Dhea Inhibits Serotonin Synthesis Due To Stress Exposure

haidut

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DHEA seems to be an inhibitor of the enzyme TPH, which as we know synthesizes serotonin from tryptophan. It seems that, as per Peat's ideas, the serotonin increases from stress is due to cortisol. DHEA being a cortisol antagonist was able to block this effect. DHEA only had an effect when rats were exposed to stress. DHEA was administred directly into the brain, so it's hard to come up with a dose, but it is safe to assume a factor of 10-15 applies to achieve the same with oral dose. So, an oral human equivalent dose that should achieve similar effects would be 15mg-20mg during or shortly after the stressful event.

http://www.ncbi.nlm.nih.gov/pubmed/8032685

"...Bilateral infusion of dehydroepiandrosterone (DHEA) given intracerebroventricularly blocked the sound stress-induced increase in tryptophan hydroxylase activity observed ex vivo in midbrain and cortex but had no effect on the level of tryptophan hydroxylase activity from sham-stressed rats. DHEA (20 micrograms total dose) given bilaterally into the region of the central nucleus of the amygdala, 30 min prior to 1 h sound stress, also blocked the increase in enzyme activity in a dose-dependent manner. The DHEA treatment did not alter the activation of the enzyme seen in vitro in the presence of phosphorylating conditions. The effect of DHEA was steroid specific in that other sex steroids, such as estrogen, androgens, or progesterone, were without any effect. Coadministration, 20 micrograms each, of the potent glucocorticoid agonist, RU 28362, with DHEA 30 min prior to 1 h sound stress completely blocked the DHEA suppressive effect on sound stress-induced increases in tryptophan hydroxylase activity. The results obtained suggest that DHEA blocks this increase in tryptophan hydroxylase activity by antagonizing the effects of glucocorticoid."
 

gretchen

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Great info. I'll hop up and go take it.

So far I've noticed some stress reducing effects, a little.
 
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haidut

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gretchen said:
Great info. I'll hop up and go take it.

So far I've noticed some stress reducing effects, a little.

Yes, DHEA is considered to be a cortisol antagonist, so this is to be expected. However, remember to not take more than 5mg-10mg at a time or it may end up increasing estrogen and achieving the exact opposite by increasing stress.
 

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haidut you've been posting lotta DHEA studies...I know tobacco increases DHEA in a big way and also has some aromatase inhibiting properties. I wonder if that's behind a lot of its benefits, it kind of lines up with a lot of what you're posting about DHEA
 
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pboy said:
haidut you've been posting lotta DHEA studies...I know tobacco increases DHEA in a big way and also has some aromatase inhibiting properties. I wonder if that's behind a lot of its benefits, it kind of lines up with a lot of what you're posting about DHEA

The aromatase inhibition is probably a major benefit. Also, smoking has been shown to increase dopamine. Interestingly, nicotine gum of patch does not usually increase dopamine in humans. I think I saw a study that smoking both tobacco and weed increases brain levels of pregnenolone and if this is true then it would explain a good deal of whatever benefits smoking has.
 

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:bump2

DHEA for the win. :D
 

pboy

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just re reading the topic, this makes total sense...serotonin only happens, from my experience, if theres either an acute toxin or disturbing sound, scent, person, or something in my close viscinity, or a perceived lack, or of course just being hungry or low on sugar, so serotonin rising due to cortisol is probably the most accurate way of it happening...I guess if you really were just trying to hibernate then eventually it would stay elevated and cortisol would lower but that's kinda the only situation I can think of that happening

