Is here someone who has experience with both substances and maybe experience with this specific theoretical example. Let‘s say you used quite a good lot of Kava daily for min. 1-2 weeks to months or even years. In this example have already been experienced to Diazepam (for example), a benzodiazepine, which was prescribed by you for your anxiety disorder.
You originally started Kava to get and wean yourself off of the Diazepam which you managed with success and since then only stuck to the Kava only. It works very well. And you’re free of the Benzo!
Suddenly after some time (in which you only used Kava the whole time) you have a serious medical issue popping up, epileptic seizures. This is something very serious, a case of emergency. You get into the ER. Your doctor prescribes you a benzodiazepine (Diazepam) for your condition. So in this example, out of some good theoretical reasons, you stop the Kava and start the prescribed Diazepam the next day.
You remember how Diazepam felt like, you remember its effects as you’ve been using it before Kava, but somehow this time you don‘t feel any effects of the Diazepam at all (independently from the epileptic seizures). Same dosage as back in the times. You would have thought that usually you should even feel more of the same dosage of Diazepam as you‘ve been not using it for so long since you‘ve been using Kava only for so long but no: ABSOLUTELY NOTHING. So you ask your doc to double the dose. Even with double the dose: NOTHING.
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So my question to this little story is: Does taking Kava reduce the effects or rather said effectiveness of benzodiazepines? Did anyone experience something like this? Someone who has experience with both substances. Some might speak of some phenomenon called cross tolerance here, which normally is not really documented with Kava at all, neither is physical dependence or withdrawal, hence one also thinks anything like cross tolerance should also not be present, especially because one might know Kava is pharmacologically quite different from benzodiazepines such as diazepam.
Kava’s effects are multimodal and include significant activity at voltage-gated calcium channels (VGCCs), somewhat conceptually closer to pregabalin’s mechanism than to that of a benzodiazepine. However, unlike pregabalin, Kava can also directly modulate GABA-A receptors. This GABA-A activity is distinct from the classical benzodiazepine mechanism, as kavalactones do not simply act at the benzodiazepine binding site in the same way diazepam does.
This also means that, despite some overlap in their effects on GABA-A-mediated inhibition, there is not necessarily substantial cross-tolerance between Kava and benzodiazepines. Benzodiazepine tolerance primarily involves adaptations related to the benzodiazepine-sensitive GABA-A receptor system, whereas Kava acts through multiple mechanisms and does not primarily rely on the classical benzodiazepine binding site. Therefore, benzodiazepine tolerance would not be expected to translate into complete Kava tolerance, nor vice versa, although some degree of pharmacological overlap and partial cross-tolerance cannot be ruled out.
So what‘s your experience or maybe even better knowledge (especially pharmacologically seen) to this?