title: Opioid-like effects of the neurokinin 1 antagonist aprepitant in patients maintained on and briefly withdrawn from methadone.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.
authors: Division on Substance Abuse, New York State Psychiatric Institute and Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. JermaineDJones@gmail.com
authors: Jermaine D
authors: JD
authors: Jones
authors: Taylor
authors: T
authors: Speer
authors: Sandra D
authors: SD
authors: Comer
authors: Stephen
authors: S
authors: Ross
authors: John
authors: J
authors: Rotrosen
authors: Malcolm S
authors: MS
authors: Reid
mesh_terms: D000328:Adult; D000932:Antiemetics / Q000494:pharmacology*; D000077608:Aprepitant; D016739:Behavior, Addictive / Q000188:drug therapy; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008691:Methadone / Q000008:administration & dosage* / Q000627:therapeutic use; D008875:Middle Aged; D009025:Morpholines / Q000494:pharmacology* / Q000627:therapeutic use; D064729:Neurokinin-1 Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D058850:Opiate Substitution Treatment; D010865:Pilot Projects; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*
chemical_list: D000932:Antiemetics; D009025:Morpholines; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; D000077608:Aprepitant; D008691:Methadone