# Zopiclone/Eszopiclone as a GABA agonist?



## ugh1979 (Aug 27, 2010)

I'm currently trying to discover and try out meds that act as a GABA agonist (GABAa and or GABAb, not sure what's best for me yet.)

I've been taking Phenibut (a GABAb agonist) once or twice a week to great effect for my SA for the last 2 months but am fully aware of the tolerance issue so I don't take it more often than that. That means I have another 5/6 days a week where my GABA levels are low and i'm trying to find something to at least plug some of that gap and give me more days with no or low SA.

My experience with Phenibut has proved to me that low GABA levels are why I suffer from SA. (My previous like/use of GHB/GBL would also indicate this but I don't take them any more for other reasons)

I've just read that Zopiclone and Eszopiclone act as GABAa agonists so could well be of interest to me.

Does anyone have any experience of using Zopiclone/Eszopiclone as an effective treatment for SA?

I've taken Zopiclone infrequently purely as a sleep aid for a couple of years but not until today after reading elsewhere have I thought of trying it for it's anxiolytic effects.

I'll try out Zopiclone's anxiolytic effects this weekend as I already have some but can anyone tell me if Eszopiclone would be any better or worse for that purpose?


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## crayzyMed (Nov 2, 2006)

Why not go for benzo's instead? Z drugs are way to amnesic imo, cant imagine using them for anxiety. Benzo's arent cross tolerant with GABAB agonists.


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## ugh1979 (Aug 27, 2010)

crayzyMed said:


> Why not go for benzo's instead? Z drugs are way to amnesic imo, cant imagine using them for anxiety. Benzo's arent cross tolerant with GABAB agonists.


I knew someone would say that.  I should have mentioned in my first post that I have very little chance of being prescribed benzo's and don't have another source, hence why I'm looking elsewhere at other similar meds that I can get.


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## crayzyMed (Nov 2, 2006)

Well, it appears that some ppl like Z drugs for anxiety so youll have to try, id pick the one with the shortest half life as possible, youll have to redose more but this gives you the chance to avoid physical addiction (if you take enough days off).


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## ugh1979 (Aug 27, 2010)

Zopiclone half life = 5 hours
Eszopiclone half life = 6 hours


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## crayzyMed (Nov 2, 2006)

ugh1979 said:


> Zopiclone half life = 5 hours
> Eszopiclone half life = 6 hours


Do you want to take those 5 days a week? Ive really got no idea wheter thats enough to avoid physical addiction tbh, i take GHB every evening and because of its short half life you can avoid this, something that is impossible to do with benzo's.

Make that 3 days a week, give yourself 2 days break, that should work.


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## ugh1979 (Aug 27, 2010)

crayzyMed said:


> Do you want to take those 5 days a week? Ive really got no idea wheter thats enough to avoid physical addiction tbh, i take GHB every evening and because of its short half life you can avoid this, something that is impossible to do with benzo's.
> 
> Make that 3 days a week, give yourself 2 days break, that should work.


I want to take it however many days I can without building addiction, hence why I'm investigating it before trying it out for any period of time.

Using it 3 days a week would be fine by me. Every Tue/Wed/Thu for example would suit my life well as I use Phenibut at the weekend.

Thanks for your input as always crazyMed.


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## crayzyMed (Nov 2, 2006)

Well that should work out.


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## Noca (Jun 24, 2005)

I've heard in the UK they use Zopiclone instead of benzos sometimes for anxiety treatment.


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## Ash09 (Apr 27, 2009)

I'm not aware of it if they do, it's not listed in the BNF and none of my psychiatrists mentioned it.


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## Area88 (Oct 4, 2010)

I've tried using Zopiclone in that way. It's very dangerous. Remember it plays the role of a sleeping tablet. You lose all your coordination and causes a feeling of drunkeness. Yes the Euphoria of Zopiclone is good but taking it 2-3 times a day like this will damage your short term memory. The only way you can function on this drug is in front of the tv since it impairs all motor function. Zopiclone is one of those drugs that are classified as addictive and easy to abuse. Your liver won't like it much since overuse causes damages to it, in the same way consistant alcohol abuse does.

