StressNon - Liquid Pregnenolone

[milk_lover]

Hi there, that was earlier experiences with Pregnenalone. It no longer does that, now it just makes me blah. So + 1 to your quote. Five to twenty milligrams will elicit utter numbness. There’s no great memory or cognitive enhancement effect like some websites market it. I’ve never dosed it at 40-100, so cant say what that’s like. I’ve never used it with Dhea either. I suspect 5 mg dhea with a little Progesterone May be better

What I like about progesterone is that it gives consistent results, while pregnenolone gives random results due to going different paths down the steroid chain. But still I think it can be feminizing if taken in large doses for subsequent days.

 

[Frankdee20]

What I like about progesterone is that it gives consistent results, while pregnenolone gives random results due to going different paths down the steroid chain. But still I think it can be feminizing if taken in large doses for subsequent days.

I can’t disagree if you paid me

 

[Frankdee20]

Straight DHEA has different mental effects I’d assume than Pregnenalone’s girly ones ? The Progesterone with DHEA would simply counter anxiety ?

 

[Dhair]

The human trials with pregnenolone on depression, bipolar disorder, schizophrenia, and even autism found benefit only from doses in the 30mg - 50mg range. Actually, another schizophrenia study found benefit from 500mg daily dose as well, but most found benefit from lower doses and no benefit (and no harm either) from the 200mg+ doses.

I have seen Ray's recommendation being consistently in the 100-150mg range, with some exceptions. I know that the lower doses have been proven to be more androgenic, but the unbearable anxiousness that so many people describe is always from the low doses, and I think that is because of the NMDA agonism and the lack of progesterone conversion. People are also using low quality brands. From Healthnatura: "Beware of cheap pregnenolone. Cheap pregnenolone is often pregnenolone acetate and companies are not required to disclose that."
I haven't really seen you comment on why pregnenolone is so hit or miss with so many people. I would actually like to see you make a post on what you think the ultimate HPA dysfunction "cure" might be for people who can't handle pregnenolone, and if thyroid is required to fix it. I'm assuming cortisol would have to be as low as possible, and then thyroid should be adjusted accordingly.

 

[Wagner83]

It would be interesting to hear about people' results from higher doses (for those who did not enjoy the low doses). I posted a study (on the "progesterone is androgenic thread") which suggested 5-ar activity was actually what protected against the anti androgenic effect of progesterone, so that may be one thing to consider when supplementing progesterone.

 

[Sobieski]

Personally I've used a few different brands of pregnenolone. The key for myself is using a bio identical brand as opposed to synthetic; the first two I used (Swanson and source naturals) caused anxiety and left me feeling spaced out. Healthnatura pregnenolone is the one I used now. Took 150mg last night topically and orally and had zero stress reaction.

 

[haidut]

I have seen Ray's recommendation being consistently in the 100-150mg range, with some exceptions. I know that the lower doses have been proven to be more androgenic, but the unbearable anxiousness that so many people describe is always from the low doses, and I think that is because of the NMDA agonism and the lack of progesterone conversion. People are also using low quality brands. From Healthnatura: "Beware of cheap pregnenolone. Cheap pregnenolone is often pregnenolone acetate and companies are not required to disclose that."
I haven't really seen you comment on why pregnenolone is so hit or miss with so many people. I would actually like to see you make a post on what you think the ultimate HPA dysfunction "cure" might be for people who can't handle pregnenolone, and if thyroid is required to fix it. I'm assuming cortisol would have to be as low as possible, and then thyroid should be adjusted accordingly.

I don't agree with the statement that pregnenolone sold by other vendors is usually pregnenolone acetate. They are considered different chemicals by the FDA and have different regulations. Pregnenolone acetate is allowed in cosmetic as a solution of up to 2% and has to be explicitly disclosed as being the acetate ester. Some vendors may put a label that says "each capsules contains 10mg pregnenolone" but then they have to list the actual "pregnenolone acetate" in the "other ingredients section". So, I am pretty sure it is illegal (in the US) to sell pregnenolone acetate labelled simply as pregnenolone. If the vendor is selling pregnenolone acetate they have to disclose that somewhere on the container.

