Benzos Uncoupling of the GABA-A receptor

[Spurs_1882]

I apologise in advance if my knowledge is poor; I don't have a science or pharmacology background.

I was reading that long-term use of benzos can cause changes in the brain relating to the "uncoupling of the GABA-A receptor", which have the effect of the brain becoming de-sensitised to endogenous GABA, which results in higher than baseline anxiety even in the absence of benzo withdrawal.

I understand it's a difficult question to answer exactly but I wonder if my usage pattern would be anywhere near high enough to cause this to happen, or if you'd need to be taking them more like daily. I'm trying to understand why my anxiety has been high and my sleep terrible recently.

- I take 30mg diazepam or equivalent in another long-acting benzo for always two days in a row (so 60mg over two days) and I do this on average once every two weeks.
- Occasionally it's been 35mg for 2 days in a row rather than 30mg but never more than this.
- I don't think I've ever done used benzos more than 2 days in any given week. So at worst I will use two days in a row and then wait until the start of the next week to use again.
- There's been occasional times when I haven't used them for a month or more. In one or two cases I didn't use them for a year.
- I've been doing this for 20 years.
- At the start the dosages were lower- like 5mg for two days in a row rather than 30mg for two days in a row- my tolerance has increased gradually over time.

Really appreciate any responses whatsoever. Thanks.

 

[emkee_reinvented]

A while ago, DETOX, they fed me Diazepam 5 days.
80, which was way too much, 40--30-20-10.

i was still feeling it and showed up in their
last urine test day 17. After de-charging myself,
it lingered noticeable till day 21.

So its one of the longest working ones. Skipping days won t really help,
but lower plasma concentration somewhat.

So is short acting better ?

 

[Spurs_1882]

A while ago, DETOX, they fed me Diazepam 5 days.
80, which was way too much, 40--30-20-10.

i was still feeling it and showed up in their
last urine test day 17. After de-charging myself,
it lingered noticeable till day 21.

So its one of the longest working ones. Skipping days won t really help,
but lower plasma concentration somewhat.

So is short acting better ?

I've definitely read numerous times that short acting benzos are easier to get physically addicted to or to get rebounds from. Something to do with the brain really not liking the ups and downs in the plasma concentration. It can handle things better when it's gradual.

 

[emkee_reinvented]

I've definitely read numerous times that short acting benzos are easier to get physically addicted to or to get rebounds from. Something to do with the brain really not liking the ups and downs in the plasma concentration. It can handle things better when it's gradual.

Gradual, 180 mg Diazepam/ 5 days, lasting over 15 days after last intake.

Its more handle able if you like being in a haze for weeks after.
But my logic s say that must accompanied by a robust uncoupling of
GABA-a receptor. Just the WD, if addicted, are less sever/
extended over a longer time

Please post some scientific s link where you got uncoupling info from.
Maybe they will some reveal some things overlooked.
And don t forget what drugs can damage dr s can destroy.
Just by not or wrong treatment, so ATM dr s vs Benzos.

Dr s [your job, mental health care and what not] are more dangerous allround,
that s what they are best at. Making a mess and not cleaning up.
Basing on assumptions instead of science or facts.

 

[fairnymph]

I apologise in advance if my knowledge is poor; I don't have a science or pharmacology background.

I was reading that long-term use of benzos can cause changes in the brain relating to the "uncoupling of the GABA-A receptor", which have the effect of the brain becoming de-sensitised to endogenous GABA, which results in higher than baseline anxiety even in the absence of benzo withdrawal.

I understand it's a difficult question to answer exactly but I wonder if my usage pattern would be anywhere near high enough to cause this to happen, or if you'd need to be taking them more like daily. I'm trying to understand why my anxiety has been high and my sleep terrible recently.

- I take 30mg diazepam or equivalent in another long-acting benzo for always two days in a row (so 60mg over two days) and I do this on average once every two weeks.
- Occasionally it's been 35mg for 2 days in a row rather than 30mg but never more than this.
- I don't think I've ever done used benzos more than 2 days in any given week. So at worst I will use two days in a row and then wait until the start of the next week to use again.
- There's been occasional times when I haven't used them for a month or more. In one or two cases I didn't use them for a year.
- I've been doing this for 20 years.
- At the start the dosages were lower- like 5mg for two days in a row rather than 30mg for two days in a row- my tolerance has increased gradually over time.

Really appreciate any responses whatsoever. Thanks.

