I definitely have had this problem for a very long time. People think I’m giving them dirty looks. Hmm, didn’t realize it was a symptom of unstable Estrogen.
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I have droopy eyelid too
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I’m really glad you got well. A great man! However, I have some comments and questions for you.
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I’m afraid of curcumin and piperine a bit because they are both reductase inhibitors (https://en.wikipedia.org/wiki/List_of_5α-reductase_inhibitors). What do you think?
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last year you wrote that we know that "5AR catalyzes and modulates these specific reactions:
Cholestenone → 5α-Cholestanone
Progesterone → 5α-Dihydroprogesterone
3α-Dihydroprogesterone → Allopregnanolone
3P-Dihydroprogesterone → Isopregnanolone
deoxycorticosterone → 5α-Dihydrodeoxycorticosterone
corticosterone → 5α-Dihydrocorticosterone
Cortisol → 5α-Dihydrocortisol
Aldosterone → 5α-Dihydroaldosterone
Androstenedione → 5α-Androstanedione
Testosterone → 5α-dihydrotestosterone
Nandrolone → 5α-Dihydronandrolone
(…) Namely, we should test all levels of endogenous hormones from the first column in our body and all metabolites from the second column (or any other compound that is able to pass these concentrations through a proxy)" (Initial Ideas - Working from First Principles).
Have you checked the levels of all these hormones and metabolites (i.e. other than 3α-Dihydroprogesterone → Allopregnanolone you wrote about) before advancing the GABA receptor hypothesis?
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Do you plan to use herbs other than bacopa or caffeine with similar effects (I’m thinking about sensitizing GABA receptors)? This is important because I read that it is recommended to use bacopa for 8-12 weeks, and then take a break of several weeks. If so, then do you know any other herbs or roots (except caffeine) with similar effects that can be used during a break from using bacopa?
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what do you think about other adaptogens? As a rule, it is recommended to use rhodiola or ashwagandha together with bacopa. The only question is, will it be beneficial for us (in the context of improving GABA receptors)?
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what do you think about using GABA antagonists? It’s a little odd, but maybe reducing GABA levels (to a lesser extent than finasteride did) will sensitize receptors - just my thought.
I will be grateful for your reply.
Hej guys,
I’m gonna try some of this protocol to see if it has any effect.
Today I’ll order these two
- Bacopa
- Curcumin
I’ll keep you guys updated.
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Hey – great questions that go fair beyond the pseudo-scientific conjecture I have seen here, so I commend you for that. I’ll try to address the questions linearly:
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You’re absolutely right about curcumin and piperine as being 5ARI’s. While their potencies as inhibitors are comparatively weak (especially in comparison to pharma-grade drugs like fin which work in the nM range as opposed to herbs/polyphenols that are generally inhibitors in the uM and mM range-- so orders of magnitude different), I would but a moratorium on using these supplements as you’re ultimately going for a recovery while using as few exogenous (and pricey) compounds as possible. A fairly comprehensive list can be found here (though I would also add quercetin to it): https://en.wikipedia.org/wiki/List_of_5α-reductase_inhibitors
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I’ve checked nearly as many of them in my CSF as is possible (some are unstable intermediates that degrade quickly or there are simply not laboratories that have the testing capabilities for some of these neuro-steroids), and I tested most other in serum tests as many can reliably portend CSF levels (though in a pathological state this is not a hard-and-fast rule). In CSF, I tested: Allopregnanolone, Isopregnanolone, Aldosterone, Androstenedione, 5α-Androstanedione,Testosterone. I felt this gave a good gauge of both precursor steroid production as well as 5-Alpha reduced steroid output in my CNS.
I also did several panels of all iterations of these steroids in serum and even in urine metabolites. Long story short, all my levels were entirely within acceptable ranges (though established ranges for CSF neurosteroid concentrations are notoriously hard to establish). This was manifestly confusing as all my symptoms seemed to reflect poor ALLO concentration. That’s when I found this paper, which was really an inflection point in my recovery:
The result was a CSF assay mRNA transcription factors for GABA(a) regulation, which were woefully downregulated. At least in my case, it wasn’t dysfunctional 5AR reduction that was the problem, but rather a pathological reaction to acute and drastic upregulation of ALLO when I quit Finasteride.
