Using High-dose Pregnenolone As An Anti-depressant

[Squatrat]

Im very itnerested in hearing if you ahd any adverse effects/symptoms, mainly speaking of the problem I have with higher dose preg which is derealization/ difficulty concentrating. Do you ever experience an intense spaced out feeling that makes it very difficult to be comfortable?

You can do a google search for "Progesterone side effects" as there are too many to remember off the top of my head and the sides can be different for men and women (obviously I didnt suffer any "bleeding issues"). My sides were water retention, watery stools, irritability, FATIGUE, some emotionality if I took way too much like the day I took 500mg of Pregnenolone. Nausea was more common which is unusual for me. I was hungry all the time and eating about 400 more calories per day then usual. Some drowsiness besides the fatigue and sleep was worse (insomnia is an offcial side effect). My allergic skin reactions to DMSO were worse which is funny now that I think about it because "allergic skin reactions" is another noted side. Basically it sucked and I got hit with everything. I had to have an emotional breakdown before I realized the high-does Pregnenolone was killing me.

And to anyone who doubts my experience ill tell you the same thing I told the other guy in the 5ar thread: Put up or shut up. If you think high-dose Progesterone is no big deal then take the amount that I was taking (75mg) for the time I was taking it (2 months) and report back here with the results.

I dont need scientific studies to tell me what I already know from first-hand experience.

 

[sladerunner69]

You can do a google search for "Progesterone side effects" as there are too many to remember off the top of my head and the sides can be different for men and women (obviously I didnt suffer any "bleeding issues"). My sides were water retention, watery stools, irritability, FATIGUE, some emotionality if I took way too much like the day I took 500mg of Pregnenolone. Nausea was more common which is unusual for me. I was hungry all the time and eating about 400 more calories per day then usual. Some drowsiness besides the fatigue and sleep was worse (insomnia is an offcial side effect). My allergic skin reactions to DMSO were worse which is funny now that I think about it because "allergic skin reactions" is another noted side. Basically it sucked and I got hit with everything. I had to have an emotional breakdown before I realized the high-does Pregnenolone was killing me.

And to anyone who doubts my experience ill tell you the same thing I told the other guy in the 5ar thread: Put up or shut up. If you think high-dose Progesterone is no big deal then take the amount that I was taking (75mg) for the time I was taking it (2 months) and report back here with the results.

I dont need scientific studies to tell me what I already know from first-hand experience.

Yeah I understand that. 75mg is to much progesterone for a man and 500mg per day seems like way too much as well. What inspied you to use such large dosages? Most people who take 300mg of preg only do it once every 10 days or so.

 

[Squatrat]

Yeah I understand that. 75mg is to much progesterone for a man and 500mg per day seems like way too much as well. What inspied you to use such large dosages? Most people who take 300mg of preg only do it once every 10 days or so.

I was "inspired" by some scientific studies that were using high dose Preg to combat depression but I didnt do my homework. I didnt understand the mechanism of Preg.

 

[sladerunner69]

I was "inspired" by some scientific studies that were using high dose Preg to combat depression but I didnt do my homework. I didnt understand the mechanism of Preg.

Which part of the mechanism, precisely? It's conversion to downstream prog, and then allopreg? It can also find itself converting to estrogen if the metabolic support system is not primed and operating at maximum efficiency turboload. Also progesterone and pregngnelone taken together is likely redundant. I do sometimes take both in one dosage but when doing so I lower the dosages of both ebcause there is a good amount of overlappign effects there.

 

[Tim Lundeen]

I posted this in another thread, reposting here.

Apparently progesterone stimulates the GABAa1 receptor, and Dr Fredrick Von Stieff says that overstimulation can cause this receptor system to downregulate and become ineffective. When GABAa1 is not working, then the glutamate system is unopposed, and you get agitated/angry, perhaps psychotic. His treatment protocols don't use GABAa1 for that reason. (See his book Brain Balance Brain In Balance: Understanding the Genetics and Neurochemistry Behind Addiction and Sobriety: Fredrick Von Stieff M.D., Katie Schuh Juarez: 9781475045673: Amazon.com: Books -- A helpful book, even if his treatment program is based on pharmaceutical drugs.)

