Discussing GHB's induced brainzaps and absence seizures

[MeDieViL]

Especially the brainzaps are a issue for many; personally i have noted that amphetamine blocks them and that serotonine antagonists like mirtazepine make them significantly worse; ive long pondered about this issue but this will provide some insights.

The first in vivo effects of GHB were described in 1964 as hypothermic, hypnotic, anesthetic, and anti-convulsant, and without marked respiratory depression or toxicity (Laborit, 1964). Since that time, the mechanisms underlying many of these effects have been further examined and elucidated. For example, as one of the initial and continued therapeutic interests in GHB centered around its potential to induce specific stages of sleep, many early studies focused on examining the electroencephalographic (EEG) effects of GHB. GHB and GBL (at 50–200 mg/kg) produced EEG patterns similar to those observed during slow wave sleep and absence seizures in rats (Winters and Spooner, 1965; Godschalk et al., 1977). The dopaminergic and opioidergic systems were initially implicated in the EEG effects of GHB because the absence seizure-like activity of GHB was blocked or reversed by d-amphetamine and naloxone, respectively (Snead, 1978; Snead and Bearden, 1980). However, later studies showed that selective GABAB receptor antagonists attenuated GHB-induced changes in EEG activity and decreases in firing rate and burst activity of dopaminergic neurons (Snead, 1996; Erhardt et al., 1998). Thus, it is likely that GABAB receptor-mediated inhibition of neurotransmitter release by GHB and baclofen is responsible for the absence seizure-like activity of these two drugs (Banerjee and Snead, 1995). Indeed, 100 mg/kg GBL did not result in absence seizure-like activity in transgenic mice that lack functional GABAB receptors (Kaupmann et al., 2003). Moreover, the GHB antagonist, NCS-382 has not always antagonized the EEG effects of GHB or baclofen, suggesting that GHB binding sites do not play a substantial role in mediating these effects (Snead, 1996; Erhardt et al., 1998; Tremblay et al., 1998).

The gabab agonism decreases glutamate; now here's the interesting part; amphetamine releases glutamate overwriting this decrease in glutamate and mirtazepine reduces glutamate trough 5HT2A antagonism wich is a glutamate releaser.

A intervention for this problem would either be downregulating GABAB however that may change its rewarding effects; or adding something that increases glutamate but that has excitoxiticy as issue.

After some thinking i came up with the idea of the addition of aniracetam; it releases glutamate while also blocking excitoxiticy.
Aniracetam also improves cognition and could counteract impairment caused by GHB.

Thats the post for the day; ive discovered alot the recent months i was away and beleive i may have a solution for many major problems; however skeptism is at its place; so slowly ill explain a idea to see ppl's results and that way really do what bluelight stands for; harm reduction.

 

[MeDieViL]

Perhaps (with enough protection as mini doses are more excitoxic because they pretty much are selective for GHB) a microdose with a low dose benzodiazepine could be a interesting alternative.

 

[Transform]

Are aniracetam's glutamate release and excitotoxicity blocking also found in other racetams?

 

[MeDieViL]

Im only sure about aniracetam; excitoxiticy is caused by oxidative stress and racetams are potent antioxidants.

 

[Transform]

Several drugs in the racetam family have been reported as producing ampakine effects, but while this has been well established for some compounds such as aniracetam and pramiracetam, it is unclear if all of the racetam family act in this way, as the racetam drugs appear to have multiple modes of action.

Could antioxidants like ALA and vit E + C go some way to help too if it's oxidative?

v I've been fortunate enough never to have experienced zaps etc, despite using once or twice a week at the most and using G for sleep on occasion.

 

[MeDieViL]

Could antioxidants like ALA and vit E + C go some way to help too if it's oxidative?

Yes they would help; but they wont help the brainzaps or convulsions.

 

[atrollappears]

excitoxiticy is caused by oxidative stress

I think they are related phenomena in some ways, but I don't think excitotoxicity is caused by oxidative stress. They're separate issues.

Also, I like this glutamate idea and and from my limited knowledge I think it's more plausible than other neurochemical conjectures about brain zaps, although it could be just related to serotonin activation/lack thereof. GHB increases serotonin turnover, mirtazapine obviously blocks serotonin, and amphetamine actually induces serotonin release (through indirect mechanisms, I think).

 

[MeDieViL]

Alteration of GLUR2 expression in the rat brain following absence seizures induced by gamma-hydroxybutyric acid.
Hu RQ, Cortez MA, Man HY, Wang YT, Snead OC 3rd.
Source
Department of Pediatrics, Faculty of Medicine, University of Toronto, Toronto, Ont., Canada.
Abstract
We explored the involvement of the glutamate receptor subunit B (GluR2) in the mechanism of absence seizures induced by gamma-hydroxybutyric acid (GHB). The expression and distribution of GluR2 protein in rat brain were examined during and after GHB-induced absence seizures. The data indicate that GluR2 protein expression significantly decreases following the onset of absence seizures. The suppression of GluR2 expression was prolonged and it outlasted the duration of the continuous absence seizure activity. The alteration of GluR2 protein levels was accompanied by a re-distribution of GluR2 expression from laminae V to IV in cerebral cortex. We also analyzed the duration and latency of absence seizures induced by GHB 72 h following an initial GHB-induced absence seizure, a time when suppression of GluR2 protein was maximal. The second absence seizure was significantly more prolonged than the first. These data may indicate that the putative down-regulation of GluR2 following GHB-induced absence seizure could have contributed to the potentiation of subsequent seizures in animals. A related hypothesis posed by the data is that down-regulation of GluR2 is involved in the mechanisms of the maintenance of recurrent absence seizure activity once it is initiated and therefore, may contribute to the chronicity of seizures in absence epilepsy.

not many comments very tired... either way its far more complex then my first post made it look like; but GHB is excitoxic and can induce toxic seizures wich cause permanent alterations in several related receptors; i did find ways to reverse those changes.

I cant take any GHB anymore without it causing brainzaps or even a abscence seizure if im not very carefull; not very pleasant.