"Stiff man syndrome", gaba receptors and gephyrin deficiency

I discovered that part of the reason that gabaa receptors may malfunction in some cases is due to a malfunction with the gephyrin protein, which is a protein that helps concentrate and localize gabaa receptors into clusters, which allows them to effectively signal and function. Notably, gephyrin deficiency is implicated in alzheimers disease. What is more interesting is that the malfunction of the gephyrin protein can cause something call “stiff man syndrome”, which is basically where there is chronic muscle stiffness in various parts of the body due to ineffective gaba signaling brought about by gephyrin deficiency. I was thinking that this correlates with numerous reports of how PFS sufferers claim to not only have problems with normal gaba functioning (IE different reaction to alcohol) but also how many PFS sufferers claim to have problems with stiff/tight muscles as well as speech problems too. In my opinion, gaba dysfunction and stiff/tight muscles could logically be interrelated, ala a very mild form of “stiff man syndrome”. Even more interesting is the fact that treatment with isotretinoin can induce stiff man syndrome:

Stiff-person syndrome associated with oral isotretinoin treatment.

Chroni E1, Sakkis T, Georgiou S, Monastirli A, Pasmatzi E, Paschalis C, Tsambaos D.
Author information
Abstract
We describe a patient with severe nodulocystic acne who developed disabling muscle stiffness and painful superimposed spasms of the neck, back and upper limbs 10 days after the onset of oral isotretinoin treatment. The muscle hyperactivity condition, which revealed the clinical and electromyographic features of the stiff-person syndrome, gradually resolved 2 weeks after drug withdrawal.

As we all know, isotretinoin (accutane) is a well known 5ar inhibitor (https://www.ncbi.nlm.nih.gov/pubmed/9298137), unfortunately this case study doesnt go much into detail about the possible mechanism through which isotretinoin may have induced stiff man syndrome, however its logical to assume that there might be some connection between 5 alpha reductase inhibitors and acquired gephyrin deficiency. Of course, there may very well be some other mechanism which causes it as well, however the point is that gephyrin deficiency can be induced by a drug therefore its entirely possible that finasteride likewise induced some kind of gephyrin deficiency in us which in turn caused gaba receptor malfunctioning and all the things associated with it (non-responsiveness to alcohol, stiff muscles etc).

That being said, I have stumbled across a substance called dihydromyricetin. This supplement is typically used for hangover relief and treating alcoholism, but it also has the effect of increasing the production of gephyrin protein in the body as well. In fact, there is being research done to see if it can be used to treat alzheimers (https://www.ncbi.nlm.nih.gov/pubmed/24728903). It is logical that if we are indeed suffering from some sort of finasteride induced gephyrin deficiency then something like dihydromyricetin might be effective in treating some of the symptoms.

I ordered dihydromyricetin a few days ago and it arrived today. I took two capsules this morning and fell back asleep, as well as taking numerous naps throughout the day (I work nightshift currently so my sleep schedule is very irregular). My experience so far is that I have had much more restful sleep than usual during my naps, and my dreams have been extremely vivid, detailed and “complex” as well. Its really quite interesting. Furthermore, upon awaking from my naps I feel pleasantly disoriented (like how I used to feel before taking accutane and then later on propecia) and my entire body (especially my shoulders) feels much more relaxed than usual instead of constantly being tense. Coincidentally, it appears that anything that modulates gaba functioning in some way (IE phenibut) tends to give very vivid dreams, therefore its logical that dihydromyricetin which restores gephyrin levels could also impact the quality of dreams as well.

That being said, I want to reiterate that I have only been taking dihydromyricetin for a single day, so I have no idea if improvement will continue or not, or if what I experienced today was even related to DHM and not just a coincidence, regardless I do think that the gephyrin angle is one that is definitely worth looking more into. I feel like its the missing element that ties together a bunch of other things regarding PFS and also it helps to definitively explain the exact problem that we may be having with gaba signaling as well. Anyways I will keep everyone updated regarding my experiments with DHM.

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Thx for sharing this.

Any updates?

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I never followed through with the experiment long term, unfortunately what I often do is start following one lead and then I drop it after a while and start doing something else. That being said, I think it wouldnt hurt for some PAS sufferers to give it a shot. I do recall the DHM slightly helping my condition but like I said, I never pursued the protocol long term