I would avoid using Zopiclone at all for GABA benefits because the drug will do more harm than good. The short term memory loss effect is scary, believe me I had it. It's like trying to use Cocaine or Alcohol to release lots of dopamine or serotoin into your brain, yes it will work for short periods of time but it's not fixing the long term cause. Please don't do any of this.

You wan't long term GABA, go out and get Nardil! You want short term GABA, get Xanax.


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## Ash09 (Apr 27, 2009)

Zopiclone has the same mechanism of action as the benzodiazepines, it's just a1 selective like quazepam, amnesia is actually less frequent with z drugs than benzos, it's not any more dangerous than alprazolam.


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## Area88 (Oct 4, 2010)

I realise they are both benzodiazepines, it's just Zopiclone is supposed to be used once a night. If used like Xanax three times a day, it would cause all sorts of dangerous problems and you'd be overdosing on the drug by doing this.

'Zopiclone (sold as Imovane®, Zimovane®) is a novel hypnotic agent used in the treatment of insomnia. It was first developed by Sepracor and introduced in 1988 by Rhône-Poulenc S.A., now part of Sanofi-Aventis. Zopiclone is a controlled substance in the United States, Canada and some European countries and may be illegal to possess without a prescription.

While it acts on the BZ1 receptor and is a short-acting hypnotic agent, it is not a benzodiazepine, but a cyclopyrrolone derivative, belonging to a novel chemical class which is structurally unrelated to existing hypnotics.

On April 4, 2005, the DEA listed zopiclone under Schedule IV, due to some evidence that the drug has addictive properties similar to benzodiazepines.

10 tablets may be fatal and this risk is greater if barbiturate use is combined with use of other downer drugs such as alcohol, heroin or tranquillisers.'

Take whatever benzodiazepines you want, just don't recommend Zopiclone for daytime use. It's too dangerous, I've been in that situation and had a few health scares from it. Please don't use the drug at all if this is what you plan to do with it.


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## Ash09 (Apr 27, 2009)

Area88 said:


> I realise they are both benzodiazepines, it's just Zopiclone is supposed to be used once a night. If used like Xanax three times a day, it would cause all sorts of dangerous problems and you'd be overdosing on the drug by doing this.


Based on what evidence?



> Take whatever benzodiazepines you want, just don't recommend Zopiclone for daytime use. It's too dangerous, I've been in that situation and had a few health scares from it. Please don't use the drug at all if this is what you plan to do with it.


The available evidence shows that the drug has less side effects than benzos if anything and has a comparable therapeutic index.

http://onlinelibrary.wiley.com/doi/10.1002/hup.470050306/abstract



> Compared to flurazepam, zopiclone was slightly less effective for sleep induction and sleep soundness variables. However, flurazepam was constantly worse than zopiclone for daytime performance. This study shows that both zopiclone dosages are shown to be active and safe in the treatment of insomnia, and exhibit a true advantage over flurazepam by its low incidence of residual effects.


http://www.smw.ch/docs/archive200x/2002/35/smw-10074.html



> We report a case of excessive use of zopiclone and its withdrawal. A 67-year-old man used almost *340 mg/d* to treat his insomnia.


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## Akane (Jan 2, 2008)

Most doctors won't prescribe more than the 1 pill once a day. It might have some usefulness since it impacts more receptors than benzos but I actually switched from lunesta to various benzos. It's just way too hard to get a prescription for a high enough or frequent enough dose after I became tolerant to it in about a month. Getting higher than average scrips of benzos is easier than off label use of z-drugs.


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## Noca (Jun 24, 2005)

Akane said:


> Most doctors won't prescribe more than the 1 pill once a day. It might have some usefulness since it impacts more receptors than benzos but I actually switched from lunesta to various benzos. It's just way too hard to get a prescription for a high enough or frequent enough dose after I became tolerant to it in about a month. Getting higher than average scrips of benzos is easier than off label use of z-drugs.


