• N&PD Moderators: Skorpio | thegreenhand

  • Neuroscience & Pharmacology Discussion Welcome Guest
    Posting Rules Bluelight Rules
    Recent Journal Articles Chemistry Mega-Thread
    FREE Chemistry Databases! Self-Education Guide

Do Z-drugs cause the same long-term cognitive impairments seen with benzodiazepines?

Z

Zilpe

Bluelighter
Joined
Apr 27, 2012
Messages
95
Question pretty much sums it up. I'm guessing they do due to similarity of action but a cursory google search doesn't lead to any conclusive answers. As a follow up how much is actually understood behind the mechanism of benzodiazepine related cognitive impairment? Is it due to a specific action of benzodiazepines or is it more related to the nature of sedative-hypnotics in general?
 
Zilpe said:
Question pretty much sums it up. I'm guessing they do due to similarity of action but a cursory google search doesn't lead to any conclusive answers. As a follow up how much is actually understood behind the mechanism of benzodiazepine related cognitive impairment? Is it due to a specific action of benzodiazepines or is it more related to the nature of sedative-hypnotics in general?
Click to expand...

It's quite likely to be as a result of the sedative-hypnotic nature.

For one, while the benzodiazepine is still active, the brain is not going to be 100%, inevitably. And since a lot of anxiety or recreational benzodiazepines involve taking them very regularly, inevitably you'll experience cognitive impairment.

As for how benzodiazepines cause cognitive impairments even after they are stopped, I'm not too sure about. Although the withdrawal process can be quite impairing in itself due to glutamate excitotoxicity and this might have something to do with it.
 
I guess the distinction I'm wondering about is if benzos cause direct cellular toxicity in some way (perhaps in the hippocampus?) or if it's more a result of brain "atrophy" from being chronically understimulated (neuroplasticity perhaps changing brain topology by wiring away from underused neurons). In the latter case you may expect impairments to be reversible. The latter case would also implicate pretty much all sedative-hypnotics as a cause of cognitive deficit as well but doesn't alcohol not share the same kind of cognitive impairments? I thought the damage from alcohol was more from either rebound excitotoxicity or vitamin deficiency (korsakoff's disease).
 
A little less I'd say, because Z-drugs are more selective for the alpha1 subtype responsible for the hypnotic effects, and it's not only the alpha1 but also importantly the alpha5 that is responsible for cognitive issues from benzos. So assuming that you are getting the equivalent action on alpha1 for your insomnia, the relative lack of alpha5 agonism may save you some cognitive impairment theoretically.

Chronic effects from damage as more indirect result is another matter though, and yeah several types of sedative use and cycling it with withdrawing may do a number on you.

Z-drugs were heralded as notably safer than benzos but you should be just as careful with them honestly.
 
I posted this in another thread today:

http://www.bmj.com/content/352/bmj.i90
Conclusion
The risk of dementia is slightly higher in people with minimal exposure to benzodiazepines but not with the highest level of exposure. These results do not support a causal association between benzodiazepine use and dementia.
Click to expand...
This meta-study says that benzos aren't linked to demetia

Plus this https://www.hindawi.com/journals/aps/2012/416864/
Zolpidem: 5-10-fold higher affinity for α 1 versus α 2/3 > 1000 fold higher affinity for α 1 versus α 5
Click to expand...
α5 subunit-containing GABAA receptors appear to be involved in learning and memory
Click to expand...
So even though α5 activation won't be the only cause of demetia/brain fog/bad memory etc. Z-drugs should be even 'safer' than benzos

Do you have any memory problems right now ?


And iirc benzos decrease brain glucose metabolism, so this, α5 activation and fucking with the glutamate system could be the cause of long term cognitive impairment
 
The Z drugs can be seen as a novel chemical skeleton which activates most of the same positive allosteric receptor sites as benzos (not all).. So basically effects, withdrawals, addiction and tolerance are pretty similar.

I took ambien nightly for like 2-3 years and my psychiatrist wanted me off of it so I tried some stuff like remeron, amitriptyline, etc and didn't like the after affects and so for the last 4-5 years I've been taking 20mg diazepam at bedtime instead of zolpidem..

