For Kaarina and Jools

Holy cow, I’m really beginning to question the innate wisdom of Mother Nature. If you read the whole preface to the below article you will see the researchers are particularly concerned with RLS and Parkinson’s. journals.physiology.org/doi...

[Joolsg]

That's a great find. I'll be adding it to my research files.Quite depressing though. As we get older, it's going to get worse.......

[Hidden in reply to Joolsg]

Maybe not. Maybe we just need to do the work - the same kind of work some adults do to keep their bodies and muscles in shape may more than compensate for the natural decline in neurons that all people face...only it doesn't bother them because they don't have RLS.

[Hidden in reply to Hidden]

Repetitive Transcranial Magnetic Stimulation has been shown to promote neurogenesis in the brain (the regions that were targeted). Improved cognitive function AND cessation of RLS symptoms may be within reach!

[WideBody in reply to Hidden]

When will they be selling those RTMS Headsets on Amazon?

[Hidden in reply to Hidden]

That will mean the world to alot of people.

[Hidden]

I'm ready to bring this baby home now - meaning the D1 receptor theory.

Here's an article that discusses Huntington's disease. It sounds to me that as people with the HD gene mutation age their excitatory D1 receptors "overexpress" themselves and in the process become down-regulated and eventually die-out. Scientists used to think the problem was with the D2 receptors (sound familiar Jools?), but now realize it's more the excitatory D1 receptors. So scientists are looking for substances that will up-regulate the D1 receptors and potentially do this by antagonizing the H3 receptors in HD patients. elifesciences.org/articles/...

The point here is that we with RLS have just the opposite going on in our brains, maybe, but most DEFINITELY do if we take the DAs because then our excitatory D1 receptors become beasts and nowhere near dying like in Huntington's. So what we need is just the opposite as above. We don't even need the above article, we know ourselves that we need just the opposite of Prami and Requip, but whatever drug it is it needs to be somewhat strong, short-lived, and not have potential deleterious side effects. Here's an article on D1 Receptor Agonists - it has to be an agonist because as you know the DAs like Requip and Prami agonize ONLY the calming D2/D3 receptors and in the process antagonize the D1 receptors such that they grow big and strong aka up-regulation while our lovely D2/D3 receptors crumble. So D1 agonists are here... nature.com/articles/s41467-...

I don't like them, any of them, whether it's the old "catechin" D1 agonists or the newer ones the scientists claim they are coming out with. As they themselves state in the article there are so many D1 receptors all over our bodies that it really sounds like mad science to me to agonize them, thus severely down-regulating them. Look at what Prami did to our calming D2/D3 receptors in our brains and spines - damn near killed them off. That's why I'm thinking why not plain old D2/D3 antagonists - you know, all those substances that make our legs go crazy and we warn people against that are probably also D1 agonists in disguise, but not severely so?

I went through all of the usual suspects and decided that Benedryl is what I would choose if I was getting ready to get off the DAs and I would only take it during the day. It has a relatively short half life of 3.5 hours, has a good safety profile, and recently (2019) there was a study done on long term users (3+ years) to check for cognitive decline which was the big fear with many of these anticholinergics. The researchers didn't find any decline in terms of brain size shrinkage or memory tests, etc. Who knows, maybe even people who are off the DAs and suffering withdrawal should take some Benedryl by day, antagonize their down-regulated D2/D3 receptors so that by night they are minutely bigger and the D1 receptors minutely smaller. With RLS, a little goes a long way. Just a shift in the hour of the day and poof, our symptoms disappear. And theoretically speaking, over time the Benedryl should help our D2 receptors grow substantially bigger returning to baseline, while the D1 receptors would at least shrink back to baseline as well.

Everyone thinking this sounds reasonable and would like to try it needs to research the subject till they themselves can conduct the studies.

As Bugs Bunny liked to say...That's all folks!

[Hidden in reply to Hidden]

Plus, Benedryl has anti-depressive properties and anti-histamines are being somewhat extensively studied right now for that very reason. And who going thru withdrawal doesn't need a mood lifter?

