Thoughts on Baclofen's anti-craving mechanism

[Colin]

What the heck is going on? We are just trying to find out what we can take to make us feel ok without the use of alcohol. Whatever GABA thing you two are talking about really does not matter.

So you are a philistine SF! That explains a lot.

[Spiritfree]

So you are a philistine SF! That explains a lot.

Wow Colen, you are brilliant. What the heck does "a philistine" mean? I guess that that is what I am if you say so (I hope that it is a good thing).

[Spiritfree]

It mattered to me because I wanted to know what affect baclofen had on my brain. I preferred to know what was physically going on with me. Apparently the gentleman also wanted to know.

Wow Kronkster, you have been taking Baclofen for 3.5 years plus and you are just now wanting to know what effect it has on your brain and your body? Goodness, I thought that you would have known the answers to these questions long before now?



--sf--

[kronkcarr]

Wow Kronkster, you have been taking Baclofen for 3.5 years plus and you are just now wanting to know what effect it has on your brain and your body? Goodness, I thought that you would have known the answers to these questions long before now?



--sf--

If you read my quote that you requoted you will see it is in the past tense. I learned how baclofen worked when I read Dr Ameisen's book before I started baclofen. I'd not heard the glass allegory.



It's sad that you try to bother me when I post.

[Spiritfree]

If you read my quote that you requoted you will see it is in the past tense. I learned how baclofen worked when I read Dr Ameisen's book before I started baclofen. I'd not heard the glass allegory.

It's sad that you try to bother me when I post.

Ok Kronkster -let us take a look at the current chain of events that lead you to make the statement "It's sad that you try to bother me when I post". (We all must recognize that I have not brought you/your avatar up in any conversation, post, etc -period- in a very long time.)

YOU MADE A POST TO ME -REMEMBER?:

"Originally Posted by Spiritfree View Post
What the heck is going on? We are just trying to find out what we can take to make us feel ok without the use of alcohol. Whatever GABA thing you two are talking about really does not matter.

(None of conversation had anything to do with you!)

"It mattered to me because I wanted to know what affect baclofen had on my brain. I preferred to know what was physically going on with me. Apparently the gentleman also wanted to know." --Kronk--

What/who "gentleman" are you referring to? What did that gentleman want to know? What was his question?

Kronk -seriously? You are a much better troll than I ever thought you to be.... I under estimated your trolling abilities... I took your bait. You got me this time.

Kronk, what you are doing is intentionally trying to discredit me and cause me harm. Your post had nothing to do with trying to help anyone learn more about Baclofen; instead it was quite simply a further attempt for you to try and discredit me and try to make yourself appear to be more in line with the 'gang'. It works with your teammates but not me.

--sf--

[Otter]

What the heck is going on? We are just trying to find out what we can take to make us feel ok without the use of alcohol. Whatever GABA thing you two are talking about really does not matter.

Yeah, sure! That's why you are so disliked here, because you post random, stupid comments which are dangerous, like your advocacy of Ibogaine which is administered in circumstances where it has resulted in people dieing because they were overdosed on some other drug before they took the Ibogaine but the clinic didn't monitor them properly.

[Otter]

Ok Kronkster -let us take a look at the current chain of events that lead you to make the statement "It's sad that you try to bother me when I post". (We all must recognize that I have not brought you/your avatar up in any conversation, post, etc -period- in a very long time.)

YOU MADE A POST TO ME -REMEMBER?:

"Originally Posted by Spiritfree View Post
What the heck is going on? We are just trying to find out what we can take to make us feel ok without the use of alcohol. Whatever GABA thing you two are talking about really does not matter.

(None of conversation had anything to do with you!)

"It mattered to me because I wanted to know what affect baclofen had on my brain. I preferred to know what was physically going on with me. Apparently the gentleman also wanted to know." --Kronk--

What/who "gentleman" are you referring to? What did that gentleman want to know? What was his question?

Kronk -seriously? You are a much better troll than I ever thought you to be.... I under estimated your trolling abilities... I took your bait. You got me this time.

Kronk, what you are doing is intentionally trying to discredit me and cause me harm. Your post had nothing to do with trying to help anyone learn more about Baclofen; instead it was quite simply a further attempt for you to try and discredit me and try to make yourself appear to be more in line with the 'gang'. It works with your teammates but not me.

