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Kava and Anxiety - A Review

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Piper methysticum, commonly known as kava, has been used for over 3000 years. Traditionally, it has been used as a tonic to treat feelings of weakness and nervous exhaustion, and as a sleep aid due to its relaxing effect. Kava has been researched extensively for its anxiolytic or antianxiety activity.[1] In addition to its use as an anxiolytic agent, it has been used to treat a range of health conditions including stress, muscle spasms, menstrual disorders, and pain.[2] Kavalactones are the chemically active constituents of kava, with approximately 96% of the total pharmacological activity resulting from the action of six kavalactones: kavain, dihydrokavain, methysticin, dihydromethysticin, yangonin, and desmethoxyyangonin.[1] Kavalactones are concentrated primarily within the rhizomes, roots, and root stems, with the distribution progressively decreasing towards the aerial parts. Toxic alkaloids are often found in the aerial parts and are therefore not used traditionally.[3]

Kava and Anxiety - A Review

Anxiety disorders are among the most common types of mental illnesses. The core symptoms involved in this disorder are feelings of uncertainty, apprehension, and fear, which are often accompanied by various psychological and somatic symptoms.[4] Generalized anxiety disorder (GAD) involves cognitive and somatic symptoms, and involves excessive chronic worry as well as anticipatory anxiety. Anxiety can be accompanied by various issues, such as restlessness, irritability, fatigue, difficulty concentrating, sleep disturbances, and muscle tension.[2] GAD can be disabling and is often chronic in nature.[5] Sleep disturbance is frequently associated with anxiety disorders and can involve impaired initiation, duration, or quality. Pharmacological treatment of anxiety disorders involves the use of tranquilizers, antidepressants, and neuroleptics. These drugs have been proven to be effective in many cases, however many people are reluctant to use them due to their side-effect profiles, dependence, development of tolerance, and their abuse potential. Therefore, alternative treatments that are effective in treating anxiety without the side effects and safety concerns are being sought after.[4]

Mechanism of Action

The exact mechanism of action responsible for kava’s therapeutic effect has yet to be determined. Research suggests that various mechanisms that may mediate the actions of specific kavalactones, such as enhanced ligand binding to GABA type A receptors, decreased excitatory neurotransmitter release due to the blocking of calcium channels, and reduced reuptake of dopamine and noradrenaline by neurons.[1]

Kava and Anxiety - A Review

Anxiety

Kava is considered an effective short-term treatment for anxiety. A review of randomized controlled trials indicated statistically significant anxiolytic activity of kava compared to placebo. Kava appears to be equally efficacious for depression and concomitant anxiety.[1] One study found a reduction of 9.9 points on the HAM‑A rating scale in the first kava phase, versus only a 0.8-point decrease in the first placebo phase. The second crossover phase showed a 10.3 reduction from kava compared to a rise of 3.3 points for placebo.[2] Another trial compared kava, buspirone, and opipramol in people with GAD over a period of eight weeks. No significant differences were found regarding efficacy and safety. Seventy-five percent of the patients experienced a fifty percent reduction of HAMA score, and sixty percent achieved full remission.[6] In one trial, kava demonstrated equivalent efficacy to synthetic agents, buspirone and opipramol, in the treatment of GAD. Kava may provide an advantage over agents such as benzodiazepines with respect to daytime sedation and cognitive impairment. No rebound symptoms occurred after discontinuing kava, which is a common occurrence with abrupt benzodiazepine withdrawal.[3][7] Kava has a rapid onset and therefore may be more applicable for acute and intermittent use.[3]

Kava and Anxiety - A Review

Other Uses

Kava has been shown to improve sleep quality without impairing rapid-eye-movement (REM) sleep. One study found statistically significant improvements in quality and recuperative effect of sleep, as well as the reduction of sleep-related symptoms. Deep-sleep periods increased and REM periods remained unchanged after the use of the kava extract. Several pharmaceutical treatment options for anxiety with accompanying sleep issues cause REM-sleep suppression and prolong REM latency. Research has been done to investigate other properties of kava such as its positive influence on the brain’s ability to process information, local anesthesia, as well as anticonvulsive and spasmolytic effects.[4] Several clinical trials have investigated the acute and chronic effects of kava on cognition. The current evidence suggests that kava has a positive or benign effect on cognition; however, it can impair motor skills at higher doses. Kava can potentially enhance cognitive task performance, such as working memory and visual processing.[3]

Safety

Concern was raised regarding kava’s safety, due to cases of reported liver toxicity, also known as hepatotoxicity, and kava was subsequently withdrawn from the market for a period of time. Research has been conducted to determine the cause of this liver damage and the following factors are potentially responsible: poor metabolizers of kavalactones, preparations made using acetone or ethanol, contaminated or poorly stored material, and the use of aerial parts or root peelings that contain higher amounts of alkaloids which are toxic at high levels. The World Health Organization commissioned a report assessing the risk of kava products and recommends that kava should be derived from water-based suspensions. Clinical trials have demonstrated that aqueous kava preparations produce anxiolytic and antidepressant activity without raising safety concerns at the dose and duration studied.[1] A review determined that kava is relatively safe for short-term treatment (one to 24 weeks), although more information is required at this time. Trials involving larger sample sizes are needed, as well as long-term safety studies.[8] In a study, kava was given for six weeks for generalized anxiety disorder: the results of this trial showed no significant differences across groups for liver-function tests, and no significant adverse reactions could be attributed to kava.[9] Acute kava intoxication upon heavy chronic consumption has resulted in headache, sore eyes, generalized muscle weakness, abdominal pain, disorientation, and hallucinations. However, the amount of kava consumed in these cases is at least a hundred times higher than recommended therapeutic doses.[10] Kava should not be used with alcohol or benzodiazepines, and should be used with caution when taking other medications that are metabolized by the same pathways.[3] There is currently no evidence of any potential for tolerance or dependency with kava use.[4]

Conclusion

Kava produces significant anxiolytic and antidepressant activity without raising safety concerns. Quality is an important issue, as it affects efficacy and safety. Evidence suggests that cheaper kava extracts may use incorrect extraction methods, plant parts, and cultivars, and therefore may be responsible for the reported hepatotoxicity.[3] It is recommended to speak with a licensed health-care provider, such as a naturopathic doctor, before using kava.