Piper methysticum, Kava

  • Written by Simon Ido, Reviewed by Prof. Shoseyov Oded
  • Last update, Jun, 2022

  • 3 mins 35 secs

Kava is a plant used traditionally by Pacific Island societies for its relaxing properties[1, 6, 8, 9]. Kava contains kavalactones, which hold anxiolytic and sleep-inducing properties[8, 10]. Kavalactones have GABAergic properties and also affect the endocannabinoid system[7, 8].


Piper methysticum, otherwise known as Kava, is a tradi- tional plant native to Pacific societies utilized for cen- turies for its soothing effects[6]. Kava has psychoac- tive properties when consumed and is classified as a narcotic[6].
Kava’s active components consist mainly of kavalactones[6], which are phenolic polyketides with anxiolytic and analgesic properties supported by over 3000 years of traditional use and recent clinical trials[8]. These effects are achieved through modulation of GABA activity via alteration of lipid membrane structure and sodium channel function, monoamine oxidase B in- hibition, and noradrenaline and dopamine re-uptake inhibition[9]. Kava’s components also act on the cannabinoid receptors[8]. More specifically, yangonin is the only kavalactone to bind to the CB1 receptor[7]. Yangonin is also a potent dopamine antagonist, and is thought to aid in limiting the euphoric actions of the kavalactones at higher concentrations[1].
Current evidence supports the use of kava for mild, generalized anxiety[5, 9, 10] in both animal and early clinical trials. These placebo-controlled trials show im- provements in neurotic, premenopausal, and chronic forms of anxiety with key themes of reductions in stress, calming effects, and improvements in sleep[9].
Kava was withdrawn from European markets in 2002 due to concerns over hepatotoxicity, however recent re- search has shown that liver damage can be caused usu- ally only in extremely high doses and alongside consump- tion with alcohol or other drugs via modulation of the cytochrome P450 system (CYP)[9]. Water-based con- sumption methods are considered safer than ethanolic extracts, which is supported by traditional methods of use[9].

Mode of action

Kavalactones are structurally related to liphophilic lac- tones, and have been characterized since the second half of the 19th century[2]. The six major kavalactones, ac- counting for 96% of kava’s lipid extract fraction, are dehydrokavain, dihydrokavain, yangonin, kavain, dihy- dromethysticin and methysticin[2]. Minor constituents include other kavalactones, chalcones, piperidine alka- loids, and essential oils[2].
The mode of action for which kavalactones affect the body has been fairly well-studied in vitro. One study showed a fast action on voltage-dependent sodium chan- nels, which contributes to the local anaesthetic and an- ticonvulsive properties of kava[3]. However, it is thought that GABAA, dopamine D2, opioid, and histamine re- ceptor interactions are responsible for kava’s anxiolytic, muscle relaxant, and sleep-inducing effects[3].
These interactions include reduced excitatory neuro- transmitter release due to blockade of calcium ion chan- nels, enhanced ligand binding (no direct binding as is seen with benzodiazepenes) to gamma-aminobutyric acid (GABA) type A receptors, reversible inhibition of monoamine oxidase B, and reduced neuronal reuptake of noradrenaline (norepinephrine) and dopamine[9]. In an- imal models, it was seen that kavalactones did not bind to GABAA receptors – however, the kavalactones were still able to activate GABAergic effects[9].
Another study examined yangonin, which is a kavalac- tone that was found to be an agonist to the CB1 receptor in vitro[7]. This has implications that kava affects the en- docannabinoid system as one of its modes of action, and also somewhat describes its anxiolytic effects as cannabi- noid antagonists have previously been studied for their anxiolytic properties[7].

While fears over kava’s hepatotoxic attributes have been found to be related primarily to excessive dosage and use with alcohol, it is considered largely safe to con- sume, especially if consumed via a water-extraction[9]. There are however also potential drug interactions via modulation of the CYP450 system or P-glycoprotein pump[9]. Frequent and heavy use of kava is discour- aged and can have some detrimental side effects such as dermopathy and lower lymphocyte counts[9]. However, infrequent and social use of kava seems to be fairly safe and effective[4, 9].

