DARK Classics in Chemical Neuroscience: Kava

Abstract

Kava (kava kava, Piper methysticum) is a common drugcontaining plant in the Pacific islands. Kavalactones, its psychoactive compounds, exert potent central nervous system (CNS) action clinically and in animal models. However, the exact pharmacological profiles and mechanisms of action of kava on the brain and behavior remain poorly understood. Here, we discuss clinical and experimental data on kava psychopharmacology and summarize chemistry and synthesis of kavalactones. We also review its societal impact, drug use and abuse potential, and future perspectives on translational kava research.

Kava as a Clinical Nutrient: Promises and Challenges

“…The psychoactive effects of kava use have been appreciated for a long time ( Table 4 ). Its neurological benefits have made it a popular non-prescription treatment for multiple neurological disorders [ 11 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 ]. Kava use, however, is not free of side effects, such as headaches, fatigue, tremors and restlessness [ 76 , 77 , 78 ].…”

“…A few lab animal results published during the past 15 years are discussed to cross-inform potential mechanisms of such toxicity issues. Results using biochemical and in vitro models are not reiterated herein because they have been covered in a number of reviews, including two recent ones [ 68 , 157 ].…”

Piper methysticum G. Forst (Piperaceae) in the central nervous system: phytochemistry, pharmacology and mechanism of action

“…Wong and Atownley (2011) in a discussion about herbal medicines highlights the local anesthetic effect of this species, which when tested in laboratory animals, enhances the sleep time induced by barbiturates, reducing the need for anesthetic agents. This effect is also directly related to anxiolytic activity, which is mainly mediated by the GABA modulation mechanism, and in some tests such as the labyrinth in the cross (performed on mice), the effect is similar to that of the benzodiazepine, Diazepam (Volgin et al, 2020;Rex et al, 2002;Raduege et al, 2004).…”

Biological Activity, Hepatotoxicity, and Structure-Activity Relationship of Kavalactones and Flavokavins, the Two Main Bioactive Components in Kava (Piper methysticum)

“…e pharmacokinetics and pharmacodynamics studies of kava in humans were carried out by means of experiments involving self-medication [85]. In humans, kavalactones as well as their metabolites were generally eliminated in the urine and feces, and the peak plasma levels usually occur around 2 h after ingestion, with a half-life of about 9 h. Orally administered kava water extracts were excreted mostly unchanged into urine [86].…”

“…The pharmacokinetics and pharmacodynamics studies of kava in humans were carried out by means of experiments involving self-medication [ 85 ]. In humans, kavalactones as well as their metabolites were generally eliminated in the urine and feces, and the peak plasma levels usually occur around 2 h after ingestion, with a half-life of about 9 h. Orally administered kava water extracts were excreted mostly unchanged into urine [ 86 ]. The metabolism of kavain studied by the human liver cell-line Hep-G2 [ 87 ] or human serum and urine [ 85 ] disclosed the metabolites of kava including p-hydroxykavain, p-hydroxy-7,8-dihydrokavain, 5,6-dehydrokavain, 6-phenyl-5-hexen-2,4-dione [ 85 ], p-hydroxy-5,6-dehydrokavain, and 6-phenyl-3-hexen-2-one [ 88 ].…”