General Information

Tramadol is a fully synthetic, centrally acting analgesic with a low binding affinity for the mu-opioid receptor. Some sources call it an opioid, 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 a 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.

Chemical Names. trans-(+/-)-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl) cyclohexanol.
Classification. Non-opiate synthetic analgesic.
Primary Uses. Analgesic (Off-label for diabetic neuropathy and restless leg syndrome).
Other Names. Ultram, Ultracet.

Pharmacology and Pharmacokinetics

The mode of action is 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 6 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 analgesic effects, pointing toward non-opiate activity.

Tramadol acts as a norepinephrine/serotonin reuptake inhibitor, so care must be exercised if one is on anti-depressants. If tramadol is used in conjunction with an SSRI, (such as Paxil, Prozac, or Zoloft) the odds of inducing serotonin syndrome increase, which could result in death. The onset of tramadol takes around one hour, while it peaks after two or three hours. The drug 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.

Law

In the United States, tramadol 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. The DEA has tramadol listed as a "Chemical of Concern" on their web page. ^[1]

Side Effects

Dizziness
Nausea/vomiting
Constipation
Headache
Sweating
Nervousness/anxiety
Euphoria/dysphoria
Seizures
Urinary retention
Insomnia

Withdrawal

Tramadol is addictive. Do not let the medical professionals fool you. The DEA is currently considering the drug for scheduling as a result of a relatively high number of emergency room visits, increased illicit consumption of the drug, and documented withdrawal symptoms. The withdrawal syndrome is similar to opioids and possible symptoms are listed below:

• Depression/dysphoric mood
• Nausea and vomiting
• Muscle aches and cramps
• Insomnia
• Mild fever
• Lacrimation
• Rhinorrhea
• Sweating
• Piloerection
• Diarrhea
• Yawning
• Waves of electric shock-type feeling

Sources

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