Tramadol (Ultram)

  • Generic name: Tramadol Hydrochloride
  • Brand/Trade names: Ultram
  • Dosages: 50 mg tablets
  • Pharmacologic category: Central analgesic, Aminocyclohexanol group
  • FDA approved: March 03, 1995
  • Manufacturer: Ortho-McNeil
  • Habit forming? Yes
  • Pregnancy risk factor: C

Medical uses

Tramadol hcl (Ultram) is a centrally-acting synthetic opioid analgesic. Tramadol is structurally related to codeine, but has a significantly lower affinity for opioid receptors than codeine. It is available in formulations for oral, rectal and parenteral administration.

Tramadol hcl is a non-scheduled analgesic: it is not classified as a controlled substance in the United States, and is available only with a prescription.

Tramadol is used in the treatment of moderate to moderately severe pain, including:

  • Pain after sports injury, trauma, or surgery
  • Back pain, sciatica
  • Fibromyalgia [6]
  • Headaches and migraine [17]
  • Restless legs syndrome
  • Toothache: tramadol is effective for moderate or severe pain after tooth extraction and may relieve toothache. However, you should consult with a dentist as your tooth pain may be due to cracked or decaying teeth.
  • Arthritis: tramadol relieves arthritis pain and permits to decrease the use of NSAIDs.

Onset: it takes about 1 hour for tramadol to work.

Duration: the pain relief lasts for 4-6 hours.

Tramadol effects on liver and kidneys

Tramadol is substantially metabolized (broken down) in the liver and excreted by the kidneys. Therefore if kidney or liver function is severely impaired, some dosage reduction (approximately by 50%) or prolonged dosing intervals should be considered.

Generally, tramadol does not carry a risk of liver damage. The animal study suggests the possible hepatotoxic effects of tramadol in long term usage, but less severe compared to morphine [2].

Analgesic potency

The analgesic potency is about 10-20% of the gold standard morphine. Parenteral tramadol (50 mg) produces the same degree of pain relief as 5 mg of parenteral morphine.

Tramadol potency lies between that of codeine and morphine. It is more potent than dextropropoxyphene and more potent than codeine per milligrams. When taken orally, tramadol is as strong as oral meperidine and pentazocine.

Pharmacological characteristics

  • Metabolism: Extensively hepatic via demethylation, glucuronidation, and sulfation; has pharmacologically active metabolite formed by CYP2D6 (M1; O-desmethyl tramadol)
  • Elimination half-life: 6.3 h
  • Excretion: Tramadol and its metabolites are mainly excreted via the kidneys; 30% of a dose is excreted unchanged in urine; 60% is excreted as metabolites.


  • Low risk of serious side-effects. Tramadol is not associated with major organ toxicity.
  • Respiratory depression is rare [4]
  • Produce less constipation, than other opioids [12]
  • Minor cardiovascular side effects [14]
  • Low dependence and abuse potential [16]
  • More effective than NSAIDs for controlling severe pain
  • More appropriate than NSAIDs for patients with gastrointestinal and kidney problems
  • Potential antidepressant efficacy [5]
  • Effective treatment for neuropathic pain [8]
  • Provides long-term relief of the symptoms of diabetic neuropathy [9]
  • Appears to be more effective than other opioids for neuropathic pain
  • Well tolerated alternative analgesic for osteoarthritis pain [10]


  • High incidence of nausea and vomiting [13]
  • Possibility of dependence with long term use cannot be entirely excluded
  • Potential to induce withdrawal of the classical opioid type, and that atypical withdrawal [3]
  • Lowers the seizure threshold. Tramadol can cause seizures when taken in overdose or in combination with serotonergic medications [11].
  • Tramadol is a prodrug, and in order to exert opioid analgesic activity it must be metabolized by the cytochrome P450 system into its active metabolite O-desmethyltramadol18. About 5-15% of people, who are so-called poor metabolizer, may not experience satisfactory pain relief with standard doses of tramadol.

Unlabeled uses

  • Premature ejaculation [7]
  • Heroin withdrawal [15]

Mode of action

Tramadol has a dual mechanism of action. It binds to mu-opioid receptors in the CNS causing inhibition of ascending pain pathways, altering the perception of and response to pain. Also, the drug weakly inhibits the reuptake of norepinephrine and serotonin, which also modifies the ascending pain pathway.

Opioid activity is due to both the parent compound and the more active O-desmethylated metabolite. Tramadol acts on the monoamine reuptake systems by inhibiting the reuptake into nerve terminals of both norepinephrine and serotonin.

Does Tramadol show up on drug test?

Tramadol (Ultram) does NOT show up as an opiate on urine tests. It will not produce a positive GC/MS urine test.

Tramadol can be detected in a urine drug test only if the test panel is set up to look for tramadol. However, this is a non-workplace screening.

The chemical structure of tramadol differs significantly from that of opioids. Since opiate immunoassays designed for codeine/morphine detection are targeted toward free morphine, it is very unlikely that tramadol would cross-react with an opiate immunoassay.


