Big Pharma - oral GABA doesn't work; Also Big Pharma - oral GABA works, can replace alcohol

haidut

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We are now living in an openly clown world, so I don't really expect many doctors to change their position based on contrarian evidence, but it is a stunning admission on behalf of medicine regardless. Namely, mainstream medicine and its partners in crime (often, literally) Big Pharma have spend a ton of money financing, ghostwriting, and publishing bogus studies claiming oral GABA does not have central (brain) effects. You see, if oral GABA worked centrally, the entire benzodiazepine industry for treating all kinds of anxiety disorders (and even seizures) will disappear overnight. Those GABA receptors that endogenous GABA activates (duh!) just happen to also be the main target of the benzodiazepine drugs - i.e. all such drugs are GABA agonists. So, it was absolutely crucial for Big Pharma to convince the public (and especially psychiatrists) that orally ingested GABA does not cross the blood-brain barrier and is thus ineffective in activating the GABA receptors in the brain. When some brave maverick doctors tried to make a case for using oral GABA as a treatment for anxiety (and even depression) back in the 1960s, Big Pharma turned on its propaganda machine, smeared those scientists/doctors, and convinced the public and medicine that oral GABA is cannot reach the brain and is thus ineffective for anxiety/depression. That propaganda is still ongoing despite hundreds of studies demonstrating oral GABA crossing the blood-brain barrier and exerting central effects.
Now, despite decades of unfounded claims that oral GABA is centrally ineffective, Big Pharma is pushing oral GABA as an alcohol substitute. Why? Well, it just so happens that most of alcohol's effects perceived as positive by people are due to ethanol's ability to also activate GABA receptors, both in the brain and elsewhere - i.e. alcohol is a powerful GABA agonist. So, on a slight tangent, if one follows this train of thought without any bias, one could conclude at least three things. One, people with anxiety would probably have a higher rate of alcohol consumption than the general population, and even an "addiction" to it in cases of severe anxiety. Two, there is probably no such thing as "alcoholism" or "addiction" as defined by the (in)famous (and completely bogus) DSM V, but rather a simple case of self-medication by people under stress by using a powerful GABA agonist (and thus anxiolytic) substances that is cheap and widely available (namely, alcohol). Three, people with anxiety are probably under chronic stress as the latter blocks the GABA system and activates the anxiogenic HPA-axis. It just so happens that all these conclusions have been proven beyond reasonable doubt. As a side note to alcohol's effects - the latter is also an NMDA antagonist and that mechanism also contributes to alcohol's positive effects such as disinhibition and rapidly acting anti-depressant (though, becoming depressant with long-term use). Thus, GABA agonism probably won't replicate all of alcohol's positive effects but could still be a close substitute. This link between GABA and alcohol was well-known as far back as the early 1970s and Big Pharma even synthesized a molecule called "DS1" (of course, a GABA agonist) reputed to replicate alcohol's positive effects almost completely, with none of the downsides. That molecule never reached the market and the official excuse was that Big Pharma was concerned about the "moral hazard" of selling such a molecule. However, a more conspiratorial (read: realist) person would probably suspect that heavy lobbying from the trillion-dollar alcohol beverage industry probably played a much bigger role in the decision not to sell DS1. In conclusion to this long diatribe, the article below discusses that there is at least one pharma company out there (GABA Labs) that is now openly claiming that oral GABA is certainly centrally active, and is thus developing an oral GABA product as an alcohol substitute that should have most/all of alcohol's positive effects but none of detrimental effects, which include not only the dreaded hangover but also serious chronic conditions such as liver disease, CVD, and even cancer. The article mentions two other companies also working on oral GABA-based drugs, and there are probably many others we don't yet know about. My only hope is that all this good publicity in regards to the benefits of oral GABA does not result in GABA being declared by the FDA a "novel drug", and thus banned from over-the-counter sales.
For those curious enough to do some self-experimentation, aside from GABA itself other amino acids with similar pro-GABA effects such as taurine, beta-alanine, theanine, and even glycine should have similar alcohol-replicating effects. What's the dose you ask? Well, based on the information below provided by a company using the GABA Labs technology, it looks like each shot of their alcohol-mimetic has 1g of GABA. Assuming similar effectiveness of GABA agonism across the various amino acids, I'd try 1g taurine or beta-alanine per shot. Theaning seems to be more potent and probably would work best in doses of no ore than 200mg per drink/shot. In addition, GABA agonist steroids such as progesterone and allopregnanolone should also have such effects, and in fact high-dose progesterone is well-known to produce a "drunk" effect described by the afflicted as very similar to alcohol's.