Pharmacological effects

The pharmacological effects of kava has been shown in multiple studies to be statistically significant in reducing anxiety[5, 9, 10].
These studies and literature searches are early clinical trials, where the patients take about 1-2 months to see an improved anxiolytic effect over the placebo[9]. These placebo-controlled trials also show improvements in neu- rotic, premenopausal, and chronic forms of anxiety with key themes of reductions in stress, calming effects, and improvements in sleep[9].
Kava also has sleep inducing effects[10] which is thought to be caused by changes of the activity of 5- HT neurons, while its relaxing effects are attributed to activation of the mesolimbic dopaminergic neurons[1].
In clinical considerations, studies highlight the impor- tance of high-quality herbal material and high standards of manufacturing[9].
There have been some reported side effects from Kava, mostly in the form of nausea and gastrointenstinal discomfort[1, 9, 10].

Potentil use

Kava has been traditionally an essential component of many Pacific Island societies, traditionally used during religious and and cultural ceremonies as a psychoactive and used in social settings as an inebriate beverage that elicits relaxation[6, 9].
As described above, kava can be used in a social set- ting as a water-based extraction (tea) for its relaxing properties[6].
It can also be recommended by clinicians for use in general anxiety disorder[1, 9, 10].


[1] S. S. Baum, R. Hill, and H. Rommelspacher. Ef- fect of kava extract and individual kavapyrones on neurotransmitter levels in the nucleus accumbens of rats. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 22(7):1105–1120, 1998.

[2] A. R. Bilia, L. Scalise, M. C. Bergonzi, and
F. F. Vincieri. Analysis of kavalactones from piper methysticum (kava-kava). Journal of Chromatog- raphy B, 812(1):203–214, 2004. Biomedically Rele- vant Plant Components: Active Principles and Tox- icants.
[3] D. Dinh, U. Simmen, K. Berger Beuter, B. Beuter,
K. Lundstrom, and W. Schaffner. Interaction of var- ious piper methysticum cultivars with cns receptors in vitro.
[4] E. Ernst. A re-evaluation of kava (piper methys- ticum). British Journal of Clinical Pharmacology, 64(4):415–417, 2007.
[5] M. Feltenstein, C. Lambdin, M. Ganzera, H. Ran- jith, W. Dharmaratne, N. P. D. Nanayakkara, I. A. Khan, and K. J. Sufka. Anxiolytic properties of piper methysticum extract samples and fractions in the chick social–separation–stress procedure. Phy- totherapy Research, 17(3):210–216, 2003.
[6] V. Lebot and J. Lèvesque. The origin and distri- bution of kava (piper methysticum forst. f., piper- aceae): A phytochemical approach. Allertonia, 5(2):223–281, 1989.
[7] A. Ligresti, R. Villano, M. Allarà, I. Ujváry, and
V. Di Marzo. Kavalactones and the endocannabi- noid system: The plant-derived yangonin is a novel cb1 receptor ligand. Pharmacological Research, 66(2):163–169, 2012.
[8] T. Pluskal, M. Torrens-Spence, T. Fallon,
A. De Abreu, C. Shi, and J. Weng. The biosynthetic origin of psychoactive kavalactones in kava. Nature Plants, 5(8):867, 878.
[9] J. Sarris, E. LaPorte, and I. Schweitzer. Kava: A comprehensive review of efficacy, safety, and psychopharmacology. Australian & New Zealand Journal of Psychiatry, 45(1):27–35, 2011. PMID: 21073405.
[10] Y. Singh and N. Singh. Therapeutic potential of kava in the treatment of anxiety disorders.

Spoon with Kava Kava root powder on wooden table