Physical dependence potential of daily tramadol dosing in humans

Ryan K. Lanier, Michelle R. Lofwall, Miriam Z. Mintzer, George E. Bigelow, Eric C. Strain

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


Rationale: Tramadol is an atypical, mixed-mechanism analgesic involving both opioid and catecholamine processes that appears to have low abuse potential and may be useful as a treatment for opioid dependence. Objectives: The current study assessed the level of physical dependence and opioid blockade efficacy produced by daily maintenance on oral tramadol. Methods: Nine residential opioid-dependent adults were maintained on two doses of daily oral tramadol (200 and 800 mg) for approximately 4-week intervals in a randomized, double-blind, crossover design. The acute effects of intramuscular placebo, naloxone (0.25, 0.5, and 1.0 mg), and hydromorphone (1.5, 3.0, and 6.0 mg) were tested under double-blind, randomized conditions. Outcomes included observer- and subject-rated measures and physiologic indices. Results: Challenge doses of naloxone resulted in significantly higher mean peak withdrawal scores compared to placebo. Withdrawal intensity from naloxone was generally greater during 800 versus 200 mg/day tramadol maintenance. Mean peak ratings of agonist effects were elevated at higher hydromorphone challenge doses, but did not differ significantly between tramadol doses. Physiologic measures were generally affected by challenge conditions in a dose-dependent manner, with few differences between tramadol maintenance dose conditions. Conclusions: Chronic tramadol administration produces dose-related opioid physical dependence, without producing dose-related attenuation of agonist challenge effects. Tramadol may be a useful treatment for patients with low levels of opioid dependence or as a treatment for withdrawal during opioid detoxification, but does not appear to be effective as a maintenance medication due to a lack of opioid cross-tolerance.

Original languageEnglish
Pages (from-to)457-466
Number of pages10
Issue number4
StatePublished - Sep 2010

Bibliographical note

Funding Information:
Funding This work was supported by the National Institutes of Health/National Institute on Drug Abuse Grant R01DA018125 to Johns Hopkins University (ECS), Midcareer Investigator Award in Patient-Oriented Research K24D023186 (ECS), and Training Grant T32DA07209 to Johns Hopkins University.


  • Abuse
  • Blockade
  • Dependence
  • Hydromorphone
  • Naloxone
  • Opioid
  • Tramadol
  • Treatment
  • Withdrawal

ASJC Scopus subject areas

  • Pharmacology


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