Meet One Startup Trying To End Hangovers With Synthetic Alcohol | ZeroHedge

"...David Orren, managing director of GABA Labs, told WSJ: “Alcohol is like playing the piano with boxing gloves on. You hit too many keys.” Dr. David Nutt, the chief scientific officer of GABA Labs, is a former psychiatrist and neuropsychopharmacologist. He has spent two years as chief of section of clinical science in the National Institute of Alcohol Abuse and Alcoholism at the National Institutes of Health, the Journal notes, and has long argued about the negative effect of alcohol on society. “It feels like what a glass of wine feels like. It feels relaxing. It makes you a bit more chatty, a bit more socially engaged with people,” he said about the company's product, called Alcarelle. GABA is looking to raise $10.3 million and finish food safety testing in the U.S. by the middle of 2026, the report says. Orren and Nutt have been testing the product themselves, with Orren commenting: “It feels like a warm glow. You’re being you. And you’re being with somebody that’s being them. You’re being real.” The next step will be testing the product, including testing it when mixed with actual alcohol. Dr. Mack Mitchell, senior medical advisor for Amygdala, a company working to inhibit alcohol cravings with an oral drug that targets similar receptors, commented: “People who can’t control drinking don’t always want to stop drinking completely. They just want to be able to drink normally.” Another company, Indivior, is working on a nasal spray to inhibit alcohol cravings as well. Its CEO Mark Crossley added: "I arrive in the parking lot. I don’t want six or seven drinks. I’ll top up with a nasal spray.”"
 

-Luke-

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Interesting. Another serious blow after the depression/serotonin and menopause/estrogen began to crumble in the last few years. Dr. Peat often talked about the alcohol-like effects of progesterone. Didn't he also have a story about pregnenolone, were he took or gave someone else a high dose and noticed some drunk effects?
 

TheSir

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I think a random company from Wales hardly qualifies as Big Pharma. And if it did, Big Pharma is not a single person, there are diverse views even within its own structures. Interesting development in any case.
 

HumanLife

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I have taken GABA and there is definitely a calming effect. I would take it with water but looking back I should have probably taken it more consistently with something sweet, and it wouldn't surprise me if sugar helped boost its effects.
I think a random company from Wales hardly qualifies as Big Pharma. And if it did, Big Pharma is not a single person, there are diverse views even within its own structures. Interesting development in any case.
Even if it doesn't qualify as Big Pharma, if the science that consumption of GABA passes the BBB is not being objected to as it once was, it would give the idea to the public that there is truth to it when there is no voice to give them doubt. Then again, I don't know about how much attention this is getting, so it's also possible Big Pharma just does not see it as a threat for now. It would be hard to go against it if it gets in the culture and is offered as a kind of drink by every alcoholic beverage company.
 
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Good write up but sad to see no mention of ghb in this gaba write up.
You are typing up the effects of ghb, and giving these effects to gaba.
The other things you mention like taurine, beta-alanine, theanine, and glycine. While these are all ok for overall health, none of those will replicate ghb's effects.

I am going to agree with big pharma about what they are saying about gaba's effects here.

