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Mifepristone for Depression & HPA axis Dysfunction

hpa axis mifepristone

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#61 Nemo888

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Posted 15 October 2014 - 02:06 AM

I have a pituitary injury that damaged my HPA axis. I am wondering why a dangerous abortifacient instead of bioidentical hormone replacement. I had low resting cortisol and my FT3 was not being converted to FT4 due to insufficient HGH.

With the supplementation of Testosterone and growth hormone I feel just like I did before I was injured. Bioidentical is so much easier than trying to metabolize bizarre synthetics.

If I miss my hgh shot I find coffee can actually help sometimes. Lacking cortisol and FT4 my body tends to then produce adrenalin to make up the metabolic shortfall. A big coffee can shut down the adrenalin cascade and really calm me down.

#62 Flex

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Posted 15 October 2014 - 12:05 PM

In my case, Caffeine increases a depression, who I highly assume that its caused by either GR or MR de-regulation.

 

Basically, the advantage of Mifepristone is the possibly lasting modulation.

In contrast, a substitute needs to be admistered every time.



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#63 Nemo888

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Posted 15 October 2014 - 01:04 PM

But my drugs have the side effects of big muscles, lots of energy, effective birth control and boners. What does Mifepristone have? ;)

#64 YoungSchizo

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Posted 15 October 2014 - 04:14 PM

But my drugs have the side effects of big muscles, lots of energy, effective birth control and boners. What does Mifepristone have? ;)

 

The ability to maintain all of that  ;)



#65 Flex

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Posted 15 October 2014 - 07:13 PM

But my drugs have the side effects of big muscles, lots of energy, effective birth control and boners. What does Mifepristone have? ;)

 

I would never call this adverse :-D 


Edited by Flex, 15 October 2014 - 07:15 PM.


#66 Joe Monroe

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Posted 17 October 2014 - 06:14 AM

I have a pituitary injury that damaged my HPA axis. I am wondering why a dangerous abortifacient instead of bioidentical hormone replacement. I had low resting cortisol and my FT3 was not being converted to FT4 due to insufficient HGH.

With the supplementation of Testosterone and growth hormone I feel just like I did before I was injured. Bioidentical is so much easier than trying to metabolize bizarre synthetics.

If I miss my hgh shot I find coffee can actually help sometimes. Lacking cortisol and FT4 my body tends to then produce adrenalin to make up the metabolic shortfall. A big coffee can shut down the adrenalin cascade and really calm me down.

your situation is very unique and I don't think is comparable to the majority of those on the thread. Thanks for the input though.

Also mifepristone isn't dangerous just because it's used for abortions, it is approved by the FDA and for long term use of people with cushings. 

 

Cola cola has the ability to corrode metal, does that mean it's toxic in small amounts? no. 

 

Also I find caffeine makes me feel terrible after it wears off. 



#67 computeTHIS

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Posted 17 October 2014 - 08:49 AM

Before anyone messages me again, I have no source for Mifepristone.  Mine came from: http://www.eurodrugs...tone__3029.html.  I might create another thread for peptide therapies, but I really don't want to put the time into it, so I'll post my results here for now.

I feel like I am completely over my 3-year season of lethargy and wasting.  I rely on nothing to keep me going now.  Before Mifepristone, I used to use Piracetam, NAC, and/or Alpha Lipoic Acid to get temporary relief.  All were very good, but results were only temporary.  I would force myself to go to the gym, work out, go for a 3-mile run, get good nutrition, and the wasting and lethargy persisted.  My body didn't respond to anything I did, and all the lab results from my doctors showed my hormone levels at the lower end of the "normal range", so to them there was nothing wrong with me.  I was incredibly sensitive to certain vitamins and minerals.  I would easily overdose on a multivitamin, leaving me feeling sick and tired, leading me to believe my metabolism was incredibly low.  Maybe others feel this too, but all the lethargy put me in a very negative, persistent mental state.  Piracetam, NAC, and ALA alleviated negative ideation temporarily.  Mifepristone definitely changed my mental state to something more positive, and did wonders for my energy level.

 

One thing that stood out on my labs was that my IGF1 level was exactly half of the entire US-population average.  Following the literature that IGF1 plays an important role in neural growth, I found CJC-1295 (with DAC) and GHRP-6.  The trouble is that injected HGH or IGF1 do not easily cross the blood-brain-barrier.  With CJC-1295 and GHRP-6, if you have a working pituitary, these chemicals will cause IGF1/HGH upregulation from within your brain, thus getting around the blood-brain-barrier problem.  Following the same line of thought, a nasal spray consisting of low-sialic acid EPO (called "neural EPO") and IGF1 have been demonstrated to aid stroke victims.  The mental and physical results were immediate from CJC/GHRP, I used these for a 2-week period.  I actually felt like "a normal person", able to be sociable and think more creatively, and I still do, even without using these chemicals anymore (it's been about 2-3 weeks since using them).  Improvements to my libido were slowly coming back, most noticeably with GHRP-6.  If you read about CJC-1295 and GHRP-6, the same sites typically sell Triptorelin.  A single dose of 100mcg has had user reports of at least 9 months of upregulated testosterone via pituitary stimulation.  Repeated high-dose Triptorelin is used for chemical castration, so be warned.  Triptorelin is even in clinical trials for fertility treatment, with reports that when taken alone, or in conjunction with human chorionic gonadotropin (HCG), it helped women conceive (with anologous results in men).  I took the single 100 mcg dose 2 weeks ago, and I feel fantastic.  I am productive, more sociable, and maintaining a healthy athletic regimine.  I'm still hyper-sensitive to caffeine.  2 cups of coffee might leave me without energy for the next 1.5 days.  I've noticed that caffiene before a workout doesn't have the same energy drop as without physical activity. 