--sf--

No SF, you don't need any help in discrediting yourself. You are a one-man self-destructing machine. Kronk doesn't need any advice from you and is a long standing, well respected member of this forum who we all like. It's not a part of being part of any gang. You earn your stripes here.

[terryk]

Ameisen explains it in his book.



I was contacted a while ago by someone who had been taking baclofen under the care of Dr. Chick, who was his prescribing doctor. He also sought advice from Olivier Ameisen and from Phil Thomas. After all that advice from the top people in baclofen he still continued to drink, and, he had a Master's degree in chemistry so he was totally switched on to the science of it.



Anyway, I agreed to give him some counselling and we discussed the theory of baclofen and he said he couldn't figure out how a Gaba b agonist could have an effect on the Gaba A receptors, which is where most mood drugs have their effect. Because of this, he made a rational decision that baclofen could not work as Ameisen said and he lost interest in it and relapsed badly.



I explained to him that he had plainly not read Ameisen's book properly because what Ameisen says, which is significant in alcohol treatment, is that researchers have overlooked the Gaba B receptors as having any involvement in the type of anxiety which actually underlies alcoholism and that is what sets baclofen apart from all other drugs. GHB, a chemical occuring naturally in the brain, calms the brain by acting on the Gaba B receptor. Alcohol mimics GHB. That is why GHB as a synthetic drug is not noticed when used as a date rape drug, because its effects are indistinguishable from alcohol. The two are interchangeable, but obviously alcohol makes you drunk while GHB just calms anxiety.



So, because baclofen is an analogue (the same thing) as GHB, if you take it you won't feel like taking alcohol. I used an analogy of an empty glass. Imagine your Gaba B receptor is just like an empty glass in you head. If you fill it with GHB, you can't then add any alcohol, because there is no more room in the glass. So, you don't crave alcohol. If you are short of GHB, you can then fill the glass with baclofen, and by filling it up, you can't then put any alcohol in the glass.



After I used this analogy and explained Ameisen's theory the person I was advising had a "eureka" moment. None of the people who had advised him explained it in this way. He agreed with the analogy and got back on baclofen. After a few more chats he said he was fine and has been fine ever since, which is nearly a year now. He went back to a high stress job and writes to me now and then to thank me for helping him and all I really did was to give him the glass analogy.



I try not to get to deep into the chemical analysis of the brain. Baclofen acts on dopamine... I prefer the simple analogy of filling the glass because that is what an agonist is, it acts in the same way as the missing brain chemical while Naltrexone is an antagonist so you can't use the same analogy. With baclofen you are not substituting alcohol with another drug which acts in the same way, ie., to give you a Gaba A euphoria. You are replacing missing GHB. Chick is incorrect in saying baclofen is replacement therapy. It isn't. Naltrexon, subudone, methodone and all the drugs which give you a high similar to the drug of choice are replacements for the drug. Baclofen is a treatment of a chemical deficiency and it supplements the organic, natural chemical which your brain misses and it does not give you a Gaba A high.

We've gone over this many times. Some of the things you write above are inaccurate.



Endogenous GHB does not affect GABAB receptors, from GHB receptor targets in the CNS: focus on high-affinity binding sites:

In the CNS, GHB binds to both high- and low-affinity binding targets . The most well-established target for GHB is the GABAB receptor, at which GHB displays weak affinity and is a partial agonist with millimolar potency . However, endogenous GHB levels are in the micromolar range and thereby several orders of magnitude too low to activate GABAB receptors. Consequently, GABAB receptor activation is most likely only observed after exogenous GHB intake, e.g. after therapeutic drug administration or recreational use. Under such circumstances, GABAB receptors are highly relevant pharmacological targets for GHB and account for most of the reported in vivo effects of GHB as described in Section 3.

