Index General Discussion The Science of N Understanding Narcoleptic Sleep/Wake Cycles

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  • #5107
    WWPWWP
    Participant

    Can you shed light on this extremely annoying aspect of N? @Jasonm – anyone?

    I understand we still have the our circadian rhythm effect in place, but since our orexin-a switch is broken, what drives our inappropriate, but real, daytime cycles?

    In my case, I’m basically on a 4 x 6 hour cycle, and while my sleep is horribly fragmented, I’m mostly concerned with the daytime cycles. Once I wake-up fully in the a.m., I’m able to be fairly productive physically and mentally until about early afternoon. At that point, the brain and body seems to shut right down to the point of being unbearable – napping is ineffective for me – and yet, by evening I often get quite noticeable relief, although I’m still somewhat beat up from the p.m. hit.

    I don’t really understand the drastic swings. Is it just a release of restored neurotransmitters without appropriate orexin-a control or is it something else? If stimulants do not work, and dawn-to-dusk physical activity to release natural endorphins isn’t going to be feasible everyday, what can be done? A trip on Elon’s Falcon Heavy?

    • If you take, or plan to take, mind-altering drugs or supplements, read this book first:
    penguinrandomhouse.com/books/189611/anatomy-of-an-epidemic-by-robert-whitaker/9780307452429/
    • Do not ever take internet health advice without first doing your own research, and always consult a health care professional. Each individual is unique - if you make a mistake, you may not be able to reverse the effects that may take decades to reveal themselves.
    • Be kind to Mother Nature and the Little Ones! 🙂

    #5113
    Sk8aplexySk8aplexy
    Participant

    Can recall at a N conference one of the presenters described N to involve a 90 minute (term I don’t recall) rhythm rather than the 24 hour circadian rhythm.

    Napping doesn’t work for me unless I really need it, then I’m either not sleeping well that night or falling asleep way later and throwing off the normal routine somewhat (it’s always fluctuating to an extent, 2-4 hrs bed / wake times). Part of the issue is my naps always are 2-3 hrs long, and I’ve not figured out a way to set a clock for 20 minutes of naptime…

    I only get into bed when I know I’m ready to fall into sleep, otherwise it can become an insomnia battler, I can not try to sleep (unless I’m conked, or ill, headache for example). I’ll get a solid 2-4 hr chunk right off the bat, then I have awakenings which can be just a time or two that I get up to pee, or can be basically laying there going in and out of very lucid dreams (due to the fact I’m more than awake, now and then), for hours. Generally I’m in bed 7-9 hrs.

    A weird thing that I think is common for us with N perhaps, is that we can be somewhat both awake and asleep at the same time, or seem asleep in the early stages of sleep while really still being awake (in our mind, or something). I’m speaking to Polysomnographies or MSLT’s, so many others seem to experience being told they’ve been asleep when they knew they were not, or being surprised by MSLT results in regards to napping during nap times, there after the person thought they weren’t sleeping during the nap time, etc..
    With that last bit, I want to say that meditation is basically a form of early sleep stages (?), and to practice it at some point, better yet have it be within one’s normal weekly or daily routine, can do a lot of good. It’s what I do, or the state of mind that I go into, when I experience moderate or severe Cataplexy, and it helps dissipate it. It’s also basically what I do in bed every morning, before my mind starts telling me to get up, I’ll admit I dream too!.

    #5114
    JasonJason
    Keymaster

    @WWP I feel your pain. The current theory is that orexin is more of a sleep/wake stabilizing substance than a purely stimulating one. Essentially it controls the on/off switch between wake and sleep, hence the disturbed wakefulness as well the disturbance found in nighttime sleep. To add to the problem, generally the more alert and awake people are during the day, the better they sleep at night so if you’re struggling to stay awake during the day, it can result in even worse sleep at night. Sucks, right?

