Rationale: Preclinical studies demonstrate that the NK1 receptor is involved in opioid reinforcement and withdrawal expression. Few studies have examined the impact of treatment with NK1 antagonists on opioid response in humans. Objective: To explore the potential for a selective NK1 antagonist, tradipitant, to attenuate the abuse liability and reinforcing and analgesic effects of oxycodone in opioid-experienced individuals. Methods: Participants with recreational opioid use, but without opioid physical dependence, were enrolled as inpatients for ~6 weeks (n = 8). A within-subject, double-blind, randomized, placebo-controlled, crossover design was employed. The pharmacodynamic response to intranasal oxycodone across a range of doses (0 to 30 mg) was examined during two counterbalanced maintenance periods (tradipitant 0 or 85 mg/bid). Oxycodone self-administration was assessed with a modified progressive ratio procedure, and analgesia was assessed with the cold pressor test. Results: Oxycodone produced significant and dose-related increases on a broad array of prototypic opioid measures, including subjective ratings related to abuse liability (e.g., liking) and physiological outcomes (i.e., expired CO2). Oxycodone self-administration increased with increasing dose, as did analgesia. Tradipitant largely did not alter any of these effects of oxycodone, with the exception of producing a reduction in ratings of desire for opioids. Conclusions: Given that the vast majority of oxycodone effects were unchanged by tradipitant, these data do not provide support for the utility of NK1 antagonists as a potential treatment for opioid use disorder.
|Number of pages||10|
|State||Published - Jul 2021|
Bibliographical noteFunding Information:
This study was supported by the National Institute on Drug Abuse (R01 DA040637). Vanda Pharmaceuticals provided the active tradipitant and matched placebo capsules without charge. Vanda Pharmaceuticals had no role in the design, conduct or analysis of this project.
© 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
- Abuse liability
- NK1 antagonist
ASJC Scopus subject areas