GABA A3/4/5, inflammation and mitochondria

[Ciprofloxacin]

Glad to see talking and reaserching about gaba. Gaba plays a big role in our pathogenesis. We need to upregulate naturally
allopregnenolone and alpha4 gaba receptor subunit. Chronic SSRI downregulate both ( while acutely upregulate allpregnanolone biosynthesis).

Hey, I had seen many articles that saying it increases allopregnanolone, but never saw opposite of it. Can I look some of that articles please?

[R3m3dy]

See my introduction here viewtopic.php?f=14&t=2481

As per my introduction, I suffer permanent effects to my cognition from cannabis consumption as an adolescent. This was before I ever took SSRIs. Cannabis consumption in adolescence affects the GABAa receptors https://www.nature.com/articles/s41598-017-11645-8

If effects on GABAa through SSRI consumption plays a role in PSSD, is it possible that I made myself more susceptible to PSSD through the previous impact of cannabis on GABAa?

I also touch on pregnenolone in my introduction.

[Zolofthater420]

I think you are pointed in the right direction.

https://naturalsupremacy.com/2018/06/08 ... -lower-it/

So, what are the strats to get GABA back to normal? Do we have too much or too little of GABA?

The symptoms in this link above point out, that we maybe have to much of them.
So should i give it a try in lowering it?

I would use Gingko biloba, Snus(Nicotine), Zinc, Aspirin and maybe smth. more.

[Jaxx]

so ive been reading the kudzu topic here and noticed it is also mentioned as " having properties of" gaba antagonist, next to muira puama, which gave me a clear window in the past. Quick search also shows SJW having GABA inhibition properties.
anyone ever looked in or tried real gaba antagonists?

[Jaxx]

Maybe i totally missed the post in the past, but i was not aware that GABA inhibits dopamine..

https://www.ncbi.nlm.nih.gov/pubmed/6137869

The article mentioned by Juvo indeed seems to tick many boxes
https://naturalsupremacy.com/2018/06/08 ... -lower-it/

In fact alot of possible drugs discussed recently seem to decrease Gaba, e.g. imipramine https://www.ncbi.nlm.nih.gov/pubmed/1965914

[Ciprofloxacin]

Good. I just say one more thing.

You can't inhibit the GABA signalling with every substances when it's being activated by neurosteroids.

6. Not all antagonists at GABAA receptors antagonize
allopregnanolone and THDOC
Several studies have found that the benzodiazepine antagonist
flumazenil does not antagonize steroids that positively modulate
the GABAA receptor. For example, it has no effect on allopregnanolone’s potentiation of the GABAA receptor current according
to patch-clamp studies of hippocampal cultures [3], and in vivo it
does not antagonize allopregnanolone-induced hyperphagia in
rats [56], or pregnanolone discriminative stimulus effects in
Rhesus monkeys [26]. Similarly, in humans flumazenil does not
antagonize the reduction in saccadic eye velocity induced by
allopregnanolone [5]. However, at least one study has reported an
antagonistic effect: that flumazenil antagonizes allopregnanolonedecreased probe-burying in female Wistar rats, and thus apparently counters allopregnanolone’s anxiolytic effect in them [25].
The ethanol antidote Ro15-4513 is a weak benzodiazepine
antagonist that in vivo does not antagonize the contextual learning
disruption caused by allopregnanolone in C57Bl6 mice [22].
However, in vitro the allopregnanolone potentiation of the GABAA
receptor current has been shown to be antagonized [3].
In contrast, GABAA receptor antagonists directed against the
GABA site, like bicuculline, or chloride channel blockers such as
picrotoxin, or the GABAA receptor negative allosteric modulator
pregnenolone sulfate block both the effect of GABA and
allopregnanolone/THDOC potentiation of the receptor [45,42,29].
Use of such substances in vivo is dangerous as blockage of the GABA
effect at the GABAA receptor leads to over-excitation with
induction of seizures. This highlights the need to use GAMSAs,
i.e. specific neurosteroid antagonists that do not affect GABA
responses, when attempting to inhibit cognitive deficits or other
adverse conditions mediated by allopregnanolone, for safety
reasons.

