart and multi-dimensional measures were collected repeatedly throughout the 6-hour session duration. Oxycodone, by both routes of administration, produced significant dose-related effects on the predicted measures (e.g. subjective measures of abuse liability, respiratory depression and miosis). Pre-treatment with aprepitant (200 mg) significantly enhanced ratings of oxycodone subjective effects related to euphoria and liking and doubled the street value estimates for the highest test doses of oxycodone by both routes. Some objective measures (respiratory function, observer-rated opioid agonist effects) were similarly enhanced by pre-treatment with the highest dose of aprepitant. All dose combinations were safely tolerated. These findings are discussed in the context of the potential utility of NK1 antagonists in the treatment of opioid use disorders.

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