Baclofen- Does the brain increase Gaba-B receptors?

[Otter]

Hi

Has anyone heard of "up-regulation"? I read the following by Mark Domberg Ph.D on Healthmed.com. It relates to Naltrexone and the Sinclair Method but I wonder if it applies to Baclofen.

"Sinclair is basically extinguishing the relationship between drinking behavior and pleasure. He has the alcoholic take the anti-pleasure pill before drinking, and then when the drink is actually consumed, it just doesn't have that kick it used to have. Over time, the tight compulsion to consume alcohol just sort of fades away as the brain learns that the thrill is gone.

There is a catch here, of course. The brain isn't stupid, and it doesn't like change. When you take a pill to suppress pleasure, the brain doesn't like that and fights back by increasing the total number of opioid receptors in the brain; a process known as up-regulation. The brain's strategy is basically, that it tries to turn up the sensitivity it has to opioid agonists so as to restore normal functioning. This is no problem so long as you stay on the pills, but woe be you if you go off them and drink. If that happens, well, each drink is going to be better than ever before (magnified as its impact will be by the increased numbers of opioid receptors), and problem drinking will set in again in record time. So, to be clear, once you go on the Sinclair treatment, you are foolish to go off it if you plan on continuing to drink in any way shape or fashion."

Are the Gaba B receptors increasing? Does the brain reach a point where it stops producing more receptors so the Baclofen eventually works to completely eliminate craving? Anyone know of any information on that point?

Ameisen does not mention what happened to him as he increased his dosage. I got the impression from Ameisen's book that he was perhaps having some success in suppressing his cravings on the way up but he does not actually say what his drinking pattern was along the way. Here in the UK it is still not possible to get anyone to prescribe above 100 mg per day so I am looking for some information to put to a doctor.

[Henrietta]

Baclofen- Does the brain increase Gaba-B receptors?

Good luck Otter --the problem you have with doctors in the UK is the same the world around. Baclofen is just not prescribed in high quantities as a matter of routine, so they are very hesitant to go out on a limb. Especially in the US, if doctors even smell the possibility of a lawsuit, they?re done.

As far as drinking on Bac, many of us drank all the way up until we hit the switch. The drug simply did not affect cravings one way or another until we reached that point. I don?t pretend to know the chemistry, but having been on both I can state with certainty that Naltrexone and Baclofen work very differently than each other.

For those of us who succeeded with Baclofen, we achieved the switch at very high doses, much higher than 100 mg. We had to navigate around the medical system in many instances. We?ve had to go it alone, and as a group we are all in unchartered territory. I hope the medical establishment catches up with us one day and figures how we did it, because these drugs have enormous potential for good. But I?m not holding my breath.

My point is that it may not be in your best interest right now to try to educate your doctor. I hope I?m not overstepping here, because I don?t know you and I don?t want to make assumptions, but for most of us who have gone through this, it takes everything you?ve got sometimes just to manage the side effects and stick with it.

[herosa]

Baclofen- Does the brain increase Gaba-B receptors?

Otter can I just double check what you mean? If I understand you correctly you are saying that Naltrexone will work well when you are on it but if you come off it the brain will now have upregulated more opoid receptors leaving you worse than where you were when you started so think long and hard before you start it and you are asking if anyone knows if Baclofen will do the same?Have I got that right?

[edifice98]

Baclofen- Does the brain increase Gaba-B receptors?

That is an interesting question. I hope somebody here can provide some insight. It's possible that nobody knows because there have been no in depth long term studies using these high doses. Frustrating to say the least. I really hope we begin to see some real research about this drug soon.

[Lo0p]

Baclofen- Does the brain increase Gaba-B receptors?

Okay you've got this kinda backwards.

Naltrexone is an antagonist of the opiate receptors, meaning it latches onto them and prevents any endogenous opioids from activating them. After some time with a total opioid receptor blockade the brain 'upregulates' (increases the number of) the opioid receptors in an attempt at homeostasis (normalization).

This increase ONLY LASTS A FEW DAYS upon cessation of naltrexone. This make the statement by the researcher quoted above largely moot.

Baclofen, on the other hand is an agonist (not an antagonist) of the GABAB receptors. This means that it mimics GABA and instead of preventing activation of the receptor it actually activates it directly.

If the brain were to attempt to compensate for this (homeostasis) it would decrease the number of GABAB receptors not increase them.

This apparently is not the case as "baclofen retains its therapeutic anti-spasmodic effects even after many years of continued use" -wiki

[Cinders]

Baclofen- Does the brain increase Gaba-B receptors?

Very interesting post, lo0p. Thank you.

