The Buprenorphine FAQ - Version 2.01 WIP

The Buprenorphine FAQ - Version 2.01 WIP

By Nephalim27

Introductory Notes:

(bupe = buprenorphine, 'done/mdone = methadone, as far as this document goes)

First and foremost: Bupe is not a wonder drug! While I am writing this from a bupe advocate position generally speaking, I will keep the facts objective, and my goal is an easy to read compendium of relevant information. I have had mostly wonderful experiences with bupe and as such it is only natural that I would think it's a good drug for maintenance (not getting high, although that doesn't mean a maintance "buzz" isn't included, although it appears to happen rarely in most people.) Neither bupe nor mdone is better, period. It all depends on the person and their goals (not just their goals, however, as bupe can work wonderful in certain people as a lifelong maintenance drug.) In general, using the limited facts and studies we have at the current time, it appears that 'done “works” on more people than bupe does, but by only a very small factor, and only at higher doses of 'done (90mg+).

Secondly, and most importantly: Opioids are can be extremely individualized in their subjective, and even sometimes objective, effects. Some work for some, other work for others, all with different effects. With buprenorphine this is multiplied by infinity. Every aspect of the drug can be VERY individualized (even the science of opioids is poorly understood in a large regard, especially so in buprenorphine's case). One of the large reasons for this is the fact that the drug is a "partial agonist." These words ring fear into the ears of pharmacologists, as they try to this day understand the puzzle (progress has been made, which I will address, but in this layman’s humble opinion the science of bupe is still poorly understood). On top of that, one person's experience with bupe will likely vary from day to day. I will get into this further later. Nothing said in this FAQ can necessarily be true to you. Please keep this in mind.

Note: All of the technical information in this FAQ is relevant only to the USA unless specifically stated otherwise.

Disclaimer: I am not a doctor. I am not a pharmacist. I am not a scientist. I am not a licensed professional of any kind, nor do I possess any relevant degree. I have absolutely no qualifications to provide medical advice. This FAQ is for informational purposes and should not be treated as medical advice. All medical advice should come from your doctor, and if the case is that you doubt what he is saying for whatever reasons, then a second opinion is the next step, not disobeying his orders to follow anything in this FAQ. You may, however, discuss what you may have found in here with him/her, and I encourage you to try to find as much evidence of what you are trying to tell him/her as possible. Try to do this as gently as possible, as no doctor enjoys being told he is wrong.

What is Buprenorphine? What is the DATA?:

Buprenorphine, exactly like methadone, is a medication given to keep people off of heroin and improve their, and society in general's, quality of life. Buprenorphine's major clinical importance is as an agonist. Buprenorphine is *not* like naltrexone (in terms of a treatment for opioid addiction). It's antagonist/partial agonist nature is only important in the regard that it might effect how well it can do it's job as an agonist, and as a side bonus that it can blockade very effectively (at least as far as most medical literature says, however this has found to be not true (it being effective) by at least anecdotal evidence and at least at the lower end of the dose spectrum,) other opioids, much like ‘done. This IS like Naltrexone, but it is not the primary clinical importance of the drug. For the reason it's a "partial agonist," it's regarded with less abuse, addiction, and diversion potential, and is schedule III under the controlled substances act which allows it to be prescribed by qualified physicians out of their offices as per the Drug Addiction Treatment Act of 2000 (abbreviated as DATA, and called as such for the rest of this FAQ.)

What the DATA is, From SAMHSA (the Substance Abuse and Mental Health Services Administration):

[The Drug Addiction Treatment Act of 2000 (DATA 2000) expands the clinical context of medication-assisted opioid addiction treatment by allowing qualified office-based physicians to dispense or prescribe specially approved schedule III, IV, and V narcotic medications for the treatment of opioid addiction. In addition, DATA 2000 reduces the regulatory burden on physicians who choose to practice opioid addiction therapy by permitting qualified physicians to apply for and receive waivers of the special registration requirements defined in the Controlled Substances Act.]

What this means is that drugs approved for maintenance (which currently only included Methadone, LAAM, and Buprenorphine) that are in schedule III or above (which only includes Buprenorphine, in the Subutex and Suboxone formulations,) can be given by qualified physicians (usually psychiatrists and certain clinics) directly out of their office (via prescriptions that can be brought to your pharmacy of choice). This law was inacted (in 2000!) in order to help get more addicts into treatment by loosening some of the "klinik" restrictions, by eliminating the "klinik" completely in certain situations.

Eliminating the fat:

Can any doctor prescribe buprenorphine? What are the requirements?

No. Only doctors who meet the (simple) qualifications, and then apply to SAMHSA (who then follows through with the DEA, who issues the doctor a second, special DEA number) may prescribe maintenance medications. See the "Practical Information" section for more...practical information, including finding a doctor. The qualifications are more of a red tape then anything else. All that is necessary at minimum is an 8 hour course (if the doctor meets none of the other requirements) and a short application. If you have a doctor or psychiatrist you know and like whom isn't a part of this program, perhaps you can convince him to sign up. There is a short waiting period, which the doctor can waive by checking a box on the sign-up form. Finally, there currently is a 30 patient limit. There currently exists a bill in congress to remove this limit, due to the problems it has been causing (doctor’s using the limit as an excuse to scam patients into constant detox at high prices, and angry doctors that they have to follow such a rule they are unaccustomed to.) Stay tuned for more information on that.

Does this mean that qualified doctors can prescribe methadone or LAAM?

No. Both methadone and LAAM are in schedule II. Only Schedule III, IV, or V drugs may be prescribed by office physicians under the rules of the DATA. The drug must also be FDA approved for *opioid dependence*. Buprenorphine is the only drug that meets this criteria. There is no other drug your doctor may legally prescribe for maintenance.

UPDATE: LAAM is no longer available in the United States. Forget about LAAM. It’s bad news anyway, in this humble writers opinion, except in very very rare situations.

It is possible, and likely, that other drugs will come forth in the future that will meet this criteria, although most likely not anytime in the immediate future. Perhaps even methadone or LAAM will be rescheduled. That is fairly far out for the USA, however, although it is true of certain countries (Australia, for instance? - VERIFY). It is doubtful that mdone (or LAAM) will be rescheduled due to the highly profitable kliniks that will go out of business alone, despite the fact that both have very little abuse potential (although fairly high diversion/addiction potential.) They (the 'done lobby) are partially responsible for buprenorphine taking, what was it now, 10+ years to be FDA approved, despite it's already proven safety and it's efficiency in other countries for maintenance. They (the kliniks) were afraid of going out of business, with all their patients lining up for buprenorphine. The thought that might happen is laughable, and the possibility of them using buprenorphine in-house (as an option), without the stringent rules, would likely boost their revenues significantly.

