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.

Physical Dependence vs. Addiction in Chronic Pain Patients

A question from a reader about taking Suboxone for chronic pain, and about physical dependence vs. addiction:
Thanks for the web page. It gave me a lot of information that I had been searching for. Most of your blog deals with addiction. Will Suboxone work for dependence? I have been on Oxycontin for 7 years due to nerve damage in my back and Fibromyalgia. I have been able to get down to 30 mg per day with the help of RF ablations but unfortunately there aren’t any pain doctors in my area that will take medicare anymore. RFA’s don’t last forever and I’m being forced to increase the Oxycontin again to manage the back pain. The severe cold with snow has made this a very miserable winter which is why I’m looking for a different answer.
From what I’ve read, I don’t believe addiction is as big of a problem as the dependence in my case. I’m using the medication as prescribed and the doctor is working with me and is more than willing to increase the medication if needed. The problem is my life revolves around that once a month prescription. Every time I try to leave the state, it is a major production since the nurses think I’m trying to pull something if I ask to fill my meds early. The doctor trusts me but getting through the technician that handles the refills for the office is like dealing with the Nazi’s…and I’m being kind. I’m not sure that switching to Suboxone will change anything. I’m thinking maybe at least this way I might be able to someday get completely off all this kind of medication. I don’t actually want to increase my medication again and if I understand correctly Suboxone will take some of the pain away.
Any insight would be greatly appreciated.
My Response:
I hear your frustration over the attitudes and hassles associated with opiate treatment.  I find it ironic that many doctors act as if patients are criminals for using the very medications that the doctor prescribed!
You question is a difficult one;  I struggle with deciding the best course of action for patients who are physically dependent on opiates but who haven’t shown signs of addiction.   Just to clarify,  I do think that many pain patients do cross the line without realizing it;  it can be very difficult treating opiate addicts who initially started through legitimate use for pain, as those patients see themselves as ‘unique’—and that feeling of uniqueness gets in the way of the changes that need to occur during the recovery process.  So it is important that you take an honest look at what is happening in your own situation.


Buprenorphine is being studied for use to treat chronic pain, as are other medications (search for ‘oxytrex’ or ‘embeda’).  Partial agonists including buprenorphine (including the medication Suboxone) do offer some advantages over agonists, but have some potential drawbacks as well.  Even a pain patient not ‘addicted’ to opiates would likely notice a profound difference with Suboxone;  the feeling of needing ‘more’ would mostly go away, as would the fear of being without medication.  I use Suboxone for pain patients, and they universally report that in retrospect they see how much the pain medications were controlling their lives, and they are grateful for the change to something that leaves their mind free of those thoughts.  Some people find that their pain lessens—in my opinion because they are out of that cycle of feeling/dosing/feeling that makes up opiate pain treatment.  With Suboxone there is much less risk for ‘dose escalation’; the effect is capped at a level equivalent to 30 mg of methadone, and increases in dose do not provide much more pain relief.
The downsides of Suboxone are related to the benefits;  the ceiling effect that limits dose escalation also limits… dose escalation.  If you really DO need more analgesia, you won’t get it from Suboxone—and you will be blocked from getting it from other medications.  ALTHOUGH—the increase in analgesia from dose escalation is mostly a ruse;  you only become tolerant to the higher dose anyway, so there is little value in being able to increase the dose of oxycodone or other agonists.  Suboxone and other partial agonists present challenges during periods when big increases in analgesia are required, such as after surgery or injury.  Finally, patients taking Suboxone quickly become tolerant to the effects of buprenorphine, so I wonder sometimes whether the medication is truly reducing pain, or whether it is causing a ‘placebo effect’.  ON THE OTHER HAND—a ‘placebo effect’ feels as good as a ‘real’ effect, so the question isn’t that important.  Plus, patients will get tolerant to EVERYTHING—including agonists—and so the tolerance to buprenorphine is not specific to that medication.
A tough call—but in patients who cannot prevent the run-up in dose that occurs with opiate agonists, Suboxone is a better choice.  There is no future in being on runaway doses of oxycodone;  those situations will always end badly eventually.  I believe that for those patients, Suboxone restores a great deal of sanity to the treatment process.  With Suboxone, the patient can free himself/herself from the constant thoughts about pain medicine, and get the person to move forward into the appropriate non-narcotic treatment strategies that are usually the true road to better function.
Good luck!