    I’m not sure why there seems to be a pattern to the increased sleepiness at certain times for many of us. My sleep doctor told me it’s a very common phenomenon in his experience. He said when patients say they tend to be sleepiest at certain times, it corresponds pretty reliably with the shortest sleep onset times during the MSLT. If I get up at 7:00am, I can almost guarantee I’ll get an attack at 10:30 or 11:00 and then another later in the afternoon. The only things I’ve found that abate the attacks, is either really intense exercise at the time or taking a nap. I suppose taking a ride on a rocket would probably have a similar effect!

    But basically, the only way to overpower the flip into sleep mode is to either overpower it by activating wake enhancing substances through medication or activity or to reset the switch by taking a nap. Sometimes just laying down and closing my eyes for 20 minutes and not trying to sleep necessarily but just focusing on relaxing seems to help quite a bit (I may be falling asleep without realizing it).

    It’s interesting that stimulants don’t work for you. The inappropriate flip into sleep is primarily believed to be caused by inhibition of the wake neurotransmitters and an increase in GABAa activity. If a GABAa antagonist was available that might be worth a try. The only other pharmaceutical that might work if traditional stimulants don’t is that H3 inverse agonist that is approved in some countries.

    Oh and I totally agree with Sk8 regarding not getting into bed until being definitely ready to sleep and other sleep hygiene practices. Better sleep at night has a huge impact on the severity of the sleep attacks for me.

    #5124
    WWPWWP
    Participant

    Thanks for the replies, Jason and Sk8.

    @Jasonm

    The only things I’ve found that abate the attacks, is either really intense exercise at the time or taking a nap. I suppose taking a ride on a rocket would probably have a similar effect!

    But basically, the only way to overpower the flip into sleep mode is to either overpower it by activating wake enhancing substances through medication or activity or to reset the switch by taking a nap. Sometimes just laying down and closing my eyes for 20 minutes and not trying to sleep necessarily but just focusing on relaxing seems to help quite a bit (I may be falling asleep without realizing it).

    It’s interesting that stimulants don’t work for you. The inappropriate flip into sleep is primarily believed to be caused by inhibition of the wake neurotransmitters and an increase in GABAa activity. If a GABAa antagonist was available that might be worth a try. The only other pharmaceutical that might work if traditional stimulants don’t is that H3 inverse agonist that is approved in some countries.

    Trouble is once the meds cease to work, or be powerful enough, (and they eventually will – see Robert Whitaker’s book in my signature, and also my experience plus others – Hank3326, the guy who needed 400mg+ of amphetamines, etc.), then the other other strategies, while helpful, also will not work consistently. One thing that wasn’t mentioned is mental stimulation*, whether by pursuing an interesting idea, or by being in a stimulating conversation with like-minded friends. I think being single and getting older is NOT great with N! The meet-and-greet part of my daily 2 hour walk/jog/stairs routine is helpful. The Falcon Heavy reference was more like a cure for N – no life support system required, just like Elon’s Tesla 3.

    You refer to “inhibition of the wake neurotransmitters and an increase in GABAa activity”, but what is doing the ‘inhibition’ I wonder. It feels like a vehicle running out of gas, so more like the transmitter supply has completely run out and then gets replenished some hours later, but neither effect is gradual, so that implies switching of some sort. When you speak of “that H3 inverse agonist that is approved in some countries”, are you referring to Potolisant (Wakix)? I’m trying to get some feedback from an N Meetup group in Prague regarding this drug.
    https://www.meetup.com/Prague-Relationships-Narcolepsy-Sleep-Disorders-Meetup/
    So far Aida B. hasn’t replied, but I’ll try another member.

    Most days I’d swallow a lit stick of dynamite, if I thought it would help!

    * Some form of Trans Cranial Stimulation might be useful in this regard.