 

My goal was always to try to heal whatever was wrong with me, rather than doing hormone replacement, etc.  I believe all of the above has lead me to recovery.  I would highly recommend the CJC-1295 & GHRP-6 in conjunction with an athletic regimine.  The Triptorelin should get some special attention, I took it after taking CJC-1295 & GHRP-6, and it's not clear to me the extent that it upregulates your pituitary.  You might take Triptorelin and see improvement in all aspects of your mental and physical state of well being. 

I would describe my feeling from the last 3 years of wasting being similar to dying.  No energy, emotionally blunted or no longer able to empathize with others, a recurring negative mental state, and having no useful diagnosis from anyone.  I think the above treatments might be helpful to anyone who has incurred some stress-induced damage, being from too many all-nighters (in my case), or recovering from the lasting effects of drug addiction.  I imagine the sort of "wasting" I experienced wasn't far off from what I've seen in drug addicts.  For whatever it's worth, I wanted to leave my experiences here so that it might be of help to others.


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#68 lourdaud

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Posted 17 October 2014 - 10:38 AM

My goal was always to try to heal whatever was wrong with me, rather than doing hormone replacement, etc.  I believe all of the above has lead me to recovery.  I would highly recommend the CJC-1295 & GHRP-6 in conjunction with an athletic regimine.  The Triptorelin should get some special attention, I took it after taking CJC-1295 & GHRP-6, and it's not clear to me the extent that it upregulates your pituitary.  You might take Triptorelin and see improvement in all aspects of your mental and physical state of well being. 

I would describe my feeling from the last 3 years of wasting being similar to dying.  No energy, emotionally blunted or no longer able to empathize with others, a recurring negative mental state, and having no useful diagnosis from anyone.  I think the above treatments might be helpful to anyone who has incurred some stress-induced damage, being from too many all-nighters (in my case), or recovering from the lasting effects of drug addiction.  I imagine the sort of "wasting" I experienced wasn't far off from what I've seen in drug addicts.  For whatever it's worth, I wanted to leave my experiences here so that it might be of help to others.

 

Interesting. I have similar problems and will definitely look into the peptides you mention.

 

Something that comes to mind: what's your diet like? 

 

A part from high stress and excessive stimulant use, I believe I caused/aggravated many of my problems by excessively restricting my intake of carbohydrates. 

I believe some of the problems with low carb diets may be chronically elevated cortisol and HPA activation, causing cortisol receptors to become desensitized, leading to inflammation, depression etc.

It will also switch the body to "starvation mode", with decreased levels of both testosterone and thyroid hormones. 

See this for example:

Diet-hormone interactions: protein/carbohydrate ratio alters reciprocally the plasma levels of testosterone and cortisol and their respective binding globulins in man.

Dietary-induced alterations in thyroid hormone metabolism during overnutrition.

Effect of Carbohydrate and Noncarbohydrate Sources of Calories on Plasma 3,5,3′-Triiodothyronine Concentrations in Man


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#69 Nemo888

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Posted 17 October 2014 - 01:08 PM

It's interesting how similar symptoms can have a completely different etiology. I have blunt force trauma to my pituitary complicated by a compression fracture in my spine and the stress from military service.

My resting cortisol is low though. In most cases of stress induced PTSD/depression etc it is high. If I had a functional pituitary I think I may try mifepristone. I was having an easier time doing HRT before using peptides to regrow neuronal tissue. Before I was not aromatizing and now have excessive estrogen. Which I am finding kind of awesome for raising kids. Estrogen can be very performance enhancing for parenting duties. Coffee when I am not adrenalizing to make up for metabolic shortfalls makes me jittery too. It is a metabolic curiousity that adrenalin will try to take the place of cortisol and FT4 at which point a stimulant can have a calming effect. HGH did have a huge effect on my brain when I started taking it. I could sleep again and was infinitely calmer. This obviously made me more alert and happy. Also I could take the cold again.

HRT seems extreme, most especially because it is for the remainder of your life. But if your hormone regulation is wrecked anyway it can have some very fun side effects in regards to aging. I can't say I ever regretted it. Felt so much better almost immediately. Staying bioidentical is very good advice. The random secondary effects of metabolizing unique compounds can produce staggeringly difficult problems. When additional atypical genetics or metabolism is added it creates considerable risk in my experience. If you are over 40 you may be best served by going straight to bioidentical HRT.

