Mauritio

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The nanomolar concentrations are what is endogenously present. When administering several milligrams (or more) exogenously micromolar concentrations are likley to be achieved. In fact, the antidepressant effect of the FDA-approved Brexanolone is likely (partially) due to stimulating thyroid synthesis and metabolism. The GABA agonism alone is not enough to explain the antidepressant effect as pure GABA agonists such as the benzodiazepine class of drugs do not have antidepressant effects but only antianxiety ones. The increase in dopamine mentioned in a previous comment and antagonism of serotonin (below) are probably also involved in the overall antidepressant effects.
Interesting!

Btw there's also a great newsletter by peat on postpartum depression ! It's the may 2019 issue.
 

akgrrrl

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Ditto this.
Amazing work Georgi. I'm a sucker for any GABA agonists as they tend to feel most androgenic to me. The sedation is easily taken care off with higher doses of caffeine and at the same time makes caffeine bit easier to handle. AlloP looks very promising, now the only thing left to do is to try it out! Much obliged
 
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haidut

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Big pharma = 34 000$
Idealabs = 29,99$
??

It is not just us selling allopregnanolone - many other chemical companies are too and their prices, despite being higher than ours are still way lower than $34K for the same amount through the patented formulation.
 

Mauritio

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My talk with Ray about Allopregnanolone:

Q: I saw there's some allopregnanolone on the market now . What do you think about direct allopregnanolone supplementation?
Do you think it's safe?

A: I think its safety depends on the purity.

Q: Ok thanks!
Do you think there's any value to supplementing it compared to higher doses of pregnenolone or progesterone ?

A: Is it available at a reasonable price?

A one-time infusion that provides fast relief for postpartum depression has sparked excitement about the medicine's potential and concerns over its $34,000 price tag. Brexanolone (branded as Zulresso) provides a synthetic source of allopregnanolone — a neurosteroid that decreases after childbirth.
 

brix

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Will be an interesting experiment for those who have used Finasteride. It has been shown to directly lower Allopregnanolne levels.
 

mangoes

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Is there any evidence of it’s effects on lowering prolactin? All I can find is a study on rats and an infusion increased prolactin levels
 
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haidut

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Is there any evidence of it’s effects on lowering prolactin? All I can find is a study on rats and an infusion increased prolactin levels

Infusions/injections are traumatic/stressful. Peat mentioned that in a few interviews and I posted studies confirming it.
His comment on the stressfulness of most steroid administration methods used by doctors/scientists (in both animals and humans) was, coincidentally, in response to a person who sent him a study showing i.p. injections of pregnenolone or DHEA raised prolactin levels in animals.
So, we need data from oral or topical studies but as far as I know there are none so far. However, that may change soon if the synthetic analog of allopregnanolone (Zuranolone) developed for oral use by the same company that created Zulresso also gets approved by the FDA.
 

mangoes

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Infusions/injections are traumatic/stressful. Peat mentioned that in a few interviews and I posted studies confirming it.
His comment on the stressfulness of most steroid administration methods used by doctors/scientists (in both animals and humans) was, coincidentally, in response to a person who sent him a study showing i.p. injections of pregnenolone or DHEA raised prolactin levels in animals.
So, we need data from oral or topical studies but as far as I know there are none so far. However, that may change soon if the synthetic analog of allopregnanolone (Zuranolone) developed for oral use by the same company that created Zulresso also gets approved by the FDA.
Ahh, makes sense, thanks haidut!
 
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haidut

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Have you noticed any weight loss from this, @haidut ?

Yes, but since it is the summer (when I typically lose 10%+ weight just because of sunlight and better metabolism) it is hard to say what exactly was the cause of the weight loss. FWIW, for me at least, it is much more calming than progesterone, which suggests it lowers cortisol (as human studies have already demonstrated) and that is usually facilitating for weight loss.
 

billybrown83

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Would there be any chance of suffering some sort of discontinuation syndrome if you were to stop taking this for whatever reason? Could it be as severe as SSRI withdrawal? Or could any positive effects be permanent? I really want to try this but I've got on going issues that are at least in part to do with antidepressant discontinuation. Apologies if these are stupid questions. I'm new to the forum and still learning a lot of basic stuff.
 

