Clean Enough, Chapt 3; Primer on Buprenorphine part 2

Physical dependence vs. addiction
Tolerance and withdrawal are signs of ‘physical dependence’ on a substance.  Addiction, on the other hand, is a complicated term that has different meanings in different contexts, but generally refers to an obsession or attachment to a behavior, person, or substance.  Many people mistakenly consider physical dependence and addiction to be the same.  To illustrate the difference, there are many medications that cause physical dependence that are not addictive.  Effexor and Paxil, two common antidepressants, cause physical dependence and have very uncomfortable withdrawal symptoms.  Physical dependence occurs in non-psychiatric medications as well; suddenly stopping some blood pressure medications will cause an upward spike in blood pressure.  Most people are aware of the withdrawal from missing their morning dose of coffee.  Steroids must be tapered when they are discontinued to avoid the risk of hypotension or even shock. 
So what is addiction?  Addiction can be seen in different ways depending on who is looking.  From my perspective (as a psychiatrist), opioid addiction is the mental obsession for opioids.  Addiction is the relationship that the addict has with the drug.  Most people associate ‘addiction’ with a person using large amounts of the substance, but when addiction is understood to be not the taking of the drug but rather the obsession, it is clear that addiction does not even require the presence of the substance to be active.  In fact, addiction is in some ways most active when the substance is NOT present.  I have heard patients say ‘I’m not an alcoholic– I haven’t had a drink in weeks’.  But in AA there is recognition of a condition known as a ‘dry drunk,’ where a person who loves alcohol is not consuming alcohol, but is consciously or unconsciously thirsting like crazy for a drink!  Similarly, an opioid addict may be free of opioids for several days, but will be so obsessed with finding opioids that there is little ability to think about anything else.  So treating addiction requires much more than keeping the person from using drugs.  Successful treatment also includes removing the mental obsession for the substance and removing the relationship with the substance.  I sometimes refer to addiction to a drug as similar to having an unstable boyfriend or girlfriend.  When the realization is finally made that the relationship is toxic, it isn’t enough to stop dating– the phone calls and text messages have to end as well.
Buprenorphine is different
Drugs that bind to receptors can be classified into several categories depending on their effects at those receptors.  At the mu opioid receptor, hydrocodone (Vicodin), oxycodone (Oxycontin, Percocet), methadone, morphine, and meperidine (Demerol) cause increasing stimulation as the concentration of drug is increased. Molecules that have this effect are called ‘agonists.’  Naltrexone and naloxone, on the other hand, block mu receptors without stimulating the receptors.  Molecules with blocking activity are referred to as ‘antagonists’ and are used medically to reverse overdoses or to block opioid effects. Buprenorphine has actions at mu opioid receptors that are between agonist and antagonist molecules, and is classified as a ‘partial agonist’ or ‘agonist-antagonist.’  Buprenorphine stimulates mu receptors to a point, but beyond that point further increases in dose do not cause increased stimulation—the so-called ‘ceiling effect’.  When Suboxone is taken sublingually, the ceiling effect occurs at a buprenorphine dose of about 4 mg.  Beyond this dose buprenorphine becomes an antagonist as well as an agonist, blocking mu receptors and preventing stimulation by other opioids.  This effect of buprenorphine is unique and distinct from the effects of opioid agonists such as methadone.
It is worth pointing out that like many opioids, buprenorphine has effects at opiate receptor subtypes other than the mu receptor.  Buprenorphine is an antagonist at kappa and epsilon receptors, for example.  Actions at other receptors may be responsible for the mood effects of buprenorphine.
Buprenorphine is very potent.  Outside of the United States buprenorphine is used to treat pain in doses as low as 5 micrograms.  A patch formulation of buprenorphine in the UK (BuTrans) releases buprenorphine through the skin at a dose of 5-25 micrograms per hour.   The potency of buprenorphine creates challenges for those who try to taper Suboxone, when they taper down to two mg/day, think that they have made great progress, and assume that the rest of the taper will be a piece of cake.  They instead find that the work of tapering has just begun.

