All,

After six weeks of TSM, I have decided to combine baclofen with naltrexone. During the past six weeks my average daily intake has increased substantially. I have experienced very strong feelings of depression which I have never felt previously. I have also had persistent muscle tension that I have only recently connected with TSM. I believe these are symptoms of a protracted alcohol withdrawal. Both should be improved with baclofen, which is a muscle relaxant as well as an antidepressant.

My goals over the next several months are to decrease weekly units to 14 or less. I do not desire total abstinence in the near term. I firmly believe that extinction is a cure for alcohol addiction, and I am committed to this outcome. I simply want to use baclofen to bring my drinking to safer and more manageable levels. I'll report weekly progress in this thread.

I visited my GP yesterday, well armed with half a dozen journal articles and Ameisen's book. My GP is a jewel, and wrote me a script for baclofen that will allow me to follow the high dosage approach if and when I decide to do that. My first day was nothing short of astounding. I took three 5mg dosages; no side effects or sleepiness, but a very tranquil feeling. More interestingly, I only had three units last night, and did not finish the third. This could be a placebo effect, but it was very encouraging. I did not sleep well, but was so tranquil that I did not care.

I'll titrate as follows: 3 days at 15mg, then three days at 30mg. If this is enough to reduce my intake to a safe level, then I'll stop there for a few months. I will of course continue to take naltrexone one hour before drinking.


NEUROLIGICAL MODEL

It helps me to have a model in mind for how baclofen and naltrexone might interact together. What follows is a concise summary of what I have tried to piece together from a variety of sources. Neuroscience is very complicated, and this is undoubtedly over simplified. Corrections and suggestions are welcome. I apologize for the many acronyms, but they are unavoidable.

Alcohol affects the brain in many ways. Three important effects involve release of endorphins, gamma amino butyric acid neurotransmitters (GABA NT), and the glutamate neurotransmitter. As described in Eskapa's book, endorphins affect the brain's pleasure centers, causing a conditioned response to drink again. The GABA NT has a sedating effect on the brain. For example, Valium mimics the GABA NT much like morphine mimics endorphins. Glutamate NT's are released to counter the sedating effects of GABA. Naltrexone blocks the opioid effect of alcohol, but does nothing to affect the GABA or glutamate response. That's where baclofen comes in.

The GABA NT has two kinds of receptor sites: GABA(A) and GABA(B). When a GABA NT attaches to a GABA(A) receptor, sedation occurs. Alcohol facilitates this process (i.e. is a GABA(A) agonist), producing the sedation of the alcohol high. Too much GABA decreases muscle coordination, and to correct for this the brain releases the stimulant glutamate. The GABA(B) receptor is a glutamate throttle; engineers refer to this as negative feedback. Baclofen is a GABA_B agonist, that is, it facilitates attachment of GABA NT's to GABA_B receptors. This reduces further production of glutamate, which decreases anxiety and other effects associate with alcohol withdrawal, and in fact withdrawal from many addictive substances.

Alcoholics that respond more to alcohol's endorphin response do well with TSM. I suspect that these folks include bingers that chase the buzz. Alcoholics that are more attached to the sedating GABA effects of alcohol (e.g. Ameisen) are less responsive to naltrexone; these folks respond better to baclofen. Combining naltrexone and baclofen blocks both responses.

Ameisen has an interesting idea that a newly discovered NT called GHB might play a role in alcohol addiction. It is similar to baclofen in that it is a GABA_B agonist. People who have a GHB deficiency might be especially susceptible to alcoholism and also to baclofen as a treatment.

The stimulant glutamate is responsible for most aspects of craving and withdrawal. Alcohol blocks the glutamate receptor (NMDA receptor) and over time this results in more receptors (upregulation). When the alcoholic stops drinking, glutamate production continues, producing the jitters, craving and anxiety of alcohol withdrawal. Campral works by reducing the production of glutamate. Valium mimics the GABA NT, and thus also counters the effects of glutamate. Baclofen reduces glutamate which reduces anxiety and other symptoms of withdrawal. Upregulation of glutamate receptors is also largely responsible for development of alcohol tolerance.

