Effects of chronic l-theanine administration in patients with major depressive disorder: an open-label study
Open accessAbstract
Objective: l-theanine, an amino acid uniquely contained in green tea (Camellia sinensis), has been suggested to have various psychotropic effects. This study aimed to examine whether l-theanine is effective for patients with major depressive disorder (MDD) in an open-label clinical trial. Methods: Subjects were 20 patients with MDD (four males; mean age: 41.0±14.1 years, 16 females; 42.9±12.0 years).l-theanine (250 mg/day) was added to the current medication of each participant for 8 weeks. Symptoms and cognitive functions were assessed at baseline, 4, and 8 weeks after l-theanine administration by the 21-item version of the Hamilton Depression Rating Scale (HAMD-21), State-Trait Anxiety Inventory (STAI), Pittsburgh Sleep Quality Index (PSQI), Stroop test, and Brief Assessment of Cognition in Schizophrenia (BACS). Results: HAMD-21 score was reduced after l-theanine administration (p=0.007). This reduction was observed in unremitted patients (HAMD-21>7;p=0.004) at baseline. Anxiety-trait scores decreased after l-theanine administration (p=0.012) in the STAI test. PSQI scores also decreased after l-theanine administration (p=0.030) in the unremitted patients at baseline. Regarding cognitive functions, response latency (p=0.001) and error rate (p=0.036) decreased in the Stroop test, and verbal memory (p=0.005) and executive function (p=0.016) were enhanced in the BACS test after l-theanine administration. Conclusion: Our study suggests that chronic (8-week)l-theanine administration is safe and has multiple beneficial effects on depressive symptoms, anxiety, sleep disturbance and cognitive impairments in patients with MDD. However, since this is an open-label study, placebo-controlled studies are required to consolidate the effects.
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Four weeks L-theanine administration (250 mg/day) had multiple favourable effects in patients with major depressive disorder, in an open-label study.
“In accordance with this, we have reported multiple favourable effects of four weeks L-theanine administration (250 mg/day) in patients with major depressive disorder (MDD), although this was an open-label study [40].”
From Effects of L-Theanine Administration on Stress-Related Symptoms and Cognitive Functions in Healthy Adults: A Randomized Controlled Trial (2019) · cites this paper as [40]
The L-theanine administration section describes an open-label study in patients with MDD using 250 mg/day, and the Discussion reports multiple favourable effects. But treatment lasted eight weeks, not four; the Statistics section says the reported comparisons were between baseline and eight weeks. Four-week measurements were recorded, but they do not support describing this as a four-week study. (LLM, conf=0.90)
Experimental — accuracy not yet measuredThe sample of 30 participants provided >0.80 power to detect an effect size of 0.61 on depression score from a previous study.
“The current sample (30 L-theanine and 30 placebo) had a power of> 0.80, based on the effect size (0.61) of L-theanine on depression score in our previous study [40].”
From Effects of L-Theanine Administration on Stress-Related Symptoms and Cognitive Functions in Healthy Adults: A Randomized Controlled Trial (2019) · cites this paper as [40]
The findings of improved cognitive function after L-theanine are consistent with previous preclinical studies and a clinical trial for MDD, but inconsistent with acute attention-improving effects in healthy humans.
“These findings are consistent with previous preclinical studies [11,20,21] and our clinical trial for MDD [40], whereas they are inconsistent with the acute attention-improving effects reported in healthy humans [28,29,30,36,37,38].”
From Effects of L-Theanine Administration on Stress-Related Symptoms and Cognitive Functions in Healthy Adults: A Randomized Controlled Trial (2019) · cites this paper as [40]
The present study was performed on individuals without clinical depression, which may have resulted in inconsistency concerning the cognitive-enhancing effects compared to a previous study.
“In contrast to our previous study [40], the present study was performed on individuals without clinical depression, which may have resulted in inconsistency concerning the cognitive-enhancing effects.”
From Effects of L-Theanine Administration on Stress-Related Symptoms and Cognitive Functions in Healthy Adults: A Randomized Controlled Trial (2019) · cites this paper as [40]
L-theanine may be a psychoactive reagent broadly useful to improve mental health in humans.
“In addition to the possible efficacy in the treatment of clinical depression [40], the present study suggests that L-theanine may be a psychoactive reagent broadly useful to improve mental health in humans.”
From Effects of L-Theanine Administration on Stress-Related Symptoms and Cognitive Functions in Healthy Adults: A Randomized Controlled Trial (2019) · cites this paper as [40]
Hidese's study was open-labelled, so its interpretation requires caution.
“It is however worth noting that Hidese's study was open-labelled, thus caution may be necessary on its interpretation.”
From Psychotropic effects of L-theanine and its clinical properties: from the management of anxiety and stress to a potential use in schizophrenia (2019) · cites this paper as [24]
Hidese et al found that L-theanine administration reduced depressive symptoms and improved cognitive function in patients with major depressive disorder.
“As discussed earlier, Hidese and colleagues found that L-theanine administration reduced depressive symptoms and improved cognitive function in MDD patients [24].”