Great thread so far. Very interesting.

Edited by Nemo888, 17 October 2014 - 01:16 PM.

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#70 computeTHIS

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Posted 18 October 2014 - 03:04 AM

 

My goal was always to try to heal whatever was wrong with me, rather than doing hormone replacement, etc.  I believe all of the above has lead me to recovery.  I would highly recommend the CJC-1295 & GHRP-6 in conjunction with an athletic regimine.  The Triptorelin should get some special attention, I took it after taking CJC-1295 & GHRP-6, and it's not clear to me the extent that it upregulates your pituitary.  You might take Triptorelin and see improvement in all aspects of your mental and physical state of well being. 

I would describe my feeling from the last 3 years of wasting being similar to dying.  No energy, emotionally blunted or no longer able to empathize with others, a recurring negative mental state, and having no useful diagnosis from anyone.  I think the above treatments might be helpful to anyone who has incurred some stress-induced damage, being from too many all-nighters (in my case), or recovering from the lasting effects of drug addiction.  I imagine the sort of "wasting" I experienced wasn't far off from what I've seen in drug addicts.  For whatever it's worth, I wanted to leave my experiences here so that it might be of help to others.

 

Interesting. I have similar problems and will definitely look into the peptides you mention.

 

Something that comes to mind: what's your diet like? 

 

A part from high stress and excessive stimulant use, I believe I caused/aggravated many of my problems by excessively restricting my intake of carbohydrates. 

I believe some of the problems with low carb diets may be chronically elevated cortisol and HPA activation, causing cortisol receptors to become desensitized, leading to inflammation, depression etc.

It will also switch the body to "starvation mode", with decreased levels of both testosterone and thyroid hormones. 

See this for example:

Diet-hormone interactions: protein/carbohydrate ratio alters reciprocally the plasma levels of testosterone and cortisol and their respective binding globulins in man.

Dietary-induced alterations in thyroid hormone metabolism during overnutrition.

Effect of Carbohydrate and Noncarbohydrate Sources of Calories on Plasma 3,5,3′-Triiodothyronine Concentrations in Man

 

 

That's very interesting reading.  That makes sense in my context as well.

Right now I'm on a high protein, lower-carb diet.  Back when I was all stressed out pulling all-nighters, and trying to maintain athletics, I practiced caloric restriction but ate more carbs than protein.  My protein intake was entirely insufficient.  During a very busy week, I would eat very little, then several weeks later I would eat huge meals with family.  It was a vicious cycle.  It was the epitome of intermittent fasting, whereby you can permanently downregulate your IGF1 levels. 

 

At least for the very active, I think balanced diet is more important than caloric restriction.  There's a reconciliation that has to happen between the longevity evidence of caloric restriction and your body's energy needs. 



#71 Sunifiramses II

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Posted 19 October 2014 - 08:27 AM

This thread is getting more and more interesting to me... I'm pretty sure I have HPA dysfunction, in the form of chronically low cortisol, possibly from blowing out my adrenal glands via excessive stimulant use (Adderall, Vyvanse, Ritalin, etc.).

 

But I should probably get my cortisol levels tested before I go around making such bold claims!  ;)

 

So, I gather from reading this thread that we haven't found a source yet...?



#72 Flex

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Posted 19 October 2014 - 11:47 AM

From what I´ve read and understood, Cortisol levels in the brain arent allways measurable as in contrast to the body level.

Furthermore, Cortisol on its self acts like a stop signal on the HPA activation, like an autoreceptor agonist

and a functioning Hippocampus can (should?) repress those overactivation of the HPA axis to a certain degree.

(Please correct me on any of these claims, if I´m wrong)

 

Yes there is a source in the USA and EU

See post #44 from binder23

and # 67 from compute this



#73 Flex

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Posted 19 October 2014 - 11:53 AM

Before anyone messages me again, I have no source for Mifepristone.  Mine came from: http://www.eurodrugs...tone__3029.html.  I might create another thread for peptide therapies, but I really don't want to put the time into it, so I'll post my results here for now.
 

 

 

Seems that they dont have it in stock :dry:

Are they reliable ?
 



#74 Flex

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Posted 19 October 2014 - 12:10 PM

Flex,

 

That's super interesting.

 

Do you know if Dan Shen has stronger antagonistic effect on GR or MR? Or are the effects similar on both the glucocorticoid and mineralocorticoid systems ? I ask because I don't see mineralocorticoids as being a problem with me - my sodium and potassium levels are normal. Yet I display all the symptoms of hyercortisolism (or, more accurately, corticoid sensitivity).

 

I have some Dan Shen that I will try today as I'm waiting for the Mifeprestone to arrive.

 

 

Thanks

 

Sry I´ve overlooked Your message.

 

I dont know it exactly and the subjective experience is problematic, because Dan Shen is a weak dopamine releaser.

