Bupe Buprenorphine Ceiling Effect relative to Individual and Tolerance?

[Znegative]

Hi-I recognized this most likely should be merged with the Suboxone/Buprenorphine Megathread, but after my first week on Suboxone and my experience today, I had a question and I wanted to get some feed back from some members who are well versed in Buprenorphine.

So I got on Suboxone this last Tuesday. It had been six days since I had used heroin, and had been maintaining with kratom as I didn't have an ID, nor did I have a SS card to get a new Ohio State ID. Luckily I got my ex-girlfriend to Fed-Ex me my NY ST NDL ID, and that was good enough to get in on an appointment with a suboxone dr, who immediately wrote me a script for 8mg 2xday.

Now I know a thing or two about Suboxone and have had a lot of experience with it at a lot of different dosages. The common mantra on these boards is that less is more bla bla bla. With that in mind, I purposely started off taking 4mg which got me well, but I needed to redoes another 4mg later that night. Then, throughout the past few days I'd been experimenting with dosages and ROA (going back and forth between SL and rectal use) I never went above 2mg at a time if I plugged it, and I never went above 4mg if I took it sublingually. I was trying to take as little as possible, because, as we all know 'less is more', and not only that, Suboxone has a ceiling effect (which I think we all know is below 32mg). In my prior experience, it always seemed to me to be around 4-6mg when taken sublingually. However, Each day this week I found myself having to redose at night (not just because I wanted to) as my nose would start running and my eyes would get teary and I'd feel that anxiety start to kick in. Not unbearable withdrawals for sure, but if you're going to be on suboxone for maintenance, one should be comfortable, that is the idea right?

So today I said fuck it, and took a whole 8mg strip sublingually, and holy shit, it made a huge fucking difference. I dare say I was even nodding as little as a few hours ago, and it was early this morning when I dosed. Now my question is this, and its something I never quite understood- Buprenorphine, as a partial agonist, fills up a certain amount of receptors and binds to them with a high affinity. However, at some point taking more buprenorphine is not going to do any more good as its agonism plateaus. I have also heard that Buprenorphines agonism is about equivalent to 30mg of methadone, though it is hard to accurately equate narcotic effects due to the fact that it is a partial agonist rather than a full one.

What I'm getting at is this-does that mean that if your tolerance is above 30mg of methadone, Buprenorphine will not cut it for you? Does Buprenorphine only fill up say X amount of receptors and if you have any additional ones your just destined to feel shitty until they die off or you relapse?

OR does Buprenorphine partially stimulate all your extra receptors, and does this then mean that the ceiling effect is relative to each individual and his or her tolerance? I should clarify that not only did the 8mg dose hold me longer but I also felt more stable immediately. I definitely noticed more out of taking more suboxone today- I'm not discounting that 'less is more', I agree with that but I also think that in order to benefit from low dose buprenorphine you have to first stabilize at a dose that comfortable holds you and then start to taper at a pace that suits you, and then you can start to get slightly more recreational effects off of the drug.

But without getting off topic...

I hope this question makes sense, I sometimes have a hard time articulating myself, so I apologize if this was kind of rambling. Any feedback would be appreciated, and mods, should you decide to merge this with the megathreads, by all means..

PS-just to throw in there, my heroin habit had been that of about a g or more a day IV for the last two and a half years (no exceptions except a three day jail stint which I more than made up for), and prior to that 2 years of methadone (50 mg) with periods of months where I would shoot bundles of ECP on top of my dose. In short I had a monster of a monkey on my back.

 

[kleinerkiffer]

Does Buprenorphine only fill up say X amount of receptors and if you have any additional ones your just destined to feel shitty until they die off or you relapse?

No, it will bind to all of your receptors if you take enough, because it has a really high affinity. But being a partial agonist bupe as a lower intrinsic activity than full agonists, meaning that it doesn't activate the receptors as much. As an example (numbers are devised) morphine has an intrinsic activity of 100% and bupe just about 50%,so your receptors are activated twice as much by the morphine when you take an equivalent dose.

 

[Screaming_Skull]

If 8mg holds you I would stay on just that(tell your doctor your taking the full 16mg though...it's an expensive med and you never know what could happen, so it's nice to have so your not shit outta luck.) I started off at 16mg and stupidly took that dose the first few months and was on the 'pink cloud' phase feeling pretty good everyday(no nodding though...until I started taking multiple gabageric drugs with it, don't do that unless your prescribed and take them as there suppose to be.) Anyway stay on the 8 for a while then drop down to 4mg, you most likely will not notice a differene.. for a while I mean a couple weeks, or if you do notice a difference take 4mg in the morning and 2mg at night for a while, then go down to 4mg). Ive tried it all on the doses, really I feel best on 4mg, I can get a LITTLE glow for a bit, but not if I take the whole 8mg, I just feel the same... So bassicaly what I'm trying to say is start at 8 and go down till your confortable at 4, after that try to get down to 2-3... Look into the alchol mehtod for using it SL, if you don't have a problem with booze.

