Guinevere Gets Sober

Recovery news, reviews and stories, by Jennifer Matesa.

Coming to a Doctor’s Office Near You: Buprenorphine Implants!

Titan Pharmaceuticals, the California manufacturer of a product designed to release a steady stream of buprenorphine over a period of six months, yesterday released what they called positive results of a study of this product in yesterday’s Journal of the American Medical Association.

There’s lots of stuff that none of the journalists have reported about this study.

Beginning with the funding. The JAMA piece said Titan Pharmaceuticals funded this study. What it didn’t say was that last year Titan was awarded $7.6 million in federal funds from the National Institutes on Drug Abuse to study this product over three years. So a big chunk of federal money was awarded to a private pharma corporation.

Also: Titan and the UCLA study authors are calling the implants a success, but more than two-thirds of the implant participants received supplementary Suboxone tablets. That’s like saying, We gave them extra heroin to curb the cravings, but hey! the implants still worked. People do not understand: buprenorphine is an opioid, no matter what formula it comes in, no matter whether you call it an “implant” or a “medication” or a “drug.”

The product, which Titan has named Probuphine, is a 26-mm rod impregnated with the opioid buprenorpine. It’s designed to be surgically placed underneath the skin on the non-dominant arm. (Women have long used technology like this with contraceptive hormone implants.) Over time it keeps drug levels at a steady state in the bloodstream.

Titan’s people are calling this steady-state release one of the big advantages of Probuphine—no fluctuations in drug-plasma levels, the way there are with pills like Suboxone, or liquids like methadone.

Suboxone pills

Suboxone, the dissolving orange tablet whose drug sticks like super-glue to your mu receptors

They may have a point here. Suboxone has a 37-hour half-life. Let me explain how half-life works: When the drug is orally dosed every 24 hours, many physicians believe, Suboxone stacks up in the bloodstream—the body does not metabolize it faster than it’s dosed. But if it can be released in a steady trickle dose, then it might not stack up.

Titan and NIDA are also saying that because the drug is implanted, it’s impossible to divert. This is the big selling-point for the rods. Patients can’t hawk it on the black market, the way they do with Suboxone or other drugs. Code for this: they say it “improves patient compliance,” which means patients simply have no choice other than to take the drug, because it’s stuck inside the body.

How the study worked

The study involved a group of patients that received four Probuphine rods, and another group that received placebo rods. Both groups could also receive Suboxone pills if they were experiencing withdrawal or craving (up to 12 or 13mg per day!—an equivalent of about 525mg morphine. I mean, why even give your patients implants if you’re going to let them take an extra 12mg of Suboxone?) in the first 16 weeks of the study; for the last eight weeks, participants who elected to get an extra implant were limited in the amount of extra Suboxone they could receive. And everyone had to go to “counseling.”

Results of the study that everybody’s reporting (source: JAMA—I wish I could provide a link to the entire study, but the link above only gives you the abstract):

  • “Success” was measured solely in terms of urine tests free of illegal opioids (i.e., heroin). Results: 40 percent of implanted patients dropped “clean” urine, as opposed to 28 percent of the placebo group.
  • Withdrawal and craving scores for the implant patients were “significantly lower” (whatever that means) than those for the placebo patients.
  • Biggest result touted by the study’s lead author, Walter Ling, M.D. of UCLA’s Integrated Substance Abuse Programs: two-thirds of the implant patients stuck with the program (that is, continued to receive counseling—either that, or continued to receive their Suboxone), while only one-third of the placebo patients finished.


