Missing the Point of Buprenorphine Treatment

A forum reader wrote about concerns over a partner on buprenorphine.  Her concerns pointed out a common misperception about the goals of treatment of opioid use disorder using buprenorphine, or using methadone for that matter.

Her question, amended for privacy:
I married the love of my life.  He is still he love of my life but has been an addict for 15 of them. Our children have been greatly affected by his addiction.  He made promise after promise that he was clean, and I dove back in with complete faith time after time only to get burned.

His addiction started with recreational pills increasing over time, but now he is abusing Suboxone.   He was taking up to 12 mg depending on the day, but no pain pills for the last year. I suggested a Suboxone doctor and a plan to get off, and my husband called one and was able to get right in.

At the visit the doctor did a half ass intake and called in a prescription for an 8 mg tab for induction.   After induction they called in prescription for 20 mg/day.   My husband stayed with 4 mg once a day and was “blah” in the afternoon and irritable but not physically sick.  On his next visit to the doctor he was proud, but when he told the doctor he had only take 4mg in the mornings she got angry. She told him she wouldn’t see him anymore if that’s what he was going to do. He asked how long he would be on it and she wouldn’t give any kind of answer. I asked again before we left and she snapped at me.

I see a profound change in him after each time we see her and she tells him to take more. We walked away last time with another prescription for 16 mg a day which is just about double what he’s been taking for the last year and a half. So my question is, how does it make sense to treat someone taking 8 mg as their addiction with the same medication at double the dosage? Since seeing her he has decided he needs to take it more than once a day as well as up the dosage.  Is this right? Is it right to treat Suboxone addiction with Suboxone? A heroin addict isn’t treated with more heroin and a pill addict isn’t treated with more pills.  While I understand the concept of treating his original pill addiction with Suboxone, I am having a very hard time wrapping my head around what’s happening.

Me again… 
The writer raises interesting questions.  Regarding the ‘drug for a drug’ questions, buprenorphine has significant pharmacologic differences from heroin or pain pills. Those differences, including the long half-life and ceiling on agonist effects, allow the medication to create a level degree of mu-receptor agonism across the dosing interval.  Tolerance to that level mu agonism allows patients on the medication to feel ‘normal’ throughout the day, or at least normal from an opioid standpoint.

But her broader point provides an example of the basic misunderstanding many people have about medication assisted treatment, in focusing on the same short-term goals that their addicted loved ones have focused on: controlling the dose of opioid and tapering off.  That goal is natural, of course;  anyone who loves a person addicted to opioids wishes and hopes that the person will reverse the using behavior and climb down from opioid use.  Those hopes are bolstered by ads for rapid detox, even as studies show that detox is mostly useless.

My response to her:
I would not be concerned about increasing the dose of buprenorphine, because there is no increase in effect after a dose of about 8 mg per day.  A higher dose might reduce mild withdrawal symptoms at the end of the dosing interval, and sometimes provides a reduction in cravings through a placebo effect.

So why increase? Because the goal with buprenorphine treatment is to put cravings into remission for a considerable length of time. If your husband is still having cravings as he gets by on 8 mg, then his dose is not high enough. Buprenorphine is a safe medication that is used as a tool to extinguish the conditioning that was part of your husband’s addiction.

One of my patients saw a different buprenorphine physician for years, and her dose was constantly lowered over the past year. She would run out of medication after 24 days each month and then go without for 6 days, craving opioids and experiencing wtihdrawal during that time.  In some ways, her entire time in treatment was a waste.  She could boast, I suppose, that she was prescribed less buprenorphine over time. But in most ways she is just as far from stopping opioids as when she entered treatment, still lying to her husband, lying to her doctor, and feeling ashamed of herself.   All of those things  keep her addiction in the dark, where it stays active.

When I started treating her my goal was to promote legitimate behavior. I increased her dose to 12 mg per day, from 8 mg.   After a month she still ran out early, So I raised the dose to 24 mg per day. Now, after 6 months, she has taken the medication as prescribed. Her focus on buprenorphine is going down, as we want it to do. She isn’t lying, and she isn’t craving pain pills or buprenorphine. My goal is for her to take the medication like she would take a vitamin or blood pressure pill, without any special attention or interest.

