Continued from the above post:

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.

 Continued in next post..not enough space left in this one. 

 

  Source and credit to:

Nephalim of