  • Conflicts of interest in the researchers: Dr. Ling, the lead author of the study, is receiving research money from both Reckitt Benckiser (maker of Suboxone) and Titan (maker of Probuphine), and speaker fees from Reckitt. The other authors are also receiving either research money or speaker fees from these and many other big pharma companies, as well as NIDA (the federal government, whose projects are supposed to remain independent of commercial influence).
  • How these earnings influence the market: Buprenorphine, especially in maintenance form, is huge business. It is The Biggest Drug Treatment for opioid addicts right now, with sales of more than $900 million in the U.S. alone. That’s a 2010 statistic—it’s certainly grown since then. Reckitt and Titan are targeting not only “treatment resistant” addicts such as IV heroin users, chronic relapsers, and so on, but also to chronic pain patients who have become addicted to opioid medications—the fastest growing sector of addiction today. Enormous markets they’re mining. (In fact lots of curious investors read this post and come away with the conviction that, no matter what happens to the drug addicts, they better invest in Titan.)
  • Treatment assumptions: Built into Probuphine is the assumption that the only “real” way to treat addicts is to give them a drug for the rest of their lives.
  • Induction doses: All participants were inducted at fixed doses of 12-16mg per day of Suboxone over three days before they were randomized. Why give them this much to begin with? 12-16mg is an enormous dose of Suboxone. As in, equivalent to bags and bags of heroin, or around 525-750mg of morphine. Most people do not understand how powerful buprenorphine is.
  • How much bupe were they really getting? Finally, the authors admitted that with the way the study was conducted, it’s difficult to know exactly how much buprenorphine is getting into the body with the implant vs. Suboxone supplements. They say that their blood tests were consistent with “a constant buprenorphine release of 1 to 1.3mg/d from 4 to 5 implants.” If it’s true that the implant patients were getting only one milligram per day, then that would be brilliant, because that’s a low dose for addicts trying to get off junk … but it might also explain why nearly two-thirds of the implant group wanted extra Suboxone.

Especially if “counseling” was the only other solution offered to them.


  1. I hope that the peer reviewers for the JAMA article were without conflict of interest. Publishing is a rigorous process, as you know, and one hope that data were collected without any fatal flaws in the design.

  2. guinevere

    October 15, 2010 at 6:15 pm

    I don’t think I’m pointing out flaws in the design of the study. I’m pointing out gaps in the lazy journalism around the study… Everyone’s focusing on the “soundbites” offered by the study’s authors. Soundbites are opinion, not fact. Whether a study is a “success” or not is an opinion that ought to be questioned by knowledgeable journalists. It’s easy to look at data and interpret it this way or that.

    Most people do not understand addiction. That includes journalists… who may not understand what it means when a study says that 2/3 of the participants were given supplemental Suboxone. They may not even understand that Suboxone is an opioid drug stronger than morphine… After all, it’s usually referred to as a “medication that can cure drug addiction” in the press. That makes it sound rather benign.

  3. Wow! Sounds like ‘dirty’ research with lots of conflicts of interest. I’ve published scientific articles in medical journals myself and know from experience that many studies are inherently ‘tainted’ and compromised by funding sources and competitive interests.

    My heroin addict daughter told me that black market methadone led her directly to cheaper street heroin. When we did our rescue intervention with her last May, she was insistent on wanting to use suboxone during her ‘recovery’. Thankfully, her treatment center did not allow suboxone – which is, unfortunately, just another drug to become addicted to/dependent on.

    Addicts are so resourceful, I can’t help but think they’d figure out a way to ‘use’ the buprenorphine implant illicitly.

  4. guinevere

    October 16, 2010 at 8:01 am

    Buprenorphine is an effective detox tool. I could never have gotten off the level of fentanyl I was on without a physician willing to prescribe a limited run of suboxone.

    There was a moment during my detox at which I thought I might just as well stay on buprenorphine forever. Buprenorphine is hell to get off of once on for longer than a couple months… If I hadn’t gone through the work of tapering off at that time, I might not be talking to you right now.

  5. Anthony Etzkorn

    January 31, 2011 at 6:31 pm

    Ok my name’s anthony and i’ve been on subutex & suboxone for years now. It is hell to come off of. I’ve tryed three or four times to stop but i”m a drug addict and a month of withdrawls seems like a long f***ing time to me… they told me i would taper down and things would be groovy sick as hell a week, cranky and bit**y another so i said cool. Even on a dose of like a half milligram you’re sick for three weeks! So i figured I’d get one of these implants of buprenorphine to taper down… Maybe they are a bad thing for people with active addictions and no plan of stopping, but i can’t live like a junky running to the pharmacy every time i run outta pills anymore. So for someone who has dealt with trying to stop the buprenorphine that doesn’t want to be on all this sh** this is a huge breakthrough.