- I’m now really only using a small amount of Bacopa (two does of 300mg @ 24% extract twice daily and fasting daily). I also drink coffee but not for therapeutic benefit–mostly just because I really like it. I have a fair amount of knowledge about GABA(a) and GABA(b) regulation and cell surface expression, and I can share that in a more granular way if you want. For the time being, Bacopa is a good option per this collection of studies that demonstrate consist upregulation of δ subunit-containing GABAA receptors in various brain regions:
https://www.sciencedirect.com/science/article/abs/pii/S0378874110002965
https://www.sciencedirect.com/science/article/abs/pii/S152550501000017X
I want to comment that I’ve seen the fairly erroneous idea floated that Bacopa is a potent 5ARI; this is patently untrue and these ideas represent the nadir of collective pseudo-scientist delusion that I really dislike about this site. The truth is that a minor component of Bacopa is Beta-Sitosterol which is a 5ARI (but is only .12% to .01% of Bacopa by weight depending on the sample under HPLC analysis), and even then this 5ARI is orders of magnitudes weaker than many other common inhibitors like zinc and vitamin b3.
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I would be careful with any other adaptogens that have any activity at GABA(a) or GABA(b) receptors both as agonists or as PAM. As the above novel ALLO tolerance study delineates, potnet tolerance to PAM’s is a strong possibility and might just further exacerbate your problems. I would do a deep dive on Examine.com with respect to the mechanisms of action for any substance you are considering putting in your body.
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That’s a very intelligent question, and I don’t have an answer for you. It seems to me that even in the use of an antagonist the upregulation would only be transient and dose-dependent w/ antagonist use. This would be problematic as you’d be experiencing the full gamut of negative side effects from increased neuronal depolarization (and subsequently heightened excitability). You could try it and see how you respond (just don’t use Zn as it’s a 5ARI). In a roundabout way, caffeine is a GABA receptor antagonist, so this may also be a route to pursue.
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I would hold off on the Curcumin for now, and please reference the above comment.
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You’re being weirdly antagonist for what I see as a cordial exchange about the underlying mechanism for my condition-specific pathology. Again, I really dislike this site because I’m not claiming to have a unifying theory for each and every case; I’m giving input on how I have substantially ameliorated all of my PFS problems and the concomitant neurobiological considerations. This hedging gets really old and these exchanges are frankly exhausting. For many reasons, I don’t blame people like my who have abrogated our symptoms from not coming back here, and I plan not to once I have hopefully helped those looking for help in earnest.
As far as what I can tell you were saying substantively, certainly others have not regained sufficient 5AR functionality and thus have downregulated ALLO production, but this would actually manifest as symptoms very similar to my own and necessitate an entirely different treatment strategy given the underlying problem (in this instance Etifoxine is what i would pursue – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4364751/). Either way, I think you can see the point I am making: the underlying mechanism is a crucial component of finding an effective treatment. Antagonizing someone like me who is doing what amounts to substantial charity to aid those who were in a similar position to me is a losing strategy. Take my advice or don’t, but at the end of the day I feel normal and I’m not so sure you do.
As far as Bacopa “5ARI” status is considered, I’d refer all concerned to this study @ table 3 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721057/), specifically “Percentage of 5α-DHT formation in HHDPCs after being treated with various methanolic plant extracts (at 10 μg/ml) and dutasteride (also at 10 μg/ml). The 5α-DHT formed in the standard bioassay system was set to be 100 %”. Bacopa’s value is 105 ± 9%; though there is a larger confidence interval here, these data suggest that Bacopa may in fact be a 5AR catalyst to a modest degree.
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Are you going to be able to post those csf results?
I think the results would further validate everything you have been saying, more than what could ever be typed or explained otherwise.
That would be a great contribution that i’m sure many would appreciate.
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Honestly, there is no point in saying those things, sorry, I think I overreacted because I was waiting for some simple advice that i can understand, but its all scientific things that I don’t understand at all. Could you give some simple advice to us people that don’t have a deep knowledge of biology? I have very similar symtoms with you, I also noticed sacadic eye movements but only when i read, my eyes just wander around. My blood results showed normal DHT and high cortisol, my doctor will probably give me treatment for this. My cortisol isnt sky high but i have Cushing symptoms and prednisone face. The last years I drink about 3-10 coffee cups a day and this didnt help. Maybe the supplement will. I cant understand all these things you are talking about except at some basic level.
