Picture of Tramadol molecule

Tramadol

Chemical Name:
trans-(+/-)-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl) cyclohexanol
Classification:
Non-opiate synthetic analgesic
Primary Uses:
Analgesia
Brand Names:
Ultram, Ultracet, Tramal
Slang:
Tram cars

General Information

Tramadol is a fully synthetic, centrally-acting analgesic with a low binding affinity for the mu-opioid receptor. Some sources classify tramadol as an opioid, though others claim the opposite because it is not derived from any constituent of the poppy plant. Due to its dissimilarity to other opioids, it acts via methods other than the opioid pathways. Tramadol affects the GABAergic, noradrenergic, and serotonergic systems in the brain. It was developed by a German pharmaceutical company named Grünenthal GmbH. In 2004, the DEA began considering tramadol as potential substance of abuse, as well as possibly scheduling the drug. As of today, tramadol remains unscheduled which makes possession without a prescription in some places legal.

Pharmacology & Pharmacokinetics

Tramadol's mode of action is still not completely understood; however, opioid activity is suggested to be the result of two mechanisms. (1) Binding of tramadol and M1 metabolite to mu-opioid receptors; (2) Inhibition of reuptake of norepinephrine and serotonin. The M1 metabolite is six times more potent in producing pain relief than tramadol, and 200 times more potent in binding to mu-opioid receptors. The opiate overdose remedy, naloxone, only partially reverses the analgesic effects of tramadol, pointing towards non-opiate activity.

Tramadol acts as a norepinephrine and serotonin reuptake inhibitor, so extreme care must be exercised if a patient is taking anti-depressants. If tramadol is used in conjunction with an SSRI—such as Paxil, Prozac or Zoloft—the odds of inducing serotonin syndrome drastically increase, which could potentially result in death. The onset of tramadol is about one hour, and peak plasma levels occur after two to three hours. Tramadol is metabolized by the liver, and excreted by the kidneys. The average elimination half-life of tramadol is six to seven hours, depending on dosing frequency.

Legal Status

The DEA currently has tramadol listed as a Chemical of Concern,1 and several states have enacted legislation placing restrictions on the drug.

In the United States, this drug is not currently controlled under the Controlled Substances Act (CSA). Because it is not controlled, there are no CSA regulations regarding distribution, manufacturing, or prescription of this chemical. According to FDA regulations, sales and distribution are only allowed by those with a valid license. Possession is not illegal for those without a prescription; however, law may differ from state-to-state.

Side Effects

  • Dizziness
  • Nausea and vomiting
  • Constipation
  • Headache
  • Sweating
  • Nervousness
  • Anxiety
  • Euphoria or dysphoria
  • Seizures
  • Urinary retention
  • Insomnia

Withdrawal

Despite what doctors or other healthcare professionals may claim, tramadol is addictive. The DEA is currently considering the drug for scheduling as a result of a relatively high number of emergency room visits, increased illicit consumption, and documented withdrawal symptoms. Tramadol withdrawal symptoms are similar to opiate withdrawal symptoms, and include some of the following:

  • Depression
  • Electric shock-type feeling
  • Dysphoric mood
  • Nausea and vomiting
  • Muscle aches and cramps
  • Insomnia
  • Mild fever
  • Lacrimation
  • Rhinorrhea
  • Sweating
  • Piloerection
  • Diarrhea
  • Yawning

Sources

[1] Drugs and Chemicals of Concern: Tramadol. DEA: Office of Diversion Control. June 2006. Accessed: November 7, 2006.