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Comment by snsr | Hacker News Reader

Notably, the drug Ambien disrupts the norepinephrine oscillation that is part of this process.

Once upon a time I had severe difficulty sleeping due to high and sustained levels of stress.

I had gotten prescribed some Zopiclone which is similar to Zolpidem as found in Ambien. Zopiclone makes me feel like I have a brain injury the day after. Sometimes after the first night, always after the second night if I find I need to take it two nights in a row. It’s frightening.

I came across a paper: ”Pharmacokinetic and Pharmacodynamic Interactions Between Zolpidem and Caffeine”

https://www.researchgate.net/profile/Roberta-Cysneiros/publi...

Based on my understanding of the results that a significant dose of caffeine counteracts “some but not all” of Zolpidem’s effects on cognition—and the two Z-drugs being similar—I tried drinking a tiny little bit of coffee with the tiny little bit of Zopiclone. (I take 2-3mg; a whole tablet is 7.5mg.)

The result is that I am able to sleep and do not feel brain-damaged the day after, and the effect also seems to be that the failure rhythm of stress-related waking up at precisely 5:30 is broken. In other words, the combination seems to fix the problem.

I suspect that part of the reason might be that the caffeine counteracts the disruption of the norepinephrine oscillation you mention. (Thanks!!)

That's quite interesting. I take half a Zolpidem once a week or so and I'll try taking it with caffeine.

I've tried Zolpiclone but found it affects my sleep much more. Zolpidem is faster acting and gets out of your system quicker, while Zolpiclone continues working during the night.

So if your issue is getting to sleep and not staying asleep I would recommend you try the original.

I know and trust that the implicit disclaimers are clear, that this comes with absolutely no guarantees of not being terrible for anyone else :)

—I would indeed prefer the shorter duration of Zolpidem! Zopiclone was the only Z-drug option the doctor was willing to use. Fortunately, the caffeine seems to kind of mitigate the longish duration of Zopiclone. And Zolpidem has somewhat dangerously recreational effects on me :sweat_smile: … and is slightly addictive to me as well.

I’d very much like to be able to try Zaleplon instead. It’s more recent than the two other Z-drugs and the shortest-acting; Not available in my country.

https://en.wikipedia.org/wiki/Zaleplon

Ambien, to me, is an extremely scary drug. People in my life have become extremely reliant on it to sleep and it has strange side effects. Sleepwalking with no recollection is one of them, not going to the kitchen, but getting in the car types of sleepwalking.

> Ambien, to me, is an extremely scary drug.

Meanwhile, older drugs that are less distressing aren't used any more because "We don't use it any more". -Dr: If I ask about Librium.

You're talking about "older drugs" like Chlordiazepoxide like they don't have any drawbacks or the drawbacks are less heavy compared to other more modern drugs. I'll give you that everyone is different, and doctors should evaluate what works for each patient, but I don't think it's ever as simple as "older drugs == better, newer drugs == worse".

> but I don't think it's ever as simple as "older drugs == better, newer drugs == worse".

I don't think anyone here was making that assertion. As far as there is a broad, common experience, it is Dr's who won't consider older meds, even if they come with less baggage than their newer counterparts.

I agree, Ambien is a scary drug to rely on as it can create dependency and also masks underlying issues that are causing not inability to sleep. In emergencies when one needs to get some form of sleep it could be useful to break the cycle of not being able to sleep and restore sleep hygiene. I had some sleep issues back in my 20s (luckily they haven't come back) and found that sometimes being too tired made falling and staying asleep quite hard. One thing that helped me is to forcefully yawn before going to sleep, doing it for a couple of minutes.

> Ambien is a scary drug to rely on as it can create dependency and also masks underlying issues that are causing not inability to sleep.

That just sounds like you think every sleeping-pill is scary, as that's true for literally all of them.

Sleeping pills are mostly effective together with other types of therapy to address the underlying causes, just like most "temporary solutions". They're supposed to be used as "We'll try to figure out what's wrong, but in the meantime, so you can feel relatively human, here is a temporary crutch", not as a long-term solution.