    • If you take, or plan to take, mind-altering drugs or supplements, read this book first:
    penguinrandomhouse.com/books/189611/anatomy-of-an-epidemic-by-robert-whitaker/9780307452429/
    • Do not ever take internet health advice without first doing your own research, and always consult a health care professional. Each individual is unique - if you make a mistake, you may not be able to reverse the effects that may take decades to reveal themselves.
    • Be kind to Mother Nature and the Little Ones! 🙂

    #5125
    JasonJason
    Keymaster

    @WWP activating neurotransmitters don’t really run out. Their firing can be suppressed temporarily, however like when you need sleep. With N, it’s believed that’s what’s happening; your brain is going into sleep mode and suppressing the wake neurotransmitters inappropriately during the day. When you get sleepy (at least at night), GABAa transmission increases. Orexin stabilizes the system but without it, it’s broken.

    It’s more like getting dosed with a sleeping pill in the middle of the day because Orexin isn’t there to regulate the system. Sleeping medications that enhance GABAa make you sedated because GABAa suppresses the wake promoting neurons in the brain. So the options are to either increase the activity of the wake promoting transmitters or to inhibit the suppressing action of GABA. There’s a GABAa antagonist in development for N2 under this theory. What sucks about GABAa going haywire is often times, stimulants simply can’t overpower the suppression.

    And yes, pitolisant, was the medication I was referring to. No way to know if it’d work for you without trying it but it works differently than other stimulants. A strategy you might be able to try is taking something like focalin (which is shorter acting) about an hour or so before your crash. If taken just once per day because of it’s short half-life, you might not have the same tolerance problems.

    #5128
    WWPWWP
    Participant

    @Sk8aplexy

    Can recall at a N conference one of the presenters described N to involve a 90 minute (term I don’t recall) rhythm rather than the 24 hour circadian rhythm.

    Napping doesn’t work for me unless I really need it, then I’m either not sleeping well that night or falling asleep way later and throwing off the normal routine somewhat (it’s always fluctuating to an extent, 2-4 hrs bed / wake times). Part of the issue is my naps always are 2-3 hrs long, and I’ve not figured out a way to set a clock for 20 minutes of naptime…

    I only get into bed when I know I’m ready to fall into sleep, otherwise it can become an insomnia battler, I can not try to sleep (unless I’m conked, or ill, headache for example). I’ll get a solid 2-4 hr chunk right off the bat, then I have awakenings which can be just a time or two that I get up to pee, or can be basically laying there going in and out of very lucid dreams (due to the fact I’m more than awake, now and then), for hours. Generally I’m in bed 7-9 hrs.

    I believe 90 minute sleep cycles are perfectly normal, even for a healthy individual – it’s just that you shouldn’t be aware of each cycle, just as you state you sometimes consolidate the first 2 cycles on a good night. Your description of an ‘average’ night’s sleep pretty much describes mine as well, although I’m not a heavy-duty dreamer. The 90 minute sleep cycle (Stages 1-3 +REM), is thought to be an evolutionary leftover from the era when you might become a late-night snack for a Sabre-toothed Tiger, if you slept too soundly.

    I envy those who can ‘nap’ productively for hours. If I could, I would just try to structure my day around those 2 sleep periods.

    • If you take, or plan to take, mind-altering drugs or supplements, read this book first:
    penguinrandomhouse.com/books/189611/anatomy-of-an-epidemic-by-robert-whitaker/9780307452429/
    • Do not ever take internet health advice without first doing your own research, and always consult a health care professional. Each individual is unique - if you make a mistake, you may not be able to reverse the effects that may take decades to reveal themselves.
    • Be kind to Mother Nature and the Little Ones! 🙂

    #5129
    WWPWWP
    Participant

    @wwp activating neurotransmitters don’t really run out. Their firing can be suppressed temporarily, however like when you need sleep. With N, it’s believed that’s what’s happening; your brain is going into sleep mode and suppressing the wake neurotransmitters inappropriately during the day. When you get sleepy (at least at night), GABAa transmission increases. Orexin stabilizes the system but without it, it’s broken.

    It’s more like getting dosed with a sleeping pill in the middle of the day because Orexin isn’t there to regulate the system. Sleeping medications that enhance GABAa make you sedated because GABAa suppresses the wake promoting neurons in the brain. So the options are to either increase the activity of the wake promoting transmitters or to inhibit the suppressing action of GABA. There’s a GABAa antagonist in development for N2 under this theory. What sucks about GABAa going haywire is often times, stimulants simply can’t overpower the suppression.

