Opioid challenge evaluation of blockade by extended-release naltrexone in opioid-abusing adults: Dose-effects and time-course

George E. Bigelow, Kenzie L. Preston, John Schmittner, Qunming Dong, David R. Gastfriend

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Background: Oral naltrexone's effectiveness as an opioid antagonist has been limited due to poor patient adherence. A long-acting naltrexone formulation may be beneficial. This study evaluated the effects of extended-release injectable naltrexone (XR-NTX), targeted for a one-month duration of action, in blocking opioid agonist challenge effects in humans. Methods: Outpatient non-dependent opioid abusers (N= 27) were randomly assigned to a single double-blind IM administration of 75, 150, or 300. mg XR-NTX. To assess the extent of opioid blockade, hydromorphone challenges (0, 3, 4.5, 6. mg IM in ascending order at 1-h intervals [up to 13.5. mg total]) were given at pretreatment baseline and on days 7, 14, 21, 28, 42, and 56. Opioid blockade was assessed via (1) tolerability of the ascending hydromorphone doses; (2) visual analog scale (VAS) ratings of subjective opioid effects and (3) pupil diameter. Effects on the VAS and pupils were assessed via the slope of the time-action function over ascending hydromorphone doses, with zero slope indicating complete blockade. Results: Blockade of the VAS " any drug effect" response to 3. mg hydromorphone was complete for 14, 21, and 28 days, respectively, for the XR-NTX doses of 75, 150, and 300. mg. Subjective effects were more readily blocked than was pupil constriction. Higher hydromorphone doses produced only modest increases in agonist effects. With the 300. mg XR-NTX dose the slope of VAS responses remained at or near zero for one month even with maximal cumulative hydromorphone dosing. Conclusions: These data quantify the month-long opioid blockade underlying XR-NTX's efficacy in opioid dependence treatment.

Original languageEnglish (US)
Pages (from-to)57-65
Number of pages9
JournalDrug and alcohol dependence
Issue number1-3
StatePublished - Jun 1 2012


  • Depot naltrexone
  • Extended-release naltrexone
  • Hydromorphone
  • Injectable naltrexone
  • Naltrexone
  • Opioid blockade
  • Opioid challenge
  • Vivitrol

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)


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