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 Post subject: Increasing efficacy of NAL?
PostPosted: Mon Mar 26, 2012 4:20 pm 
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Posts: 156
Hello everyone. First an important disclaimer:

I AM NOT A MEDICAL DOCTOR.

I am a scientist, but I study cancer not opioid receptors. Anyway in my reading about NAL on pubmed today, I came across this article:

http://www.ncbi.nlm.nih.gov/pubmed/22056608

Which states that ORAL naltrexone has a modest effect on ethanol intake in rats, but if the treatment is preceded by oral loperamide administration, it becomes as effective as injected naltrexone (>2x greater reduction in drinking levels). The authors claim this is because of the mu-opioid receptors in the gastrointestinal tract affecting availability of naltrexone.

Anyway, I only bring it up because loperamide is the active chemical in many anti-diarrheal OTC medicines, like Imodium. Has anyone here ever taken naltrexone while on Imodium, and if so did you notice any difference? Thanks!

_________________
Former out of control, literally fall-down and piss-yourself Black Label fiend. First dose of Nal 3/29/2012. Transformation became undeniable on 5/18/2013. The bottle used to scream my name, but now it has shut up.


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 Post subject: Re: Increasing efficacy of NAL?
PostPosted: Tue Mar 27, 2012 11:51 am 
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Crazy, never heard of this. Chances are, if I'm taking Immodium, I'm not drinking lol but it's worth a try if someone wants to be a guinea pig!

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Attempting to keep my drinks below 3 for each session, and below 10 for the week.


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 Post subject: Re: Increasing efficacy of NAL?
PostPosted: Sat Mar 31, 2012 10:56 pm 
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I wouldn't take a single rat paper very seriously (as a researcher you are probably aware that majority of published papers are wrong, right?).

To get back to humans: if availability of naltrexone were a limiting factor (say, by the stated mechanism of peripheral receptors competing for the drug) then one would expect a sharp dose-dependence in at least some range of concentrations. So if loperamide were to be helpful, a simple doubling of the dosage would have been felt with regard to CNS effect (if any, of course). Which does not seem to be the case - several human trials of naltrexone included different dosages and there were no obvious differences above ~ 50 mg daily. Some people do report that 100 mg seems to work better but none of it is solidly documented. I experimented with 100 mg and saw no improvement - and in every respect naltrexone has very mild effects on me. In addition, I'd guess that GI mu-opioid receptors are not a major target of naltrexone in humans. If they were, wouldn't naltrexone have significant effects on GI tract? As opposed to a very mild side effect observed among minority of users?

If you do decide to experiment, please report back. Knowledge is good but nothing beats real experiments :-)


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 Post subject: Re: Increasing efficacy of NAL?
PostPosted: Mon Apr 02, 2012 12:14 pm 
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I have to say... your tone is quite dismissive/disrespectful. It seems weird to try and discredit me to refute an argument that I didn't make.

In fact, I made a point to say that this isn't my exact field of study, then posed the question of whether people had any experience with coincidentally being on nal and imodium simultaneously.

There was a time in my life when I would have been willing to get in to this kind of posturing to argue about a paper, but those days are long gone for me. I was just asking a simple question to try and gather data if they are out there.



Nutella wrote:
I wouldn't take a single rat paper very seriously (as a researcher you are probably aware that majority of published papers are wrong, right?).

To get back to humans: if availability of naltrexone were a limiting factor (say, by the stated mechanism of peripheral receptors competing for the drug) then one would expect a sharp dose-dependence in at least some range of concentrations. So if loperamide were to be helpful, a simple doubling of the dosage would have been felt with regard to CNS effect (if any, of course). Which does not seem to be the case - several human trials of naltrexone included different dosages and there were no obvious differences above ~ 50 mg daily. Some people do report that 100 mg seems to work better but none of it is solidly documented. I experimented with 100 mg and saw no improvement - and in every respect naltrexone has very mild effects on me. In addition, I'd guess that GI mu-opioid receptors are not a major target of naltrexone in humans. If they were, wouldn't naltrexone have significant effects on GI tract? As opposed to a very mild side effect observed among minority of users?

If you do decide to experiment, please report back. Knowledge is good but nothing beats real experiments :-)

_________________
Former out of control, literally fall-down and piss-yourself Black Label fiend. First dose of Nal 3/29/2012. Transformation became undeniable on 5/18/2013. The bottle used to scream my name, but now it has shut up.