Wow, really valuable answers. Thanks!
Let me ask you a few more questions.
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Ok, then I won’t use curcumin and piperine. They may not give PFS to healthy people, but it should be remembered that some of us are particularly sensitive to the effects of even mild antiandrogens. It’s enough to see in this forum that some people reacted badly to 5ARI like coconut oil.
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I’m not a specialist, but I’m wondering that your body started to regenerate so quickly. I have read that GABA receptors regenerate very slowly (perhaps the slowest of all) and it may take many years before they recover. I do not question your hypothesis, I just see it as a great opportunity for our community - after all, after a few days of using bacopa I started to feel an improvement.
3a. Of course, I will be grateful for more information about bacopa. As a person with a lot of knowledge, you can notice much more and combine the facts. I also started looking for something that works similar to bacopa. This is mainly due to the fear of developing tolerance for bacopa - I want to have something in reserve. And what do you think about gotu kola (centella asiatica)? It is almost a twin plant relative to bacopa. And also has anti-epileptic effects:
I would be grateful if you could verify that the action of gotu kola is right for us.
3b. I’m not sure, but when you wrote about reductase inhibitors, you meant vitamin b2, not b3, right?
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Another interesting issue. For some time I have been reacting badly to ashwagandha, which is a positive GABA positive allosteric modulator (https://selfhacked.com/blog/natural-ways-to-increase-gaba/, https://www.ncbi.nlm.nih.gov/PubMed/1660034). Perhaps there is an answer here (although I would be grateful if you would briefly specify why positive GABA positive allosteric modulators are bad for us in the light of your hypothesis). In turn, rhodiola does not affect me in any way, but I also did not find a connection between GABA receptors and rhodiola (only something like this: https://www.ncbi.nlm.nih.gov/pubmed/23975866).
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Ok, but I’m not ready for another disaster. I have already lost to a reductase inhibitor (proscar) and an aromatase inhibitor (arimidex), so I think that if I tried it, I would have to add a GABA inhibitor to this list.
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You saw these threads?
A few years ago, molybedenu wrote something similar to your hypothesis, but without a precise scientific foundation, although it pointed to water fasting and bacopa monnieri as a form of treatment. He also wrote about theanine, the only question is whether we need it, if it is responsible for the increase in GABA concentration? What do you think? BTW does not appear to have reported any molybedene report on the application of the above protocol.
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You probably know the cdnuts method (in short: diet, exercise and rotation of herbs and roots). I know it is controversial, but I wonder if behind some of his followers’ successes there is a bacopa? As a rule, in his method herbs and roots such as muira puama, suma, maca, eleuthero should be rotated (a different herb every day), but herbs such as bacopa or gotu kola are recommended to be taken daily. I admit that I use a certain modification of this method myself, only that so far I have also rotated the bacopa and gotu kola. As a result, I gained a lot of muscle and strength gains (I only train 5-10 minutes every other day), but it didn’t work for my brain in any way (paradoxically, the stronger I get, the more brain fog and headache I have - is there any rational explanation of this phenomenon against the background of your hypothesis?). Assuming that I would like to continue using this method (I mean the daily rotation of 20 different herbs), can it destroy the effect of bacopa? Can I, however, continue this protocol, assuming that using one herb (even if it is a GABA agonist) once every 3 weeks will not spoil the good effects of bacopa?
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As you know, our site also contains former SSRIs or isotretinoin users. Can your hypothesis also apply to them?
https://www.ncbi.nlm.nih.gov/pubmed/21989809 https://www.ncbi.nlm.nih.gov/pubmed/20707986
https://www.ncbi.nlm.nih.gov/pubmed/23157628
Research on SSRIs suggests that this may be the case, but the question is whether (assuming your hypothesis is correct) the mechanisms of PFS and PSSD are the same?
I will add a few sentences to point 7. I wrote above I feel the negative effects of anaerobic exercises (including weight lifting or pulling up) in terms of psychological side effects (even though I have hard and significantly larger muscles - my body looks completely different than immediately after the disaster). It is a bit strange for me, because I eat clean, exercise lightly, sleep 8-9 hours, and yet the brain fog in recent months is as strong as after a disaster. Intolerance to anaerobic exercises is common to many of us.