What will it take for you to change your position on gaba & ghb? It appears you have not tried ghb yet.
I am willing to bet $ for a challenge you would change your position. Instead of the Pepsi challenge, we will have a gaba challenge.
We will have a 1 gram shots lined up with 1 product of gaba, ghb, taurine, beta alanine, theanine.
5 shots total. None will be labelled. 1 shot every 30 mins.
Or 1 shot of ghb vs 1 shot of gaba/taurine/beta-alanine/theanine/glycine all mixed. To make the challenge quicker.
This will be done during a live podcast to see visual, and verbal effects of each product.
It will be easy to see which one was the ghb(not from taste but effects). You will become a believer!
 

Validus

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Good write up but sad to see no mention of ghb in this gaba write up.
You are typing up the effects of ghb, and giving these effects to gaba.
The other things you mention like taurine, beta-alanine, theanine, and glycine. While these are all ok for overall health, none of those will replicate ghb's effects.

I am going to agree with big pharma about what they are saying about gaba's effects here.

What will it take for you to change your position on gaba & ghb? It appears you have not tried ghb yet.
I am willing to bet $ for a challenge you would change your position. Instead of the Pepsi challenge, we will have a gaba challenge.
We will have a 1 gram shots lined up with 1 product of gaba, ghb, taurine, beta alanine, theanine.
5 shots total. None will be labelled. 1 shot every 30 mins.
Or 1 shot of ghb vs 1 shot of gaba/taurine/beta-alanine/theanine/glycine all mixed. To make the challenge quicker.
This will be done during a live podcast to see visual, and verbal effects of each product.
It will be easy to see which one was the ghb(not from taste but effects). You will become a believer!
Isn't GHB a "drug" though? Gaba can be purchased as easily as amazon. Curious to know how you're getting GHB.
 
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haidut

haidut

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Good write up but sad to see no mention of ghb in this gaba write up.
You are typing up the effects of ghb, and giving these effects to gaba.
The other things you mention like taurine, beta-alanine, theanine, and glycine. While these are all ok for overall health, none of those will replicate ghb's effects.

I am going to agree with big pharma about what they are saying about gaba's effects here.

What will it take for you to change your position on gaba & ghb? It appears you have not tried ghb yet.
I am willing to bet $ for a challenge you would change your position. Instead of the Pepsi challenge, we will have a gaba challenge.
We will have a 1 gram shots lined up with 1 product of gaba, ghb, taurine, beta alanine, theanine.
5 shots total. None will be labelled. 1 shot every 30 mins.
Or 1 shot of ghb vs 1 shot of gaba/taurine/beta-alanine/theanine/glycine all mixed. To make the challenge quicker.
This will be done during a live podcast to see visual, and verbal effects of each product.
It will be easy to see which one was the ghb(not from taste but effects). You will become a believer!

GHB is considered a "hardcore" drug here in the US, in the same category as heroin. Also, unlike heroin, GHB is also known to the public as a "rape drug" and is actually more heavily enforced against here than heroin, precisely due to this negative social reputation of the drug. I know people who got a visit by the police simply b/c they advocated GHB use on a public forum to people who had severe mental issues and/or cancer. So, I think you can see why I am not writing about GHB.
On a more technical note - to my knowledge, GABA does not activate the "GHB" receptor, and neither does alcohol or any of the other amino acids I mentioned. GHB only activates the GABA-b subreceptor, so one can't claim it reproduces GABA's effects either. Ethanol, on the other hand, does seem to be a non-selective GABA agonist, so prob has more overlap with GABA than GHN does. So, considering the article is about oral GABA, I think the discussion should be about oral GABA and those other aminos that can fully replicate the effects of GABA (at least in regards to receptor binding). While GHB may have partially overlapping effects with oral GABA, the main point of the post and the article is not so much about replacing alcohol or seeking a new way to get high, but that oral GABA is effective, which automatically makes most anti-anxiety drugs at best useless, and at worst a scam.
Just my 2c.
@Ionson
 
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haidut

haidut

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I think a random company from Wales hardly qualifies as Big Pharma. And if it did, Big Pharma is not a single person, there are diverse views even within its own structures. Interesting development in any case.

