Effect of L-theanine on glutamatergic function in patients with schizophrenia

Acta Neuropsychiatr. 2015 Oct;27(5):291-6. doi: 10.1017/neu.2015.22. Epub 2015 Apr 21.


Objectives: Glutamatergic dysfunction in the brain has been implicated in the pathophysiology of schizophrenia. Previous studies suggested that L-theanine affects the glutamatergic neurotransmission and ameliorates symptoms in patients with schizophrenia. The aims of the present study were twofold: to examine the possible effects of L-theanine on symptoms in chronic schizophrenia patients and to evaluate the changes in chemical mediators, including glutamate + glutamine (Glx), in the brain by using 1H magnetic resonance spectroscopy (MRS).

Method: The subjects were 17 patients with schizophrenia and 22 age- and sex-matched healthy subjects. L-theanine (250 mg/day) was added to the patients' ongoing antipsychotic treatment for 8 weeks. The outcome measures were the Positive and Negative Syndrome Scale (PANSS), Pittsburgh Sleep Quality Index scores and MRS results.

Results: There were significant improvements in the PANSS positive scale and sleep quality after the L-theanine treatment. As for MRS, we found no significant differences in Glx levels before and after the 8 week L-theanine treatment. However, significant correlations were observed between baseline density of Glx and change in Glx density by l-theanine.

Conclusions: Our results suggest that L-theanine is effective in ameliorating positive symptoms and sleep quality in schizophrenia. The MRS findings suggest that L-theanine stabilises the glutamatergic concentration in the brain, which is a possible mechanism underlying the therapeutic effect.

Keywords: glutamine+glutamate; l-theanine (N-ethyl-l-glutamine); magnetic resonance spectroscopy; schizophrenia.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antipsychotic Agents / administration & dosage
  • Brain / drug effects
  • Brain / metabolism
  • Case-Control Studies
  • Female
  • Glutamates / administration & dosage*
  • Glutamic Acid / metabolism*
  • Glutamine / metabolism*
  • Humans
  • Magnetic Resonance Spectroscopy / methods
  • Male
  • Middle Aged
  • Schizophrenia / drug therapy*
  • Schizophrenia / metabolism*
  • Sleep / drug effects
  • Treatment Outcome


  • Antipsychotic Agents
  • Glutamates
  • Glutamine
  • Glutamic Acid
  • theanine