Vile side effects but really want to plough on. Any advice?

[Ne/Neva Eva]

(Ne, how is the new forum coming along?)

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During that year, I still drank alcohol, but not alcoholically.

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I guess this might be why some people can actually come off it & remain sober, but only time will tell whether these changes are permanent or whether the brain reverts to its default "alcoholic state" after a while.

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Baclofen only really worked for me when I stopped drinking while increasing the dose. Once I did that, the somnolence & the tinnitus were much less troublesome (alcohol intensifies all the SE). Just saying- that was MY experience, no need for anyone to jump in & tell me "You don't have to stop drinking...."

Thanks, Molly, for sharing your experience. I agree with you, and of course, with Tk, about the blood alcohol levels and all that. Keeping it consistent in the beginning is probably pretty (very?) important, but after a while, it doesn't seem to make a big difference.



I really don't know many people who have successfully stayed off of baclofen without reverting to some kind of alcoholic drinking. I know there are some, so I won't say it's impossible, but I agree with you about that, too. I wouldn't chance it.



As far as your experience when you were titrating up the second time, I am confused. You didn't drink at all when you were titrating up, but over the next year you did occasionally drink but never alcoholically? Is that right?



And I suppose I should know, but when you went up the first time, did you have any success or were the SEs just too much and so you stopped taking it altogether?



The forum is going to be open soon. I had to stop the ball rolling for a little while to focus on 3-D stuff, but I'm back online now and will get it completed very soonish. Thanks for asking.



Hope you're well!

[terryk]

I know this is a little off topic, but since you posted this here, I thought I'd ask. The subject of GABAb receptors came up on the Naltrexone thread, and Otter mentioned that he thought it was only some alcoholics that had GABAb issues.

But isn't GABAb dysfunction a fundamental problem for people with alcohol use disorders? At all levels (or just about) of "use disorder"? I mean, booze, on a regular basis, messes up our GABAb, right?

Sorry for distracting from the OP's thread!

All I say is that Ameisen describes how baclofen works on Gaba-b deficits. Lots of people without this deficit drink, and stop drinking using many methods or don't stop and enjoy drinking into old age. Few people, I would suggest, with a serious Gaba-b problem can stop drinking without baclofen.

"Gaba-b deficits" is not a thing. There is GABA the neurotransmitter, and there are GABA receptors (subtypes a,b, etc.) where GABA acts to inhibit the CNS. Baclofen, Phenibut, and GHB act at at GABAb - benzos at GABAa, and alcohol hits both plus many other receptors. Ameisen postulated that alcoholism (or at least anxiety driven alcoholism) was a result of a deficiency of endogenous GHB (which, when exogenously supplemented, can be used to treat alcohol craving with good results). He believed that baclofen served as a replacement for GHB. I've gone on about this before as to why I do not think this is true - but maybe a simple way to disprove the theory is to look at baclofen and cocaine addiction. Cocaine does not affect GABAb receptors - it is a stimulant, and it also affects dopamine directly, yet baclofen has been proven to attenuate cocaine cravings in humans. If baclofen treats alcoholism by being a replacement for GHB, how can it work to treat cocaine craving if GABAb receptors are not direcly involved in cocaine use?

I think the key is the dopamine receptors attached to the GABAb receptors as mentioned here. Whether you use substances for anxiolysis, euphoria, or mood elevation, it's the reinforcement through dopamine in the mesolimbic reward system that is thought to drive addiction. Dopamine isn't a "feel good" chemical per se, it conditions the brain to continue behavior essential for for immediate survival. That works well for hunter-gatherers that have to problem solve to find food to stay alive, but in a post-scarcity world it's very easy to over consume anything for the sheer pleasure of it. When those things are chemicals that we overuse to sooth our mental or physical pains, a negative feedback loop develops where we need more and more of those substances to feel normal. Physical addiction is a result of the downregulation of the individual receptors that become accustomed to the substances that affect them, and mental addiction and craving is a product of the dopamine driven "learning" that tells us these chemicals make us "feel good" and drive us to seek more of them to feel "better."

-tk

[Molly78]

Thanks, Molly, for sharing your experience. I agree with you, and of course, with Tk, about the blood alcohol levels and all that. Keeping it consistent in the beginning is probably pretty (very?) important, but after a while, it doesn't seem to make a big difference.

I really don't know many people who have successfully stayed off of baclofen without reverting to some kind of alcoholic drinking. I know there are some, so I won't say it's impossible, but I agree with you about that, too. I wouldn't chance it.