The effects of alcohol on the brain is complex. For example, endorphins release dopamine NT's, which are also responsible for the cocaine high. Alcohol also stimulates release of the serotonin NT, responsible for the high of Ecstasy. Drugs such as morphine, cocaine and Ecstasy that involve a single NT are sometimes called chemical scalpels. Alcohol involves a host of NTs and in this analogy is more like a chemical bomb.

The seasoned alcoholic gets positive reinforcement from the pleasurable effects of alcohol, and negative reinforcement from withdrawal symptoms that are relieved by drinking again. Both create the conditioned learning that leads to alcohol addiction. Extinction is the only permanent cure that is currently known.

EXTINCTION

TSM reverses the conditioned response to endorphins. I am hopeful that the same is true for baclofen. In other words, would drinking while taking baclofen produce extinction of the conditioned response to the sedating effects of GABA and to the negative effects of withdrawal? The trouble is, baclofen works too well, so most folks that take it often just stop drinking. Part of this may be due to adopting Ameisen's high dosage approach, which apparently completely eradicates the desire to drink. My fear is that without extinction, one would quickly relapse after stopping baclofen treatment, especially if the alcoholic is a GABA drinker that is particularly conditioned to desire the sedating effects of alcohol.

As I proceed, I will titrate up to a baclofen dosage high enough to reduce intake, but then titrate back down to a level where I can drink very moderately with AF days interspersed. That's my plan anyway. I'll post my progress.

-wort

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Abstract only, but very interesting:

http://www.ncbi.nlm.nih.gov/pubmed/15607845

-wort

Great post Wort -- excellent summary, you are teaching me a lot. Everything you say entirely makes sense. As a binger I was definitely addicted to the high produced by endorphins and so TSM worked for me. The 20% may very well fall into the other two neurotransmitter categories. I, too, will be watching your progress with interest.

Wort -- Thanks for your synthesis of what's out there. Nothing occurs in isolation in the brain. If you look at the illustrations in Appendix B in Eskapa's book, you'll see that glutamate is implicated in the endorphine release process. This caught my eye because one very prominent side effect I had when starting naltrexone is, the volume of the tinnitus I occasionally experience went up to a roar. I've learned that tinnitus is related to overabundant glutamate, so I flipped through the book to find an explanation, and the illustrations were all I found.

As you point out, our body is continually trying to balance the yin/yang of glutamate and GABA in the brain. And we all face a wide variety of issues in our attempts to intervene when the process is out of whack. So it makes sense to me that there is not a one-size-fits-all solution. For those for whom naltrexone alone does not do the job after several months, it certainly makes sense to consider adding another drug. Hopefully, everyone eventually finds exactly what works for them. And, hopefully, naltrexone will obviate the need to continue the add-on drug indefinitely.

The real shame is that we have to fumble around and experiment on ourselves. The science has been around long enough that we should be much further along by now. And naltrexone continues to be studied as an anti-craving drug. There is not much past Sinclair's work testing it for extinction. The most compelling evidence (apart from Sinclair)are the meta analyses that have noted a pattern of decreased consumption in clinical trials where the subjects were noncompliant with instructions to abstain. Now, baclofen, naltrexone and topamax have expired patents, and there is no money to be made from generics. The exception is the long acting Vivitrol for naltrexone, which is IMO a shameful waste. I've heard some talk of effort to develop a time-release baclofen, which as I understand it would be equally as problemmatic, as it would preclude fine-tuning the dosage.

We truly are pioneers. Thankfully we live in an age when we have access to information as never before -- and we have access to one another.

I really would be dead right now if I hadn't found this site.

I'll be pullin' for ya wort!