To help recover, you can take magnesium and up to 15mg/day of zinc, which both block the NMDA receptor activated by glutamate. Vitamin E mixed tocopherals also helps calm down the cells; gamma tocopheral blocks the inflammation caused by excessive glutamate, and alpha tocopheral opposeds estrogen so that will help calm things down too. Folinic acid (e.g. calcium folinate instead of activate folate) also helps. I've seen all of these help someone.

Ray Peat's protocols for increasing cellular energy should also help (e.g. caffeine, asprin, sugar with enough calcium to prevent parathyroid increase), because they increase cellular energy, which should help damp down the inflammation -- but I didn't know about these the last time it would have been relevant, so can't say for sure.

 

[TubZy]

To the OP, why not add in a few milligrams of DHEA to your megadose preg experiment? That would have boosted DHT and eliminated the anti androgenic effects.

This is what ray suggests anyways either with preg or preg.

 

[TubZy]

.

 

[sladerunner69]

To the OP, why not add in a few milligrams of DHEA to your megadose preg experiment? That would have boosted DHT and eliminated the anti androgenic effects.

This is what ray suggests anyways either with preg or preg.

Mixing dhea with high dose preg will cause me too feel really out of whack, and has demonstrated to cause mania in studies.

 

[DavePalumbo]

TAKE NOTE. The irritability, racing thoughts, fatigue, affective flattening with paradoxical emotionality, is caused by overstimulation of the NMDA glutamate receptor. Pregnenolone is a strong NMDA agonist.
Overstimulation of the NMDA receptor leads to hypersensitivity of the 5HT2A receptor, and thus irritability, fatigue, etc.
When women take estrogen and become irritable, what causes it? It's estrogen increasing the amount of 5ht2a receptors and thus the 5ht2a receptor becoming overstimualated.

There are many 5ht2a antagonists, search Google.. Zinc and Ginkgo Biloba are some of them and as for ginkgo biloba it works instantly as you take it.

Slowly dosing pregnenolone. Going from 30mg to 60, to 90 and to hundreds of miligrams over a few days will totally avoid all these side-effects. Or just take the same dosage and ignore the side-effects. Eventually the receptors will become downregulated enough.

 

[DavidGardner]

Mixing dhea with high dose preg will cause me too feel really out of whack, and has demonstrated to cause mania in studies.

Yeah, I've done a lot better on fewer supplements rather than more. Diet and sleep trumps supplementation any day. I really don't see how anyone can handle so much pregnenolone at once. I get a very noticeable effect from just 10 mg oral--fluid retention in both muscle and fat tissue and increased libido. I can't imagine what even 100 mg would do to me.

 

[DavePalumbo]

Yeah, I've done a lot better on fewer supplements rather than more. Diet and sleep trumps supplementation any day. I really don't see how anyone can handle so much pregnenolone at once. I get a very noticeable effect from just 10 mg oral--fluid retention in both muscle and fat tissue and increased libido. I can't imagine what even 100 mg would do to me.

Try a higher dosage like 100mg. You will find that the stimulation fades and it had much different effects than 10mg does.

 

[DavidGardner]

And for the record, Vyvanse is not meth. But if you take it for long enough on a daily basis, it will mess with your head in ways that you are not even aware of. And no study is gonna tell you that. Speaking from experience....

 

[Such_Saturation]

TAKE NOTE. The irritability, racing thoughts, fatigue, affective flattening with paradoxical emotionality, is caused by overstimulation of the NMDA glutamate receptor. Pregnenolone is a strong NMDA agonist.
Overstimulation of the NMDA receptor leads to hypersensitivity of the 5HT2A receptor, and thus irritability, fatigue, etc.
When women take estrogen and become irritable, what causes it? It's estrogen increasing the amount of 5ht2a receptors and thus the 5ht2a receptor becoming overstimualated.

There are many 5ht2a antagonists, search Google.. Zinc and Ginkgo Biloba are some of them and as for ginkgo biloba it works instantly as you take it.

Slowly dosing pregnenolone. Going from 30mg to 60, to 90 and to hundreds of miligrams over a few days will totally avoid all these side-effects. Or just take the same dosage and ignore the side-effects. Eventually the receptors will become downregulated enough.

