52 replies to this topic

[Bukujutsu]

http://www.sciencedi...30645221100786X

Pregnenolone is a neurosteroid with pleiotropic (multiple effects stemming from something, essentially) actions in rodents that include the enhancement of learning and memory, neuritic outgrowth, and myelination. Further, pregnenolone administration results in elevations in downstream neurosteroids such as allopregnanolone, a molecule with neuroprotective effects that also increases neurogenesis, decreases apoptosis and inflammation, modulates the hypothalamic-pituitary-adrenal axis, and markedly increases GABAA receptor responses. In addition, pregnenolone administration elevates pregnenolone sulfate, a neurosteroid that positively modulates NMDA receptors. There are thus multiple mechanistic possibilities for pregnenolone as a potential therapeutic agent in schizophrenia, including the amelioration of NMDA receptor hypofunction (via metabolism to pregnenolone sulfate) and the mitigation of GABA dysregulation (via metabolism to allopregnanolone).

Studies:

Proof-of-Concept Trial with the Neurosteroid Pregnenolone Targeting Cognitive and Negative Symptoms in Schizophrenia (Fantastic. Well worth reading)
http://www.ncbi.nlm....les/PMC3427920/
BACS and MCCB explanation:
http://www.matricsinc.org/MCCB.htm
http://www.neurocogt...psych, 2006.pdf

http://www.nature.co...do.2013.31.html
http://www.ncbi.nlm....pubmed/23348009
http://www.ncbi.nlm....pubmed/24548129
http://www.ncbi.nlm....pubmed/24496044
http://www.ncbi.nlm....pubmed/20584515 ^ shaped response curve, unsurprisingly.

PrivateMDLabs offers a test for pregnenolone: http://www.privatemd...=14&search=#705

Thoughts? This sounds extremely promising. Healing and modulation/optimization of the brain. I would genuinely need it as I strongly, moderately at best, display all the negative symptoms of schizophrenia and have suffered from lifelong anxiety, even as a young child.

Edited by Bukujutsu, 17 March 2014 - 11:18 PM.

[Strelok]

Very interesting. I wonder if pregnenelone would negatively interfere with the endocrine system, since it is a prohormone and a lot of different steroid hormones are made from it. Is there a such thing as a sensible dosage for a healthy male in his mid twenties?

[Bukujutsu]

I would not recommend it for someone who is free of the problems that it may help alleviate. I also happen to suffer from hypogonadism, so I'm not concerned about that. My estradiol levels are also low. But, I don't know how significant its effects are as a prohormone, how much of a difference it will make at the doses used, as I didn't find any data on that.

Regardless, with testing you can find out if your levels are below the optimal range. If you aren't, attempting to use as an enhancer may be too dangerous, or at least detrimental due to the response curve.

Unreliable website AFAIK and no reference, but it's something:

http://articles.merc...7/adrenals.aspx

Despite its powerful metabolites, pregnenolone is acknowledged to be without significant side effects, with minimal or no anabolic, estrogenic or androgenic activity.

It's what I expected. It doesn't seem likely that it would be responsible for a significant percentage of hormone production.

Here's a paper from the Life Extension Foundation: http://www.lef.org/m...nenolone_01.htm

Edited by Bukujutsu, 18 March 2014 - 12:48 AM.

[Strelok]

I am interested in its potential as a nootropic (essentially everything you bolded in your OP). So while I may have no form of mental illness, I think things can be improved. If I can get those benefits without screwing up my hormones, I think I'm interested in a trial run. I read the LEF article, and they are talking about relatively high doses (50+ mg). I'm thinking of trying it out at, say, 5mg 3x/week, or at most 10mg 3x/week. And this would only be for a couple months or so, not as something to rely on long-term.

[Bukujutsu]

Eh, go for it. What's the worst that's likely to happen? You'll probably be fine and could provide some interesting anecdotal data. Considering modern diets and lifestyles, there are so many detrimental impacts that it wouldn't surprise me if most people were deficient.

