Anxiety

Kava and l-theanine for COVID-19 Anxiety

Both are safe and effective alternatives to benzodiazepines.

Posted Nov 13, 2020

This is the second post in a series of non-pharmacologic management of anxiety during the COVID-19 pandemic. In the first post, I commented on the limited efficacy of benzodiazepines for anxiety and highlighted the medical and psychiatric risks associated with benzodiazepine use, which are greater during the COVID-19 pandemic. In this post, I briefly review the evidence for kava-kava and l-theanine, two natural products widely used for stress and anxiety. In future posts, I will review the evidence for other non-pharmacologic approaches for stress and anxiety.

Kava (Piper methysticum)

In traditional Polynesian culture, the herbal Kava is used for ceremonial purposes and as an inebriant. In contrast to prescription benzodiazepines, individuals who take Kava at doses recommended for anxiety (between 60 and 300mg/day) do not experience sedation, mental slowing, or impaired cognitive functioning. Kava is believed to reduce anxiety by interfering with norepinephrine reuptake and binding with GABA and NMDA receptors in the brain. Kava preparations standardized to 70% kavalactones at doses between 70mg to 240mg/day effectively reduce symptoms of “stress” and moderate generalized anxiety but are probably not effective against severe anxiety. An early systematic review of 11 controlled double-blind studies concluded that Kava was superior to placebo for the short-term management of generalized anxiety (Pittler & Ernst 2003). A comprehensive review of the safety and efficacy of Kava for anxiety published in 2011 found significant positive effects in 4 out of 6 randomized placebo-controlled studies (Sarris & Schweitzer 2011).

Kava compares favorably to benzodiazepines and other conventional anti-anxiety medications. The findings of a small double-blind controlled study suggest that persons who have generalized anxiety adequately manage their symptoms by gradually increasing their daily dose of kava (up to 300mg/day) while slowly tapering off of a benzodiazepine such as lorazepam (Ativan™) or diazepam (Valium™), without experiencing worsening anxiety or withdrawal (Malsch &Kieser 2001). A randomized placebo-controlled multi-center study enrolling 129 outpatients concluded that a standardized Kava preparation (LI 150) was as effective as two commonly prescribed anti-anxiety agents (Buspirone™ and Opipramol™) for the treatment of generalized anxiety (Boerner, Sommer, et al 2003). Three-fourths of patients in both the Kava group and the conventional treatment group were classified as “treatment responders,” and experienced 50% or greater reductions in standardized measures of anxiety.

Rare safety problems

Rare cases of liver toxicity have been reported with Kava use. Researchers subsequently confirmed that kava hepatotoxicity was due to a hepatotoxic mould that contaminated poor raw material prior to processing, and not the active ingredients of Kava (Teschke, Sarris & Schweitzer 2012). Kava is generally well tolerated. Uncommon adverse effects include gastrointestinal upset, rash, headaches, and dizziness (Schulz 2001). Individuals who take Kava on an ongoing basis should limit their alcohol intake and use conventional sedative-hypnotic medications only under supervision from a physician.

L-theanine

Green tea contains the amino acid L-theanine. The anti-anxiety benefits of L-theanine are achieved through enhanced alpha brain wave activity and increased synthesis of GABA, the brain’s principal inhibitory neurotransmitter. Increased brain levels of GABA affect other brain neurotransmitter levels, resulting in general feelings of calm and well-being. Changes in brain electrical activity as measured by EEG recordings are related to the dosage of l-theanine and are comparable to beneficial changes observed during meditation. Calming effects of l-theanine are often experienced within 30 to 40 minutes after the amino acid is taken at a dose of 50 to 200mg, and may last 8 to 10 hours. Moderate symptoms of generalized anxiety often improve when l-theanine is taken at a dosage of 200mg once or twice daily. More severe anxiety may require doses up to 600mg to 800mg daily taken in increments of 100mg to 200mg spaced over the day. 

Research findings on l-theanine for stress and anxiety

A small placebo-controlled study found that daily l-theanine 200mg/day has beneficial effects on anxiety and cognitive performance related to stress in healthy adults (Hidese, Ogawa, et al 2019). A systematic review of 9 randomized placebo-controlled studies found that l-theanine in daily doses of 200 to 400mg reduced symptoms of stress and anxiety (Jackson, Everett, et al 2020). In addition to its anxiety-reducing benefits, emerging findings suggest that l-theanine has beneficial effects on mood, sleep, and cognitive performance in depressed individuals (Hidese, Wakabayashi, et al 2017).

No reported safety issues

l-theanine is generally safe when used at doses known to be beneficial for symptoms of stress and anxiety. There have been no reports of l-theanine causing serious adverse effects or interactions with other natural supplements, benzodiazepines, or other prescription medications. In contrast to prescription anti-anxiety medications such as benzodiazepines, l-theanine does not cause drowsiness or impair concentration, and there is no risk of addiction.

Bottom line

During this time of widespread stress and anxiety due to the COVID-19 pandemic, many people are relying on prescription benzodiazepines. Although benzodiazepines are sometimes beneficial, they have limited effectiveness and significant safety risks. The herbal Kava and the amino acid l-theanine are safe and effective alternatives to benzodiazepines for the management of moderately severe symptoms of stress and anxiety.

References

Sarris J, LaPorte E, Schweitzer I. Kava: a comprehensive review of efficacy, safety, and psychopharmacology. Aust N Z J Psychiatry. 2011 Jan;45(1):27-35. 

Pittler, M. H., & Ernst, E. (2003). Kava extract versus placebo for treating anxiety. The Cochrane Database of Systematic Reviews, 2003(1), 

Boerner RJ, Sommer H, Berger W, Kuhn U, Schmidt U, Mannel M. Kava-Kava extract LI 150 is as effective as Opipramol and Buspirone in Generalised Anxiety Disorder--an 8-week randomized, double-blind multi-centre clinical trial in 129 out-patients. Phytomedicine. 2003;10 Suppl 4:38-49. 

Malsch U, Kieser M. Efficacy of kava-kava in the treatment of non-psychotic anxiety, following pretreatment with benzodiazepines. Psychopharmacology (Berl). 2001 Sep;157(3):277-83. 

Teschke, R., Sarris, J., & Schweitzer, I. (2012). Kava hepatotoxicity in traditional and modern use: the presumed Pacific kava paradox hypothesis revisited. British journal of clinical pharmacology, 73(2), 170–174.

Hidese S, Ogawa S, Ota M, Ishida I, Yasukawa Z, Ozeki M, Kunugi H. Effects of L-Theanine Administration on Stress-Related Symptoms and Cognitive Functions in Healthy Adults: A Randomized Controlled Trial. Nutrients. 2019 Oct 3;11(10):2362. 

Williams JL, Everett JM, D'Cunha NM, Sergi D, Georgousopoulou EN, Keegan RJ, McKune AJ, Mellor DD, Anstice N, Naumovski N. The Effects of Green Tea Amino Acid L-Theanine Consumption on the Ability to Manage Stress and Anxiety Levels: a Systematic Review. Plant Foods Hum Nutr. 2020 Mar;75(1):12-23. 

Hidese S, Ota M, Wakabayashi C, Noda T, Ozawa H, Okubo T, Kunugi H. Effects of chronic l-theanine administration in patients with major depressive disorder: an open-label study. Acta Neuropsychiatr. 2017 Apr;29(2):72-79.