GABA-yaba-do! Anyone tried Baclofen?

Phenibut is what lead me to Baclofen. I was looking for a drug that is available and subsidised in Australia that has similar pharmacokinetics. The trouble with Phenibut is the tolerance potential. Typically folks recommend limiting its use to two days in seven.

In starting this thread, I’m hoping to open a discussion regarding GABAergic drugs and your experiences with them. Baclofen seemed to me to possess the best qualities of phenibut, but with much lower probability of dependency.

… Baclofen does not have significant affinity for the GHB receptor, and has no known abuse potential.

A beneficial property of baclofen is that tolerance to its muscle-related therapeutic benefits does not seem to occur to a significant degree — baclofen retains its therapeutic anti-spasmodic effects even after many years of continued use

Now I know it says “muslce-related”. I actually have musculo-skeletal pains. I have attempted addressing them with countless other modalities. It has only been since caving in and taking a benzo at night that I have noticed my positive responses to GABA in general. Including muscle pains almost completely disappearing. I have tried taking half (2.5mg) and a quarter (1.75mg) of diazapam in my experimentation and, although its effects are different and not long lasting in nature. The results are uplifting in terms of what this means regarding finding effective treatments for some of my more prevalent issues.

I do not want to rely on benzos for this benefit though, of course. Enter Baclofen.

Experiences, thoughts etc.?

http://www.ncbi.nlm.nih.gov/pubmed/25754761

Yeap. I should just look on pubmed properly before I do my own research. ha.

Yes. Evidence suggests systemic GABAergic and glutamatergic dysfunction are the most significant affective pathogenesis underpinning Autism neurology. A deficiency in beta-3, alpha-5, and gamma-3 GABA-A receptor sub-units is hypothesised to be largely responsible for the GABA-A receptor deficiency seen in many patients postmortem.

GABA-B receptor deficiency is what underpins the lower level of FMRP protein identified in autistic patients who don’t have a genetic FMRP mutation, which in turn causes problems with group I mGluRs and consequently, NMDA receptors.

Downregulation of Glutamate decarboxylase (GAD) is likely causal to impaired GABA synthesis.
Makes me wonder if Memantine + Baclofen could present as a novel treatment proposition …

My apologies for the lack of relevance this has to Sz in part, though not entirely …

There. It’s back to being relevant now:

https://en.wikipedia.org/wiki/Glutamate_decarboxylase

Substantial dysregulation of GAD mRNA expression, coupled with downregulation of reelin, is observed in schizophrenia and bipolar disorder.[11] The most pronounced downregulation of GAD67 was found in hippocampal stratum oriens layer in both disorders and in other layers and structures of hippocampus with varying degrees.[12]

GAD67 is a key enzyme involved in the synthesis of inhibitory neurotransmitter GABA and schizophrenic patients have been shown to express lower amounts of GAD67 in the dorsolateral prefrontal cortex compared to healthy controls.[13] The mechanism underlying the decreased levels of GAD67 in schizophrenic patients remains unclear. Some have proposed that an immediate early gene, Zif268, which normally binds to the promoter region of GAD67 and increases transcription of GAD67, is lower in schizophrenic patients, thus contributing to decreased levels of GAD67.[13] Since the dorsolateral prefrontal cortex (DLPFC) is involved in working memory, and GAD67 and Zif268 mRNA levels are lower in the DLPFC of schizophrenic patients, this molecular alteration may account, at least in part, for the working memory impairments associated with the disease.

I take baclofen! I didn’t realize it was used for cognitive impairments!

I take it for muscle spasms in my neck, for which I have had chronic pain these past few years. I was told it was just a muscle relaxant.

As a muscle relaxant, it works pretty good! I’ve noticed that I’m not cracking my neck obsessively like I used to when I had neck pain. I’m at 10 mg, but i take only half a pill, three times a day.

I have taken it for about four months now and my pain has noticeably disappeared, so long as I remember to take the pill.

It doesn’t really have any side effects that I’ve noticed, except sleepiness and lethargy.

Thanks for chiming in @HQuinn :slight_smile:

Its impact on cognition is dependent on the individual … if you have genetic mutations affecting GAD or FMRP then yeap.

It causes sleepiness because … well let’s just say that diazepam, for example, operates in similar mechanisms. GABA is intrinsically inhibitory.

Baclofen is pretty much only prescribed for the reason you are using it. I have similar problems to what you describe … which is to be expected if I do indeed have GAD issues, which I suspect I do … but I also have cognitive and social issues that are inherent in ASD and all intertwined.

I need to get some money together and organise the 23andme kit. I’ll find the bottom line in there.

1 Like

@anna was just saying yesterday that benzos are basically taking a lot of GABA…

been taking it for 5 days… noticeable difference

1 Like

Anna is not entirely incorrect!

The most noteworthy difference between a GABA supplement and a GABAergic drug, however, is that the former entails consuming the actual GABA molecule, whereas the latter activates/agonises GABA transitters and/or receptors.

