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 Post subject: Ceiling
PostPosted: Sun Aug 07, 2016 5:03 pm 
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Hello Dr. J., I have two questions that probably only you could answer. What is the EXACT ceiling dose for buprenorphine because I can never find a definitive answer.

Also, say that this ceiling does is 4 mg. Then does that mean that 4 mg worth of suboxone fully absorbed into the bloodstream (like intravenously) is the ceiling dose or that 4 mg worth of sublingual suboxone taken and resulting in a bloodstream level/equivalence of ~1 mg is the ceiling?

Thanks!


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 Post subject: Re: Ceiling
PostPosted: Sun Aug 07, 2016 5:57 pm 
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Mu opioid receptors have the same structure across humans. My receptors are identical to yours. They both consist of protein molecules, made up from a chain of amino acids. The sequence of those amino acids, and the genes that encode for them, have been fully sequenced for a number of years... and can even be synthesized.

In an artificial membrane, those receptors would respond to levels of buprenorphine in a characteristic way that readers here refer to the 'ceiling effect'.

In different people, I suspect that the response of those receptors would vary, even if the level of buprenorphine in the receptor environment was the same. The same receptors probably act differently depending on features specific to the neurons where they have their actions. An opioid receptor in a membrane of one of my neurons may act a bit differently than one of your receptors-- even though the receptors have the same structure. The different actions would be due to slight differences in membrane potential, or other differences related to tolerance that aren't fully understood--- at least not fully understood by me. Some receptor actions lead to changes in the lipids that make up cell membranes-- for example changing the amount of phosphatidylinositol, which acts as a 'second messenger' when ligands bind to other receptors. Cell membranes are very complicated structures, for any tissue-- containing many receptors, ion channels, enzymes, etc.

So keep in mind those differences-- and then realize how many things affect the level of buprenorphine at the receptor, including local blood flow, receptor density, presence of non-mu opioid receptors, non-specific buprenorphine binding, small differences in capillary permeability, interstitial CSF flow, actions of glial cells...

Then keep in mind that after a certain amount of buprenorphine is in the bloodstream, people will clear the drug at different rates at the liver. People will also have differing amounts of plasma proteins that bind buprenorphine, preventing it from entering the brain. Maybe some people have blood-brain-barriers that are 'leakier' to buprenorphine. There are enzyme systems that actively transport some opioids into or out of the spinal fluid (loperamide, for example, is pumped out). Maybe those enzymes play roles in some people.

And yes-- there are big differences between DOSE of buprenorphine and bioavailable, absorbed buprenorphine.

So there is no easy universal answer. But from my understanding, when people on this forum share their experience with buprenorphine, they describe a ceiling to the effects of buprenorphie corresponding to a DOSE of 4-8 mg of buprenorphine. SOME people insist that they have cravings if doses are not higher, and some docs just dismiss those thoughts. But who knows. Maybe in some people higher doses of buprenorphine are necessary to fully reach a ceiling effect. To me, it seems that having cravings all day long is NOT suggestive of a need to increase buprenorphine dose. If cravings or other symptoms are caused by insufficient buprenorphine levels, then those symptoms would worsen near the end of the dosing interval, and be relieved from 2-12 hours after dosing.


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 Post subject: Re: Ceiling
PostPosted: Sun Aug 07, 2016 8:18 pm 
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Thanks! I mean I don't have 2 or 3 different doctorate degrees like you do, but I do have a masters degree. I research for a living and do study this type of thing a great deal. But the amount of knowledge you have on this subject is absolutely awe inspiring -just wanted you to know that.

Follow up question: When people get on here and say they are "high" from suboxone day after day. Given all the unique differences within a person's biochemistry....then is that possible? For example, maybe Person A has a subjective ceiling experience that feels very nice while Person B feels just the absence of withdrawal.


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 Post subject: Re: Ceiling
PostPosted: Mon Aug 08, 2016 9:44 pm 
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Thanks for the nice comments! I don't understand how people 'get high' from buprenorphine medications, at least the people using other opioids. Regardless of the dose of buprenorphine that creates that ceiling, the maximal effects of buprenorphine are limited in EVERYONE. Those maximal effects are limited to an amount of mu opioid activation similar to what a person gets from 30-40 mg methadone per day-- which is far below the tolerance of most opioid addicts. It is hard to compare effects of oxycodone and heroin, but most opioid addicts I meet these days, either in my buprenorphine practice or at the methadone clinic I provide services to, are using a half gram to a gram of heroin per day. They substitute around 160-200 mg oxycodone per day if heroin is not around. And the maximum effect of buprenorphine has about 30% as much opioid effect, maximum.

So if a person taking those amounts of oxycodone or heroin takes buprenorphine, it won't measure up. If they are ON those levels of an agonist at the time they take buprenorphine, they will experience withdrawal. If they wait 24 hours, the buprenorphine will partially relieve their withdrawal-- but won't cause a 'high'. I suspect that some people blur the lines between 'getting high' vs. stopping withdrawal, and maybe that's what they are referring to.

Of course if a person with no or low opioid tolerance takes buprenorphine, the drug will be very potent, and cause a strong opioid 'high'. Most overdoses related to buprenorphine (which are very uncommon) occur when the drug is taken by someone who doesn't use opioids, who also takes a second respiratory depressant.


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Fond Du Lac Psychiatry
Dr. Jeffrey Junig, M.D., Ph.D.

  • Board Certified Psychiatrist
  • Asst Clinical Professor, Medical College of Wisconsin

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