Paul Waters:
It´s clear you are either a fucking idiot or a Merck employee (which makes you a fucking idiot eitherway).
I was just reading through the following study and came across some sections which I thought may be of interest to this thread.
Remember, Finasteride inhibits 3,5-THP (AKA allopregnanolone) production as shown here: jneurosci.org/cgi/content/fu … IG1?ck=nck
Perhaps there may be something to the Ethanol, Progesterone & GHB treatment theory after all?
Brain Steroidogenesis Mediates Ethanol Modulation of GABAA Receptor Activity in Rat Hippocampus
jneurosci.org/cgi/content/fu … 521?ck=nck
“Ethanol, progesterone, CB34, and GHB stimulate 3,5-THP production in isolated hippocampal tissue.”
"…pretreatment of animals with the 5-reductase inhibitor finasteride, which inhibits the biosynthesis of 3,5-THP (see Fig. 1), reduced the extent of the ethanol-induced increase in the cerebrocortical concentration of 3,5-THP and prevented certain neurochemical, electrophysiological, and behavioral effects of ethanol. "
"The effects of ethanol, progesterone, CB34, and GHB were prevented by pretreatment of the tissue with 1 µM finasteride for 10 min (data not shown). "
"Finally, we tested the effect of GHB on GABAA receptor function. The systemic administration of this compound, like that of ethanol, increases the plasma and brain concentrations of neuroactive steroids in rats (Barbaccia et al., 2002). "
"Progesterone, CB34, and GHB also each increased the amplitude and the decay time of GABAA receptor-mediated mIPSCs. Because these latter drugs also increase 3,5-THP biosynthesis, these results further support the role of brain steroid metabolism in shaping GABAA receptor-mediated inhibition in a discrete brain area (Belelli and Herd, 2003). "
"Progesterone is metabolized by neurons and glial cells to 3,5-THP (Hu et al., 1987; Bitran et al., 1995; Follesa et al., 2000), whereas CB34 is a selective agonist of the PBR and stimulates steroidogenesis in the brain and peripheral organs (Serra et al., 1999).
The capacity of GHB to increase both plasma and brain levels of 3,5-THP as well as other neurosteroids after systemic administration has been proposed to involve GABAB receptors (Barbaccia et al., 2002). "
"Furthermore, prolongation of current decay time by ethanol, progesterone, CB34, and GHB was abolished by finasteride, again supporting the role of 3,5-THP in the modulatory action of these drugs in hippocampal pyramidal cells. "
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Mew…seriously, what does posting that study have to do with anything? What the hell does that mean.
Did you forget that everyone on this forum suffers from brainfog…urself included. How the hell can you make anything out of all that mumbo jumbo stuff.
Studies like that are the same ones that said Finasteride is acceptable in 1mg form and side effects will go away if discontinued.
Jack
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What it means is that what Paulwaters proposed – ie GHB to stimulate GABA via increased Allopregnanolone – may have some merit if this study is any indication, since “The capacity of GHB to increase both plasma and brain levels of 3,5-THP [allopregnanlone] as well as other neurosteroids after systemic administration has been proposed to involve GABAB receptors.” Therein may lie another factor – GABA-B, not GABA-A.
Secondly, we know that Finasteride inhibits Allopregnanolone production as seen here: jneurosci.org/cgi/content/fu … IG1?ck=nck
What we don’t know is wether such inhibition leads to somewhat permanent neurochemical changes for those of us that have these problems after taking the drug… nobody has baseline Allopregnanolone levels to compare against, nor has anyone ever tested for it. But the fact that “Ethanol, progesterone, CB34, and GHB stimulate 3,5-THP [allopregnanolone] production in isolated hippocampal tissue” in the rat is very interesting, considering Paul’s theory and claims of GHB “curing” his Finasteride issues via such stimulation, and possibly by aiding with REM sleep (which another poster claims helped him recover as well – sleep, that is: propeciahelp.com/forum/viewtopic.php?t=695 )
I agree this all sounds somewhat farfetched (REM sleep/GHB aiding with recovery) but at the same time the above study piqued my interest in this topic. Certainly however, REM sleep is important and I do recall for myself not having much of it during my 11 months on Finasteride, and not sleeping as deeply since quitting the drug.
I also just want to mention that I am not necessarily advocating anyone jump on GHB. I do not consider myself easily lured by “miracle cures” or quackery. But at the same time, Finasteride also impacts neurosteroid production in the brain – this much has been proven via scientific literature and studies done on both animal and human subjects. So I believe keeping an open mind and doing more investigating into such areas (neurochemicals/neurosteroids/neurotransmitters effected by finasteride) is certainly warranted, as it will only help us grasp the bigger picture of how this drug affected us beyond just “blocking DHT”.
Such investigation is even more important considering the anecdotal reports of some guys getting their hormones back into range and feeling no different, or looking at the bloodwork of guys on this site that have high T levels and are by all accounts “normal” in their pathology, yet who are still having problems.