Big Pharma companies likely own shares in all of those startups - i.e. the fundraising for $10.3mil that GABA Labs is planning would basically sell shares to "undisclosed" investors in return for the money. Big Pharma companies are very likely to be among those investors. That's how Big Pharma avoids the spotlight. Officially, a mega-copmpany like Pfizer can still gaslight the public that oral GABA is ineffective while behind the scenes Pfizer can own controlling shares in many "startups" selling oral GABA formulations. Since the investors of most private companies are not easy to find, Pfizer (and others like it) get to basically semi-anoymously bet on both sides and win no matter which side wins. Case in point - Pfizer makes, promotes and sells an SSRI called Zoloft while touting its benefits for all sorts of conditions well beyond mental health (COVID-19 is a recent marketing effort they did for that drug), while at the same time running clinical trials with the anti-serotonin drug terguride for preventing/treating all of the side effects Zoloft causes.
 
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haidut

haidut

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Interesting. Another serious blow after the depression/serotonin and menopause/estrogen began to crumble in the last few years. Dr. Peat often talked about the alcohol-like effects of progesterone. Didn't he also have a story about pregnenolone, were he took or gave someone else a high dose and noticed some drunk effects?

Progesterone certainly reproduces the drunk feeling from alcohol, while I think pregnenolone somewhat antagonizes it. Ray did mention a friend of his who had alcohol "addiction" and managed to substitute alcohol with 100mg pregnenolone and told Ray the effects were what he hoped to get from alcohol but only rarely did. As an extra benefit, pregnenolone, progesterone, allopregnanolone, and other steroids that block CRH/CRF also likely block the "addiction" to not just alcohol but many other drugs of (ab)use as well, since the vast majority of "addiction" is simply self-medication for controlling stress.
 

Sumbody

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For those curious enough to do some self-experimentation, aside from GABA itself other amino acids with similar pro-GABA effects such as taurine, beta-alanine, theanine, and even glycine should have similar alcohol-replicating effects.
I love the enthusiasm around here, but let's be real. There is no way these amino's can come even close to mimicking the effects of alcohol on one's self.

As someone who drinks alcohol regularly, there is nothing that compares. Sure, these things work similar in theory and technically by mechanism of action, but not necessarily in practice or application.

I could take gram upon gram of these amino's and feel nothing. Exception being maybe GABA as that can make one drowsy. Even drugs like Phenibut, which in a way have their own quirks and unique effects, come close, but still not quite as effective as alcohol.
 

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chrstn4o

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I take 2 x 500mg GABA every night before bed and sleep so much better. Or rather, definitely do not sleep as well if I don't take it, at least some of the time I've noticed that. More recently, I've been experimenting with 500mg during the day, usually if I feel like I had a bit too much coffee or something annoys me... and it does work. But yesterday, for some reason I decided to take 1000mg at around noon... about 90-mins later I was falling asleep on the couch even though I had three coffees in the morning. So, hard to convince me that it doesn't work centrally! Good that research is showing once again the lies perpetrated in the mainstream.
 
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haidut

haidut

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I could take gram upon gram of these amino's and feel nothing. Exception being maybe GABA as that can make one drowsy.

Well, if you chronically consume alcohol, the GABA receptors will be downregulated and you'd probably need much higher doses of those GABA agonist aminos. Even then, I have yet to see even a chronic alcoholic who does not get a sedation effect from say 5g taurine or 100mg progesterone.
 
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haidut

haidut

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HAHAHA!

That was the best part of an outstanding post. Thanks.

Why did you take the quote out of context? That part on the "moral hazard" was preceded by "...and the official excuse was...". So, you made it sound like I claim Big Pharma was concerned about the "moral hazard" when I actually implied it was the exact opposite.
 
