the chemistry of drinking while taking alcohol and other things

[henry]

As regards taking baclofen while taking alcohol, its effect on hangover and withdrawal symptoms must vary from individual to individual. It has in fact been my experience ? and not only mine ? that taking baclofen while taking alcohol greatly subdues the hangover and withdrawal symptoms the morning after ? in fact makes them really nonexistent. This may of course be a poisoned chalice: it may lead one to think that one can take alcohol the night beofore while taking baclofen - and not suffer the hangover and withdrawal effects that lead us to want to drink immediately on waking up.

The reason for this latter phenomenon that we experience as a craving for alcohol ? and is sadly our alcoholic downfall - appears to be the neuroadaptation that the brain uses to restore balance to the brain on its reception of alcohol. It involves the inhibitory effect of alcohol on the GABA system ? the main inhibitory system in the brain - and the compensatory balancing effect of increased glutamate production and activity ? the major excitatory neurotransmitter in the brain.

When a person consumes alcohol, its acute effect (which often is the effect the person is seeking) is to unbalance the neurochemical equilibrium of the brain, thereby tilting the brain like a seesaw. If the alcohol exposure continues, the brain institutes an opposing adaptation (neuroadaptation) to balance the effect of the alcohol and restore neurochemical equilibrium. This it does by increasing glutamate production and excitatory activity thus compensating for the inhibitory effects of alcohol. But this means that the brain develops tolerance for the drug. And it also means that the brain is also in a state of physiological dependence at this point: when alcohol exposure ceases, the new neuroadaptation now unbalances the brain?s neurochemistry. And, like tilting the seesaw to the opposite side, the unbalanced adaptation produces a functional effect on the brain (i.e., the withdrawal syndrome) that is opposite from the effects originally produced by alcohol. This is caused by the increased Glutamate production and activity in the excitatory system in the face of the withdrawal of alcohol?s effects on the inhibitory system.

Now according to Ameisen?s theory one major reason we become alcoholics is because of a GABA deficiency. But it can also be that that GABA activity decreases anyway (again through neuroadaptation because of excessive alcohol intake). As a result when we cease taking alcohol, we have an unbalanced excitatory activity brought about by the glutamate system ? hence the awful experience that we alcoholics have the morning after. Hence also the desire to drink alcohol first thing in order to counteract the excitatory activity of this system. But if we take baclofen ? which binds on the BABA B receptors (our saving grace here is that alcohol does not bind to the b receptors!) ? we do have a counteracting compensatory effect to the excitatory activity of the glutamate system. And this is the reason ? at least in my case and others I know ? why there is not remotely the same desire to drink alcohol first thing after having taken baclofen (say last thing before going to bed) with alcohol the night before. I should add that I reached the switch at taking 275mg for two months so have no desire to take alcohol at all now. So all this is in the past while tritrating up slowly.

This leads to a concern that has recently been raised in another context. This is the question whether one should remain at one?s switch level as has been recently be attributed to Dr Ameisen or follow his method of tritrating down as he did before he apparently changed his mind. I would find it extremely inconvenient to remain at 275mg since it caused an extremely dry mouth for one thing which was rather unpleasant. But if it turned out that there was good evidence for this new advice (and thus far we have not been given reasons if the good doctor has changed his mind) then I for one would have to accept that the costs of taking baclofen at this level for the rest of my life is far far surpassed by the cost to me of taking alcohol in the way that I have done. Baclofen is not a toxic drug like cancer chemotherapy is ? so if need be I will follow this new advice (though I like many others await the reasons).