What route of administration are you going to try? I don't know what the bioavailability is for oral and sublingual.

A simple google found this: http://www.drlam.com...and_hormone.asp

Oral pregnenolone pills work well. Sublingual administration is an excellent option by bypassing the initial liver metabolism that occurs after swallowing an oral pill but it tends to be "spiky" and not well tolerated by those who are sensitive or in advanced s adrenal fatigue state.

And a mention of how common deficiency is here: http://thinksteroids...-134246448.html

Here is a cut and paste on what Dr. John said.
I quit running pregnenolone assays--they are ALWAYS low. Dr. Rothenberg made this same comment in one of his lectures.

Some books have been published on it as well: http://www.amazon.co...rnid=2941120011

Lots more reading to be done.

Edited by Bukujutsu, 18 March 2014 - 07:46 AM.

[zeropoint]

I would not recommend it for someone who is free of the problems that it may help alleviate. I also happen to suffer from hypogonadism, so I'm not concerned about that. My estradiol levels are also low. But, I don't know how significant its effects are as a prohormone, how much of a difference it will make at the doses used, as I didn't find any data on that.

Regardless, with testing you can find out if your levels are below the optimal range. If you aren't, attempting to use as an enhancer may be too dangerous, or at least detrimental due to the response curve.

Unreliable website AFAIK and no reference, but it's something:

http://articles.merc...7/adrenals.aspx

Despite its powerful metabolites, pregnenolone is acknowledged to be without significant side effects, with minimal or no anabolic, estrogenic or androgenic activity.

It's what I expected. It doesn't seem likely that it would be responsible for a significant percentage of hormone production.

Here's a paper from the Life Extension Foundation: http://www.lef.org/m...nenolone_01.htm

According to one study you quoted:
Absence of conversion to other steroids

Pregnenolone administration for 8 weeks to patients with schizophrenia or schizoaffective disorder did not result in downstream elevations of cortisol, testosterone, free testosterone, DHEA, androstenedione, or estradiol (Table 6). As pregnenolone is a potential precursor to a number of steroids, pregnenolone could theoretically be metabolized to all of these molecules. Our data suggest, however, that pregnenolone metabolism is weighted toward biosynthetic pathways resulting in pregnenolone sulfate and allopregnanolone formation, rather than toward glucocorticoid or sex steroid synthesis involving testosterone or estradiol

maybe this only applies to schizophrenics but I doubt it, effectively making this not so useful for hypogonadism....

[Bukujutsu]

Ah, great! I didn't want elevation of that anyway. I'm already on testosterone replacement therapy.

[Strelok]

I got some 10mg capsule of pregnenolone. I empty the capsule under my tounge for sublingual administration, 10mg daily. I'll report back if there is any type of noticable effect after several weeks of use.

[Absent]

I'm about to order some of this. Sounds very interesting. I wonder what effect it will have on effortful mental training

[nowayout]

Gave me heart arrhythmias.

[Strelok]

Gave me heart arrhythmias.

Almost meaningless without stating dosage and frequency.

[nowayout]

Gave me heart arrhythmias.

Almost meaningless without stating dosage and frequency.

It was a regular recommended dose of a transdermal you'll probably find on google or amazon.

Heart palpitations was not uncommon as a side effect of prenenolone as reported on anther forum I read sometimes.

[Strelok]

Gave me heart arrhythmias.

Almost meaningless without stating dosage and frequency.

It was a regular recommended dose of a transdermal you'll probably find on google or amazon.

Heart palpitations was not uncommon as a side effect of prenenolone as reported on anther forum I read sometimes.

Thanks. I'll definitely keep an eye on any side effects potentially manifesting. I'm hoping my low dose will allow me to reap the benefits of pregnenolone without any pesky side effects. I've taken 10mg three days in a row so far and there has been nothing negative. If anything, an improvement in mental energy/clarity.