Scientific studies show aerobic exercise improves GABA function, but I can’t find equally convincing evidence for the positive effects of anaerobic exercise on GABA and GABA receptors. I found information that anaerobic exercises mainly increase serotonin levels (in turn aerobic exercises modify dopamine, acetylcholine and GABA levels), which (again - assuming that your hypothesis is correct) can be unfavorable if this excessive serotonin level it is not properly inhibited by malfunctioning GABA receptors.
https://physoc.onlinelibrary.wiley.com/doi/full/10.14814/phy2.14107
Correct me if I am wrong, especially since 1) I am not a scientist 2) English is not my first language 3) My brain fog has a negative effect on my understanding of these processes.
I have mentioned this in another thread. Our symptoms can be accurately described in the side effect section of the antibiotic called minocycline. People have reported gray blue skin, even depersonalization is there. The symptoms are reversed after discontinuation, could our syndrome be an autoimmune disease? Is my opinion legitimate, thinking about trying mitotane and ceasing it, maybe my body will come to its original state. Also cortisol, whats the significance?
In view of what you wrote, I wonder about the nature of PFS. In view of the large number of reactions at which 5ar is involved, perhaps PFS is actually a set of various disorders caused by blocking these reactions. For one person it may mean a failure at the level of “Testosterone → 5α-dihydrotestosterone”, for another at the level of “Cortisol → 5α-Dihydrocortisol”, and for another “3α-Dihydroprogesterone → Allopregnanolone” or several different failures simultaneously. Perhaps this explains the variety of our symptoms, their severity and the ways of effective treatment. Then both hypotheses, e.g. androgen receptor insensitivity, GABA receptor, epigenetic and autoimmune hypotheses may be correct. To the question about which one is correct for each of us, the answer may be at what level the 5ar failure occurred.
It’s just my thought. Does that make sense? I would be grateful if someone more competent than me would reply.
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Not more competent here but I would like to note that I have seen mentions on reddit of many people treating post finasteride syndrome with steroids. I dont know if these people know about pfs but they are aware that finasteride cause their symptoms. I have read a guy treating his symptoms simply with test injections and aromatase inhibitors, his protocol as he claimed cant function without aromatase inhibitors. Relief of his symptoms was immediate. What you say, hrihor is very possible, people have different symptoms BUT they are all persistent which makes me think that there must be some connection between all these symptoms. Also people with pfs usually present many of these symptoms while the general population doesnt except the common dip in libido and ED. I would also like to note that all my symptoms even derealization INSTANTLY DISAPPEAR once i get drunk. There must be a channel in my brain blocked by alcohol which brings me back. Maybe I should dry anticonvulsant channel blockers, can anyone spot possible channels so i dont have to go through 50 anticonvulsants before i find it?
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First, thanks so much for sharing all your information. Very helpful.
Please ignore any negativity. You are doing God’s work by contributing. People will benefit from your insight.
I am much like you. I don’t have libido issues at all, but definitely the mental issues from finasteride. However I never had the physicals symptoms you do, such as headache, muscle pains, eye issues, etc. I did have 2 bouts of meningitis, but those were more so detoxifications and my baseline improved after those painful illnesses.
My PFS hit while I was on the drug, not when I came off, and was triggered by a stressful event one evening, and after that my body could not calm down and severe insomnia and anxiety ensued, followed by CFS and the works. It’s as if my brain was racing and I could not stop it, likely due to not enough gaba action at the time, and nothing to metabolize cortisol to thdoc.
Once my PFS hit, I did stop taking finasteride, at the same time I started lifting and taking creatine, which made my mental side effects worse, but my libido was uncontrollable with a ton of anxiety. It has settled down since then.
1-2 years into PFS I improved my baseline considerably through a raw carnivore diet, intermittent fasting and especially through the use of GHB. It acts on the gaba-b receptors and indirectly acts on the gaba-a receptors due to the increase in neurosteroids progesterone, pregnenolone, allo and thdoc. I believe you posted a study that points out this mechanism of indirect stimulation on gaba-a.
Help me understand…We have insensitive gaba, so we want to upregulate gaba(a), normally you would use antagonists to upregulate…right? Yet…using agonists on gaba(b), will upregulate gaba(a)? It’s confusing.