 

[kleinerkiffer]

You should read this, it's really interesting http://www.ncbi.nlm.nih.gov/books/NBK64236/#A72334

 

[Znegative]

^that's great, exactly what I was looking for.

 

[silverfucked]

I was indected and stabalized on 12 mg..over the cpurse of a year, I tapered down to 4mg..I would essentially take it properly as my head hit the pillow for sleep at night because I found that it stabalized the dose the most..

Then A few weeks back I got decided on a whim to take my dose 4 hours before bed at 6mg Defintely caught a buzz then, and have been for almost three weeks now..Unfortunately, now I gotta taper back down to four :/

So four me, 4 is definitely under the ceiling as I increaded the dose and got a buzz. I'm thinking it sits somewhere around 8.. But to answeer your question, I believe it is your mu sytstem in totality..Meaning when you hit the ceiling, the bupe just has no where to go at that point..There is an image on Google that shows opiate receptor saturation via EKG(?)...And you can see that the difference between 2 and 4 is huge, 4 and 8 is decent, 8 and twelve pretty miniscule and 16, 24, and 32 all look like the same brain.

 

[sm0kestack]

I went thru the same thing yesterday. I had reinducted suboxone at 24 hours of last heroin use. My first dose was 2mg SL with ideas to titrate up, but I think I caught a little bit of PW, since I was actually just beginning to enter full withdrawal and didn't wait too long while in it. About half hours later I wasn't feeling much relief, so I just said fuck it if that was PW, that first dose should have bumped any lingering heroin off my receptors, so I just went ahead and plopped another 4mg under my tongue. So this was 6mg taken within an hour, and I waited another 30min, I still hadn't felt much relief, in fact maybe even a little more PWDs, but I dismissed it, and said come on 6mg had always done me good no matter how much dope I was using, so I decided to wait another hour to let it settle in. An hour later I was feeling a lot better, but I was surely not 100%... Which baffles me, usually 6mg had taken all WDs away completely in the past. So now I am very familiar with the ceiling effect, and figured that taking any more if the sub would just not make any difference and I would just have to feel kind of shitty, I was feeling 50% I would say. So I just sat on this dose for the rest of the day.

12 or 13 hours later I was laying in bed trying to sleep, my nose was running yawning, but I couldn't sleep, teary eyes, watery mouth. Chills. Mild withdrawal symptoms were present, but by no means severe. So I still had a 2mg piece of that strip, and I think my tolerance is just way up to doing this all the time, making the switch back and forth over and over, so instead of taking that 2mg SL, I was like fuck it, I am gonna IV it. So I did, and BAM, all WD symptoms gone, and I even felt that agonist activity going on in the body. It felt good!

So yeah, I am thinking tolerance is an issue here. If I want to take the sub SL, I am going to have to prolly take 8mg or so for it to work all all the way, because of BA issues. IVing it gave 100% BA of a 2mg dose. So if SL use is around 33% BA that makes sense.

 

[sm0kestack]

PS. I don't advise IVing suboxone!! It is terrible for your veins and can cause terrible complications!!

 

[Znegative]

I think what happened in my case, and most peoples that have a fast metabolism is that for the first week or two, the Bupe still hasn't built up sufficiently in ones system, so the blood levels are constantly fluctuating. After a while this evens out, as it did for me, and that's when you can start tapering down. Another thing that's so weird to me is that Buprenorphine has different listed half lives depending on the dosage, like Temgesic and Buprenex which are both formulations of Bupe under 1mg, microgram range, have the half life listed as something like 4 hours (in the medication pamphlets), whereas Suboxone/Subutext which come in way higher dosages list 37 hours as the half life. And as many people know, when you IV buprenorphine at low dosages (dosages prescribed for pain) it most definitely does leave your system incredibly fast.

 

[sm0kestack]

Yeah, I have used bupe in all different ROAs, and for sure, it does leave the system faster by IV ROA. If I IV 2mg, I notice the WDs coming back in 12-18hours, and I can dose a full agonist and feel it almost full strength. If I take it SL, the half-life is definitely way more drawn out 24-36hours. Closer to the 36. Especially if I take it in higher doses like 4mg or more.

When I was in a detox last fall, they gave me those .3mg buprenex shots every 6 hours, over the span of 4 days. It was a 6 day detox, and they took the buprenex shot away at day 5, and on day 5 , I most certainly noticed the WD coming back around midday. It sucked, and on day 6, they released me and I was still sick, thus going and scoring, right after my release. So yeah, I am sure that thought about bupe having different half lives at different dosages is true. If I use bupe at higher dosages for 4 days, then stop, after those 4 days, it will take a couple days to get out of me. I have experienced this, taking high amounts of bupe before checking into rehab, or turning myself into jail. I was good for a couple days still after I stopped the bupe at high dosage.