[VERITAS INCORRUPTUS]

^^^

The enhanced mental energy and clarity is probably a good sign you are in the right ballpark

Some find their vision enhanced and a notable mood improvement as good indicators when at their optimal dose 

A considerationg for titrating up to 20mg

[Absent]

Has anyone taking this experienced any notable negative long-term effects? (over the course of a week+?) 

[Jeoshua]

I've been taking 10-20mg per day as part of a stack, for the past two weeks straight. No real negative side effects to report, other than a slight amount of weight gain that I can't definitively link to Pregnenolone itself, and which may just as easily have come from something else in my stack, like possibly the Creatine, or even the fact that I've been walking around much more recently now that my bike is in a state of disrepair. I've always been underweight anyways, so that's not exactly an unwanted effect.

 

As far as a reasonable dosage for someone in their 20s, there really isn't one. Endogenous pregnenolone production starts falling around the age of 30. When young, the body synthesizes around 100mg per day, and this figure falls by about 5-10mg every decade, starting at around 30 years of age. A reasonable life extension protocol would keep that production up to it's levels in youth, so around 5-10mg at 30, 10-20 at 40, 15-30 at 50 years, etc. A nootropic level of supplementation would attempt to get that level somewhat higher than normal levels, in the hopes that the excess would be converted into allopregnenolone in the brain.

 

While it is possible to get pregnenolone in pills ranging all the way up to 100mg, I wouldn't personally recommend this. I bought some of those pills in the assumption that it would be good, but the side effects were noticeable at that range, and really did a number on some acne I hadn't seen since I was 18.

Edited by Jeoshua, 09 April 2014 - 02:50 PM.

[Absent]

I ordered some 50mg tablets so that I could crush them and dose them that way. Seems like it should be viable. Would you say the effects are noticable at 10-20mg per day? Explicitly, what is most noticeable? Mood, functioning? 

[Jeoshua]

The effects that I noted and that could definitely be linked to Pregnenolone were a stabilization in mood, primarily. I also felt much more outgoing than usual, and my vision felt brightened, as if the color and sharpness had been turned up (but that might well be placebo). There may have been some effects on memory, but I can't disentangle them from the rest of the stack. I can say that with the Pregnenolone, my stack makes me feel 10 feet tall. Literally, I mean that. I literally felt as if I were floating above everything, even when it was above me. I wish I could get a more definite qualitative assessment than that, and not rely on metaphor and subjective feelings... but I can definitely say that at 10-20 mg I feel it, I like it, and intend to keep with it.

[Gerrans]

My experience of pregnenolone went like this.

 

I habitually experiment with one or two supplements at a time, to see if they do anything. I bought some 50mg pregnenolone capsules and took one every Monday. I chose to take it weekly because I had read that that is a sufficiently high dose, and that it stores up. This went on for months, and I did not notice any effect from it--so I assumed that, like most supplements I try, pregnenolone has no discernible effect on me.

 

Then I became ill (nothing to do with the pregnenolone), and having read that pregnenolone is particularly useful when ill, I took four capsules, and thought no more of it. That evening, I had a two-hour migraine, starting with full aura. I do suffer from the occasional migraine so did not connect this one with the pregnenolone. The only odd thing about it was that after two hours the very unpleasant, drilling, right-side headache went away quickly, leaving no trace of the headache behind. That had not happened to me with a migraine before. But I was still unwell, and the next day I again took four pregnenolone. That evening, at exactly the same time as the night before, another migraine aura started. The migraine repeated the pattern of the previous one and vanished after two hours. As I lay on the bed in the throes of this migraine, I remembered the pregnenolone.

 

So the next day, I took no pregnenolone; and, sure enough, had no repeat migraine. I binned the rest of the tub.

 

But there was one extra thing. For a couple of hours before each of the two migraines (the phase sometimes called the prodrome), I felt mentally blissed and pure. It is hard to describe, but it was as if cool distilled water was bathing my brain, after which pictures and music became slightly more intense than usual. I would love to have experimented more with pregnenolone, to try to recreate that beautiful effect--except that my fear of the migraines won the day. I have toyed with the idea of trying some 10g capsules and building up a dose towards one that might reproduce the brain clarity without triggering migraines. But discretion gained the better part of valour; and I think it wiser not to take again a substance that caused me so much pain, overdosed with it though I stupidly was.

