Misc GABAergic resistant?

[Limpet_Chicken]

This isn't specifically a benzo question...so under misc. it goes.

It does apply to benzos though, amongst others.

But to a fair proportion of GABAa agonist sedatives, including alcohol to a degree, although not nearly so much as benzos, but benzos to a strange degree, I seem very resistant to being sedated to the point of being put out by them.

I am scripted nitrazepam, and have both temazepam and diazepam at my disposal, should I ever desire to use either. However, I rarely ever used any of them. I drink alcohol, but not excessively, and not daily, although do occasionally get lightly drunk a couple of times a day, for 2-3 successive days at most...occasionally..not regularly.

I don't really find benzos recreational, and alcohol, I enjoy it, in moderation, to the degree I get a light to moderate buzz from a portion of a bottle spirits (mainly drink gin, rum by preferance, occasionally vodka), and I like the odd beer now and then, scripted pregabalin also, although I don't use it daily, only when my neuropathy gets the better of me, or occasionally plug a few hundred milligrams recreationally.

So I think it most unlikely I have an existing benzo tolerance, or alcohol tolerance...yet I get nights sometimes when I just cannot sleep. Which is when I resort to using the nitrazepam (use the valium mainly during the day, very rarely, to stamp down on any autistic overload I get when that happens (I'm spesh, classically autie, so it comes with the otherwise brilliant package)

These odd nights with no sleep, taking up to, on some occasions, 80mg of nitrazepam, relaxes, but leaves me still wide awake, which considering the potency of nitrazepam, is quite shocking really for somebody with no GABA agonist tolerance.

Z-drugs are, having tried all three, ineffective, zopiclone is at RX doses, unnoticeable, almost completely, where sedative effects are concerned, larger doses are pleasant with opioids, adding some funky audio hallucinations and mild visuals, but thats about it. Zaleplon appeared no different to an inactive drug, and zolpidem....fuck....10mg had me tripping my arse off..apparently...leaving no memory of it whatsoever, and being told afterwards I was up all night talking utter random crazy shite to my then GF online.

Some GABAergics do work just fine, barb site agonists do, and muscimol (which is selective for the GABA binding site itself, puts me in a very deep, refreshing sleep, and induces very vivid dreams), and chlormethiazole does.

I at one point, did have a dependence problem from 1mg daily use of lorazepam for some months, prescribed, decided to taper off, did so too fast, resulting in voluntary, non-emergency, but incredibly unpleasant admission to hospital, after tearing a chest wall muscle due to the way I ended up doubled over with chest pains, and muscle twitching/spasms, temporal lobe seizure afterwards, otherwise no sequelae.

Been dependent on barbs and forcibly withdrawn with np adequate treatment (got banged up) but GABAa agonists for the benzo-sensitive binding sites have worked since, this was years ago.

Chlormethiazole works.

Long time since I have tasted any chloral, although 1,1,1-trichloro-2-methylisopropyl alcohol will be tried soon, can't really remember how well chloral worked as a sedative...its a funny one as far as EEG activity and sleep architechture go if I remember rightly.

So what the fuck gives....a nontolerant person should not be able to shrug off a whomping dose of nitrazepam or temazepam in such a manner, and be unable to sleep.

Those occasions that did happen, rectal doses of tizanidine were used, which had to be repeated frequently throughout the night, after waking repeatedly, each night this was the case, which is only occasional, with no predictable proceeding events, habits, actions etc. but repeated 10mg doses rectally (a pretty damn hefty dose by any standards, plugged, although I am somewhat used to the drug, taking a lesser dosage on a regular basis)

Also physically dependent on opioids, although at the moment tapering down, using MXE to do so rapidly, aided by pregabalin. These wierd events happened before this though, and at no time was I in withdrawal while trying to sleep, and indeed had both taken a stable dose of dihydrocodeine tartrate before going to bed, and a further dose on waking up during the night, so it was most definately not withdrawal from my pain meds, or pain itself (knee joint pain, tendonitis and neuropathy) causing this.

Any ideas what could make somebody so insensitive, who does not have a tolerance to these drugs? even normally on an average day, or night, I could take an entire 2 weeks script of nitrazepam, for instance, and remain completely conscious and aware, even if my memory would be shite afterwards possibly.

Only excitatory drug I use regularly is piracetam (I do sometimes use stimulants, but occasionally, for functional cognitive purposes, and the resistance appears uniform, timewise, including both these wierd sleep/drug resistant episodes, and normal seeming hardwired resistance to benzo/z-drug and similar sedatives acting on GABAa ion channel kinetics as benzos do (rather than similar to barbs or chlormethiazole, and completely unlike muscimol)

This was the case before I started back on racetams (after a long time having none available)

 

[Captain.Heroin]

You have already had a dependence problem with lorazepam. Because of this, you aren't probably ever going back to baseline benzodiazepine tolerance.

BTW, for those interested in knowing how benzo tolerance develops (I have 5 minutes to spare, so why not share....):

The GABA-A receptor is an ion channel which has an orthosteric site which binds GABA and a number of allosteric sites. When GABA binds to the orthosteric site the channel opens briefly allowing an influx of Cl- ions into the neuron causing hyperpolarisation (inhibition of neuronal firing). Allosteric sites bind modulators such as benzos which potentiates the channel-opening effect of GABA.

The ion channel consists of 5 subunits (pentameric); 2 alpha subunits, 2 beta subunits and a gamma subunit. The benzo allosteric site is at the alpha-gamma subunit interface, and it is here that benzos stick to the complex and in doing so, change the shape of the GABA-A receptor enough so that it is now more efficient at allowing Cl- influx, but only when endogenous GABA binds to the orthosteric site. What this means is that on their own, benzos have no effect; they need the endogenous GABA to have their effect (this is what makes benzos so safe on their own).

Benzo tolerance probably arises when the neuron attempts to counteract the benzos action by changing the protein subunits that make up the GABA-A ion channel. When there is no longer an alpha and a gamma subunit next to each other, the benzo allosteric site no longer exists. This explains why there is incomplete cross tolerance between barbs, z-drugs (like zolpidem), and benzos.

Class dismissed!

Due to the eventual loss of the benzo allosteric sites due to benzodiazepine addiction, it is unlikely that you will ever regain full sensitivity to benzodiazepines again.

Just look at how many "why isn't xanax/ativan/klonopin/valium working for me anymore?!?" threads there are in BDD/OD.

My advice to you is to not use ethanol, and to only use benzoidazepines once a month or even less frequently, to have near-full effects remain in place when you need them the most.

 

[burn out]

yeah once you get a benzo dependence you cant expect them to put you out again, ever.

 

[Limpet_Chicken]

Thats understandable...but if its the only reason, its quite surprising as to the extent, considering that the actual use period and amount wasn't great, compare to the extent of the tolerance, this wasn't a huge 'feeedd meeee' angry, half-starved baboon of a monkey on my back, but a couple of months at 1mg/d.

I don't drink really often anyway, maybe a few times a month, not every month. When I do, its perhaps 4-5 shots, although my personal measure as to what consistitutes a shot would probably could as several for some people. I don't drink every month, and at most its for a few consecutive day, barring the off 1, maybe two shots on isolated days otherwise, maybe buy one bottle of my preferred spirits, and finish a good deal within a few days, then leave it, near completely, other than if I choose to have the odd ice cold beer on a roasting hot, tiring day, and barely use the benzos, it has to be a huge dose if I do, but when I do? maybe twice a month, perhaps, possibly three times occasionally.

So my GABA agonist use isn't heavy, and the only recreational use, ever, is very, very seldom, to the extent of bioassaying novel substances once in a while.