Cindi

[Otter]

Baclofen- Does the brain increase Gaba-B receptors?

Thanks Loop

That answers the question. I am still not sure why Baclofen seems to work to stop craving for a while at low doses but then the cravings come back. I am interested as to why there is a trigger point. We are pushing the dose up to a much higher level now anyway as we have some more Baclofen.

For me it is not just a question of educating my doctor. I deal with alcoholism and its effects every day in my profession. I live in a city with one of the worst alcohol/violence problems in the world and there is apparently not a single doctor here who prescribes!!! Added to that the medical profession in the UK is ultra-conservative. Here doctors only have a bachelors degree which they take straight from school and they are on the wards by their second year. They have a very poor backgound, if any, in biology or chemistry and generally just prescribe according to guidelines. While I take the point that doctors are reluctant to stick their necks out because of the risk of law suits, equally, they should be concerned about law suits if they do not prescribe properly. It is a professional duty for a doctor (under General Medical Council rules) to make enquiries where there is no information from the manufacturer of a medication as to its usage for a particular illness. If the only information on Baclofen dosage is that provided by Ameisen then there is no possible basis for any doctor to prescribe, as ours has, at a lower, ineffective level. That is not just an ethical issue but a question of professional negligence. Also, the lack of knowledge of Baclofen should soon become a matter of negligence. If you had curable illness and went to a doctor who either did not know about a cure or prescribed at the wrong dose you would sue him and report him to his professional body.

There was an article in major newspaper here, The Guardian, on Ameisen. Here is an exerpt:
Ameisen has built up a network of supporters, some of them in senior, influential positions – Jerome Posner, chair of Neuro-oncology at the prestigious Memorial Sloan-Kettering Cancer Center, and Jean Dausset, for example. When we meet, he is about to fly to America to speak at the McLean Hospital Division of Alcohol and Drug Abuse of Harvard University, and reports on his return that they have "asked me to write them my protocol on a piece of paper, which I did, and that they will simply start prescribing". He has also been made a visiting professor at State University of New York which, as he points out, is "not out of charity".

The point is that in the US doctors are going to start prescribing now. No doubt many may feel that if they do not they could be facing lawsuits from people who discover in a few years time that their doctor has failed them by not prescribing. This movement has to reach a critical mass at some point and the best way to push it is to write to whoever you can think of and put them on the spot, make them think, worry and wonder what might happen if doctors and healthcare providers don't start taking this seriously. There is absolutely nothing to lose and it is very easy to find pressure points within the system and to hit them with information that they cannot ignore. If everybody did this the process would speed up even more quickly.

You may think I am some sort of nut case but at the moment my wife is in bed dying from alcoholism and we have a doctor who doesn't give a damn and is too stupid to bother finding out. If that is typical of UK doctors, which I am sure it is, they deserve everything, individually and as a group, that I and anybody else can dish out to them.

[beatle]

Baclofen- Does the brain increase Gaba-B receptors?

You are definitely not a nutcase.

I'm looking forward to some "addiction specialists" I've encountered being exposed for what they are-- and losing their face and their business.

It will be little salve for the wounds, though, for all the people who have suffered needlessly.

[Road to Recovery]

Baclofen- Does the brain increase Gaba-B receptors?

Otter,
First of all, I am so sorry for what your wife is going through. I am in Canada, but I think this issue is worldwide. I was lucky because I have a doctor who took a chance and put me on baclofen - granted he did not have to go above 80mg for me. I am going to put this out there though. I have an appt. coming up with him soon and I believe he is involved with a networking group of Doctors that discuss various therapies. I am going to discuss this issue with him as he is astonished by what baclofen has done for me. I hope that there is some way for him to reach out tp the medical world and raise awareness as to the effects baclofen has made in the world of Alcohol addiction.
I hope your wife comes through this - truly breaks my heart.

[Otter]

Baclofen- Does the brain increase Gaba-B receptors?

Thanks for the support

Road to Recovery;870166 wrote: Otter,
First of all, I am so sorry for what your wife is going through. I am in Canada, but I think this issue is worldwide. I was lucky because I have a doctor who took a chance and put me on baclofen - granted he did not have to go above 80mg for me. I am going to put this out there though. I have an appt. coming up with him soon and I believe he is involved with a networking group of Doctors that discuss various therapies. I am going to discuss this issue with him as he is astonished by what baclofen has done for me. I hope that there is some way for him to reach out tp the medical world and raise awareness as to the effects baclofen has made in the world of Alcohol addiction.
I hope your wife comes through this - truly breaks my heart.

