I am very sensitive to the side effects of this drug, which is causing restless/sleepless nights, with wild nightmares so bad to the point of not wanting to go back to sleep. Accordingly, I have a STRONG desire to keep my dosage at a minimal level.

Question: if 50 mg blocks opiate receptors for 24 hours, is it safe to estimate that 25 mg blocks them for 12 hours and 12.5 mg blocks them for 6 hours? All of my drinking occurs within six hours of taking the pill. At 6' 1" 200, am I safe taking a 12.5 mg dose of naltrexone if the drinking definitely occurs within, say, three hours of taking the nal?

My point is this: I want to ensure blockage at the lowest dosage and I only drink over a 3-5 hour period, one hour after taking nal. If I take 12.5 mg is this sufficient, or is there a higher level threshold that you need to take in order to have the receptors blocked?

Please don't repeat "the studies were done with 50 mg" -- I know, I read the book. I'm trying to reduce the dosage keeping in mind my time frame for drinking. And thanks for the book -- IT IS SAVING MY LIFE.

I have looked around the board and woud like to know the same thing myself. Has this been answered before?

Hope this helps answer your question:

viewtopic.php?f=15&t=339

Netty

Nick, all,

It is my understanding that 50mg is sufficient to block 100% of the average person's opioid receptors. A smaller dosage may not block 100%. I am not sure how you would tell; the difference in buzz would probably be very subtile.

I am also fairly certain that the timing is not as you describe. Naltrexone lasts for 8-12 hours. With 50mg, most folks will have 100% of their receptors blocked for 8-12 hours. With a smaller dosage, then perhaps 75% of your sites will be blocked for the same 8-12 hour period. Extended periods of drinking require refresher doses of naltrexone.

If you are having serious side effects, then reducing the dosage does seem to make sense. A factor of two is a lot. Have you tried 37.5mg?

Best,
-wort

We have to look at one other factor in the dosage question. Bioavailability (the proportion of unchanged drug that reaches the blood). The bioavailability of oral Naltrexone is 5-40% and that is a huge variation among individuals and may not necessarily be related to the size of the individual. So if I happen to be the person with 5% bioavailability it may be that 25mg of Nal may not block 100% of my receptors. If I also am someone who metabolizes the drug quickly then it may not block my opioid receptors for 10-12 hours. Contrast this with someone who has 40% bioavailability and metabolizes naltrexone slowly. 25mg may well indeed block 100% of their receptors for more than 12 hours. Unfortunately there is no way to know which one of these you are without directly measuring the blood levels of naltrexone and it's metabolites so we have to rely on our perceived response to the drug for clues. You have to remember that dosage recommendations are just averages so they work for most but not every individual.

Note: Nothing in this post should be construed as medical advice. Prescription drug dosages should only be altered in conjunction with your prescribing physician's consultation.

Regarding dosing - here is the email response I got from Dr. Eskapa:

"While about 78 % of people in a large Finnish trial testing the Sinclair Method were drinking on average 9 units after three years TSM it is true that there is a percentage of non-responders (apart from those who did not comply with instructions - they may have abstained while on naltrexone or drank alcohol without naltrexone). In practice most people notice a drop in craving and actual drinking levels within 3 to 4 months though 8 to 9 months may be the time frame for some people. So TSM is not - just like any other treatment - 100 % effective. (It is 100 % effective for AA lab rats bred over many years to be high drinkers and have a mutation of the mu opioid receptors - it is thought ... alas not for humans.)

David Sinclair mentioned some reports where 25 mg was anecdotally effective - again we have seen anecdotal reports where 75 mg was right and 100 mg as well .. always 30 to 60 minutes before drinking.

I note that you are not under a doctor's care - I cannot offer you medical advice as I am a psychologist. It would be best if you could see a doctor but from my reading of the research I would not recommend going down to 25 mg if you can tolerate the medication. If you are unable to abstain through 'will power' and you have to drink (that is after all the nature of the beast) then it is a good idea to take naltrexone always before you do. There is a chance that you are not responding because the addiction in your case is mediated by some other system (GABA for instance) more predominantly ... if after another 9 months you show no reduction in drinking levels and craving then I fear TSM might just not be working for you and some other treatments - traditional or other - might be in order. If you are drinking an average of 35 to 49 units per week it is over the safe limit and therefore worth the expense of at least taking the standard dose.

I wish you all the best and hope that TSM will benefit you eventually as it has done for so many. "

Not very encouraging I'm afraid and also contradictory to the above link. And so the debate continues!

His answers don't appear to be contradictory to me. he told netty , "If you are responding well to 25 mg naltrexone 30 minutes to an hour before drinking then by all means proceed." because netty's numbers had drastically dropped on 25mg.

In a case in which the numbers hadn't drastically dropped, seems to me to make sense to stick with the suggested TSM dosage. maybe I missed something here.

I think the bottom line so far is that it's a matter of totally blocking the receptors more than anything. if 25mg does the job, it does the job. probably safest to stick with 50 though. in my case I may go back up to 75.

It is not possible to answer your question. It is assumed that TSM works with 'most" of your opioid receptors blocked when you drink. What % of the receptors are blocked? Probably close to 100% at 50 mg/day for baseline endorphin activity. It is a competitive blockade at the receptor site, and medics can overwhelm it if necessary, say for surgical pain.

But we don't know at what % of blockade you start getting nightmares. You can cut down on your dose, but we don't know at what dose you no longer get 100% blockade.

Practically, since according to your sig you are cured, it is a trade-off between drinking or sleeping well.

I will add to my last post, and then stop being the pedant.

If 50 mg blocks 99% of the opioid receptors in 95% of the people (I am picking numbers out of a hat since in a competitive block it is not possible to get 100% block), then in most people the dose is much higher than needed. But we don't know where any one person is along this curve.

The average half-life of NAL is only 4 hrs., but that of its active metabolite is much longer. In any given person, what is the half-life of receptor blockade? I don't know, but let's say 6 hours. The usual (and arbitrary) stated time of five halflives means 30 hours for a wash-out.

Since for many (?most) people 50 mg is probably supra-maximal, wash-out means longer than that.

So....... if person A gets 99% receptor blockade with 50mg, and person B gets 99% blockade at 12.5mg, the washout for both of them is the same - 30 hours, given my assumptions above.

Yeeeash, I feel like I'm back in college. Sorry.

I guess I am taking Dr. Eskapa too literally when he wrote from his reading of the research he would not recommend going down to 25 mg if you can tolerate the medication.

If one responds slowly to TSM how does one really know if 25 mg is having the same effect as 50 mg. That is really the question. In Nettys situation, the response to Nal was extremely fast and noticeable as was the difference between 25 and 50 mg. Maybe for those of us that are taking months (and months and months:-) to notice anything would do ok on 25 mg but how would we know. I tried 75 mg for a few weeks and did not notice any difference from 50mg so I would not notice any difference on 25mg , logically. Just sayin. Ok, ramble over.

I drink daily for 4-5 hours so I thought that 25 mg would be enough but then you guys got into the half life and metabolite and complicated my simple way of looking at it

I am curious though about the Gaba receptors vs. opiate. I thought that addiction to alcohol was the same for everyone. How is it that my addiction could be Gaba and other Al addicted folks are opiate. If this is indeed Gaba then the route I would have to take would be Bac. Which, I do not want to take.