Revisiting Theanine!

 Today looking at  l-theanine (again!)
"aka Zen in a bottle :)"


One of my favorite materials to formulate with!

Over the years I've written some general articles about its use in cognitive support, modulating caffeine, and even endurance recovery... Super safe, no adverse effects,

 Here's a link to a Suite101 article!



Standard dosage -at least 50 mg/day...





OK, here are some recent studies:


Zarse, K., S. Jabin, et al. (2012). "L: -Theanine extends lifespan of adult Caenorhabditis elegans." Eur J Nutr.
PURPOSE: Compounds that delay aging in model organisms may be of significant interest to anti-aging medicine, since these substances potentially provide pharmaceutical approaches to promote healthy lifespan in humans. We here aimed to test whether pharmaceutical concentrations of L: -theanine, a putative anti-cancer, anti-obesity, blood pressure-lowering, and neuroprotective compound contained in green tea (Camellia sinensis), are capable of extending lifespan in a nematodal model organism for aging processes, the roundworm Caenorhabditis elegans. METHODS: Adult C. elegans roundworms were maintained on agar plates, were fed E. coli strain OP50 bacteria, and L: -theanine was applied to agar to test (1) whether it may increase survival upon paraquat exposure and (2) whether it may promote longevity by quantifying survival in the presence and absence of the compound. RESULTS: L: -theanine increases survival of C. elegans in the presence of paraquat at a concentration of 1 micromolar. L: -theanine extends C. elegans lifespan when applied at concentrations of 100 nM, as well as 1 and 10 micromolar. CONCLUSIONS: In the model organism C. elegans, L: -theanine is capable of promoting paraquat resistance and longevity suggesting that this compound may as well promote healthy lifespan in mammals and possibly humans.

Attia, S. (2012). "Modulation of irinotecan-induced genomic DNA damage by theanine." Food Chem Toxicol.
The possible chemoprotective activity of theanine against irinotecan-induced genomic DNA damage towards mouse bone marrow cells was investigated. Chromosomal aberrations, DNA damage, micronuclei formation and mitotic activity were studied in the current study as markers of genomic damage. Oxidative DNA stress markers such as 8-hydroxydeoxyguanosine, lipid peroxidation, reduced and oxidized glutathione levels were assessed as a possible mechanism underlying this amelioration. Theanine was neither genotoxic nor cytotoxic in mice at doses equivalent to 30 or 60mg/kg for 12days. Pretreatment of mice with theanine significantly reduced irinotecan-induced genomic damage in the bone marrow cells and these effects were dose dependent. Irinotecan induced marked biochemical alterations characteristic of oxidative DNA stress, including increased 8-hydroxydeoxyguanosine, enhanced lipid peroxidation and reduction in the reduced/oxidized glutathione ratio. Prior administration of theanine ahead of irinotecan challenge ameliorated these oxidative DNA stress markers. Overall, this study provides for the first time that theanine has a protective role in the abatement of irinotecan-induced genomic damage in the bone marrow cells of mice that resides, at least in part, on its ability to modulate the cellular antioxidant levels and consequently protect bone marrow from irinotecan genotoxicity.

Shibakusa, T., T. Mikami, et al. (2012). "Enhancement of postoperative recovery by preoperative oral co-administration of the amino acids, cystine and theanine, in a mouse surgical model." Clin Nutr.
BACKGROUND & AIMS: Glutathione (GSH) is important in the control of immune responses, and its levels decline following trauma. We previously reported that the oral administration of cystine/theanine (CT) increased GSH synthesis and that CT intake inhibited intense exercise-induced inflammation. Based on these results, we hypothesised that CT inhibits surgically induced inflammation and promotes postoperative recovery. Our aim was to confirm this hypothesis using a mouse surgical model. METHODS: CT or a vehicle (V) was administered orally to mice once a day for 5 days, until the day of surgery. On the day of surgery, a sham operation or an intestinal manipulation was performed 2 h after the oral administration of CT or V. Levels of IL-6 in the blood and GSH in the intestine were analysed 2 h after surgery. Behavioural analysis was also undertaken after surgery. RESULTS: Treatment with CT inhibited the manipulation-induced increase in IL-6 in the blood and decrease in GSH in the intestine. There was a significant negative correlation between IL-6 in the blood and GSH in the intestine. In addition, behavioural analysis revealed that CT administration improved locomotor activity and food intake after surgery. CONCLUSION: These results suggest that CT suppresses inflammatory responses by inhibiting the surgically induced decrease in GSH in the small intestine and promotes postoperative recovery.