I agree :yes


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## jim_morrison (Aug 17, 2008)

Ash09 said:


> Zopiclone has the same mechanism of action as the benzodiazepines, it's just a1 selective like quazepam.


Zaleplon and Zolpidem (and quazepam) are a1 selective but Zopiclone is not, it binds to a1, a2, a3 & a5.



> Between 1987 and 1989, the different protein subunits that make up the receptor for the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) were identified. (Bourin M., 2004) These make up the alpha, beta, gamma and delta families, for each of which exist several subtypes. This receptor is the molecular target of modern hypnotic drugs (i.e. benzodiazepines, zopiclone, zolpidem and zaleplon). Receptor subtype specificity of hypnotics has been explained in terms of differential affinity for receptors containing different alpha subunits, which are expressed in different brain regions. Zolpidem and zaleplon bind preferentially to alpha1-containing receptors, whereas benzodiazepines and zopiclone are aspecific.


http://www.who.int/medicines/areas/quality_safety/4.6ZopicloneCritReview.pdf


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## Noca (Jun 24, 2005)

jim_morrison said:


> Zaleplon and Zolpidem (and quazepam) are a1 selective but Zopiclone is not, it binds to a1, a2, a3 & a5.
> 
> http://www.who.int/medicines/areas/quality_safety/4.6ZopicloneCritReview.pdf


Zaleplon is the ****tiest sleep aid EVER! (in my experience)... an excuse for a Z-drug.


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## jim_morrison (Aug 17, 2008)

Dr House said:


> Zaleplon is the ****tiest sleep aid EVER! (in my experience)... an excuse for a Z-drug.


Yeah it seems to go Zolpidem > Zopiclone > Zaleplon in terms of effectiveness.


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## ZeroG64 (Oct 14, 2010)

Well, I've personally been using Zopiclone daily now over the past 2 and a half weeks and I think it is OK so long as you don't take too much. I don't just sit in front of a TV all day either, although having said that I wouldn't advice driving a car, I did and noticed I didn't have the greatest co-ordination.

I think 3.75mg x 3 over the day would be OK for most people but I'm not a professional. I have found it to completely remove my anxiety and make me more social than just about any other drug I've tried, and trust me that's an awful lot. 

I think the main problem with this drug is when the initial euphoria wears off it can bring about some bad judgement as you may feel like the drug isn't working (you feel sober) but it very much is, you could be tempted to take more than you should and this is when it gets a bit sketchy.

By all means be careful if you do choose to use this drug during the day, I have found it's helped me but I am not looking at it as a long term solution.


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## ugh1979 (Aug 27, 2010)

OK well that is interesting and I'm going to try it. If nothing else it will provide me with valuable information on effective lines of treatment for me. After talking about it yesterday here and elsewhere I brought 1x 3.75mg with me to work to try out at midday so will see how it works out for me soon.

I don't drive or operate heavy machinery so no worries there.


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## Area88 (Oct 4, 2010)

Well I used Zopiclone at 7.5mg for 4 months and it had terrible consquences on my body. The more I took it in the day, the more my short term memory was being damaged. I couldn't remember what I was doing, what I had said and my motor function was really, really poor. I couldn't remember whole days or weeks.

Long term use of Zopiclone, pretending it's Xanax, will only lead you to hospital in my opinion. I almost died becaue I had spread out my doses and took 8 over 16 hours, 2 off a fatal dose. My eyes were red when I woke up the next day and I could barely talk or walk, my breathing was really shallow as well.

Seriously guys, I warned ZeroG64 abou this. As you become more tolerant to the drug, the effects of Euphoria will wear off and your need more and more to get the same effect, eventually you will reach toxic levels that damage your memory and liver very dramatically. A fatal dose causes cardiac arrest. Look on the internet at all the celebrities that have died in the past, messing with potent sleeping meds.

I'll say it again, if you want short term Euphoria and GABA, get Xanax. You can use it for up to 8 weeks without any concerns for your health. If you want long term GABA, do whatever it takes to get Nardil (Phelezine).