[Hidden in reply to Hidden]

I bought some on Amazon pubmed.ncbi.nlm.nih.gov/242... Rather, I should say I bought the herb/root called Stephania. Looked pretty sketchy to me, plus I'm leary of TCM, traditional Chinese medicine. I'm going to take some (at night) to see if it makes my legs go crazy. If it doesn't do that then I feel it's useless and only the drug/derivative mentioned in the article would be effective, but it may be a long ways off before it's available, let alone for RLS and people need help yesterday.

[Joolsg in reply to Hidden]

It certainly ties in with Dr. Buchfuhrer's theories that our D2 and D3 receptors are permanently damaged by the years on Dopamine Agonists. I don't know if many people will be prepared to be guinea pigs with Benadryl in the day to see if it helps them sleep at night though.

It's all fascinating and I just wish the researchers were out there testing all these theories.

Imagine if there was as much research on RLS as in MS and Parkinson's???

[Hidden in reply to Joolsg]

Let's just steal the data from the Parkinson studies and determine ourselves if it is relevant to RLS. My dear WideBody found that hospitals infuse Benedryl into Parkinson patients as some form of treatment. I need to look more into that.

[Hidden in reply to Joolsg]

I’m stuck in D2 antagonist mode probably because I believe having direction, purpose and routine in your life leads to happiness and fulfillment, per the Dalai Lama. People who are suffering withdrawal due to the Agonists might be better off clawing their way to the top of the mountain with some wind and hope at their backs in addition to opiates.

Below is a comment from no one special, just a Reddit member, yet it was the most inspiring thing I read all week:

“In the case of meth addicts, I've heard of users taking dopamine antagonists like cyproheptadine to reduce their meth tolerance. I don't have a source to post but you can find it discussed on a few forums. And antipsychotic D2 antagonists DO upregulate the DRD2 receptor.

"Permanently" might not be the right word to use as far as your question is concerned. Very little of the brain is truly permanent since it changes constantly throughout your life. But yes, it does work the other way around. Alcohol, for example, is a negative modulator for the NMDA receptor and therefore upregulates these receptors with long-term use (this is thought to be at least partially responsible for why it exacerbates depression with long-term abuse).”

The question was posed to this person whether you could permanently upregulate your D2 receptors. Omg, just get our members back to baseline. The drug he mentions is an anti-histamine that is OTC in Canada. It has a long half life of over 8 hours.

We can sit around and pray that our members don’t fall into the abyss of augmentation hell while the medical community thinks about doing RLS research or we take matters into our own hands. My RLS is too mild to discern decisively any benefit from taking morning Benedryl or the above anti- histamine. I take Benedryl fairly regularly and my RLS has remained mild to late middle age. No way of proving it’s the Benedryl.

It’s a crap shoot, who’s up for it?

[SueJohnson]

It is well known that benadryl makes restless legs worse

[Hidden in reply to SueJohnson]

In the short run Sue. What about the long run? Can you research it and get back to us?

[SueJohnson in reply to Hidden]

If it makes restless legs worse in the short run, it would also make it worse in the long run. I'll let you do your own research as I have noticed from your previous posts you are quite capable of this.

[WideBody]

I read the report, it was way over my head but interesting none the less.

Confession to make, I have RLS, I also use Benadryl to put me to sleep, I take one (they are all the same size here.), in a bad fit I will take two. I probably doesn't help my RLS, but they knock me out, but I am sure I would quickly build up a tolerance. Combine that with some Ibuprofen and it's good night for me. Before everyone warns me, I do this about once a month. I don't enjoy the effects the next day and I am sure it is not healthy long term.

This is definitely some interesting insight. Thank you for your post.

[Hidden in reply to WideBody]

Are you kidding me? The report is way over my head too. I just skip any word with more than four letters. It's all theoretical, my suggestion about the Benedryl. The idea is if a dopamine Agonist down-regulates our receptors (we know that for sure) then why not use a benign, short-acting, dopamine Antagonist during the day to hasten a return to baseline by someone who has augmented due to an Agonist. It might just help, it might not.