Note: just as Methadone Maintenance Treatment is abbreviated MMT, Buprenorphine maintenance treatment is abbreviated BMT.

Bupe vs. Methadone:

A lot of heroin addicts or methadone maintenance patients have preconceived notions that bupe won't work. That is just not true. Bupe is not in general inferior to Methadone. That is a widely believed myth. It's different, but not generally inferior. It all depends on you, personally. For some people 'done will work better, for some 'bupe will work better, it's that simple. While the ceiling level for bupe is only equal to about 30mg 'done in potency, you can get it so that *you dose that twice a day or more*, and it reduces your tolerance! This mostly due to it's antagonistic/partial agonist nature. Because of this, it makes what would be equal to 30mg of 'done a hell of a lot more effective, in some people. *I am not saying bupe could ever be more potent than a full agonist. I am saying due to other factors it CAN in SOME cases work better, especially over time* Granted, it is likely very rare that bupe will get someone "higher" than 'done in general. It *can* work better though, if you give it time, and give you more flexibility. If you are on it long term and you are successful with it I am nearly positive you will get a buzz, given the fact that you were successful with it. This as always is individualized, and there are plenty of people who don't receive a buzz, but are usually on lower dosages. (UPDATE: It seems that there are a lot more people who don’t receive a buzz than I thought, but oddly enough they are happy with that, that was their aim (very little side-effects seem to go along with not getting a buzz). You shouldn’t rule out bupe because of this, but if getting a buzz is of #1 importance to you, then that should definitely effect your choice). I strongly believe either it'll work or it won't, once you give it time and find the right dose. Struggling on buprenorphine therapy is unlikely. If it doesn't work, it doesn't work, and switching to methadone is a fairly simple process, the klinik will probably be happy to have you.

Luckily there have been a lot of addicts in the community who have had good experiences with bupe and have shared those experiences, so that the community is more informed. Street addicts, however, are not, and bupe is still grossly underused. There is also the prevailing belief that bupe is for pill addicts not for heroin addicts, and this is totally bogus, minus the fact that I wouldn’t recommend a hydrocodone addict to get on methadone, of course.

A simple example of the possibilities of maintenance treatment: (4 possible scenarios of dependence, not including the guy who suceeds at abstinence the first go around. I don't think i've ever met him :P)

Person A has an "ordinary" opioid dependence. He needs a dose of agonist to keep him maintained. Methadone works, at doses most likely anywhere in the double digits, and he is happy. Buprenorphine works, and he is happy. He is the most likely to succeed with abstinence, but not necessarily so. Don't rule yourself out of this spot so quickly. This also includes the person who wants the least "opioid" necessary, he doesn’t want to get a buzz or get high, and he doesn’t want side effects. (If that’s the case, while it is totally possible bupe can give you a buzz and give you side effects equal to methadone, the chances of it not doing so warrant it being your first choice IMO).

Person B has an "ordinary" opioid dependence, but her tolerance and addiction level is sky high. She needs a high dose of agonist to keep her happy. Methadone at normal levels isn't enough. She needs a dose (most likely) of 100mg or more to be happy on methadone. Had she tried buprenorphine, it would have never reached her level of opioid dependence. She would have failed, and she would have relapsed or switched to methadone.

Person C has a "special" opioid dependence. Methadone at any dose doesn't work. Buprenorphine doesn't work. I feel bad for her. Let's hope she can get into Holland.

Person D has a "special" opioid dependence. He has a certain predisposition that makes him a good candidate for bupe. He is *likely* to have a high level of addiction, although this could depend on how long he has been using opioids, and which ones. He also is quite likely (but far from definitely, it's individualized like everything else) would have failed on methadone. Buprenorphine lowers his tolerance and addiction level, and seems to fit right, and gives him the proper maintenance that he needs.

Now, the Person A and Person B scenarios I gave you are very typical. It's what you would expect. Person C is less typical, but is still there. However, the Person D scenario tends to be overlooked. While I can't prove that certain people have a predisposition to having success on buprenorphine, I don't see how you could argue against it. Just look at how individualized opioid use is in general, and the responses people have to which drugs. What could be argued is just how often Person D comes strolling along.

Exactly what criteria Person D is likely to fall into I don't know for certain. It is entirely possible that they would have failed on methadone. Don't rule out bupe because 'done didn't work. Also, I strongly believe tolerance has nothing to do with it. I can say this from personal experience among other things. Hopefully future research will give us answers to these questions.

I will give reasons for my beliefs as to what people would fall into the "Person D" category throught this FAQ. See my personal experience and partial agonist (in pharmacology) sections especially for more information.

Effectiveness of treatment:

In many studies done SL (sublingual) 8mg buprenorphine (a low-average maintenance dose) was shown to be slightly less effective as a maintenance drug than ~90mg 'done (keeping people in treatment and having clean urine). It was shown to be much more effective than low dose mdone (~20mg.) It was also, interestingly, shown to be more effective than LAAM, which is a full agonist. (PROVIDE REFERENCE.) Given that 8mg is basically the lowest line in terms of dose for maintenance (4mg for maintenance is possible, even lower is possible but not generally speaking,) it can be fairly safely assumed that bupe is generally as effective as 90mg of 'done in terms of effectiveness as a maintenance medication, and can also be somewhat assumed that bupe, once it your body adjusts to it, at an optimal dose, is equal to about 90mgs mdone in potency for you vs. potency for some guy on 90mgs 'done, however this is a major simplification.

The 48 hour rule:

There is one other difference to be noted. Bupe has an extremely high affinity for the opioid receptors, which means it “blockades” them, not allowing other opioids to bind to them and forcing other opioids that do bind to them off pretty quickly and unpleasantly.

