How to get high and sustained allopregnanolone to heal the brain

[themartian1000]

I have come to understand that allopregnanolone is key to healing the brain. However, it seems like I can't get progesterone high enough topically, and orally I am on a roller coaster. Absorption is not great vaginally / rectally, but maybe ok? I feel like if I could get allopregnanolone levels high and keep them there for a while (then taper slowly), perhaps I could heal this injury and taper off the pregabalin I was put on (another potentially bad drug).

I've tried Idealabs allopregnanolone without any results also.

At this point, I have even considered just filling gel caps with Progest-E and sucking on them all day and night...

I do all of the other things (optimize thyroid, body temp, PUFA, protein, carbs, stress, cortisol and so on), but this one has been so hard!

 

[bk_]

I have come to understand that allopregnanolone is key to healing the brain. However, it seems like I can't get progesterone high enough topically, and orally I am on a roller coaster. Absorption is not great vaginally / rectally, but maybe ok? I feel like if I could get allopregnanolone levels high and keep them there for a while (then taper slowly), perhaps I could heal this injury and taper off the pregabalin I was put on (another potentially bad drug).

I've tried Idealabs allopregnanolone without any results also.

At this point, I have even considered just filling gel caps with Progest-E and sucking on them all day and night...

I do all of the other things (optimize thyroid, body temp, PUFA, protein, carbs, stress, cortisol and so on), but this one has been so hard!

Can you provide more details such as:
1. What makes you believe your problem is specifically with allo?
2. What are your symptoms?
3. Did you take medications in the past?
4. Are you on any medications at the present?
5. You mentioned an injury, do you have a TBI?
6. How much progesterone are you taking? How often?

 

[themartian1000]

Can you provide more details such as:
1. What makes you believe your problem is specifically with allo?
2. What are your symptoms?
3. Did you take medications in the past?
4. Are you on any medications at the present?
5. You mentioned an injury, do you have a TBI?
6. How much progesterone are you taking? How often?

Thanks for asking

1. I believe it is allo because at the peak of my luteal phase, I feel the best. All other times I feel awful. There are some in hormone groups who say this is high estrogen paired with progesterone, but I believe Peat on the matter of estrogen and think it just happens to be there, possibly even blunting progesterone's effects. However, it could be the progesterone itself that makes me feel better. Or something else? When I take Idealabs allo, I feel nothing, but the old 5 alpha DHP made me feel a lot better. So, it is unclear for sure.

2. I have anxiety, depression, irritability mostly and some insomnia

3. I was put on a low dose horrible benzo for insomnia 18 months ago. It caused horrid side-effects that I only realized were the benzo after 3 months. I was taken off cold turkey. I believe because my brain was unprotected with proper neurosteroids at the time (stress, perimenopause, etc), I had a horrific reaction. I went from someone with just insomnia but good mental health to feeling like I was having a seizure for 15 hours a day (mysteriously it got better at night but then that went away too). At month 10, I was still non-functional (could not tolerate sound, light, or stimulation of any kind, had to be cared for by my husband) and not getting better and was put on pregabalin. This artificially slowed brain activity enough to allow me to return to 75%, but with symptoms above.

I am tapering now slowly off pregabalin (but hoping progesterone / allo might help me get off of since progesterone has calcium channel blocking activities and allopregnanolong has GABAergic activities, thus reducing neural excitation, which rebounds badly with dropping pregabalin). I would have started progesterone way back then but unfortunately had a bad experience with it in the past. I basically used 50-100mg oral extended-release compounded progesterone at bed that caused panic attacks and swollen breasts. I believe now that it was due to the progesterone being too low and not the optimal kind (I didn't know about Progest-E back then unfortunately). I had also tried cream but it didn't seem to do much at all.

4. I am only on pregabalin and tapering it very slowly at about 10% a month. It is hard to detect withdrawal symptoms in the background noise, but so far nothing has worsened. I do feel this is not a good drug long term, but it has reduced glutamate and norepinephrine enough to allow me to function again. Since nifedipine appears to block T3 entry into cell, I am increasing my T3 also (Cynomel). I do poorly with T4, with a drop in temps and pulse every time (current pulse is around 80, temp 98.4 - 99.5)

5. My injury was medication induced. I will never take another pharmaceutical again, and actually have taken very few in my life. I am slowly re-reading all of Peat's posts and working my way through the posts on this forum as well

