Nalrexone Facilitated Discontinuation of Buprenorphine
Status:
Completed
Trial end date:
2013-09-01
Target enrollment:
Participant gender:
Summary
The efficacy of buprenorphine as a long-term agonist treatment has been offset by the
emergence of intolerable withdrawal phenomena in a subset of individuals on chronic
maintenance who attempt to discontinue the medication. Efforts are needed to better
understand these challenges encountered with buprenorphine, as well as to develop
interventions to facilitate medication discontinuation.
Emerging evidence suggests that these difficulties may be related to the unique effects of
buprenorphine on sites other than mu-opioid receptors, such as kappa-opioid receptors.
Kappa-opioid agonism produces aversive, dysphoric-like effects, and can also increase the
likelihood of reinstatement to drug use through stress-mediated mechanisms. Some of the
discomfort observed during drug taper may therefore be due to the attenuation or loss of
kappa-opioid antagonism afforded by buprenorphine, as well as to rebound kappa-opioid
activation. Naltrexone represents a promising candidate for extending kappa blockade and
therefore for facilitating discontinuation attempts. Naltrexone and its active metabolite
6-Beta-naltrexol are competitive antagonists at the mu and kappa receptors, and to a lesser
extent at the delta receptor. Naltrexone and buprenorphine have comparable affinity for the
mu-opioid receptor and thus buprenorphine is displaced by naltrexone more gradually than are
other opioids with less affinity; a careful titration of naltrexone is less likely,
therefore, to precipitate severe withdrawal states in individuals coming off buprenorphine,
and the two have been combined to good effect in other settings.
The purpose of this study is therefore to investigate the feasibility of naltrexone
augmentation on discontinuing buprenorphine in eligible patients on long-term maintenance.