What I wrote previously was, “This means (in this case) that within 48 hours of dosing, you won't be getting high on any other opioids. So if you still plan to get high "once in a while," then bupe isn't for you. It's fairly easy to do and i've done it before without much issue, but it's not "fun." It's like the 'done blockade, but stronger. The only case where this "48 hour" rule doesn't apply (generally) is in the case of doses under 8mg. However, this is, like everything else, individualized. Just don't expect to be the exception. Generally speaking, it can take up to a week before another opioid agonist can exert it's 100% full effects.”

This has recently found to be largely untrue. If you are on a dose of 16mg or more, you really can’t get high for a solid 48 hours-72 hours, this is true as it was written. You get what is called an “attenuated rush”. You get a small rush, and then feel like crap. It’s like the ‘done blockade, but with an antagonistic backlash that is VERY unpleasant and I strongly recommend you don’t test the waters. However, if your dose is 12mg or less, more-so with 8mg or less, and extremely so with 4mg or less, you can get a solid 75% effect from stronger opioids, namely heroin or oxycontin, about 24 hours later. I do believe the reason this holds true is after being on buprenorphine for a long period of time, which the studies regarding this do not properly account for, your tolerance is lowered to such a large extent that you can get high easily. This is merely hypothetical, however.

If you do this however, there is the potential for an antagonistic backlash that must be mentioned. Even after those 24 hours, that bupe will be sitting there in your system for a solid week, even after taking other opioids. Occasionally it can decide “hey, get out of there, those receptors are mine!” (not literally of course, drugs can’t “decide” anything,) and push the other opioid off the receptors and retake it’s space. This causes nausea mainly, and other unpleasant symptoms, although they do NOT clearly resemble opioid withdrawal. This can easily be fixed by another dose of your drug of choice, even a tiny one (if you are going to do this, I strongly suggest a tiny one, opioids can kill you ESPECIALLY in the scenario I have just described! You are a prime risk for overdose, DO NOT FORGET IT).

Finally, I will mention that if you do this, which *I am not suggesting, I am merely providing information*, switching back to buprenorphine is fairly easy, if you binge for 2-3 days, just wait until you are sick (WAIT) and then take your bupe, and *hopefully* the transition back will be smooth, but there are no guarantees. I have personally found that quite ironically the higher your tolerance is, up to a point, the better bupe works.

Of course, this, again, is individualized, and your tolerance and metabolism will play a large role in all of this.

Less than daily dosing?:

With recent data, it seems that buprenorphine can be given with less than daily dosing, with every other day to tri-weekly (three times a week) still being effective in some people (PROVIDE REFERENCE). However, as always, this is very individualized, and with the recent laws in the US there seems to be no reason to attempt such a dosing schedule unless for some reason you want to (having a very slow metabolism for buprenorphine for instance, which could possibly *lower* your ability to be maintained on buprenorphine (more != better once you reach that ceiling level,) in which case less than daily dosing would be a good idea.) Discuss it with your doctor.

UPDATE:

There is currently a depot formulation of bupe in clinical testing. It seems to be doing well, and you can expect it to be available in a few years. It is a little “pill” that gets injected under your skin (like the naltrexone depot) and keeps you with a steady state of bupe for a month. No more sucking on that damn pill anymore! This, most certainly, is not for everyone, and we’ll have at the bare minimum a year to think about it.

Should I switch from 'done to bupe?:

Probably not. You WILL go through at least some withdrawals, and it won't be worth it, unless you really want out of the klinik or want to detox. If one klinik doesn't suit your needs, perhaps another will. If 'done isn't working for you though, then that doesn't mean 'bupe won't, and in that case also it's worth a try. However, a mdone -> bupe conversion can be tricky, and if bupe just doesn't work for you, you are in for a very rough week or so.

Should you switch from 'done to bupe if you are going to detox? Absolutely! I see absolutely no reason why this should not be done. Buprenorphine detox has been shown to be very effective. 'Done withdrawals are TERRIBLE. Bupe withdrawals are a joke in comparison. On top of that, it will work sort of like an UROD (bupe will force the 'done out of your system,) while giving you enough opioid stimulation in your brain to help the withdrawals, at the same time. If anyone knows any reason why this shouldn't be done, i'd love to hear it, as I can't think of a single thing (unless of course 'done withdrawals aren't that bad for you, but I don't think i've ever heard anyone say this.) See the withdrawals section for more information.

To further sum up:

If you want to get off H, and have not been in maintenance, should you try bupe? Of course! It's very likely to work just fine on you. And if it doesn't, there is always 'done. It's your call, of course, but it isn't something that should be ruled out without at least a full investigation.

Does bupe give you a "buzz"? YES, it does. (dependent on dose) Can you get high off of it? YES, you can (and if you say no, try telling that to the gigantic population in France that went from having a heroin problem to having a Subutex problem.) Is it as good for getting high as a full agonist? Of course not. As always, this is individualized, but not strictly linked to tolerance.

Bupe is a very individualized experience. I strongly believe that it works the best on people with a certain type of predisposition to heroin use. It seems to fix certain broken indogeneous opioid systems. Some people will LOVE bupe, and some people will find it ineffective. This is the way it goes.

One final thing to note - i'm not 100% positive, but if you are on mdone a long time generally speaking the dose has to go up once and a while, yes? (not everyone, but usually or sometimes, right?) Well with bupe, once you find that dose you will never have to increase it. (VERIFY)

General rules for starting buprenorphine:

Try to cut down as much as you can before starting bupe. If it's just for a day or two, it won't make that much of a difference.

You must wait until you are *in* withdrawals before taking your first dose of bupe. If you don't, you WILL be *in* withdrawals after taking it, and it will be much less pleasant than if you wait. In general, with the short acting opioids, including heroin, this means (from your last dose) waiting at minimum 8 hours, but 12-24 hours is strongly recommended (sleep some of it out). This is THE most important thing when starting bupe. The longer, the better. The only potential downside is the rare case where bupe doesn't work for you *at all,* then it'll be longer before you can get a working dose of another agonist.

When starting bupe, lower is better. Start with a dose of 4mg (SL), and work up slowly from there, with 2 additional doses of 2mg to a maximum first day dose of 8mg (just a general recommendation.) Exceeding 8mg during the first day will most likely just make you regret it, and is not recommended in any case. I am saying this for *your* well being, trust me.

Your doctor will be in control the first three days, and give you your doses. Be completely honest with him and do what he says.