But I can say that everytime when using it, my Mood is up for several days.

So it cant be just dopamine.

The MR could afaik increase the bloodpressure and Aldosterone also anxiety.

 

If I remeber correctly ( not 100% sure),

Cortisol increases Dopamine and Dopamine decreases Aldosterone.

But GR´s decrease MR receptor expression and increase 11ßHSD 1 expression.


Edited by Flex, 19 October 2014 - 12:17 PM.


#75 totflare

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Posted 19 October 2014 - 12:46 PM

I've been experimenting with Danshen for the past week and it immediately has a very calming and slight mood brightening effect.

 

Turns out one of its components is a partial GABA-A agonist.

 

Miltirone, a central benzodiazepine receptor partial agonist from a Chinese medicinal herb Salvia miltiorrhiza. http://www.ncbi.nlm..../pubmed/1652718

 

Would really like to try Mifepristone though..


Edited by synchronizing89, 19 October 2014 - 12:47 PM.


#76 Flex

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Posted 19 October 2014 - 01:18 PM

It seems that this, at least for me, isnt responsible because kava kava and rosmarinic acid dont have the same effect.

Actualy they dont do much.

And Coffeine reverses it i.e. downs my mood.

 

Next thought would be A1 &A2 receptors.

Because Coffeine is a adenosine antagonist.

 

Polygala tenuifolia an alleged oral active adenosine A2A receptor agonist dont have the same effects

as well as Valerian an adenonsine a1 agonist dont has the same  effects as Dan Shen for me.

Polygala is not bad but weaker and different in contrast to Dan Shen.

 

http://www.researchg...ortical_neurons

 

http://www.pubfacts....ia-root-extract.

http://examine.com/s...lia/#summary4-0


Edited by Flex, 19 October 2014 - 01:24 PM.


#77 datrat

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Posted 19 October 2014 - 06:13 PM

I've been experimenting with Danshen for the past week and it immediately has a very calming and slight mood brightening effect.

 

Turns out one of its components is a partial GABA-A agonist.

 

Miltirone, a central benzodiazepine receptor partial agonist from a Chinese medicinal herb Salvia miltiorrhiza. http://www.ncbi.nlm..../pubmed/1652718

 

Would really like to try Mifepristone though..

 

I've also been using danshen with good results, although the MR antagonism is problematic; high blood pressure and anxiety after prolonged intake. I also would like to try Mifepristone.
 



#78 totflare

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Posted 19 October 2014 - 06:30 PM

Could you please tell me how long have you been using it, what are your symptoms and how has it helped with them?



#79 datrat

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Posted 19 October 2014 - 07:44 PM

Could you please tell me how long have you been using it, what are your symptoms and how has it helped with them?

 

Sure, the reason I started using danshen is because I have seasonal affective disorder and, iirc, the glucocorticoid system is implicated in this.

 

About 20 days ago I started using 2.5 gms 3X/day. It stopped the seasonal affective disorder symptoms dead in their tracks, while prescription AD's had no effect.

 

At day 9 I started to notice some anxiety and on day 10 it became pretty bad. Based on Flex's posted studies I'm assuming that was because of the mineralocorticoid receptor antagonism.

 

I stopped using it at that point and the anxiety went away.

 

I waited 10 days and re-started yesterday at 2.5 gms 2X/day (late afternoon and before bed to mimic normal drop in cortisol levels). I'm going to cycle this at 4 days on and 4 days off to see how it goes.

 

I have no idea how to use danshen, so this is all just guesswork and that is why I would prefer to try mifepristone.
 



#80 Flex

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Posted 19 October 2014 - 07:50 PM

Edit


Edited by Flex, 19 October 2014 - 07:52 PM.


#81 Joe Monroe

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Posted 24 October 2014 - 11:47 PM

Before anyone messages me again, I have no source for Mifepristone.  Mine came from: http://www.eurodrugs...tone__3029.html.  I might create another thread for peptide therapies, but I really don't want to put the time into it, so I'll post my results here for now.

I feel like I am completely over my 3-year season of lethargy and wasting.  I rely on nothing to keep me going now.  Before Mifepristone, I used to use Piracetam, NAC, and/or Alpha Lipoic Acid to get temporary relief.  All were very good, but results were only temporary.  I would force myself to go to the gym, work out, go for a 3-mile run, get good nutrition, and the wasting and lethargy persisted.  My body didn't respond to anything I did, and all the lab results from my doctors showed my hormone levels at the lower end of the "normal range", so to them there was nothing wrong with me.  I was incredibly sensitive to certain vitamins and minerals.  I would easily overdose on a multivitamin, leaving me feeling sick and tired, leading me to believe my metabolism was incredibly low.  Maybe others feel this too, but all the lethargy put me in a very negative, persistent mental state.  Piracetam, NAC, and ALA alleviated negative ideation temporarily.  Mifepristone definitely changed my mental state to something more positive, and did wonders for my energy level.