After my brief use of GHB, my baseline increased a lot, as did my tolerance to stress and sleep improved. However, with that improvement, I am still far from cured. Brain fog and lack of cognitive capacity seems to be the biggest issues, especially the anhedonia/derealization. Absolutely no passions and very difficult to feel things or get excited, although I am not depressed. I am a happy person, I can laugh easily and the works, but I just cannot feel these things.
Furthermore, I find that when I take glycine before bed, I tend to get very poor sleep and my mind feels quite excitable and my brain won’t stop talking, however I tend to feel better the next day, more emotions and connected to the world. There are studies showing that certain doses of glycine stimulate 5ar activity, and in higher doses, more so 3a-hsd. Apparently the excitability I feel is from nmda receptor activation?
I no longer have anxiety and I am quite a calm person but good stress resilience, however sometimes when the cognitive issues become too great, that stress tolerance dips as well.
You mentioned Mg BHB. Can you go over what doses and how many times per day? I am currently taking Sodium Butyrate as well as Sodium (Na BHB).
You also mentioned to be careful with any other adaptogens that have any activity at GABA(a) or GABA(b)…Unfortunately I mega-dosed Ashwagandha for several months to try and combat my PFS side effects, I feel this may have caused new problems I’ve yet to address. People seem to get the same anhedonia/derealization from Ashwagandha use. Some people have reversed this with St. Johns Wort, which I may try as well.
I’d like your opinion on what direction to head in, although I am currently on an HCG protocol.
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Hey @thisisarealbummer
I’m quite curious about trying curcumin. As someone has mentioned before it is a 5ari. you gave some ic50 values. do you have one for curcumin?
Took Bakopa again last night. No positives except a worsening of symptoms which I hope are temporary. Tread carefully lads.
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Congrats on your recovery! I found your account very interesting and I was hoping you could elaborate on the possible direct neurobiological causes of brain fog that is induced by rapid fluctations in 5ARIs as well as their possible remedies. Both to satisfy my newly-piqued scientific curiousity about these issues and to help me address my own particular situation (not necessarily PFS but persistent brain fog following a crash – I’m a professional mathematician so I am acutely sensitive to any cognitive changes and cannot afford a long period of brain fog).
I took 0.5mg of fin for 40 days and stopped due to intense testicular pain and tingling in the extremities. These symptoms subsided over the next month before suddenly returning in force. In the middle of writing a paper, I felt the tingling migrate to my head, a sudden ‘brain zap’, and the onset of an intense brain fog. For three or four days, I experienced many of the symptoms you mention: strong head pressure, intense anxiety, difficulty concentrating e.g. unable to read a sentence, derealisation.
That crash was nine days ago. Since then, the degree of symptomatic severity has fluctuated with a general trend towards slow improvement. I am most alarmed by the difficulty concentrating, slowed thought process, and poor memory recall, (and concomitant head pressure) as improvement in this area seems to have stalled or slowed to a crawl. At this point, I am able to mark undergraduate student work with the aid of solutions but I can’t solve the problems myself! (No physical symptoms other than testicular tingling.)
I am considering trying some of the supplements you suggest, e.g. bacopa and curcumin. My questions are:
- are there any potential direct causes of post-5ARI-crash brain fog consistent with these symptoms for which these supplements might be counterproductive?
- should I wait longer before intervening to see if this resolves spontaneously? or is there no risk in intervening at this point?
- what is the main difference between the majority of people who recover quickly and the minority who experience persistent brain fog? an inability to normalise receptor sensitivity after up or downregulation?
Thanks for your help! My doctor/the internet haven’t been helpful for this issue and my current cognitive impairment makes doing my own research into neurobiology impossible. BTW, I hope you consider writing a scientific paper about your experience!
what symptoms? according to the examine page it can lower dopamine
I would like to second this @thisisarealbummer
I know the results may be a bit personal for you (even with the obvious removal of all personal data from it).
However, this is one of the most promising & clinically-relevant topics on here. As it is evident, multiple people are already trying different variants of your protocol, and more will be trying them in the future. Since this is the reality of it, having the results shared here will give much more credibility to not only your experience & protocols, but also for the various attempts people will make based off it.