I’ve been on 10 mg of diazepam daily (with several breaks a year) since 2008. I can stop taking it and I have no problems - I do have to take regular breaks to keep my tolerance down/maintain efficacy. But, I’m taking it for muscle tension, not anxiety. Still, I’m positive that I less anxious now than I was in the past. I think that’s due to self work though. I would definitely recommend taking longer breaks more frequently to lower your tolerance. Maybe that’s what has saved me from any potential issues.

 

[emkee_reinvented]

This is from Neuroscience Forum Bluelight.
Goes into the long vs short acting, and what is the lesser evil.
Might enlighten some of it, not yet read it myself, about to.

https://www.bluelight.org/community...nzos-what-are-the-comparative-dangers.944701/

 

[bigjackaal96]

I was reading that long-term use of benzos can cause changes in the brain relating to the "uncoupling of the GABA-A receptor", which have the effect of the brain becoming de-sensitised to endogenous GABA, which results in higher than baseline anxiety even in the absence of benzo withdrawal.

Benzo's/Z-drugs are GABA-A PAM's. They bind like a agonist but the effects are from CNS GABA think a very dirty Reuptake Inhibtor. Which then leads to the brain unable to produce GABA because the levels have ran out, In panic It forces Benzo/Z-drugs to act as GABA source while never repairing Itself. If anything they aren't Addictive they are inducing mild brain damage since the brain downregulates GABA receptors for zero reason. Edit : Forgot to add that the Brain will pluck out GABA-A receptors as well meaning many are left with only 0.5 ~ 20%. Which Is common with heavy Xanax users.

Alcohol & Muscimol differ hard because there full GABA-A agonists meaning the brain can just live off Ethanol or Muscimol instead of It own GABA. But Alcohol can act as a false PAM in people with livers that can't make up It mind on converting It or not, Which ditctates on wither Alcoholism will happen. Extra : It why careful Binge drinking can be far safer than just spreading out beer/mixed drinks.

Muscimol a whole different beast It binds as If were GABA itself even kicking away CNS GABA. Like with Ethanol your brain for the 8+ hours your living off Muscimol. Meaning in theory you could do 15g Muscimol rich shrooms or brew for 4 ~ 6 days with the same quality as the first, Also you never get sick stopping by the 6th day.

It actually still safer getting a 4 pack of Beer to use on LSD or Shroom comeup panic.

 

[Spurs_1882]

Gradual, 180 mg Diazepam/ 5 days, lasting over 15 days after last intake.

Its more handle able if you like being in a haze for weeks after.
But my logic s say that must accompanied by a robust uncoupling of
GABA-a receptor. Just the WD, if addicted, are less sever/
extended over a longer time

Please post some scientific s link where you got uncoupling info from.
Maybe they will some reveal some things overlooked.
And don t forget what drugs can damage dr s can destroy.
Just by not or wrong treatment, so ATM dr s vs Benzos.

Dr s [your job, mental health care and what not] are more dangerous allround,
that s what they are best at. Making a mess and not cleaning up.
Basing on assumptions instead of science or facts.

A few here. Would be interested to hear anyone's take on what kind of level of use is needed for this kind of thing to happen, especially from personal experiences of anxiety getting worse. Thanks for your replies Emkee.

Mechanism of Action - Benzodiazepine Information Coalition

Benzodiazepines, like alprazolam (Xanax), lorazepam (Ativan), clonazepam (Klonopin) and clonazepam) act on the central nervous system (CNS) and brain. They are known pharmacologically as GABAergic agents, sedative-hypnotics, or minor tranquilizers....

www.benzoinfo.com

Uncoupling of GABA(A) and benzodiazepine receptor binding activity in the hippocampal formation of schizophrenic brain - PubMed

A recent postmortem study has reported that there is a widespread upregulation of GABA(A) receptor binding activity throughout most subregions of the hippocampal formation of schizophrenic brain. The current study has been undertaken to determine whether the benzodiazepine (BZ) receptor, which...

pubmed.ncbi.nlm.nih.gov

https://pharmrev.aspetjournals.org/article/S0031-6997(24)00858-5/abstract#title27

https://www.sciencedirect.com/science/article/abs/pii/S0306452213009378

https://www.jbc.org/article/S0021-9258(20)61531-9/fulltext

 

[Spurs_1882]

I’ve been on 10 mg of diazepam daily (with several breaks a year) since 2008. I can stop taking it and I have no problems - I do have to take regular breaks to keep my tolerance down/maintain efficacy. But, I’m taking it for muscle tension, not anxiety. Still, I’m positive that I less anxious now than I was in the past. I think that’s due to self work though. I would definitely recommend taking longer breaks more frequently to lower your tolerance. Maybe that’s what has saved me from any potential issues.