 

One thing that stood out on my labs was that my IGF1 level was exactly half of the entire US-population average.  Following the literature that IGF1 plays an important role in neural growth, I found CJC-1295 (with DAC) and GHRP-6.  The trouble is that injected HGH or IGF1 do not easily cross the blood-brain-barrier.  With CJC-1295 and GHRP-6, if you have a working pituitary, these chemicals will cause IGF1/HGH upregulation from within your brain, thus getting around the blood-brain-barrier problem.  Following the same line of thought, a nasal spray consisting of low-sialic acid EPO (called "neural EPO") and IGF1 have been demonstrated to aid stroke victims.  The mental and physical results were immediate from CJC/GHRP, I used these for a 2-week period.  I actually felt like "a normal person", able to be sociable and think more creatively, and I still do, even without using these chemicals anymore (it's been about 2-3 weeks since using them).  Improvements to my libido were slowly coming back, most noticeably with GHRP-6.  If you read about CJC-1295 and GHRP-6, the same sites typically sell Triptorelin.  A single dose of 100mcg has had user reports of at least 9 months of upregulated testosterone via pituitary stimulation.  Repeated high-dose Triptorelin is used for chemical castration, so be warned.  Triptorelin is even in clinical trials for fertility treatment, with reports that when taken alone, or in conjunction with human chorionic gonadotropin (HCG), it helped women conceive (with anologous results in men).  I took the single 100 mcg dose 2 weeks ago, and I feel fantastic.  I am productive, more sociable, and maintaining a healthy athletic regimine.  I'm still hyper-sensitive to caffeine.  2 cups of coffee might leave me without energy for the next 1.5 days.  I've noticed that caffiene before a workout doesn't have the same energy drop as without physical activity. 

 

My goal was always to try to heal whatever was wrong with me, rather than doing hormone replacement, etc.  I believe all of the above has lead me to recovery.  I would highly recommend the CJC-1295 & GHRP-6 in conjunction with an athletic regimine.  The Triptorelin should get some special attention, I took it after taking CJC-1295 & GHRP-6, and it's not clear to me the extent that it upregulates your pituitary.  You might take Triptorelin and see improvement in all aspects of your mental and physical state of well being. 

I would describe my feeling from the last 3 years of wasting being similar to dying.  No energy, emotionally blunted or no longer able to empathize with others, a recurring negative mental state, and having no useful diagnosis from anyone.  I think the above treatments might be helpful to anyone who has incurred some stress-induced damage, being from too many all-nighters (in my case), or recovering from the lasting effects of drug addiction.  I imagine the sort of "wasting" I experienced wasn't far off from what I've seen in drug addicts.  For whatever it's worth, I wanted to leave my experiences here so that it might be of help to others.

 

That's great to hear, thanks for listing those things... it's amazing how much supplements/ drugs are out there, always learning something new. I'll have to look into them. Most of your symptoms sound VERY similar to me. 

 

Also thank you everyone again for your posts and contribution to this thread.



#82 Flex

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Posted 25 October 2014 - 12:53 PM

Found this:
Increased prevalence of psychopathology and maladaptive personality traits after long-term cure of Cushing's disease.
RESULTS: Mean duration of remission was 11 yr (range 1-32 yr). Compared with matched controls, patients cured from CD scored significantly worse on virtually all questionnaires. Compared with nonfunctioning pituitary macroadenoma patients, patients treated for CD scored worse on apathy (P<0.001), irritability (P<0.001), anxiety (P<0.001), negative affect and lack of positive affect (P<0.001 on both scales), somatic arousal (P<0.001), and 11 of 18 subscales of the Dimensional Assessment of Personality Pathology short-form (P<0.05).
http://www.uptodate....ior/abstract/68
 EFFECT OF ORAL CORTICOSTERONE ADMINISTRATION ON LOCOMOTOR DEVELOPMENT OF NEONATAL AND JUVENILE RATS
In humans, increased basal cortisol secretion has frequently been shown to be associated with psychiatric disturbances ranging from mild depression and apathy to severe psychotic illnesses
in endogenously depressed patients (Rupprecht, Rupprecht, Rupprecht, Noder, Lesch & Mossner, 1989; Weick, 1989; Murphy, 1991; Klein,1992).
http://ep.physoc.org.../3/469.full.pdf
Memantine treatment reverses anhedonia, normalizes corticosterone levels and increases BDNF levels in the prefrontal cortex induced by chronic mild stress in rats.
http://www.ncbi.nlm....pubmed/22327556
Our results demonstrated that chronic stressful situations induced anhedonia, hypertrophy of adrenal gland weight, and an increase of corticosterone levels in rats, but did not alter BDNF protein levels in the rat brain.
 
