Sinclair method, naltrexone, and genetics geek-out thread

[EraserHead]

I've learned a few things reading about the science behind the use of naltrexone for the treatment of alcohol dependency, so I thought I'd start this thread as a place to collect and discuss that information.

One of the compelling things about naltrexone, aside from the many endorsements by the good people at this site, is that body a of scientific evidence supports its efficacy.

One interesting area of research involves a genetic mechanism that correlates well with naltrexone treatment. A couple interesting studies are:

A micro opioid receptor gene polym... [Psychopharmacology (Berl). 2009] - PubMed - NCBI
An evaluation of mu-opioid receptor (OPR... [Arch Gen Psychiatry. 2008] - PubMed - NCBI

...among many others.

Let me first summarize the scientific theory, as I understand it (please correct me if I say anything wrong): Certain people who show alcohol dependency may do so because their brains produce more happy juice (dopamine) when they drink alcohol, which acts as a reinforcement mechanism. This juice is due to opioid receptors that become more active in some people than in others when they drink alcohol. The increase in activity for some people can be traced to a single genetic polymorphism (i.e., the letters on a single gene) that will cause production of a protein called Asp40, rather than a different protein called Asn40.

The gene location in question is OPRM1, or SNP rs1799971, or position 154360797 on Chromosome 6. It's also referred to as A118G. It can take one of two different nucleobases: A (adenine) or G (guanine). Every SNP has two nucleobases on it. So in this case, either you are homozygous (both letters are the same) with AA (Asn40/Asn40) or GG (Asp40/Asp40), or you are heterozygous (one of each letter) with AG (Asp40/Asn40).

You can find this info here:
Rs1799971 - SNPedia

The standing theory is people who are GG or AG at this location produce Asp40 (while AAs only produce Asn40), and the Asp40 protein leads to the greater opioid response to alcohol. The naltrexone interferes with that greater response, so these people are better candidates for nal treatment. Indeed, a number of studies have shown that Asp40 carriers show better outcomes with naltrexone, while homozygous AA people don't seem to do any better taking nal than they would just taking a sugar pill placebo. (Though a sugar pill must taste better than the nal!)

There have been some criticisms of the findings of these studies, which should be taken into account.

TL;DR: If you do not have a "G" at location rs1799971, studies imply that naltrexone treatment probably won't help you much.

That said, I had my own genome sequenced by 23andMe last year (they do it for $99), and my own value at this location is AA. So in theory, the naltrexone would be wasted on me. However, as I've said elsewhere, I definitely have noticed some effect. So I'm going to continue to take it and see what happens.

If anyone else has access to their genetic information, I'd be curious to see how this has panned out for other people. If you've done 23andMe, you can access your particular SNP here by logging in to your account and then going to this link:

https://www.23andme.com/you/explorer/snp/?snp_name=rs1799971

Cheerio

[spiritwolf333]

Sinclair method, naltrexone, and genetics geek-out thread

HI Eraser -I find your posts detailed, thorough, relevant, and to the point. Your links to other areas of information are great!

If you had not told me that you were a part time drunk, I would never have believed -at least by my reading your writings.

I have my DNA readings -just by another site and those were for family genealogy. I am now wondering if these results would be relevant for the naltrexone information purposes and even other genetic based alcoholism purposes?

Once that I had started Baclofen and found that it was working, I was not interested in taking the Naltrexone that had been prescribed to me. (I did try it for three days concurrently with Baclofen so that was probably a waste.

After many discussions with others and conducting my own research, I found out that Naltrexone does NOT address the anxiety and depression that I was experiencing. (However, by not drinking for a bit of time, anxiety and depression will reduce automatically.)

Thanks for the thread and your post format.

[Molly78]

Sinclair method, naltrexone, and genetics geek-out thread

Thanks, EraserHead, I hope others will visit this thread, despite it being for geeks according to your title, because you have started an interesting discussion about medication generally, & the genetics of alcoholism, which is important in a wider sense (anyone else got children theuy are worried about???)

