This is for those of you who are really struggling with the remedies for RLS. Apologies for not referencing all my research but I’ve been completely wiped out for weeks now. However I wanted to share some insights I’ve had recently and hope it inspires thoughts and research.
Adenosine is a chemical that normally builds up in the blood during the day and causes sleep pressure in the brain in the evening. We basically sleep it off. Being active during the day is helpful for the build up of adenosine, and this is obviously bad news for those of us who suffer from chronic fatigue and immobility. This process is known by researchers to be problematic in people with RLS. Adenosine regulates dopamine and glutamate and as we know, these excitatory neurotransmitters are also at the heart of RLS.
The problem with Buprenorphine is that it acts very much like coffee. Coffee is a well known inhibitor of adenosine receptors, but tea and chocolate have this effect as well. In other words, when you take Buprenorphine (or any other opioid), you are very likely to feel awake. (I already have this problem at midnight and Buprenorphine exacerbates it). Another problem with Buprenorphine and other opioids is that they mess with the sleep quality. Also - the more of such stimulating substances you use, the more adenosine receptors are being created, it seems. This could explain surplus tiredness. (I’m aware that some people find some coffee helpful and so it’s possible that a small amount of either stimulates the dopamine needed to sleep, but I won’t go into that here).
Researchers are suggesting that Zopiclone can reverse the adenosine blockage. This is also my experience. Here is an article:
ncbi.nlm.nih.gov/pmc/articl...
(Warning: contains graphic descriptions of animal trials).
I have personally struggled with Buprenorphine for a host of reasons. That’s despite the fact that it’s a whole lot better than any other opioid I’ve tried! After a year of usage, it has become clear that I must try and keep the dosage as low as humanly possible, otherwise I will be up all night doing all those things I should be doing during the day (suddenly cleaning the bathroom seems like a great idea, and so does spending money on shopping for things online! This is all dopamine induced behaviour). It’s also clear that the Buprenorphine dosage is relative to the amount of Zopiclone I’m allowed to take (max 2 x 7.5 mg/night). Because of Buprenorphine, I also experience severe daytime depression and severe sweats both day and night. These opioid induced hot flashes often wake me up so I have a fan running through the night.
There is nothing much I can tolerate as a counter remedy other than good old Zopiclone. I also use some Diazepam and tiny amounts of Quetiapine. The latter also counteracts some of the excitatory events that promote insomnia although it has a negative effect on the RLS. For instance, opioids stimulate mast cells, and this increases histamine release. Quetiapine is, amongst other things, antihistaminic and anticholinergic. It also lowers serotonin so would theoretically have a positive effect on melatonin induced RLS since melatonin is made from serotonin, but unfortunately as we all know, sedating antihistamines trip us up. (I’ve been stuck with it all these years because there’s a cap on the amount of Zopiclone I’m allowed to use).
I get some stomach acidity from Buprenorphine and often use Rennies as all other acid controlling substances increase RLS (note that one of the inactive ingredients in Gaviscon is aspartame, and it’s made from phenylalanine, which in turn is the precursor to dopamine). Dry mouth is also a problem, especially if you snore. My GP found one remedy that didn’t contain the dreaded sorbitol like all the others: Galen Salivix spray.
All this is very tricky. I have tried every remedy under the sun and there is almost nothing left that I tolerate in one way or another. Whatever is supposed to put people to sleep, seems to trip me up. The sleepier I feel, the more likely I am to wake up from RLS. I don’t tolerate most supplements including iron and magnesium. I tried THC which is said to increase adenosine, but I didn’t tolerate it over time. I have even quit drinking green tea (one of few pleasures I have left) as I suspected it was blocking adenosine build up during the day. This seems to have helped a little bit. Food wise I just continue with a healthy diet, but I avoid fortified products. I found for instance that some smoothies are packed with vitamin B’s that, in my case, trip up the RLS. I need a sensible snack before bed because otherwise I’ll wake up from severe hunger pangs (one reason could be that adenosine stimulates ghrelin, which regulates the appetite).
My sleep quality is very poor and I tend to have the best sleep in the afternoon. Of course, some RLS researchers suggest doing just that i.e. sleep in the afternoon, but for obvious practical reasons, I can’t continue like this. I’ve been trying to establish some kind of routine and effective timing so that break through RLS is dealt with early in the evening with a small dose of Buprenorphine, and then a little later I take some more. If I take too little, I keep waking up with restlessness, and if I take too much, I’m awake all night and sleep all day. Driving can be down right dangerous as Buprenorphine and a short night can cause the experience of sleep debt (I’m guessing it’s the adenosine acting out in the day time instead of the night because of having been stimulated, but not consumed).
I keep experimenting and I’m writing a diary to keep track of the fluctuations. I’m now totalling at about 350 mcg per night, but as I said, I’ve been enormously tired during the day, and sometimes I’ve slept some crazy amount of hours that then obviously keeps me up the next night. 400 mcg would be more ideal if it didn’t keep me awake and cause day time tiredness. And so on - it’s chaotic beyond belief. Thankfully I have an understanding GP (not sure he understands much but he’s quite accepting).
I have also discovered that I have the genetic variant for RLS. The gene concerned is BTBD9. It’s known to contribute to RLS and it does have something to do with poor iron metabolism and adenosine build up. Nothing much one can do about that! In addition, it’s clear to me that I suffer from serotonin toxicity which is a mild form of serotonin syndrome. Symptoms include nightmares, tachycardia, frequent need to pee, agitation, diarrhoea, vomiting and more (i.e. it’s all very similar to problems I also experience when RLS is high). You can read more here, for example: academic.oup.com/painmedici... .
The article elucidates the problem some of us have with both serotonin and dopamine agonists. I don’t know if this equals RLS or if it’s a deeper issue that encompasses the RLS, or what..?. This problem is known to occur in individuals with connective tissue disorders, and this interesting to me since I have hEDS - but little else is known. There are black lists online of medication that can cause serotonin syndrome and I have found that I have problem with a huge number of them (i.e. all the ones I’ve tried). The lists contain all the drugs that are problematic for RLS but there are also drugs that many people with RLS do tolerate (e.g. dopamine agonists) that I don’t tolerate for (what seems to be) this very reason. It leaves me with a very small pool of options. For instance, I do use Tramadol (a serotonin inducing opioid) occasionally because it has a calming effect when I’m really out of my wits, but it quickly builds up in my system and starts causing severe problems, so I can’t take it regularly. Even paracetamol, which acts on pain by engaging serotonin receptors, will have a negative effect on the RLS. I still take small amounts for pain relief and sedation but have to weigh it carefully against the Buprenorphine. RLS is such a paradoxical problem because it sits at the opposite end of the popular idea that more melatonin will produce better sleep - melatonin, which is made from serotonin, seems to be the culprit in our case.
I hope this is helpful. Sorry if it’s an overwhelming amount of information. I wanted to share this, not look for any of the usual responses along the lines of ‘have you tried this’ :). Feel free to fact check.
experience with Buprenorphine
Buprenorphine, Tephine 
buprenorphine for RLS
buprenorphine study