But there is a difference between Humans and other Mammals.
According to the sometimes not reliable wiki !?
http://en.wikipedia..../Corticosterone

 
Recapitulation and reversal of a persistent depression-like syndrome in rodent
Here we demonstrate that CORT, a major stress substrate, is itself sufficient to persistently decrease hippocampal CREB phosphorylation up to one month after CORT exposure, and subsequent treatment with chronic AMI or FLX can also normalize expression
http://www.ncbi.nlm....les/PMC2774936/
 Effect of green tea on reward learning in healthy individuals: a randomized, double-blind, placebo-controlled pilot study
http://www.nutrition...content/12/1/84
 Green Tea and One of Its Constituents, Epigallocatechine-3-gallate, Are Potent Inhibitors of Human 11β-hydroxysteroid Dehydrogenase Type 1
http://www.plosone.o...al.pone.0084468
 
A further research is needed to determine the regulatory effect of green tea on glucocorticoids receptors expression and the target genes involved in the reward learning process and the improvement of depressive symptoms. Furthermore, a significant antidepressant-like effect was detected in mice that received a single intraperitoneal injection of green tea in the forced swim test when compared with the control
Biphasic effects of Morus alba leaves green tea extract on mice in chronic forced swimming model.
http://www.ncbi.nlm....pubmed/18386251

 

Saikosaponin D acts against corticosterone-induced apoptosis via regulation of mitochondrial GR translocation and a GR-dependent pathway.
Next, mPTP, MMP, [Ca(2+)]i, translocation of the GR to the nucleus and Western blot analyses for caspase-3, caspase-9, cytochrome C, GR, GILZ, SGK-1, NF-Κb (P65), IκB-α, Bad, Akt, Hsp90 and HDAC-6 were investigated.
http://www.ncbi.nlm....pubmed/24636912
 
And this is my new Panacea :dry:
At least, my ideas wont end..
Anyway I´ve seen the full article and read that Corticoserone re-inforces it self via the mechanisms above and Bupleurum falcatnum aka Radix Bupleuri can reverse this and the epigenetic alteration.
(if I read it right and I dare somehow to post this passage. PM if You want it)

 

I´ve allways looked for any epigenetic and non-epigenetic mechanisms which induced a perresitent alteration of GR and MR and their receptors.
Thats how I´ve found this and perhaps 21-hydroxilase as possible further target.
http://en.wikipedia....oidogenesis.svg
Hope it helps anyhow in this (or my) chaotic picture of GR and MR´s.


Edited by Flex, 25 October 2014 - 12:57 PM.

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#83 datrat

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Posted 25 October 2014 - 09:17 PM

 

Saikosaponin D acts against corticosterone-induced apoptosis via regulation of mitochondrial GR translocation and a GR-dependent pathway.
Next, mPTP, MMP, [Ca(2+)]i, translocation of the GR to the nucleus and Western blot analyses for caspase-3, caspase-9, cytochrome C, GR, GILZ, SGK-1, NF-Κb (P65), IκB-α, Bad, Akt, Hsp90 and HDAC-6 were investigated.
http://www.ncbi.nlm....pubmed/24636912
 
And this is my new Panacea :dry:
At least, my ideas wont end..
Anyway I´ve seen the full article and read that Corticoserone re-inforces it self via the mechanisms above and Bupleurum falcatnum aka Radix Bupleuri can reverse this and the epigenetic alteration.
(if I read it right and I dare somehow to post this passage. PM if You want it)

 

I´ve allways looked for any epigenetic and non-epigenetic mechanisms which induced a perresitent alteration of GR and MR and their receptors.
Thats how I´ve found this and perhaps 21-hydroxilase as possible further target.
http://en.wikipedia....oidogenesis.svg
Hope it helps anyhow in this (or my) chaotic picture of GR and MR´s.

 

Thanks for these informative posts. I'm also going to give Bupleurum a try.
 



#84 Flex

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Posted 25 October 2014 - 09:23 PM

Youre welcome :-)

Ok anyway here´s the paper

http://www.sciencedi...278584614000402

Look at the bottom at conclusions for the reversal potential.

 

And as usual check for bloodthinning properties, like tipping in google:

Herb xx + coagulant and platelet- or thrombocyte-aggregation

 


Edited by Flex, 25 October 2014 - 09:40 PM.


#85 Flex

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Posted 28 October 2014 - 04:54 PM

Have to correct my spelling for possbile search results (YKN)

 

Corticosterone re-inforces it self via the mechanisms above and Bupleurum falcatnum aka Radix Bupleuri can reverse this and the epigenetic alteration.

 



#86 Joe Monroe

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Posted 29 October 2014 - 11:48 PM

Have to correct my spelling for possbile search results (YKN)

 

Corticosterone re-inforces it self via the mechanisms above and Bupleurum falcatnum aka Radix Bupleuri can reverse this and the epigenetic alteration.

 

Do you have any studies about bupleurum falcatnum? sounds interesting. I tried looking for it on amazon but most were mixed with other herbs



#87 Joe Monroe

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Posted 30 October 2014 - 12:28 AM

Before anyone messages me again, I have no source for Mifepristone.  Mine came from: http://www.eurodrugs...tone__3029.html.  I might create another thread for peptide therapies, but I really don't want to put the time into it, so I'll post my results here for now.