It's the Paradigm, Silly!

I talk quite a bit about the letters from ‘flamers’, but don’t often mention the messages of support from grateful people on Suboxone, and the nice comments from my patients.  I enjoy speaking to patients on Suboxone about the things said for example by the silly pharmacist in the last post, and as I try to explain things I realize that they KNOW– and I can say:  ‘well- you know how it works!  You’ve TAKEN it!’  And they nod their heads with recognition.
The primary purpose of 12-step groups is supposedly to help addicts;  some groups seem more concerned with something other than ‘help’.  Suboxone, as I have said many times, is not perfect… but it is a great step in the right direction.  If we DID have the perfect medication– say a medication that instantly cured addiction– would NA be for it or against it?  Given those comments in the last post, you have to wonder!  Even with the imperfections of Suboxone, we have a medication taken once per day, with relatively few side effects, that instantly virtually eliminates the desire to use opiates, that maintains it’s actions long-term, that has no known serious toxicity…   And the complaint of people is… it is hard to stop.  To which I say… GREAT– BECAUSE WE DON’T WANT PATIENTS TO STOP IT!  One problem with naltrexone ‘treatment’ (among many other problems) is that the addict can (and does) simply stop it, and use the same day– you can’t do that with Suboxone!
People with awareness of the harm done by addiction, who have minds open to to the progress of science, understand the new paradigm for treating opiate dependence.  To elaborate:
Some of the mis-statements of the anti-Suboxone crowd relate to their confusion over ‘addiction’ vs. ‘physical dependence’. Suboxone does cause physical dependence– if you stop it abruptly you will have significant withdrawal, as with other opiates. BUT… ‘addiction’ is a different issue. Psychiatrists think of ‘addiction’ as the ‘mental relationship with the drug’. Suboxone, when taken properly, eliminates ‘addiction’– or at least holds it in remission;  people who take Suboxone clearly notice that their relationship with opiates– their obsession over them– quickly vanishes. Too often people equate ‘recovery’ with the amount of drug taken or NOT taken; a person can be free of alcohol and be in a ‘dry drunk’ and not in ‘recovery’; Similarly, a person can take Suboxone and be in recovery–as ‘good’ of recovery as any other recovery!

It is true that if you stop Suboxone you will have withdrawal. On the other hand, if you take 8-16 mg of Suboxone once per day, in the morning, you will no longer think about opiates, and they will no longer control your life. THAT doesn’t happen with methadone or with other opiates–and frankly it doesn’t happen with NA either.  Rather, it is a function of the partial agonist effects of buprenorphine. This is the ‘new paradigm’ that has impressed and provided hope for the scientists and physicians looking for a way to reduce the harm done by narcotics.

If you look at ‘addiction’ as the ‘mental obsession for the drug’– and I believe that is the appropriate way to look at addiction, as it is the obsession that destroys intimacy with others, leads to criminal behavior, and demoralizes the addict– if you use this definition, I see a strong argument that a ‘Suboxone recovery’ is BETTER than ‘NA recovery’. Why? Because with NA, the relationship with the substance is often still largely present.

Who is more ‘recovered’: the NA addict who talks about his addiction constantly and attends meetings three times per week… or the Suboxone patient who takes a vitamin pill and a Suboxone tablet each morning, and hasn’t had a thought about using for weeks? The NA addict who crosses the street to avoid walking past a bar… or the Suboxone patient who has lunch in the bar without any fear of falling down a slippery slope that leads to using? The NA addict/pharmacist who hovers over blogs about Suboxone and boasts over whose recovery is better, or the Suboxone patient who no longer needs to meet three times per week with such judgmental people?

Keep it real,

SD