I left a comment on Naltrexone Confidential, but I don't expect it to be approved (the blogrunner doesn't like me), so I'll post it here as well:

"The plasma half-life of naltrexone is about 4 h, and for its active metabolite 6-β-naltrexol it is 13 h.

Therefore one 50 mg tablet of naltrexone blocks opiates and endorphins for at least 24 hours."

I'm not sure this is necessarily an argument against booster naltrexone. 6beta-naltrexol is a neutral antagonist, while the naltrexone itself is an inverse-agonist. The neutral antagonist doesn't block basal signaling and should be expected to have a lesser effect. 6beta-naltrexol has significantly less affinity for the mu-opioid receptor as well as not blocking signaling.

It isn't about "more is better" but about a sufficient dose to keep the desired effect after the four-hour half-life of the inverse-agonist.

Melissa,

I am Joanna, owner of Naltrexone Confidential.

I need to point out the following:

1. I neither like, nor dislike you. I do not know you, therefore how can I like or dislike you?

2. When I received your comment, I immediately put it to Dr Eskapa for his clarification, as I said I would in the article. How presumptuous of you to assume I would not approve your comment when I have approved other comments you have made on naltrexone confidential blog on occasions. And then how inappropriate for you to almost immediately come onto this forum and advise others that I would not post your comment because I supposedly don't like you!

3. Dr Eskapa has just come back to me with the following reply;

''Naltrexone WILL block opiates and endogenous opioid endorphins released as a result of drinking for 24 hours. We do not want, from a Sinclairian point of view, opioid blockade when there is no reinforcement coming from positive endorphins - such as exercise... Naltrexone is a pure opiod antagonist.

Clinical studies indicate that 50 mg of naltrexone hydrochloride will block the pharmacologic effect for periods as long as 24 hours. No booster is required after such a short a period of time as 6-8 hours at a minimum, and even then only with advice from a doctor.

Following oral administration, naltrexone undergoes rapid and nearly complete absorption with approximately 96% of the dose absorbed from the gastrointestinal tract. Peak plasma levels of both naltrexone and 6-β-naltrexol occur within one hour of dosing.''

This information above is quoted by Dr Eskapa from the Naltrexone Package Insert and Clinical Trials.

Also, he goes on to say that in continuous drinking.....

''In fact if 50 mg are taken every 4 hours in a 24 hour period the dose would be 300 mg / 24 hour period - the maximum dose and it would tax the liver unnecessarily -- and without benefit''


Therefore after consulting with Dr Eskapa himself, your comment will not be published on my website on this occasion as I prefer readers to take advice on the booster tablet situation direct from Dr Eskapa.

4. Lastly, I would also ask that you remove both Naltrexone Confidential AND myself personally from your newly formed google+ Unchained Mouse circles. I do not wish to be in your google+ circles. Since you consider me to be your 'First TSM Enemy' (as per a previous post on this forum) I do not understand why you would want me in your circles. I have consulted Google on this matter, and they advise me that I can request you to remove me. If you do not remove me, then I will advise google of this.

I wish you all the best on a personal level but am disappointed that you have seen fit to do nothing than constantly criticise Naltrexone Confidential throughout your time on this forum.

Is this sentence correct? I should think it should read:

"We do not want, from a Sinclairian point of view, opioid blockade when there is [] reinforcement coming from positive endorphins - such as exercise." i.e., the protocol wants the naltrexone to be flushed prior to positive reinforcement from exercise.

Yes you are correct I think BV, but....


I copied the text exactly from the response Dr Eskapa emailed me back so at least I could not be accused of altering his wording to fit the facts I want it to fit. He has likely mistyped here, I think.

Joanna.

Okay, thanks. I agree that one should not change RE's text. Maybe he'll revise it. Maybe he's referring to the neuroscience professionally, which is not intuitive for us.

I have two longstanding questions that perhaps you could address in your FAQ.

a. What is the recommended, clinically validated interval over which to achieve extinction? That is, does one take naltrexone for 30 days with alcohol? 60? 90? 180? I have never seen this question addressed by Eskapa.

b. What is the recommended number of alcohol units to consume daily with naltrexone in order to achieve maximal extinction? Currently I take 2.

Naltrexone has an immediate impact on me and after a few days I wish not to drink or take the pill. But I wish to create maximal extinction effects, and thus these two questions have relevance. If you can point me in the direction of some reliable answers, I'd appreciate it. Otherwise, again, I recommend these two for your FAQ, because Sinclair must have the data from his clinical studies. Even if it's an "everybody's different" answer, there will be a distribution of results, and there will be a mean.

Hi again BV,

I have some of the clinical data 'paperwork' that Roy forwarded to me for my research and general interest.

I would be happy to forward this onto you.

As for your questions they are two very good questions and I will be the first to admit I don't know the answers to!

My understanding (though it could be wrong) is that the answer to your questions would be the same - and that would be that the book advises to drink 'as you normally would'. So, if you drank say 5 times a week, at say 6 units per session then you would not alter this to try achieve extinction quicker, but just continue with your normal drinking routine until extinction occurs.

If you would like to drop me a quick email to Joanna@naltrexoneconfidential.com I will forward the pdf files that I have to you (they are interesting to read anyway) and also give you Dr Eskapa's email so you can ask him directly. Like I say, I am very much one for putting people to the correct source if I am not 100% sure of the answer to any questions.

Once you have emailed me, keep an eye on your junk folder. I have found that sometimes my initial reply to a query drops into the junk folder. I do not know if I can attach a file if I pm'd you on here as I am not used to this forum and do not visit often. I was only here today as I felt a reply was needed when I was told what had been posted.

Joanna.

Joanna:



Well, I don't know what "extinction" is-- because the first day on Nal I lose interest in alcohol. I think it's a lot deeper than that. Second, the first day on Nal I have to force myself to drink. As Melissa said, it really is a sledgehammer. BarryB told me his experience is not dissimilar.

I did not drink lightly, as my earlier posts discuss. As in, when in the field I might start the day with a hit while waiting for the coffee.

I think it's crucial to understand what the mean daily alcohol ration is to effect extinction. And to understand what the mean number of days to extinction is. Whatever the mean is, I'm going to emulate. They cannot have completed all these studies without this info being documented and vetted. It's very curious that no one knows what these numbers are.

Thank you for replying and I will email you. Subject line with be "BV from TSM".

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