Drug Court Organization Lobbied Against Suboxone

For years, people familiar with the benefits of buprenorphine have wondered– who is the idiot standing in the way of increasing access to this life-saving treatment?  One of the idiots was recently identified, when an open-records request by the Huffington Post uncovered a letter to HHS Secretary Sylvia Burwell from West Huddleston, then-CEO of the National Association of Drug Court Professionals.
In the letter, Huddleston wrote that allowing doctors to see more than the current limit allows ‘will result in the expanded use of buprenorphine in a manner that is less responsible and presents greater risk to the health and safety of the individuals and communities we both serve.’   The Huffington Post correctly points out that over 28,000 Americans died from opioid overdose in 2014, when the letter was written.
People familiar with buprenorphine know that the medication virtually eliminates the risk of death by overdose– even when taken incorrectly.  The anti-medication lobby, fueled by the large profits of revolving-door ‘abstinence-based’ treatments, has used fear of diversion of buprenorphine as a weapon against greater access to the medication.  But stories about diversion always fail to mention key facts about buprenorphine– for example that of the 30,000 US opioid overdose deaths last year, only about 40 had buprenorphine identified as one of the drugs in the bloodstream at the time of death.  And of those 30,000 deaths, none were CAUSED by buprenorphine.
There have been overdose deaths that were in-part due to buprenorphine or buprenorphine/naloxone medications (i.e. Suboxone, Bunavail, and Zubsolv).  But such deaths are rare.  In order for buprenorphine to contribute to overdose, the victim must 1. Have a low tolerance to opioids, and 2. Have a low tolerance to a second respiratory depressant, taken around the same time in sufficient amount.   In other words, someone physically dependent on opioids cannot overdose on buprenorphine.  In fact, buprenorphine products would precipitate severe withdrawal if taken by opioid addicts within a few hours of heroin, oxycodone, or other opioid use.
Drug courts in my area tend to avoid medication assisted treatments, with the exception of Vivitrol or IM Naltrexone.  There is no evidence that blocking opioid receptors for a year has any effect on death rates from opioids.  Studies have reported that patients who stay compliant with treatment, who return each month for another injection of naltrexone, don’t waste their money on agonists that would have no effect on them.  But what happens 6-12 months later, when probation ends and those patients are no-longer required to take naltrexone?
I wish I could tell you what happens– but I can’t, because nobody has done the studies to find out.  The cynic in me takes it further, wondering if anyone even cares what happens when people are temporarily maintained on naltrexone and then allowed to stop the medication?  I’ve asked physicians, prosecutors, and law enforcement the same question:  what happens to the person when the naltrexone is discontinued?  In response I usually hear ‘what do you mean?’  Or ‘how would I know, since I don’t see them anymore?’, or ‘I assume they do fine… don’t they?’
I don’t see much concern when I explain that people who stop naltrexone are in a state of ‘reverse tolerance’ making them more susceptible to death by overdose.   So I remind them of the large number of overdose deaths in people who were recently released from a controlled environment, such as residential treatment or incarceration, after tolerance dropped to normal levels.  Maybe I’ll point out the Australian studies that show a 12-fold higher death rate in addicts who were maintained on naltrexone.   But by that time I’ve lost the person’s attention– just as their attention leaves each addict when his/her probation expires.  ‘Not my problem anymore.’
Huddleston is no longer the CEO, but the NADCP continues to express a muddled message about buprenorphine medications.   If you have a minute, you might consider educating the NADCP staff about the value of buprenorphine treatment.
Meanwhile, HHS Secretary Burwell says changes to the cap are coming.  I received 12 calls last week from people looking for help.  I’ll keep telling them to try to be patient.