I've tried to taper off valium like 4 times and I've always had seizures so I said fuck that I'll just keep taking it. Now I'm facing a situation where my wife is basically forcing me into in patient (even though I only fucked up once in over a year as far as relapse. I take all my psych meds as scripted, don't abuse any of them). At least it'll look good in court..

Honestly I'm most worried about letting go of some of my psych meds that've been the only thing keeping me for the last 6 years. I pretty much have to be willing to try if I'm gonna keep my family together, and I NEVER EVER don't want to be they for my daughter. My parents divorced when I was 2 (Same age as my daughter). I don't want her to grow up not knowing what a healthy family environment is like (something that I've never had)...
 
Why would you go to court? doesn't sound to me like there are the least grounds for legal action. And cannot you once you get to the physical location of the in-patient center explain that somebody is trying to force you for no good reason but personal disapproval, which is putting your health at risk. Has your use of either the diazepam or the Z-trash actually negatively impacted your ability to care for and be there for your spawn?
 
There must be some other type of anticonvulsant they can give you during your taper from diazepam? Pregabalin maybe? IDK.
20 mg is not that high, if you apparently are sensitive to getting seizures that sucks but you are not the first one to withdraw from benzos either. Luckily I never really seized when I got off benzos myself.

Possibly in-patient the medical care makes it all much safer especially if they are prepared for seizure activity.

Speaking for myself, I didn't abuse benzos either when I took them... but still I don't think taking Z-drugs or benzos regularly enough to become dependent is sustainable and would definitely not shrug off having to take such drugs daily. Eventually you just grow tolerant, then what do you do? If people didn't grow tolerant, then it's still a bit sketchy but I would be less concerned about it.

It also depends on whether you have alternative options for anxiety or insomnia.
 
Carbamazepine has proven effective for benzo withdrawal and I'm sure it will help with the seizures as well, other sodium channel blocker type anti-epileptics are around too.
 
To add something: Z-drugs, as opposed to benzos, are eliminated very quickly from the organism, and don't linger for extended periods of time. So that significantly decreases unneeded exposure time (when the drug's not "active" enough to produce needed therapeutic results, but still acting on the CNS).

As much as a sample size of 1 can provide in terms of info. I prefer zopiclone (~5 h half-life Z-drug hypnotic, but also anxiolytic) to benzos like diazepam, as I've never noticed any cognitive decline with the zopiclone, which is important to me as my job requires cognitive work.
 
The short half-life is the thing I despise second-most about Z-drugs actually. They are piss-weak to begin with and even if they DO anything then its gone before it even starts, more or less. Redose and its just more of the same. In, out, in out, don't even get to shake it all about. Z-drugs are just a tool for doctors who have a personal hatred of dispensing benzos under any circumstances to give some kind of alleged sedative to patients so miserable they just will not take 'no' for an answer. They are piss poor excuses for dog muck in tablet form. Like such benzos as chlordiazepoxide, diazepam or oxazepam are to the oldschool sedatives like barbs, chlormethiazole, chloral, bromethiazole and maybe even tert-pentanol.

To make it a sample size of 2. Zolpidem takes a huge shit on cognition, but not for an extended period, but it also causes weird fucking shit hallucinogenic effects, visual and auditory, zopiclone doesn't impair cognition nearly as much as zolpidem, and its got, in my experience, next to zero sedative or hypnotic effects, sod all in the way of anticonvulsant effects that I can discern (prone to seizures, still have had them whilst on these garbage drugs)

As for zaleplon, I'm not even going to bother speaking of it. It is simply that completely, totally and utterly inert. Couldn't make a mouse less prone to slight twitching of its whiskers, much less fucking well put it to sleep for five minutes.
 
Last edited:
The short half-life is the thing I despise second-most about Z-drugs actually. They are piss-weak to begin with and even if they DO anything then its gone before it even starts, more or less. Redose and its just more of the same. In, out, in out, don't even get to shake it all about. Z-drugs are just a tool for doctors who have a personal hatred of dispensing benzos under any circumstances to give some kind of alleged sedative to patients so miserable they just will not take 'no' for an answer. They are piss poor excuses for dog muck in tablet form. Like such benzos as chlordiazepoxide, diazepam or oxazepam are to the oldschool sedatives like barbs, chlormethiazole, chloral, bromethiazole and maybe even tert-pentanol.

