How Might Benzodiapines (Ativan, Clonazapem) help with ME/CFS?

I read where for Whitney Dafoe ativan increases his strength for a short period. I am also interested in this as clonazapem does the same for me. I am completely bed bound and have had periods of months at a time when I am too weak to talk at all. I can currently talk in short sentences but only a few times a day. But after I take clonazapem as well as the expected calming effects it also strengthens me allowing me to talk much easier and do more leg movements in bed for several hrs.

I did find some research that GABA down regulates proinflammatory T cell states. I thought this might have some potential relevance to the Mike Davis T-CELL clonal expansion hypothesis but figured that any effect that these drugs have on potentially reducing t-cell activity would take longer than the 1-2 hr for these drugs to have their effect.

Any ideas appreciated

 

It's interesting that you should mention this as I experienced a similar phenomenon when taking Ambien, which acts on GABA receptors in the same way as a benzodiazepine.

Perhaps a totally different phenomenon: Some people with brain damage - including some in otherwise vegetative states - experience substantial improvements when taking Ambien, specifically. It seems likely this is not closely related to our experience because only Ambien has this effect for these patients.

I'm afraid I don't have much insight as to why these things happen, though. For us I would assume it's directly related to the GABA-ergic effects.

 

I think it definately must be the gaba effects @James Morris-Lent I just wonder how it is resulting in increased strength. I guess it is plausible that by relaxing muscles they are working better for that period but I also wondered if a dampening of t-cells could somehow be involved...

 

I agree

I get the same benefit from zopiclone ambien and benzos, though sadly I haven’t had the option to try clonazapam, GABA drugs, . Ativan Whitney uses is lorazepam, a benzodiazepine. Quite a few very severe people do report it and I think it’s important. I don’t know if it has the effect on higher function ME people as they are not so shut down.

I too think it’s related to the phenomenon reported not just in PVS but many serious brain affecting illlness. I think it’s potentially important in helping us understand what’s going on in severe ME, what Ron Davis has described as the brain going into survival mode, as well as by association with other illnesses getting this response being validating. There’s videos on YouTube of people with PVS responding quickly and like them I have a short onset time for small but important benefits to show very apparently to those around me, from the drugs being administered

“Experts from the University of Michigan looked at how the drug affected over 20 neurological disorders, including comas, people in vegetative states, Parkinson’s disease, stroke and those who have suffered traumatic brain injuries.“


https://www.express.co.uk/news/science/822399/BACK-FROM-THE-DEAD-Zolpidem-insomnia

The science more

https://www.sciencedaily.com/releases/2017/06/170626131745.htm

I think the mechanism for us Is the same for them,

“Another topic for more research is to assess whether the effects of zolpidem depend on the part of the brain that's injured. The researchers report zolpidem's unique effects may be present in patients whose basal ganglia, which help process information to perform an action, are no longer functioning correctly.

"The restorative effects on the basal ganglia may surpass the hypnotic effects on the frontal cortex," says Bomalaski, who is headed to the University of Washington for a brain injury fellowship.”

I’ve no science knowledge but personally I don’t think it’s something different in us to these other responders, ie less T cells more GABA. but maybe it’s beneficial in many ways. In neuro injury This article discusses the “paradoxical activating effect”

https://theness.com/neurologicablog/index.php/can-zolpidem-wake-people-from-coma/

What would be interesting to hear is the effect of benzodiazepines and hypnotics on the less severe too.

 

This is a very good question. I think we may come up with a few potential explanations. I've just recently finished watching the DVD of a recent IiME conference where Ron said that Ativan does something to ATP, probably increases it, although I don't remember exactly, so that's one.

Another possibility is that they seem to be useful for mast cell inhibition, because mast cells have benzo receptors, or maybe because it reduces stress response.

One more possibility would be the vasodilatory effects, which could potentially help deliver oxygen to muscles.

There is an alternative theory, which most of you will hate me for saying, but it could also explain the perceived effectiveness of the bogus LP and Gupta "therapies".
I think it's not impossible that there is a grain of truth to the idea of a feedback loop in the brain which reinforces the symptoms in the body to some degree. Assumimg we have inflammation in the body, or lack of oxygen in tissues, the brain senses that, tries to compensate, creates even more problems, because HPA axis is not functioning as it's supposed to. So benzos may brake that loop by blunting the compensation mechanism which only creates more problems anyway.