On Biodelivery and Norbuprenorphine

Over the past few months, I’ve read a few posts at the forum that are worth sharing.  I’ve been torn whether to share them with the general buprenorphine community, or only with doctors who prescribe the medication.  I’ve decided that since the ideas came from a layperson community, I’m not opening the floodgates to irresponsible behavior by repeating what I’ve read.  Feel free to comment if you believe I’ve made the wrong decision.
But first, a word of warning to persons taking buprenorphine:   Do NOT take steps to deliberately alter drug delivery beyond the things that your doctor approves of, such as avoiding drinking liquids right after dosing, or placing the film against your cheek instead of under the tongue—a useful step particularly for someone with dentures.  Do NOT try to increase the effects of buprenorphine by taking substances that block metabolism of the drug.  Such actions risk turning a lifesaving medication into just one more drug of abuse, putting you back into the miserable condition where you existed before buprenorphine treatment!
Bioavailability has become a significant issue for differentiating buprenorphine products.  Late-generation products have increased bioavailability— from 25% with Suboxone Film to 40% and 50% in Zubsolv and Bunavail, respectively.  One result of higher bio-availability is that lower doses of buprenorphine are needed to create identical buprenorphine blood levels.  A second result is lower blood levels of buprenorphine’s primary metabolite, norbuprenorphine, resulting in less constipation during buprenorphine treatment.
Some buprenorphine patients have learned about bioavailability, and have used the forum to describe their efforts to maximize delivery of buprenorphine to the bloodstream.  Over the past few weeks two discussions popped up that relate to different aspects of the same general issue.   And while similar discussions have come and gone over the years, there seems to be a growing sophistication to the discussions.
One recent discussion focused around the use of grapefruit juice to boost the actions of buprenorphine by delaying drug metabolism at CYP3A4, a cytochrome enzyme found in the liver.  Several writers described feeling a boost in mu-receptor activity when they dosed their buprenorphine after drinking grapefruit juice, a side effect that I considered unlikely given the ‘ceiling effect’ of buprenorphine and the rather limited impact of delaying metabolism in a medication that already has a long half-life.  But I realized, during the discussion, that grapefruit juice may be doing far more than reducing the breakdown of sublingually-absorbed buprenorphine.
When a person takes a buprenorphine product, 50% (Bunavail) to 75% (Suboxone Film) of the buprenorphine is swallowed, absorbed at the intestine, and converted to norbuprenorphine at the liver via ‘first pass metabolism.’  But blocking CYP3A4 may allow swallowed buprenorphine to escape first pass metabolism, causing swallowed buprenorphine appear in the inferior vena cava as buprenorphine rather than norbuprenorphine.  In such a case, blood levels of buprenorphine would increase not by the small factor expected from delayed metabolism of a long-half-life drug, but instead by a very large amount—doubling or even tripling the blood levels of buprenorphine.
I have not researched the issue, so I don’t know whether the effects of grapefruit juice on CYP3A4 are strong enough to eliminate or reduce the second-pass effect on swallowed buprenorphine.   But the topic is worth a look—a hint to some aspiring grad student out there!
In another discussion, a patient wrote that he is about to be kicked out of treatment because his doctor doesn’t think he is taking the buprenorphine that he is prescribed.  The patient wrote that he is not only taking the medication, he is INJECTING the medication, ‘so there should be even more buprenorphine in his system than normal.’
Lost on the patient, besides the general  folly of injecting non-sterile, non-IV-grade substances, is that many doctors measure levels of norbuprenorphine to make sure that their patients didn’t just ‘dose’ on the day of their appointments.  I suspect that this patient delivers far less buprenorphine to his liver by dosing intravenously, resulting in very little production of norbuprenorphine.
Why does he inject, by the way?  Like most people who inject buprenorphine, he says he doesn’t really know the answer to that question.  He says that injecting is a means of drug delivery that he has become used to, and that he is hesitant to give up. He is used to getting everything that he can out of heroin…. and he wants to get everything he can now, out of buprenorphine.  He says he doesn’t experience any ‘high’ when he injects buprenorphine.  I explained to him that by behaving so foolishly, he opens the door to huge risks – including the risk of losing access to buprenorphine.
Hope everyone had a nice Thanksgiving.

Does Suboxone Make You Blind?

Thought I’d share a quickie from a reader, who asked if Suboxone or buprenorphine were affecting his vision.
He asked:
One thing I’ve noticed when I’m not on any drugs is my pupils are fairly large.  For some reason after I stopped the Vicodin, my vision got really blurry.  I’ve worn glasses most of my life, nearsighted but even with the glasses, they were blurry.  Then when I started taking Subutex, things got sharp again.  I didn’t change my prescription or anything.  It’s got to have something to so with opiates or drugs like them.
I answered:
The vision issue is fairly straightforward.  The smaller the pupils (the ‘aperture’), the sharper the vision—a phenomenon that results from basic optics.  All opioids except Demerol (meperidine) cause our pupils to constrict (meperidine has an ‘anticholinergic’ effect that dilates the pupils.  The drug has other anticholinergic effects that doctors often remember using a mnemonic: Dry as a bone, red as a beet, mad as a hatter, and blind as a bat).  But again, the actions of most opioids make pupils smaller, and therefore vision becomes sharper.  The effect is less helpful during low-light conditions thought, when smaller pupils results in less light reaching the retina, which reduces or prevents color vision and makes images harder to define.
Vicodin likely improved your vision by constricting your pupils, as long as you were not in withdrawal, and I’m just assuming you didn’t notice the vision change during withdrawal because of all the other things to worry about!
Why should buprenorphine cause pupillary constriction through an opioid-mediated effect, though, if we accept that people on buprenorphine become fully tolerant to the mu opioid effects of the drug?  There may be some residual opioid effects even during full tolerance, but there is another explanation that I think is more interesting.    When people take a standard tab of film of 8 mg of buprenorphine or Suboxone, respectively, they absorb 25% of the buprenorphine into the bloodstream, and swallow the other 6 mg of drug.  That swallowed buprenorphine is absorbed at the small intestine and converted, at the liver, to norbuprenorphine.  Essentially no buprenorphine makes it past the liver (a phenomenon called the ‘first pass effect’ of buprenorphine), but 6 mg of norbuprenorphine DOES enter the general circulation.
We tend to ignore norbuprenorphine except for forensic or quantitative urine drug testing, because norbuprenorphine does not cross the blood brain barrier in humans.  But norbuprenorphine does have opioid effects elsewhere in the body, including at the pupil and at the intestine.  The effects of norbuprenorphine are NOT subject to a ceiling effect.  It is worth noting that the new buprenorphine drug Bunavail has lower incidence of constipation, possibly because of the reduced exposure to norbuprenorphine (2 mg of buprenorphine is swallowed with a standard dose of Bunavail, compared to 6 mg with Suboxone film).   What else does all that norbuprenorphine do?   Is night vision better with Bunavail than with Suboxone Film?  Where is a good grad student when you need one?
(addendum for the real scientists out there… I realize I’m out on a limb.  But that’s the most enjoyable part about having a blog– I just get to wonder about things!)