New sleep molecule discovered

[Wishful]

https://www.sciencedaily.com/releases/2022/04/220429144940.htm

"We discovered that miR-137 helps regulate hypocretin. To experience normal sleep, you need to have the right amount of hypocretin in the brain at the right time, and miR-137 helps with that."

Also interesting, since ME involves immune system dysfunction:

"Most people know that when you are ill you often feel tired. And when you have a fever and the immune system is hard at work, you often suffer from poor sleep. So we know that something happens to the hypocretin level when the body is trying to fight off a virus infection, for example, and we are trying to understand this process," says Birgitte Kornum.

"In the study, we show that one of the immune system's transmitter substances, IL-13, has a special effect on hypocretin. We can tell that when we add IL-13, it affects miR-137 and thus also the level of hypocretin in the body. We still do not know why, though, but we are currently doing tests that may be able to give us an answer."


Another report on sleep studies: https://www.sciencedaily.com/releases/2022/04/220429145059.htm

 

[Alvin2]

They all wanted to treat daytime sleepiness or to turn off the brain at night. And a lot of them focussed on hypocretin, which is a protein found in brain cells and which has recently attracted a lot of attention within sleep research.

The new bandwagon

The drug that turns it off is a poor sleeping pill becasue its only the consolidator of wakefulness. Turning it off makes people feel groggy, but thats it.
And its screwing with the sleep stages was explained by the REM sleep switch needing hyprocretin to turn off, without it people crash into REM sleep (as in narcolepsy). There was an interesting paper on this from 2006.

 

[heapsreal]

Sounds alot like belsomra. It was first approved in 2014. I was hoping it was going to be the answer to my insomnia.
I felt groggy but couldn't fall asleep and eventually had to take a normal sleep Med to fall asleep. When I woke up I felt crappy all day, hangover effect. I can't say it really helped sleep much at all. I tried it several times and same reaction each time.
Maybe a shorter half life might help with the hangover but it just didn't hit the right button to initiate sleep. I think the Gaba receptors play the most important part of sleep. Needs to be a way to improve our gaba receptor sensitivity and or tolerance to gaba agonists would be good.😉

 

[Alvin2]

Sounds alot like belsomra. It was first approved in 2014. I was hoping it was going to be the answer to my insomnia.
I felt groggy but couldn't fall asleep and eventually had to take a normal sleep Med to fall asleep.

Thats the medication.
And yup thats what people report, it doesn't work well.

When it was being developed drug companies thought they had found the magic silver bullet.
Around 2010ish before it was released more research was being published that found hypocretin was only a modulator of wakefulness, the symphony conductor as it were.

It seems the shine hasn't worn off yet, drug companies still think its a matter of finding the right way to modulate hyprocretin instead of realizing its a dead horse.

 

[heapsreal]

Thats the medication.
And yup thats what people report, it doesn't work well.

When it was being developed drug companies thought they had found the magic silver bullet.
Around 2010ish before it was released more research was being published that found hypocretin was only a modulator of wakefulness, the symphony conductor as it were.

It seems the shine hasn't worn off yet, drug companies still think its a matter of finding the right way to modulate hyprocretin instead of realizing its a dead horse.

I haven't found anything better than a Z drug benzo and an antihistamine combo.

 

[Alvin2]

I haven't found anything better than a Z drug benzo and an antihistamine combo.

I have avoided going down the benzo rabbit hole but i know how hard it is for many of us.
I wish i had some good advice

 

[Wishful]

I wasn't interested in this as a possible sleep aid; I was interested in a possible mechanism to explain ME's brainfog/grogginess. I found the link between the viral infection and its possible pathway to the cognitive symptoms particularly interesting. My ME symptoms initially mimicked flu symptoms, so why/how does a viral infection (or other immune activation) cause those symptoms? I think that's something that should be researched properly.

 

[Boba]

I wasn't interested in this as a possible sleep aid; I was interested in a possible mechanism to explain ME's brainfog/grogginess. I found the link between the viral infection and its possible pathway to the cognitive symptoms particularly interesting. My ME symptoms initially mimicked flu symptoms, so why/how does a viral infection (or other immune activation) cause those symptoms? I think that's something that should be researched properly.

Polybio points to the vagus nerve as a sensor for inflammation causing the flu like symptoms.

she talks about it around minute 52

 

[Alvin2]

I wasn't interested in this as a possible sleep aid; I was interested in a possible mechanism to explain ME's brainfog/grogginess. I found the link between the viral infection and its possible pathway to the cognitive symptoms particularly interesting. My ME symptoms initially mimicked flu symptoms, so why/how does a viral infection (or other immune activation) cause those symptoms? I think that's something that should be researched properly.

A lack of hyprocretin makes you feel groggy, think of when your waking up in the morning and are not quite with it.

 

[heapsreal]

Thats the medication.
And yup thats what people report, it doesn't work well.

