I Know this topic has been raised a billion times but I'm going to revive it for more current input-
Aside from the obvious, Acetaminophen (paracetamol), what other prescription meds are likely going to be problematic mixing with Kava?
Generally with GABAergic medications such as benzos, Lyrica, and any other types of medications that cause sleepiness you'd want to keep an eye out for.
Kava, more specifically kavain, currently is thought of as a general positive allosteric modulator of the GABA-A receptor. What this means is that it causes GABA receptors to increase their response when in the presence of natural GABA. Benzos and other GABAergic meds do this as well, and adding kava on top compounds the sedation.
There is a little evidence that dopaminergic drugs may not play well with kava's dopamine actions such as levodopa in Parkinson's disease patients. It seems kava, more specifically yangonin causes a steep drop in dopamine levels in certain areas of the brain which may interfere with medications looking to increase them. This is about as much as I can say about the pharmacodynamic interactions of kava with other drugs.
In regards to the pharmacokinetic profile, Kava in vitro (or the lab) shows to inhibit several classes of enzymes which are used by the body to break down many types of drugs and chemicals we encounter. Be that as it may, the in vivo (real tests in humans) results show something different. Kava shows in the human body to only affect CYP1A2 and CYP2E1, both of which are quite specific in which drugs they metabolize.
Acetaminophen breaks down into what's known as N-acetyl-p-benzoquinone imine or NAPQI for short. This is known as a liver toxic compound, and can cause severe liver damage [1]. CYP1A2 is the pathway that APAP uses to further metabolize this compound. When CYP1A2 is inhibited APAP will stay in it's NAPQI form for longer, thus leaving higher opportunity to cause cellular damage [2].
There are a limited number of drugs that also use this pathway such as clozapine, Luvox, caffeine, melatonin and antipsychotics such as Haloperidol [3]. They should be used with caution when combining them with kava. They may end up staying in the system longer than anticipated and in certain forms when kava is present.
Basically an easy way of seeing if your drug will interact with kava is by doing the following:
1. Identify the drug (Example: valium)
2. search the drug on
https://go.drugbank.com/
3. On the left, click "Pharmacology", and then "Metabolism"
The metabolism screen will show you which enzymes are used in the metabolization of the drug in question. If it involves CYP1A2 or CYP2E1 then they may interact (as in decreases the body's ability to metabolize those drugs) with kava.
[1] Wikimedia Foundation. (2021, April 25).
NAPQI. Wikipedia.
https://en.wikipedia.org/wiki/NAPQI.
[2] Tonge, R. P., E. J. Kelly, S. A. Bruschi, T. Kalhorn, D. L. Eaton, D. W. Nebert, and S. D. Nelson. 1998. “Role of CYP1A2 in the Hepatotoxicity of Acetaminophen: Investigations Using Cyp1a2 Null Mice.”
Toxicology and Applied Pharmacology 153 (1): 102–8.
https://doi.org/10.1006/taap.1998.8543
[3] Ghodke-Puranik, Yogita A., and Jatinder K. Lamba. 2017. “Chapter 7 - Pharmacogenomics.” In
Innovative Approaches in Drug Discovery, edited by Bhushan Patwardhan and Rathnam Chaguturu, 195–234. Boston: Academic Press.
https://doi.org/10.1016/B978-0-12-801814-9.00007-6.