In the case of methadone:

It is strongly recommended that you lower your dose to 30mg or less. I think this is a little on the conservative side, but until further data is available, you shouldn't stray from this number. Methadone has a nasty backlash, as you probably know, so it's much better safe then sorry.

It is strongly recommended that you wait 24 hours minimum (I STRONGLY recommend 48 hours in the case of 'done) before taking your first bupe dose.

What to expect:

This part is the most individualized. It depends on four things:

1. Your level of opioid addiction

2. The current level (amount) and state (time since your last dose) of your opioid of choice in your body

3. Your reaction to buprenorphine

4. Dose of buprenorphine (remember, less is best)

Now, I honestly can't tell you what to expect. It varies far too much. Unfortunately since not only is it individualized it's weighing on a combination of four different things, it makes it nearly impossible to predict. I can promise you almost definetely you will go through at least some withdrawals, unless you really shouldn't be on buprenorphine in the first place. These withdrawals will either come before or after your first buprenorphine dose, depending on the above four things (see the guidelines for further info.) It most likely will be a mixture of both, but will weigh more to one side, and this will be mostly your choice.

These withdrawals could last anywhere from 4 hours to 4 days. It is possible that you could have mild lingering withdrawal after this period. It is also possible that you could decide to wait it out and keep trying, making the withdrawals last longer. I will make a rough estimate and say average withdrawal lasts about 24 hours. I will search for more information on this (for the next version.)

How long should you wait it out if you are struggling? My opinion - if you are still having major withdrawal symptoms after 4 days since your first buprenorphine dose it's time to move on. It is unlikely that you will find buprenorphine to work for you if you are suffering *greatly* after 4 days. If you are still having mild symptoms, this is normal. This is my opinion, and I will search for more information on this as well (for the next version.)

In the case of switching over from 'done the above is not necessarily true as was already pointed out earlier. Dose (and your level of addiction that comes along with that) weighs in much heavier than with short acting opioids, and withdrawal time could be longer. See the guidelines for more information.

Once again, this does not *strictly* depend on tolerance by any means.

Side effects of treatment:

There have only been 3 confirmed side effects from long term methadone maintenance treatment: Constipation, Sexual dysfunction, and Sweating. ( ) With buprenorphine, you can expect the same. The constipation is still there, but not as bad as heroin (can't compare to mdone, will try to find more information.) The sexual dysfunction is definetely still there, I can unfortunately say that personally. I have never experienced the sweating, but there is no reason to believe it is not part of buprenorphine maintenance. It's importance, however, is practically nothing. Unfortunately tolerance does not develop, or develops very little, to these three side effects of opioids. ( )

My Personal Experience:

I personally am fairly certain I would have failed on methadone. My tolerance was so high that ANY dose of anything other than good heroin (1 bag minimum) going straight into my *vein* did absolutely nothing. This was *good* quality dope, trust me. There was only one brand that I liked, the rest were no comparison. I took my last dose of H in the evening. The next morning I was sick as a dog (I smoked some opium later that night (the one before) to try hold the withdrawals longer. I didn't wait long enough. BAAAAD idea.) By the end of that day, I recieved my bupe dose and was a hell of a lot better. Those were the worst withdrawals I have ever experienced (before taking the bupe.) I was puking every 3-5 minutes, cramped so bad I couldn't hold a thought, kicking and screaming...it was actually like the movies. Anyway, the withdrawals were over by the end of day 2. In about a week, I started feeling *REALLY* high (I hadn't felt high in ages.) One night I was so high I nearly OD'ed (I was barely breathing and couldn't move,) it was the best high i've ever felt. Obviously, that ended fairly quickly, but it shows clearly that tolerance doesn't necessarily mean that bupe won't work for you. In fact IMO I think they will find it to be the opposite. I still get a buzz off 'bupe, and sometimes a fairly strong sedative effect, but rarely anything really nice, usually just a buzz. HOWEVER, it's different every day. It holds me every day, but some days are much better than others. That is my experience with bupe and my opinion.

In case you are wondering, i've cheated twice. (two small binges.)

I address my experience some more scattered throughout this document.

Bupe Pharmacology:

First of all i'd like to get something out of the way: there is alot of conflicting data about bupe. (Miller et al., 2001) I think it has to do with many factors, dose being #1. On top of that, the concept of a "partial agonist" is poorly understood. This further emphasizes how bupe can be very individualized, and work differently every time you take it. Alot of the pharmacological information you may find may be outdated and incorrect.

By the Textbook:

Buprenorphine is a semi-synthetic narcotic opioid, derivitave of thebaine. It is a mixed partial agonist-antagonist. It is a mu partial agonist and a kappa antagonist (Subutex full prescribing information). At low doses (~100mcg-1mg,) it works as a full agonist, and is slightly selective for mu. At higher doses, the antagonistic property becomes more dominate (and the partial-agonist as well) and it is competitive. (Buprenex full prescribing information, (1), (Miller et al., 2001)

Chemically, it is 1 7-(cyclopropylmethyl)-? -(1,1-dimethylethyl)-4, 5-epoxy- 18, 19-dihydro-3-hydroxy-6-methoxy- ? -methyl-6, 14-ethenomorphinan-7-methanol, hydrochloride [5?, 7?(S)]- **

It has a molecular formula of C29 H41 N04 HCl and the molecular weight is 504.10

Buprenorphine hcl is a white powder, weakly acidic with limited solubility in water (17mg/ML) (Subutex full prescribing information)

** Holy fuck, that's all i've got to say. (excuse my language) What's up with the ?'s? Is it different in each molecule? Could this mean, even if the chances are extremely slim, that some molecules are more effective than others? Further mystery surrounding bupe, or just simple, clinically insignificant, biochem information that I don't know, who knows. Look forward to the answer next version...

At the receptors:

Bupe has a high affinity at all 4 major opioid receptors (mu, delta, kappa, and ORL1) (Miller et al., 2001, (1))

Order of affinity (How much attraction to and how tightly it binds to each receptor):

mu > kappa > delta > ORL1 (Miller et al., 2001)

(delta has about 30 fold less affinty than mu) (Negus et al., 2002)

Bupe is a partial agonist at mu, delta, and ORL1. It is a full and potent antagonist at kappa*. (Miller et al., 2001) It's efficacy at the receptors is related to dose. The higher the dose, the less efficacious it works, (1) until it reaches a dose (~32mg SL) where increasing it any more would make it work less efficacious, although more data is necessary. (See Bupe and Dose)

Order of efficacy (how strong it works as an agonist):

ORL1 (34%) > mu > delta (Miller et al., 2001, )

The fact that it is efficient at ORL1 is very signinficant, as I don't think any other traditional opioids can stimulate ORL1 (this definetely includes morphine and heroin.) Unfortunately it has a very low affinity for it, which would require large doses to create a significant effect there.Fairly large doses have been attempted in limited studies with no interesting results, other than the apparent reversal of agonist effects. ( ) I Believe ORL1 has been shown to have similar effects to mu. Describing ORL1 is beyond the scope of this document and my knowledge.