I feel like I am completely over my 3-year season of lethargy and wasting.  I rely on nothing to keep me going now.  Before Mifepristone, I used to use Piracetam, NAC, and/or Alpha Lipoic Acid to get temporary relief.  All were very good, but results were only temporary.  I would force myself to go to the gym, work out, go for a 3-mile run, get good nutrition, and the wasting and lethargy persisted.  My body didn't respond to anything I did, and all the lab results from my doctors showed my hormone levels at the lower end of the "normal range", so to them there was nothing wrong with me.  I was incredibly sensitive to certain vitamins and minerals.  I would easily overdose on a multivitamin, leaving me feeling sick and tired, leading me to believe my metabolism was incredibly low.  Maybe others feel this too, but all the lethargy put me in a very negative, persistent mental state.  Piracetam, NAC, and ALA alleviated negative ideation temporarily.  Mifepristone definitely changed my mental state to something more positive, and did wonders for my energy level.

 

One thing that stood out on my labs was that my IGF1 level was exactly half of the entire US-population average.  Following the literature that IGF1 plays an important role in neural growth, I found CJC-1295 (with DAC) and GHRP-6.  The trouble is that injected HGH or IGF1 do not easily cross the blood-brain-barrier.  With CJC-1295 and GHRP-6, if you have a working pituitary, these chemicals will cause IGF1/HGH upregulation from within your brain, thus getting around the blood-brain-barrier problem.  Following the same line of thought, a nasal spray consisting of low-sialic acid EPO (called "neural EPO") and IGF1 have been demonstrated to aid stroke victims.  The mental and physical results were immediate from CJC/GHRP, I used these for a 2-week period.  I actually felt like "a normal person", able to be sociable and think more creatively, and I still do, even without using these chemicals anymore (it's been about 2-3 weeks since using them).  Improvements to my libido were slowly coming back, most noticeably with GHRP-6.  If you read about CJC-1295 and GHRP-6, the same sites typically sell Triptorelin.  A single dose of 100mcg has had user reports of at least 9 months of upregulated testosterone via pituitary stimulation.  Repeated high-dose Triptorelin is used for chemical castration, so be warned.  Triptorelin is even in clinical trials for fertility treatment, with reports that when taken alone, or in conjunction with human chorionic gonadotropin (HCG), it helped women conceive (with anologous results in men).  I took the single 100 mcg dose 2 weeks ago, and I feel fantastic.  I am productive, more sociable, and maintaining a healthy athletic regimine.  I'm still hyper-sensitive to caffeine.  2 cups of coffee might leave me without energy for the next 1.5 days.  I've noticed that caffiene before a workout doesn't have the same energy drop as without physical activity. 

 

My goal was always to try to heal whatever was wrong with me, rather than doing hormone replacement, etc.  I believe all of the above has lead me to recovery.  I would highly recommend the CJC-1295 & GHRP-6 in conjunction with an athletic regimine.  The Triptorelin should get some special attention, I took it after taking CJC-1295 & GHRP-6, and it's not clear to me the extent that it upregulates your pituitary.  You might take Triptorelin and see improvement in all aspects of your mental and physical state of well being. 

I would describe my feeling from the last 3 years of wasting being similar to dying.  No energy, emotionally blunted or no longer able to empathize with others, a recurring negative mental state, and having no useful diagnosis from anyone.  I think the above treatments might be helpful to anyone who has incurred some stress-induced damage, being from too many all-nighters (in my case), or recovering from the lasting effects of drug addiction.  I imagine the sort of "wasting" I experienced wasn't far off from what I've seen in drug addicts.  For whatever it's worth, I wanted to leave my experiences here so that it might be of help to others.

 

hey compute this, thanks again for this post, I'm curious how you found out about cjc, ghrp, and triptorelin? Was it on another thread on longecity? 

 

I'm reading about them and they seem really great, especially ghrp. Where would you recommend buying them if you're in the USA? Did you have any negative side effects. I'm often worried about this since I sometimes react poorly to drugs/ supplements. 



#88 Flex

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Posted 30 October 2014 - 05:34 PM

 

Have to correct my spelling for possbile search results (YKN)

 

Corticosterone re-inforces it self via the mechanisms above and Bupleurum falcatnum aka Radix Bupleuri can reverse this and the epigenetic alteration.

 

Do you have any studies about bupleurum falcatnum? sounds interesting. I tried looking for it on amazon but most were mixed with other herbs

 

 

Yes right above:

Saikosaponin D acts against corticosterone-induced apoptosis via regulation of mitochondrial GR translocation and a GR-dependent pathway.

http://www.ncbi.nlm....pubmed/24636912

 

Its actually a bit misleading because its sometimes not the herb but the compound stated. Nevertheless I found that this is present in Bupleurum Falcatnum.