  6. guinevere

    February 2, 2011 at 6:28 pm

    Thanks, Anthony. Suboxone is indeed hell to come off of. … So tell me how you’re using the implants to taper down? Because they’re meant for staying on the drug. Right? … with every good wish, G

  7. Shouldn’t Ling write the conclusion to the trial since he was the head researcher? Of course he was employed by Titan; he had to spend over a year of his life setting up, running, and analyzing the trial. Is it not typical for the head researcher to do the write up on the trial data?

  8. guinevere

    February 18, 2011 at 8:28 am

    Sure, Dr. Ling should write the conclusion to the trial since he was the head researcher. However, I don’t in the least think it goes without saying that he should be employed by Titan. He received money from them them, not only in a research capacity, but also for speaking for the company (and for Reckitt) about its products to other practitioners. This doesn’t add up to “independent” research.

    “Another concern is the extensive involvement of the implant manufacturers in not just the funding but the conduct, analysis and reporting of the trial.”

  9. melissa mccoy

    March 7, 2011 at 4:08 pm

    i am interested in implants and need to find a doctor near williamson wv I am willing to drive 100 miles to get treatment

  10. guinevere

    March 8, 2011 at 5:07 pm

    @Melissa, this product is not on the market.

  11. Thanks for your blog. It was interesting, but first I will disclose that I am still on Suboxone as well as a believer in it, who’s had good experience. And still do. I’ll explain why in a minute why I’m still on it. Also, I’m a shareholder of Titan because I’m such a believer. I don’t know if that matters to disclose, but for some reason it does to me. =) The first point I’d like to make is that in a different life, at a younger age, I was a former “research assistant” (totally glorified “researcher” because I was doing it for free to get into med school at the time), I can tell you typically that when they refer to “significance” (I’ll reference your quote: “… implant patients were ;significantly lower’ (whatever that means)”.) they mean that statistically the results were significant. Without giving an exegesis of Statistics 101, which I was forced to take, it simply means that the results were significant enough to account for unforeseen variables, etc. So mathematically, they typically refer to “significance” in a trial to show that there was a “statistical significance”. I’m sure i’m not doing the definition justice, but one can look up the meaning of “statistical significance”. Now, i’m not saying that the trials here in question was 100% referring to statistical significance, but other scientists would have thrown a “hissy fit” and typically there would have been some kind of retraction – they simply couldn’t get away with “significance” without some kind of backlash if that wasn’t what they were referring to (statistically speaking).

    But the bigger point I wanted to throw out there was that you appear to speak about addicts who are simply seeking pleasure or a “high”. I’m still on Suboxone (+ – 1 mg / day) for a life-long pain. (I personally started with an opiate from the dentist, but I’m on Suboxone for over a year now for a different reason.) So, yes, the study may not be perfect, but I can tell you that from the perspective of someone who represents a people who are in daily pain, which is why they probably got addicted to opiates in the first place, this new system is a godsend. That is, of course, my opinion. And I thought it would be great of you to also see it from that perspective as well.

    Thanks for the post. I always enjoy a good discussion on this subject.

  12. guinevere

    June 9, 2011 at 10:05 am

    @Pauly, thanks so much for your response. Wanted to clarify a few issues you raise… I don’t think I mentioned anything in the post about assuming folks on bupe were trying to get high or were seeking pleasure. My primary purpose with this post was to point out information that the general press was not reporting about the study. In other words, I had more problems with the way the study was being reported by the press than with the study itself (although I think it’s highly problematic for researchers to receive fees from the companies whose products they’re studying).

    I also live with two chronic pain conditions and agree that many people are becoming addicted because of seeking opioid treatment for chronic pain. I also believe that physicians need to be better educated about the risks of addiction, in order to prepare their patients for the possibility that addiction may occur if daily opioids are taken. In addition, I think there’s a need for more research into ways of treating pain for people with both chronic pain and addiction. There needs to be more compassion for people with addiction AND chronic pain—instead of this punitive and patient-blaming attitude we have now.