Thanks that's really helpful to know. And yes the longer breaks is definitely a good plan. I haven't taken any for 5 weeks atm, but really I think I could do with a good six months off, it's just hard to manage this practically for various reasons. I should be able to manage two full months off but then it's my fucking 40th birthday and I'm going to want/need them!

 

[fairnymph]

Thanks that's really helpful to know. And yes the longer breaks is definitely a good plan. I haven't taken any for 5 weeks atm, but really I think I could do with a good six months off, it's just hard to manage this practically for various reasons. I should be able to manage two full months off but then it's my fucking 40th birthday and I'm going to want/need them!

I don’t think I could manage six months off. I mean I could, but I don’t want to. So I totally get you here. It’s just too fundamental for managing my pain. Plus, whenever I’m off my diazepam, I have to take way more opiates which I hate.

 

[Spurs_1882]

I don’t think I could manage six months off. I mean I could, but I don’t want to. So I totally get you here. It’s just too fundamental for managing my pain. Plus, whenever I’m off my diazepam, I have to take way more opiates which I hate.

Ah, sorry to hear you have chronic pain. But pleased to hear you have found a way of managing it. I have intermittent really bad headaches from long-Covid which I can't manage without a benzo, opiate or carisoprodol, though having said that, massage is helpful. It's probably not as bad as what you are experiencing pain-wise but perhaps I can still relate.

 

[fairnymph]

Ah, sorry to hear you have chronic pain. But pleased to hear you have found a way of managing it. I have intermittent really bad headaches from long-Covid which I can't manage without a benzo, opiate or carisoprodol, though having said that, massage is helpful. It's probably not as bad as what you are experiencing pain-wise but perhaps I can still relate.

Yeah, it sucks, but it’s amazing how we can adapt if we want to, and while there aren’t many things that help my pain, I am very glad that there’s anything that helps at all. I’ve tried every type of bodywork you can possibly imagine and it’s very hard for me to even find a regular masseuse that is strong enough to work on me. But unfortunately, even a four hour long massage from a super strong expert masseuse doing everything exactly as I need doesn’t provide much relief. Within hours I feel back to the way I was before. The only thing that actually provides lasting relief and treats the underlying causes is rolfing, but there aren’t any practitioners near me. And the closest ones are super booked up for over a year. I would need to be able to see one weekly for it to really be worth it.

I really wish carisoprodol was available here! I actually haven’t tried it since my pain got so bad but I remember it being useful when my back would get strained from carrying heavy stuff or sitting too long and studying etc.

I’m so glad I’m not prone to headaches. I do get hormonal migraines, or I used to - but fortunately, migraine medicine taken promptly works really wellm and since I’ve been regular black seed oil, they’ve basically stopped. So you might consider trying that. You want to get the highest percent thymoquinone you can find, and take at least a teaspoon daily. The way I’ve been using it is generally taking 1 to 3 tablespoons several days a month but that seems to work too. Anything that is intermittent and sporadic is very difficult to deal with, because you can’t really adapt to it. I hope at least the meds that you have manage your headaches decently.

 

[Spurs_1882]

Yeah, it sucks, but it’s amazing how we can adapt if we want to, and while there aren’t many things that help my pain, I am very glad that there’s anything that helps at all. I’ve tried every type of bodywork you can possibly imagine and it’s very hard for me to even find a regular masseuse that is strong enough to work on me. But unfortunately, even a four hour long massage from a super strong expert masseuse doing everything exactly as I need doesn’t provide much relief. Within hours I feel back to the way I was before. The only thing that actually provides lasting relief and treats the underlying causes is rolfing, but there aren’t any practitioners near me. And the closest ones are super booked up for over a year. I would need to be able to see one weekly for it to really be worth it.

I really wish carisoprodol was available here! I actually haven’t tried it since my pain got so bad but I remember it being useful when my back would get strained from carrying heavy stuff or sitting too long and studying etc.

I’m so glad I’m not prone to headaches. I do get hormonal migraines, or I used to - but fortunately, migraine medicine taken promptly works really wellm and since I’ve been regular black seed oil, they’ve basically stopped. So you might consider trying that. You want to get the highest percent thymoquinone you can find, and take at least a teaspoon daily. The way I’ve been using it is generally taking 1 to 3 tablespoons several days a month but that seems to work too. Anything that is intermittent and sporadic is very difficult to deal with, because you can’t really adapt to it. I hope at least the meds that you have manage your headaches decently.

I know what you mean about the massage. The pain relieving effect doesn't last long for me either. No way could I afford frequent massages but luckily I have a very kind wife...sadly she has LC as well so I will give her massages in return.