    And yes, pitolisant, was the medication I was referring to. No way to know if it’d work for you without trying it but it works differently than other stimulants. A strategy you might be able to try is taking something like focalin (which is shorter acting) about an hour or so before your crash. If taken just once per day because of it’s short half-life, you might not have the same tolerance problems.

    It certainly is a complicated issue, and gets more so as we age and cause additional issues with our drugs, not to mention accumulated damage from our ongoing poor sleep. Still, I think it’s worth trying understand, if only to avoid throwing things like more stimulants at a brain that can no longer respond.

    The normal daytime sleepiness is supposed to come gradually and only become strong enough for a serious effect in late evening. I think this is largely governed by the ATP->adenosine cycle. Orexin-A would be involved as well, I suppose. Would its role be in regulating a steady supply of wakefulness neurotransmitters, rather than having the brain just kind of squirt them out (and then soak them up) in the first 2/4/6 hour cycle of wakefulness that some of us can manage to eke out sans drugs? I know, in my case, that simply throwing more stimulants (dopamine) at the problem will not work for long at all; think in terms of up-regulated neuroreceptors that have, over a period of years to decades, finally ‘curled-up and died’. And yet, 6 hours or so later, I can often get moving again, and if I allowed it, could go half the night. It’s puzzling, but NOT fun. For one thing, it’s not just the EDS I have to deal with, but the mood and motivation (not to mention physical heaviness and poor balance) go out of wack as well. Oh joy! 😡

    • If you take, or plan to take, mind-altering drugs or supplements, read this book first:
    penguinrandomhouse.com/books/189611/anatomy-of-an-epidemic-by-robert-whitaker/9780307452429/
    • Do not ever take internet health advice without first doing your own research, and always consult a health care professional. Each individual is unique - if you make a mistake, you may not be able to reverse the effects that may take decades to reveal themselves.
    • Be kind to Mother Nature and the Little Ones! 🙂

    #5132
    JasonJason
    Keymaster

    @WWP Sleep and wake are complicated and poorly understood, which adds to the frustration of trying to understand what’s going on.

    This video on the the science of sleep/wake might be interesting to you.

    #5271
    JasonJason
    Keymaster

    @wwp Found some much more comprehensive research on wake and sleep for your viewing pleasure:

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325713/

    #5284
    WWPWWP
    Participant

    @wwp Found some much more comprehensive research on wake and sleep for your viewing pleasure:

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325713/

    Thanks! ‘Pleasure’ may not be the right word with this disorder, but this article should be required reading for all sleep doctors.

    There’s much more involved than just the lateral hypothalamus and its orexin-a. As far as the switching between states goes, it does seem to be a sudden teeter-totter effect without proper circadian regulation.

    Since the brain stem areas are so importantly involved, as well as adjacent brain structures, this should be a wake-up call to those who like to drink, smoke, vape, or ingest toxins that affect the CNS.

    • If you take, or plan to take, mind-altering drugs or supplements, read this book first:
    penguinrandomhouse.com/books/189611/anatomy-of-an-epidemic-by-robert-whitaker/9780307452429/
    • Do not ever take internet health advice without first doing your own research, and always consult a health care professional. Each individual is unique - if you make a mistake, you may not be able to reverse the effects that may take decades to reveal themselves.
    • Be kind to Mother Nature and the Little Ones! 🙂

    #5292
    JasonJason
    Keymaster

    @WWP you’re very welcome! This is actually a great topic you’ve started. It’s hard to find an optimal treatment without understanding the wake and sleep system from a fundamental standpoint. Maybe it’ll give someone some new ideas on treatment options or lifestyle choices that will help. I’ll continue to post studies, etc I find regarding it. Sleep science has been neglected historically but thankfully it’s getting much more attention these days. No one is absolutely certain about how everything works in the brain obviously but it’s exciting all of this research is being done to try to understand this most fundamentally important system.

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