* There is alot of conflicting studies in regards to kappa. Some say that it does indeed produce kappa agonism. This isn't the case, i'm fairly positive of it, but i'd like to know why this is. It possibly has something to do with in vitro testing, however the in vitro testing summary (Miller et al., 2001) has determined bupe to be a kappa antagonist. I look forward to finding further information on this, as always, for the next version...

Bupe has an extremely long half-life at the receptors. It takes about a month for the drug to be completely removed from your system.

Finally, buprenorphine has a major active metabolite, norbuprenorphine, which has activity at the receptors. See metabolism for more information.

General Pharmacological Information:

Bupe has a slow onset of action, with peak effects taking place in approximately 100 minutes. (Suboxone full prescribing information.) The peak effects for methadone take place in approximately 120 minutes (VERIFY.) The onset of action for bupe is approximately 30-60 minutes ()

The duration of action depends heavily on the dosage. At a low dose (~<4mg), it is approximately 8-12 hours. At a high dose (~>16mg), it can last approximately 24-72 hours (and thus the reason less than daily dosing is possible.) ()

Bupe readily crosses the blood brain barrier, and is highly lipophilic.

Bupe is about 10x more potent IM than PO (oral), which is about the same ratio as morphine. You CAN eat bupe, although there is no reason to do so.

Sublingual absorption varies greatly, and can be anywhere from 25%-75%. ( ) The same percentages can be applied to an IM/SL potency comparison. However, in most people, their personal variation from one dose to another is low. (Subutex full prescribing information)

A comparison of bupe to 'done for respiratory effects found that bupe had a much higher incidence of respatory depression *not* requiring medical intervention. Bupe can cause respiratory depression, but *very* rarely anything resembling life threatening. Both drugs decreased 02 saturation to the same degree. The chances of severe respiratory depression are increased via the injection route. (Suboxone full prescribing information)

Bupe is a very safe drug for an opioid. Overdose is very difficult, even for opiate niave individuals. (Subutex full prescribing information)

See "Bupe and Dose" for further information on this topic.

Buprenorphine is approximately 96% plasma bound, primary to alpha and beta globulin (Subutex full prescribing information)

Bupe has a mean half-life plasma elimination of 37h (this can greatly vary between people) (see metabolism for further information) (Suboxone full prescribing information.) The half-life of methadone is 15-22 hours, although recent data suggested this could increase with repeated administration, and be as high as 150 hours.

Note about Suboxone: The Naloxone is present in a 4:1 ratio in both dosage strengths (8mg/2mg and 2mg/0.5mg). See "Subutex vs. Suboxone" for further information on the naloxone component.

Metabolism:

Buprenorphine undergoes N-dealkylation into norbuprenorphine and glucuronidation. This is done by the cytochrome P-450 3A4 isozyme (Subutex full prescribing information.) Norbuprenorphine is an active opioid. It is similar to bupe from what is known of it, which isn't much. From one in vitro test, it has a very similar affinities to bupe. Norbupe is a full agonist at delta and ORL1 with a low potency, but bupe antagonizes it's effects. This study also states that at the ?- (mu?) and Kappa- receptors, both bupe and norbupe are potent partial agonists, with bupe having a low effacacy and norbupe having a moderate effacacy, which we know is not true (in terms of kappa), and makes me doubt this study. (Huang et al., 2001) Further studies are necessary, or more access to information for me.

NOTE: Whether you take it orally or sublingually, approximately the same amount of norbuprenorphine is bioavailable. If, for some reason, you would want to maximize norbupe and minimize bupe, oral would be the way to go. This shows that the first-pass liver breakdown is responsible for the low oral availability of buprenorphine, quite similar to morphine. This also hints that *possibly* the reason for IV use resulting in a better high being the minimization of norbupe, but that is pure speculation.

Inhibiting/Inducing P450 3A4 will cause differences to you personally on how bupe works. What those changes would be are impossible to say without further investigation. Unfortunately, this includes HIV protease inhibitors, just like 'done. It is doubtful any significant differences/problems would arise that dose adjustment wouldn't solve.

NOTE TO CHEMISTS: There are several direct derivatives of bupe that are of much greater potential for use for pleasure, certaintly worth a try to *experienced* people. I imagine this could be difficult, due to bupe's complex structure. I'd like to find out more information about this.

Pregnancy:

Bupe is very similar to mdone when it comes to pregnancy. The good part, however, is that neo-natal withdrawals are less, for obvious reasons. (Fischer et al., 1998) Bupe also being the unique drug that it is that very rarely causes tolerance would be less likely to cause problems related to neo-natal addiction later in life if such problems do indeed exist. I have not backed this up, nor has problems later in life have been confirmed (making this impossible to back up,) this is mostly assumption and logic. I am fairly certain if you become pregnant or are planning on becoming pregnant it will be recommended you switch to bupe, if this didn't require a major dose reduction. This, however, is 150% better told to you by a doctor, and a decision made with his advice.

Partial Agonist?:

Buprenorphine best classified as a mixed partial agonist-antagonist. Does the fact that it's a mixed -antagonist make it weaker? Nope, in fact if anything it's a good thing (that it antagonizes, or rather doesn't agonize, kappa.) Does the fact that it's a *partial*-agonist? Yes. They are two different things as far as Buprenorphine's classification is concerned. Bupe is a *very* bizarre drug, mostly due to the fact that it's a partial agonist.. I can't emphasize this enough. It has a ceiling for agonist effects (due to it's partial agonist nature), and, for example, 16mg is not twice as strong as 8mg.