But I think, rather than dealing with GABA, we have to be solve what's the cause of its change. For example, as I posted about ammonia:

Allopregnanolone and THDOC have both negative and positive actions. Allopregnanolone can impair
encoding/consolidation and retrieval of memories. Chronic administration of a physiological
allopregnanolone concentration reduces cognition in mice models of Alzheimer’s disease. In humans
an allopregnanolone challenge impairs episodic memory and in hepatic encephalopathy cognitive
deficits are accompanied by increased brain ammonia and allopregnanolone. Hippocampal slices react in
vitro to ammonia by allopregnanolone synthesis in CA1 neurons, which blocks long-term potentiation
(LTP). Thus, allopregnanolone may impair learning and memory by interfering with hippocampal LTP

Many details of the pathophysiology leading to encephalopathy remain unclear. The pathogenesis of minimal hepatic encephalopathy is believed to be similar to that of overt hepatic encephalopathy, with increased ammonia levels derived from enteric bacterial flora playing a key role. This leads to astrocyte swelling, which may result in brain edema, increased intracranial pressure, and brain herniation.9 Astrocytes are the only cells in the brain that are able to detoxify ammonia. They contain glutamate transporters that are downregulated by the high ammonia level, leading to abnormal glutamatergic neurotransmission.10 Moreover, within astrocytes, glutamate combines with ammonia to form glutamine, which is responsible for astrocyte edema, reactive nitrogen, and oxygen species production.11 Neurosteroids are synthesized in the brain mainly by astrocytes, and are suggested to play a role in the pathogenesis of hepatic encephalopathy. Ammonia also induces upregulation of peripheral benzodiazepine receptors, which results in increased synthesis of neurosteroids, which bind to gamma-aminobutyric acid A receptors and cause neuroinhibition.12

I got serious gut problems since pssd and they are worsening too by time. Actually that's nearly worse problem than PSSD because I can't never stay in the class for 8 hours without making noises I will try lactulose because of this.

[Jaxx]

But I think, rather than dealing with GABA, we have to be solve what's the cause of its change. For example, as I posted about ammonia:

I wonder. Of course scientifically there is a great need to understand what would cause an increase in Gaba in the first place.
But looking at several cures, protentially they simply broke a reinforcement mechanism, and reset the balance somehow.

Enough potential for me to trial and error a bit with this line of reasoning anyway. Will likely combine Muira Puama and prami next week in my cycle.

[Jaxx]

dhm is something being discussed to antagonise/modulate gaba at hackstasis forum.
some interesting reading;
http://www.sobur.co/dihydromyricetin
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3292407/

[Jaxx]

just wondering, many here feel better after alcolhol (alcohol withdrawal). do people feel the same after taking a benzo?
I took 1 mg clonazepam yesterday, but so far didnt make me feel better or worse, but could still be in my blood atm.

[Mesolimbo]

PSSD gave me bad excessive daytime sleepiness, sleeping up to 21 hours a day. My pdoc prescribed methylphenidate which wasn't enough to offset this sleepiness, so I also came to the conclusion that my GABA receptors are dysregulated.

I tried Clarithromycin for a short while, it's a GABA-A antagonist. This was enough to keep me awake but eventually made me very depressed. My pdoc was also afraid of potentially serious long-term side effects (liver, kidney, heart etc), so she told me to stop taking it at once.

GABAergics like benzos make me very anhedonic the next day and ones like valproic acid (used it as a HDAC inhibitor..) made me so depressed.

I came to the conclusion that I have a major glutamate-GABA imbalance, caused by excessive progesterone -> allopregnanolone through chronic Venlafaxine intake.

Ciprofloxacin, do you also suffer from unrefreshing sleep? no matter how much I sleep, I wake up feeling sleep deprived.

N.B. several brain MRIs were also normal.