Also,
Benzodiazepines antagonize central corticotropin releasing hormone-induced suppression of natural killer cell activity

 

Dr. Paul Cheney mentioned seeing this effect among a number of his patients many years ago. I have also been on a stable dose of clonazepam for decades, and I often experience this effect as well. Specifically, orthostatic intolerance makes it difficult for me to sit up for anything except short periods of time. However, a small amount of clonazepam (the amount varies per person) often ameliorates this problem.

The theory behind this is that the sympathetic nervous system is often overstimulated in PWME, causing excessive expenditures of energies to do ordinary things less efficiently. It's sort of like the way a car with a poorly tuned motor will perform worse that a car with a properly tuned motor, while at the same time consuming more gasoline (or petrol, if you prefer). The clonazepam reduces the extra activity of the SNS, allowing it to function more normally with less energy.

I have also noticed a similar effect with magnesium, which can also reduce SNS overactivity, as it's the main NMDA antagonist, and overactivity of the NMDA receptors will often produce overactivity in the SNS in general.

 

To clarify, I'm not severely affected. When I was, I didn't get any boost from ambien and frankly couldn't tolerate it. (I also don't take it anymore because it started messing with me pretty badly after taking it for ~3 years with no issue.)

 

Thanks everyone for your replies. Like many things in this illness it seems there are many possibilities to what could potentially contribute to the strengthening affect. Interesting that Ron Davis mentioned ATP production as I hadn't seen that link in research I have reviewed

 

Interesting ideas in many ways. @zzzz, I too have been on a stable dose of clonazepam (.5 to .75 mg. per day) since 2003, before ME; it was prescribed for years of crippling insomnia. People react with horror when I’ve mentioned that I take it regularly - but it was and is a necessity, and I have not increased the dose in 15 years. Since ME, I too have very bad Orthostatic Intolerance (though not as severe as yours; I can mostly sit up, and on a good day, walk a bit - it is far easier than standing up.) However I never thought of clonazepam as increasing strength - though that makes sense, if it obliterates anxiety.

I was tried on many things, including Ambien, Diazepam, and many of the other Benzos - and none had any effect whatsoever on the insomnia - but the night I had that first 5mg. of clonazepam changed my world, physically and mentally.

My daytime medication is 4 x 50mg of Tramadol. Again, I sense disapproval if I mention it. Nevertheless, I discovered after a bad injury (when I already had ME), that it gave me, not strength exactly, but a bit of energy. Some days enough to sit up and read, some days to do a short walk. And it eases the OI (and hypersensitivity and pain, etc, etc).

Since reading last year about Whitney Dafoe and Ativan, I have looked at my ‘addictions’ in a different light.

I wish the mechanism were better understood, that makes these reactions so specific: how one particular form, of a particular type of drug, works for a particular person.

 

Makes sense, because it's also an SNRI, and SNRIs I think are sometimes mentioned in the context of POTS, since they can increase norepinephrine.

 

I looked at it again and the direct quote is: "We did find one drug that seems to improve ATP production and that is a drug called Ativan. I know that it helps because we've given it to my son" That was in response to someone asking about using the nanoneedle device to test for drugs.

 

Whatever the mechanism I guess its likely that clonazapem is working in the same way. If these drugs are down regulating the clonally expanded T cells as in the Mike Davis hypothesis is it reasonable to think this would lead to more ATP production/better nano needle response and how quickly might it have this effect if it is the mechanism through which it is working?

For me I become stronger about an hour after taking clonazapem and can talk more for several hr...

 

I note that everyone except @Cinders66 here appears to be male (sorry - not sure about @Sidney), and wonder whether this is a factor in the effectiveness of the drugs. Males and females have very different chemical make-ups according to some researcher (can't remember who).

It's one thing that makes me hesitate to try.