So in my mind, there may be something more going on with us that were affected by this drug, besides just hormone levels – such as a neurochemical/neurosteroid/neurotransmitter imbalance or change… or possibly an alteration to the way the liver’s P450 Cytochrome system metabolizes hormones and enzymes, such as 5AR.
Anyway this is all theory and I’m no doc… I’m just looking for alternative avenues to explore.
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Mew, I’ll add one important point here: the study you reference is in a rat model.
As you probably know, it has been shown that finasteride acts in the rat to inhibit both 5AR type I as well as type II with equal potency.
This is not the same case for humans. In human type I 5AR contains a 4 amino acid sequence that confers resistance finasteride. While finasteride does inhibit type I somewhat, the affinity for type II is 100 fold greater than that for type I.
Also, I’d point out that in subjects taking finasteride, DHT is generally reduced by 2/3, exactly the proportion of type II to type I. This would imply that type I is carrying on business as usual.
Naturally though, there is some inhibition, but somehow I doubt it’s enough to be an important factor. If it was, we should expect that dutasteride (a truly potent inhibitor of type I) would have much more drastic effects than has been shown. Dutasteride crosses the blood brain barrier just as finasteride does, as well.
Also, recall this study: pomology.org/003/555/003555228.html
“In conclusion, allopregnanolone suppressed hypothalamic GnRH release in vitro and this effect appeared to be mediated by an interaction with the GABAA receptor”
If we in fact were suffering an allopregnanalone deficiency, we would expect, if anything, increased gonadotropins, which is not at all the case (unless, of course, said deficiency was in conjunction with some other ailment…but the simplest answer is often the correct one).
(However, were we talking about an allopregnanalone excess, on the other hand, we could in fact tie this to low testosterone).
I, for one, am thinking nowadays that this is primarily a testosterone issue for most people - which could in fact explain brainfog (see: propeciahelp.com/forum/viewt … highlight=) As far as I can see, most issues can be attributable to testosterone deficiency alone. Recall, for instance, that this is the case for dopamine, which increases when testosterone returns.
I think neurosteroids would definitely be worth examining, but again I doubt it’s the real issue. Then again, biology is full of grey areas…maybe for some people it is the real issue. Who knows, I guess…
The liver thing would also be interesting to look into but I doubt my idea about increased CYP3A4 activity having any impact on testosterone levels really has any merit - there would be a study to show it! Doesn’t entirely rule out it being a liver issue though…
Anyways, just my 2 cents.
Actually, hold on, I have found another source indicating that liver enzymes can indeed affect testosterone.
Simple google search turned up this:
t-nation.com/findArticle.do?article=13stron
"T: A few weeks ago, we theorized in one of our columns that it might be a good idea to take supplements with grapefruit juice. We suspect that a chemical in the grapefruit juice might block an enzyme in the body that breaks supplements down. What do you think of that?
DS: I think it’s a great idea. Most things are absorbed through the liver. But, if you can stop the liver from breaking down certain pro-hormones and supplements, my God, think about it. You might actually be able to use affordable amounts of HMB. The problem is that many professional athletes use steroids, and if we’re going to use something that prevents steroid breakdown, you might run into some problems. But, I can see using grapefruit juice with your Tribex. If you can increase testosterone levels, and you can prevent the breakdown of one of the chemicals or herbs, you can get more impact per pill and increase testosterone levels even more. I can see that as a great benefit."
So perhaps grapefruit juice might be worth a try…but still, this is all very speculative.
Hello,
I feel 100% cured like the prepropecia days. But like the prepropecia days, my hairloss is increasing dramatically! I am starting to get down about it and am thinking about embarking on a propecia routine again. I need advice??? I felt like absolute shit for 3 years? Is it work the risk?
Also, go to a naturopath and get tested for candida, parasites and leaky gut syndrome. Honestly I was cured about 4 weeks after I cleared this shit out of my body (which took 8 weeks of a strict anti sugart/wheat diet + nystatin). Why? because the adrenal glands which have severely atrophied from propecia (and the combination of candida/parasites that have entered the body after a very low immune system), have the chance to recover and thus produce the remaining 20% of the hormones (pregnonelone, testosterone, DHT, progesterone e.t.c) can be produced (as are done when adrenal glands are healthy, as ARENT DONE WHEN THEY ARE NOT!) I am starting to get that REAL Dht feeling back again, like constant erections, but on the negative note of DHT can feel an itchy like sensation on the scalp (which is actually the process of shrinking hair follicles in the presence of DHT, my hairloss has worsened!).
Would you guys trade your hair for a complete recovery? Or would you rather keep your hair and feel like a caged animal with no libido?
I dunno whether it is worth risking taking again and slowly monitoring, taking saw palmetto, or forgetting that there was ever any drug that can slow hairloss.
Please help.
Regards,
Pauly!
want to get well! positive mind!
So your GHB treatment worked out well then? Are you still taking GHB?