When it was being developed drug companies thought they had found the magic silver bullet.
Around 2010ish before it was released more research was being published that found hypocretin was only a modulator of wakefulness, the symphony conductor as it were.

It seems the shine hasn't worn off yet, drug companies still think its a matter of finding the right way to modulate hyprocretin instead of realizing its a dead horse.

Just a thought, belsomra which is an orexin/hypocretin antagonist, the opposite is modafinil which works through indirectly activating the release of orexin and works as a dopamine reuptake inhibitor.
It's sometimes classed as a stimulant and I guess it initially feels abit like that when one first uses it, but i wouldnt class them as stimulants. It seems to feel like it makes me feel less tired but not stimulating and energizing. It effects more mental side of things than actual physical fatigue, if that makes sense???

 

[GlassCannonLife]

Sounds alot like belsomra. It was first approved in 2014. I was hoping it was going to be the answer to my insomnia.
I felt groggy but couldn't fall asleep and eventually had to take a normal sleep Med to fall asleep. When I woke up I felt crappy all day, hangover effect. I can't say it really helped sleep much at all. I tried it several times and same reaction each time.
Maybe a shorter half life might help with the hangover but it just didn't hit the right button to initiate sleep. I think the Gaba receptors play the most important part of sleep. Needs to be a way to improve our gaba receptor sensitivity and or tolerance to gaba agonists would be good.😉

Yeah I tried belsomra for a month with no noticeable benefit unfortunately

 

[Alvin2]

Just a thought, belsomra which is an orexin/hypocretin antagonist, the opposite is modafinil which works through indirectly activating the release of orexin and works as a dopamine reuptake inhibitor.
It's sometimes classed as a stimulant and I guess it initially feels abit like that when one first uses it, but i wouldnt class them as stimulants. It seems to feel like it makes me feel less tired but not stimulating and energizing. It effects more mental side of things than actual physical fatigue, if that makes sense???

Its been hard to understand how Modafinil works, in Orexin knockout mice Modafinil worked better than in wild type mice.
But is does work differently than Dexedrine which is simply a Dopamine pumper.

 

[perchance dreamer]

Belsomra helps me, but only if I take it every other night instead of nightly. I use Trazodone on the nights I don't take Belsomra.

 

[Wishful]

A lack of hyprocretin makes you feel groggy, think of when your waking up in the morning and are not quite with it.

Based on how I feel some days, I'm probably lacking hyprocretin.

My guess is that treating grogginess probably isn't as simple as one chemical.

 

[Alvin2]

Based on how I feel some days, I'm probably lacking hyprocretin.

My guess is that treating grogginess probably isn't as simple as one chemical.

There are many options, but they are all chemical uppers, from caffeine to Modafinil to Armodafinil to Methylphenidate to Dexedrine and more.
Without knowing what is causing your grogginess treating the actual source is hard.
There are even some histamine raising drugs coming on the market.

That said if its ME induced we know even less about its cause than or other diseases.

 

[heapsreal]

Belsomra helps me, but only if I take it every other night instead of nightly. I use Trazodone on the nights I don't take Belsomra.

I think if someone was new to sleep meds, it's probably enough??

 

[heapsreal]

Its been hard to understand how Modafinil works, in Orexin knockout mice Modafinil worked better than in wild type mice.
But is does work differently than Dexedrine which is simply a Dopamine pumper.

Possibly multiple pathways. I have heard it increases alertness through histamine as well as through adenosine. There was a study where it shows it has neuroprotective effects in people who are sleep deprived. It's all trial and error with us 🤔

 

[Alvin2]

Possibly multiple pathways. I have heard it increases alertness through histamine as well as through adenosine. There was a study where it shows it has neuroprotective effects in people who are sleep deprived. It's all trial and error with us 🤔

Caffeine will take care of adenosine.
Modafinil is not a stimulant in the traditional sense, some have said the effect is no better than taking a cup of coffee, probably because their wakefulness issue is just that they need to cram for an exam the night before vs those who have actual sleep wake conditions.
I've been offered it multiple times but have refused since its not my issue and i don't need new problems.

 

[heapsreal]

Caffeine will take care of adenosine.
Modafinil is not a stimulant in the traditional sense, some have said the effect is no better than taking a cup of coffee, probably because their wakefulness issue is just that they need to cram for an exam the night before vs those who have actual sleep wake conditions.
I've been offered it multiple times but have refused since its not my issue and i don't need new problems.

I understand.

I look at these people who are healthy but try to enhance their quality of life. Some of them call it biohacking. I'd say some of us cfsers are biohacking but we are starting from a very different position and trying to get to normalish.

My cfs biohacking has kept me going for 20yrs now, where I can keep managing to work and keep the wolves away from the door. I don't work full-time and I'm not a picture of health but I believe I'd be worse if I didn't and or be living In the gutter.

People do what they got to do and find ways to adapt and keep their heads above water. I think many of these posts and discussions help people make better informed decisions.
👍💊🤪😁