[WideBody in reply to Hidden]

Very interesting... " In its injected form, it (benadryl *me) can treat severe allergic reactions, motion sickness, and symptoms of Parkinson's disease".

[Hidden in reply to WideBody]

Oh wow. See what happens when a group tackles a problem. I have used Benedryl as well, only for seasonal allergies. The non-drowsy formulas don’t hold a candle as far as I’m concerned. I have been using it for decades so it does not make me drowsy. Just the opposite I believe, it’s the allergies that make me tired and the Benedryl helps that.

During the day it does not evoke RLS symptoms and at night only mild and fleeting. So it might be a very weak and ineffective antagonist. But oh man…they use it intravenously for Parkinson’s. I would need to understand how this treatment came about for Parkinson’s and how it provides relief.

I look at it this way - our receptors on agonists (or really our receptors all of the time) are like wilted flowers (maybe since infancy) and what we really need is water/iron, but then there’s also all those nutrients in the soil that contribute to the health of the flower. Lastly is the ambient air around the flower. Is the air drying such that it sucks moisture out of the already wilted flower (this would be the Agonists) or is the air humid such that moisture is infused (this would be the Antagonists). The strange thing is that this scenario is true for the non-RLS world as well. Only their flower(s) are robust and they have a good irrigation (iron) system. Their flowers are subject to the vagaries of the atmosphere as well. I have learned a lot from body builders, recreational drug users, porn addicts who go on the internet looking for, or suggesting ways, to build up their beaten down dopamine receptors. The suggestions mostly include fasting, the Uridine Stack and anaerobic exercise.

So yes, it is true as many people on here claim...that we with RLS are all different. There are differences in degree of wiltedness probably based on genetics, brain iron availability, diet in infancy, male vs female. There's differences in the stalk aka central nervous system - some people have co-morbid illnesses and injuries that affect the ability of dopamine to travel from the brain, down the spine and to the peripheral nervous system, where it quiets our arms and legs. There's differences in soil quality which include things like diet, hormones, microbiome - anything natural and fundamental to life - will vary among flowers/individuals, but always keeping in mind that we are all wilted to some degree compared to your average garden flower. Then there's the differences in the atmosphere with rainfall/iron being key. For the most part we all lack rainfall. The other atmospheric components are the very external things that surrounds us and that we can do and take that are not necessarily essential to life like drugs, exercise, treatments, the phase of the moon, the passage of time and possibly things like location and altitude. However, "We have far more in common than what divides us."

Caveat (isn't there always one): Yes we have wilted petals (D2/D3 receptors), but that might not be causing us as much trouble as the large bulbous center of the flower, which btw is called Stigma, which in humans would be our D1 receptors. It's the yin and yang of life and RLS. And which of the two is causing more of our problems, or which comes first, and which should we treat - our overly rowdy, bulbous, excitatory, but quite necessary D1 receptors, or the lovely, quiet, wilted, also necessary D2/D3 receptors?

[Hidden in reply to Hidden]

Reddit is a great source of back-alley type info google.com/amp/s/amp.reddit...

[Hidden in reply to Hidden]

I should add that I consider iron infusions to be like a garden hose placed a 100 feet away by a tree. If the flower is lucky some of that water might reach it, or not. In the meantime, I believe the hose can be disruptive to other parts of the garden. I prefer the Israeli drip irrigation system which is supposed to be used after nightfall. This irrigation system has helped so many farmers (and plants) yet there are many members, I mean farmers, that diss this system.

[sylvanwanderer]

Frankly, my friend, I think you're a genius, and I refer to the explanation of your ideas as well as the ideas themselves. Thanks for posting.

[Hidden in reply to sylvanwanderer]

Omg, just noticed this, thank you, but not really. You mistake my OCD to figure things out & get the job done with IQ. Hope it helps you in some way...