How long will we do this? I can’t say now. We know from research that the longer a person stays on medication, the less risk of relapse after stopping. I don’t like to push anyone off buprenorphine, because I’ve seen so many people who have relapsed after being pushed off by their former doctors.  I find that many people eventually decide that the time has come to taper off buprenorphine, and those efforts are usually successful.  From my perspective, people forced to taper off buprenorphine do not generally do well.  That perspective is just an opinion, but an opinion based on treating 800 people with buprenorphine over the past 11 years.

Opinions aside, the goal is not about getting off opioids as fast as possible. Your husband can accomplish that in a couple weeks with a remote hotel room and a bottle of clonidine, or a couple weeks in jail. But those experiences rarely lead to prolonged abstinence, and they sometimes precede overdose, when people return to using with a lower tolerance.

I can’t tell whether your husband’s doc is on the right track or not– but she might be. She is a better doctor telling you that she can’t give a time estimate, than a doctor telling you he will be off in 3 months.  Ideally, your husband will be in a state of ‘remission’– on a dose of buprenorphine that virtually eliminates interest in opioids– for a year or more. He can taper for some of that time, but the taper should be slow enough that he doesn’t return to using.  If he returns to active use, he starts over in many ways.

Try to drop the focus on ‘how much’ or ‘how long’. Those things are not important; what is important is to get his interest back on you and the family, not on buprenorphine or other opioids. That will be easier if you let him know that he has your support, even if he takes a medication, and even if he needs that medication for a long time. You would want the same from him if you ever needed a medication for hypertension, diabetes, or anything else.

