Kavalactones are a class of

lactone Lactones are cyclic carboxylic esters, containing a 1-oxacycloalkan-2-one structure (), or analogues having unsaturation or heteroatoms replacing one or more carbon atoms of the ring. Lactones are formed by intramolecular esterification of the co ...

compounds found in

kava Kava or kava kava ('' Piper methysticum'': Latin 'pepper' and Latinized Greek 'intoxicating') is a crop of the Pacific Islands. The name ''kava'' is from Tongan and Marquesan, meaning 'bitter'; other names for kava include ''ʻawa'' (Hawaiʻi ...

roots and Alpinia zerumbet (Shell ginger). Kavalactones are under research for potential to have various

psychotropic A psychoactive drug, psychopharmaceutical, psychoactive agent or psychotropic drug is a chemical substance, that changes functions of the nervous system, and results in alterations in perception, mood, consciousness, cognition or behavior. Th ...

effects, including

anxiolytic An anxiolytic (; also antipanic or antianxiety 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

sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or excitement. They are CNS depressants and interact with brain activity causing its deceleration. Various kinds of sedatives can be distinguished, but ...

hypnotic Hypnotic (from Greek ''Hypnos'', sleep), or soporific drugs, commonly known as sleeping pills, are a class of (and umbrella term for) psychoactive drugs whose primary function is to induce sleep (or surgical anesthesiaWhen used in anesthesia ...

activities.

Enzyme inhibition

Kava extract has been shown in vitro to potentially inhibit a wide range of hepatic enzymes, suggesting a possible potential for interactions with many pharmaceuticals and herbal medications. In human volunteers in vivo inhibition is currently limited to CYP1A2, and CYP2E1 through use of probe drugs to measure inhibition.

Research

Several preliminary studies are assessing potential effects of kava, including its

actions and

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cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn fr ...

, but the role specifically of kavalactones among many other kava compounds for these effects remains under study. Kavalactone type compounds may help protect against high glucose induced cell damage.

Toxicity

Several kavalactones (e.g. methysticin and

yangonin Yangonin is one of the six major kavalactones found in the kava plant. It has been shown to possess binding affinity for the cannabinoid receptor CB1 (Ki = 0.72 μM), and selectivity vs. the CB2 receptor (Ki >10 μM) where it behaves as an agon ...

) affect a group of

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...

s involved in

metabolism Metabolism (, from el, μεταβολή ''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 c ...

, called CYP1A1.

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

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 have been identified to date, 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 (also known as elimination half-life, pharmacologic 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 bl ...

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

*
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