Assessment of agonist and antagonist effects of tramadol in opioid-dependent humans

C. Patrick Carroll, Sharon L. Walsh, George E. Bigelow, Eric C. Strain, Kenzie L. Preston

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


The subjective, behavioral, and physiologic effects of racemic tramadol, an analgesic with low abuse liability and dual mu-opioid agonist and monoamine reuptake actions, were evaluated in 2 clinical pharmacology studies in dependent opioid abusers. In the withdrawal precipitation study, participants (N = 8) were maintained on methadone 60 mg/day orally and challenged with intramuscular tramadol, hydromorphone, naloxone, and placebo 20 hr after methadone administration. In the withdrawal suppression study, participants (N = 6) were maintained on hydromorphone given orally 10 mg 4 times daily, and spontaneous opioid withdrawal was produced by withholding doses for 23 hr. During the experimentally induced withdrawal, oral tramadol, hydromorphone, naltrexone, and placebo were given. In both studies a comprehensive panel of participant-rated, observer-rated, and physiologic measures were collected. In both studies, naloxone and naltrexone significantly increased measures of opioid withdrawal, whereas tramadol showed no discernible antagonist effects. In contrast, tramadol's pattern of effects was more similar to that of hydromorphone and suggestive of mild opioid-agonist effects (withdrawal suppression), though not to a statistically significant degree.

Original languageEnglish
Pages (from-to)109-120
Number of pages12
JournalExperimental and Clinical Psychopharmacology
Issue number2
StatePublished - May 2006


  • Opioid agonist
  • Opioid withdrawal
  • Tramadol

ASJC Scopus subject areas

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


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