Kava (Piper methysticum)
Kava, (Piper methysticum), also known as Kava Kava, is an indigenous plant in Polynesia and throughout the South Pacific, including Melanesia and Micronesia. It has been safely used for over 1,500 years in these cultures as a beverage for both ceremonial and casual consumption. Europeans documented its use when they traveled to Polynesia in the 18th century. In modern Fijian culture, Kava is used as a welcome beverage for visitors, and used in some religious contexts as well. These beverages are prepared from either the fresh or dried roots of the plant.
Usos
It has been traditionally used as a beverage to relieve anxiety, stress, and treat insomnia.
Química/Farmacología
Analysis of the composition of kava rhizome indicates that the fresh material is on average 80% water. When dried, the rhizome consists of approximately 43% starch, 20% fibers, 12% water, 3.2% sugars, 3.6% proteins, 3.2% minerals, and 15% kavalactones, although the kavalactone component can vary between 3% and 20% of the dry weight of the rhizome, depending on the age of the plant and the cultivar. The bioactive principles of kava rhizome are mostly, if not entirely, contained in the lipid-soluble resin. The compounds of greatest pharmacological interest are the substituted α-pyrones or kavapyrones, commonly known as kavalactones. At least 15 lactones have been isolated from kava rhizome. The following six compounds are present in the highest concentrations and account for approximately 96% of the lipid resin: kavain, dihydrokavain, yangonin, desmethoxyyangonin, methysticin, and dihydromethysticin. Other constituents of kava include chalcones and other flavanones, and conjugated diene ketones.
Kavalactones in kava are thought to be the active constituent that produces skeletal muscle relaxation, non-narcotic anesthesia, and local anesthetic effects.
Estudios clínicos
Clinical data suggest benefits with kava as short-term use for generalized anxiety and promoting calmness and has been suggested as an alternative to benzodiazepines. In a human study the authors concluded, “the aqueous Kava preparation produced significant anxiolytic and antidepressant activity and raised no safety concerns at the dose and duration studied. Kava appears equally effective in cases where anxiety is accompanied by depression. This should encourage further study and consideration of globally reintroducing aqueous rootstock extracts of Kava for the management of anxiety.”
A study using chickens experiencing social stress suggested that a particular constituent of Kava, dihydrokavain, may be enough to produce the anxiolytic properties of Kava extract. The amount of anxiety reduction and calmness observed was dose-dependent, with improved benefits observed as the dose concentration increased. Studies of mice show similar benefits with regards to reducing anxiety. Dose dependent, statistically significant behavioral changes of decreased anxiety were shown with the use of Kava extract. With the use of the Kava extracts, the mice exhibited significant anxiolytic-like behavioral changes and sedation that were not mediated through the benzodiazepine binding site on the GABA(A) receptor complex.
Mecanismo biomecánico
The active compounds in kava are called kavalactones. In studies in animals and humans, these compounds appeared to provide pain relief and act as muscle relaxants and anticonvulsants. Kavapyrones are centrally acting skeletal muscle relaxants, anticonvulsants, and peripherally acting local anesthetics. Kavain, one of the main active components of Kava, may effectively modulate excitatory signals in the hippocampus of guinea pigs.
There has been concern regarding hepatotoxicity with Kava use. Possible hepatotoxicity mechanisms are thought to be CYP450 inhibition, reduction in liver glutathione content, or inhibition of COX activity. Thus, patients with history of hepatic impairment of any kind should avoid Kava.
Fuentes/Artículos
Bilia, Anna Rita, Sandra Gallori, and Franco F. Vincieri. "Kava-kava and anxiety: growing knowledge about the efficacy and safety." Life Sciences 70, no. 22 (2002): 2581-2597.https://neurobiologix.com/v/vspfiles/downloadables/Abstract_Kava_Kava_Kavalactones_2020.pdf
Chua HC, Christensen ET, Hoestgaard-Jensen K, et al. Kavain, the Major Constituent of the Anxiolytic Kava Extract, Potentiates GABAA Receptors: Functional Characteristics and Molecular Mechanism. PLoS One. 2016;11(6):e0157700.
Ernst E. Herbal remedies for anxiety - a systematic review of controlled clinical trials. Phytomedicine. 2006 Feb;13(3):205-8.
Jacobs BP, Bent S, Tice JA, Blackwell T, Cummings SR. An internet-based randomized, placebo-controlled trial of kava and valerian for anxiety and insomnia. Medicine (Baltimore). Jul 2005;84(4):197-207.
Keledjian J, Duffield PH, Jamieson DD, Lidgard RO, Duffield AM. Uptake into mouse brain of four compounds present in the psychoactive beverage kava. J Pharm Sci. Dec 1988;77(12):1003-1006.
