Pharmacodynamic profile of tramadol in humans: influence of naltrexone pretreatment

Rationale Tramadol is a prescription analgesic that activates mu opioid and monoamine receptor systems. Tramadol is thought to have limited abuse potential compared to mu opioid agonists, but laboratory data indicate that it shares some of their pharmacodynamic effects. Objectives This study evaluat...

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Bibliographic Details
Published in:Psychopharmacologia 2012-10, Vol.223 (4), p.427-438
Main Authors: Stoops, William W., Lofwall, Michelle R., Nuzzo, Paul A., Craig, Lori B., Siegel, Anthony J., Walsh, Sharon L.
Format: Article
Language:English
Subjects:
Adult
Analgesics
Analgesics, Opioid - administration & dosage
Analgesics, Opioid - pharmacology
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Data processing
Dose-Response Relationship, Drug
Double-Blind Method
Drug abuse
Female
Humans
Hydromorphone - administration & dosage
Hydromorphone - pharmacology
Male
Medical sciences
Middle Aged
monoamines
Naltrexone
Naltrexone - pharmacology
Narcotic Antagonists - pharmacology
Neurosciences
Opioid receptors (type mu)
Original Investigation
Pharmacodynamics
Pharmacology/Toxicology
Psychiatry
Psychopharmacology
Receptors, Opioid, mu - drug effects
Tramadol
Tramadol - administration & dosage
Tramadol - pharmacology
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Summary:Rationale Tramadol is a prescription analgesic that activates mu opioid and monoamine receptor systems. Tramadol is thought to have limited abuse potential compared to mu opioid agonists, but laboratory data indicate that it shares some of their pharmacodynamic effects. Objectives This study evaluated the effect of mu opioid receptor blockade with naltrexone on the pharmacodynamic action of tramadol in humans. Methods This inpatient, double-blind, randomized, within-subject study examined the effects of oral placebo, tramadol (87.5, 175, and 350 mg), and hydromorphone (4 and 16 mg; positive control) after 1 h pretreatment with oral naltrexone (0 and 50 mg). Ten recreational opioid users completed the study. Pharmacodynamic effects were measured before and for 7 h after initial drug administration. Results Lower doses of tramadol and hydromorphone were generally placebo-like. Hydromorphone (16 mg) produced prototypic mu opioid agonist-like effects that were blocked by naltrexone. Tramadol (350 mg) produced miosis and increased ratings of “Good Effects” and “Liking” but also increased ratings of “Bad Effects.” Naltrexone reversed tramadol-induced physiological effects and mydriasis emerged, but unlike results with hydromorphone, naltrexone only partially attenuated tramadol’s positive subjective effects and actually enhanced several unpleasant subjective ratings. Conclusions Naltrexone can be used to disentangle the mixed neuropharmacological actions of tramadol. High-dose tramadol produces a mixed profile of effects. These data suggest that both mu and non-mu opioid actions play a role in tramadol’s subjective profile of action.
ISSN:0033-3158
1432-2072
DOI:10.1007/s00213-012-2739-4