Bupe can also be classified a mixed antagonist at mu because it has a very high affinity, which means it pushes whatever is there off of the receptor and takes it's place, and it's partial agonist nature (low efficacy, to put it simply) means it can't do the job that was just being done. This can cause it to be classified as having mixed -antagonistic effects, however partial agonist is a better classification as long as the dose is proper. It doesn't simply have a "low efficacy", it's better put as a "partial agonist." Read on for more theories on this.

Taking a large enough dose of bupe, out of proper clinical dosing, can be enough to do a UROD, as it pushes all the opioids out of your brain (VERIFY AND PROVIDE REFERENCE). This is what causes the problem with starting bupe. You have to go through some withdrawals. See the part on starting buprenorphine and methadone vs. buprenorphine for further information.

So what exactly does all this mean? It is easiest (and still largely accurate) to describe buprenorphine as a normal opioid agonist with a sliding ceiling (by sliding I mean different in every person, and dose and effects aren't linearly linked.)

See the section "Partial Agonist Theory" for more information on what exactly a partial agonist is, in theory (and in practice.)

Bupe and dose:

Bupe is a very weird in one regard when it comes to dose. As I already explained, double the dose doesn't equal double the effects. The reason for this is because as the dose goes up the efficiency goes down. (1) The reason for this is unknown, and related to partial agonist theory. I honestly wish I knew.

Dose for highest efficiency: 0.3mg (IM.) At this dose, it's effects are maximized and it behaves almost completely like a full agonist, acting equal to 10mg IM morphine in opiate nieve individuals. (Buprenex full prescribing information)

32mg is about the ceiling level. This ceiling level is different in every person (see bottom of this section.) For this reason, it is *possible* that in people who have a very low ceiling are those that would likely fail at buprenorphine, but further information is necessary. Increasing the dose higher than this will have the loss in efficacy overtake this increase in amount in your system. Taking doses higher than the ceiling will eventually lower it's effects, and taking very high doses will function as a straight up antagonist, (1) although again more information is necessary. (see below)

There is one study to this regard available, in rats a dose of about 1mg/kg caused an end to increase in agonist effects and a linear reversal in effacacy. In the average human this would be a dose of about 80mg, which is way more than ~32mg. Obviously, since it's a different species, the numbers can't be applied. It does seem however that this same mechanism happens in humans, but at a lower dose. Further studies are necessary. (VERIFY AND PROVIDE REFERENCE)

An 8mg-24mg dose is highly suggested for maintenance, depending on your personal reaction to the drug and dose. If you go over 16mg, I STRONGLY suggest you take it more than once a day.

It is also important to say that 32mg is the *GENERAL* ceiling. This depends on the individual, but in every individual a ceiling was reached, and usually above 8mg. (Subutex full prescribing information.) So please remember, more doesn't necessarily mean better with buprenorphine. If this is the drug for you, you will find the proper dose, and don't feel like you are getting gyped because you are only on 8-24mg.

Tips for getting the most out of bupe: (This is one of the reasons I kept emphasizing this. I wanted to make sure people knew how to get the most out of it.)

1. First and foremost, see "bupe and dose" in the above section.

2. Cut your dose in half, and take it twice a day. This is because of efficacy as I just explained. By taking it twice, you get more bang for your buck, and it's long half-life makes sure that it's effects are cumulative the second time you take it. I strongly believe this makes a big difference. However, for you, as always, it could be different. Certaintly worth a try, and definetely if your dose is over 16mg daily, or if it's just not working and you've reached the ceiling.

3. Take your dose in the evening. I have personally found that when I take it in the morning, it leaves me wanting more and having very little effect. If I wait it out and take it later in the day, it works great. Granted, I have to be a *little* sick for about an hour or two, but it's nothing really, for me at least.

4. Hold it under your tounge for longer than 15 minutes. At first it didn't take as long as it does now, it took about a half hour (to ABSORB, not to DISSOLVE.) Nowadays it takes at least an hour for it to absorb as best as it will. SL absorption varies greatly from individual to individual, which is one possible reason why bupe works for some people and not for others.

How can I tell that it's absorbing and how long it takes? I have been taking this drug for several years. I can feel it tingle on my tounge. I can taste the drug in my mouth. If my tounge is in it, it will tingle. If I take my tounge out before it's done, it will stop tingling to some extent. This is how I can tell.

You have nothing to lose by trying.

I will add more as I think of them and find out about them.

Partial Agonist Theory:

A very fascinating section coming soon. This may help to explain the reasons bupe works the way it does, and may even in the future help to find a way to maximize the drug's effacacy. (Not my summary, the theory itself).

Buprenorphine, Withdrawals, and Detox:

There are two aspects to this, withdrawals when switching to bupe and withdrawals from quitting bupe.

Withdrawals from switching to bupe:

You do have to go through at least a little withdrawals if you are addicted to opiates. This is unavoidable. Now, if you are switching from heroin, it really isn't that bad. See "General rules for starting buprenorphine" for further information.

Buprenorphine withdrawals:

Bupe withdrawals are mild at best (in comparison to other opioids.) For this reason, it is a great thing for people wanting to get off 'done but unable to deal with the withdrawals. Unfortunately, due to it's long receptor half-life like 'done, the withdrawals will last at least a month (although this too is individualized, and can be shorter.) Bupe has one major unique symptom of withdrawal that will be the centerpiece: this unbeatable fatique that will outlast all the other symptoms. All of the other symptoms, except a few minor and not worth mentioning unique ones such as stomach grumbling, are similar to other opioids. I have been told that the withdrawals are the worst during the first week and then proceed to lighten up alot. Once again, individualized.

It is strongly recommended you do NOT taper your dose really low before quitting. It doesn't work, and doesn't help. It'll make the withdrawals linger much longer. It is not a good idea. Reports of withdrawals cold turkey have been much more positive than taper attempts. (PROVIDE REFERENCE) The suggested dose to go cold turkey from is 4mg. Your body will take care of the rest (via the slow dissassociation of the drug from the receptor, lasting quite a long time, creating an auto-taper.)

I must say however, as I have in just about every other section, this is individualized. There have been people who have had bad withdrawals from buprenorphine. In this case, a different strategy is warranted, *possibly* involving a longer and lower taper.

Treatment with Naltrexone (although strongly frowned upon by myself) is possible very early after the cessation of low-dose buprenorphine treatment, within days, and does not cause severe withdrawal symptoms. (Bell et al., 1999) This certaintly is individualized, and if you are in the rare situation of having bad withdrawals after stopping low-dose buprenorphine, it is a very bad idea. (ADD BELL)

Buprenorphine for detox:

Coming soon.

