Thoughts on Baclofen's anti-craving mechanism

[Ne/Neva Eva]

I'm curious as to how and why (and if?) baclofen is different than say, Suboxone (or methadone). I have a friend who recovered from his opioid addiction taking Suboxone. I tried to explain to him how the two are not the same, and did a really poor job of it!

I feel like xanax is to the alcoholic what Suboxone is to the opioid addict. And that baclofen works very differently. (More like an antibiotic? That's a lousy metaphor. Is there a better one?)

I know that Chick published an article some time ago that said that baclofen is a substitute for alcohol. And I think he made a correlation between suboxone (or methadone) and baclofen. But others don't draw the same conclusions.

I spent some time this morning re-reading what Otter's written on BaclofenUK. The explanation page for how baclofen works seems to imply that baclofen is calming for the CNS. But that sounds a lot like the way a benzo would work, and I know that isn't the case.

I also understand that one affects GABAa, and the other GABAb. But again, how does that make baclofen different than something that substitutes for alcohol?

Also, as an aside, where can I find the answers?


For those that don't know about the other site, and there is a wealth of information there: Baclofen UK World Forum - How Does Baclofen Work?

[Xadrian]

Thoughts on Baclofen's anti-craving mechanism

Hi Ne,

If alcohol (ethanol) only were an agonist for GABA, it wouldn't be much of a problem: Gaba controls (counteracts) the dopamine and endorphin (which gives a pleasant, rewarding feeling) levels, so basically the more GABA is available, the more dopamine and endorphin are being suppressed. Compare it with an air conditioning and a heating system that keep the temperature in a room at the right temperature. When it's too hot (dopamine, endorphin), the heating switches off and the air conditioner (GABA) switches on, causing the temperature to drop to a normal level.

The problem with alcohol is, that it is not only an agonist for GABA, but also for dopamine, endorphins and serotonin (Addiction: Alcohol's Effect on Neurotransmitters). This will spin those levels out of control and give a rewarding, pleasant feeling that makes the brain addicted eventually. Compare it to when you switch on the air conditioning (GABA) and the heating (endorphin, dopamine) at maximum at the same time, eventually overheating the compressor of the air conditioner, so the capacity of the air conditioner is also effected in a negative way.

Baclofen, on the contrary, is only an agonist for GABA(B), so it will reduce dopamine and endorphin levels and therefore it doesn't give a rewarding and pleasant feeling and consequently is not addicting. (You open the door of the room next to your room with the too warm air. This room has only an air conditoning (GABA) and no heating (endorphin, dopamine), so now the air conditioner of the other room helps the cripple air conditioner of your room, to get the temperature at a normal level)

Although science does not exactly know how baclofen works, my own experience is that drinking alcohol on baclofen eventually doesn't give the pleasant, rewarding feeling, just because the baclofen (which subtitutes for the GABA the brain can not produce enough anymore), will suppress dopamine and endorphin. (With the help of the air conditioner of the room next door, there's sufficient cooling capacity to prevent heating up your room).
This causes the switch.

Eventually, the heating is not being switched on so often (reducing or quitting alcohol) and the compressor of the air conditioner is not overheated that fast anymore, so you can shut the door to the other room a little bit (titrating down to the maintenance dose).

After that, it depends on how bad the air conditioner of your own room has been damaged (the capacity of the brain to restore its production of GABA) whether you can shut the door completely or have to leave it open a little (taking baclofen) for the rest of your life.


Does this comparisation with the heating/air conditioning help you to understand the principles?

[Lo0p]

Thoughts on Baclofen's anti-craving mechanism

I have a theory. But I'm off to work. I may have time tonight.

It short it involves the amygdala, the brain's low level center for very strong emotional memories. Baclofen and agonization of the Gaba B receptor prevents the amygdala from releasing copious amounts of dopamine, epinephrine and norepinephrine to the CNS. This is a fact, to the best of my knowledge.

Upon the amygdala triggering release of these chemicals you can have two reactions: An excitatory reaction which is positive and pleasurable if you are about to indulge in the substance (this has been studied). And also, I believe, the epinephrine and norepinephrine specifically can cause a reverse feedback effect to your lower level brain stem (fight or filght and fear which feeds back into the amygdala-->memories of the fear, pain and discomfort-->more release of neurotransmitters) causing extreme distress if you are unable to acquire or indulge in the substance.

A cue, thought, billboard, smell, sight or anything like that is processed by the amygdala and causes the devastating feedback loop to occur.

Baclofen prevents the signal of the release of the excitatory neurotransmitters to the CNS, thus halting the Lo0p from beginning.

