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By Jacob Schor, ND, FABNO

Natural Medicine JournalSlideshow Series

L-Theanine and Anxiety

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Overview The Root of Relaxation

Cultivation

Mechanism of Action

+The Root of Relaxation

Since ancient times, people have drunk green tea to induce relaxation. The substance responsible for this effect is the amino acid L-theanine (delta-glutamylethylamide), a significant amino acid present in green tea (camellia sinensis).

L-theanine accounts for nearly half of the total amino acids found in green tea and makes up from 1%–2% of the leaf dry weight.

+Cultivation

L-theanine is made in the roots of the green tea plant.

It concentrates in the leaves, where sunlight converts it to polyphenols.

Cultivating tea in the shade preserves L-theanine content.

+Mechanism of Action

L-theanine increases dopamine and serotonin production in the brain, producing a sense of relaxation.

It balances and controls the excitement caused by caffeine also found in the plant.

L-theanine us used therapeutically to reduce anxiety and has been approved as a food additive in Japan since 1964.1,2

1. Juneja LR, Chu D-C, Okubo T, Nagato Y, Yokogoshi H. L-theanine—a unique amino acid of green tea and its relaxation effect in humans. � Trends in Food Science & Technology. 1999;10:199-204. Available here.

2. L-Theanine. Alternative Medicine Review. 2005;10(2):136-138. Available here.

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Human StudiesAt least 6 different human clinical trials have documented L-theanine’s effect on anxiety. These data are augmented by a number of animal studies that bring greater understanding of pharmacokinetics and mechanism of action.

+1998 Nippon Nogei Kagakukaishi

Kobayashi et al reported L-theanine increases alpha-brain wave activity, inducing a sense of relaxation.

Eight female college students, half rated as high anxiety and half low anxiety, took 200 mg doses of L-theanine dissolved in water.

The researchers concluded: “These results indicate the possibility for L-theanine to be applied to foods and beverages as a new type of functional food ingredient for its relaxation effect.”3

3. Kobayashi K, Nagato Y, Aoi N, et al. Effects of L-theanine on the release of α-brain waves in human volunteers. Nippon Nōgei Kagakukaishi. 1998 (72)2:153-157.

+2004 Human Psychopharmacology Lu et al reported on the effect of l-theanine on anticipatory

anxiety, comparing it to the prescription benzodiazepine anxiolytic drug alprazolam.

Sixteen healthy volunteers took either alprazolam (1 mg), L-theanine (200 mg), or placebo in a double-blind, placebo-controlled repeated measures design.

The acute effects of alprazolam and L-theanine were assessed under a relaxed and experimentally induced anxiety condition.  

L-theanine showed some effect on baseline anxiety but did not exert an antianxiety effect when the subjects were performing anxiety-producing tasks. Alprzolam had no significant effect either.4

4. Lu K, Gray MA, Oliver C, et al. The acute effects of L-theanine incomparison with alprazolam on anticipatory anxiety in humans. Hum Psychopharmacol. 2004;19(7):457-465.

+2007 Biological Psychology

Kimura et al reported results of a double-blind trial that L-theanine reduces psychological and physiological stress responses.

A series of mental arithmetic problems were used as a stressor on 12 participants who underwent 4 separate trials, taking L-theanine at the start of the procedure and midway through, as well as 1 trial taking a placebo and 1 taking nothing.

L-theanine reduced heart rate and salivary immunoglobulin response because of a decrease in sympathetic nervous system activation.

Conclusion: “L-theanine reduces psychological and physiological stress responses.”5

5. Kimura K, Ozeki M, Juneja LR, Ohira H. L-Theanine reduces psychological and physiological stress responses. Biol Psychol. 2007;74(1):39-45.

+2011 Journal of Clinical Psychiatry

Ritsner et al examined the effect of L-theanine on 60 patients with schizophrenia or schizoaffective disorder who participated in an 8-week, double-blind, randomized, placebo-controlled study taking 400 mg/d of L-theanine in addition to their regular medications. Forty patients completed the study.

Compared with placebo, those taking L-theanine scored lower on measures of anxiety (HARS scale) and improved on measures of general psychopathology (PANSS 3-dimensional model), suggesting it may be a useful addition to antipsychotic medications.6

6. Ritsner MS, Miodownik C, Ratner Y, et al. L-theanine relieves positive, activation, and anxiety symptoms in patients with schizophrenia and schizoaffective disorder: an 8-week, randomized, double-blind, placebo-controlled, 2-center study. J Clin Psychiatry. 2011 Jan;72(1):34-42.