LaPorte E, Sarris J, Stough C, Scholey A. Neurocognitive effects of kava (Piper methysticum): a systematic review. Hum Psychopharmacol. 2011 Mar;26(2):102-11.
Lehrl S. Clinical efficacy of kava extract WS 1490 in sleep disturbances associated with anxiety disorders. Results of a multicenter, randomized, placebo-controlled, double-blind clinical trial. J Affect Disord. Feb 2004;78(2):101-110.
Malsch, U., and M. Kieser. "Efficacy of kava-kava in the treatment of non-psychotic anxiety, following pretreatment with benzodiazepines." Psychopharmacology 157, no. 3 (2001): 277-283. https://www.researchgate.net/profile/Meinhard-Kieser/publication/11745607_Efficacy_of_kava-kava_in_the_treatment_of_non-psychotic_anxiety_following_pretreatment_with_benzodiazepines/links/56cc6ad408ae96cdd071b455/Efficacy-of-kava-kava-in-the-treatment-of-non-psychotic-anxiety-following-pretreatment-with-benzodiazepines.pdf
Matsuda H, Hirata N, Kawaguchi Y, et al. Melanogenesis stimulation in murine B16 melanoma cells by Kava (Piper methysticum) rhizome extract and kavalactones. Biol Pharm Bull. 2006 Apr;29(4):834-7.
Pittler MH, Ernst E. Efficacy of kava extract for treating anxiety: systematic review and meta-analysis. J Clin Psychopharmacol. Feb 2000;20(1):84-89.
Pittler MH, Ernst E. Kava extract for treating anxiety. Cochrane Database Syst Rev. 2003(1):CD003383.
Russmann S, Lauterburg BH, Barguil Y, et al. Traditional aqueous kava extracts inhibit cytochrome P450 1A2 in humans: Protective effect against environmental carcinogens? Clin Pharmacol Ther. May 2005;77(5):453-454.
Russmann S, Lauterburg BH, Helbling A. Kava hepatotoxicity. Ann Intern Med. Jul 3 2001;135(1):68-69.
Sarris J, Kavanagh DJ, Byrne G, Bone KM, Adams J, Deed G. The Kava Anxiety Depression Spectrum Study (KADSS): a randomized, placebo-controlled crossover trial using an aqueous extract of Piper methysticum. Psychopharmacology (Berl). 2009 Aug;205(3):399-407.
Sarris J, Scholey A, Schweitzer I, et al. The acute effects of kava and oxazepam on anxiety, mood, neurocognition; and genetic correlates: a randomized, placebo-controlled, double-blind study. Psychopharmacol. 2012 May;27(3):262-9.
Sarris J, Stough C, Bousman CA, et al. Kava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled study. J Clin Psychopharmacol. Oct 2013;33(5):643-648
Sarris J, Stough C, Teschke R, et al. Kava for the treatment of generalized anxiety disorder RCT: analysis of adverse reactions, liver function, addiction, and sexual effects. Phytother Res. Nov 2013;27(11):1723-1728.
Sarris J, Stough C, Teschke R, et al. Kava for the treatment of generalized anxiety disorder RCT: analysis of adverse reactions, liver function, addiction, and sexual effects. Phytother Res. Nov 2013;27(11):1723-1728.
Sarris J, Byrne GJ, Bousman CA, et al. Kava for generalised anxiety disorder: A 16-week double-blind, randomised, placebo-controlled study. Aust N Z J Psychiatry. Mar 2020;54(3):288-297.
Singh YN, Devkota AK. Aqueous kava extracts do not affect liver function tests in rats. Planta Med. 2003 Jun;69(6):496-9.
Steiner GG. The correlation between cancer incidence and kava consumption. Hawaii Med J. 2000 Nov;59(11):420-2.
Teschke R.Kava hepatotoxicity: pathogenetic aspects and prospective considerations. Liver Int. 2010;30:1270-1279.
Whitton, Peter A., Andrew Lau, Alicia Salisbury, Julie Whitehouse, and Christine S. Evans. "Kava lactones and the kava-kava controversy." Phytochemistry 64, no. 3 (2003): 673-679. http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.608.3868&rep=rep1&type=pdf
Witte S, Loew D, Gaus W. Meta-analysis of the efficacy of the acetonic kava-kava extract WS1490 in patients with non-psychotic anxiety disorders. Phytother Res. 2005 Mar;19(3):183-8.
Yang X, Salminen WF. Kava extract, an herbal alternative for anxiety relief, potentiates acetaminophen-induced cytotoxicity in rat hepatic cells. Phytomedicine. 2011 May 15;18(7):592-600.