 

@Rossy191276 I have been wanting to reply to your thread re: benzos (either here or on PR and found it here first) and share my experience when I worked in a hospital. When we had patients who were catatonic, benzos were the first line of therapy (and I just Googled this to confirm I was remembering it correctly)! I want to clarify that I am NOT in any way whatsoever comparing your situation to schizophrenia although many patients who were hospitalized with catatonia were schizophrenic. However, some were not and had catatonia as part of other neurological conditions (such as encephalitis, autism, stroke, etc) or due to an unknown condition.

I am mentioning it b/c these patients were completely unable to move their muscles. It was beyond muscle weakness, it was complete muscle immobility as if their muscles were frozen. Some had "waxy flexibility" where someone else could position their muscles for them and then the muscles would remain in that position. Many also could not speak and were completely mute. I remember that I had naively assumed that benzos would be the LAST thing you would give a patient who was literally catatonic b/c it would further weaken their muscles or make them more sedated/sleepy, etc.

However, there was some kind of paradoxical reaction and benzos, such as Clonezapam, would literally reverse the catatonia and often very quickly. I remember asking the doctors about it (I am an LCSW/social worker) and learned that benzos were the standard treatment and that they did indeed work. At the time I did not understand why they worked, and to be honest, I still do not really understand why. They also did not treat the underlying condition (i.e. schizophrenia, depression, autism, stroke, etc) but they reversed the catatonia so the person could move and speak again.

I believe excess glutamate is involved in catatonia which makes sense why GABA-agonists (meds that increase GABA) like benzos would help. Although I have never personally been catatonic, there was a period when my doctors thought it was possible that I had SPS (Stiff Person Syndrome) due to my symptoms combined with having the anti GAD65 autoantibody. It turned out that I did not have SPS although I had an extremely exaggerated startle reflex to every day stimuli (like my dog barking or someone knocking at the door) with painful muscle contractions and one episode when our fire alarm went off that I was basically unconscious on the floor for a few minutes and might have been a "startle seizure". The med that was the absolute first line of defense for SPS per my doctor, and which helped me in those episodes, was again Clonezapam.

Once I started high dose IVIG, the startle reflex episodes completely stopped and have never returned. I've had the fire alarm go off unexpectedly since then, and while it is still very loud and annoying, it doesn't phase me.

I don't know if any of this helps but wanted to add it just in case.

 

I am female! Though I quite like my unspecific name!

 

@JaimeS

Was lorazapam (ativan) the only benzo that improved the blood of PWMECFS using the nanoneedle? Were all (major) benzo's tested? If many benzos were tested and only lorazapam worked, do they have any idea why this might be the case?

Thanks.

 

It's strange how often it's the "overlooked" aspects of a drug that turn out to be meaningful.

I took ornidazole and it (briefly) restored me to perfect function. I went for a jog.

For awhile I thought it was its anti-fungal, anti-microbial properties but now I'm not so sure. For instance, in a random screening, it was one of the best drug (out of many hundreds!) at inciting insulin release in high-blood-sugar situations. If it has metabolic/endocrine effects that are that pronounced, perhaps that's why it helped!

We may have to 'go around Robin Hood's barn' to really get at things that will help with symptoms: affecting metabolism, immune function, and endocrine function in unexpected, indirect ways like you're describing.

@Jaybee00 I'm not sure what all has been tested on the nanoneedle at this point. I'd suggest looking for articles by OMF -- I can't say anything they haven't published anyway.

 

@JaimeS

Thanks. I thought Ron Davis was a proponent of rapid data sharing in lieu of/in addition to normal publication....

Therefore it would be really great if the nanoneedle data could be shared on their web site.....

[Sorry for off-topic]

 

Not off-topic at all! And that's precisely what I mean -- they probably have shared some things in articles and conferences ahead of publication.

 

I thought Whitney and others reported that lorazepam not only helps with strength but multiple other ME symptoms, like noise and sound sensitivity, ability to talk again, etc?

It was posited by Davis that efficacy of lorazepam might also involve its other mechanism of action at the mitochondrial TSPO/PBR receptor, for which it’s an agonist. It could be immunomodulatory. Clorazepam has no affinity for the TSPO/PBR receptor, so would be interested to hear if Whitney ever tried clorazepam and if it worked the same, as this would answer an important question.