Foxe, J. J., K. P. Morie, et al. (2012). "Assessing the effects of caffeine and theanine on the maintenance of vigilance during a sustained attention task." Neuropharmacology.
Caffeine and l-theanine, both naturally occurring in tea, affect the ability to make rapid phasic deployments of attention to locations in space as reflected in behavioural performance and alpha-band oscillatory brain activity (8-14 Hz). However, surprisingly little is known about how these compounds affect an aspect of attention that has been more popularly associated with tea, namely vigilant attention: the ability to maintain focus on monotonous tasks over protracted time-periods. Twenty-seven participants performed the Sustained Attention to Response Task (SART) over a two-hour session on each of four days, on which they were administered caffeine (50 mg), theanine (100 mg), the combination, or placebo in a double-blind, randomized, cross-over fashion. Concurrently, we recorded oscillatory brain activity through high-density electroencephalography (EEG). We asked whether either compound alone, or both in combination, would affect performance of the task in terms of reduced error rates over time, and whether changes in alpha-band activity would show a relationship to such changes in performance. When treated with placebo, participants showed a rise in error rates, a pattern that is commonly observed with increasing time-on-task, whereas after caffeine and theanine ingestion, error rates were significantly reduced. The combined treatment did not confer any additional benefits over either compound alone, suggesting that the individual compounds may confer maximal benefits at the dosages employed. Alpha-band oscillatory activity was significantly reduced on ingestion of caffeine, particularly in the first hour. This effect was not changed by addition of theanine in the combined treatment. Theanine alone did not affect alpha-band activity.

Jang, H. S., J. Y. Jung, et al. (2012). "L-theanine partially counteracts caffeine-induced sleep disturbances in rats." Pharmacol Biochem Behav 101(2): 217-221.
L-theanine has been reported to inhibit the excitatory effects of caffeine. The present study examined the effects of L-theanine on caffeine-induced sleep disturbances in rats. Rats received the following drug pairings: saline and saline (Control), 7.5mg/kg caffeine and saline, or 7.5mg/kg of caffeine followed by various doses of L-theanine (22.5, 37.5, 75, or 150mg/kg). Vigilance states were divided into: wakefulness (W), transition to slow-wave sleep (tSWS), slow-wave sleep (SWS), and rapid-eye-movement sleep (REMS). Caffeine significantly increased the duration of W and decreased the duration of SWS and REMS compared to the Control. Although L-theanine failed to reverse the caffeine-induced W increase, at 22.5 and 37.5mg/kg (but not at 75 and 150mg/kg), it significantly reversed caffeine-induced decreases in SWS. In conclusion, low doses of L-theanine can partially reverse caffeine-induced reductions in SWS; however, effects of L-theanine on caffeine-induced insomnia do not appear to increase dose-dependently.

Song, J., H. Xu, et al. (2012). "Tea and cognitive health in late life: current evidence and future directions." J Nutr Health Aging 16(1): 31-34.
This review summarizes the literature on the association between tea consumption and cognitive health in late life. Population-based studies reviewed in this article suggest that tea drinking has beneficial effects on cognitive function of elderly persons. However, a cause-effect relationship between tea consumption and cognitive decline and dementia could not be drawn given inconsistent findings from only two longitudinal cohort studies. The neuroprotective effects of tea consumption could be due to catechins, L-theanine and other compounds in tea leaves. More longitudinal observational study is needed. Information on life-time tea consumption and blood concentrations of catechins and L-theanine could be collected in future studies.