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## ugh1979 (Aug 27, 2010)

Area88 said:


> Well I used Zopiclone at 7.5mg for 4 months and it had terrible consquences on my body. The more I took it in the day, the more my short term memory was being damaged. I couldn't remember what I was doing, what I had said and my motor function was really, really poor. I couldn't remember whole days or weeks.
> 
> Long term use of Zopiclone, pretending it's Xanax, will only lead you to hospital in my opinion. I almost died becaue I had spread out my doses and took 8 over 16 hours, 2 off a fatal dose. My eyes were red when I woke up the next day and I could barely talk or walk, my breathing was really shallow as well.
> 
> ...


I appreciate your concerns but I'm still going to at least give it as short trial run, just so I can see what it does for me personally, and so I can feedback to my psych in a few weeks the findings which may go towards helping in getting a script for benzos like Xannax.

Edit: I've just read that Xanax is not available on the NHS and can only be obtained on private prescription. That rules Xanax out for me then.


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## Ash09 (Apr 27, 2009)

ugh1979 said:


> Edit: I've just read that Xanax is not available on the NHS and can only be obtained on private prescription. That rules Xanax out for me then.


Not at all, any NHS doctor can prescribe alprazolam, you just have to pay privately for it, I pay £3.50 for my prescription.


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## ugh1979 (Aug 27, 2010)

Ah right, OK well that's good to know. Thanks.


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## ZeroG64 (Oct 14, 2010)

My GP didn't want to prescribe me Alprazolam, I'm not sure why but he seemed quite agaisnt it. He pretty much drove me to the Zopiclone by prescribing me a pathetically small dose of Diazepam instead and making a point of saying he would not be prescribing me anymore no matter what. 

Whether it is because I am currently on a program of Buprenorphine I'm not sure, but I ended up ordering some Zopiclone online because I knew how effective Zopiclone was with it's similar effects on the GABA receptor as benzo's (alleviating anxiety), even if it was not the appropriate choice (which it is not). 

I just want to say, please tread carefully with Zopiclone, it works very well but I've noticed it's addictive and as Area88 says it's toxic if you build a tolerance. If you have the willpower to use it in small doses and infrequently then it's all good, nice drug in that respect.

Xanax isn't good either, I've heard enough horror stories about Xanax withdrawals too and will probably end up thanking my GP in the long run for not prescribing it to me....


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## ugh1979 (Aug 27, 2010)

Yeah our UK GP's don't seem to be nearly as happy to prescribe benzo's as US docs it seems.

I tried 3.75mg Zopiclone yesterday at 1300 which had no effect, then again about 1900, but with again no effect. A few hours after that I called it a day and went to bed. I got a good sleep at least. 

I'll maybe try 7.5mg at some point to see if it has any anxiolytic effect but if not, I'll just keep it for what it's normally used for.


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## ZeroG64 (Oct 14, 2010)

I think that's probably the wise choice tbh. I have already caught a slight glimpse into the hell of what Area88 is talking about, I feel the pull of the drug, the psychological effect it is having on me when I've not taken for 24hrs; quite severe anxiety, my worst enemy.

No physical symptoms other than acid indigestion and very sensitive teeth, makes eating anything that's hard quite painful, I guess it's changed my body PH levels which has in turn affected the enamel on my teeth. That can't be healthy. It's very acidic, it actually feels toxic.

The most worrying thing about this drug is how good judgement goes out of the window, you can easily munch your way through several pills without even thinking twice about it, then wake up one morning and think "oh ****!, I have to go careful now!" etc. Short term memory is terrible too as mentioned, I can't remember most of the past few days. It's when you are sober you realise and think about it, then get depressed. Take a pill and it all goes away again.... an evil circle indeed.

I have 50 pills on their way to me and I plan to taper the hell off this **** asap. I'm afraid I have to admit I don't have the willpower to be sensible with this drug. 

Thanks for looking out for me Area88.