From Psychotropic effects of L-theanine and its clinical properties: from the management of anxiety and stress to a potential use in schizophrenia (2019) · cites this paper as [24]
In individuals with major depressive disorder who received 250 mg L-theanine, verbal memory and executive function improved on the Brief Assessment of Cognition in Schizophrenia.
“Additionally, verbal memory and executive function were improved in individuals diagnosed with Major Depressive Disorder (MDD) supplemented with 250 mg of L-theanine and tested for the Brief Assessment of Cognition in Schizophrenia (BACS) [24].”
From Psychotropic effects of L-theanine and its clinical properties: from the management of anxiety and stress to a potential use in schizophrenia (2019) · cites this paper as [24]
The anxiety and stress findings were obtained using validated psychometric tools including HARS, Tension Anxiety Scores, PSQI, and PANSS.
“Such findings were obtained through the employment of several validated psychometric tools, including the Hamilton Anxiety Rating Scale (HARS), Tension Anxiety Scores, Pittsburgh Sleep Quality Index (PSQI), Positive and Negative Syndrome Scale (PANSS) [24,25], and others.”
From Psychotropic effects of L-theanine and its clinical properties: from the management of anxiety and stress to a potential use in schizophrenia (2019) · cites this paper as [24]
GABA-mediated central nervous system inhibition may be associated with L-theanine's anxiolytic effects and may help sleep disturbances, particularly in individuals with major depressive disorder.
“Regarding its clinical features, inhibition of the central nervous system mediated by the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) may be associated with the anxiolytic effects of L-theanine, and such association may be helpful for sleep disturbances, particularly in MDD individuals [24,31].”
From Psychotropic effects of L-theanine and its clinical properties: from the management of anxiety and stress to a potential use in schizophrenia (2019) · cites this paper as [24]
In an open-label study, L-theanine at 250 mg/day added to current medication for eight weeks decreases Hamilton Depression Rating Scale score (P = 0.007) and State-Trait Anxiety Inventory score (P = 0.012) in individuals with major depressive disorder.
“This chronic administration of L-theanine decreased the Hamilton Depression Rating Scale (HAMD-21)-score (P = 0.007) and STAI (P = 0.012).”
From How does the tea L-theanine buffer stress and anxiety (2022) · cites this paper as [30]
L-theanine at 250 mg/day improves cognitive function in major depressive disorder, shown by decreased response latency (P = 0.001) and error rate (P = 0.036) in the Stroop test, and increased verbal memory (P = 0.005) and executive function (P = 0.016) in the Brief Assessment of Cognition in Schizophrenia test.
“In the study mentioned above performed by Hidese et al. [30], cognitive function was improved after L-theanine treatment (250 mg/day) as shown by decreased response latency (P = 0.001) and error rate (P = 0.036) in the Stroop test, and increased verbal memory (P = 0.005) and executive function (P = 0.016) in the Brief Assessment of Cognition in Schizophrenia test [30].”
From How does the tea L-theanine buffer stress and anxiety (2022) · cites this paper as [30]
Reduction in heart rate and s-IgA mediates attenuation of sympathetic nerve activation or suppression of excitation of cortical neuron.
“The reduction in heart rate and s-IgA mediate attenuation of the sympathetic nerve activation or suppression of the excitation of cortical neuron [53][54][55][56] .”
From l -theanine: A potential multifaceted natural bioactive amide as health supplement (2017) · cites this paper as [55]
The antidepressant mechanism of L-theanine involves heart rate reduction and salivary immunoglobulin A decrease responses to an acute stress task.
“The antidepressant mechanism of L-theanine involving heart rate reduction and salivary immunoglobulin A (s-IgA) decrease responses to an acute stress task.”
From l -theanine: A potential multifaceted natural bioactive amide as health supplement (2017) · cites this paper as [55]
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- Authors
- Hidese, S., Ota, M., Wakabayashi, C., Noda, T., Ozawa, H., Okubo, T., & Kunugi, H.
- Affiliations
- Tokyo Medical and Dental University (JP)
- National Center of Neurology and Psychiatry (JP)
- Taiyo Kagaku Co., Ltd. (Japan) (JP)
- Corresponding author
- Kunugi, Hiroshi
- Venue
- Acta Neuropsychiatrica
- Publisher
- Cambridge University Press (CUP)
- Published
- 2016-07-11
- Volume
- 29
- Issue
- 2
- Pages
- 72-79
- ISSN
- 0924-2708 (ISSN-L)
- 1601-5215
- OpenAlex
- W2461254030
- Cited by
- 81
- References
- 50
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 4 · 2023: 6 · 2022: 10 · 2021: 9 · 2020: 14 · 2019: 7 · 2018: 7 · 2017: 7
- FWCI
- 5.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Acta Neuropsychiatrica (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Funders
- National Center of Neurology and Psychiatry (24-11, 24-11, 27-1)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plant Extracts Effects
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- theanine, major depressive disorder, depression treatment, anxiety, sleep disorders, cognitive function, executive function, verbal memory, Stroop task, BACS, adjunctive therapy
- MeSH terms
- Adult, Anxiety, Cognition, Major Depressive Disorder, Depressive Disorder, Major, Female, Glutamates, Humans, Male, Mental Status Schedule, Middle Aged, Treatment Outcome, Stroop Test
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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