Lyon, M. R., M. P. Kapoor, et al. (2011). "The effects of L-theanine (Suntheanine(R)) on objective sleep quality in boys with attention deficit hyperactivity disorder (ADHD): a randomized, double-blind, placebo-controlled clinical trial." Altern Med Rev 16(4): 348-354.
INTRODUCTION: The purpose of this study was to investigate the efficacy and safety of L-theanine as an aid to the improvement of objectively measured sleep quality in a population of 98 male children formally diagnosed with attention-deficit/hyperactivity disorder (ADHD). METHODS: A randomized, double-blind, placebo-controlled trial was conducted involving boys, ages 8-12 years, who had been previously diagnosed with ADHD. An experienced physician confirmed the diagnosis of ADHD in each subject. Randomization was stratified based upon current use of stimulant medication to ensure an equal distribution of stimulant/non-stimulant treated subjects into active and placebo treated groups. Participants consumed two chewable tablets twice daily (at breakfast and after school), with each tablet containing 100 mg of L-theanine (total 400 mg daily Suntheanine(R), Taiyo Kagaku, Yokkaichi, Japan) or identical tasting chewable placebo for six weeks. Subjects were evaluated for five consecutive nights using wrist actigraphy at baseline, and again at the end of the six-week treatment period. The Pediatric Sleep Questionnaire (PSQ) was completed by parents at baseline and at the end of the treatment period. RESULTS: Actigraph watch data findings indicated that boys who consumed L-theanine obtained significantly higher sleep percentage and sleep efficiency scores, along with a non-significant trend for less activity during sleep (defined as less time awake after sleep onset) compared to those in the placebo group. Sleep latency and other sleep parameters were unchanged. The PSQ data did not correlate significantly to the objective data gathered from actigraphy, suggesting that parents were not particularly aware of their children's sleep quality. L-theanine at relatively high doses was well tolerated with no significant adverse events. CONCLUSIONS: This study demonstrates that 400 mg daily of L-theanine is safe and effective in improving some aspects of sleep quality in boys diagnosed with ADHD. Since sleep problems are a common co-morbidity associated with ADHD, and because disturbed sleep may be linked etiologically to this disorder, L-theanine may represent a safe and important adjunctive therapy in childhood ADHD. Larger, long-term studies looking at the wider therapeutic role of this agent in this population are warranted.

Zhao, Y. and B. Zhao (2012). "Natural antioxidants in prevention and management of Alzheimer's disease." Front Biosci (Elite Ed) 4: 794-808.
Alzheimer's disease (AD) is the most common neurodegenerative disease that causes dementia in the elderly. As the aging population increases, the prevalence of AD has increased remarkably worldwide and AD has become one of the leading causes of disability and death among the elderly. A number of drugs have been approved for the treatment of AD; however, they produce only modest benefits and have a wide range of side effects. Therefore, extensive studies are underway to identify effective drugs that are free of undesirable side effects. As accumulating evidences have implicated oxidative stress in the initiation and progression of AD, the potential of using nature antioxidants for prevention and treatment of AD has attracted considerable attention. The present review discusses the involvement of oxidative stress in the pathogenesis of AD and the neuroprotective effects of natural antioxidants, such as Ginkgo biloba flavonoids, soybean isoflavones, theanine and nicotine in cell culture and AD transgenic animal models, specifically, their inhibition on Abeta-induced neurotoxicity and the underlined molecular mechanisms.

Cooper, R. (2012). "Green tea and theanine: health benefits." Int J Food Sci Nutr 63 Suppl 1: 90-97.
Historically, the medicinal use of green tea dates back to China 4700 years ago and drinking tea continues to be regarded traditionally in Asia as a general healthful practice. Numerous scientific publications now attest to the health benefits of both black and green teas, including clinical and epidemiological studies. Although all tea contains beneficial antioxidants, high-quality green and white teas have them in greater concentrations than black tea. Today, scientists believe that the main active ingredients of green tea include the polyphenols, in particular the catechins and the amino acid, theanine. Studies on the health benefits of drinking tea, particularly green tea, are finding exciting results, particularly in cancer research. Modern studies in both Asia and the West have provided encouraging results indicating that drinking green tea contributes to fighting many different kinds of cancers including stomach, oesophageal, ovarian and colon. Recent studies describing the health benefits of these compounds will be reviewed.