2 thoughts on “Clean Enough, Chapt 3; Primer on Buprenorphine part 2”

  1. Wow, you’ve really blown my mind here. Where do I start… I’ve been on and off many drugs for about 15 years now- at 32 years of age. Because of periods of residential treatment, there have been times when I was not physically dependent to opioid drugs- and even times when I wasn’t even addicted..;-) I was just reading what seems to have been your first post here- perhaps your second. Point being, while registering to comment to your post, I believe this post was added.
    So I’m responding to both. You mentioned in the first one taking 100 steps and feeling like dying, basically. I have been on methadone maintenance 5 times- 2 times for a year or more. The last (LAST!) time I sat in a bed- girlfriend gone for good / waiting for eviction- and there are times when I thought I was dead. I later remember someone being in the bathroom with me at times, though no one’s ever been in the apt except for me and my girl who was long gone. I was either talking to myself and believing it, or hallucinating, or both. I had no job, no family around, and my nice Lexus- nice as he was- just would not run without gasoline. The clinic would dose me for free, but it was about 4 miles away, and I didn’t know if that was nearer or farther than my bathroom- they were both far… I had a cat I was keeping for my father who had passed from cancer. I remember stretching across town- bad license plate and sick- to Target where I opened a credit card in my ex-girlfriend’s name (which was Ryan) so I could get a bag of cat food and some spaghetti-O’s.
    The clinic had kicked me off for not getting there enough. After a year and a half, and flashes of what I would prefer my life be like, I thought I could just lay there in the bed and it would go away eventually…. They sent me from 120 mg a day to 0, all in 3 days worth of “detox”. (of which I made 2 days).
    The point about the 100 step thing was that I remember thinking about walking to the clinic, but I thought I would seriously die in the NC summer heat. I mean when you just CANNOT walk up a flight of stairs, how are you going to walk 4 miles in the heat? That crap is sad… It’s for the birds.
    I had been accepted to law school in Durham, NC after 4 years of Dean’s List work, but I just couldn’t pull it together. Your story is truly encouraging to me, because my experience has found many, many doctors, many addicts, many shrinks and psychologists, but never one who was all three in the same. Not one, did I meet EVER, that I feel has been to the same extent of physical dependence on an opioid drug and also truly knows about the drug. I’ve heard doctors spat off about the mu , kappa beta and delta, :), but none who actually knows how what they’re talking about FEELS when it happens or doesn’t happen but needs to.
    After 15 years of using pain killers, et. al., and since age 15, I feel like my brain is just BENT that way. I don’t feel right a YEAR after not using opioid drugs. Perhaps I’ll change my mind. I’ve been taking suboxone illegally for about a year now. I can’t afford to take it legally, but did just get accepted for medicaid today! I’ve never been accepted for any state programs; this is well welcomed. I feel depressed when I don’t take it. Moreover, I feel very normal when I do take it. I don’t feel high- as a matter of fact I don’t even care to be high… Otherwise I’d just find some Oxycontin or Methadone.
    So I’ll finally get to go to a Suboxone clinic. I’ll finally be able to carry a job, and perhaps go back to law school with a stable mind. I can’t believe how much I’ve learned about suboxone just from your three postings here. You have a tremendous amount of information and knowledge to share and I look forward to hearing it. My daughter is 2, and when you mentioned your daughter of 12- that got me… She is the reason I don’t want anything but suboxone- I don’t want to be high or addicted to anything…
    I hope in your work and through your book you’ll be able to make some progress towards making this drug as cheap and accessible as methadone, which should then be banned for the purpose of recovery. I did not know they used Suboxone for depression in England (where my sissy’s studying for a Ph.D in public health). Being prone to depression, possibly because of years of opioid abuse, I really think that’s an answer. One last thing- THANK YOU for saying that Suboxone comes in doses less, far less, that 2mg. I thought I was crazy. When I’m out of it- just a FLAKE of one pill will set me at ease… It’s amazing. I wish most doctors had your knowledge….
    I will comment on your blog here often, and I thank you for being a person I can understand, fully. That has made a great deal of difference to me today… I’ll comment regularly as I start (legal) Suboxone treatment!
    Cheers,
    MV
    by the way, it took me 2 full months as well to even get off of a couch after the last Methadone detox….. it couldn’t have been much better than dying….:)

    1. Thank you very much for your comments. I want to strongly encourage you to go forward; finally there is a treatment for opioid dependence that truly works, and I have seem many people do amazingly well in life once treated– as if they were fighting with rocks tied to their legs, and then were freed! Buprenorphine won’t fix everything in life, of course– I suspect you already know that life is hard, and that ultimately we all have the responsibility to work our hardest to deal with the challenges that come our way. But for the person willing to carry his/her own load, buprenorphine has the potentially to make a person ‘whole’ again. Good luck!

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