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.