Li, G., Y. Ye, et al. (2012). "l-Theanine prevents alcoholic liver injury through enhancing the antioxidant capability of hepatocytes." Food Chem Toxicol 50(2): 363-372.
l-Theanine is a unique amino acid in green tea. We here evaluated the protective effects of l-theanine on ethanol-induced liver injury in vitro and in vivo. Our results revealed that l-theanine significantly protected hepatocytes against ethanol-induced cell cytotoxicity which displayed by decrease of viability and increase of LDH and AST. Furthermore, the experiments of DAPI staining, pro-caspase3 level and PARP cleavage determination indicated that l-theanine inhibited ethanol-induced L02 cell apoptosis. Mechanically, l-theanine inhibited loss of mitochondrial membrane potential and prevented cytochrome c release from mitochondria in ethanol-treated L02 cells. l-Theanine also prevented ethanol-triggered ROS and MDA generation in L02 cells. l-Theanine restored the antioxidant capability of hepatocytes including GSH content and SOD activity which were reduced by ethanol. In vivo experiments showed that l-theanine significantly inhibited ethanol-stimulated the increase of ALT, AST, TG and MDA in mice. Histopathological examination demonstrated that l-theanine pretreated to mice apparently diminished ethanol-induced fat droplets. In accordance with the in vitro study, l-theanine significantly inhibited ethanol-induced reduction of mouse antioxidant capability which included the activities of SOD, CAT and GR, and level of GSH. These results indicated that l-theanine prevented ethanol-induced liver injury through enhancing hepatocyte antioxidant abilities.

Wakabayashi, C., T. Numakawa, et al. (2012). "Behavioral and molecular evidence for psychotropic effects in L-theanine." Psychopharmacology (Berl) 219(4): 1099-1109.
RATIONALE: L-Theanine (N-ethyl-L: -glutamine) is an amino acid uniquely found in green tea and historically considered to be a relaxing agent. It is a glutamate derivative and has an affinity for glutamatergic receptors. However, its psychotropic effects remain unclear. OBJECTIVES: To elucidate effects of L: -theanine on psychiatric disease-related behaviors in mice and its molecular basis focusing on brain-derived neurotrophic factor (BDNF) and N-methyl-D: -aspartate (NMDA) receptor. METHODS: We examined the effects of L: -theanine on behaviors in mice by using the open-field test (OFT), forced swim test (FST), elevated plus-maze test (EPMT), and prepulse inhibition (PPI) of acoustic startle. By western blot analysis, we looked at the effect of L: -theanine on the expression of BDNF and related proteins in the hippocampus and cerebral cortex. To determine whether L: -theanine has agonistic action on the NMDA receptor, we performed Fluo-3 intracellular Ca(2+) imaging in cultured cortical neurons. RESULTS: Single administration of L: -theanine significantly attenuated MK-801-induced deficits in PPI. Subchronic administration (3-week duration) of L: -theanine significantly reduced immobility time in the FST and improved baseline PPI. Western blotting analysis showed increased expression of BDNF protein in the hippocampus after subchronic administration of L: -theanine. In cultured cortical neurons, L: -theanine significantly increased the intracellular Ca(2+) concentration, and this increase was suppressed by competitive and non-competitive NMDA receptor antagonists (AP-5 and MK-801, respectively). CONCLUSIONS: Our results suggest that L: -theanine has antipsychotic-like and possibly antidepressant-like effects. It exerts these effects, at least in part, through induction of BDNF in the hippocampus and the agonistic action of L: -theanine on the NMDA receptor.