+2011 Clinical Neuropharmacology

Miodownik C et al examined circulating levels of neurochemical indicators and the beneficial clinical effects of L-theanine augmentation.

Brain-derived neurotrophic factor (BDNF), DHEA, DHEA-sulfate, cortisol, cholesterol, and insulin were monitored in the 40 who successfully completed the prior study.

Among L-theanine-treated patients, BDNF levels and cortisol-to-DHEA-sulfate ratio were significantly associated with the beneficial clinical effects of L-theanine supplementation, suggesting changes in both chemical markers play a role.7

7. Miodownik C, Maayan R, Ratner Y, et al. Serum levels of brain-derived neurotrophic factor and cortisol to sulfate of dehydroepiandrosterone molar ratio associated with clinical response to L-theanine as augmentation of antipsychotic therapy in schizophrenia and schizoaffective disorder patients. Clin Neuropharmacol. 2011 Jul-Aug;34(4):155-160.

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Animal StudiesAt least 3 animal studies of interest on L-theanine and anxiety have been published.

+2009 American Association of Nurse Anesthetists Journal

In 2009 Hesse et al divided 55 rats were into 5 groups: control (saline), L-theanine (positive control), flumazenil (a known benzodiazepine receptor antagonist) and L-theanine, and midazolam and L-theanine.

L-theanine does not decrease anxiety by modulation of the GABAA receptor. Combining L-theanine with midazolam produced a synergistic or additive effect measured by decreased anxiety and both fine and basic motor movements.8

8. Heese T, Jenkinson J, Love C, et al. Anxiolytic effects of L-theanine—a component of green tea—when combined with midazolam, in the male Sprague-Dawley rat. AANA J. 2009;77(6):445-449.

+2012 Pharmacology, Biochemistry, and Behavior

In 2012 Wise et al tested L-theanine on monkeys addicted to opioids and found it reduced signs of withdrawal.

The authors “suggest that L-theanine may be useful in the pharmacotherapy of treating opioid withdrawal as well as anxiety-associated behaviors … L-theanine attenuates abstinence signs in morphine-dependent rhesus monkeys and elicits anxiolytic-like activity in mice.”9

9. Wise LE, Premaratne ID, Gamage TF, et al. l-theanine attenuates abstinence signs in morphine-dependent rhesus monkeys and elicits anxiolytic-like activity in mice. Pharmacol Biochem Behav. 2012;103(2):245-252.

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Safety & Other Considerations

+Safety Profile

Tea is the single most popular beverage in the world after water. Significant toxicity is unlikely.

L-theanine was approved in Japan in 1964 for unlimited use in all foods, including chocolates, soft drinks, and herb teas (except infant foods) and has been granted GRAS (generally recognized as safe) status by the US Food and Drug Administration (FDA).

In a 13-week rat toxicity study published in 2006, “The no-observed-adverse-effect-level (NOAEL) was 4,000 mg/kg bw/day, the highest dose tested.” This would be equivalent to a 100-pound person taking 200 grams of l-theanine per day for a year (1,000 times the typical dose).11

11. Borzelleca JF, Peters D, Hall W. A 13-week dietary toxicity and toxicokinetic study with l-theanine in rats. Food Chem Toxicol. 2006;44(7):1158-1166.

+Absorption

L-theanine crosses the blood-brain barrier, with effects noticeable in 30 minutes and measurable up to 5 hours after administration.12,13

12. Bryan J. Psychological effects of dietary components of tea: caffeine and L-theanine. Nutr Rev. 2008;66(2):82-90.

13. Nobre AC, Rao A, Owen GN. L-theanine, a natural constituent in tea, and its effect on mental state. Asia Pac J Clin Nutr. 2008;17(suppl 1):167-168.

+Contraindications

Information regarding safety and efficacy in pregnancy and lactation is lacking.14

Little information adverse reactions from l-theanine is available. One study using older participants reported more headaches in those taking 1,000 mg per day.15,16

14. Ernst E. Herbal medicinal products during pregnancy: are they safe? BJOG. 2002;109(3):227-335. 15. Kell CF, Kennedy DO, Milne AL, Wesnes KA, Scholey AB. The effects of L-theanine, caffeine and their

combinationon cognition and mood. Biol Psychol. 2008;77(2):113-122.

16. Haskell CF, Kennedy DO, Milne AL, Wesnes KA, Scholey AB. The effects of L-theanine, caffeine and their combination on cognition and mood. Biol Psychol. 2008;77(2):113-122.