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ThinPicking

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I love the enthusiasm around here, but let's be real. There is no way these amino's can come even close to mimicking the effects of alcohol on one's self.

As someone who drinks alcohol regularly, there is nothing that compares. Sure, these things work similar in theory and technically by mechanism of action, but not necessarily in practice or application.

I could take gram upon gram of these amino's and feel nothing. Exception being maybe GABA as that can make one drowsy. Even drugs like Phenibut, which in a way have their own quirks and unique effects, come close, but still not quite as effective as alcohol.
Seasoned drinker, drug and supplement tinkerer here. Currently on one of my longest runs without a perceptible degree of intoxication thanks to Taurine, Theanine and a very occasional top with 5mg of Baclofen (I'm not advocating the latter, beware of it).

I think they actually can but the user has to be smart about it. Regular alcolol consumption is liable to leave us with deranged fluid and electrolyte status, modifying our response to all other drugs and supplements. In addition it and/or or its adaptations can perturb the senses, so for example a regular drinker could easily find themselves hypodipsic in their sober days or hours, despite a volume or electrolyte deviance that they'd otherwise self correct on instinct. Alcohol itself can be more forgiving of it's own effects in this regard, for it is a liquid found in all manor of concentrations and palatable carriers.

Drinkers will often chase a sweet spot that's likely explained by alcohol's biphasic and concentration dependant effects on dopamine. So the concentration and rate at which it's consumed, in addition to gastrointestinal contents are very important to get and stay there. The same probably applies to replacements, but they're almost always found in solid form.

This is a big subject and I've felt it out in myself to a greater extent than I currently possess evidence to explain. So I can't say too much. But anyone attempting replacement should pay special attention to their relationship with food and fluid, their prior behaviour and a possible need to lean in to some absent sensations until they return of their own accord. A person can think this doesn't apply to them, but physiological adaptations to regular consumption can be a very long and slippery slope. This can be insidious.
 

Sumbody

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Seasoned drinker, drug and supplement tinkerer here. Currently on one of my longest runs without a perceptible degree of intoxication thanks to Taurine, Theanine and a very occasional top with 5mg of Baclofen (I'm not advocating the latter, beware of it).

I think they actually can but the user has to be smart about it. Regular alcolol consumption is liable to leave us with deranged fluid and electrolyte status, modifying our response to all other drugs and supplements. In addition it and/or or its adaptations can perturb the senses, so for example a regular drinker could easily find themselves hypodipsic in their sober days or hours, despite a volume or electrolyte deviance that they'd otherwise self correct on instinct. Alcohol itself can be more forgiving of it's own effects in this regard, for it is a liquid found in all manor of concentrations and palatable carriers.

Drinkers will often chase a sweet spot that's likely explained by alcohol's biphasic and concentration dependant effects on dopamine. So the concentration and rate at which it's consumed, in addition to gastrointestinal contents are very important to get and stay there. The same probably applies to replacements, but they're almost always found in solid form.

This is a big subject and I've felt it out in myself to a greater extent than I currently possess evidence to explain. So I can't say too much. But anyone attempting replacement should pay special attention to their relationship with food and fluid, their prior behaviour and a possible need to lean in to some absent sensations until they return of their own accord. A person can think this doesn't apply to them, but physiological adaptations to regular consumption can be a very long and slippery slope. This can be insidious.
I agree.

But I was in most part calling out the statement and the way it read.

This forum has a way about things like that, in that we need to be more cautious and meticulous or thorough about what is stated.

The average forum user and or newcomer reads things like that and takes it as gospel. Next thing you know folks across the internet are saying that peeps on Ray Peat forum say that you can get drunk on taurine, GABA, etc. It can remove credibility from the vast and important information found here.

We see exactly that with the whole "Ray Peat Diet" thing.

