Tramadol and Tapentadol: Ultram and Nucynta


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. [1]

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.

  1. Leavitt, MA, PhD, “Methadone-Drug Interactions,” Pain Treatment Topics, Addiction Treatment Forum, January 2006


7 responses to this post.

  1. Posted by Andrew angelos on May 22, 2016 at 9:12 pm

    Wow. Never would have thought. I was once prescrobed ultras because I was tring to stop norco I found it to be totally useless. My wife however who didn’t not take any opioids said it made her feel high. It’s hard to see someone becoming addicted to that medication but I suppose if you started out on that before more powerful opiates one could get addicted. The doctor hat gave it to me said it had no reaction with the mu receptor. Goes to show you how much the mind plays a roll in addiction not just the physical. Had I known this back then I would have probably continued use at very unhealthy ammount. As alway you have a interesting topic.


  2. Posted by N. Goldberg on May 23, 2016 at 10:52 am

    I treated a patient in a MAT with buprenorphine for tramadol withdrawal as an outpatient. Brought her up to about 16mg, held her there for several weeks, then weaned the dose over another 2 to 4 weeks. She reported a previous terrible experience with Tramadol withdrawal. I addressed this approach to ASAM elites who acknowledged that they have done the same.


  3. Posted by Todd Michael on May 24, 2016 at 7:19 pm

    Jana, didn’t see on the blog if I could send an email, but the talkzone from suboxforum, brought me to your blog, and I’m thrilled to read. First, let me say thanks for spending the time, since I know how busy you must be, but I find your information very useful, informative, and intriguing. I read from the most recent to late last year, as you’re easy to read, stay on point/topic, and I’m a recovering addict on suboxone for 2 years after 5 or so in patient rehab failures over the past 6 years (been addicted for 15 years, wasn’t until 2009 when I HAD to get help). I get that the abstinence based recovery field has owned the area for years and years, so change is hard to accept, but there are so many qualified intelligent front line people like yourself who know MAT is has more success than meditation, yoga, and 12 steps. I still read my big book from time to time, because I value some of the info, but man it seems like MAT is the obvious solution, and too many people want to protect their jobs, instead of actually help addicts. I see both sides of the coin, I’ve tried multiple approaches to recovery, even stayed in a 9 month recovery center in Houston (Open Door Mission), which did give me the most time in abstinence based recovery, even when I left the program, I stayed clean for about 20 months. Anyway, this doesn’t comment on your most recent post, but just wanted to say what you write is important, and that people like me are paying attention, God bless, and keep up the fight!!


    • Thank you so much.
      I do think the tide is – slowly – turning.
      When lots of people started dying with treatment-as-usual, the U.S. had to start looking at MAT.


  4. Posted by MyBackHurts on March 10, 2019 at 9:44 am

    Have been an am on a regiment of pain medication due to server degenerative discs. I’m curious. Would this work with or in place of roxicodone for daily breakthrew pain ?


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