Subutex vs. Suboxone:

OK, alot of you hear "naloxone" and get scared. The fact of the matter is that naloxone is not absorbed sublingually. It is added so that people don't bang it. If you bang Suboxone, you will get very sick and will deeply regret it. There is no clinical difference between sublingual Subutex and sublingual Suboxone.

OK, now to get a little more technical. A tiny tiny amount of naloxone is absorbed. So little in fact, it wouldn't even qualify for ULD antagonist therapy (as told by my doctor, and Mike Strates, "inventor" of ULD Naloxone therapy, as I can't personally make sense of the numbers.) So, you ask, if it does nothing why are there two formulations? Quite honestly it's because the company wants more money. Supposedly the Subutex is supposed to be used for initiation so the naloxone doesn't cause withdrawals. Quite honestly, this is a crock of shit. The picograms you are absorbing is not going to make a difference to your withdrawals, it is downright silly. Doses of Naloxone at much higher levels have been shown not to cause withdrawals, so why would this ridiculously tiny amount do so? (PROVIDE REFERENCE)

The company decided to push to get Subutex approved sometime in the middle of the clinical trials. This is one of the reasons FDA approval took so long! It was the company that pushed for Subutex - no one else.

The difference in maintenance between Suboxone and Subutex is absolutely nothing. As someone who has taken both formulations for long periods of time at least twice each, I can personally say that from experience.

Now, the fact that you are getting a drug that has another drug merely in there to prevent you from shooting it IS insulting. It shows a real lack of trust. But it's not really up to the doctor. This is the way the USA is, and there is no way around it. So try not to think about it, and just take comfort in the fact that there is no difference, even though, alas, you cannot try and shoot it (you were thinking about it, weren't you? See, a lack of trust is warranted :P)

Practical information:

First and foremost - SUBOXONE IS 100% AVAILABLE. We are still waiting for the Subutex, with no promise of a date from the company.

Not every doctor is authorized to prescribe bupe. Any doctor who wishes to be only needs to take an 8 hour course, or meet any of the other easily meetable requirements. For this reason, I am positive bupe will be very easy to come by (in the near future.) When a doctor is "authorized" (s)he gets a second DEA number to be used for this purpose, which the pharmacy quite honestly has no way to verify unless they physically call up samhsa or the DEA.

Here is a link to the doctor locator: (Note: Not every doctor authorized is listed here. Not every doctor listed here is competent.)

http://buprenorphine.samhsa.gov/bwns_locator/index.html

Sadly, even though Suboxone is available, and the DEA numbers are issued, that doesn't mean getting into the program will be easy. Doctors have little clue of what they are doing, nevermind what is going on. Pharmacies are skeptical of catering to heroin addicts. Let me address some of this.

SAMHSA has been spreading misinformation. They have been telling doctors that Subutex/Suboxone won't be available for three months. If your doctor doesn't know the drug (Suboxone, not Subutex yet) is available, have him call 1-877-SUBOXONE. This is the company's helpline, and they will tell him all about it.

Doctors are under the impression, thanks to Reckitt Benckiser (the company who makes Subutex/Suboxone,) that they should use Subutex for induction. There is no reason for this other than to be cautious for extreme hypersensitivity/allergy to naloxone. (See Subutex vs. Suboxone for more information on this.) Be sure to tell him that you are not afraid to be inducted with Suboxone. For this reason, and for many others, doctors do not have their induction doses, and probably won't for several months. This will delay the majority of buprenorphine maintenance a great deal.

There is a solution, and Reckitt suggests it themselves: have your doctor write a script for 3 8mg tablets or so, and then you can bring it back to the office for induction or the pharmacy could deliver it. (Suboxone full prescribing information.) If he is willing or prefers to do inductions with Suboxone, have him/her call 1-877-SUBOXONE. They will connect him to warehouses in order for him to get his induction doses.

Pharmacies are not going to have Suboxone in stock. They will most likely order it on a per prescription basis. This is even more the case because of it's price, nevermind it's use. Be sure to keep this in mind. Almost all pharmacies have next day delivery, provided that it's not backordered (which it's not at the current time.) You should have your doctor call in this induction dose the day before so it will be available. Then we come to the next problem. Pharmacies don't want to cater to junkies. Most will be very skeptical. In major cities, this really isn't an issue, but in rich/suburban communities, this can pose quite a problem. Be sure to call around and try to find a good pharmacy. A good pharmacy will make your life a whole lot better, and you should not quit until you find one. I suggest you try and find one before finding a doctor, as he may bring this up.

Moving on, here is a list of *approximate* prices. I have no idea whether your insurance will cover it, call them and ask. As of my last (and only) script for 'bupe, it came up as drug not found on my insurance. When further information is available regarding information I will provide it.

(These prices are for a month supply (30 days) at the specified daily dose. I have *roughly* extrapolated these numbers from the price of the 8mg daily monthly supply, and as such the other numbers are far from perfect. This can also vary regionally, and by pharmacy. Some pharmacies offer discounts, 10% for such a large cost is not uncommon.)

8mg - $175

12mg - $250

16mg - $340

24mg - $510

32mg - $650

The average daily dose is 16mg. 32mg is NOT *necessarily* the best dose, due to pharmacological reasons, regardless of whatever your tolerance may be. (See "Bupe and dose" in the "Bupe Pharmacology" section)

Bupe comes in bottles of 30 and is available in 2 strengths: 8mg and 2mg, in both Subutex and Suboxone formulations. They will likely come in the original bottle for as much as your dose is divisible by 30.

The procedure for switching to bupe is simple. You go to the doctor's office the first 3 days where he administers a dose of most likely Suboxone. (S)he will likely have you in the office for 2 hours during the first dosing. The second and third days will be shorter. You will then go once or twice a week for the first month, and it is unknown how large a script you will be given. After the first month is up, you will get monthly supply scripts, once a month (obviously,) and will see your doctor (most likely) once a month for maintenance and once a week if you are recieving psychotherapy. Psychiatric fees are usually in the $200-300 range for one visit, at least in New York.

