Kavain, or “K” is one of the, if not the most studied and pharmacologically important kavalactones in the plant. Kavain receives the number 4 in chemotypes because this kavalactone was the fourth to exit the HPLC column at 19–20 min [1]. The initial resorption time of orally applied kavain is approximately 15 min, and its half-life in the body is approximately 9 h [2]. Kavain has long been thought to be the constituent of kava that causes a euphoric, uplifting, yet calming effect. Being the most sought after kavalactone, kavain typically resides in the first 2 positions of a noble kava’s chemotype. Its direct physical actions include inhibition of voltage-gated sodium channels in neurons and potentiation of GABA ligand binding. Kava has been thought to act similarly to benzodiazepines; however, none of these studies detected significant affinity of kavalactones for the benzodiazepine binding site, contrary to popular belief [3]. Kavain has many interesting functions. Studies have shown anti-inflammatory effects, cancer reduction [4], anxiety reduction [5], MOA-B inhibition [6], Parkinson’s symptom reduction, and neuroprotection [7]. The list of beneficial effects of this compound is long, and topics related to it are still being researched even today.
[1] Lebot, V. and J. Levesque. “The origin and distribution of kava piper methysticum forst. f. piperaceae a phytochemical approach.” (1989).
[2] Tarbah F, Mahler H, Kardel B, Weinmann W, Hafner D, Daldrup T. Kinetics of kavain and its metabolites after oral application. J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Jun 5;789(1):115-30. doi: 10.1016/s1570-0232(03)00046-1. PMID: 12726850.
[3] Chua HC, Christensen ETH, Hoestgaard-Jensen K, Hartiadi LY, Ramzan I, et al. (2016) Kavain, the Major Constituent of the Anxiolytic Kava Extract, Potentiates GABAA Receptors: Functional Characteristics and Molecular Mechanism. PLOS ONE 11(6): e0157700. https://doi.org/10.1371/journal.pone.0157700
[4] Xiaoren Tang and Salomon Amar. "Kavain inhibition of LPS-induced TNF-α via ERK/LITAF." Royal Society of Chemistry, Toxicol. Res., 2016, 5, 188-196
[5] Singh, Y. N., & Singh, N. N. (2002). Therapeutic Potential of Kava in the Treatment of Anxiety Disorders. CNS Drugs, 16(11), 731-743. doi:10.2165/00023210-200216110-00002
[6] Prinsloo, D., Dyk, S. V., Petzer, A., & Petzer, J. P. (2019). Monoamine Oxidase Inhibition by Kavalactones from Kava (Piper Methysticum). Planta Medica, 85(14/15), 1136-1142. doi:10.1055/a-1008-9491
[7] Schmidt N, Ferger B. Neuroprotective effects of (+/-)-kavain in the MPTP mouse model of Parkinson's disease. Synapse. 2001 Apr;40(1):47-54. doi: 10.1002/1098-2396(200104)40:1<47::AID-SYN1025>3.0.CO;2-S. PMID: 11170221.