I thought you already took Propecia again after quitting, as noted in one of your previous posts in this thread?
You know the answer – no it’s not worth the risk. And what’s all this about candida and an 8 week diet “curing” you when the very title of this thread is GHB is your secret to success?
You’re all over the map!
Dude, I doubt he’d spend his time posting this well written and sensical explanation for why he thought he was able to get over it and how, if it wasn’t somewhat true.
His recovery description definately hits a note with me. I feel like I still just have this small lingering infection (it goes awaya for short short periods once in a while and i feel normal) but this small infection that once gone i will feel fine. I feel my gear and pipes about to react. I can just feel the lingering blockage. But am optimistic i can get over this soon once I get rid of the infection. Its just so so obvious to me.
And whether this was caused by hormone imbalances or not, and I believe it must have been, I hope to correct it soon.
Whether it takes more dietary, natural, and herbal remedies, or HRT prescribed by an endocrinologist, I am ready to get myself cured.
I believe Paul, and i am glad he has just made this most recent posting. Thank you Paul for your detailed post.
ps. with regard to the GHB, I was thinking just recently as a matter of fact about how I haven’t recalled any dreaming much at all since all this Propecia problems started. So in agreement probably with most of you all, I think the REM sleep is probably very very important, and had probably just played a role in his recovery.
Paul. I’m coming for ya. you better be right
I went over some symptoms of “leaky gut syndrome” and noticed a bloated stomach, fatigue, difficulty concentrating and memory lapses were mentioned. Many of us have experienced these issues… particularly, the bloated stomach is a side-effect I have yet to comprehend. I’ve had a slightly bloated stomach for some time and feel slight cramps, like abdominal muscles tightening usually after eating. Not sure if this would be why, but I thought I would just mention that.
Again, here’s what Paul said about how Propecia could cause this:
Leaky gut is something that can occure without inviting candida either.
It happens when your body gets upset of using propecia, when you get alergies from the drugs and foods afterwords.
leaky gut is a problem that may interfere with your hormonal output via toxic reaction that spreads toxins from you gut throughout your body.
I believe that might be an issue since I eat less, sleep better and get almost everyday slight progress.
Well, perhaps we can say that post-fin sufferers who have bloated stomach issues experience this due to developing leaky gut syndrome (isolating excess estrogen causing stomach fat for a moment) ? I suppose getting tested for this would be the only way to know for sure.
Also, this allegedly contributes to the imbalance of hormones in the body, in addition to fin causing atrophy/apoptosis in the prostate (& whatever else Fin does to prevent our natural hormonal balance).
And obviously, the effects of Fin are not local to the gonads since it induces brain fog by inhibiting the conversion of progesterone to allopregnanolone. These areas of damage seem to be among the primary reasons for our problems, right?
Well, depression from all of this can easily cause brainfog, or many of these other symptoms too as well.
Although, I also have the stomach bloating, and churning, and intermittent upset stomach and pains, which I also attribute to a bad T:E balance or hormone levels that are off. Simply because it still just wont go away.
I agree that becoming depressed can cause a state of brain fog. To be perfectly honest though, I distinctly remember after my experience with Propecia that I nearly became a recluse. Back then, I only suspected it had a role in temporarily causing sexual dysfunction, NOT in brain fog as well.
Propecia definitely caused my brain fog… and still is, because my symptoms have not ceased, despite not taking it for 6 months.
It’s weird too 'cause one study which found Finasteride to cause depression concluded that stopping the drug cured the cases. Not with us I suppose.
Thinking logicaly.
If I have some of this DHT sensation in the morning after good sleep, this efect would propably be accumulated through the long period of refreshing sleep. The problem is that only 3 days out of 7 of the week I can classify as more less satisfying. Rest of the days it is preety disturbing.
I hope exhausting exercise will help me to get it to the point of good every day sleep.
Try some then! one of our members can cook it…
This is a very interesting post. Amazingly, I was also researching possible mechanisms behind GHB induced recovery and came across the same article. None of the previous argumentation in this thread, as to why GHB helps in recovery, was convincing. After all, we are dealing with a persistent change in homeostasis in our bodies. The only mechanisms known to do this are point mutations or of epigenetic nature. Methylation and histone modifcation through deacetylation fall into this category. If these GHB stories are true - and I assume people are telling the truth until proven otherwise - there must be a link between GHB and epigenetic action. Your quote clearly proves there is, plausibly explaining why GHB may assist in recovery.
Now, before everyone tries to get their hands on illegal substances, I strongly suggest to take the easier/safer route and try this first:
viewtopic.php?f=5&t=3901&p=24587&hilit=deacetylase#p24587
I certainly will. Excellent!
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Has this been the only GHB recovery? I swear I have seen another two on the forums. Anyway, unless your one of those people who doesn’t do any drugs or drink, surely you have to think this is worth a shot. As long as your not an idiot, do your research and dose properly, this stuff is meant to be amazing.