Intractable sleep conditions exist. I have narcolepsy which is incurable. I'm on sodium oxybate which is basically just GHB. It's a "scary" drug to be taking every night, but it's very effective and usually very safe in controlled dosage.

That drug is not a drug designed to put you to sleep though (I mean it kinda does, but that's not its purpose). The purpose of that drug is to change your sleep architecture during the night. I'm on the newer form of that drug (because of idiopathic hypersomnia) and most nights I still take 1–2 hours to fall asleep.

Lumryz? GHB is metabolized very quickly and would be out of your system within 2 hours. Lumryz is supposed to process slower. I have had a few bad nights on xyrem, but mostly it puts me sleep quickly enough. And more importantly puts me on a better sleep cycle so I'm actually sleepy at bed time by dint of being awake during the day.

Xywav, with the 2-dose schedule. My impression based on how I feel waking up at various times in the morning is each dose produces effects that last somewhere around 3–5 hours. My understanding is most people taking this drug are falling asleep much more quickly than I am, and I do feel it trying to make me sleepy shortly after taking it, but not enough to defeat my delayed sleep phase disorder and various insomnia issues. But my point was that "falling asleep quickly" is not a direct goal of the drug, even if it is a common effect, the goal of the drug is to change what your brain does while you're asleep.

I use 5mg a few nights a week to get a full night’s rest. I’ve worked hard over the years on good sleep hygiene—no screens, wearing a sleep mask, and avoiding food (especially carbs or alcohol) before bed.

No direct link has been found to this, but eating carbs has always given me deeply vivid (and often exciting) dreams since I was little. Unfortunately, from these I wake up exhausted, which isn’t great for the day.

I’ll continue being careful, and especially stay mindful when life stress—like love or money—picks up. It’s good to be aware if anything is being masked or overlooked in the process.

Carbohydrates have been a big part of what I’ve needed to figure out in order to reach sleep again after an unusually tough period.

Carbohydrate metabolism has histamine intimately involved in it; Histamine – as per its inflammatory role – is basically used by the body to open tissue to receive blood glucose.

As it happens, histamine is also a neurotransmitter! An excitatory alertness neurotransmitter!

Both these aspects have been extant as scientific knowledge on record for some significant time, but are only really becoming known-known as of recent.

I have ADHD. I take lisdexamfetamine. Upon starting medication at 39.5 years of age, I quickly noticed that I had to be really careful with coffee, and especially to not at all touch any sweet foods or desserts around evening or so. Or I would wake up at 5:30 AM. (Exactly and precisely 5:30. Reliably. It’s sort of fascinating.)

As it turns out, amphetamine releases histamine! And! Caffeine inhibits the enzymatic breakdown of histamine! And sugar causes histamine to be released.

5:30 AM in the same place, or different places? If same place, I'd assume some environmental/technical reason. Some machine somewhere near starting up, producing infra- or ultrasonics, a manifest freight train rumbling by far away, doing the same, some other thing (electro-/static/magnetic fields changing), and so on. 'Technical' because nature would vary that with the seasons because of https://en.wikipedia.org/wiki/Solar_time

Ah!! Thank you! Hadn’t thought of it that way. Aaand… When it happens, it’s 5:30 anywhere… in this timezone? I think? In other words, it happens in different houses in different parts of the country. (My thanks include the prompt to try to get this into words.)

It seems to be very tightly attached to the base circadian rhythm as attrained to the cycling daylight.

As far as I know, this time during night is very very likely to be the start of the cortisol spike that occurs before we wake up. The start of the wake-from-standby process.

https://en.wikipedia.org/wiki/Cortisol_awakening_response

Cortisol raises blood sugar, and histamine as an alertness neurotransmitter will then probably rise as far as I know? Have tried my best to understand this in order to escape the cycle when it starts; There seems to exist a rhythm in histamine release, and disrupting this rhythm seems to cause this 5:30 bs, haha.

Could be, but wasn't what I had in mind/meant to say.

Local solar time means it's exactly 'high noon'/12:00PM when the sun is at its highest point in the sky. The farther away to the left/west or right/east (in the northern hemisphere(swap these if 'down' under)), the bigger the real difference in minutes would be. If moving up/down/north/south nothing changes. See https://en.wikipedia.org/wiki/Terminator_(solar) for why.