Peater

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Yes, but since it is the summer (when I typically lose 10%+ weight just because of sunlight and better metabolism) it is hard to say what exactly was the cause of the weight loss. FWIW, for me at least, it is much more calming than progesterone, which suggests it lowers cortisol (as human studies have already demonstrated) and that is usually facilitating for weight loss.

Do you take orally? (Just out of curiosity, I understand any answer you give is not advice)
 
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haidut

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Do you take orally? (Just out of curiosity, I understand any answer you give is not advice)

I find that orally it gives the best mental effects.
 
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Being a positive allosteric modulator of the GABA-A receptor, why shouldn't this substance have the same dependence and side effects as benzodiazepines?
 

Makrosky

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Being a positive allosteric modulator of the GABA-A receptor, why shouldn't this substance have the same dependence and side effects as benzodiazepines?
Because as you said, it is allosteric modulator. Not a direct agonist.
 
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Will be an interesting experiment for those who have used Finasteride. It has been shown to directly lower Allopregnanolne levels.
my thought exactly, it seems like the allopreg level is the main or one of the main issues with finasteride... i dont get it though if you discontinue finasteride, the levels are still low, i wonder how this would impact that system... it seems like taking pregnenlone isnt the exact solution, maybe this could be different, maybe combined with pregnenlone it would be interesting

does anyone have any reviews yet that took finasteride before ? super curious...

@haidut is this the first time it has even been sold before like this in supplement form? even if i search allopregnenlone supplement on google, its completely empty lol
 
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haidut

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my thought exactly, it seems like the allopreg level is the main or one of the main issues with finasteride... i dont get it though if you discontinue finasteride, the levels are still low, i wonder how this would impact that system... it seems like taking pregnenlone isnt the exact solution, maybe this could be different, maybe combined with pregnenlone it would be interesting

does anyone have any reviews yet that took finasteride before ? super curious...

@haidut is this the first time it has even been sold before like this in supplement form? even if i search allopregnenlone supplement on google, its completely empty lol

Well, we are not allowed to sell it as a supplement. We are selling it as a lab chemical, in solution, similar to the other chemical companies that I listed earlier in the thread. What is unique in our product, is the solvent (tocoherols, fats). Most other companies sell it as either solid/crystals, or dissolved in ethanol, DMSO, etc.
 
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Well, we are not allowed to sell it as a supplement. We are selling it as a lab chemical, in solution, similar to the other chemical companies that I listed earlier in the thread. What is unique in our product, is the solvent (tocoherols, fats). Most other companies sell it as either solid/crystals, or dissolved in ethanol, DMSO, etc.

ah, thanks for the background, yes that's right it's sold as a lab chemical... i do see ZULRESSO is the one being sold as a medication in that way, seems like it pretty new.. interesting thanks for the info.
 

equipoise

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The nanomolar concentrations are what is endogenously present. When administering several milligrams (or more) exogenously micromolar concentrations are likley to be achieved. In fact, the antidepressant effect of the FDA-approved Brexanolone is likely (partially) due to stimulating thyroid synthesis and metabolism. The GABA agonism alone is not enough to explain the antidepressant effect as pure GABA agonists such as the benzodiazepine class of drugs do not have antidepressant effects but only antianxiety ones. The increase in dopamine mentioned in a previous comment and antagonism of serotonin (below) are probably also involved in the overall antidepressant effects.

Being a positive allosteric modulator of the GABA-A receptor, why shouldn't this substance have the same dependence and side effects as benzodiazepines?
Positive feedback loop. That's the whole idea of using bio identical progesterone for treatment of benzodiazepine withdrawal / glutamate storm.
Allopregnanolone is a bio identical hormone, and as such (in physiological doses) has mechanisms that prevent dependence and witihdrawal from it.

The main thing is the strength of a substance, and benzos lacking any positive feedback loop AFAIK. Thus tolerance settles in fairly fast and a 3 week course of 10mg diazepam or 0,5mg of alprazolam can leave you with rebound anxiety, insomnia, restlessness. Not to mention, aside from the fact they're anti serotonin agents, there's no health benefits to benzodiazepines. They lower your pulse rate, lower your metabolism, make you unnecessary reckless, dull your inhibitions, numb your mind and basically any original anti serotonin mechanism is replaced by a state of high serotonin in the next few days from the original dose.

Just no comparison to the likes of Progesterone with its thyroid mimetic effects and basic anti-stress effects it showcases. You should be quite safe with bio-identical hormones, given you respect them and don't overdo them.
 

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