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## crayzyMed (Nov 2, 2006)

ZeroG64 said:


> I think that's probably the wise choice tbh. I have already caught a slight glimpse into the hell of what Area88 is talking about, I feel the pull of the drug, the psychological effect it is having on me when I've not taken for 24hrs; quite severe anxiety, my worst enemy.
> 
> No physical symptoms other than acid indigestion and very sensitive teeth, makes eating anything that's hard quite painful, I guess it's changed my body PH levels which has in turn affected the enamel on my teeth. That can't be healthy. It's very acidic, it actually feels toxic.
> 
> ...


Have you tried taking it with one of the racetams (piracetam, aniracetam, oxiracetam)? Ive read they can help with benzo (or simular drugs) induced cognitive impairment.


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## Area88 (Oct 4, 2010)

He just needs to get off it now, he sounds as if his body has already become very physically addicted to it. I've pmed ZeroG64. 

crayzyMed, he really just needs to get off the zopiclone and replace it with Xanax for now. If his doctor won't give it to him then there's something seriously wrong with the NHS. Find a different doctor or surgery if you have to. UK doctors are notorious for not listening to their patients.

He clearly needs to be a on a benzo and a long term drug like an MAOI. His story is very similiar to mine from a year ago.


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## nonbeing (Nov 20, 2010)

I have been prescribed Zopiclone a few times over the past couple of years. The doctor did emphasise to take *one* at night just before sleeping. I am currently finding this a godsend, as I wasn't sleeping at all and waking up exhausted and unable to function properly.

When I took more than one at once, I was getting gastrointestinal disturbances, probably my liver complaining, but feeling very sick, my whole gut seemed to slow down to a stop and passed nothing, and I couldn't eat. When I ate something, I was violently sick. I noticed that my urine turned a deep reddish-brown, of which significance I don't have a clue, wouldn't know how to distinguish bilirubin from porphyrins. I have recently been extremely careful to only take one at night, and still I get feelings of nausea, and my urine is dark reddish-brown whenever I use Zopiclone. That one dose just before sleeping does just that. When I was taking one earlier in the evening to quell anxiety it felt calming too, but taking more than one a night is a luxury I can't afford, and I am not even sure if my system will not allow me to continue to take even that one I use for sleeping.

I did find that using Zopiclone had an interesting effect of giving me a closer look at my own psyche and unconscious, and was giving me intense and interesting dreams, and pulling out of my mind old memories with all their sensory content, tastes, smells, feels. I suppose that blocking of anxiety for even a brief time gave me back what normal people have all the time, a sense of connection to their own being?


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## Area88 (Oct 4, 2010)

nonbeing, what you are describing is the normal effect of Euphoria for Zopiclone users. It does make you feel happier and more connected to yourself and the world. Unfortunately it's only a side effect and Zopiclone is dangerous and should never be used in the same way as Xanax.

If you are having problems, get Xanax for short term relief until you figure out a decent medication plan.


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## nonbeing (Nov 20, 2010)

Probably a silly question, but surely all the medicines that act on the GABA A receptor, from Zopiclone to Xanax, all act in the same way and have the same downside of swift tolerance build-up, and depression when you stop taking them?

I read a learned article which explained the connecton of GABA to autism, it really seemed to make sense, and also why no antidepressant has ever had any effect on me, except of course Zopiclone, which seems to be, for me at least, for short term use because it builds tolerance so fast.

I wondered what else hits the GABA A receptor without causing a lot of effects like tolerance?

And presumably if your intense anxiety symptoms are more part of you than depression, then antidepressants and no amount of serotonin would help, because it is the GABA system that is causing you such soul pain?

Can anyone link me to anything that shows how the GABA system links with other neurotransmitter symptoms? I need to get a clear overview of what is happening, the kind of thing jealously guarded by the dragon of respectable learned biochemical science against those of us who couldn't afford to do a proper degree.


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## Area88 (Oct 4, 2010)

nonbeing said:


> I wondered what else hits the GABA A receptor without causing a lot of effects like tolerance?