And guys like Haidut are very well respected around here, he brings a tremendous amount to the table. But loosely woven statements like that can easily be misconstrued by the less imaginative reader.

I just felt compelled to say something. Because I myself read it that way, when even I know better.
 

ThinPicking

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Next thing you know folks across the internet are saying that peeps on Ray Peat forum say that you can get drunk on taurine, GABA, etc.
Under the "right" conditions, you probably can. But the concentration and carrier composition would need to be found. It would be amusing to see us consume GABA in a carrier fluid at 10 - 20 %, bottle after bottle, trying to maintain wakefulness and composure.

Personally I think of "drunk" as the overlap between the dopaminergic sweet spot and the sedative-hypnotic zone thereafter. Beer, cider, wine, mixers, they can all get me there are different rates and with different tones. Assuming my stomach is "empty" and my mind is "fresh".
 
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haidut

haidut

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I agree.

But I was in most part calling out the statement and the way it read.

This forum has a way about things like that, in that we need to be more cautious and meticulous or thorough about what is stated.

The average forum user and or newcomer reads things like that and takes it as gospel. Next thing you know folks across the internet are saying that peeps on Ray Peat forum say that you can get drunk on taurine, GABA, etc. It can remove credibility from the vast and important information found here.

We see exactly that with the whole "Ray Peat Diet" thing.

And guys like Haidut are very well respected around here, he brings a tremendous amount to the table. But loosely woven statements like that can easily be misconstrued by the less imaginative reader.

I just felt compelled to say something. Because I myself read it that way, when even I know better.

Actually, the main point I was trying to convey, and which most of my OP diatribes focuses on, is not so much that people can get "buzzed" by popping GABA-ergic aminos instead of alcohol, but that the article and the work of those companies is an admission that oral GABA works (centrally). So, hopefully this could potentially put a dent in the massive benzo industry whose entire existence was originally justified with the claim that while GABA works as an anti-anxiety substance it has to be administered into the brain directly since it does not cross the blood-brain barrier. Half a century later, we have (tacit) admission that oral GABA does work, so it could be something people can push their doctor about before they get put on benzos, which the study below shows that (surprise!) are anything but benign.
 

cjm

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oral GABA is effective, which automatically makes most anti-anxiety drugs at best useless, and at worst a scam.

The anti-anxiety meds are (worse than) useless middlemen just like so much else in Western society. I only have secondhand experience with Xanax, and it's a cruel joke of a drug to hijack the GABA system and cause dependency in a matter of days even at sub-mg doses.

I have personal experience with oral GABA. It takes my breath away at around 1g bolus, I don't know what is going on with that, if it's my diaphragm relaxing and "falling out" of nervous perception momentarily, if it's something with the lungs, but the tack-on effects are like a warm bath for my emotions. At higher doses (2g+), my verbal fluidity makes speaking my mind (and adapting to rough social situations) effortless.
 
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Frankdee20

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Well, if you chronically consume alcohol, the GABA receptors will be downregulated and you'd probably need much higher doses of those GABA agonist aminos. Even then, I have yet to see even a chronic alcoholic who does not get a sedation effect from say 5g taurine or 100mg progesterone.
I purchased Progesterone from Idealabs and only take it topically in small one or two drop doses
The anti-anxiety meds are (worse than) useless middlemen just like so much else in Western society. I only have secondhand experience with Xanax, and it's a cruel joke of a drug to hijack the GABA system and cause dependency in a matter of days even at sub-mg doses.

I have personal experience with oral GABA. It takes my breath away at around 1g bolus, I don't know what is going on with that, if it's my diaphragm relaxing and "falling out" of nervous perception momentarily, if it's something with the lungs, but the tack-on effects are like a warm bath for my emotions. At higher doses (2g+), my verbal fluidity makes speaking my mind (and adapting to rough social situations) effortless.
thats a common reaction but it dissipates
 
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