Tramadol, the generic for the brand name Ultram, is a pain reliever that has actions on several types of brain receptors: the mu opioid, serotonin, norepinephrine, NMDA, and other receptors.
Because it stimulates the mu opioid receptors, it can cause feelings of pleasure as well as pain relief. Tramadol is a pared-down version of codeine, and it is far less active at the mu opioid receptors than its metabolite. Because it takes time for the tramadol to be metabolized in the liver to its first metabolite, some experts thought it wouldn’t appeal to addicts, who prefer an immediate high. Overall this is probably true, and tramadol has a much lower rate of addiction than other opioids, but it still causes addiction in some patients.
Some of tramadol’s pain relieving properties may also be produced by its actions on serotonin and norepinephrine receptors, since tramadol’s pain relieving capability is only partially reversed by a pure opioid antagonist like naloxone.
When this medication was first released, it wasn’t a controlled substance. That is, the DEA didn’t control it strictly like medications that can cause addiction. Now, it’s a Schedule IV drug, in some states. It does have some benefit for pain relief, but also some risk of addiction, though lower than that of hydrocodone, for example.
Tramadol is usually dosed in 50mg pills, one or two every six hours, giving the maximum dose of 400mg per day. Recreational use of this medication (to get high) is dangerous, since it causes seizures at doses higher than 400mg. In susceptible patients, it can even cause seizures at lower prescribed doses.
I’ve seen patients in tramadol withdrawal who were so sick it frightened me. This drug can produce a severe withdrawal. If a patient taking high doses stops taking tramadol suddenly, some patients have opioid withdrawal symptoms like sweating, nausea, diarrhea, high blood pressure and heart rate, and severe muscle and joint pains. The sickest patient I’ve ever seen in opioid withdrawal had been using only tramadol, in doses of around 600mg per day. She had fever to 103 degrees, and dehydration from the diarrhea and vomiting. That patient needed hospitalization.
Besides the opioid-withdrawal symptoms, some of these patients also have withdrawal symptoms similar to those seen when certain serotonin-affecting antidepressants, like Paxil and Celexa, are stopped suddenly. They can have fairly severe anxiety, depression, mood swings, and restlessness. Many times they have weird sensory experiences, often called “brain zaps,” or the sensation of electric shocks throughout the body. They can have seizures during this withdrawal.
If the patient had only physical dependency and no addiction, the dose of tramadol can usually be tapered slowly over a few weeks to months, as an outpatient. But if the patient has not only physical dependency but also the disease of addiction, the obsession and craving for the medication will usually prevent a successful outpatient taper, unless a dependable non-addict holds the pill bottle, and dispenses it as prescribed.
Traditional treatment for tramadol addiction starts with detoxification. As above, that can rarely be done as an outpatient, so medical inpatient detoxification admissions for five to seven days can be helpful. However, since tramadol acts so much like an opioid, patients ready to leave detox probably need to go on to an inpatient residential treatment center for at least thirty days. Intensive outpatient treatment probably isn’t enough support for these addicts. But that’s only my opinion, since I haven’t found any studies describing success rates with tramadol addicts.
Opioid maintenance medications like methadone and buprenorphine do stop the opioid-type withdrawal symptoms from tramadol, but there’s no information about the use of maintenance medications in these patients. Most doctors working in clinics won’t start a patient on maintenance medications unless the patient is also using other opioids.
Often, methadone patients at the opioid treatment centers where I work are given tramadol by their primary care doctors who think it’s a low risk medication for opioid addicts. It probably is lower in its risk for abuse, but it can cause withdrawal in patients on stable, blocking doses of methadone. 
Tapentadol, sold under the brand name Nucynta, is becoming a drug of abuse in my area. It is a schedule II drug, presumably because it has a higher abuse potential than tramadol. Tapentadol stimulates opioid mu receptors, and also acts as a norepinephrine re-uptake inhibitor, like some antidepressants.
Unlike tramadol, tapentadol is not a prodrug; that is, it doesn’t have to be metabolized to be active at the opioid receptor. For that reason, pain relief starts within thirty minutes of swallowing the drug. Also unlike tramadol, it has little action at the serotonin receptor. It’s marketed for use in patients with moderate to severe pain, and can be useful in patients who don’t respond to more traditional opioid medications.
If you check various drug use forums, some people clearly are able to inject the tapentadol, and even the extended-release formulation, which was manufactured to be more abuse-resistant.
I saw my first patient who was addicted to Nucynta a few years ago, and have seen other patients similarly afflicted since then. Usually, Nucynta isn’t the only drug that’s being misused, but one of many.
The bottom line is this: if you are in recovery from addiction (alcohol or drugs), this medication should be used with caution. Let your doctor know that you’re in recovery from addiction. If you must take a potentially addicting medication, be careful, and let all of your doctors know about all of your medications. Let a dependable non-addict hold the pill bottle and dispense as prescribed.
- Leavitt, MA, PhD, “Methadone-Drug Interactions,” Pain Treatment Topics, Addiction Treatment Forum, January 2006