Edited by Gerrans, 09 April 2014 - 09:30 PM.

[VERITAS INCORRUPTUS]

^^^

It would have made sense to have kept the 50mg capsules and trialed the 50mg ED firstly as there was no adverse effects there.  Potentially may have become a nice therapeutic level.  An acute dose of 100mg as well might appear to be a sweet spot for you.

 

It is of course understandable the intense migraines scared you off completely, but there may as well yet be a dosing window for therapeutic benefits sans adverse effects.  

 

As well, indeed it can be used to create a moderate 'recreational effect', though that is likely not the best course on a health benefit oriented protocol (at least to do so with any frequency).  Not all will find a level here that completely accommodates, but there exists the potential (again perhaps 100mg, if you wish to brave it).  

 

Anyway, best of success if you embark on experimenting with this again

Edited by VERITAS INCORRUPTUS, 09 April 2014 - 09:27 PM.

[Bukujutsu]

g. I bought some 50mg pregnenolone capsules 

 

I took four capsules, and thought no more of it. That evening, I had a two-hour migraine, starting with full aura

 

200mg is way too high. Even 50 is likely too much. It's no surprise you were having side effects.

 

 

 

 

I have toyed with the idea of trying some 10g capsules and building up a dose towards one that might reproduce the brain clarity without triggering migraines. 

 

Did you mean 10mg? It might be better to start with 5mg, and I would not start supplementation without having your levels tested.

[Gerrans]

 

g. I bought some 50mg pregnenolone capsules 

 

I took four capsules, and thought no more of it. That evening, I had a two-hour migraine, starting with full aura

 

200mg is way too high. Even 50 is likely too much. It's no surprise you were having side effects.

 

 

 

 

I have toyed with the idea of trying some 10g capsules and building up a dose towards one that might reproduce the brain clarity without triggering migraines. 

 

Did you mean 10mg? It might be better to start with 5mg, and I would not start supplementation without having your levels tested.

 

 

Yes, meant 10mg.

 

I admit I got this experiment wrong. But I suppose it provides an anecdote about the effect this stuff could have on certain people if they take too much.

 

One thing I have learned from all my experimenting is that I may be nitric oxide sensitive. I do not know if that was a factor here; but supplements that promote nitric oxide seem often to provoke headaches or migraines for me.
 

Edited by Gerrans, 09 April 2014 - 11:28 PM.

[Jeoshua]

I've never seen any information to suggest that pregnenolone has any effects on NOS, either directly or indirectly. I'd love to be proven wrong on this, of course.

[VERITAS INCORRUPTUS]

^^^

Pregnenolone is a precursor to DHEA.  DHEA activates endothelial nitric oxide synthase (eNOS), which produces the potent vasodilator nitric oxide (NO).  Such can lead to headaches in those with a sensitivity.

[Jeoshua]

It is, but increasing Pregnenolone hasn't really been shown to increase the synthesis of either Androgens or Corticosteroids to any significant amount, instead, most of the excess is turned into Allopregnenolone.

[VERITAS INCORRUPTUS]

It is, but increasing Pregnenolone hasn't really been shown to increase the synthesis of either Androgens or Corticosteroids to any significant amount, instead, most of the excess is turned into Allopregnenolone.

 

Pregnenolone has significant conversion to DHEA within the pathways of conversion that can be elicited from endogenous or exogenous pregnenolone.  The body can only manufacture DHEA from pregnenolone so obviously all endogenously produced DHEA is derived via this pathway.  Pregnenolone is the master hormone in which all steroids are derived (in itself derived from cholesterol).  One can assertain a significant conversion of exogenous pregnenolone to DHEA and subsequent DHEA downstream steroids via a notable increase in acne.