Buprenorphine is a schedule *III* (not V) narcotic under the controlled substances act. This was changed recently. Bupe most definetely deserves to be a CIII, and I believe the prior scheduling (via Buprenex) was automatic due to it's relation to thebaine, and has not been examined directly. (VERIFY)

There is one other formulation that exists: Buprenex. (as was just mentioned) They come in 0.3mg injection vials (possibly 0.6mg but i'm not sure.) They are very expensive I hear. It is important to note that Buprenex is NOT FDA approved for maintenance, it is approved for pain, and it IS illegal for that use (for your doctor (Special rules apply to opioid maintenance, see the first section). If you had a legit script, it's not illegal for you.) People have used it in desperation in the past, with mixed results, although generally the results are surprizingly favorable for such a small dose.

Overseas:

In some countries Subutex comes in an 0.4mg strength as well. This has no practical use except for PRN (as needed) use during induction. This will not be happening in the USA (the doctor will personally induct you for the first three days, making this dosage unnecessary.) It could possibly be used for tapering purposes, however the only reason why one should taper so low is if they are having unusually strong withdrawals from buprenorphine, which is uncommon. See the withdrawals section for more information.

There is also another formulation, Temgesic, but it isn't available in the USA. It's generally useless, and comes in 0.2mg and 0.4mg SL tablets. It's only use is for the same reasons listed above for the 0.4mg Subutex, and for pain, which is what it is approved for in the countries it's approved. It is interesting to note that Temgesic contains no listed inactive ingredients. I find it hard to believe it's nothing but buprenorphine, however, as 0.2mg is barely visible to the naked eye if it is at all (VERIFY), and on top of that handling the tablets could easily cause destruction of the drug. The reason why this would be worth mentioning is because it is almost asking you to inject it. There is also Temgesic-NX, which contains Naloxone just like Suboxone. You do NOT want to inject that under any circumstances.

And this leads us to our final topic, getting high...

Getting high:

YES, it IS possible to get high off of bupe. In France they have a HUGE problem with bupe being used illicitly, where they use bupe in abundance. Heroin has virtually dissapeared and bupe has become the street opioid you are likely to find. Heroin does exist there, don't get me wrong, but Subutex seems to be far more popular (VERIFY.) I can't tell you exactly how they do it, I wish I knew myself. I can tell you that they sniff or bang it. Do NOT sniff or bang Suboxone, you will get very sick.

There have 120-something or so deaths from bupe in France. Almost always the bupe was banged, and also almost always mixed with another drug, usually a benzo.

It should be noted that respiratory depression is increased when the drug is injected. This shows that injection probably increases the euphoria aspect of buprenorphine.

The euphoric aspect of Buprenorphine appears to be increased by injection/sniffing. The drug IS highly lipophillic, which means it rushes the brain like heroin (and theoretically should provide a rush if not for it's partial agonist nature,) however, and also due to it's partial agonist nature (?), it has a very long onset of action, of approximately 100 minutes to peak effects.

I feel 100% confident in saying that bupe works just fine for getting opioid nieve individuals high. It's quite potent in that case, actually. The downside is it's long onset of action, which can take 1-2 hours if taken SL. In this case, a dose from 0.2mg to 1mg SL works wonders, however even in opioid nieve individuals overdose is difficult. Don't try it out, though! People HAVE died, and it will most likely be unpleasant at an extremely high dose. If you don't have a tolerance, 0.2mg SL should be your first dose. And give it time!

I am *NOT*, nor will I *EVER*, say bupe is superior to a full agonist for getting high.

A personal report of getting high on 0.3mg via IV in an opioid tolerant/non-dependent individual: http://www.erowid.org/experiences/exp.php3?ID=15694

He compares it to Vicodin and Xanax all rolled into one, mild (without the rush, nod, or intense euphoria), yet glorious. This is just one account, however, and is far from what you will experience if you try.

Another one:

http://www.erowid.org/experiences/exp.php3?ID=13581

This one uses Temgesic 0.2mg SL tabs. He had a very strong reaction to the 1mg he took the first time, and enjoyed the rest of the bottle of 30, taking only one at a time. He takes them SL, as they are designed for.

Getting high while on buprenorphine is difficult to say the least. The drug can work with a fairly similar efficacy to oral Naltexone in blocking opioid agonists. See the "48 hour rule" in Buprenorphine vs. Methadone for further information.

This FAQ, while comprehensive for buprenorphine (USA), is meant to focus on maintenance, not recreation.

Bibliography:

G Fischer, P Etzersdorfer, H Eder, R Jagsch, M Langer, M Weninger (1998). Buprenorphine Maintenance in Pregnant Opioid Addicts. European Addiction Research;4(suppl 1):32-36

Miller W; Hussain F; Shan S; Hachicha M; Kyle D; Valenzano K J (2001). In Vitro pharmacological profile of buprenorphine at mu, kappa, delta, and ORL-1 receptors.

(1) Dum JE, Herz A. In vivo receptor binding of the opiate partial agonist, buprenorphine, correlated with its agonistic and antagonistic actions. Br J Pharmacol. 1981; 74:627-33.Heel RC, Brogden RN, Speight TM et al. Buprenorphine: a review of its pharmacological properties and therapeutic efficacy. Drugs. 1979; 17:81-110. (IDIS 121541)Kareti S, Moreton JE, Khazan N. Effects of buprenorphine, a new narcotic agonist-antagonist analgesic on the EEG, power spectrum and behavior of the rat. Neuropharmacology. 1980; 19:195-201.Sadée W, Richards ML, Grevel J et al. In vivo characterization of four types of opioid binding sites in rat brain. Life Sci. 1983; 33:187-9.

Negus SS, Bidlack JM, Mello NK, Furness MS, Rice KC, Brandt MR. (2002?) Delta opioid antagonist effects of buprenorphine in rhesus monkeys.

Huang P, Kehner GB, Cowan A, Liu-Chen LY (2001) Comparison of Pharmacological Activities of Buprenorphine and Norbuprenorphine: Norbuprenorphine Is a Potent Opioid Agonist J Pharmacol Exp Ther 2001 May 1; 297(2):688-695

Buprenex full prescribing information (USA)

Subutex/Suboxone full prescribing information (USA)

To be continued...

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Contact Information: Email: [email protected]

Feel free to email with any (non-insulting) comments at all. I'd love to hear from you. Also feel free to share your experiences. I am looking forward to making a more complete collection of personal experiences with BMT.