pregnenolone effects in normal humans

[stat1951]

Was hoping that one of our "medical types" could translate this into layman terms.... Are they saying that consistent use of preg reduces sedation effect of benzos?

Chronic pregnenolone effects in normal humans: attenuation of benzodiazepine-induced sedation.

Psychoneuroendocrinology. 2004 May;29(4):486-500.

Meieran SE, Reus VI, Webster R, Shafton R, Wolkowitz OM. , University of California, San Francisco School of Medicine, San Francisco, CA,

Pregnenolone is the major steroid precursor in humans. It is also a "neurosteroid" and possesses intrinsic behavioral and brain effects in animals, affecting the GABA(A) and other receptors. In two preliminary studies, we sought to characterize tolerability and psychotropic effects of pregnenolone in humans. In Study 1, 17 normal volunteers received pregnenolone and placebo for 4 weeks each (15 mg PO per day x2 weeks followed by 30 mg PO per day x2 weeks, vs. placebo x4 weeks) in a within-subject, double-blind, cross-over design, with a 4 week drug-free washout period separating the two arms. Subjects' behavioral responses were assessed at the beginning and end of the 4-week pregnenolone arm and the 4-week placebo arm. Pregnenolone was generally well-tolerated but, by itself, had no significant effects on mood, memory, self-rated sleep quality or subjective well-being. In Study 2, 11 subjects from Study 1 received a single dose of diazepam (0.2 mg/kg PO) immediately following completion of Study 1 in order to assess, in a between groups design, the impact of 4-weeks' pre-treatment with pregnenolone (N=5) vs. placebo (N=6) on the acute sedative, amnestic and anxiolytic effects of this benzodiazepine. Pregnenolone-pretreated subjects showed significantly less sedation following diazepam; this effect was clinically apparent. Diazepam's amnestic effects were non-significantly attenuated, and ratings of anxiety were unaffected. These pilot data, based on small samples, raise the possibility that chronically administered pregnenolone antagonizes certain acute effects of benzodiazepines and may enhance arousal via antagonist or inverse agonist actions at the benzodiazepine/GABA(A) receptor complex. Further larger-scale pregnenolone studies, utilizing a broader range of doses and experimental conditions, are warranted.

I also noted that researchers specifically said:

Pregnenolone was generally well-tolerated but, by itself, had no significant effects on mood, memory, self-rated sleep quality or subjective well-being.

This is the part that I questioned, as to just what it means:

Pregnenolone-pretreated subjects showed significantly less sedation following diazepam; this effect was clinically apparent. Diazepam's amnestic effects were non-significantly attenuated, and ratings of anxiety were unaffected.

Larry

[cpeil2]

Originally Posted by stat1951

Was hoping that one of our "medical types" could translate this into layman terms.... Are they saying that consistent use of preg reduces sedation effect of benzos?




I also noted that researchers specifically said:



This is the part that I questioned, as to just what it means:



Larry

I'm not a medico-type Larry, so take it for what it's worth. But I understand it to say that after pregnenolone, the valium didn't make them sleepy or stupid, but did relieve their anxiety, so it made the effect of the valium more selective, which, I would guess, is a good thing.

[stat1951]

Originally Posted by cpeil2

I'm not a medico-type Larry, so take it for what it's worth. But I understand it to say that after pregnenolone, the valium didn't make them sleepy or stupid, but did relieve their anxiety, so it made the effect of the valium more selective, which, I would guess, is a good thing.

Thanks.

That how I interpreted it also.

Wonder what it would be with the Preg that would be "activating" or "energetic" - in the sense of reducing the sedating effect of the benzo - while yet "calming" in the effect of helping the benzo further relieve the anxiety?

I have been looking into Preg as I have been supplementing it at doctor's orders. Between Test A (doing 100 mg of Test Cyp) and test B (60 mg of Test Cyp) my Total T levels dropped about 50%, my E2 levels dropped about 20% and my Total Es (already elevated) increased by 35% - where they are now at almost 150 "points" above the normal max end of reference range!

Looking at my supplementations, the only thing that I can see that I have done differently (as to prior to Test A and during time between Test A and Test B) was to start the Pregeneolone supplementation (10 mg twice daily) and increased by DIM from 100 mg with 500 mg TMG to 200 mg with 500 mg TMG. With that large of a drop in T, well, I can't even credit the DIM with lowering the E2. In fact, I have never noted a connection between taking DIM (and I've tried all of the varieties) and any reduction in E2... but something is causing an unusual elevation in total estrogens. One would have thought that they would have gone down with the Test B ressults also.... Or it could have simply been inaccuracies and variances one sees in using serum draws for testing hormone levels (which tend to fluctuate on various cycles and metabolizing processes).

Anyway, I realize that the cited clinical study has nothing to do with the estrogen issue, but found it to be an interesting aspect of Pregeneolone. If HcG in fact enhances natural Preg production, then this aspect could be another positive point for HcG therapy.

Larry

[pmgamer18]

Hi Larry I though you were going to post your new tests results maybe some of the guys can make some thing out of them. How do you feel right now with your T levels down 50%.

[Sunkist]

This is very interesting stuff. The Benzo's work on the GABA side as I remember. A lot of minor surgery is done with oral valium (et al.) and N2O inhalation and the problem is the combined sedative effect and relation to breathing.

The relation between hormones and brain chemistry never ceases to amaze me.

[1cc]

I know that since I started HRT, if I need to use a benzo, I have had to use twice as much as before HRT. This observation was very interesting to me too.

[stat1951]

Originally Posted by Sunkist

This is very interesting stuff. The Benzo's work on the GABA side as I remember. A lot of minor surgery is done with oral valium (et al.) and N2O inhalation and the problem is the combined sedative effect and relation to breathing.

The relation between hormones and brain chemistry never ceases to amaze me.

Yes, the Benzos work on the GABA aspect (in the sense that SSRIs like Prozac work on the serotonin aspects). I believe (rough explanation) that the Benzos inhibit or reduce the nerve firings that are "out of control" and causing the anxiety. With many (most?) people this is due to insufficient GABA, as GABA acts as a brake which slows the process down. Benzos - as best I recall - are like GABA reuptake inhibitors (or similar in action) in that they make what GABA neurotransmitters that are present of longer use. One would think "AHA, taking GABA supplementation would solve this problem... but unfortunately GABA basically is not able to cross the BBB (Brain Blood Barrier) to get into the brain where it is then useful. Now L- Glutamine amino acid does cross the BBB fine and that's what the brain uses of make GABA, so one would think that supplementing with L- Glutamine would do the trick. Unfortunately, in taking doses all the way between 250 mg to 2 - 4 grams daily, I never found that this helped with me (maybe anxiety also involves losing the elements that the brain uses to convert L- Glutamine to GABA also???).

1cc:

RE: I know that since I started HRT, if I need to use a benzo, I have had to use twice as much as before HRT. This observation was very interesting to me too.

I find that interesting as getting on some strong levels of TRT actually reduced my anxiety (slightly, but enough to be noticeable). And possibly my recent improvements in anxiety have not only been due solely to the increase in Xanax XR and addition of Lyrica, but also maybe some improvement was due to the supplementation of Pregeneolone (as indicated in the above cited study)???

Larry