Note: There are a substantial number of neurotransmitters in the brain. Four of the most important with respect to alcohol are glutamate, gamma aminobutyric acid (GABA), dopamine (DA), and serotonin. Glutamate is the major excitatory neurotransmitter in the brain. Ethyl alcohol acts to inhibit a subset (N- methy-D-aspartate, NMDA) of glutamate receptors, thus diminishing the excitatory actions of glutamate. GABA is the major inhibitory neurotransmitter in the brain. Alcohol acts primarily at the GABAa receptor to facilitate its action, thus in essence creating enhanced inhibition. Changes in the number of both NMDA and GABA receptors and ability of these receptors to bind their neurotransmitters appear to be involved in the development of tolerance to and dependence on alcohol. Baclofen binds to GABAb receptors just as GABA does. The third important neurotransmitter in alcohol action, Dopamine, is involved in reward processes and thus seems to be responsible for the rewarding aspects of alcohol consumption. Other things that people find rewarding such as food, sex, and other drugs of abuse also act to release DA in the brain. Serotonin also appears to play a role in reward processes and therefore seems to be important in alcohol use and abuse. In addition, serotonin is a prominent player in mood states, compulsive disorders, aggression, and effects of other drugs of abuse like methamphetamine and LSD.

[Topsy-Turvy-Tracy]

the chemistry of drinking while taking alcohol and other things

"Now according to Ameisen’s theory one major reason we become alcoholics is because of a GABA deficiency. But it can also be that that GABA activity decreases anyway (again through neuroadaptation because of excessive alcohol intake)."

Then a prolonged period of being alcohol free should result in a "normal" person with a "normal" desire for alcohol. I've been without alcohol for six months - I never got anywhere near normal, so I suspect Ameisen is correct.

Glad the bac is working for you!

[henry]

the chemistry of drinking while taking alcohol and other things

thanks Tracy: if I understand you correctly, the reason an alcholic cannot go back to drinking normally even after prolonged abstinence is because the biochemical changes to the brain remain. ie on drinking alcohol after say a year without, the same excitatory system kicks into compensate for the onrush of alcohol into the brain. it does not revert back to its state at say 14-18years of age (if only!) but remembers what it did the last time it received alchol (a year, two years ago, whatever). Then you are kind of back to square one except that you know you have had a years abstinence and know that if you have done it once you can do it again (except the depressing thought hits you that this cycle of abstinence and bingeing will never cease). Until in my case baclofen came along - as I am sure it did in the case of many of us here!

On the matter of taking alcohol while taking baclofen: my experience was that I fell asleep much earlier in the evening and sometimes I was out literally like a light - quite unlike me. I explain this by the fact that both alchol and baclofen work on the inhibitory system - the former on the GABA a receptors the latter on the GABA b ones. For the record the greatest danger of taking both was that you could conk out - not due to drunkenness - and if this occurred outside the home it was dangerous. it happened to me twice - one minute I was fine and the next minute I was not! This obviously is one more reason not to drink while taking baclofen!

Do you happen to know for how long one is automatically logged in? My email above had to be rewritten from memory because as I was writing in as a post in this system it had logged me out without my knowing it. So when I submitted it it simply disappeared into the internet stratosphere never to be seen again (from now on I will write them first as Word documents!)

[henry]

the chemistry of drinking while taking alcohol and other things

My experience of conking out happened on a train literally one stop before my destination. i ended up 20 miles away from my destination and had to grap some sleep in a church graveyard. it wasnt too cold a night! but i couldnt believe how quickly it had happened. One minute I was fine and the next minute not: out like a light! i didnt even have the opportunity of trying to stay awake (a bit like the effect an anaesthetic has on you before an operation!)

[Publius]

the chemistry of drinking while taking alcohol and other things

That's a great post Henry, I love that you've looked at the other effects on the brain other than just what is going on with GABA. I too have noticed less of a hangover with baclofen, but that hangover I am used to is hardly the only reason I drink. I think, and I am far from an expert, that the GABA deficiency, while possibly exacerbated by the long term alcohol use, was present prior to using alcohol. I think that the compensatory reactions happening in the brain as a result of heavy alcohol use probably probably go back to normal, or reset themselves, after a time of limited alcohol use, making proper transmission of GABA the most important factor in treating this affliction. As for the question on a lot of people's mind regarding staying at the threshold dose, while I don't have a definitive answer, I can speculate that logically, when someone has reached their threshold dose of baclofen, their GABAb receptors are fully saturated with GABA, making the alcohol totally ineffective and unnecessary when used, as alcohol acts as a substitute chemical for the GABAb receptors. Tapering off to a maintenance dose would leave less than saturated GABAb receptors, leaving the subject susceptible to relapse. That is pure speculation, but it's all I've got. I'm sure there will be more information regarding that forthcoming, and I wouldn't be surprised if there is a happy medium reached, i.e. you're on 275 for threshold, maybe you taper to 230, hardly a 50mg maintenance dose, but close to threshold with lesser side effects.

