Another death in the tribe and this one is…close to home.

The initial news reporting from Baltimore led with “Post-Doctoral Fellow Charged After Girlfriend’s Death”. Oh Christ.

A post-doctoral fellow at the University of Maryland School of Medicine has been charged with illegal drug possession after his live-in girlfriend, also a fellow, died.

Not. Good. Not good in the least.

According to investigators, Dr. Carrie Elisabeth John injected herself Monday with a drug known as “bupe” in the house she and McCracken shared.
Bupe is intended to help addicts break their dependency on heroin.
Court documents said John stopped breathing and was pronounced dead in the university hospital emergency room.

“Bupe” or buprenorphine [Wikipedia] is an mu opioid receptor partial-agonist used as agonist therapy for opiate dependency under trade names such as Subutex® and Suboxone®.

Of course we will have to wait as more information develops on this story but dying of respiratory suppression is certainly consistent with opiate overdose. The partial agonist buprenorphine is supposed to provide some margin of safety relative to full opioid agonists…but Dr. John may have been using other opiate drugs as well:

Guglielmi says several drugs, including more than 25 marijuana plants, were found in her Baltimore home.
“Medications were that of buprenorphine, oxycontin, oxycodone, morphine — very potent painkillers.”

There’s some interesting general stuff in this story, while we await additional detail, about opiate abuse and the general problems with agonist therapy. Buprenorphine is an opioid partial agonist which means, as with other agonist therapy, it is supposed to work as a weenie version of the preferred drug. The idea is that a weaker signal can alleviate the withdrawal effects while hopefully not accelerating the addiction. Combined with additional counseling and intervention, agonist therapy can be quite helpful in weaning people out of their addiction.
Of course, since it does have pharmacological activity similar to the preferred drug that means it comes with some level of abuse potential. Indeed, people inject buprenorphine to get high and the smart money assumes that that is why Dr. John was injecting the stuff.
The comment about Dr. McCracken obtaining the drug from an online source in the Phillipines could just be an access thing but it made me think about commercial formulations as well. Subutex, the sublingual oral commercial product with only buprenorphine was reformulated as Suboxone which has 4:1 buprenorphine to naloxone ratio. Naloxone is an opiate antagonist. The “bought from the Phillipines” quote made me wonder if perhaps they had found a source for Subutex instead of Suboxone- but that is pure speculation.
Why add an antagonist to an agonist therapeutic?
The idea is that naloxone taken sublingually doesn’t make it into the brain in great amounts because of a high first-pass metabolism by the liver (monkeys, humans). If you try to inject the stuff, however, you end up with a good fraction being available to the brain which leads to a precipitated withdrawal effect. It is sort of like accelerating the drop-off in drug effect that would normally be occurring because of metabolism and excretion- introduce a sufficiently competing antagonist drug at the receptor level and you shut off the signal quickly.

Figure 1: Higher street price for buprenorphine than for the buprenorphine + naloxone combination. Respondents reported the prices they had paid for 8 mg of the two products. The graph shows the percentage of respondents willing to purchase the drug at a particular price. For example, 89% were willing to pay €25 for 8 mg of buprenorphine but only 3% would pay that much for 8 mg of the combination.
I’m trying to see how this theory is panning out- addicts are willing to put up with lots of stuff to get high and MSM reports quickly pointed to abuse patterns. You will find some mixed results in pubmed quite easily. In this example from Alho et al, 2007, Finnish opiate injecting drug users were willing to pay for the combined product, albeit they liked the pure buprenorphine product much better.
I have a few closing remarks for the tribe of science and particularly the drug abuse fields. These postdoctoral fellows worked in and around the addiction areas and I have little doubt that many of their colleagues, past and present, are beating themselves up. “How could we have missed this, we are supposed to be addiction specialists!??!“. Please don’t hold yourselves responsible for this tragic death and the likely disruption of Dr. McCracken’s career. You could not have foreseen this coming to pass.
One clear factor that comes out time and again in cases of middle-class, so-called “functional” drug dependence is that people are fantastically good at concealing their drug use. Fantastically. And when it all comes out, people around the addicted person are AMAZED how much/often the person was using…and still nobody clued in. Addicts are good at concealing their actual drug administration and their state of being high. I have a thought for all of their colleagues who might be casting about for answers- it is not your fault for not noticing.
Dammit.