As far as your experience when you were titrating up the second time, I am confused. You didn't drink at all when you were titrating up, but over the next year you did occasionally drink but never alcoholically? Is that right?

And I suppose I should know, but when you went up the first time, did you have any success or were the SEs just too much and so you stopped taking it altogether?

The forum is going to be open soon. I had to stop the ball rolling for a little while to focus on 3-D stuff, but I'm back online now and will get it completed very soonish. Thanks for asking.

Hope you're well!

That's right, for the last 2 years I have continued to drink about 2 or 3 times a week, up to 4 units each time (half a bottle of wine). It's interesting that the anticipation is way more enjoyable now than the actual drinking! I guess over time some sort of extinction will happen & I will just give up. But for now I'm happy that I can keep within recommended guidelines & still have a drink to be sociable when needed. IL if that makes sense? I started cautiously trying alcohol again after 2 weeks AF, increasing the dose quite fast. I found to my joy that after an evening out with a few drinks I could go back to AF the day after, so that's how I have continued.

The first time I tried baclofen I kept increasing the dose but my alcohol intake hardly altered. It perhaps went down a bit, but the somnolence was a problem, the alcohol made that much worse so that I actually fell asleep a couple of times when out socialising! I was drowsy by day & awake at night. Also, because I was drinking I kept forgetting whether I had taken the bac, so I ended up taking a double dose & getting really horrendous tinnitus. In the end I just gave up - I didn't seem to be achieving anything & I was paying out for bac & AL.

The second time I stopped drinking because I was afraid I was developing an alcoholic neuropathy & that frightened me, so I had a really good reason to stop. Because I wasn't drinking I could take up the dose much more quickly, also I knew from the first attempt that I am actually relatively tolerant of bac, I don't get anything like the SE some people do. I really think that couple of weeks was a window of opportunity. I could have gone on longer without drinking but it was Christmas (my first AF day was Dec 13th 2013) & it was so tempting to go to a couple of social events.

Sorry to read about all your problems recently, Ne. I'm not surprised you haven't managed to get the forum going, but it is eagerly anticipated!

[lex]

I think the key is the dopamine receptors attached to the GABAb receptors as mentioned ...
-tk

tk- let's assume TSM does indeed reduce cravings and volume consumed. Would this assumed fact tend to support, or to contradict, your hypothesis? (If you know.)

[terryk]

tk- let's assume TSM does indeed reduce cravings and volume consumed. Would this assumed fact tend to support, or to contradict, your hypothesis? (If you know.)

I think that it supports the theory that dopamine drives addiction. The idea behind naltrexone, and TSM in particular, is that the nal (a mu-opioid antagonist) blocks the euphoria that alcohol consumption produces. Extinguished cravings would be the result of your brain learning from the diminished returns of continued drinking with no euphoria.

Here's a model of how GABA, dopamine, and mu-opioid (MOR) receptors work together under the influence of alcohol:

Since the mesolimbic pathway is most intricately involved with the perception of a ‘reward’, NTX effectively reduces the positive reinforcement associated with alcohol consumption by preventing/reducing dopamine release in the N. Acc [9] and hence reduces cravings for alcohol as well as the likelihood of a relapse to abusive drinking upon culmination of the treatment process [10] [11] . In addition, to ?? - opioid receptors, naltrexone is also known to bind to δ– opioid receptors, inducing similar effects on the mesolimbic pathway as the ?? - opioid receptors [9]. Evidence for the reduction of reinforcement and cravings for alcohol consumption upon administration of NTX is shown by ?? - receptor null mutant mice that do not self-administer alcohol [12] . Drugs such as NTX and Nalmefene (another opioid receptor antagonist) have also been known to activate the HPA axis resulting in higher levels of Cortisol & ACTH in circulation [12]; which increases the possibility of reduced craving, relapse and the positive reinforcement associated with repeated alcohol consumption due to concurrent stress responses induced upon administration of naltrexone. The efficacy of naltrexone as a pharmacotherapeutic agent has been previously related to family histories of alcoholism. The varied susceptibility to beneficial effects of naltrexone has been suggested to be caused by single nucleotide polymorphisms in the OPRM1 gene which encodes for the ?? - opioid receptor; with OPRM1 - 118G polymorphism carriers showing a better response to NTX over non-carriers.

In rough terms, Baclofen directly modulates dopamine release (and also has modest anxiolytic action), while naltrexone indirecly affects dopamine by blocking the opioid effect (endorphin release) from alcohol.

Note my bolding of the last sentence of the quote which suggests that the nal drugs are probably more effective in a specific population of people with a particular genetic makeup.

-tk