As I have stated, baclofen modulates dopamine - from GABA(B) modulation of dopamine release in the nucleus accumbens core:

Modulation of the concentration of dopamine (DA) released from dopaminergic terminals in the nucleus accumbens (NAc) influences behaviours such as the motivation to obtain drugs of abuse. γ-Aminobutyric acid type B (GABAB ) receptors are expressed throughout the mesolimbic circuit, including in the NAc, and baclofen, an agonist of GABAB receptors, can decrease drug-seeking behaviours. However, the mechanism by which GABAB receptors modulate terminal DA release has not been well studied. We explored how baclofen modulates the concentration of DA released from terminals in the NAc core using fast-scan cyclic voltammetry in brain slices from adult male C57BL/6J mice. We found that baclofen concentration-dependently decreased single pulse-evoked DA release. This effect was blocked by the GABAB antagonist, CGP 52432, but not by a nicotinic acetylcholine receptor antagonist. Suppression of DA release by a saturating concentration of baclofen was sustained for up to 1 h. The effect of baclofen was reduced with electrical stimulations mimicking burst firing of DA neurons. Similar to the D2 receptor agonist, quinpirole, baclofen reduced the probability of DA release, supporting a mechanistic overlap with D2 receptors. Baclofen-mediated suppression of DA release persisted after a locomotor-sensitizing cocaine treatment, indicating that GABAB receptors on DA terminals were not altered by cocaine exposure. These data suggest that baclofen-mediated suppression of terminal DA release is due to GABAB activation on DA terminals to reduce the probability of DA release. This effect does not readily desensitize, and persists regardless of chronic cocaine treatment.

Therapeutic doses of exogenous GHB *also* modulate dopamine, which could explain how low dose GHB substitution therapy (Alcover) can treat alcohol craving - from Extracellular events induced by gamma-hydroxybutyrate in striatum: a microdialysis study:

The modification of dopamine release and accumulation induced by gamma-hydroxybutyrate (GHB) was studied using both striatal slices and in vivo microdialysis of caudate-putamen. GHB inhibited dopamine release for approximately 5-10 min in vitro, and this was associated with an accumulation of dopamine in the tissue. Subsequently, there was an increase in dopamine release. In the microdialysis experiments, low doses of GHB inhibited dopamine release, whereas higher doses strongly increased release; the initial decrease seen in slices could not be detected in vivo. Thus, GHB had a biphasic effect on the release of dopamine: An initial decrease in the release of transmitter was followed by an increase. A time-dependent biphasic effect was observed when GHB was added to brain slices, and a dose-dependent biphasic effect was seen in dialysate after systemic administration of GHB. Naloxone blocked GHB-induced dopamine accumulation and release both in vitro and in vivo. GHB also increased the release of opioid-like substances in the striatum. A specific antagonist of GHB receptors completely blocked both the dopamine response and the release of opioid-like substances. These data suggest that GHB increases dopamine release via specific receptors that may modulate the activity of opioid interneurons.

Lastly Naltrexon(e)(sic) does not provide a "high," as it is an opioid antagonist. Methadone and Subudone are substitution therapies for opiate addicts. Methadone is a direct replacement with a somewhat safer abuse profile, while Subutone is a novel combination of a partial opioid agonist (buprenorphine) and a μ-opioid antagonist (naloxone) to minimize abuse.



-tk

[Otter]

Hi Terry

All of what you say is in Ameisen's book so if I haven't quoted it properly I apologize. You mention Alcover which is GHB. That is a synthetic of endogenous GHB.

Here's my take on Ameisen's theory:

Olivier Ameisen postulated in an article in Alcohol and Alcoholism that a GHB deficiency may underlie substance dependence through a GABAb-mediated dysphoric syndrome. “A biological deficit of GHB would thus be experienced as a loss of sedative effect, leading to anxiety, muscular tension, insomnia, and/or depression. Alcohol and other drugs would serve to “correct” these uncomfortable states. The fact that the sedative-hypnotic effects of GHB are mediated by the GABAb receptor could explain why baclofen, the only other substance known to act on that receptor, can be so useful against addiction and its underlying dysphoria.” Others, such as Dr. Felice Nava, have commented that, in light of both GHB and baclofen acting on the GABAb receptor, alcoholism may indeed be a disease characterized by a GHB-deficiency in the brain. If this hypothesis is demonstrated, the role of endogenous GHB will be elucidated. A 2003 Synapse article reported on baclofen dose-dependently reducing nicotine-, morphine- and cocaine-evoked dopamine release, demonstrating the “ability of baclofen to modulate...[dopamine transmission,” which indicated “baclofen as a putative candidate in the pharmacotherapy of poly-drug abuse.” Dopamine release is stimulated by several drugs of abuse. Dopamine is a neurotransmitter which plays important roles in executive, motor, motivation, arousal, reinforcement and reward functions in the brain. "

I don't think we are worlds apart in how we understand baclofen to work and I am not a scientist. What I don't like is some people here taking the view that any drug is ok because it is only about making people "feel better" and "stop drinking". "Any road up", I think they say, but it doesn't really apply to medicine, imho.

