Reason for lack of amnesia with GABAb agonist?

[Nexus298]

I have had a prescription to Xyrem (GHB) for about 6 months now. One thing has stuck out in my mind. I never have even the slightest bit of amnesia when taking it. For everyone who's taken G before you know how fast, and without warning you can fall asleep. I will be watching TV some nights when I take the Xyrem and the next morning I can go on my DVR and tell exactly when I fell asleep because I remember everything on the show until the moment I fell asleep. There is no memory loss at all. How is it that your GABAa receptor causes blackouts while GABAb doesn't? I know this is an oversimplified way of looking at it but I was under the impression amnesia from compounds working on GABA happened because of the inhibition of your Glutamate receptors being able to form new memories.

I know that Xyrem also works on the GHB receptor, but for since phenibut also lacks amnesia I don't think it is pertinent to the lack of amnesia.

If anyone could shed some light on the subject it would be greatly appreciated.

 

[Limpet_Chicken]

I think, that responses will vary per person as to amnesic effects of GABAb agonists.

In animals at least, GABAb agonists are used in research, alongside muscarinic acetylcholine receptor, AMPA/NMDA antagonists, mecamylamine and some alpha2 adrenoreceptor agonists (the latter have varying effects on memory, at varying doses, depending on subtype selectivity amongst other things, and doses causing heavy sedation vs inhibiting the effects of adrenergic drugs in causing hyperactivity/crappy attention span)

GABAb agonists can cause blackouts...look at GHB...its known for knocking people out in doses not much above a fair sized recreational dose.

GHB receptor agonism should be pertinent to amnesia IMO, activation by selective GHBr agonists is excitatory, via increased glutamate release. This actually makes GHBr agonists pretty excitotoxic. A glutamate release inducer in combination with a drug acting via GABAb to reduce glutamate release, logically will counteract that effect, to an extent correlating with the ratio of GABAbR-induced retardation of glutamate release vs GHBr agonist-related stimulation of glutamate release.

GHB has a biphasic mode of action also, its affinity for the GHB receptor is far greater than that for the GABAbR, meaning lower doses (or the quantity remaining after the levels decrease from a concentration sufficient to stimulate GABAb receptors (thus reducing glutamate release and providing temporary at least, protection from excitotoxic damage) preferentially activate GHBrS rather than GABAb, which much higher concentrations of GHB are needed to activate.

I believe, given some research published showing strongly excitotoxic properties of low-dose GHB, that it is a dangerous drug, regardless of how responsibly, as regards abuse/physical dependence-inducing levels of use, and that it will be neurotoxic regardless, and indeed more so if low doses are taken. I won't touch the stuff, ever again (I was screwed over by my abuse of it more than once, severe withdrawals, but now I refuse to take even a single recreational dose, after reading that..excitotoxic damage often is irreparable)

 

[Nexus298]

I'm prescribed to Xyrem and take it every night. I don't really get much of a recreational feeling to it, I use it as directed 3.75 grams 2x a night. It works as a miracle drug for me. For the past 10 years I have needed 12+ hours of sleep a night and even then was dead tired all day. The only remedy was dexedrine, but with natural anxiety taking stimulants just made me on edge 24/7. Now I have Xyrem and I sleep 7-8 hours and have tons of energy, without the use of stimulants.

I have never had an instance where I blacked out and didn't remember what happened like on a benzo or GABAa working drug. It makes you fall asleep almost without warning if thats what you mean by black out. But I find that I remember everything crystal clear until I spontaneously fall asleep.

I was incorrect in my assumption the GHBr action was insignificant though. The increased glutamate would counteract the GABAb inhibition. But there is still the example of Phenibut, I find that it relaxes me as much as something working on GABAa, except without the sloppiness and forgetfulness.

I realize the reasoning behind neurotoxic effects at low doses, but taken as directed Xyrem has made my quality of life immensely greater.

I have noticed a down-regulation of my NMDA receptors though, 5 mgs of Methoxetamine has the same effects on me now as 20 mgs did when I first started my Xyrem treatment.

 

[Limpet_Chicken]

I wouldn't be too confident that all it is capable of doing is downregulating receptors via excess glutamate. There is a VERY fine balance between a little extra floating about which the systems in place to remove/metabolise it are capable of dealing with, and between a large influx of calcium into neurons, specifically in the prefrontal cortex and hippocampus where a large density of AMPA and NMDA receptors are expressed, which ends up tearing neurons to shreds.