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 Post subject: Re: Increasing efficacy of NAL?
PostPosted: Fri Apr 06, 2012 12:18 am 
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Quote:
I have to say... your tone is quite dismissive/disrespectful.


Wow, you sure have a thin skin. Sorry if I unintentionally struck wrong nerve. Nothing personal was ever intended!

You speculated (quite interestingly) based on a single paper and with little regard to the surrounding issues. I merely commented on why I felt that it did not sound very plausible. It's an experimental issue of course and you may be right - it's just that I view that possibility as unlikely (for the reasons I quickly outlined). This isn't a paper review situation, so please relax - we aren't earning points here. Like I said, I'd be very interested to hear from your N=1 if you decide to experiment but the theoretical basis is not enough for me to possibly contribute to being N=2. I don't see anything disrespectful in stating this simple fact.


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 Post subject: Re: Increasing efficacy of NAL?
PostPosted: Sat Apr 07, 2012 11:31 am 
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Hehe, yeah, I probably overreacted there a little bit. It's my hot headed nature. I likely misread your tone because where I do science things tend to be subtle; no one would ever talk to a colleague they respect like you are talking to me. I am, however, totally willing to believe that it was only a perceived slight, so thank you for your apology and I am sorry for misconstruing your meaning.

Anywho, this is the part where I re-iterate (three-iterate?) that I didn't speculate anything. I posted a link to a paper and asked if anyone had any anecdotes in support of the authors' findings. I won't argue the paper because that would amount to a tacit endorsement, which I won't give.

_________________
Former out of control, literally fall-down and piss-yourself Black Label fiend. First dose of Nal 3/29/2012. Transformation became undeniable on 5/18/2013. The bottle used to scream my name, but now it has shut up.


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 Post subject: Re: Increasing efficacy of NAL?
PostPosted: Sat Apr 07, 2012 12:53 pm 
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I read the synopsis. I don't have any particular experience with imodium and naltrexone, I think I took it for two days my entire stint (airline food.)

But I did find this statement interesting: "oral naltrexone only had modest effects on ethanol intake, and the response was not dose-dependent." That runs counter to the experience of those on this board. Either the rats have been given naltrexone before, i.e. no honeymoon, or there is something different about them.

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Pre TSM: 80-90 au per wk, Regained Control May, 2012.


After control: 3-6 units per month, 25+ alcohol free days!


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 Post subject: Re: Increasing efficacy of NAL?
PostPosted: Sat Apr 07, 2012 2:10 pm 
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Hahahaha! Airline food has a way of... speeding up your digestion I suppose.

Good point HF about the honeymoon and the differences in response. Seems likely to me that psychology is playing a larger role in humans than in rats... I am sure many of us have been white knuckling for so long that when something finally comes along to help lighten the load, it feels amazing to finally loosen our grips. Rats I am sure don't put themselves through such exertions. Oh to be a rat sometimes.

_________________
Former out of control, literally fall-down and piss-yourself Black Label fiend. First dose of Nal 3/29/2012. Transformation became undeniable on 5/18/2013. The bottle used to scream my name, but now it has shut up.


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 Post subject: Re: Increasing efficacy of NAL?
PostPosted: Tue Apr 10, 2012 10:22 pm 
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Quote:
"oral naltrexone only had modest effects on ethanol intake, and the response was not dose-dependent." That runs counter to the experience of those on this board.


Actually, it does not. Best I could tell from following this BB for 2.5 years is that users' experience is all over the board. Some really do experience only modest decrease (and some not at all). In the range 25-100 mg/day, dose dependence, if there is one, does seem to be rather flat. But yes, rats are not humans. That's why it would be so lovely to see a large double blind human trial clearly demonstrating TSM effectiveness. Alas, there does not seem to be one. Those few that exist are all small and really do show only modest effects.


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 Post subject: Re: Increasing efficacy of NAL?
PostPosted: Wed Apr 11, 2012 8:55 am 
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If the rats responded like this board, the description would be something like "responses varied widely" not "oral naltrexone only had modest effects on ethanol intake," even based on your correction for the wide variation. Our posters have done everything from over 50% to no effect.

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Pre TSM: 80-90 au per wk, Regained Control May, 2012.


After control: 3-6 units per month, 25+ alcohol free days!


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