This an excerpt from www.centersite.net "The Paradoxical Sinclair Method For Treating Alcohol Dependence" by Mark Dombeck, Ph.D.

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.

The Sinclair treatment attacks the behavioral basis for alcohol addiction; it does not work directly on the physiological addiction itself (e.g., that body dependence which requires gradual detox to remove). Importantly, this treatment is based on learning, and learning can only occur if drinking continues. So paradoxically, it is important, vital even that alcoholics continue to drink while following the Sinclair protocol. If they don't drink and take pills as prescribed, they will not learn that alcohol's thrill has gone flat, and will not stop drinking. The fact that this therapy absolutely requires that drinking continue has got to be terrifying to most treatment providers who are thinking (quite rightly) that excesses of drinking need to be shut down as fast as possible. The idea with the Sinclair method is that the straightest path to the goal of drinking reduction is NOT a straight line, but rather a winding road.

Interesting article Cheeto.

His comments about up regulation made me think experimenting with less than the reccomended 50 mg might be a bad idea. Ramping up to a full dose makes sense, but long term it might be playing with fire.

receptor increase + dosage decrease = ?

This is all true, but don't forget that the upregulation is temporary. If you haven't had nal in a week, you're back to normal.

Dr. Dombeck sounds a little weirded out and scared of the idea. If that's so, an additional hooray for him for touting its positives anyway. It's harder to be fair to ideas which challenge us.

Thanks for the post Cheeto. I like reading outsider perspectives on our chosen method. As one who still struggles with the idea that I must continue to drink for this to work, this is a really good kick in the butt summary.

Interesting info, I was under the impression that the upregulation was permanent. Too bad in a way since I was anticipating an eventual permanant uplift in the exercise and sex life departments.

And yes, you definitely get the impression that he hasn't made up his mind about TSM.

Heh, I wish.

Magda was doing an experiment with low-dose naltrexone, taking a microdose every night to try to maintain upregulation. She seems gone, though. Haven't seen her in a while. Well, maybe she'll be back.

Hi Cheeto, Thanks for the research. Hmmm, I'm a little confused on the up regulation thing and what Melissa said about starting back at square one in a week. Does this mean if you are a binge drinker once every couple of weeks and take the Nal, then you are not extinguishing any opioid receptors? If you do the The Sinclair Method and deem yourself cured then want a drink, are there extra sensitive opioid receptors left in your brain? or desensitized ones? I am one who tends to over- think things, but want to be reassured that I am squelching those little buggers every time I take the Nal as opposed to making them even more sensitive. You know what I mean?

We extinguish behaviors ("learning"), not receptors. The receptors are physical things in our brains. Our brains want to "regulate" the amount of opioid we receive, keeping it more or less consistent. They get worried when there's way too much or way too little opioid/endorphin reward kicking around.

The receptors can "downregulate" (become fewer in number) after we drink alcohol or otherwise flood them, as the brain tries to maintain equilibrium. They can "upregulate" (increase in number) after we take naltrexone, because they are blocked by the nal and the brain makes more to try to get them to work.

It all wears off, though, and our brains lazily ooze back to the way they were originally.



I'd think you'd be okay with doing that once every few weeks. No guarantees, of course. A more practical objection is to wonder how many alcohol addicts can resist the Alcohol Deprivation Effect, for weeks at a time, on a regular basis.



Unlikely. Your brain will be back to its own normal by the time it would be reasonable to call it.



You don't want to eliminate your opioid receptors. You need them to enjoy your life. You will have more sensitive receptors on no-nal days, and if you want you can leverage that to get a little extra enjoyment out of pleasures like food and sex and exercise. You don't have to, though. All this stuff is sort of "advanced TSM." All you really need to do is follow the Golden Rule, and the behavior will gradually be extinguished.

You know the golden rule sounds so ridiculously simple, that I have to remind myself that it was written on the basis of (what is now) a large body of research. I'm not going to monkey with it in any way, just going to do it by the book and let it happen.

Take the pill.

Drink as you feel.

That's it.

I was a binge drinker (although I did have daily drinking episodes). TSM cut my units in half which meant I could drink every night, there was no reason to hold off so I ended up drinking 5 days out of 7 for approximately 4-5 weeks.

I then decided that wasn't good, so started to increase AF days.

Some people say TSM works better for binger drinkers.

Thanks for posting the article about drinking without nal, this is what I understood from the book - that I can never drink without nal again, and I haven't.