But if its for sleep, and you want something to pack a good degree of hypnotic effects as well as sedation but do not want the drug to leave you monged out the next day, fuck Z-drugs, they are garbage. Bugger benzos, too weak, cognition impairing, as some Z-drugs to some people are.

Go for, and I confess I do rather write hymns to it that I may sing them from the rooftops, but chlormethiazole (or bromethiazole if your chem-handy. Do be aware if making them yourself that neither drug appreciates strong bases and will easily hydrolyse in same. And the bromo homologue is less stable than chlormethiazole but both are properly and fully active, of intermediate duration, and really do pack a whallop, STRONGLY hypnotic as well as sedating, damned powerful stuff. Do NOT drink alcohol with it as it inhibits alcohol (not aldehyde, it won't make you sick like disulfiram) dehydrogenase and makes it very easy to reach the stage of acute alcohol poisoning. Safe to drink the day after if not still on it (I.e take in the )

, fine to drink the next day which makes me think it could perhaps be a substrate for alcohol dehydrogenase, or maybe a reversible inhibitor. But whilst on it its a dangerous, very dangerous combination.

Doesn't last too long, and one always wakes up perfectly clear headed and lucid. No hangover whatsoever, but it nevertheless is extremely effective, you could probably tranq a moderately sized horse using heminevrin. Actually it surprises me how effective it is given how damn clean it is.

As long as dosage is enough (considering duration of action) its also both pretty effective at preventing seizures (mine are either of the pure myoclonic type or myoclonic turning into atonic), and when I actually HAVE a seizure, the moment I get my shit together enough to get a dose down the hatch then as soon as some is absorbed then it reliably brings me out of it. And at that, its pretty damn fast acting, since the medical form comes either as the ethanedisulfonate salt in syrup form, although this I have never had, or flexible, fairly thick-walled gelcaps full of chlormethiazole base, they break open quickly and take effect fast.
 
At what doses have you tried zopiclone? It's definitely hypnotic for me, and it's not only to fall to sleep (like zolpidem which indeed can be very on the short acting side), but fine to stay asleep in my experience. Enough to consider not taking it at too late a time in the night.
I do prefer zolpidem though, if only because the dysgeusia of zopiclone is absolutely terrible.
Have had zopiclone powder on hand for many years rationing it as it slowly ran out. I'm down to the last crumbs.
 
I somewhat doubt it. The Z drugs don't last for very long, and by-and-large only hit one sub-unit of the benzodiazepine receptor (a1).
 
I've had a two week script's worth (forget the exact dose per intended, scripted dose) in hours. And its just piss poor.

And when given, after asking for something to help me sleep whilst in hospital for something (a physical, rather than CNS issue), a 7.5mg dose of zopiclone, it was completely, and absolutely without the slightest effect. Inactive. Quite honestly, the only way I have ever, ever had effects from zopiclone, is when combining high doses (2 weeks worth of script for the zopiclone) with a nodding dose of opioids, in which case it added pleasantly to the experience in that it caused some weird ass auditory hallucinosis, every so often; and at random intervals I'd hear a volley of funny ass sounds that wouldn't at all be out of place in those old hanna-barbera cartoons, and loony toons, e.g 'boiiiing' (sound of a cartoon giant spring being stretched to near break point then let go at both ends), something that sounded like a slinky being dropped down a ladder made of an oversize water bed, sounds that resembled a whip being cracked, volleys of gauss pistol/moderate powered gauss rifle shots hitting wood and thin sheet metal, and fruit being hit by a 'dum-dum' slug fired from the same, exploding into pulp. Weird twangings, zingings, sudden !POP! noises, that would often bring me back out of my nod, although only for short time, startled out of it when I began to really relax into it.

Weird shit. But otherwise, I've found zopiclone to be empty of effect, and zaleplon utterly inert under any circumstances and any dose whatsoever. And it wasn't even up to doing sweet fuck all on a barbeque masturbating with a frozen jellyfish for very long. Garbage the both of them. To be honest I'm really on the fence as to whether I would even cross the street to piss down the throat of zolpidem were its heart on fire.

The Z-drugs thus far have proved to be, in a word, complete fucking shit.
 
You must log in or register to reply here.
Top