6. My progesterone intakes have been all over the place, as I have been trying to figure this out. I have Progest-E, Health Natura progesterone, Biomatrix progesterone, prometrium, compounded SR progesterone, and compounded progesterone suppositories. I have not found an optimal way to use these. I use the following metrics 1) body temperature using an Oura ring. My luteal phase temps always go to +0.7 when I am feeling better. If I can even get my temps to +0.2, I do feel a bit better. I occasionally get a +0.5. I also go by symptoms. When I get very low, I feel absolutely horrid and my stomach muscles are rigid oddly. I have not found any form of progesterone to give me any consistent relief or increase in body temperatures. That said, I had the best luck swallowing Progest-E every 4 hours, around 50mg (but this is a ton of Vit E). My liver does get used to this over a few weeks, and temps fall again. Prometrium has an immediate calming effect likely due to a huge spike in allo, but doesn't last long, likely to it's extraordinarily short half life. Everything else has been kind of meh. I have tons of references if you would like any.

If you got through all of this, thank you! And if not, I understand. I feel like Peat has the clearest path to possible health for me. I have optimized just about everything else I can think of including protein, nutrients, carbs, and PUFA (milk, OJ, oysters and liver on occasion, coconut oil, etc). But because of the profound damage to my glutamate receptors, I feel like I need a strong intervention (but not a pharmaceutical).

 

[dand]

Have you tried aspirin? Still with the Progest-E or porgestene in my experience? How is your caloric intake?

 

[Rasaari]

Caffeine dose depedently increases neurosteroids potently in the (rat) brain. High dose niacinamide can be useful as gaba-agonist.

Caffeine-Induced Increases in the Brain and Plasma Concentrations of Neuroactive Steroids in the Rat | Request PDF

Request PDF | Caffeine-Induced Increases in the Brain and Plasma Concentrations of Neuroactive Steroids in the Rat | The effects of caffeine, a naturally occurring stimulant, on the brain and plasma concentrations of neuroactive steroids were examined in the rat.... | Find, read and cite all the...

www.researchgate.net

 

[themartian1000]

Have you tried aspirin? Still with the Progest-E or porgestene in my experience? How is your caloric intake?

I am taking aspirin - I have trouble with my stomach so take two baby aspirin with food. I've tried the various tricks for taking it - might try them again. I am not sure how much I eat, but I am not gaining or losing so I guess enough?

 

[themartian1000]

Caffeine dose depedently increases neurosteroids potently in the (rat) brain. High dose niacinamide can be useful as gaba-agonist.

Caffeine-Induced Increases in the Brain and Plasma Concentrations of Neuroactive Steroids in the Rat | Request PDF

Request PDF | Caffeine-Induced Increases in the Brain and Plasma Concentrations of Neuroactive Steroids in the Rat | The effects of caffeine, a naturally occurring stimulant, on the brain and plasma concentrations of neuroactive steroids were examined in the rat.... | Find, read and cite all the...

www.researchgate.net

Thanks! I am a slow metabolizer of caffeine and take niacinamide but maybe I should take more (I take 500mg a day).

 

[Rasaari]

Thanks! I am a slow metabolizer of caffeine and take niacinamide but maybe I should take more (I take 500mg a day).

500 is what I was thinking. Regarding the aspirin, its good to dissolve in baking soda and hot water and take after a meal. Stomach tolerance to aspirin comes slowly, but I for example have crohn's and can take grams of it nowadays. Took a while though.

 

[themartian1000]

500 is what I was thinking. Regarding the aspirin, its good to dissolve in baking soda and hot water and take after a meal. Stomach tolerance to aspirin comes slowly, but I for example have crohn's and can take grams of it nowadays. Took a while though.

Thanks, I'll give that a try with the aspirin and baking soda after dinner!

 

[dand]

Get aspirin from toxinless.com Gericare is the brand. If aspirin gives you issues you want to have gelatin/glycine. It will help. I think it's important you get an accurate understanding of your average caloric intake so you can assess if you need more fuel to heal. My guess is that you do. If you don't respond to caffeine well it suggests liver issues and vitamin k2 (from idea labs) and caffeine are therapeutic and will help rehab liver

 

[PeskyPeater]

Oh. How do you know allopregnanolone is really low?

It seems that you have got the notion that the upregulation of brain neurosteroidogenesis is a preferred thing to do, probably from reading that propaganda of how use SSRI is known to have this seemingly cool effect.