Takeda, A., H. Tamano, et al. (2012). "Unique induction of CA1 LTP components after intake of theanine, an amino acid in tea leaves and its effect on stress response." Cell Mol Neurobiol 32(1): 41-48.
Theanine, gamma-glutamylethylamide, is one of the major amino acid components in green tea. This study was undertaken to evaluate the effect of theanine intake on long-term potentiation (LTP) induction at hippocampal CA1 synapses and exposure to acute stress. Young rats were fed water containing 0.3% theanine after birth. Key findings: Serum corticosterone level was markedly decreased by theanine intake. Because this decrease can modify synaptic plasticity, the effect of theanine intake was examined focused on CA1 LTP induction. CA1 LTP induced by a 100-Hz tetanus for 1 s was almost the same extent in hippocampal slices from theanine-administered rats, whereas that induced by a 200-Hz tetanus for 1 s was significantly attenuated. 2-Amino-5-phosphonovalerate (APV), an N-methyl-D: -aspartate (NMDA) receptor antagonist, significantly attenuated CA1 LTP induced by a 200-Hz tetanus in the control rats, but not in theanine-administered rats. Interestingly, APV completely blocked CA1 LTP induced by a 100-Hz tetanus in the control rats, while scarcely blocking it in theanine-administered rats. These results indicate that theanine intake reduces NMDA receptor-dependent CA1 LTP, while increasing NMDA receptor-independent CA1 LTP. Furthermore, neither 100-Hz tetanus-induced LTP nor 200-Hz tetanus-induced LTP was attenuated in theanine-administered rats after exposure to tail suspension stress, suggesting that the lack of NMDA receptor-dependent CA1 LTP by theanine intake is involved in ameliorating the attenuation of CA1 LTP after tail suspension. This study is the first to indicate that theanine intake modifies the mechanism of CA1 LTP induction.

Vuong, Q. V., M. C. Bowyer, et al. (2011). "L-Theanine: properties, synthesis and isolation from tea." J Sci Food Agric 91(11): 1931-1939.
Theanine is a non-protein amino acid that occurs naturally in the tea plant (Camellia sinensis) and contributes to the favourable taste of tea. It is also associated with effects such as the enhancement of relaxation and the improvement of concentration and learning ability. It is also linked with health benefits including the prevention of certain cancers and cardiovascular disease, the promotion of weight loss and enhanced performance of the immune system. Thus, there has been a significant rise in the demand for theanine. While theanine has been chemically and biologically synthesised, techniques to isolate theanine from natural sources remain an important area of research. In this review article, the properties and health benefits of theanine are summarised and the synthesis and isolation of theanine are reviewed and discussed. Future perspectives for the isolation of theanine from natural sources are also outlined.

Miodownik, C., R. Maayan, et al. (2011). "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 34(4): 155-160.
OBJECTIVES: L-Theanine (gamma-glutamylethylamide) augmentation to antipsychotic therapy ameliorates positive, activation, and anxiety symptoms in schizophrenia and schizoaffective disorder patients. This study examines the association between circulating levels of neurochemical indicators and the beneficial clinical effects of L-theanine augmentation. METHODS: Serum levels of neurochemical indicators such as brain-derived neurotrophic factor (BDNF), dehydroepiandrosterone (DHEA), its sulfate (DHEAS), cortisol, cholesterol, and insulin were monitored in 40 schizophrenia and schizoaffective disorder patients during an 8-week, double-blind, randomized, placebo-controlled trial with L-theanine (400 mg/d). Multiple regression analysis was applied for searching association between improvement in symptom scores and changes in circulating levels of neurochemical indicators for an 8-week trial. RESULTS: Regression models among L-theanine-treated patients indicate that circulating levels of BDNF and cortisol-to-DHEAS*100 molar ratio were significantly associated with the beneficial clinical effects of L-theanine augmentation. Variability of serum BDNF levels accounted for 26.2% of the total variance in reduction of dysphoric mood and 38.2% in anxiety scores. In addition, the changes in cortisol-to-DHEAS*100 molar ratio accounted for 30% to 34% of the variance in activation factor and dysphoric mood scores and for 15.9% in anxiety scores. Regression models among placebo-treated patients did not reach significant level. CONCLUSIONS: These preliminary results indicate that circulating BDNF and cortisol-to-DHEAS*100 molar ratio may be involved in the beneficial clinical effects of L-theanine as augmentation of antipsychotic therapy in schizophrenia and schizoaffective disorder patients.