[Otter]

Tk, I'll clarify that point about Naltrexone, from my perspective.

The one person I know who took it said it made her feel drugged. My understanding of the drug is that it shields the neuroreceptor from the drug of choice. I have probably assumed that the reason, after taking Naltrexone, that one doesn't feel like drinking, is that it gives one this sensation of already having had a drink because of the reported feelings. I thought other people were saying it has the effect of making you feel woozy and I was under the impression that doctors are advising patients that taking it can impair driving ability.

If I have got that wrong, I apologize. I was not trying to say it was like Methadone so I retract what I said about it giving a person a "high" as that is not accurate.

[Spiritfree]

Yeah, sure! That's why you are so disliked here, because you post random, stupid comments which are dangerous, like your advocacy of Ibogaine which is administered in circumstances where it has resulted in people dieing because they were overdosed on some other drug before they took the Ibogaine but the clinic didn't monitor them properly.

Ok. You nailed me on that one Ottor----

Ottor, what US government agency has agreed to fund trials, research, etc. using Baclofen for AUD (alcoholism)? Have any US government agencies agreed or (or now considering) funding research using Ibogaine? (Yes Ottor, Ibogaine studies have been and are now being funded by the US government and some state governments.)

Ottor -you truly do not make a lot of sense sometimes but that is ok. As long as most people understand this fact and most current members do, you are not really causing harm to anyone and you really are trying to help others to take Baclofen for their AUD -so this is a good thing imo.

Ottor: A perfect quote for you:
"People who think they know everything are a great annoyance to those of us who do. Isaac Asimov"
Thank you for having patience with us all.

[JanCan]

I think that is a perfect quote for you too.

[Spiritfree]

I think that is a perfect quote for you too.

LOL. You all crack me up. You hurt my feelings, but you still make me laugh.

Jancan -you spend your modest little time posting negatively towards me. Have you considered that YOU might just have a problem? Of course not; you feel a need to degrade others in order to make yourself 'feel' better about you. Please do not take this negatively, instead, consider this an opportunity to look at yourself, and I mean really look at yourself and your motives.

[Spiritfree]

NE/Never/Ever: have you considered the fact that you are one of the most hypocritical, harmful, negative members on this forum? Of course you are excited about starting your new forum -it is not about helping others; instead, it is about boosting your own ego -inflating your own self worth. Sure, you will have your member friends here stand with you as you start out and the excitement will be big at first. In the end NE, you will still be an active drunk, with no job, and still desiring and needing confirmation from your forum friends. If it were not for your husband's income, you would be that gutter drunk that you said that you were not.

Carry on NE. Your MWO friends will be with you till the end. However, how long are you going to be able to be with yourself. Go have another cigarette, take some Baclofen, drink a few drinks, and report back to yourself in the morning -and hope that your financial support system sticks with you.

[Otter]

Ok. You nailed me on that one Ottor----

Ottor, what US government agency has agreed to fund trials, research, etc. using Baclofen for AUD (alcoholism)? Have any US government agencies agreed or (or now considering) funding research using Ibogaine? (Yes Ottor, Ibogaine studies have been and are now being funded by the US government and some state governments.)

Ottor -you truly do not make a lot of sense sometimes but that is ok. As long as most people understand this fact and most current members do, you are not really causing harm to anyone and you really are trying to help others to take Baclofen for their AUD -so this is a good thing imo.

Ottor: A perfect quote for you:
"People who think they know everything are a great annoyance to those of us who do. Isaac Asimov"
Thank you for having patience with us all.

There is something called "Socratic Ignorance" SF, which you have probably never heard of. It means that the more intelligent among us know how little they actually do know. A Guide to Socratic Ignorance

I suggest you have a think about this when you feel the urge to make foolhardy comments about some drug which has lethal side effects but could, maybe, possibly, with more research, and investigation, and support from governments somewhere BE THE WORLD'S GREATEST DISCOVERY EVER FOR ALCOHO...OOPS, I MEAN ADDICTION (including alcoholism of course, obviously)

Gee people, why can't we understand this? Duh.

PS, It's Otter. I don't know what an Ottor is. My handle comes from where I once lived, Otterburn, by the way. It's not a reference to an animal.