  • 1. U.S. FDA. Ultram Prescribing Information PDF
  • 2. Atici S, Cinel I, Cinel L, Doruk N, Eskandari G, Oral U. Liver and kidney toxicity in chronic use of opioids. J Biosci. 2005 Mar;30(2):245-52. PubMed
  • 3. Senay EC, Adams EH, Geller A, Inciardi JA, Munoz A, Schnoll SH, Woody GE, Cicero TJ. Physical dependence on Ultram (tramadol hydrochloride): both opioid-like and atypical withdrawal symptoms occur. Drug Alcohol Depend. 2003 Apr 1;69(3):233-41. PubMed
  • 4. Vickers MD, O'Flaherty D, Szekely SM, Read M, Yoshizumi J. Tramadol: pain relief by an opioid without depression of respiration. Anaesthesia. 1992 Apr;47(4):291-6. PubMed
  • 5. Rojas-Corrales MO, Berrocoso E, Gibert-Rahola J, Mico' JA. J Psychopharmacol. 2004 Sep;18(3):404-11. PubMed
  • 6. Biasi G, Manca S, Manganelli S, Marcolongo R. Tramadol in the fibromyalgia syndrome: a controlled clinical trial versus placebo. Int J Clin Pharmacol Res. 1998;18(1):13-9.
  • 7. Safarinejad MR, Hosseini SY. Safety and efficacy of tramadol in the treatment of premature ejaculation: a double-blind, placebo-controlled, randomized study. J Clin Psychopharmacol. 2006 Feb;26(1):27-31. PubMed
  • 8. Duhmke RM, Cornblath DD, Hollingshead JR. Cochrane Database Syst Rev. 2004;(2):CD003726.
  • 9. Harati Y, Gooch C, Swenson M, Edelman SV, Greene D, Raskin P, Donofrio P, Cornblath D, Olson WH, Kamin M. Maintenance of the long-term effectiveness of tramadol in treatment of the pain of diabetic neuropathy. J Diabetes Complications. 2000 Mar-Apr;14(2):65-70. PubMed
  • 10. Malonne H, Coffiner M, Sonet B, Sereno A, Vanderbist F. Efficacy and tolerability of sustained-release tramadol in the treatment of symptomatic osteoarthritis of the hip or knee: a multicenter, randomized, double-blind, placebo-controlled study. Clin Ther. 2004 Nov;26(11):1774-82. PubMed
  • 11. Ripple MG, Pestaner JP, Levine BS, Smialek JE. Lethal combination of tramadol and multiple drugs affecting serotonin. Am J Forensic Med Pathol. 2000;21(4):370374.
  • 12. Crighton IM, Martin PH, Hobbs GJ, Cobby TF, Fletcher AJ, Stewart PD. A comparison of the effects of intravenous tramadol, codeine, and morphine on gastric emptying in human volunteers. Anesth Analg. 1998 Aug;87(2):445-9.
  • 13. Hopkins D, Shipton EA, Potgieter D, Van derMerwe CA, Boon J, De Wet C, Murphy J. Comparison of tramadol and morphine via subcutaneous PCA following major orthopaedic surgery. Can J Anaesth. 1998 May;45(5 Pt 1):435-42.
  • 14. Ellmauer S, Dick W, Otto S, Mu"ller H. Different opioids in patients at cardiovascular risk. Comparison of central and peripheral hemodynamic adverse effects. Anaesthesist. 1994 Nov;43(11):743-9.
  • 15. Threlkeld M, Parran TV, Adelman CA, Grey SF, Yu J. Tramadol versus buprenorphine for the management of acute heroin withdrawal: a retrospective matched cohort controlled study. Am J Addict. 2006 Mar-Apr;15(2):186-91. PubMed
  • 16. Cami J, Lamas X, Farre M. Acute effects of tramadol in methadone-maintained volunteers. Drugs. 1994;47 Suppl 1:39-43.
  • 17. Engindeniz Z, Demircan C, Karli N, Armagan E, Bulut M, Aydin T, Zarifoglu M. Intramuscular tramadol vs. diclofenac for the treatment of acute migraine attacks in emergency department: a prospective, randomised, double-blind study. J Headache Pain. 2005 Jun;6(3):143-8.
  • 18. Gan SH, Ismail R, Wan Adnan WA, Zulmi W. Impact of CYP2D6 genetic polymorphism on tramadol pharmacokinetics and pharmacodynamics. Mol Diagn Ther. 2007;11(3):171-81. PubMed

By HealthyStock Research Group, October 2009
Medical resources reviewed: August 2018

Interesting facts



  • Tramadol has been in clinical use in Germany since the late 1970s and in the US since 1995 under the brand name Ultram.
  • Its mode of action and safety profile distinguishes it from other opioids. Unlike other centrally acting analgesics, Tramadol exerts a dual action by binding to the opioid receptor site in the central nervous system and by weakly inhibiting the reuptake of biogenic amines.
  • Compared with narcotics, Tramadol does not induce significant respiratory depression, constipation, or have significant abuse potential.

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