Methadone maintenance patients lack analgesic response to a cumulative intravenous dose of 32 mg of hydromorphone

Gabrielle Agin-Liebes, Andrew S. Huhn, Eric C. Strain, George E. Bigelow, Michael T. Smith, Robert R. Edwards, Valerie A. Gruber, D. Andrew Tompkins

Research output: Contribution to journalArticlepeer-review


Objectives: Acute pain management in patients with opioid use disorder who are maintained on methadone presents unique challenges due to high levels of opioid tolerance in this population. This randomized controlled study assessed the analgesic and abuse liability effects of escalating doses of acute intravenous (IV) hydromorphone versus placebo utilizing a validated experimental pain paradigm, quantitative sensory testing (QST). Methods: Individuals (N = 8) without chronic pain were maintained on 80−100 mg/day of oral methadone. Participants received four IV, escalating/incremental doses of hydromorphone over 270 min (32 mg total) or four placebo doses within a session test day. Test sessions were scheduled at least one week apart. QST and abuse liability measures were administered at baseline and after each injection. Results: No significant differences between the hydromorphone and placebo control conditions on analgesic indices for any QST outcomes were detected. Similarly, no differences on safety or abuse liability indices were detected despite the high doses of hydromorphone utilized. Few adverse events were detected, and those reported were mild in severity. Conclusions: The findings demonstrate that methadone-maintained individuals are highly insensitive to the analgesic effects of high-dose IV hydromorphone and may require very high doses of opioids, more efficacious opioids, or combined non-opioid analgesic strategies to achieve adequate analgesia.

Original languageEnglish (US)
Article number108869
JournalDrug and alcohol dependence
StatePublished - Sep 1 2021


  • Analgesia
  • Hydromorphone
  • Methadone maintenance
  • Pain
  • Quantitative sensory testing

ASJC Scopus subject areas

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


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