But alas I have come to understand that allopregnanolone is made when the brain is being damaged by substances like SSRI. I know this because Dr. Peat told me. And I was on SSRI myself unfortunately. Are you on certain medication?

Stress and social isolation lowers allopregnanolone. Maybe you are a little bit lonely or too addicted to the WWW haha ?

 

[themartian1000]

Oh. How do you know allopregnanolone is really low?

It seems that you have got the notion that the upregulation of brain neurosteroidogenesis is a preferred thing to do, probably from reading that propaganda of how use SSRI is known to have this seemingly cool effect.

But alas I have come to understand that allopregnanolone is made when the brain is being damaged by substances like SSRI. I know this because Dr. Peat told me. And I was on SSRI myself unfortunately. Are you on certain medication?

Stress and social isolation lowers allopregnanolone. Maybe you are a little bit lonely or too addicted to the WWW haha ?

Well, I feel best at the peak of my luteal phase. That is really the only thing that seems to make me feel better. So it's either allopregnanolone or progesterone (or estrogen, but that doesn't seem quite right). There are a number of studies on allopregnanolone and anxiety/depression (including some posted by haidut for what it's worth), and these seem to correlate. Also, since I suspect my glutamate receptors are upregulated (and it seems very difficult to down-regulate them due to the brain's desire to protect itself from glutamate itself, which would seem to be the only thing to down regulate them), I have a constant imbalance / neuroexcitation state (due to being put on then taken off benzos - my mistake for every seeking medical care - this was 15 months ago so something has not repaired yet).

I was placed on pregabalin as I was ready to end it all and my brain couldn't seem to repair at all under the conditions it was forced into. I am tapering pregabalin, a strange drug that has to be carefully tapered. So yeah, the situation is complex. I'd not touch an SSRI as serotonin, even a bit, seems to make my brain crazy (I was asked to try and stopped after a few days due to extreme agitation). So, yeah, I think my brain was damaged and as the brain does produce allopregnanolone when damaged, this is likely a protective and healing substance. I have a supportive and loving family with whom I spent a lot of time daily as I live with them, and I also have a number of friends with whom I speak frequently. Addition to the www is legit though. I try to spend a lot of time outside, away from the computer, but my work is all online.

Anyway, hoping someone here might have additional insights, concrete things that might help.

 

[PeskyPeater]

Allopregnanolone acts like a positive allosteric modulator of GABA-A receptor and is high at luteal phase via increased progestrone. Apparently even adding more of Prog has little effects. Seems like GABA system is desensitized by the chronic administration of the synthetic gaba medication.

Salvia Officinalis extract has flavonoids that act the same way, positively modulating GABA-A, and could be helpful as alternative, maybe even restore sensitivity.

Estrogen modulates serotonin, blocking estrogen could bring out serotonin inhibiting effects. Have you tried anti-serotonin ?

 

[themartian1000]

Allopregnanolone acts like a positive allosteric modulator of GABA-A receptor and is high at luteal phase via increased progestrone. Apparently even adding more of Prog has little effects. Seems like GABA system is desensitized by the chronic administration of the synthetic gaba medication.

Salvia Officinalis extract has flavonoids that act the same way, positively modulating GABA-A, and could be helpful as alternative, maybe even restore sensitivity.

Estrogen modulates serotonin, blocking estrogen could bring out serotonin inhibiting effects. Have you tried anti-serotonin ?

Thanks, I will look into Salvia. The benzo was for a short period (a few months), not daily, but because I was taken off cold turkey and my neurosteroids were low, I think I had a severe reaction. It was truly crippling, but was 15 months ago. I do respond very well to having high progesterone, it just seems that I have trouble absorbing it. I think if I could find a reliable way to get it into my body, my brain seems to know what to do with it so that I feel better. I think that I may need temporary supraphysiologic levels to heal my brain, but it's just a theory based on how I feel.

Do you have any recommendations for effectively blocking serotonin. Tianeptine is a serotonin reuptake promoter, but isn't super helpful. Anything anticholinergic (cyproheptadine) seems to make me feel worse. I have tried estroban. My last estrogen numbers were not too high, but I know this can be deceiving. I do have some lisuride, but I think that's mixed in terms of serotonin. I do work on my gut - perhaps some doxycycline a few days a week to lower gut serotonin?