I found phenibut to be really sloppy and like feeling very, very drunk, only without the same sort of cognitive cloudyness. Likewise with the quite selective agonist baclofen (have loads of the stuff around, was scripted it for ages, but rarely ever took it, as it was utter shite for dealing with the back pain I have been having to deal with, until I recently got switched to pregabalin, much more effective for me)

As far as blacking out goes, I wasn't applying it to medical doses, although the close to 4g you say is enough to make me pretty euphoric and messed up. But full recreational doses, I meant, that there is a very steep dose-response curve, just right=high as a kite, a bit too much over that=nausea, dizzyness, vertigo, and throwing up all over the place, more than that by a little bit=out cold sat on the crapper, bottle of GBL beside me, (now former by several years) kicking the door off its hinges, after an unknown time elapsing, but obviously enough time not responding to whatever was said to make damn sure it was too long for even the worlds worst case of constipation to take a shit

with benzos, temazepam in question, after a huge, huge quantity, can't remember prescise amounts, but the quantity I at the time, was scripted for a month, almost, I remember a fair bit of it, yet the myorelaxant effect at that dosage was substantial enough to lay me flat on my back, unable to even sit up, fucked off my face. Likewise after 60-70mg nitrazepam I was sedated, heavily so, on one occasion such a dose was taken, no tolerance was present, as no GABAergic drugs were used even weekly, save for the odd 10-20mg of diazepam or 20-30mg temazepam, once in a while for a sleep aid (no recreational doses), and I chose to go to sleep, wasn't knocked unconscious, but just very inclined to finally sleep.

People vary, hugely, in their individual responses to drugs.

 

[negrogesic]

Dose dependent...............drugs lke GHB can cause marked amnesia.........True, these drugs are anecdotally less notorious amnestics, but do possess this property.

 

[Wizzle]

Funny, I was wondering this exact same thing today :D

In my personal experience, GHB only causes amnesia when going in and out of consciousness, which really isn't that different from the kind you get when being half awake and falling asleep again. Where benzodiazepines can cause significant amnesia in myself even at quite reasonable dosis, GHB doesn't do this at all. Midazolam is especially notorious. Even alcohol is a lot more amnestic then GHB in my experience, and I have never had a huge blackout from alcohol.

On the biphasic action: I read somewhere (can't find where, sorry) that Dutch anesthesiologists where very much against using GHB in anesthesia because it's action is unpredictable. In some countries it is used frequently in childbirth.

 

[Wizzle]

@Limpet Chicken

3.75 grams is higher then most people take recreationally when not already tolerant to it's effects. It can be considered a full recreational dose.

 

[Limpet_Chicken]

I am aware of that, I consider 3-4g to be about right as a recreational dose, at least I did, when I was willing to use it at all.

I have, unfortunately, extensive experience with GBL and GHB, although my use was very much more with GBL than GHB, don't get me wrong, I have been through perhaps half to 3/4 a kilo of the stuff, but in the case of GBL, a few liters of the stuff, so I know about dosing the stuff alright...

My main mode of use was rectal GBL...hits fast, and hard, within minutes, but as I said, I won't use it now, at any dose. My concerns about the excitotoxic potential preclude it from my drug 'menu' completely.

 

[Nexus298]

Never had the opportunity to use GBL or even street GHB for that matter. All my experience has been with Xyrem. Even with the tolerance incurred from using it everynight twice at 3.75 grams I usually can't last more than 45 mins without falling asleep. I get the slightest euphoria off of it but nothing like a benzo euphoria.

The lack of cognative cloudiness is what I am most intrigued about. It just seems like it should create the same disruption of memory and clarity of thought that GABAa acting compounds create.

As stated by Limpet chicken though individual responses vary greatly. Phenibut for me creates a calm relaxed state without the interference of thought pattern. IMO GABAb agonist would be much more suited for anxiety disorders in those that it doesn't disrupt their thought patterns as much as GABAa.

@Wizzle even when losing consciousness from GHB I remember even the last few second before I fall out. Last night I was reading something very interesting online and ignored the impending signs that I was about to fall out. In the morning I remembered everything I had read prior to falling out and could even pick out the sentence I had left off on.

 

[Limpet_Chicken]

I get NO benzo euphoria, only have perhaps once or twice in my life, with massive doses of temazepam or nitrazepam.

Phenibut, for me, only acts the day after its taken, and makes me feel very drunk, more clearheaded, without the NMDA antagonist signature of alcohol, but swimmy-headed and pissed as a fart, didn't like it, took a full day to kick in.

Wasn't street GHB I used at the time, so purity/dose can be guaranteed, taken as recrystallised powder/crystalline GHB, or as neat GBL up the..well..enough said

 

[Wizzle]

I don´t think you can measure this yourself. I can remember several instances where I remembered exactly when I was gone and then others would tell me I did things I couldn´t remember.. With GHB the amnesia I have had would not feel like a blank, to me, it really didn´t exist at all.

@Nexus
The idea that benzo's would be more euphoric then GHB sounds crazy to me, but anything is possible. GHB does seem to be less 'stupid' then benzo's and alcohol.

 

[bignbrown]

gbl/ghb are far more europhic than benzos, but once you've abused them enough the europhia goes.

Benzos can give me europhia sometimes in a very anxious situation.

Gaba b agonists do cause amnesia if you over do it, but its different than a booze/benzo blackout. I once took far too much gbl whilst out with friends and just woke up at his house, apparantly was just falling over and having mini seizures, and repeating words, weird