All,

Week 1 passed with no side effects to speak of, other than a touch of nausea mid-week. I'm at 80mg/day now, having titrated up perhaps too quickly. Units for the week were substantially down - 37u, this despite the fact that I was on vacation for the week. This was a complicated week. I had a tooth extraction on Wed. so I suspended naltexone last Friday to allow for pain medication. This was fortunate, since the extraction did not go smoothly. I will start back on naltrexone this weekend, so hopefully next week will be more routine. My titration proceed as follows:

3/5: 15mg (5, 5, 5)
3/6: 40mg (5, 5, 10, 10, 10 (1:300am))
3/7: 50mg 10 10 10 20
3/8: 60mg 10 10 20 20
3/9: 75mg 20 20 15 20
3:10 80mg 20 20 20 20
3:11 80mg (20, 20, 20, 20)

Stopping nal temporarily was interesting. I experienced pharmacological enhancement for almost every sensory experience except drinking. Again, the experiment was not clean since I started baclofen on the same day as stopping nal.

Baclofen has been extremely interesting. The only side effect, if you could call it that, was an overwhelming and very welcome tranquility. I also slept better than I can ever remember. I have always had problems sleeping, and my guess is that this is a big part of why I drink. I've had a prescription for Ambien for about two years now, and am getting very tired of taking it. I have not taken Ambien since beginning baclofen, and have absolutely not needed it. I wonder if my troubles with sleeping have been due to undiagnosed anxiety. I've never thought of myself as anxious, but the calming and restful effects of baclofen have been unexpectedly therapeutic. Hopefully, these effects will not go away as I acclimate to baclofen.

I might hold at 80mg/day next week, or maybe go to 100mg/day. I hope to reduce weekly units to 20 or so but not much less in order to proceed with extinction.

ART, DOMD, Nick and LoOp: thanks for the feedback. Nick especially, since I worry that I am a dissapointment to you. So far I can tell you that at least for me, TSM+baclofen has been a resounding success.

Best,
-wort

wort - I am watching and reading this w/ great interest. Printing out your original post as part of my going in "armed" to my DR very soon....

Keep us posted. Thx so much for this much so far & Good Luck!!

XXXOOO

Hi houtx,

Yes, it is essential to go well armed to you GP appointment. I took several journal articles and Ameisen's book. Unfortunately, I did not keep a list of the articles I took, and my GP kept them for my file. This makes sense; he prescribed enough baclofen to allow me to persue the high-dosage approach. This meant he had to RX about three times the published safe dosage level. Keeping the articles as a record of our conversation gave him a better comfort level.

I can remember most of what I took. The strategy is to take articles that will allow your GP to quickly determine that the high-dosage approach is OK. Here is a list of candiates:
1. Ameisen's book.
2. Ameisen's published self-case report.
3. An article describing Ameisen's interesting hypothesisthat alcholism might be due to a deficiency in the GHB neurotransmitter. If so, this would explain the effectiveness of baclofen as a treatment, especially for long-term use.
4. An interesting case report published by phychologist W. Bucknam.
5. Ameisen's latest publication describing a study using the high-dosage approach.
6. There is a very recent clinical trial that looks at naltrexone+baclofen. This study is flawed in that it inexplicably followed a low-dose strategy for baclofen. Furthermore, the lead researcher J.C. Garbutt had the gall to criticize baclofen as being ineffective in an ABC interview. The only reason I can think of for his attitude is that he (or Chapel Hill) gets research money from sources that have financial interests in the alcohol rebab industry. As evidence, see the add at the bottom of this page. Baclofen and naltrexone are out of patent, and more importantly, they have a much larger sucess rate than rehab centers that cost thousands of dollars per week. Oh well - so much for the hippocratic oath.

You might also look at LoOp's baclofen info page on MWO for more ideas.

I wish you the best of luck with your GP. If he will not prescribe, or only prescribes 80mg/day, you can always supplement with off-shore sources.

-wort.