The thing with taking plain old GABA is that unless you have a compromised blood brain barrier (BBB) (typically caused by nuero-inflammation), it is unlikely to cross said barrier. As such, if what you are experiencing is more than placebo, it could be indicative of a compromised BBB. Not something to freak out about, just some interesting science.

Phenibut is essentially the GABA molecule with a phenyl group attached. Much like phenylpiracetam is to piracetam. The result is a molecule that is capable of penetrating the BBB. And in the case of phenylpiracetam, a significantly more bioavailable form that improves cost-scaling.

1 Like

The GABA i’m taking is bonded with vitamin b6. From my understanding this allows it to cross the blood brain barrier.

Even as a placebo it has allowed me to find new psychological state of comfort and distance from the noise.

I’m curious as to if that checks out with your understanding @polymorphed.

WIthout reading the product description, I expect B6 is added because it is involved in GABA synthesis, not to mention its complimentary role in nerve health via other inhibitory mechanisms. I take B6 to ease my carpal tunnel syndrome symptoms, for example.

There are plenty of other completely logical and viable reasons why GABA supplementation would help you, Azley, beyond simply being needed on the other side of your BBB. I do not want you to think the benefits are purely placebo - what I want to convey with that message is that people who take GABA with the expectation of immediate nootropic benefits, whether in the presence of GABAergic dysfunction or not, are possibly experiencing placebo resulting from expectation bias.

With Sz physiology, I could write 100,000 words supporting why just taking that GABA+B6 supplement could help. I wouldn’t stop taking it while you are feeling a rise of positives. :slight_smile:

1 Like

Thanks for the info man. I feel a lot calmer placebo or not.

What would it mean if the bbb is compromised? What would cause such a thing?

Would it explain my sensitivity to things like caffeine, nicotine and other neurochemicals?

Firstly, I’ll reiterate this important point - experiencing a positive response to GABA+B6 in the presence of Sz physiology is to be expected. So whether or not you have a “leaky brain” is not able to be determined by this discussion nor something I recommend getting hung up on!

A ■■■■ load of things could lead to a compromised BBB - most fundamentally, issues within the immune system. I feel like a psychologist answering your question this way lol From a scientific standpoint, my answer is like saying “anything is possible”. But even that answer is not too far off the mark, realistically.

Yes it could. But being sensitive to excititory chemicals goes hand in hand with responding positively to inhibitory chemicals. The list goes on and on too. You could just be in a state of adrenal overdrive (sympathetic nervous system overtone).

1 Like

Well I haven’t been physically sick in a long damn time. I think my immune system is good.

The overstimulation needs to be curbed…

Thanks for the info. I might have more questions later on.

Wait man… What would be the procedure to check if the BBB has been compromised?

I wouldn’t accept anything less than an MRI conducted under the premise of BBB permeability investigation and a report written by a specialist in that field.

1 Like

@Polymorphed are you related to notmoses?

You make me feel about as smart as Peter Griffin. Lol!

Considering I don’t know who that is, it is more than likely that I am, yes!

The sardonism above is a useful segue into addressing your other assertion:

Peter is my idol! And mate, I have the emotional intelligence of a 5 year old and the social smarts of a basket of fruit.

2 Likes

For the benefit of others wondering about consuming GABA supplements and not GABA nootropics like phenibut or picamilon etc. I did some research. The results are mostly inconclusive, but there are two interesting things worth mentioning.

  1. There appears to be an overwhelming number of positive anecdotes regarding regular GABA supplements asserting nootropic benefits (which is commonly thrown around as purely placebo and a myth. Point is the large number of these personal accounts is interesting.

  2. There appears to be some kind of relationship between systemic GABA concentrations and brain GABA concentrations. GABA regulates its own synthesis somewhat (ideally). Through whatever mechanisms this take place, there seems to be some evidence that brain GABA synthesis could be influenced by systemic GABA levels. In other words, it is a possibility that mega-dosing GABA could stimulate GABA synthesis in the brain.

The higher the systemic GABA concentration, the less likely the brain is to do this. So, my personal stance is feel free to experiment with mega-dosing GABA, but don’t pay for a yearly subscription etc… You’ll likely be wasting your money just as soon as your body is GABA saturated. How long this would take is individual. And this is all hypothesis. None of the publications were conclusive.

  1. Worth adding I guess. If the brain is still developing (which can continue up to age 25), BBB permeability of GABA has been reported to be higher. So if you’re younger than that, you might gain some nootropic benefits without any implication of BBB permeability issues such as neuro-inflammation etc.

I am so tired right now that I think I’m just typing by muscle memory alone. Hopefully this makes sense to you all. Time stamp: 2:25am. I am so naughty. haha

And now it’s 2:41. I need a curfew lol Anyway, I just thought I would quickly get this off my chest: hmmm you should Google TH1 dominance. Not getting sick often is actually not necessarily a sign of a well balanced immune system, interestingly. Though you could be completely correct in that assertion too. So take it more as a reading recommendation that might set off some lightbulbs that only you can really see due to knowing yourself better than anyone else.

Good night world :slight_smile:

1 Like