See at the top:

S9321 - Saikosaponin D from Bupleurum falcatnum

http://www.sigmaaldr...ng=de&region=DE

 

Bupleurum is used traditionaly in China:

 

http://altmedicine.a...l/Bupleurum.htm

http://www.positiveh...a-and-psychosis

( Interresting table btw. I´ll take a further look, if I run out of ideas ^^)

 

Bupleurum falcatum prevents depression and anxiety-like behaviors in rats exposed to repeated restraint stress

...Hypothalamicpituitary- adrenal axis activation in response to repeated restraint stress was confirmed base on serum corticosterone levels and CRF expression in the hypothalamus...

http://www.ncbi.nlm....pubmed/22450800

 

In regards of the sources:

This is also a bit tricky.

You have sometimes to search for the chinese name i.e.

Bupleuri radix =  chai hu

Note: that every syllable is important, because it could mean something like processed or another part, so roots instead of flowers

Anyway here we go:

http://www.eastearth...-ji-gu-cao.aspx

http://www.acuatlant...l?mclick=search

 

Those two brands Sun Ten and Sanjiu999 appeared to me reliable because

1) they are GMP

2) TCM practioneers use them too.

Actually it could be problematic to obtain them because they are "for professionals only"

But where´s money, there´s a chance ;-)

 

Therefore do some recherche for side effects and especially for bloodthinning

i.e. google: herb " xx + coagulation and platelet/ thrombocyte aggreagation "

and buy perhaps 20mg/ml vitamin K drops or tablets for the coagulation (You never know)

Example:

http://www.unserekle...IT_Tropfen.html

 

And in the case of pulverized+extracted herbs probably like above, divide the recommened dose to 6

e.g. 12 grams recommened /6 = 2 grams of the extract-powder

 

Do better a recherche on Your own to verify that or buy the Herb from e.g.:

http://www.activeher...bs/chaihu.shtml

 

Edit: man, what a huge story again -.-


Edited by Flex, 30 October 2014 - 06:16 PM.

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#89 Flex

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Posted 30 October 2014 - 08:20 PM

Wait, actually forget that with the Vitamin K.

This could cause clots even when the thrombocytes are inhibited.

 

Sry I didnt know it better even for me.

That are the risks of half-knowledge..

 

http://www.longecity...-10#entry695620

 



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#90 Joe Monroe

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Posted 05 November 2014 - 03:39 AM

 

 

Have to correct my spelling for possbile search results (YKN)

 

Corticosterone re-inforces it self via the mechanisms above and Bupleurum falcatnum aka Radix Bupleuri can reverse this and the epigenetic alteration.

 

Do you have any studies about bupleurum falcatnum? sounds interesting. I tried looking for it on amazon but most were mixed with other herbs

 

 

Yes right above:

Saikosaponin D acts against corticosterone-induced apoptosis via regulation of mitochondrial GR translocation and a GR-dependent pathway.

http://www.ncbi.nlm....pubmed/24636912

 

Its actually a bit misleading because its sometimes not the herb but the compound stated. Nevertheless I found that this is present in Bupleurum Falcatnum.

See at the top:

S9321 - Saikosaponin D from Bupleurum falcatnum

http://www.sigmaaldr...ng=de&region=DE

 

Bupleurum is used traditionaly in China:

 

http://altmedicine.a...l/Bupleurum.htm

http://www.positiveh...a-and-psychosis

( Interresting table btw. I´ll take a further look, if I run out of ideas ^^)

 

Bupleurum falcatum prevents depression and anxiety-like behaviors in rats exposed to repeated restraint stress

...Hypothalamicpituitary- adrenal axis activation in response to repeated restraint stress was confirmed base on serum corticosterone levels and CRF expression in the hypothalamus...

http://www.ncbi.nlm....pubmed/22450800

 

In regards of the sources:

This is also a bit tricky.

You have sometimes to search for the chinese name i.e.

Bupleuri radix =  chai hu

Note: that every syllable is important, because it could mean something like processed or another part, so roots instead of flowers

Anyway here we go:

http://www.eastearth...-ji-gu-cao.aspx

http://www.acuatlant...l?mclick=search

 

Those two brands Sun Ten and Sanjiu999 appeared to me reliable because

1) they are GMP

2) TCM practioneers use them too.

Actually it could be problematic to obtain them because they are "for professionals only"

But where´s money, there´s a chance ;-)

 

Therefore do some recherche for side effects and especially for bloodthinning

i.e. google: herb " xx + coagulation and platelet/ thrombocyte aggreagation "

and buy perhaps 20mg/ml vitamin K drops or tablets for the coagulation (You never know)

Example:

http://www.unserekle...IT_Tropfen.html

 

And in the case of pulverized+extracted herbs probably like above, divide the recommened dose to 6

e.g. 12 grams recommened /6 = 2 grams of the extract-powder

 

Do better a recherche on Your own to verify that or buy the Herb from e.g.:

http://www.activeher...bs/chaihu.shtml

 

Edit: man, what a huge story again -.-

 

 

 

Thanks man have you tried this at all? It seems like it is similar to other adaptogens, no?

Also what was that link you posted about vitamin k? I dunno i clicked on the link and was a very long thread lol






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