Takeda, A., K. Sakamoto, et al. (2011). "Facilitated neurogenesis in the developing hippocampus after intake of theanine, an amino Acid in tea leaves, and object recognition memory." Cell Mol Neurobiol 31(7): 1079-1088.
Theanine, gamma-glutamylethylamide, is one of the major amino acid components in green tea. In this study, cognitive function and the related mechanism were examined in theanine-administered young rats. Newborn rats were fed theanine through dams, which were fed water containing 0.3% theanine, and then fed water containing 0.3% theanine after weaning. Theanine level in the brain was under the detectable limit 6 weeks after the start of theanine administration. Theanine administration did not influence locomotor activity in the open-field test. However, rearing behavior was significantly increased in theanine-administered rats, suggesting that exploratory activity is increased by theanine intake. Furthermore, object recognition memory was enhanced in theanine-administered rats. The increase in exploratory activity in the open-field test seems to be associated with the enhanced object recognition memory after theanine administration. On the other hand, long-term potentiation (LTP) induction at the perforant path-granule cell synapse was not changed by theanine administration. To check hippocampal neurogenesis, BrdU was injected into rats 3 weeks after the start of theanine administration, and brain-derived neurotropic factor (BDNF) level was significantly increased at this time. Theanine intake significantly increased the number of BrdU-, Ki67-, and DCX-labeled cells in the granule cell layer 6 weeks after the start of theanine administration. This study indicates that 0.3% theanine administration facilitates neurogenesis in the developing hippocampus followed by enhanced recognition memory. Theanine intake may be of benefit to the postnatal development of hippocampal function.

Kakuda, T. (2011). "Neuroprotective effects of theanine and its preventive effects on cognitive dysfunction." Pharmacol Res 64(2): 162-168.
Theanine (gamma-glutamylethylamide) characteristically present in tea leaves (Camellia sinensis). It has a similar chemical structure to glutamate, which is a neurotransmitter related to memory. Theanine passes through the blood-brain barrier and has been shown to have a cerebroprotective effect and a preventive effect on neuronal cell death after transient cerebral ischemia. The neuroprotective effect is partly due to the antagonistic action of theanine on glutamate receptor subtype AMPA and kainate receptors, but the affinity is very low. Theanine also acted on glutamine (Gln) transporter strongly and inhibited the incorporation of extracellular Gln into neurons, which in turn suppressed the conversion of Gln to glutamate by glutaminase, a reaction required for condensation into synaptic vesicles to form a neurotransmitter pool responsible for subsequent exocytotic release upon stimuli. In an investigation of elderly persons with normal or slight cognitive dysfunction, volunteers who ingested powdered green tea containing a high theanine concentration (equivalent to 47.5mgday(-1) of theanine) showed significantly lower decline in cognitive function compared with that of the placebo group. This result suggested that theanine might have improved a slight cognitive dysfunction in elderly persons.

Park, S. K., I. C. Jung, et al. (2011). "A combination of green tea extract and l-theanine improves memory and attention in subjects with mild cognitive impairment: a double-blind placebo-controlled study." J Med Food 14(4): 334-343.
A combination of green tea extract and l-theanine (LGNC-07) has been reported to have beneficial effects on cognition in animal studies. In this randomized, double-blind, placebo-controlled study, the effect of LGNC-07 on memory and attention in subjects with mild cognitive impairment (MCI) was investigated. Ninety-one MCI subjects whose Mini Mental State Examination-K (MMSE-K) scores were between 21 and 26 and who were in either stage 2 or 3 on the Global Deterioration Scale were enrolled in this study. The treatment group (13 men, 32 women; 57.58 +/- 9.45 years) took 1,680 mg of LGNC-07, and the placebo group (12 men, 34 women; 56.28 +/- 9.92 years) received an equivalent amount of maltodextrin and lactose for 16 weeks. Neuropsychological tests (Rey-Kim memory test and Stroop color-word test) and electroencephalography were conducted to evaluate the effect of LGNC-07 on memory and attention. Further analyses were stratified by baseline severity to evaluate treatment response on the degree of impairment (MMSE-K 21-23 and 24-26). LGNC-07 led to improvements in memory by marginally increasing delayed recognition in the Rey-Kim memory test (P = .0572). Stratified analyses showed that LGNC-07 improved memory and selective attention by significantly increasing the Rey-Kim memory quotient and word reading in the subjects with MMSE-K scores of 21-23 (LGNC-07, n = 11; placebo, n = 9). Electroencephalograms were recorded in 24 randomly selected subjects hourly for 3 hours in eye-open, eye-closed, and reading states after a single dose of LGNC-07 (LGNC-07, n = 12; placebo, n = 12). Brain theta waves, an indicator of cognitive alertness, were increased significantly in the temporal, frontal, parietal, and occipital areas after 3 hours in the eye-open and reading states. Therefore, this study suggests that LGNC-07 has potential as an intervention for cognitive improvement.