Anyways, the thing ive realized with tobacco, I don't know if its increasing my DHEA or if its just high naturally cause of my diet/lifestyle/mentality, but its kinda like coffee in the sense...well, I guess any stimulant, that it can aggravate cortisol if you smoke too much at once, or on an empty stomach, or just like late at night when your bodies metabolism has wound down...interstingly though it seems to be anti serotonin, but still the cortisol isn't ideal. I used to use it a lot for that exact reason, when stress was like backed up or overbearing, even though cortisol would be there pretty much regardless, tobacco like provided the spark that would shut mostly down serotonin and allow me to start tackling problems, which might be adrenaline induced...either way though, its better than serotonin. However, I think cortisol has its own problems for sure even if nothing else bad is triggered...just alone its no good, it really like messes up your appetite, senses, and I suspect is bad for the heart...because in a cortisol state its really hard to have heart felt vibes, as if the heart was tightened and cold, I could see it leading to fibrosis over time in people that didn't have a certain mentaility. I have my own reasons to believe this, but I think DHEA and I guess T are highly related to mentality, experience, and things like that...its almost like the opposite of learned helplessness...the more times you've overcome odds, the more confidence, just life experience, and obviously some level of physical agility and capability helps a lot...but just like the shite ive had to overcome in my life and all that has taken has left me feeling like no challenge is insurmountable, even tho I avoid bad situtations cause they still suck, whatever happens, I maintain a certain confident focus and it keeps my heart rate steady, and feels like no damage is being left, no residue, I suspect this is high DHEA, and in that case...just being in a meditative mind set, but again, this really only comes from experience and confidence and mostly your brains wiring, and even higher thoughts, really protects against the negative effects of various stress hormones. I think the highest form of confidence is developing an ability to listen and skill in understanding your own being...senses and signals, in the sense you arent depending on others or looking for answers outside yourself...reattatching your umbilical cord to the ethers and your higher faculties...this ensures that no stress really can get to you wherever you may be. For me now days, the worse thing there is probably is becoming hypotonic of fluid in the body...for some reason the body like gets major effed up by that, its the only condition that like has the ability to really irritate me, and the only real solution is to consume something hypertonic. Every other condition of stress, even hunger, lack of sleep, feeling trapped, whatever...cant really bother me that much in the sense of getting under my skin. But if I become hypotonic it like really messes with me, so that's like my prime thing I avoid

without a doubt hypotonicity will tank, temporarily at least, your DHEA

I don't like the idea of people playing with hormone supplements...it seems like there would be a very narrow window that wouldn't lead people who naturally don't pruduce enough DHEA to not just have any supplemental DHEA be converted into estrogen, that would make sense actually. Or if it did work for a little while without being converted to estrogen, you'd have like a semi false sense of resilience kinda thing...maybe a perceived sense of it, but not the skills or mentality to back it up
 

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pboy said:
I don't like the idea of people playing with hormone supplements...it seems like there would be a very narrow window that wouldn't lead people who naturally don't pruduce enough DHEA to not just have any supplemental DHEA be converted into estrogen, that would make sense actually. Or if it did work for a little while without being converted to estrogen, you'd have like a semi false sense of resilience kinda thing...maybe a perceived sense of it, but not the skills or mentality to back it up

Exactly.
 

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haidut said:
https://raypeatforum.com/forums/posts/80986/
pboy said:
haidut you've been posting lotta DHEA studies...I know tobacco increases DHEA in a big way and also has some aromatase inhibiting properties. I wonder if that's behind a lot of its benefits, it kind of lines up with a lot of what you're posting about DHEA

The aromatase inhibition is probably a major benefit. Also, smoking has been shown to increase dopamine. Interestingly, nicotine gum of patch does not usually increase dopamine in humans. I think I saw a study that smoking both tobacco and weed increases brain levels of pregnenolone and if this is true then it would explain a good deal of whatever benefits smoking has.

Nicotine alone does seem to participate in the dopamine effect from what I read.
 
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sladerunner69

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Haidut what would be your advice on how long to continue DHEA supplementation? I've been doing 15mg a day for a couple months. At first it had a profound, mood/energy/focus boosting affect, I mean it was keeping me wired, hot, aggressive all day long. Now, however, that feeling has dampened considerably and only has a very subtle effect. What's going on here? Should I take a week off of DHEA or is that unnecessary?
 
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sladerunner69 said:
post 118014 Haidut what would be your advice on how long to continue DHEA supplementation? I've been doing 15mg a day for a couple months. At first it had a profound, mood/energy/focus boosting affect, I mean it was keeping me wired, hot, aggressive all day long. Now, however, that feeling has dampened considerably and only has a very subtle effect. What's going on here? Should I take a week off of DHEA or is that unnecessary?