@haidut

 

[DavePalumbo]

5HT2a causes female-like irritability or borderline personality disorder-like rage. The mglur5 receptor causes autistic-like rage fits, also potentially the cause of bodybuilders' "roid-rage" (androgens cause increased activity of glutamate).
For the 5ht2a receptor there are many antagonists. For the mglur5 receptor, which becomes overactive with excessive glutamate levels, you simply take creatine as creatine uses one of the same transporters as glutamate and thus you deplete glutamate levels. There are also mglur5 antagonists out there but not many.

A third option of irritability or rage is noradrenaline, but not likely the case with pregnenolone.

 

[Frankdee20]

5HT2a causes female-like irritability or borderline personality disorder-like rage. The mglur5 receptor causes autistic-like rage fits, also potentially the cause of bodybuilders' "roid-rage" (androgens cause increased activity of glutamate).
For the 5ht2a receptor there are many antagonists. For the mglur5 receptor, which becomes overactive with excessive glutamate levels, you simply take creatine as creatine uses one of the same transporters as glutamate and thus you deplete glutamate levels. There are also mglur5 antagonists out there but not many.

A third option of irritability or rage is noradrenaline, but not likely the case with pregnenolone.

Wouldn't these hypersensitive 5ht2a receptors eventually down regulate from over activation ?

 

[DavePalumbo]

That's what I implied but obviously it's a major cause of Asperger's and other diseases so it seems at least in some cases it doesn't. But personally I have no issue with larger doses of pregnenolone, no irritability.

 

[Frankdee20]

That's what I implied but obviously it's a major cause of Asperger's and other diseases so it seems at least in some cases it doesn't. But personally I have no issue with larger doses of pregnenolone, no irritability.

Yeah, Pregnenalone has a sweet spot for many folks. I used to react terribly from starting at 10. Now, I take 5-10 mg and get a nice feeling from it. I can't imagine going over this dose though.

 

[haidut]

@haidut

The irritability could just as easily be caused by allopregnanolone, as it is a known effect of raising the levels of this steroid in the brain, and pregnenolone raises allopregnanolone (especially in higher doses). Also, I think pregnenolone itself is not an NMDA agnist, but rather pregnenolone sulfate (PS). However, even PS is a relatively weak NMDA agonist compared to something like endogenous glutamate.
Pregnenolone sulfate - Wikipedia

So, taking a lower dose pregnenolone should avoid the increase in PS but has still been reported to cause irritability in some people, which makes me think the conversion into allopregnanolone is a much more likely cause. That being said, I have always felt best on 30mg - 50mg pregnenolone daily. Higher doses seem to have anti-androgenic effects for me.
Btw, pharma companies recognize the anti-depressant effects of pregnenolone and have developed a non-metabolizable alternative which has been patented as depression treatment.
3β-Methoxypregnenolone - Wikipedia

 

[Frankdee20]

The irritability could just as easily be caused by allopregnanolone, as it is a known effect of raising the levels of this steroid in the brain, and pregnenolone raises allopregnanolone (especially in higher doses). Also, I think pregnenolone itself is not an NMDA agnist, but rather pregnenolone sulfate (PS). However, even PS is a relatively weak NMDA agonist compared to something like endogenous glutamate.
Pregnenolone sulfate - Wikipedia

So, taking a lower dose pregnenolone should avoid the increase in PS but has still been reported to cause irritability in some people, which makes me think the conversion into allopregnanolone is a much more likely cause. That being said, I have always felt best on 30mg - 50mg pregnenolone daily. Higher doses seem to have anti-androgenic effects for me.
Btw, pharma companies recognize the anti-depressant effects of pregnenolone and have developed a non-metabolizable alternative which has been patented as depression treatment.
3β-Methoxypregnenolone - Wikipedia

Is PS getting its conversion in the brain ? Thought it doesn't cross BBB

 

[haidut]

Is PS getting its conversion in the brain ? Thought it doesn't cross BBB

No, I think it happens in the intestine if you take pregnenolone exogenously. But high levels of PS have been seen in the brain since the brain can synthesize its own pregnenolone and convert it to PS as a long term storage form.