 

[PeskyPeater]

Benzo's can alter GABA system pretty fast after 3 days, and not tapering off can give brain zaps. I don't think the progesterone is not absorbing, it is not constantly effective because you developed tollerance to the allogpreg. And the pregabalin is keeping the gaba system issue from repairing. Better to wean it off over a couple of weeks.
Good anti serotonin is Telmisartan or maybe Losartan but that can have bad fillers.

 

[PeskyPeater]

You can find info about Sage / Salvia bioactive constituents here

 

[PeskyPeater]

Tianeptine increases the uptake of serotonin in platelets, but not specifically block serotonin neurons in the brain. And would not be good choice here because it potentiates AMPA glutamate system, but having used benzodiazepine that enhances AMPA, GluR1* specifically so this has to be downregulated to reduce overexcitation. *-source

Lisuride can work as anti-serotonin, but I think you have to focus on negatively modulating AMPA. Some GABA modulators do that but it's difficult to find exactly which one. I'm hoping Sage to do the job, but it's experimenting.

Doxycyline is a good option because serotonin and endotoxin go hand in hand. Or Cascara.

 

[PeskyPeater]

When looking at other chronic Benzo effects, it seems to desensitize the Glu2 and Glu3.

The mRNA expression levels of mGluR2 and mGluR3 were lowered in the cerebral cortex of mice pretreated with diazepam or alprazolam. Our findings suggest that the reduction in the expression of group II mGluRs subunits may be involved in the development of benzodiazepine dependence. -source

You indicated getting bad effects from cholinergic blockade from cyproheptadine.
I found that Acetyl-L-Carnitine (ALCAR) has the ability to restore cholinergic function.

Immunocytochemistry showed an increase in choline acethyltransferase and tyrosine kinaseB receptors in motoneurons treated with ALCAR but not with L-CAR. These results suggest that ALCAR treatment improves the motoneurons activity, acting as a neurotrophic factor. -source

And ALCAR has been found to have the ability to improve the Glu2 system, that in this case, could have been affected by chronic Benzodiazepine administration.

Recent evidence suggests that the acetylating agent L-acetylcarnitine (LAC), a drug marketed for the treatment of neuropathic pain (9), causes analgesia increasing type 2 metabotropic glutamate (mGlu2) expression via an epigenetic mechanism shared by HDAC inhibitors (10⇓–12). mGlu2 and its cognate receptor, mGlu3, are coupled to Gi/Go proteins and are preferentially (albeit not exclusively) localized in the preterminal region of axons, where they negatively modulate neurotransmitter release (13). Expression and function of mGlu2/3 receptors is reduced in the hippocampus of spontaneously depressed Flinders Sensitive Line (FSL) rats, and pharmacological activation of mGlu2/3 receptors shortens the time required for the therapeutic efficacy of conventional antidepressants in these rats (14, 15). Together with the observation that there is a clear overlap between the brain regions of the “pain matrix” and the regions involved in the pathophysiology of depression and anxiety, including the prefrontal cortex (16, 17), these studies led us to hypothesize the acetylating agent LAC as a unique epigenetic antidepressant with a fast onset of action. -source

...Taken together it seems that ALCAR is a potential solution to the ill effects of chronic benzo use. Reviews indicate an effective dosing of 630-2,500mg per day. -source

 

[themartian1000]

When looking at other chronic Benzo effects, it seems to desensitize the Glu2 and Glu3.



You indicated getting bad effects from cholinergic blockade from cyproheptadine.
I found that Acetyl-L-Carnitine (ALCAR) has the ability to restore cholinergic function.



And ALCAR has been found to have the ability to improve the Glu2 system, that in this case, could have been affected by chronic Benzodiazepine administration.



...Taken together it seems that ALCAR is a potential solution to the ill effects of chronic benzo use. Reviews indicate an effective dosing of 630-2,500mg per day. -source

Thank you so much for taking the time to write all of this. I actually recently ordered some ALCAR for it's potential to heal the brain, but hadn't seen any of this, so I greatly appreciate it. I am going to give it a try and report back in a few weeks / months.

 

[PeskyPeater]

Thank you so much for taking the time to write all of this. I actually recently ordered some ALCAR for it's potential to heal the brain, but hadn't seen any of this, so I greatly appreciate it. I am going to give it a try and report back in a few weeks / months.

You're welcome, I like to do research like this, very intriguing, for me it's like quest or a puzzle that has to be solved hehe.
And what a nice coincidence, I'm looking forward to reading about your exp with it, good luck!