Author: Diary of a Quitter
Posted: Tue Nov 01, 2011 4:17 pm
Ok, what were we arguing about again?
To recap:
Ironic argues that:
| Quote: |
| I don’t know if this topic has been addressed here yet, but I find that with buprenorphine, less is more..and many on the interwebz seem to agree.
Doing some reading, I have learned a (simple) explanation: At <4 mg of buprenorphine per day, there are still receptors open to norbuprenorphine, which is what buprenorphine is metabolized into. Norbuprenorphine is more depression/pain relieving than the buprenorphine itself. |
For the record, this topic actually has been addressed here before. Some people agree that they do better, have less side effects and a fatter wallet on a lower dose of Suboxone. Other people experience the opposite – they feel better on a higher dose, have less cravings, manage pain better, etc.
It appears there is not a consensus on this issue, but the "less is more" idea is certainly food for thought.
I am personally interested in learning more about the norbuprenorphine issue and will look into that as time allows.
And then…
It seems the "ceiling level" or "ceiling effect" thing became a point of contention. Ironic understands the term "ceiling level" to mean "the dose at which the agonist effects of bperenorphine reach a maximum and do not continue to increase linearly with increasing doses of the drug" which is stated by SAMHSA to be between 16 and 32 mgs of bupe taken sublingually per day.
Breezy Ann and others understand the "ceiling level" to be the minimum dose of bupe at which a person’s opiate receptors would be completely engaged, thus preventing cravings and withdrawal symptoms. They also understand this dose to be the dose at which the opiate-agonist effects of buprenorphine level off. Per Dr Junig, this dose is around 4mgs per day. Also per Dr. Junig, the benefit of taking a dose higher than 4mgs per day, despite the fact that this is where he indicates the ceiling effect is reached, is that the higher dose guarantees a stable blood level of buprenorphine at a level sufficient to prevent the patient from feeling withdrawals or the ups and downs that may be felt at lower-level dosing. This stability is held to be an important factor in a patient’s ability to break the response-reward cycle that is the hallmark of addiction.
So it appears that we have a conundrum! Someone here must be wrong. Is it SAMSHA or Dr. Junig? 16-32mgs or 4mgs?
What is the TRUTH?
I’m going to attempt to make the case that BOTH understandings are true. Hang on, I’m about to get all pedantic.
First, let’s get clear on what we’re actually talking about. I’m sure that we’ve all seen some variation on this chart:
This chart illustrates the "ceiling effect" of buprenorphine. The ceiling effect is the point at which increased doseage no longer creates an increase in "opiate effect."
What do they mean by opiate effect? Is it a measure of feeling of euphoria, withdrawals, or analgesic effect? Can they actually look at our brains or do a blood test to see what percentage of our opiate receptors are occupied? No.
They are measuring increased respiratory depression as indicated by Pco2 (partial pressure of carbon dioxide) levels. When Pco2 levels no longer increase with increased doseage, you have encountered the ceiling effect. Respiratory depression is how they measure "opiate effect," which makes sense because it can be objectively measured and it relates to the safety of the medication. But it doesn’t really tell us much about the subjective experience of the patient and it doesn’t directly describe things like how many receptors are occupied, level of cravings or withdrawal symptoms, etc. For example, this measure does not tell us that at 4mgs, 95% of your opiate receptors are engaged while at 16mgs 98.7% are engaged. All it tells us is how repiratory depression correlates with buprenorphine dose.
Samsha, NIDA and the rest of the Feds have determined that the dose where this ceiling effect occurs is between 16mg and 32mgs sublingually. Dr. Junig says 4mgs. How can they both be right?
Look at the line on the chart that represents Buprenorphine. You’ll notice that it begins to rise in a linear (straight) way. Then, right around the part of the line that is directly beneath the red arrowhead, the line begins to curve. This is the point on the curve where it begins to transition from a steeper slope to a shallower slope.
This point on the line is known as "the knee in the curve." It is also known as "the point of diminishing returns." This is the point where the level of opiate effect begins to decrease exponentially with each subsequent increase in doseage.
The "knee in the curve," "point of diminishing returns" is also known as "the sweet spot." This point indicates the point where you are getting the MOST opiate effect for the LEAST dose of buperenorphine.
Because the graph doesn’t supply any raw data, I can’t say what this "sweet spot" dose is. But looking at the chart, we can reasonably state that the "sweet spot" dose is lower than the 16-32mg dose indicated by that pointing arrow as where the "ceiling effect" occurs.
Dr Junig has made known his opinion that the "ceiling level" for bupe is around 4mgs sublingually. I think it is entirely possible that what he has found is that the 4mg dose is right in that "sweet spot" indicated by the bend in the line of the graph. It is below the dose found to be the point where Pco2 levels no longer continue to rise, but it is not far enough below that level to really matter as far as the lived experience of the patient is concerned.
Looking at this chart it’s possible to see that the actual difference in opiate effect (as measured by respiratory depression) between a dose of 4-8mgs and a dose of 16-32mgs is pretty negligible. It’s a pretty flat line. But we don’t go around as Sub patients taking measure of our respiratory depression and resultant Pco2 levels to determine what dose is best for us. We subjectively measure how we feel physically, mentally and emotionally. How are our withdrawals? Our cravings? Our mood?
I think that what Dr. Junig is getting at with his 4mg ceiling is that 4mgs is the dose at which he finds most patients begin to see those diminishing returns with incresed doseage. More than 4mgs may get you slightly more "opiate effect" as measured by Pco2, but it really doesn’t get you more "opiate effect" as measured by patient experience with regard to cravings and withdrawals. To Dr. Junig, 4mgs is the dose where the line on the graph flattens out enough that the differences between 4mgs and a higher dose begin to matter significantly less.
(The one caveat that he places on his 4mg ceiling estimate is that Sub patients will want to take a high enough daily dose that they do not dip below the blood level concentration required to maintain that 4mgs, thus eliminating withdrawals and ups and downs. For him, this is where the higher doses come into play.)
To Samsha, NIDA and all, the ceiling effect is the point where Pco2 no longer increases with dose. Period.
I argue that Dr. Junig and the Feds are BOTH right – because the actual difference between the "opiate effect" of 4mgs and the "opiate effect" of 16-32mgs is insignificant enough that it becomes basically meaningless.