Pregnenolone is not a simple NMDA agonist. In fact, its effects on this receptor are not currently well known and at least one study shows mixed agonism/antagonism.
Inhibition of the NMDA response by pregnenolone sulphate reveals subtype selective modulation of NMDA receptors by sulphated steroids

Furthermore, it is pregnenolone sulfate (PS) that has the highest affinity for NMDA. Pregnenolone itself is possibly an antagonist, hence the rapid antidepressant effects in rodent studies (similar to ketamine - an NMDA antagonist)). In lower doses part of pregnenolone stays as pregnenolone and other parts get converted to downstream steroids like progesterone, DHEA and a number of pheromones which are only beginning to understand. Lower doses of pregnenolone are sedative in humans. There is an old study showing 1mg - 5mg pregnenolone dose improved sleep in stressed out people and most people on the forum using doses of 10mg or less reported sedative/calming effects. User/admin @charlie is one of them. The higher pregnenolone doses convert mostly into PS and as such should be much more stimulating. This is confirmed by using HED in the range of 50mg - 100mg to reverse benzodazepine sedation and HED around 1,000mg to reverse/block alcohol intoxication and addiction.
So, the exact role and effects of pregnenolone are far from known but the human studies so far show that steroidogenic enzymes have a fixed capacity to process pregnenolone, so lower doses will likely act as a precursor to downstream steroids, while higher doses will be shuttled to the long-term storage form PS. As far as HPA, an in vitro study I posted on the forum shows that a 500nM/L concentration prevented glutamate toxicity in the brain and blocked translocation of the glucocorticoid receptor (GR) to the nucleus (which blocks cortisol's genomic effects). That concentrations is achievable with doses of way less than 100mg. Higher concentrations in that study did not have beneficial effect, so yet another study suggests there is a sweet spot for pregnenolone.
Anyways, I am not saying I have all the answers but I am saying that low and high doses clearly have widely different effects.

 

[Dhair]

I don't agree with the statement that pregnenolone sold by other vendors is usually pregnenolone acetate. They are considered different chemicals by the FDA and have different regulations. Pregnenolone acetate is allowed in cosmetic as a solution of up to 2% and has to be explicitly disclosed as being the acetate ester. Some vendors may put a label that says "each capsules contains 10mg pregnenolone" but then they have to list the actual "pregnenolone acetate" in the "other ingredients section". So, I am pretty sure it is illegal (in the US) to sell pregnenolone acetate labelled simply as pregnenolone. If the vendor is selling pregnenolone acetate they have to disclose that somewhere on the container.

Pregnenolone is not a simple NMDA agonist. In fact, its effects on this receptor are not currently well known and at least one study shows mixed agonism/antagonism.
Inhibition of the NMDA response by pregnenolone sulphate reveals subtype selective modulation of NMDA receptors by sulphated steroids

Furthermore, it is pregnenolone sulfate (PS) that has the highest affinity for NMDA. Pregnenolone itself is possibly an antagonist, hence the rapid antidepressant effects in rodent studies (similar to ketamine - an NMDA antagonist)). In lower doses part of pregnenolone stays as pregnenolone and other parts get converted to downstream steroids like progesterone, DHEA and a number of pheromones which are only beginning to understand. Lower doses of pregnenolone are sedative in humans. There is an old study showing 1mg - 5mg pregnenolone dose improved sleep in stressed out people and most people on the forum using doses of 10mg or less reported sedative/calming effects. User/admin @charlie is one of them. The higher pregnenolone doses convert mostly into PS and as such should be much more stimulating. This is confirmed by using HED in the range of 50mg - 100mg to reverse benzodazepine sedation and HED around 1,000mg to reverse/block alcohol intoxication and addiction.
So, the exact role and effects of pregnenolone are far from known but the human studies so far show that steroidogenic enzymes have a fixed capacity to process pregnenolone, so lower doses will likely act as a precursor to downstream steroids, while higher doses will be shuttled to the long-term storage form PS. As far as HPA, an in vitro study I posted on the forum shows that a 500nM/L concentration prevented glutamate toxicity in the brain and blocked translocation of the glucocorticoid receptor (GR) to the nucleus (which blocks cortisol's genomic effects). That concentrations is achievable with doses of way less than 100mg. Higher concentrations in that study did not have beneficial effect, so yet another study suggests there is a sweet spot for pregnenolone.
Anyways, I am not saying I have all the answers but I am saying that low and high doses clearly have widely different effects.

Could I have your permission to email Ray this quote from you? I know that everything you are saying is backed up by studies, I just want to see if he has anything to add to this. Given the research, pregnenolone seems to be a much more complicated substance than he would have us believe.
Anyway, like I said before, this stuff has had a profound effect on how I experience the world. Colors brighter, and sometimes everything seems to become "hyperreal," which can be uncomfortable, but this effect is transient. Stressnon has such a powerful effect that I can feel this effects for days after taking just half a dose. If I take too much several days in a row, I tend to hold water and feel more bogged down, which is to be expected. My question to you is, would you take this as a sign that my brain/body needs more of this stuff and the neurosteroids it produces in order to start functioning normally again?
Ray once said that in healthy young people pregnenolone will likely have no effect at all.

 

[johnwester130]

wow this is powerful stuff when done topically on the wrist,

It sends a very strange calm throughout my body, and has wonderful synergy with glycine.