[ignominous]

the chemistry of drinking while taking alcohol and other things

Henry

I find the title of this thread a little confusing "of drinking while taking alcohol",

However the rest of what you wrote is very informative. I followed with interest everything up to the last paragraph. Things like 'alcohol facilitates the GABA receptor which is an inhibitory neurotransmitter and therefore GABAb binders like Baclofen reduce GABA and therefore stop you wanting to be drunk', get lost on me. Maybe I'm trying to deal with too many unknowns at once. Any chance of a 101 guide to neurotransmitters and GABA. I think its about time I learnt what you're talking about!

EDIT: I'm talking about your first post.

[henry]

the chemistry of drinking while taking alcohol and other things

ignominous;975905 wrote: Henry

I find the title of this thread a little confusing "of drinking while taking alcohol",

However the rest of what you wrote is very informative. I followed with interest everything up to the last paragraph. Things like 'alcohol facilitates the GABA receptor which is an inhibitory neurotransmitter and therefore GABAb binders like Baclofen reduce GABA and therefore stop you wanting to be drunk', get lost on me. Maybe I'm trying to deal with too many unknowns at once. Any chance of a 101 guide to neurotransmitters and GABA. I think its about time I learnt what you're talking about!

EDIT: I'm talking about your first post.

Ignominous

This is the paragraph you refer to: I simply put it in for information - as a kind of footnote providing a glossary of terms.

'Note: There are a substantial number of neurotransmitters in the brain. Four of the most important with respect to alcohol are glutamate, gamma aminobutyric acid (GABA), dopamine (DA), and serotonin. Glutamate is the major excitatory neurotransmitter in the brain. Ethyl alcohol acts to inhibit a subset (N- methy-D-aspartate, NMDA) of glutamate receptors, thus diminishing the excitatory actions of glutamate. GABA is the major inhibitory neurotransmitter in the brain. Alcohol acts primarily at the GABAa receptor to facilitate its action, thus in essence creating enhanced inhibition. Changes in the number of both NMDA and GABA receptors and ability of these receptors to bind their neurotransmitters appear to be involved in the development of tolerance to and dependence on alcohol. Baclofen binds to GABAb receptors just as GABA does.'

Baclofen is essentially a substitute for GABA (Gamma-Aminobutyric acid). GABA as I understand it binds to both a and b receptors (both the GABAb and GABAa receptors are inhibitory receptors causing an inhibitory effect on the CNS). But baclofen a derivative of GABA only binds to the GABAb receptors Alcohol does not bind to the GABAb receptors which is our saving grace since it allows space for drugs such as baclofen to bind to the GABAb receptors. The consequence of this is that when we stop drinking alcohol - and fall sleep for example which means we are effectively withdrawing alcohol from our bodies - the excitatory system which has overcompensated kicks in to our sad detriment and gives us these horrible withdrawal symptoms that normally require immediate alchol intake. Except when we have taken baclofen which provides significant compensation to the excitatory condition of our brains.

I take your point about the title being confusing! it started off as a response to a fellow member electron who was asking about the interaction between alchol and baclofen but in order to explain my own experience i found it necessary to take the email in another direction so it really fell between two horses - which is why I began a thread instead of adding to electron's thread!

Hopes this helps

[ignominous]

the chemistry of drinking while taking alcohol and other things

As clear as,,,,,,,,,,,,,,,,,,,,,,,,,,,Oh I've lost my train of thought again.