    Congratulations on finding a solution to your pain problem… I hope it continues to work for you as time goes on. cheers G

  13. So in your opinion is the implantable rod a viable solution to help drug addicts with their craving for their habit?

  14. 12 to 16mg of suboxone isnt a high dose 16mg is the average dose and 24mg is used a lot for people with really bad IV Heroin problems or people who have been taking large doses of methadone. I would like to see more about this implant but if an addict wants to use he/she is going to use nomatter what drug theyre on.

  15. You don’t know much about suboxone, or opiate addiction, let alone implants.
    Peddling misinformation for page views.

    Get back to us when you need treatment for opiate addiction.

    Often drug replacement therapy is indeed the only way. For me it is anyway.
    And I wish I had access to the implant, then I wouldn’t need to even think about the problem ever again.

  16. Thanks for visiting. Your condescending attitude speaks volumes for you. I know a great deal about Suboxone and opioid addiction. I hope you find a solution that works for you.

  17. Bobbiandcharlie

    April 8, 2012 at 5:41 pm

    I have been on suboxone for one month along with my boyfriend, we have been on opiates for 7 years and suboxone has changed our lives. I couldn’t have done it without suboxon and we are happier then we have ever been. Unless u have been there u don’t know what it talking about

  18. 12-16 mg a day isn’t an “enormous” dose. From experience, the cravings can start to come back within 12 hours after taking 8 mg. so the extra 4-8 mg 12 hours later can curb the need to go out and find something to satisfy that craving. so in 24 hrs its a much better option than buying 5 or 6 30mg oxycodone pills and still being sick the next morning. But then again, 4mg will work too if people want to make it work.

  19. First of all your assumtion that 12 to 16 mg of buprenorphine is the equivilant to 525-750 mg is very misleading. People that are on suboxone do not get high from it or experience any kind of buzz at all. I was an IV heroin user for 5 years and have been on suboxone for 4. 24 mg is an average starting dose and the doses that you seem to think are high are very common. The whole point of suboxone is to prevent people from using again. If people who are on suboxone need even up to 32 mg to have a normal life what is the harm in that. Like I said if people who truly had an opiate problem take suboxone how their supposed to, there is no way they are getting high from this. Even if someone takes 100 mg of suboxone, they wont get high from it. Suboxone has a ceiling dose that maxes out at 32 mg which means if you take more than that you dont get any more effect from it by taking more. Please do some more research before you post something like this that could be misleading.

  20. Sam, thanks for reading. It’s not an assumption. Buprenorphine is an exceedingly strong drug. I didn’t just make this up; many physicians who have prescribed the drug have told me this, and I know it from experience. Secondly, interesting that you think because a dose is “common,” that must mean it’s low. A common dose can also be quite high, and 24mg buprenorphine (an average daily dose) is a big dose. Finally, it would be nice to believe that people who “truly had an opiate problem” could take an opioid drug as prescribed. That’s a conundrum inherent in treating addiction with addictive drugs—it’s difficult for addicts to take them as prescribed. A serious fallacy in your argument.

  21. Wow, Guinevere…I can feel the “Love” all over the place…I am sorry so many feel so angry at your well-thought out “assumptions.” No matter what anyone says, that (12 to 16 mg) is a LOT of pain med! When it comes time to “pay the piper” there will be a lot of people asking for something to take the pain (drug sicks) away. It is a horrible cycle and the bottom line is…eventually you have to have a “correction.” (like the stock market) Can’t always increase the fake endorphins. Big Pharma will soon offer something worse…sorry, BETTER to get off THAT. Then, there will be folks with NO testosterone, adrenal fatigue, depressed, think of the market(s) that will open up. It is sad to me that we allow this to go on. I feel for all those with pain and addiction, I have much personal “skin in the game” myself. This is a no win people. Guinevere is on to something here. Please stay open minded to the endless road this could lead you all down. Wishing you all the best.

  22. Steven Stewart

    April 3, 2015 at 1:44 am

    Buprenorphine is actually mainly a kappa-agonist.

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