Toward Understanding Ibogaine

First Posted 12/30/2013
Paul Dessauer, Outreach Coordinator at WASUA, the Western Australian Substance Users’ Association, often adds insight to issues that come up on my blog.  He shared a few comments in response to my post about ibogaine, and at my request gave permission to post his remarks here. His comments include a summary of the receptor actions of ibogaine known to date, a description of the legal status of ibogaine ‘down under’, and several links to further information.
The information provides a good example of how knowledge is gained about psychoactive substances through combining research data from different areas of study.  Psychologists  assess the effects of the drug on different aspects of behavior.  Neurochemists identify the actions of the substance at different receptor systems, with an understanding of the anatomy and interconnections of those receptor systems. Neurophysiologists identify the effects of the substance on firing patterns in different brain regions. All of this knowledge is added to the things we already know about brain function, to push our understanding a bit further. Neuroscience is inefficient, as single studies rarely provide significant gains, and some studies yield results counter to the findings of other studies.  But little by little, over years, we gain an understanding of how a substance affects brain function.
I thought it appropriate to share some information about WASUA:
WASUA Vision:
To improve the health and social circumstances of substance users, utilising a framework underpinned by harm reduction and peer education.
Mission Statement:
To provide support, education and advocacy and to reduce transmission of Blood Borne Viruses and the harms and hazards associated with substance use amongst people in Western Australia.
His Comments:
We should always be skeptical in the extreme of any treatment modality that is presented as a universal “cure” or “magic bullet”, but at the same time we must be careful that the blind zeal of enthusiasts doesn’t cause us to dismiss potentially useful tools out of hand.
Pharmacologically, Ibogaine is a very interesting substance, as it’s a psychedelic tryptamine that is an agonist at 5-HT2A (serotonin receptors) but also acts as an antagonist at NMDA receptors, is an agonist for kappa-opioid receptors and also non-competitively inhibits nAChR (nicotinic acetylcholine receptors).
Serotonin agonists include LSD and a great many other hallucinogenic drugs.
Like dopamine and glutamate, NMDA (N-methyl-D-aspartate) is heavily implicated in the development and maintenance of dependence to many drugs.
Nicotine binds to nAChR (nicotinic acetylcholine receptors), and the drug Zyban (bupropion), which is used as a smoking cessation treatment, blocks acetylcholine receptors.
Just to complicate this pharmacological profile further, Ibogaine is metabolized in the liver (via CYP450 2D6) to produce a psychoactive metabolite noribogaine (12-hydroxyibogamine).
Noribogaine is most potent as a serotonin reuptake inhibitor, reinforcing the serotonergic effects of the parent molecule. It also acts as a moderate κ-opioid receptor antagonist and a weak µ-opioid receptor full agonist, (mu-opioid receptors mediate the euphoric effect of opioids).
(Opioid receptors come in three classes- kappa, mu, and delta. Ibogaine binds most strongly to κ- opioid receptors, shows less affinity for μ receptors, and no affinity for δ receptors. Noribogaine binds to all three classes more strongly than Ibogaine does). http://www.ibogaine.desk.nl/ch05.pdf
It is possible that this action of noribogaine at the κ-opioid receptor may contribute to the psychoactive effects; the hallucinogenic plant Salvia divinorum contains the chemical salvinorin A which is a highly selective kappa opioid agonist.
As an opioid receptor agonist, Ibogaine actually potentiates opioids. It’s been demonstrated in a couple of small studies that co-administering Ibogaine with morphine stops the development of tolerance and decreases the chance of dependence- but no-one has used this effect clinically, apparently because the dangers of overdose due to potentiation.
Animal studies show that Ibogaine appears to reduce or repress the urge to self-administer morphine in some, but not all, rats who are morphine-dependent, eg;http://www.sciencedirect.com/science/article/pii/0014299991904745
It also inhibits cocaine self-administration, eg;http://www.sciencedirect.com/science/article/pii/001429999390212Z
Both of those rodent studies show a dose-response relationship, with more of the rats ceasing or reducing self-admin if they were given three doses over a three week period, than from a single dose.
More; http://jpet.aspetjournals.org/content/288/1/88.short andhttp://jpet.aspetjournals.org/content/275/2/753.short
Although Ibogaine treatment is apparently not illegal in Australia, Ibogaine is a very strictly controlled substance.
The import of ibogaine is specifically prohibited under Schedule 4 (import regulations) of the Customs Act. Under the definition of the law ANY material containing the listed substance is deemed to be that substance. Hence, all ibogaine containing material is a drug prohibited import.  However, there are no restrictions on possessing ibogaine containing material, seed or live plants in Australia, except that pure ibogaine may not be sold or possessed as a therapeutic product without prescription.
NOTE: Under customs law the importation of 1g of ibogaine is equivalent to importing 1g of heroin. The importation of 100g of iboga bark is equivalent to importing 100g of heroin. The importation of 1g of ibogaine dissolved in 100ml of water/alcohol (eg a tincture) is equivalent to importing 100g of heroin.
Legal status in Australia; http://shaman-australis.com.au/shop/tabernanthe_spp_cp_110.php  andhttp://www.shaman-australis.com/forum/index.php?showtopic=26958.
New Zealand’s regulators decided to classify Ibogaine and its primary metabolite as a prescription medicine, but this actually makes it more difficult to legally source, as previously it was unregulated. Interestingly, in their review they mention that Ibogaine in NZ as an un-regulated drug was associated with about the same number of deaths per annum as the most strictly regulated prescription drug, methadone.  Here is the decision; http://www.medsafe.govt.nz/Profs/class/mccMin03Nov2009.htm
Scroll all the way down the page to item 10. “General Business”, and you’ll see that Ibogaine is Item 10.1 There is actually a good, concise summary of what we know about this drug at 10.1, – well worth a quick read if you are interested in Ibogaine.
There is a native Australian Ibogaine Shrub, containing extractable quantities of the drug, although there appears to be no surviving tradition of Aboriginal people ever using it. (Although just because there is no surviving evidence of current or pre-European-settlement Aboriginal cultures using it, doesn’t mean none have ever done so during the 60,000 years or more that they’ve populated Australia. Other psychoactive plants, like Pitjuri (contains nicotine and scopolamine) and Psilocybin mushrooms were exploited ritually and recreationally by traditional Aboriginal peoples, and Pitjuri was traded all over the continent).
Australian Ibogaine (or Iodine) Bush ;http://www.somemagneticislandplants.com.au/index.php/plants/87-tabernaemontana-orientalis
I’ve met a handful of people who have used Ibogaine to treat drug dependency, but not a large or broad enough sample to have a strong opinion about its effectiveness. (In a similar fashion, I’ve met a couple of Americans and one Mexican guy who, every six to nine months, go out in the desert with Huicol people and eat peyote, and all three swear this is what has allowed them to overcome serious drug addictions). Because of the ambiguous legal status in Australia, only 1 or two places advertise Ibogaine treatment, I don’t know how many customers they get, and I don’t know how professional these outfits are.
Ibogaine treatment centres in Australia and New Zealand; http://www.ibogaine.co.uk/options.htm#Aus
Testimonials about Ibogaine treatment; http://www.iboga.com.au/testimonials.html
More; http://shaman-australis.com.au/Website/Constituents/Ibogaine.html
Hope this is a useful info.