Meaning real sunrise would drift forwards and backwards in one location with the seasons/time of year, and also if you move left or right within that timezone because that is an artificial construct.

So I'm having real difficulties to accept a natural cause for that exactly 5:30AM :-) Something more technical, like machines starting according to some timetable/start of shift/schedule seems way more likely, because those are aligned to the artificial construct called 'timezone'.

Got it?

Ah, indeed – we’re on the same page! (I wish this wasn’t a belated reply…)

One thing is that I’m “forced” to pretty strictly wire my circadian rhythm to the societally defined clock.

This also defines much of what is the actual input into my circadian sensorium: Artificial light :)

I am able to have a remarkably consistent circadian rhythm, going to sleep arounnnnd, say, 11 PM? Waking up around 8-ish. Those times wiggle around a little.

It’s subtly tricky to put into words –meaning it’s interesting! — and I’m not even absolutely sure that this is everything that defines the machinery, but given this, uh, “framework”?, it’s ludicrously consistent: If I back my neuroendocrine system into a corner, it will bite at 5:30. Sometimes a bit earlier.

Thanks for the discussion! I hope we are actually on the same page w.r.t. premises and that I’m continuing this on the avenue you’re looking down!

It's bad enough that there's a whole subreddit dedicated to the shit people get up to on it [1]. Telling thing: the description for it starts off with CHOP OFF ALL YOUR HAIR, probably a reference to a toothpaste for dinner comic about "the ambien walrus" which is a popular meme in the uhhh ambien community

[1] https://www.reddit.com/r/ambien/top/?t=all

i used it daily for a couple years and had no idea the impact it was having on me. i was an angry, irritable, grumpy person, and i completely changed when i finally stopped taking it.

i had an addiction but didnt abuse it. it got to the point that i craved ambien during the day for reasons i can't even explain. i just inexplicably wanted to take it. i wasnt even taking full pills of the usual dose, i usually cut them in half.

it took me a long time to learn to put my phone away before taking it. i would text people i was causally dating overly romantic and loving things and have zero memory of it. thankfully whenever it happened the people involved always just thought it was funny, and i did have the awareness to preface those texts with "maybe its just bc i took some ambien". After a few dates with someone i warned them i take ambien and might text them something stupid but loving, so they were well prepared

I personally know of one ambien addict and it's scary. He just went through a divorce and lost his job. His barely coherent (and angry) voice messages while off the drug don't seem too different from addicts of illegal substances.

I completely agree. I once took Ambien on a flight from San Fran -> London, but I didn't sleep. I suffered from crazy short term amnesia by the time I got to the other end, walking towards the Hilton just outside the airport in that long tunnel... I kept forgetting where I was and why I was there and then I'd snap back to reality. To the alarm of a friend that was supposed to be picking me up, I simply checked into the Hilton. What happened on the flight was another story altogether. I think I was repeatedly telling the attendants that I'd taken Ambien, they ended up shifting me to first class. Looking back, it was fun for reasons I won't talk about here - but belongs strongly in the recreational category. Sitter required.

I took Ambien for one of my sleep studies and I had sleep paralysis and nightmares (bordering on hallucinations because I swear I was awake or at least in a lucid state). That was my first and last time doing Ambien.

They gave us Ambien (no go pills) and Provigil (go pills) in the miltary during long ready states. After a while, I became dependent on Ambien and would sleep walk (among other things). My roomates would zip me up in my sleeping bag to deal with it.

Took me about 2 years after the military to get back to "normal"

I do miss the Provigil, though... that stuff made able to focus so well.

If you have sleep issues try magnesium.

https://hn.algolia.com/?query=magnesium%20sleep&type=comment

What if blood magnesium levels tested normal?

My understanding is that magnesium blood tests are not reliable. Since magnesium is a natural element found in foods such as spinach, nuts, seeds, and whole grains, you know it is safe. Try a supplement and if it helps with muscle stiffness or sleep then you have a magnesium deficiency.

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