 

[dirzted]

I understand what people get at with the whole "less is more" thing, BUT....
there's no way that makes any sense in doses below 8mg IMO, I've been on subs for two years at 16 mg and let me tell you there is NO DOUBT i feel 16 mg more than 8 mg. I experienced this before I read any of this stuff on norbupe micro-dosing and all that, so I really do not think its just the placebo effect of taking more of a substance that's giving me the level of effect i experience on a DAILY basis for the last 600+days. That's another point of contention I have with the "micro-dose theory" if i can call it that, most of the people that write about it are those that are recreational sub users, NOT maintenance sub users, which i think can play a big difference in perceived effects. If you're chasing full agonism high, than ya once you go above 8mg, you're probably not gettting much out of it, but if you're tolerant to bupe already then the effects don't ceiling out until AT LEAST 24mg. Not to mention that those on maintenance have taken exponentially more doses than the aforementioned recreational user, giving their experiences much more legitimacy. For me, I've only dosed more than 16mg in a day and that was on accident- i took an extra 8mg pill and started to almost feel nauseous the buzz was so strong, this was after being on 16mg daily for more than a year. The pamphlet says ceiling is around 32mg, and i can well imagine people's ceilings being higher/lower, but to me the whole "micro-dose theory" isn't at all concrete and only concerns those who aren't tolerant maintenance users.

Lol sorry kinda a rant there but i feel like if you ever try to say that anything above 8mg can be productive on this forum you get shot down faster than a noob in a COD game, and my life has been incredibly productive on 16mg, and I even agree that dose is probably a little high for me, but when you're first getting clean a slight up in your dose is definitely not the worst thing that can happen, so to be so adamently against it is very unwarranted IMO. In which case you really should just try and stabilize and forget about anything else, not to say you shouldn't try and keep it low as possible, but being succesfully off of Heroin is worth alot more than a high sub dose to me at least.

But anyways good luck to ya you do a great job on this forum so i assume you're already extremely knowledgeable on the subject and don't need me ranting on about it.

 

[Znegative]

I understand what people get at with the whole "less is more" thing, BUT....
there's no way that makes any sense in doses below 8mg IMO, I've been on subs for two years at 16 mg and let me tell you there is NO DOUBT i feel 16 mg more than 8 mg. I experienced this before I read any of this stuff on norbupe micro-dosing and all that, so I really do not think its just the placebo effect of taking more of a substance that's giving me the level of effect i experience on a DAILY basis for the last 600+days. That's another point of contention I have with the "micro-dose theory" if i can call it that, most of the people that write about it are those that are recreational sub users, NOT maintenance sub users, which i think can play a big difference in perceived effects. If you're chasing full agonism high, than ya once you go above 8mg, you're probably not gettting much out of it, but if you're tolerant to bupe already then the effects don't ceiling out until AT LEAST 24mg. Not to mention that those on maintenance have taken exponentially more doses than the aforementioned recreational user, giving their experiences much more legitimacy. For me, I've only dosed more than 16mg in a day and that was on accident- i took an extra 8mg pill and started to almost feel nauseous the buzz was so strong, this was after being on 16mg daily for more than a year. The pamphlet says ceiling is around 32mg, and i can well imagine people's ceilings being higher/lower, but to me the whole "micro-dose theory" isn't at all concrete and only concerns those who aren't tolerant maintenance users.

Lol sorry kinda a rant there but i feel like if you ever try to say that anything above 8mg can be productive on this forum you get shot down faster than a noob in a COD game, and my life has been incredibly productive on 16mg, and I even agree that dose is probably a little high for me, but when you're first getting clean a slight up in your dose is definitely not the worst thing that can happen, so to be so adamently against it is very unwarranted IMO. In which case you really should just try and stabilize and forget about anything else, not to say you shouldn't try and keep it low as possible, but being succesfully off of Heroin is worth alot more than a high sub dose to me at least.

But anyways good luck to ya you do a great job on this forum so i assume you're already extremely knowledgeable on the subject and don't need me ranting on about it.

Yeah, I totally agree with you, the whole 'less is more' mantra is thrown at people way too often, and while I agree, if you taper down to dosages under 2mg you feel the effects of the buprenoprhine much stronger, it's not always 'the best' way to go about using suboxone. I've been on dosages as low as .5-1mg/day and as high as 24mg/day, and experimented a lot with dosing. When someone inducts themselves on to buprenorphine, if they've got a really heavy habit, then they most likely will need 8mg or more the first day or two, because the drug has not yet built up in their system. I also agree that their is a difference in terms of increased opioid effects from 16mg to 24mg, but IMO the increase in effect is pretty negligible, compared to say the difference between 2-8mg. I don't buy into the whole norbupe theory as to why subs feel more like a full agonist at micro dosages. I believe it's just that the suboxone at that dosage is metabolized at a rate that their isn't a consistent blood level of buprenorphine, which results in a spike when the dosage is taken, explaining the stronger effects. Its kind of like when you're really fucking dope sick and it's been 24 hours or so, you know that shot is going to hit you way harder than the same shot would if it's only been 3 hours.

 

[sm0kestack]

Correct. I get way stronger rushes when I am well into and especially severe withdrawal, than what I might feel if my receptors are already occupied.