Carisoprodol is not available here either but when I was in Costa Rica I bought a load (it appears to be OTC there) and took it home with me. How does the black seed oil help? I'd never heard of it before and suddenly saw it mentioned here twice.

I've no idea if your pain is neuroplastic (i.e. caused by misfiring of your brain) or structural, but if you even think it might be neuroplastic, or part neuroplastic, I'd recommend listening to a podcast called Tell Me About Your Pain by Alan Gordon. I'm seeing a therapist for my long-Covid who turned me on to that and it's been very, very helpful for me so far (I strongly believe my long-Covid is at least in part neuroplastic).

 

[fairnymph]

I know what you mean about the massage. The pain relieving effect doesn't last long for me either. No way could I afford frequent massages but luckily I have a very kind wife...sadly she has LC as well so I will give her massages in return.

Carisoprodol is not available here either but when I was in Costa Rica I bought a load (it appears to be OTC there) and took it home with me. How does the black seed oil help? I'd never heard of it before and suddenly saw it mentioned here twice.

I've no idea if your pain is neuroplastic (i.e. caused by misfiring of your brain) or structural, but if you even think it might be neuroplastic, or part neuroplastic, I'd recommend listening to a podcast called Tell Me About Your Pain by Alan Gordon. I'm seeing a therapist for my long-Covid who turned me on to that and it's been very, very helpful for me so far (I strongly believe my long-Covid is at least in part neuroplastic).

A partner who knows your body can be a very good masseuse indeed.

Black seed oil is really great for inflammation. So if you have any type of pain that is at least partially due to inflammation it will likely help. It’s also a very strong antimicrobial. I no longer use antibiotics since finding it.

My pain is entirely due to muscle tension and spasticity, so unfortunately, I don’t think that would be very helpful for me. :/

 

[4DQSAR]

My pain is entirely due to muscle tension and spasticity, so unfortunately, I don’t think that would be very helpful for me. :/

In the UK at least, baclofen (which is after all a GABA analogue) is sometimes used to treat such symptoms.

It's certainly not abusable but it does produce a certain amount of sedation. Have you come across it?

It apppears to increase the effect of opioids. It may be an alternative to diazepam. I'm pretty sure it's cheaper.

 

[fairnymph]

In the UK at least, baclofen (which is after all a GABA analogue) is sometimes used to treat such symptoms.

It's certainly not abusable but it does produce a certain amount of sedation. Have you come across it?

It apppears to increase the effect of opioids. It may be an alternative to diazepam. I'm pretty sure it's cheaper.

Yep, it was prescribed to me fairly early on in my process of trying literally every pharmaceutical that could possibly help me. It had a very mild effect (better than nothing but even gabapentin is better) & that was before my pain got severe. Nothing compares to diazepam, except for local lidocaine injections, and that only works in a very small area of my back. But it does provide basically complete relief for that one knotted muscle for several hours. The relief is so sudden that I experience a brief feeling of extreme relaxation that is somewhat sedating and can even make me a little wobbly. Wish I knew why none of my other many trigger points responded.

 

[4DQSAR]

I know that feeling. I suspect it's the fact that one's body is dumping nuerotransmitters to dampen the pain. If that pain suddenly stops, you can become light headed amd as you say, 'wobbly'. In fact, I've felt like I just wanted to sleep. I suppose if you have been in pain for a long time, you will not sleep well so maybe the body decideds that now is the time to catch up.

 

[fairnymph]

I know that feeling. I suspect it's the fact that one's body is dumping nuerotransmitters to dampen the pain. If that pain suddenly stops, you can become light headed amd as you say, 'wobbly'. In fact, I've felt like I just wanted to sleep. I suppose if you have been in pain for a long time, you will not sleep well so maybe the body decideds that now is the time to catch up.

Pain is a hell of a stimulant! I have the same theory.

 

[4DQSAR]

Not many people can claim to be 'casual' pain users although I remain convinced that their is a minority addicted to pain - or, rather, the endogenous opioids pain releases.

 

[Spurs_1882]

A partner who knows your body can be a very good masseuse indeed.

Black seed oil is really great for inflammation. So if you have any type of pain that is at least partially due to inflammation it will likely help. It’s also a very strong antimicrobial. I no longer use antibiotics since finding it.

My pain is entirely due to muscle tension and spasticity, so unfortunately, I don’t think that would be very helpful for me. :/

Ah I see, that makes sense. Your pain issues sound difficult and very challenging. I hope you find a cure, and if that's not possible, better treatment. I guess it's good you at least have diazepam and you have managed to avoid a tolerance so far.