I had the same experience. After 2 months on 10mg DHEA daily it stopped having profound effects and instead it only had a slight cognition boosting effect. After stopping for a week and then taking 5mg I felt like I was superman. My muscles got huge without food or exercise...and it subsided in a few days. I guess it does build up, which explains why Ray only takes 2-3 mg daily.
 
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sladerunner69

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So then your recommendation would be to take it daily but in small doses? I agree with you on the muscle synthesis, I haven't been this muscular since before I was stricken with propecia syndrome. It's really impressive how potent this stuff is... close to steroids or something. Clearly much safer considering it doesnt intercept the hpa axis or anything like that. I should get my bodybuilder friends on this stuff, they'd love it. I'll probably try a few days break here and there for a receptor reset... :thumbup
 
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sladerunner69 said:
post 118021 So then your recommendation would be to take it daily but in small doses? I agree with you on the muscle synthesis, I haven't been this muscular since before I was stricken with propecia syndrome. It's really impressive how potent this stuff is... close to steroids or something. Clearly much safer considering it doesnt intercept the hpa axis or anything like that. I should get my bodybuilder friends on this stuff, they'd love it. I'll probably try a few days break here and there for a receptor reset... :thumbup

Yes, I'd do smaller doses like Ray but my capsules are 5mg each so it's not that easy. I guess I will try to open one of them and separate the powder into 2 equal piles of 2.5mg each and take that for 2 days. I think lower doses would go completely towards DHT but I''ll report back when I have some real data.
 
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sladerunner69

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haidut said:
post 118023
Yes, I'd do smaller doses like Ray but my capsules are 5mg each so it's not that easy. I guess I will try to open one of them and separate the powder into 2 equal piles of 2.5mg each and take that for 2 days. I think lower doses would go completely towards DHT but I''ll report back when I have some real data.


You use caps? Aren't you recommending to use it topically? Or you break open the caps and mix the powder with a binding agent like alcohol or a cream or what exactly? As of now Im using life-flow dhea cream which is a pretty decent product but it has someother ingredients like msm and shea butter, grape seed extract that are pretty unnecessary for me. I'm going to use that pansterone stuff when Im done with this bottle though!
 
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sladerunner69 said:
post 118025
haidut said:
post 118023
Yes, I'd do smaller doses like Ray but my capsules are 5mg each so it's not that easy. I guess I will try to open one of them and separate the powder into 2 equal piles of 2.5mg each and take that for 2 days. I think lower doses would go completely towards DHT but I''ll report back when I have some real data.


You use caps? Aren't you recommending to use it topically? Or you break open the caps and mix the powder with a binding agent like alcohol or a cream or what exactly? As of now Im using life-flow dhea cream which is a pretty decent product but it has someother ingredients like msm and shea butter, grape seed extract that are pretty unnecessary for me. I'm going to use that pansterone stuff when Im done with this bottle though!

Topical and oral DHEA have different metabolism and effects. Since Ray said he was taking it orally, my response was in the context of oral use. Topically I use Pansterone, but I wanted to see if I can replicate the results Ray had with oral use.
 
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Greg says

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sladerunner69 said:
Haidut what would be your advice on how long to continue DHEA supplementation? I've been doing 15mg a day for a couple months. At first it had a profound, mood/energy/focus boosting affect, I mean it was keeping me wired, hot, aggressive all day long. Now, however, that feeling has dampened considerably and only has a very subtle effect. What's going on here? Should I take a week off of DHEA or is that unnecessary?

This is also my experience. Great results for a few months (that nice assertive aggressive testosterone feeling, strong libido, stress resilience) but now I've had to stop it as it isn't doing much, maybe even causing negative feelings, libido decreased.
 

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haidut said:
post 118026
sladerunner69 said:
post 118025
haidut said:
post 118023
Yes, I'd do smaller doses like Ray but my capsules are 5mg each so it's not that easy. I guess I will try to open one of them and separate the powder into 2 equal piles of 2.5mg each and take that for 2 days. I think lower doses would go completely towards DHT but I''ll report back when I have some real data.


