Genetics vs. Weight

[PbarE]

I know that it was originally suggested that we use a formula (3.6 mg/kg) to determine the amount of baclofen necessary to hit The Switch. Now that formula is no longer used. The amount is determined by chemistry and genetics. I got this from beatle?s excellent thread about a conversation with Dr. L. (Thanks for the beatle!) It is the most current info from a doctor that I can find.

Does anyone know what genetic and chemical factors are used?

[bleep]

Genetics vs. Weight

As far as I know, that's the answer at the end of the road. "It's down to genetics" seems to imply that nobody knows when you'll reach indifference.

Again, we await results of studies to sort through all this.

[PbarE]

Genetics vs. Weight

bleep;1084333 wrote: As far as I know, that's the answer at the end of the road. "It's down to genetics" seems to imply that nobody knows when you'll reach indifference.

Again, we await results of studies to sort through all this.

Thanks, bleep. Any idea why it changed? Were people hitting the switch at less than 3.6 mg/kg rate?

[_serenity_]

Genetics vs. Weight

I can tell you that NE and I weigh the same amount, are very close to the same age, and had similar hard-drinking histories. And we hit our switches at vastly different mgs. I was 190 and she was at 300+. I can really see no rhyme or reason as to what dose "does" it for us.

[redhead77]

Genetics vs. Weight

I asked him about it Pbar and he told me that genetics seem to play the biggest part, but that really petitie woman might hit the switch a little faster. He said really petite like in exceptionally short and tiny. He said there is no rhyme or reason it seems. Drinking or not drinking. Although, in our last conversation he did admit that drinking while doing may increase the sides. He seems to be getting a little more open minded that even following a slow protocol that the sides do happen.

[Ne/Neva Eva]

Genetics vs. Weight

OA found indifference at that point, so I think the early bac-ees looked to that.
The studies on rats went up to 4mg/kg and that was OA's personal limit.

I think there is evidence of indifference being reached all over the place. Seethepony found it at less than 100mg/day. (can't remember now... 65mg rings a bell though.) I'm gonna assume that wasn't 3.7mg/kg in his case!
And what Serenity said is true. Same just about everything relevant! Vastly different mgs. Even now I'm maintaining at 240mg! 4mg/kg in my case...

[Murphyx]

Genetics vs. Weight

PbarE;1084361 wrote: Were people hitting the switch at less than 3.6 mg/kg rate?

It's all over the place. 1.2mg/kg in my case.

[beatle]

Genetics vs. Weight

I've been writing this for a while, so probably others have said this already... but...
I think the whole weight thing came in because OA mentioned that he reached indifference at 3.6 or 3.7mg/kg, which was about the same mg/kg level at which rats reached their natural indifference level.

Makes sense to me.

But not so, says Dr. L. (I've never heard if OA has since weighed in on this).

Dr. L says it is genetics and chemistry, and weight is not part of the equation.

Makes sense, too. Unless our brain weight is proportional to our body weight (in which case my brain would be miniscule... have I painted myself into a corner here?)

BUT, and an important point from our conversation was that Dr. L said that most people reach their switch at something like 240-280... (sorry, I don't remember the numbers exactly, and they changed a little during the course of our conversation)... so, why? And why do so many need to go far higher, and so many reach it at far lower levels? How is this related to the chemistry and the genetics?

I have not spoken with Dr. L again since that conversation, but when I do, my precise question would be to define the "chemistry" and "genetics" .

Genetics: We assume we know what this is-- but does it refer to a propensity, a latent trait ready to be triggered by something (in our environment or an event in our lives), or is it an inevitable part of our physiology?

Chemistry: This is the one I am most unsure about. If we are talking about the chemistry of the brain, and that the chemistry is off... well, I think we all more or less get that. My big question would be: is the screwed-up chemistry a result of the amount we have been drinking over the time period we are looking at, or is the chemistry already screwed up before the drinking starts? If the chemistry is screwed up from the start, isn't it the same as genetics, then?