What is an inhibitory effect on the CNS?

If alcohol doesn't go for GABAb and Bac does why do we need less alcohol?

I seem to be on a different page here. I guess bit by bit it will sink in if I look long enough.

Is there a book called "CNS synaptic GABAb enhanced inhibitory receptors and the facilitation of excitatory bonding neurotransmitter related chemicals for Dummies"?

[PhoenixRising]

the chemistry of drinking while taking alcohol and other things

I am another for whom Baclofen LESSENS the effect of a hangover.

[ignominous]

the chemistry of drinking while taking alcohol and other things

Phoenix

I think you literally are on the wrong page. Maybe Electons thread?

LOL

[Publius]

the chemistry of drinking while taking alcohol and other things

hey this is a pretty decent article about the gaba business and isn't too hard to wrap your head around language wise. Interestingly, it was written all the way back in 2002...hope it helps

Research Reveals More About Alcoholism’s Complex Action on Brain — Psychiatric News

[henry]

the chemistry of drinking while taking alcohol and other things

Publius

I think Dr Ameisen's point is that there is a (genetically inherited?) GABA deficiency prior to taking our first drink but the other dimension is one that explains how we got to the inglorious state I myself found myself in is the following. I didnt say anything about this since it further complicates the point i was making regarding the relationship between baclofen alchol and withdrawal and may not be entirely relevant anyway. This is the reward process that occurs on taking alcohol. Essentially the thinking is this: alcholic-predisposed individuals are those who much greater reward from taking alcohol - so great that it outweighs any punishment it brings to our brains. Normal drinkers do not get this kind of reward (euphoria, reduction of anxiety etc). Normal drinkers normal state is not to drink unless there is a reason for drinking. Alcholic drinkers normal state is to drink unless there is a reason not to (which ultimately reduce to zero!). And this comes about due to the enhanced reward system in the alcholic brain - which is why some people say they knew they were alcholics on taking their first drink

I used the following site to provide a framework in which to place the more detailed information I used in the initial message I sent:

Alcohol Chemistry and You

This is what it had to say (I quote it in full!):

'The current thinking on the biochemical basis of addition: two general processes contribute to alcohol addiction.
1. A modified reward process where by drinking of alcohol provides an overall positive effect (euphoria or decrease in an unpleasant situation). This is coupled in those vulnerable individuals with a pattern of diminishing or ignoring the negative impacts of overconsumption - the hangovers, loss of memory, fights, violence and arrests. The less vulnerable individual equates heavy alcohol consumption as overall unpleasant as result of the negative effects outweighing the positive. It is this reward system that kicks in in an intense way given the alcoholic-predisposed individual brain.
2. Neuroadaptation where by the brain attempts to compensate for something (ethanol) which influences normal functioning.
Types of rewarding (positive) experiences gained after drinking include the taste of the alcohol itself and the feelings (e.g. relaxation) gained after drinking ethanol. One can also gain a positive experience by avoiding negative situations such as those felt in anxiety provoking situations (public speaking, attending a party) or avoiding the effects of withdrawal from ethanol (see below). The rewarding aspects of ethanol use involve the brain?s reward system. This system is comprised of brain structures and circuitry (e.g. ventral tegmental area, extended amygdala and the nucleus accumbens within) that appears to be important in the reinforcing (rewarding) properties of a variety of drugs.
The second process important in addiction has to do with the ability of the brain to adapt to influences, which affect its normal function. The ability is called neuroadaptation. For example, the drinking of one or two beers or one or two drinks (acute intake of ethanol) activates a variety of processes in the body and in particular impacts the functioning of the brain.