 The best drug to hit the GABA receptors is a drug called Nardil (Phenelzine) - http://en.wikipedia.org/wiki/Phenelzine

If GABA is your problem, then read as much as you can on Phenelzine aka Nardil.

It really is a wonderful drug, probaly the best, I had to stop taking it briefly because my GP thinks I may have bipolar and thats the reason I keep geting manic episodes but once thats under control, I will go back on the Nardil.


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## nonbeing (Nov 20, 2010)

Area88 said:


> The best drug to hit the GABA receptors is a drug called Nardil (Phenelzine) - http://en.wikipedia.org/wiki/Phenelzine
> 
> If GABA is your problem, then read as much as you can on Phenelzine aka Nardil.
> 
> It really is a wonderful drug, probaly the best, I had to stop taking it briefly because my GP thinks I may have bipolar and thats the reason I keep geting manic episodes but once thats under control, I will go back on the Nardil.


Thanks, I read your link. I have never taken an MAO inhibitor before, and not sure how kindly a doctor takes to being told by me the patient what to prescribe.

SSRI's do nothing for me, and I was wondering if anxiety is different from other kinds of depression. I was researching a bit about GABA and it does seem significant in autism, which is common in my (genetic, there was no contact during my childhood) family.

There are some websites advertising GABA itself, and I wondered if it can simply be taken orally without being broken down? One autism site was suggesting combining GABA with Magnesium Sulphate (Epsom salts, it can give you diarrhoea, but apparently can be absorbed through the skin if put in a bath). Apparently the sulphate part is just as important as the magnesium, which made me think of us soul-dead ones going down below the city's underground tunnels searching for Hades to give us back our souls.....

Sounds as though serotonin just isn't my issue at all. I have had intense uni-polar depression since childhood, I don't get manic or creative ever, I just feel as though my soul was murdered at a very young age and that I don't exist.


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## nonbeing (Nov 20, 2010)

Also as I was searching for information about GABA, I read that it is a major player in the formation (and playback?) of memories. This ties in with my experience of the comedown from Zopiclone, when I stop taking it I get flooded with memories through all the senses, such as smell, taste, and of course vision. Though intrinsically mostly horrible memories because my childhood was horrible, re-connecting with them feels good, though again paradoxically the comedown from Zopiclone, apart from this accessing of old memories in all their sensory details, does not feel good as I don't sleep for a few nights, feel very tense and as though I am shaking slightly all the time, if I am lucky just don't feel hungry, but was getting reactions of my digestive system seeming to stop completely and feeling and being sick, which I thought was my liver especially as I got this weird sign of my urine being dark red-brown. I recall being curled into a tight ball, unable to get on with my life, or to sleep, and when after a couple of days the effect lifted, I got a few hours' sleep and when I woke up and went to the loo, noticed that my urine was that dark colour, which it always is when I take Zopiclone.

(I wondered, as GABA is so linked to autism, and a high percentage of autistic people in some experiment tested high for porphyrins in their urine, and the porphyrins that poison porphyria sufferers block/somehow affect the GABA receptor which is how they cause their psychoneurological effects, and a lot of GABA agonist drugs are contra-indicated in porphyria, particularly benzodiazepams and barbiturates. Can't find any specific reference to Zopiclone and the other non-benzodiazepams with reference to porphyria, yet.)

http://onlinelibrary.wiley.com/doi/10.1002/ana.410020415/abstract
*δ-Aminolevulinic acid: Influences on synaptic GABA receptor binding may explain CNS symptoms of porphyria*

*γ-Aminobutyric acid* (*GABA*)


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## jim_morrison (Aug 17, 2008)

nonbeing said:


> which I thought was my liver especially as I got this weird sign of my urine being dark red-brown. I recall being curled into a tight ball, unable to get on with my life, or to sleep, and when after a couple of days the effect lifted, I got a few hours' sleep and when I woke up and went to the loo, noticed that my urine was that dark colour, which it always is when I take Zopiclone.


Be careful with that side effect, if you get dark or red urine from any medication then you should go to your doctor immediately as it can be a sign of something pretty serious.


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