Ritsner, M. S., C. Miodownik, et al. (2011). "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 72(1): 34-42.
OBJECTIVE: L-theanine is a unique amino acid present almost exclusively in the tea plant. It possesses neuroprotective, mood-enhancing, and relaxation properties. This is a first study designed to evaluate the efficacy and tolerability of L-theanine augmentation of antipsychotic treatment of patients with chronic schizophrenia and schizoaffective disorder. METHOD: 60 patients with DSM-IV schizophrenia or schizoaffective disorder participated in an 8-week, double-blind, randomized, placebo-controlled study. 400 mg/d of L-theanine was added to ongoing antipsychotic treatment from February 2006 until October 2008. The outcome measures were the Positive and Negative Syndrome Scale (PANSS), the Hamilton Anxiety Rating Scale (HARS), the Cambridge Neuropsychological Test Automated Battery (CANTAB) for neurocognitive functioning, and additional measures of general functioning, side effects, and quality of life. RESULTS: 40 patients completed the study protocol. Compared with placebo, L-theanine augmentation was associated with reduction of anxiety (P = .015; measured by the HARS scale) and positive (P = .009) and general psychopathology (P < .001) scores (measured by the PANSS 3-dimensional model). According to the 5-dimension model of psychopathology, L-theanine produced significant reductions on PANSS positive (P = .004) and activation factor (P = .006) scores compared to placebo. The effect sizes (Cohen d) for these differences ranged from modest to moderate (0.09-0.39). PANSS negative and CANTAB task scores, general functioning, side effect, and quality of life measures were not affected by L-theanine augmentation. L-theanine was found to be a safe and well-tolerated medication. CONCLUSIONS: L-theanine augmentation of antipsychotic therapy can ameliorate positive, activation, and anxiety symptoms in schizophrenia and schizoaffective disorder patients. Further long-term studies of L-theanine are needed to substantiate the clinically significant benefits of L-theanine augmentation.

Cross, D. R., G. Kellermann, et al. (2011). "A randomized targeted amino acid therapy with behaviourally at-risk adopted children." Child Care Health Dev 37(5): 671-678.
BACKGROUND: Increasing numbers of children are at-risk for behavioural and emotional disorders, a phenomenon contributing to increased use of pharmacological interventions for paediatric clients. Adverse side effects and other risks associated with pharmacological approaches have helped fuel interest in nutritional interventions for behaviourally at-risk children. METHODS: The current randomized clinical trial evaluates the efficacy of a neurochemical intervention involving the glutamine and glutamate analogue L-theanine and 5-hydroxytryptophan, the precursor for serotonin, with children adopted from traumatic backgrounds. RESULTS: Results include significant increases in urinary levels of the biomarkers for serotonin and gamma-aminobutyric acid, coupled with significant decreases in parent reports of the children's behaviour problems. CONCLUSIONS: While further research is needed, these initial findings are encouraging and are consistent with a growing number of studies indicating the efficacy of nutritional approaches to help behaviourally at-risk children.

Giesbrecht, T., J. A. Rycroft, et al. (2010). "The combination of L-theanine and caffeine improves cognitive performance and increases subjective alertness." Nutr Neurosci 13(6): 283-290.
The non-proteinic amino acid L-theanine and caffeine, a methylxanthine derivative, are naturally occurring ingredients in tea. The present study investigated the effect of a combination of 97 mg L-theanine and 40 mg caffeine as compared to placebo treatment on cognitive performance, alertness, blood pressure, and heart rate in a sample of young adults (n = 44). Cognitive performance, self-reported mood, blood pressure, and heart rate were measured before L-theanine and caffeine administration (i.e. at baseline) and 20 min and 70 min thereafter. The combination of moderate levels of L-theanine and caffeine significantly improved accuracy during task switching and self-reported alertness (both P < 0.01) and reduced self-reported tiredness (P < 0.05). There were no significant effects on other cognitive tasks, such as visual search, choice reaction times, or mental rotation. The present results suggest that 97 mg of L-theanine in combination with 40 mg of caffeine helps to focus attention during a demanding cognitive task.