Document Detail


Opioid-like effects of the neurokinin 1 antagonist aprepitant in patients maintained on and briefly withdrawn from methadone.
MedLine Citation:
PMID:  23421568     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Jermaine D Jones; Taylor Speer; Sandra D Comer; Stephen Ross; John Rotrosen; Malcolm S Reid
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Publication Detail:
Type:  Controlled Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The American journal of drug and alcohol abuse     Volume:  39     ISSN:  1097-9891     ISO Abbreviation:  Am J Drug Alcohol Abuse     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-20     Completed Date:  2014-01-17     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  7502510     Medline TA:  Am J Drug Alcohol Abuse     Country:  England    
Other Details:
Languages:  eng     Pagination:  86-91     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Antiemetics / pharmacology*
Behavior, Addictive / drug therapy
Cross-Over Studies
Double-Blind Method
Drug Interactions
Female
Humans
Male
Methadone / administration & dosage*,  therapeutic use
Middle Aged
Morpholines / pharmacology*,  therapeutic use
Neurokinin-1 Receptor Antagonists / pharmacology*,  therapeutic use
Opiate Substitution Treatment*
Pilot Projects
Receptors, Neurokinin-1 / metabolism*
Substance Withdrawal Syndrome / drug therapy*
Grant Support
ID/Acronym/Agency:
K01 DA030446/DA/NIDA NIH HHS; T32 DA007294/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Antiemetics; 0/Morpholines; 0/Neurokinin-1 Receptor Antagonists; 0/Receptors, Neurokinin-1; 1NF15YR6UY/aprepitant; UC6VBE7V1Z/Methadone
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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