Comment · Tue, January 26, 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
Direct reply to the original post — see the thread post above.
u/MisterYouAreSoDumb · ND Owner
The mechanisms behind dependency and withdrawal are complex, and we often simplify affinities down too much. One substance acting on GABA-A can be totally different than another acting on the same receptor complex. If you look at the 3D representations of compounds binding to receptors you will see what I mean.
Here is the GABA receptor complex.
Here is a long paper about the GABA-A receptor.
So I think many people don't realize the complexities in these receptors and systems. They see GABA or GABA-A and assume they are more simple than they are in reality. Take magnolia bark for instance. Magnolol and honokiol are positive allosteric modulators of the GABA-A receptors, showing particularly high efficacy at δ-containing receptors. Benzodiazepines are also positive allosteric modulators, but have their own binding site between the α and γ subunit. So if you were to just see GABA-A and positive allosteric modulator, you might think magnolia bark and benzodiazepines act the same way, but they don't. The α1 containing GABA-A receptors have been shown to be crucial in the dependence seen in some GABAergic compounds. In fact, some pharma companies are developing non-dependence-forming alternatives by leveraging that knowledge. It also explains why benzos can form tolerance and dependence so quickly, where other compounds that are targeting the non-α1 binding sites don't. Admittedly, that's simplifying it down even more than reality. You have to get even more detailed to really get a full picture, like separating the α1β3γ2 subreceptor from the α1β3δ ones. However, the main idea is the same. Which specific receptors you are hitting, and how you are hitting them, is crucial to the dependence and withdrawal effects. That's to say nothing of GABA-B or other affinities, which all affect signaling cascades.
So remember that things are much more complex than they seem on the surface. I've personally used gotu kola, lemon balm, magnolia bark, etc. daily for longer periods, then stopped cold turkey without any issues. I get very strong rebound effects from benzos, though. There is a very clear difference. That's not saying that some people might not have issues.. Everyone is different, and I have seen people with strange reactions to all sorts of things. However, when talking about dependency and withdrawal, you are talking two totally different leagues with these botanical extracts and proper benzos.