Rapid Opioid Rip-Off

While I’m on the subject of rip-offs, I’ll mention an extreme form of ‘detox capitalism’; a process called rapid opioid withdrawal, rapid detox, or ‘the Waismann Method.’
The name of the process supposedly comes from a certain ‘Dr. Waismann’ who helped Israeli soldiers get off opioids after they were treated for various injuries.  It sounds like a pretty exciting history, but to be honest there is nothing in the technique that takes a rocket scientist to figure out.  The basic idea is to precipitate withdrawal using an opioid antagonist— something that is done many times over every day in emergency rooms across the U.S.—but to do it while the person is sedated with non-opioid medications.

Put me out, Doc!

I never expected to admit this back when it occurred, but I had the bright idea of putting myself through ‘rapid opioid detox’ shortly before entering treatment ten years ago, when I was desperately searching for a way to free myself from opioids.
Like any typical addict I wanted to do it entirely by myself, figuring that I knew as much about opioids and medicine as anyone else.  I loaded up on naltrexone (an oral form of naloxone) thinking that the antagonist would block my receptors, lower my tolerance, and prevent me from using for as long as I took the naltrexone.
I simplified things a bit by omitting the sedation—a good idea since there was no other doctor monitoring me, but a bad idea because I experienced about a week of withdrawal condensed into several intensely-miserable hours.  I remember being shocked at just how much sweat my body could produce in such a short time, as liquid beaded on my skin as fast as I could wipe it off!
After the real horrible period—the period that I would have slept through had I come up with $15,000 plus airfare—I remained quite ill for a matter of weeks.  And of course that is what happened, since it takes weeks for tolerant mu receptors to be replaced by new, normal mu receptors.  Until the receptors are replaced, the brain’s endorphin pathways remain quiet, causing hypersensitivity to pain—not to mention diarrhea, restless legs, cramping, gooseflesh, and depression.
There are several variations of rapid detox, but the principles are the same for all of them:
–          The addict is given a strong sedating medication or anesthetic
–          While heavily sedated, the addict is given an intravenous infusion of the opioid antagonist naloxone to precipitate withdrawal.
–          After a period of time that varies with the name of the facility, the addict wakes up;  one day of withdrawal gone, and only two more months of withdrawal to go!
–          The process costs from five to ten thousand to tens of thousands of dollars.
–          Different options are tossed in for different programs, everything short of an extended warranty: amino acid cocktails, ‘vital nutrients,’ or long-term sedatives.
–          In some cases a chip of naltrexone is implanted that slowly releases over weeks, supposedly preventing a high from using—provided the addict doesn’t become desperate and use very high doses of heroin, or dig the implant from his/her body using a fork!
Web sites for the procedure point out that opioid dependence is a relapsing illness and that people who use Suboxone relapse when they stop Suboxone (no argument from me), but go on to claim a 70% one-year sobriety rate after their rapid-detox procedure—without any explanation for how they get better numbers than Suboxone patients.  I have never seen peer-reviewed studies showing such success rates.
Speaking of peer-reviewed studies, I have seen a study of rapid detox showing what is intuitively obvious—that since it takes a number of weeks for the body to adjust to the lack of opioids, one day of sedation avoids only a tiny portion of the misery of withdrawal.  Is it worth ten grand to avoid one day of withdrawal, knowing that several more weeks of withdrawal are yet to come?  I suppose it depends on one’s checking account.
But the bigger issue is the poor long-term outcome for these people—a problem similar to what I described in my post about Sneetches.  Early in the spiral of addiction, addicts and their families are under the mistaken belief that the hardest part of ‘kicking opioids’ is to get through physical withdrawal.
They eventually they learn that they are wrong, and that it is much more difficult and rare to STAY clean than it is to GET clean—but ‘rapid detox’ makes money off their ignorance in the meantime.  Quitting opioids by rapid detox, amino acids, magic crystals, hypnosis, or a host of other expensive, highly-promoted methods reminds me of the story about the guy boasting about how easy it was to quit smoking—so easy that he’s done it over 20 times!