The first paper seems to imply that all the subjects relapsed eventually, but some took longer than others, which doesn't seem encouraging. This might be an erroneous impression from only having the abstract, but I doubt I would be up for plowing through the whole paper.

The second one gives a 50% response rate for placebo, compared to about 80% for naltrexone (hope I have recalled the info from the papers correctly, I can't do that clever computer thing of having 2 windows open at once), which again I don't find particularly encouraging - I mean, all those people on this forum taking herbal remedies & doing meditation will get a placebo response close to that. Not knocking the placebo response - it's incredibly useful, & doctors don't make enough use of it, mainly because they aren't allowed to actually prescribe a placebo! Just saying that taking a medication with recognised side effects apparently doesn't give you a huge advantage over something that won't give you any side effects at all!

DOI: I'm coming from the same place as spiritwolf as a confirmed disciple of baclofen. We haven't got the clinical trials for it that naltrexone has, so who's to say we aren't having a placebo response?!! I am fairly certain I'm not - I recently tried to drop my total daily dosage, convinced by others posting here that maintenance dose could be very low. So I should have continued to respond, according to the placebo response. But I didn't, had some successive days of drinking (nothing like as much as before, but it worried me) so I have gone back up again.

[Samandkatharine]

Sinclair method, naltrexone, and genetics geek-out thread

I did 23 and me. Unfortunately it doesn't address the paternal side if you are a woman. My screwed up genes are from my Dads side of the family:nutso: I would have loved to have had the information there.

Sam

[EraserHead]

Sinclair method, naltrexone, and genetics geek-out thread

spiritwolf, thanks for the compliment! I think one way that I am able to do this is to treat it like an experiment (with one subject!), rather than as a health or self-help effort. I think when I am able to "objectify" the situation -- distance myself from it -- it seems more manageable, and also more interesting. (I've often felt like "working on myself" feels too self-involved.) Anyhow, I do think that being a high-functioning alcoholic is perhaps the most dangerous kind to be, as you're always able to convince yourself that there is no problem....

Anyhow, what company did your DNA readings? The bottom line is, if you can get ahold of your raw sequence data from them (and you should be able to -- after all, they're YOUR genes!), then you should be able to look at your values at location rs1799971 (or position 154360797 on Chromosome 6) and see if you have a "G" there or not, which supposedly corresponds to the naltrexone responsiveness. I'm not sure if there are genes related to Baclofen response, but it would be interesting to do some research and find out if there were.

But you touch on an interesting point, which is that people drink for all kinds of reasons (anxiety being a big one), and these reasons need to be addressed in concert with the pharmacological approaches. In the studies I cited above that implicated the Asp40-producing gene, NONE of them implemented what you might call a "Sinclair Method" protocol, for which an outcome might have looked quite different. Our knowledge is growing quickly on these issues, but it's still very limited!

And Molly78, I know what you mean about the children. The first thing I did was also look at my child's gene in the same location, to see if the values were the same. Anyhow, I wouldn't read too much into the implication that "all subjects relapsed".... Without reading the full paper, we don't know how they defined "relapse" or what the observation period was. It could be that they simply meausred it by asking people at the end if they'd had a drink during the 12 weeks of study, and if so, when? If that were the case, then their results are reporting that (a) an equal number of people in both Asn40 and Asp40 reported not having a drink at all during that time, and (b) for those that did, the Asp40 people waited significantly longer on average. But without reading the methodology in detail, it's hard for us to know!

Also, on the 2nd study, we don't know the variance of the outcome rate. But they basically said that 87% of Asp40 carriers treated with nal had a "good outcome," while Asn40 treatment group and placebo groups all looked similar to each other (at around 50%). But yeah, a 50% placebo effect is pretty strong!

This brings up a question I've asked myself, having "felt" that nal was working but then realizing that I don't have the genotype associated with naltrexone efficacy in the experiments: It is entirely possible that I read about nal on this board, read about other people's experiences, tried it myself and "experienced" those same effects, when in fact the drug itself was doing nothing -- a total placebo effect! Though even last night I feel the same symptoms again, and it is phenomenally quite real. It doesn't seem to me like that is the case, but it could be true! And even if it is, does that even matter??