 

[jmojo]

@haidut is there a way for someone like me to create their own topical pregnenolone at home for initial testing? I have a bunch of pure pregnenolone powder leftover and I'd like to try the topical route to see if I get better reactions. I have a very high proof alcohol but does it need a fat source too? Do you need to reach a certain temp to create a solution?

 

[raypeatclips]

@haidut I have asked this before, but is there a non DMSO stressnon available or planned? Thanks

 

[Arnold Grape]

wow this is powerful stuff when done topically on the wrist,

It sends a very strange calm throughout my body, and has wonderful synergy with glycine.

WHAT IS?

 

[Wagner83]

@haidut I have asked this before, but is there a non DMSO stressnon available or planned? Thanks

=>

Yes, I still need to change the picture but all former DMSO supplements (except MelaNon) now use the new solvent SFA + ethanol and some have a tocopherol/MCT option as well.

 

[johnwester130]

WHAT IS?

............the pregnenolone

 

[DaveFoster]

Re: Custom supplement - "Pregnenolone in vitamin E w/ olive

Here is the thread where Ray says he gives his opinion on pregnenolone in vitamin E:
viewtopic.php?f=68&t=1035&start=20

Q: Do you know if pregnenolone dissolved in vit E has the same wound healing benefits of progest-E?
A(ray): Yes, probably better for most things.
Q: Can women take pregnenolone oil just like progest-E and get the same benefits in regards to PMS, cramps etc?
A(ray): Pregnenolone doesn't have the direct hormonal effects, but it's the precursor, and by stopping exaggerated stress reactions it is likely to help

Do you think pregnenolone in vitamin E could be applied to the gums like Progest-E?

Also, do you know the maximal solubility in vitamin E, say the amount of pregnenolone powder that could be added to a bottle of TocoVit?

 

[Arnold Grape]

Do you think pregnenolone in vitamin E could be applied to the gums like Progest-E?

Also, do you know the maximal solubility in vitamin E, say the amount of pregnenolone powder that could be added to a bottle of TocoVit?

Supposed to be highly insoluble in oil, from what I understand - Idea Labs sells the topical stuff, which you can put on your gums.

 

[haidut]

Do you think pregnenolone in vitamin E could be applied to the gums like Progest-E?

Also, do you know the maximal solubility in vitamin E, say the amount of pregnenolone powder that could be added to a bottle of TocoVit?

Yes, if pregnenolone is dissolved in vitamin E it can be applied to the gums just like any other steroids. Pregnenolone is very hard to dissolve in anything except chloroform, and this is why we don't have bigger amounts per ml in our products.
http://www.jpharmsci.org/article/S0095-9553(15)32106-5/pdf

We are testing some solubility enhancing trick but those likely won't increase the solubility of pregnenolone more than say 50% (in ethanol or oil) so it may help avoid precipitation in our supplements but won't allow one to pack up as much pregnenolone in vitamin E as say progesterone in Progest-E. Progesterone is much more soluble than pregnenolone, regardless of the solvent.

 

[DaveFoster]

@haidut

You've said that pregnenolone applied to the gonads can enhance steroidogenesis, but do you think topical StressNon (pregnenolone) applied to the temples, jaw, and penis would have a a similar effect as Pansterone (pregnenolone and DHEA)?

Also I'll post this since it answered one of my questions:
"You can raise steroid production to the point where the negative feedback mechanism kicks in. Apparently it can be triggered by either high estrogen (from DHEA conversion) or high androgens (again through conversion from pregnenolone or DHEA)."

 

[haidut]

@haidut

You've said that pregnenolone applied to the gonads can enhance steroidogenesis, but do you think topical StressNon (pregnenolone) applied to the temples, jaw, and penis would have a a similar effect as Pansterone (pregnenolone and DHEA)?

Also I'll post this since it answered one of my questions:
"You can raise steroid production to the point where the negative feedback mechanism kicks in. Apparently it can be triggered by either high estrogen (from DHEA conversion) or high androgens (again through conversion from pregnenolone or DHEA)."

If the pregnenolone dose is low enough (under 10mg) I don't think you will end up synthesizing that much of the suppressive steroids. The pregnenolone itself seems to become suppressive when taken in higher doses. I don't know what the limit in vivo is but the in vitro sudies said 2 - 3 uM/L is the suppression cutoff.

 

[DaveFoster]

If the pregnenolone dose is low enough (under 10mg) I don't think you will end up synthesizing that much of the suppressive steroids. The pregnenolone itself seems to become suppressive when taken in higher doses. I don't know what the limit in vivo is but the in vitro sudies said 2 - 3 uM/L is the suppression cutoff.

Thank you.

Anecdotally, I've reported similar effects from ~2 mg topical pregnenolone from 1 mg DHEA + 1 mg pregnenolone topically, albeit not as noticeable. I'll try a larger amount.