This suppression effect is dose based and with a high enough dose will cause the complete inhibition of the release even in the presence of the strongest of cues. For example, actually indulging in the substance. Let alone seeing something on a billboard or a sign in a supermarket.

[Ne/Neva Eva]

Thoughts on Baclofen's anti-craving mechanism

Thank you both. I'm thinking about what you've written!

Yes, Xadrian. That does make sense. It's the mechanism for all that I'm trying to reason out. For instance, Suboxone "covers" the receptors that opiates work on. It keeps the opiates from making full contact with those receptors and blocks the rush people get from using. (If and when it's used correctly.)
Xanax and other benzos work differently than that. And baclofen works, I think, in a different way than either of those.

I think what I need to do is pull out the binder with all the studies and start reading! It's been too long. I've been meaning to organize all of it for about two years, anyway. I'm kind of excited at the prospect.

(By the way, this is in many ways an exercise in futility! If people [scientists, researchers, doctors] actually knew how this stuff worked in a conclusive way, they'd pretty much be able to solve the puzzle. Right? But it's interesting to suss out what we do know. Especially since one of the ways in which this community is unique is that we have practical experience taking this medication in all kinds of ways! :H)

[Lo0p]

Thoughts on Baclofen's anti-craving mechanism

Quick, dirty and without elaboration...but I'm going to be late.

[bleep]

Thoughts on Baclofen's anti-craving mechanism

Magic.

I thought it was obvious.

[bleep]

Thoughts on Baclofen's anti-craving mechanism

I think the easiest way of putting it without using scientific jargon is to think of it in terms of rewards. There is a part of your brain that decides if something is good for you or not, and it rewards or punishes you based on how it views the world. Simply put, an alcoholics brain applies too much of a reward to alcohol. This reward is achieved regardless (and before) any consequence, which is why it sometimes seems completely irrational to have a drink, yet you do it anyway.

Baclofen balances the reward that your brain perceives (and rewards itself with) from a drink to what it should be. ie - very little

That's my take anyway.

Or in other words, magic.

[tiptronic_ct]

Thoughts on Baclofen's anti-craving mechanism

Good to see you, Bleepster

It truly is a kinda magic, isn't it? LOL

[Ne/Neva Eva]

Thoughts on Baclofen's anti-craving mechanism

bleep;1455552 wrote: Magic.

Yep.

[RedThread12]

Thoughts on Baclofen's anti-craving mechanism

I dunno', Ne.

But I've always somehow thought that this "agonist" binding factor is not unlike any or all of the "agonist-antagonist" functions of our entire neurobiology. I guess, in my part of the universe, it makes sense that when GABAa receptors are all bound up (lol), which means we keep wanting more of whatever "that" is, but more has nowhere to go, because there are no more receptors, engaging GABAb - with baclofen, in our case - and building it's stability, is kind of like what I see in yoga classes everywhere (OMG I can't believe I'm going to write this, and I reserve deletion privilege): it's not POSSIBLE to bend forward from your hips with ease UNTIL the quadriceps along the front of the femur bone (agonists) are working equally, or even more, than the hamstrings along the back of the femur bone (antagonists). I mean, my gawd . . . for how many eons has it been the primary aim of the hamstring muscles to GET us and KEEP us upright??? It takes some serious and intentional effort to re-arrange that little agonist-antagonist brain-body piece.

But your QUESTION is an awesome one, for which I spent time I didn't think I had, Goggling around. I've not found any direct reference to the GABA's working in such direct relationship, but it just makes sense to me that there is some correlation.

I DID find this guy: http://www.youtube.com/watch?v=-eBUJ-1vcjk[/video]]The GABA receptor | How does it work? - YouTube WOW!, I'm thinking this guy could give us "8 x 10 color glossy photographs with circles and arrows and a paragraph on the back of each one*" to explain how baclofen satisfies those b receptors and hi-jacks a's demands.

I have NO idea how to get in touch with this guy, but as you'll see, I'm not shy about asking!:-)

And That. is my thoroughly non-scientific, $.01.

I realized a long time ago that "metaphysics" was just physics in a dimension not yet perceived or understood. Much of what we understand today as "physics" started out as MAGIC. So I'll go with THAT, too!!

*LYRICS - Alice's Restaurant

[Greg]

Thoughts on Baclofen's anti-craving mechanism

I wonder if glutamate activity is also part of this? I remember reading in the medical literature that excess glutamate activity in the brain has been implicated in causing abstinent alcoholics cravings and a return to drinking, due to it rendering the brain over-excited/unstable. While GABA is a calming neurotransmitter, glutamate works in the opposite manner, and the normal balance between these two can be upset by long periods of drinking...too little GABA and too much glutamate activity could exist in the brains of alcoholics when the alcohol isn't there as much (or at all) anymore.