 

Allopregnanolone (to correct that it is not 'allopregnenolone') is a neurosteroid that is as well derived from pregnenolone, but is not a 'dominant' part of the pathway.  It is mediated through the progesterone pathway, the 'secondary dominant' pathway, along with the DHEA pathway. A small increase in this neurosteroid from conversion from exogenous pregnenolone goes a long way.

 

Do note that pregnenolone sulfate as well is a neurosteroid.  Just to note further, testosterone and cortisone also can form neurosteroids within 'downstream' conversion. They are 3-alpha-androstandiol and tetrahydrodeoxycorticosterone respectively.

[Jeoshua]

I've seen evidence from both sides now.

In either case, the idea of taking 100mg is extremely absurd. That goes above and beyond the normal, endogenous production of pregnenolone, and would be completely overkill. And I can corroborate that, at that dosage, acne is a big problem, even after a single dose. So at that level DHEA is certainly being produced. I haven't noticed the same at the 10-20 mg mark, however.

[Strelok]

OK, here is my report so far.  The first thing to note is that I am in my mid-late twenties.  I've no serious health issues to speak of.  I have a reasonable but non-ideal diet, and take a variety of supplements.  I usually try to exercise once or twice a weak, usually in the form of lifting weights and body weight exercises.

 

I started taking pregnenolone on March 24 at 10mg daily.  I would empty the capsule under my tounge to attempt sublingual administration; this was usually shortly before or after breakfast.  On April 7 (3 days ago), I increased my dose to 20mg daily (2x10mg), still sublingual.  Before starting, I had very mild acne.  The acne was typically confined to my upper back/shoulder blades area, a couple occasional zits on my neck, and barely noticable blackheads on my nose. Overall, it was not very noticable, though my girlfriend occasionally let me know if my back was looking particularly bad. 

 

I have seen no increase in acne since starting pregnenolone.  It's no better and no worse than it was before.  I will be interested to see if acne levels stay the same as I continue to take 20mg daily (today is my 4th day at 20mg) .  At my age, I don't think it would be wise to go beyong 25mg daily.  And if I had to do it over again, I would pay a few extra dollars for sublingual tablets designed to dissolve under my tounge, as oppose to emptying capsules, filler and all, under the tounge. 

 

As far as mental effects, nothing has been very noticable.  Overall, I would say that my mood has been more stable and positive since starting pregnenolone.  I have been, perhaps, subtly more sociable (I'm typically more of an introvert).  My stress levels were low before starting preg, but they seem to have possibly even dropped some more.  Mental clarity and energy seem slightly improved.  I'm not doing anything that tests my memory at the moment, but start a rigorous 3rd year science program this summer, and am very interested in pregnenolone's nootropic potential.

 

So far I give pregnenolone a thumbs-up verdict, and will continue to take it as long as it doesn't exaccerbate my acne.  Once I'm done with my current bottle of 10mg capsules, I think I'lll order 25mg sublingual tablets.   

[Bukujutsu]

It will probably have the greatest effect on those who are suboptimal in health, both mental and physical.

 

Anyone with a mental disorder or who's in bad physical health want to experiment? Depressed, overweight, get very little sun, even slightly schizophrenic?

[Absent]

I got my pregnenolone (Source Natural Brand) tablets today. 50mg Tablets.

 

Me and a friend split one and went to the bar. He never really takes supps but I had it on me and showed him and he was interested in trying it out. While driving there we felt something noticable coming on within 15 minutes. A sort of clear-headed energy. It was definitely easier to form more complicated and complete thoughts. Fluid Memory noticeably enhanced. Stopped being noticable when we started to drink though. Later in the evening I decided to take a whole 50mg one for myself, considering it is my first day. Within another 15 minutes I felt the clear headedness coming on.

 

This could be what I was looking for all along. My diet has never been good so it is likely I was deficient in some hormones. Quite a pleasant experience. Lets see how this continues. I will likely continue taking 25mg per day.

Edited by Siro, 12 April 2014 - 11:46 PM.