Hi

I am Canadian. I studied at the University of Toronto. Moving to Scotland is like going back 50 years it is so conservative and it shows no signs of moving forward into the 1970's. I don't remember students in Canada talking about how drunk they intended to get at the weekend and being totally uninterested in scientific advances or anything beyond the end of their own noses as is the case in the UK. It produces, here, a class of professionals who are utterly self centred and only interested in getting a big house and a Mercedes. Despair! I would be interested in knowing what the situation is amongst doctors in Canada. Hopefully your doctor won't turn to you as ours did and say, "I'm not going above 100mg a day" with a look of arrogant disdain.
Best wishes

[herosa]

Baclofen- Does the brain increase Gaba-B receptors?

Hi Otter I received your message. I do not know why your wife would have lost her cravings at lower doses only to have them return. I have searched to find out if the brain compensates in some way forcing you to try higher doses but I cant find anything-sorry. I guess its one of the downsides of this being a new treatment-there just isnt enough information on it yet.Maybe it would be worth taking a diffferent approach and just say to your wife that some people have to go all the way to 300mgs and no one knows why this is so. Look at loop-he had to go all the way to 300mgs and he continued to drink for the first 3 days on this amount,then it happened for him.If you stop now you will always wonder what if? it almost seems if you start you need to go the whole way with Baclofen.I can understand your irritation with the health system.Success is the best proof of all. If you can come to Drs in 2 weeks and say look-this cured my wife but it took 300mgs to do it then they will have to listen to you and people like you. Again I think you are paying the price for being one of the early users of this drug-the docs are nervous and jumpy and no one wants to be the first to chance it and risk px the high doses.It must be a horrible and lonely feeling for you going it alone especially when your wife is so ill. Try and focus on the two positives ie you have no problem getting the drug in Spain and you know its not unheard of for people to have to titrate up to 300mgs. Just hang in there and hope that you are nearly there. I hope we will be seeing a post from you soon saying she did it! Take care.

[scot98]

Baclofen- Does the brain increase Gaba-B receptors?

Hi Otter,

Your post's are very thought provoking and I agree with you completely regarding medical negligence etc. I also live in Scotland, I have been self prescribing Naltrexone for the past 4 months, initial 2 months were incredible but sadly increased, though It's still way better than I was pre naltrexone.
I emailed Professor Chick in Edinburgh last week and was planning to arrange an appointment until I reading the Guardian article that he will not prescribe over 100mg of Baclofen. I took the article along to my GP on Monday this week and he very strongly said he would not prescribe me bac, even under a renowned Psychiatrist's direction! This same GP would not even prescribe me campral even though I was seeing a substance abuse psychy nurse at the time. I personally have given up with the medical profession regarding alcoholism, which is really sad given I am a health professional myself.
I plan on taking Naltrexone for another 3-4 months and if no further improvement I will start on Baclofen.

Really sorry to hear about your wife, best wishes to you both.

[Road to Recovery]

Baclofen- Does the brain increase Gaba-B receptors?

Otter,
Have you seen this thread bu Corkit?
https://www.mywayout.org/community/f2...sen-41531.html

[Virgil]

Baclofen- Does the brain increase Gaba-B receptors?

Otter;870127 wrote: Here doctors only have a bachelors degree which they take straight from school and they are on the wards by their second year. They have a very poor backgound, if any, in biology or chemistry and generally just prescribe according to guidelines.

Hello Otter,

I'm not in the business of defending doctors (GPs) as I am very critical of them from lots of different angles. However, I feel the need to point out that many of the trainee doctors with whom I was at University studied physiology and biochemistry (P&B as it was then called) for their Bachelors degree. Thereafter, if they wished to train as a doctor, that would incur a further three to four years' training and study at a medical school. The whole process takes typically seven years in total after leaving school at age 18.

When you say "You may think I am some sort of nut case but at the moment my wife is in bed dying from alcoholism...", no, you are most certainly not a nut case and I appreciate your frustration. I feel for you. My thoughts are with you both.

V.

[Otter]

Baclofen- Does the brain increase Gaba-B receptors?

UK Doctors

I am sure some doctors in the UK have some background in biochemistry etc. but I went to a law school in Canada where some of my fellow classmates had already done a Bachelors degree and then a Rhodes Scholarship, Commonwealth Scholarship or a Ph.D or Masters Degree at Oxford before being accepted into law school. The average age of admission to professional faculties in the top medical faculties in the US and Canada is about 24 as opposed to 18 here and they then do more medical training that their UK equivalents so they are often still training well into their thirties. It shows. Put my antagonism down to frustration if you want. I am English so I can complain. This country needs to have a conversation with itself.