Kavalactones are a class of

lactone Lactones are cyclic carboxylic esters. They are derived from the corresponding hydroxycarboxylic acids by esterification. They can be saturated or unsaturated. Lactones are formed by lactonization, the intramolecular esterification of the corresp ...

compounds found in

kava Kava or kava kava (''Piper methysticum'': Latin 'pepper' and Latinized Ancient Greek, Greek 'intoxicating') is a plant in the Piperaceae, pepper family, native to the Pacific Islands. The name ''kava'' is from Tongan language, Tongan and Marqu ...

roots and '' Alpinia zerumbet'' (shell ginger) and in several

Gymnopilus ''Gymnopilus'' is a genus of gilled mushrooms within the fungal family Hymenogastraceae containing over 200 rusty-orange spored mushroom species. Description The basidiocarp, fruit body is typically reddish brown to rusty orange to yellow, med ...

, Phellinus and

Inonotus ''Inonotus'' is a genus of fungus, fungi in the family (biology), family Hymenochaetaceae. The genus, described by Petter Karsten in 1879, is estimated to contain about 80 species ''sensu lato'' and 30 species ''sensu stricto'' (in the strict sen ...

fungi. Some kavalactones are bioactive. They are responsible for the psychoactive, analgesic, euphoric and sedative effects of kava.

Bioactivity

Kava extract interacts with many pharmaceuticals and herbal medications. In human volunteers, in vivo inhibition includes CYP1A2 and CYP2E1 through use of probe drugs to measure inhibition.

Research

Its

anxiolytic An anxiolytic (; also antipanic or anti-anxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxie ...

and hepatotoxic properties have been investigated. The major kavalactones (except for desmethoxyyangonin) potentiate GABA_A receptors, which may underlie the anxiolytic and sedative properties of kava. Further, inhibition of the

reuptake Reuptake is the reabsorption of a neurotransmitter by a neurotransmitter transporter located along the plasma membrane of an axon terminal (i.e., the pre-synaptic neuron at a synapse) or glial cell after it has performed its function of transmi ...

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...

and

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

, binding to the CB₁ receptor, inhibition of voltage-gated

sodium Sodium is a chemical element; it has Symbol (chemistry), symbol Na (from Neo-Latin ) and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 element, group 1 of the peri ...

and calcium channels, and monoamine oxidase B reversible inhibition are additional pharmacological actions that have been reported for kavalactones.

Toxicity

Several kavalactones (e.g., methysticin and

yangonin Yangonin is one of the six major kavalactones found in the kava plant. It acts as a selective agonist at the CB1 receptor, CB1 cannabinoid receptor, inhibits monoamine oxidase (particularly MAO-B), and modulates GABAA receptor activity. Yangonin s ...

) affect a group of

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

s involved in

metabolism Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

, called the CYP450 system.

Hepatotoxicity Hepatotoxicity (from ''hepatic toxicity'') implies chemical-driven liver damage. Drug-induced liver injury (DILI) is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdr ...

occurred in a small portion of previously healthy kava users, particularly from extracts, as opposed to whole root powders.

Compounds

At least 18 different kavalactones are known, with methysticin being the first identified. Multiple analogues, such as ethysticin, have also been isolated. Some consist of a substituted α-pyrone as the lactone, while others are partially saturated. The average

elimination half-life Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the blood plasma. ...

of kavalactones typically present in kava root is 9 hr.

Biosynthesis

The kavalactone biosynthetic pathway in ''Piper methysticum'' was described in 2019.

References

External links

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The great kava boom: how Fiji's beloved psychoactive brew is going global
The Guardian, 2020 {{GABAAR PAMs Monoamine oxidase inhibitors GABAA receptor positive allosteric modulators Anxiolytics Analgesics Sedatives Anticonvulsants Nootropics