I mention this because baclofen may reduce glutamate activity (as it does with other neurotransmitters as outlined in above posts) while of course enhancing GABA activity, even though this is at the GABA-B receptor not GABA-A. I am no baclofen expert but others may be able to say if this mechanism of action is part of the whole effect. One thing that may go against this idea is that glutamate-enhancing anticonvulsants don't seem to have shown baclofen's alcohol-combating effects, although then again they have not been tried at unusually high doses (that I have heard of).

Sorry I don't have direct references to quote, but I know I have read these things in reputable medical articles.

[Ne/Neva Eva]

Thoughts on Baclofen's anti-craving mechanism

:H

Ask a little question and just look! Thanks, everyone for the input. Much to think about and very fun too.

Here's what I'm trying to get at:
Methadone-->Heroine
Baclofen-->???

This is the discussion I had with my friend:

Is baclofen like suboxone? A substitute? The red-headed stepchild of the drug itself?

I said No.
But I couldn't explain the difference. And when I couldn't explain the difference he was flummoxed and alarmed that I am still taking my "drug" and without saying so directly, hoped that I would soon feel free enough of my addiction that I would get off of my drug.

It was especially interesting because my perception is that he is still an addict, and I am free. He can't drink, doesn't take any drugs that might impact his sobriety (Nyquil) and I...don't think about any of that at all ever. If I need to sleep, I take a sleeping pill or a benzo. If I need to take cough medicine, I sometimes prefer it with something that knocks me out for 8-12 hours.

But his perspective (that of someone who used a drug to get off his drug of choice) is that I am still drugging. And the famous Dr. Chick published a paper with that implication. That baclofen is a substitute (in the way a benzo is) but without the concern of abuse.

I think of baclofen more like...insulin. Or an antibiotic. There is no question (in my mind) that I am absolutely cured of alcoholism. And my husband is cured of alcoholism and addiction. But my friend also believes that he is cured.

I don't really care about the semantics. But baclofen is not like suboxone. Then what is it like?

[nancy]

Thoughts on Baclofen's anti-craving mechanism

what is it like

I've never taken any of these drugs.
But judging by the descriptions in this thread... if it reduces the high of alcohol, isn't it more like naltrexone? That would be a crude comparison of course. Or if it reduces the anxiety which causes addiction, it's more like a benzo or other anti-anxiety/anti-depressant medication. I guess in the latter case, that's more similar to suboxone.

Has anyone here taken both naltrexone and baclofen?

[Greg]

Thoughts on Baclofen's anti-craving mechanism

Ne/Neva Eva;1455770 wrote: Here's what I'm trying to get at:
Methadone-->Heroine
Baclofen-->???

This is the discussion I had with my friend:

Is baclofen like suboxone? A substitute? The red-headed stepchild of the drug itself?

Heroin, morphine, codeine, and the other opiates are agonists of the mu opioid receptor. Methadone and buprenorphine are likewise agonists at that same receptor, so are able to act as longer-acting legal substitutes for other opiates like heroin, although I think bup. is sometimes called a partial agonist.

With baclofen being a GABA-B agonist, the only comparable other substances would be GHB/GBL and phenibut, although they are said to act on other receptors as well. To come up with a comparable (complete) alcohol substitute, a combination of substances would seem to be necessary. One would have to have alcohol's GABA-A agonism (e.g. benzodiazepines), another would have to be an opiate due to alcohol's endorphin- and dopamine-increasing effects, a third could be needed as an NMDA/glutamate antagonist, maybe a fourth as a serotonin-acting agent, and so on. I have long wondered if such a combination would be like alcohol minus alcohol's damaging effects, but I doubt anyone in a professional role will be experimenting with any such mixture of drugs any time soon. There was however a professor in the UK suggesting a benzodiazepine-like drink as a substitute for alcohol-based beverages a few years ago!

So, while baclofen definitely works for alcohol dependence, its action is somewhat different in nature to that of a direct substitute...perhaps it does indirectly substitute for some of alcohol's effects though, in particular the calming effect.

[Lo0p]

Thoughts on Baclofen's anti-craving mechanism

RedThread12;1455756 wrote: I realized a long time ago that "metaphysics" was just physics in a dimension not yet perceived or understood. Much of what we understand today as "physics" started out as MAGIC. So I'll go with THAT, too!!

That is, very nearly, a direct quote of mine.