You use caps? Aren't you recommending to use it topically? Or you break open the caps and mix the powder with a binding agent like alcohol or a cream or what exactly? As of now Im using life-flow dhea cream which is a pretty decent product but it has someother ingredients like msm and shea butter, grape seed extract that are pretty unnecessary for me. I'm going to use that pansterone stuff when Im done with this bottle though!

Topical and oral DHEA have different metabolism and effects. Since Ray said he was taking it orally, my response was in the context of oral use. Topically I use Pansterone, but I wanted to see if I can replicate the results Ray had with oral use.


I see... I have tried oral before as well but it seems to just be less absorbed through the gi tract. What do you think about coffee and increasing dht? Personally I think caffiene is very similar to progesterone, and opposes DHT but also increases Testosterone. I can't seem to drink coffee without feeling brainfogged afterwards, I've had it with a meal and with protein and extra vitamins... nothing does the trick.
 
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sladerunner69 said:
post 118079
haidut said:
post 118026
sladerunner69 said:
post 118025
haidut said:
post 118023
Yes, I'd do smaller doses like Ray but my capsules are 5mg each so it's not that easy. I guess I will try to open one of them and separate the powder into 2 equal piles of 2.5mg each and take that for 2 days. I think lower doses would go completely towards DHT but I''ll report back when I have some real data.


You use caps? Aren't you recommending to use it topically? Or you break open the caps and mix the powder with a binding agent like alcohol or a cream or what exactly? As of now Im using life-flow dhea cream which is a pretty decent product but it has someother ingredients like msm and shea butter, grape seed extract that are pretty unnecessary for me. I'm going to use that pansterone stuff when Im done with this bottle though!

Topical and oral DHEA have different metabolism and effects. Since Ray said he was taking it orally, my response was in the context of oral use. Topically I use Pansterone, but I wanted to see if I can replicate the results Ray had with oral use.


I see... I have tried oral before as well but it seems to just be less absorbed through the gi tract. What do you think about coffee and increasing dht? Personally I think caffiene is very similar to progesterone, and opposes DHT but also increases Testosterone. I can't seem to drink coffee without feeling brainfogged afterwards, I've had it with a meal and with protein and extra vitamins... nothing does the trick.

Lower doses of caffeine seem to be androgenic as they boost conversion of cholesterol into the downstream steroids and also upregulates 5-AR. Higher doses (400mg+) have progesterone-like effects and disintegrate the estrogen "receptor".
viewtopic.php?t=6488
I guess both effects are beneficial depending on what a person needs.
 
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sladerunner69

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Lower doses being under 200mg then? I don't have much more than that... I'm generally on 500mg a day. After I drink lots of coffee I wake up the enxt day feeling mega spaced-out. Like right now, it's like my pre-frontal cortex is at half power. Have you ever seen those studies where coffee reduced blood flow to the brain by 30%? I think that might have something to do with it plus the potential decrease in DHT. When I crashed on propecia It fealt like the foward half of my brain was literally missing. I couldn't concentrate on anything and was pretty much a sad zombified lump...

What does disintegrate the estrogen receptor mean exactly? Switching off or a genuine destruction?
 
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haidut

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sladerunner69 said:
post 118143 Lower doses being under 200mg then? I don't have much more than that... I'm generally on 500mg a day. After I drink lots of coffee I wake up the enxt day feeling mega spaced-out. Like right now, it's like my pre-frontal cortex is at half power. Have you ever seen those studies where coffee reduced blood flow to the brain by 30%? I think that might have something to do with it plus the potential decrease in DHT. When I crashed on propecia It fealt like the foward half of my brain was literally missing. I couldn't concentrate on anything and was pretty much a sad zombified lump...

What does disintegrate the estrogen receptor mean exactly? Switching off or a genuine destruction?

Progesterone and caffeine both destroy the estrogen "receptor" physically. Since that "receptor" is just a protein the cell makes this means that until it manufactures new estrogen "receptor" it should be more or less immune to effects of estrogen. Suicide aromatase inhibitors like exemestane acts the same way - they destroy the enzyme and until the cell makes new aromatase proteins it is not capable of making new estrogen. In the case of exmestane, this means it taks 2-3 days for the cell to recover from the aromatase destruction.
 
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