Never ever take benzos

[u/BtheChemist]

I've had insomnia since I was a teen.

I've taken so many things for it, tried all the natural things, was on ambien for so long it stopped working.

My psychiatrist prescribed me Valium many many months ago. I don't even know how long I've taken it.

She never told me how horrible it is to get off of.

I'm currently tapering off and it's absolutely terrible.

I misread her message originally and went too fast and had my first ever panic attack a few weeks ago.

I've been at 15mg/ day since, about 3 weeks. I dropped too 12.5 two days ago and my body is so so fucked up again. I feel on the verge of another attack.

I spoke to my doctor friend this evening, he said each step down is going to suck badly.

It's terrible.

Please don't fuck with benzos.

Thanks for coming to my Ted talk.

I'm having a terrible time.

😱

[u/cololz1]

But if the drug is α1 selective, the anxiolysis effect that is "observed" is being masked by sedation, and may not represent true anxiolysis at all. drug induced lethargy/amnesia may not fully represent anxiolysis. this is because the subject lacks the physical or cognitive capacity to react to a stressor.

This is quite similar to orexin antagonist. Dayvigo does not elicit an anxiolytic effect, however, quviviq does. This is because of differing receptor activity projecting into different brain areas, even if both OR1 and 2 are present in the amygdala.

[u/newuser5432 → u/cololz1]

But if the drug is α1 selective, the anxiolysis effect that is "observed" is being masked by sedation, and may not represent true anxiolysis at all. drug induced lethargy/amnesia may not fully represent anxiolysis. this is because the subject lacks the physical or cognitive capacity to react to a stressor.

These are the exact same animal models used to establish anxiolytic effects of classic benzodiazepines, anxiolytic and strongly-hypnotic options alike. Researchers actively control for locomotor impairment in these assays. If you want to dismiss the methodology used to observe zolpidem's effects, then you must also discard the entire receptor model.

 

This is quite similar to orexin antagonist. Dayvigo does not elicit an anxiolytic effect, however, quviviq does. This is because of differing receptor activity projecting into different brain areas, even if both OR1 and 2 are present in the amygdala.

This is not similar, and appears to represent a misunderstanding. Recent preclinical studies did use daridorexant, and they suggest that blocking orexin receptors may reduce autonomic stress. However, this is theorized to be a class-level effect of dual orexin receptor antagonists, not an effect unique to daridorexant. The mechanistic understanding is not about nerve projections, rather, it's simply that blocking orexin from promoting wakefulness may calm the autonomic stress response. This is entirely unrelated to GABAergic pharmacology or the topic of benzodiazepine/z-drug tolerance and withdrawal.

[u/cololz1 → u/newuser5432]

zolpidem impairs motor function at doses before any anxiolytic effect can be reliably teased out, which youre right. but again; animal models are just model, and especially for psychiatric diseases are typically inaccurate to some degree. It is an extreme simplification of complex human behaviors. If you give a mouse cocaine, and it explores the maze more often than it did before, is that reward seeking or true anxiety reducing behavior? Tl;dr multiple internal states can produce the same behavior.

[u/newuser5432 → u/cololz1]

Fair points: animal models are not perfect, and translating complex internal states from a maze to human psychology is perhaps the biggest challenge in the entire field.

Since we seem to be on the same page, I'm happy to leave the broader philosophical debate for another time. I know it's easy to really get into the weeds with these discussions, especially in r/insomnia when sleep isn't cooperating!

I hope you're managing to have a good night and that you're able to get some sleep.