Comment · Wed, January 27, 2021 · ND Owner
Herbal GABAergics and dependency
Original post in this thread
bejaq · 20 points
It seems that it's generally assumed that herbal supplements that work on GABA like gotu kola, skullcap, lemon balm, magnolia are not prone to causing dependency and withdrawal.
However there have been (relatively rare) claims to the contrary.
To be honest I am a bit concerned with the lack of information on this subject, and my intuition is that in the absence of contrary evidence, it should be assumed that substances that have similarities in receptor-action to benzodiazepines, alcohol, phenibut (if only by working on gaba) might be prone to inducing dependency and withdrawal.
Personally I like the feeling of benzos a lot and if there is safe alternative I certainly would like to take it more than occasionally.
It would be awesome to have a substance that helps the GABA system regulate itself better, and the complex pharmacology of herbs might be better suited to that?
But I feel it might be a little bit naive to believe that unless there is actual evidence for that.
It should be noted that when it comes to benzos and opiates, it took a long time and many people using them for the understanding of their true addictive potential to become clear, so that also seems good t…
What they were answering
chutney1 · 3 points
I have read that the prolonged excitotoxic shock from benzo withdrawal can lock the receptor in an inverse-agonist conformation, meaning it isn't accepting GABA as well any more. Any truth to this? I'm aware this is grossly over-simplified and probably downright incorrect but I possess no background in this sort of thing and no real apparatus for separating shit from shinola here.
Are changes to the conformation of the GABA receptor complex permanent? Can said changes be reversed pharmacologically somehow? What do you think the best treatment approach would be for someone who went through BZD withdrawal years ago but seems to be left with lasting cognitive dysfunction? What mechanisms should one be targeting to try to treat said symptom? Overall, my brain still struggles with basic memory, recall, etc. Often times I forget what I am talking about mid-sentence. I can no longer sing along with songs- I can't bring the lyrics to mind in time and when I try to sing along, I can only manage to do so with a line or two here or there. I used to be excellent at recalling songs; hearing them just a few times I could have 80% of it or so memorized. I also just generally have what I can only describe as "leaky brain." It's more or less okay when I get up in the morning but as I leave the house and get the day started, it's like my brain is just nonstop leaking glutamate or something be…
u/MisterYouAreSoDumb · ND Owner
I have read that the prolonged excitotoxic shock from benzo withdrawal can lock the receptor in an inverse-agonist conformation, meaning it isn't accepting GABA as well any more. Any truth to this? I'm aware this is grossly over-simplified and probably downright incorrect but I possess no background in this sort of thing and no real apparatus for separating shit from shinola here.
Yeah, there are structural changes that can change the default state of the GABA receptors. There are even ways to do the opposite, and have it block antagonists while also still allowing agonists. At least I know it can happen with the GABA-B receptor. Two cysteines can combine to form a disulfide bridge, locking the GABA-B receptor in its active state. I would assume similar mechanisms exist for GABA-A. You have to think about what happens with GABA receptors. When GABA binds to them, it opens the channel to allow negatively charged chloride ions inside, which results in inhibitory postsynaptic signaling. Over-activation of GABA can caused too much chloride to enter the neurons. It compensates for that by down-regulating the receptors, and can even down-regulate whole inhibitory synapses.
Are changes to the conformation of the GABA receptor complex permanent? Can said changes be reversed pharmacologically somehow? What do you think the best treatment approach would be for someone who went through BZD withdrawal years ago but seems to be left with lasting cognitive dysfunction? What mechanisms should one be targeting to try to treat said symptom?
Most things are not permanent, with the exception of actual neuron loss from too much excitotoxicity. Your body/brain has mechanisms to maintain homeostasis. It can just take a long time for some things to get back to normal. Targeting it is difficult, as we still don't fully understand all the systems at play. This is a good study on the long-term cognitive issues after benzo withdrawal.
Persistence of cognitive effects after withdrawal from long-term benzodiazepine use: a meta-analysis
It's a meta analysis, and doesn't go into mechanisms. However, it is an interesting paper. They do suggest there might be some permanent deficits, and others that take 6 months or more to recover from. I am not one to say something is permanent. I don't think much is permanent. However, there is certainly long-term and difficult to fix issues that arise from benzo withdrawals. There is evidence that getting back normal GABAergic function can help with the memory issues, though.
Restoring GABAergic inhibition rescues memory deficits in a Huntington’s disease mouse model
So things like L-theanine, lemon balm, magnolia bark, and even a good magnesium would be good. I know people that have had issues with benzos in the past might shy away from natural GABAergics, but balancing out GABA signaling is crucial to the memory recovery as well. Then I would probably try and hit BDNF, NGF, and CNTF. 7,8-Dihydroxyflavone, polygala, lion's mane, etc. would all be good. Hitting the electron transport chain wouldn't hurt, either. NMN, CoQ10, ALA, ALCAR, etc. might be something to try.
What all have you tried so far? What has worked some and not worked at all?