In order to keep the brain functioning normally, the brain attempts to chemically counteract whatever ethanol is doing to disrupt its action. A simple illustration is the reaction of the body if someone starts pushing it. The natural reaction is to compensate by correcting the balance and attempting to counteract the pressure of the push until the push is gone and the body returns to normal. Interestingly, neuroadaptation also sometimes results in an increased response to the drug (sensitization). Whether there is a diminished response or an enhanced response depends upon a variety of factors including the amount of the compound taken in and the timing of the intake. The development of sensitization to drugs such as cocaine may be more likely with intermittent exposure than with continuous exposure.

Alcohol
1. facilitates the action of the major depressant neurotransmitter in the brain (GABA) and
2. inhibits the action of the major excitatory neurotransmitter in the brain (glutamate).
alcohl acts at specific sites on a specific subset of GABA and glutamate receptors (protein molecules upon which the neurotransmitters act). By influencing the action of these receptors, alcohol "slows down" the functioning of the nervous system. Thus, ethanol is called a central nervous system (CNS) depressant.

With neuroadaptation, the brain attempts to counteract this depressant effect by increasing the activity of the glutamate system and decreasing the activity of the GABA system. This in part can be accomplished by altering the number or function of the receptors. [...] Through neuroadaptation the brain is able in many instances to up-regulate (increase) or down-regulate (decrease) its function to compensate for the presence or absence of ethanol. (It should be recognized that the body and the brain have an amazing ability to adapt and only in extreme situations or after damage, such as seen in alcoholism, do the regulatory processes fail).

If a person chooses to drink more regularly (chronic intake), the brain attempts to adapt to the increasing amounts of ethanol. Generally, neuroadaptation can take place up to a point. After chronic consumption and ongoing adaptation, it will now take more ethanol to produce the same effect as the first drink. When this is the case, tolerance has developed and substantial adaptation has taken place. If the person now chooses to quit drinking the body tries to return to its original state in doing so causes a number of withdrawal signs including tremors, seizures, nausea, and negative emotional states. Since further drinking will delay, diminish, or prevent withdrawal, the person often chooses to drink again. Even if the person stops drinking, the neuroadaptations that took place in the brain may persist for a period of time well beyond the time when ethanol is no longer present in the body. It has been speculated that these may be the source of the urges to drink again.

For most people it is relatively easy to modulate ethanol intake. Depending upon the vulnerability of the individual, as drinking progresses regulation of drinking becomes more difficult. Simultaneously, the ability of the brain to adapt is diminished or lost. Systems become increasingly disregulated, perhaps due to damage, so that in the brain communication and coordination diminishes or fails. This is particularly true after repeated withdrawals from ethanol, since the severity of withdrawal increases. Perhaps this is the reason for saying the drink appears to take on a life of its own.

"First the person takes a drink, then the drink takes a drink, then the drink takes the person".

In general there appears to be a general loss of control. The individual has lost control over drinking and neuroadaptive mechanisms have been overwhelmed. Thus alcoholism can be characterized as a disease with takes over the body and brain.'


Its very very good. The note or glossary I provided - which ignominous queried - was based essentially on a paragraph taken from one of the webpages from that site.

Ignominous - this website is a very good 101 things you wanted to know about!

[ignominous]

the chemistry of drinking while taking alcohol and other things

I nodded off about 5 times reading that last enlightening instalment Henry. And that was just the first paragraph.

I'm going to bed, see you all in 2 hours!

[Topsy-Turvy-Tracy]

the chemistry of drinking while taking alcohol and other things

henry;975862 wrote: thanks Tracy: if I understand you correctly, the reason an alcholic cannot go back to drinking normally even after prolonged abstinence is because the biochemical changes to the brain remain. ie on drinking alcohol after say a year without, the same excitatory system kicks into compensate for the onrush of alcohol into the brain.

Actually, I never said anything like that. I was countering your argument, not supporting it.

My point was that there was "already" something up, something different about the way my brain works - and it was so before I ever took my first drink. Alcohol is incidental - it didn't cause whatever is up, as you are claiming.

I don't know how long before we get bounced. If I know that I'm going to be long-winded, I use Word too.

[henry]

the chemistry of drinking while taking alcohol and other things

it has happened even when I have been short-winded!