Abstract
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.
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Acknowledgments
The authors thank Elliot Joseph, Jessica Vanderhoff, Sonia Bansal, Mary Misenhimer, Sarah Ilk, John Yingling, Linda Felch, and the nursing staff at the Behavioral Pharmacology Research Unit for their assistance in volunteer recruitment, data collection, and analysis. This study complies with current laws of the USA.
Disclosure
Tramadol was developed by Grünenthal. Dr. Strain is a paid consultant to Grünenthal. This arrangement is being managed by the Johns Hopkins University in accordance with its conflict of interest policies. In recent years, Dr. Bigelow has received consulting payments from Abbott Laboratories, Takeda Pharmaceuticals, and Teva Pharmaceuticals and through his university has received research support from Titan Pharmaceuticals and Pain Therapeutics, Inc. Dr. Lanier is now an employee of Rock Creek Pharmaceuticals.
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.
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Lanier, R.K., Lofwall, M.R., Mintzer, M.Z. et al. Physical dependence potential of daily tramadol dosing in humans. Psychopharmacology 211, 457–466 (2010). https://doi.org/10.1007/s00213-010-1919-3
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DOI: https://doi.org/10.1007/s00213-010-1919-3