Opioid-Like Effects of the Neurokinin 1 Antagonist Aprepitant in Patients Maintained on and Briefly Withdrawn from Methadone

Abstract

Background: Although opioid substitution therapy is an effective clinical tool used to manage opioid abuse and dependence, concerns regarding the current FDA-approved medications have lead to a search for efficacious, non-opioid medications. Preclinical data indicate that neurokinin 1 (NK1) receptor activity may modulate opioid effects and withdrawal. This investigation sought to examine the ability of the NK1 antagonist aprepitant to alter the effects of methadone as well as withdrawal symptoms induced by brief methadone discontinuation. Methods: This blinded, placebo-controlled, within-subjects study consisted of placebo and aprepitant conditions. Experimental assessments occurred on the first three days (days 1–3: placebo or aprepitant + methadone) and again on days 8–10 (aprepitant or placebo + methadone). Fifteen methadone-maintained patients completed the investigation. Outcome measures were the assessments of opioid withdrawal, as well as subjective measures of opioid-like effects. Results: Statistical trends indicated that aprepitant may reduce opioid withdrawal symptoms. When an active dose of aprepitant was administered an hour before methadone, participants reported less desire to use methadone. However, ratings of methadone “Liking” also appeared to increase. Conclusions: These data tentatively suggest that aprepitant has some ability to alleviate withdrawal following methadone abstinence, but also appears to increase subjective indicators of methadone’s abuse liability. Since few of the differences between aprepitant and placebo reached statistical significance, these data should only be viewed as preliminary. Findings from other studies indicate that higher doses of aprepitant may be more clinically effective. Further clinical investigations are needed in order to determine whether aprepitant is useful for alleviating opioid withdrawal.

• NK1
• methadone
• aprepitant
• opioid
• withdrawal

Acknowledgments

Study supported by an NYU Langone Medical Center Seed Grant to MSR through the NYULMC Center of Excellence on Addiction.