title: Physical dependence potential of daily tramadol dosing in humans.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Rock Creek Pharmaceuticals, Inc., 55 Blackburn Center, Gloucester, MA 01930, USA. rlanier1@gmail.com
authors.forename: Ryan K
authors.initials: RK
authors.lastname: Lanier
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Lofwall
authors.forename: Miriam Z
authors.initials: MZ
authors.lastname: Mintzer
authors.forename: George E
authors.initials: GE
authors.lastname: Bigelow
authors.forename: Eric C
authors.initials: EC
authors.lastname: Strain
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D004091:Hydromorphone / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D009293:Opioid-Related Disorders / Q000209:etiology / Q000534:rehabilitation*; D013375:Substance Withdrawal Syndrome / Q000534:rehabilitation; D014147:Tramadol / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009270:Naloxone; D014147:Tramadol; D004091:Hydromorphone