[Lo0p]

Genetics vs. Weight

Dr. OA also reported in his study that weight and sex were not factors in the amount required.

In my mind this makes the entire mg/kg thing moot.

[Lo0p]

Genetics vs. Weight

Google translation of OA's study wrote: The results show that three months 88% of the patients were categorized as "success", and 12% as "failure." The doses of baclofen were required vary from one patient to another, ranging from 15 mg / day to 300 mg / day, with an average of 145 mg / day. About two thirds of patients required a dose greater than that allowed 80 mg / day. There was nothing to predict the dose needed before treatment, this dose did not appear related to patient body size or with sex (but accurate analysis was not done).

So...inconclusive I guess.

[Ne/Neva Eva]

Genetics vs. Weight

Pbar, I would add to the equation length of abuse of AL. (and other substances if you really want to muddy the waters!)

That said, I suspect I may have found indifference a *little* lower (but not much.) I was looking for the lightbulb moment, and not the decision-making moment. It was, for me, a decision making moment, and I have remained effortlessly abstinent since that decision. *when I have kept my bac dose constant.*
Good question, but I do think that a weight ratio went out of the equation a good while ago.

[ignominious]

Genetics vs. Weight

I think Beatle hit the nail on the head with the weight of the brain.

About 6 months ago we had a discussion about the half life of baclofen in the CNS versus the body. Maybe this leads to slightly different SEs but the main effect is due to the amount of baclofen in the CNS. All humans have a similar amount of Central Nervous System (brain) regardles of how big they are or how much they use it. Babies are born with big heads to accommodate it. It doesn't change in size by very much throughout your life.

So yes the size of the body has very little to do with the switch dose.

[beatle]

Genetics vs. Weight

brain weight

ignominious;1084710 wrote: I think Beatle hit the nail on the head with the weight of the brain.

About 6 months ago we had a discussion about the half life of baclofen in the CNS versus the body. Maybe this leads to slightly different SEs but the main effect is due to the amount of baclofen in the CNS. All humans have a similar amount of Central Nervous System (brain) regardles of how big they are or how much they use it...

So yes the size of the body has very little to do with the switch dose.

So if body size has very little to do with it, and most brains are more or less the same size in all people, that must mean those who require higher doses to hit their switch have bigger brains (even if just a little) Sigh. No end in sight for beatle:H

Seriously though, what I am most interested in is if the length of time and the amount of alcohol abuse are factors that affect the chemistry, and if this is what Dr. L is referring to when he says "genetics and chemistry" -- meaning the two factors would actually be 1) genetics, and 2) history of abuse.

If that is the case, Sigh. No end in sight for beatle:upset:

[Murphyx]

Genetics vs. Weight

beatle;1084718 wrote: meaning the two factors would actually be 1) genetics, and 2) history of abuse.

Nah, I don't buy that. I come from a long line of drunks (all my siblings, my parents, my uncles and aunts, grandparents and on and on and on) many of whom have died early from the drink and I had been drunk every day for 25 years, but yet I switched after 8 days and on only 150mg.

[ignominious]

Genetics vs. Weight

Genetics and chemistry. I was thinking about what he could mean. So this is my half baked take.

I think the genetics thing affects some of us more than others, some people have come on here and sworn they don't have anxiety or problems and don't self-medicate with alcohol. They purely enjoy the sensation and have become alcoholics. The type of brain deficiencies that we have due to genetics will be different for all of us. So some people will be a better fit for baclofen than others. Possibly Murph was a good fit - their seems to be a pattern in his genes but he reacted quickly to baclofen.

The chemistry will also blur with the genetics. Maybe my brain needs more 5HTP and yours needs more serotonin, or whatever. Separate from genetics is the fact that nerve pathways become more open (easier to travel down) if they are used more often. The nerve synapses require chemicals to work so if you have a long history of drinking I would think that nerve pathway can be likened to a highway (always open and no tolls). Maybe you would need ectra chemicals to open the alternative route enough to make it an attractive option.

Hope no one's offended or depressed by this!