GHB neurotoxity at end of duration

[Nexus298]

I know that neurotoxicity of GHB has been discussed before, but I got to thinking. Even when you take a large (safer) dose, there is still a point when your body has eliminated enough out of your body to be at the lower more neurotoxic levels. I was wondering why this has been overlooked, or if there is something I'm overlooking.

 

[Epsilon Alpha]

I know that neurotoxicity of GHB has been discussed before, but I got to thinking. Even when you take a large (safer) dose, there is still a point when your body has eliminated enough out of your body to be at the lower more neurotoxic levels. I was wondering why this has been overlooked, or if there is something I'm overlooking.

If memory serves its mostly due to oxidative stress, so perhaps curcumin or CoQ10 could be useful in this case. Other than that, maybe DXM or magnesium to help combat the excitotoxic part of it. But, yeah I haven't heard anything about this before and it's a really interesting point.

 

[InsatiablePeace]

Well if I was to guess I would say you're going by past information that has been posted about the acute neurotoxic effects of GHB/GBL. Lower doses are far more stimulating and toxic wheras the higher doses are protected by significant GABAB activation?

But as you quite rightly say, once the drug leaves your body it's still going to be toxic via glutamanergic pathways. In fact I would guess the more you take the more you're going to crash and the worse the residual neurotoxicity will likely be. Maybe that's part of the reason we all feel like complete shit when coming down off it? (man I'm so glad I gave that shit up).

So what can one do in such circumstances? I have read of people using memantine and going via the NMDA route... Also stuff like curcumin isn't going to do any harm if you can tolerate it.

 

[lostie2342]

I just started taking Xyrem (GHB) for ideopathic hypersomnia/narcolepsy. I also take adderall. Viscerally and physically, it seems like somewhat a toxic mix those first few hours awake with the glutamate release. I know that PQQ, though not 100% clear, is considered neuroprotective especially against amphetamine toxicity. It also seems to protect against glutamate toxicity and even rescue hippocampal neurons from glutamate induced cell death, see here. But this says PQQ inhibits the free radical-generating response to glutamate by oxidizing the NMDA receptor redox site and not by scavenging reactive oxygen species. Also: "Under certain conditions, PQQ can lead to the formation of oxygen-derived free radicals, and we have previously observed that these reactive species can oxidize the NMDA receptor."

I'm just very confused if this would be the best thing for me or maybe the worst and accelerate oxidation. It would appear to be very good and possibly neuroprotective but trying not to take any chances.

More on GHB from my notes: known to cause oxidative stress via the glutamate system and damage neurons that express the NMDA receptor in the hippocampus and prefrontal cortex. Apparently is a precursor to an endogenous NMDAR antagonist. Heavier doses go easier on your neurons because of increased activation of GABA-B but as the dose wears off you get the after effects of what is left from the GHB receptor anyway (glutamate).

So since hippocampal damage/memory problems via excess gluatamate is how GHB/Xyrem does its damage, and PQQ has been shown to mitigate this -- it makes sense to take it to do so. And yet I can't find one word anywhere linking them or PQQ as a proposed antioxidant to prevent damage (this thread, which mentions Coq10, was the closest I found). Any insights on this would be greatly appreciated.

Edit: Also have found this which seems to corroborate my thinking: "There’s a lot more studies but glutamate Exicitotoxicty is mediated in the nmda receptor sites, and when gaba(inhibitory receptor) is decreased NMDA(glutamate receptor) releases glutamate and causes neruon death. This process can turn into Glutamate Excitiotoxicity which is a cascade of neuronal death throughout the brain, which is involved in many neurodegerative diseases. To help stop it NMDA antagonist are used. I have personally tried memantine months back but never tried it it long term, also PQQ is a natural substance that can help neurogenesis and also is a NMDA modulator."

However the exact actions of PQQ in these circumstances (either before xyrem at night, or more likely, in the morning just before/with adderall) I really have no clue if it still fits or would feed the existing oxidation.