Sam: I'm not sure what you mean when you say 23andMe "doesn't address the paternal side." Half of your genes came from your father's side, no matter what gender you are; the question is whether you got the good ones or the bad ones! ;-) But the main thing is what your own readings are, which you should already have available to you now. If you log in and click the link I posted above, you should be able to see your Asn40/Asp40 value. If you feel like sharing, let us know what it is!

[Molly78]

Sinclair method, naltrexone, and genetics geek-out thread

If it is the placebo effect, EraserHead, it doesn't matter at all! The only problem is, once you start to think this way, it's a slippery slope to thinking "This medication isn't doing anything". It's your faith in it that's important - though having said that I have read an amazing study where doctors told their patients "I am giving you a tablet which contains no active ingredient" & STILL got a significant placebo effect. I must look for that paper again, I think it was quoted in a book I read about the placebo effect. Sometihng about the consultation, having someone take an interest in your symptoms? I can't fathom it!

In the UK the argument rages about whether homeopathy should be available on the NHS since it has no research basis. Someone has pointed out it saves us a fortune in the cost of "real" medications & gives excellent results to a population of patients who have intractable symptoms - all thanks to the placebo effect!

[guapo]

Sinclair method, naltrexone, and genetics geek-out thread

Believing

It sure helps to believe in the approaches to fix the drinking problem. Since I did that, it's all been uphill (Naltrexone, etc), and other strategies. The law of good Karma is that positive thinking and optimism brings those results !!

[gracieb]

Sinclair method, naltrexone, and genetics geek-out thread

Thought this might be of interest to some of you:

http://www.recoveryranch.com/article...om-alcoholism/

Basically, the idea is that if you love spice you are more likely to have problems w/alcohol genetically.. BUT it also means nal may be more effective for you genetically as well.

I LOVE spicy food. I put raw jalapenos on most of what I eat and I don't take out the seeds. I almost feel like I can't taste anything unless I put some spice on there.

The nal seems to be working for me. I have been tracking for the past few weeks and my intake is steadily going down without much effort. I do think that for me, this is the ticket.

Hope everyone is doing well.....

[gracieb]

Sinclair method, naltrexone, and genetics geek-out thread

Sorry for the double post. Got confused with my tabs there....

[spiritwolf333]

Sinclair method, naltrexone, and genetics geek-out thread

gracieb;1680025 wrote: Thought this might be of interest to some of you:

http://www.recoveryranch.com/article...om-alcoholism/

Basically, the idea is that if you love spice you are more likely to have problems w/alcohol genetically.. BUT it also means nal may be more effective for you genetically as well.

I LOVE spicy food. I put raw jalapenos on most of what I eat and I don't take out the seeds. I almost feel like I can't taste anything unless I put some spice on there.

The nal seems to be working for me. I have been tracking for the past few weeks and my intake is steadily going down without much effort. I do think that for me, this is the ticket.

Hope everyone is doing well.....

Very interesting Graci -I too love hot spices with my food. (Jalape?os, Red Pepper, etc). On some occasions I can just eat bread and jalape?os. I almost crave hot spices with food. As I said -interesting.

[YouKayBee]

Sinclair method, naltrexone, and genetics geek-out thread

Makes a lot of sense - enjoy rewards system = enjoy addiction.

I too like chillis but have also been caught out by them in Thai and Chinese food:H

[Lostinspace]

Sinclair method, naltrexone, and genetics geek-out thread

Uh oh. Fellow spice lover here. In fact, I barely enjoy food that's not loaded with spicy goodness. The other thing that article suggests though, is that large amounts of spice seem to have a similar effect (in suppressing desire to consume excess alcohol) that naltrexone does, at least in rats bred to have alcohol problems. As someone who frequently ate VERY spicy food while drinking 24/7, I find this somewhat disappointing. I don't think we'll ever find a definitive link between which individuals will respond to which medication and who won't. It'll always be a little trial and error.