L-theanine in the adjunctive treatment of generalized anxiety disorder: A double-blind, randomised, placebo-controlled trial

J Psychiatr Res. 2019 Mar:110:31-37. doi: 10.1016/j.jpsychires.2018.12.014. Epub 2018 Dec 8.


Partial or non-response to antidepressants in Generalized Anxiety Disorder (GAD) is common in clinical settings, and adjunctive biological interventions may be required. Adjunctive herbal and nutraceutical treatments are a novel and promising treatment option. L-theanine is a non-protein amino acid derived most-commonly from tea (Camellia sinensis) leaves, which may be beneficial in the treatment of anxiety and sleep disturbance as suggested by preliminary evidence. We conducted a 10-week study (consisting of an 8-week double-blind placebo-controlled period, and 1-week pre-study and 2-week post-study single-blinded observational periods) involving 46 participants with a DSM-5 diagnosis of GAD. Participants received adjunctive L-theanine (450-900 mg) or matching placebo with their current stable antidepressant treatment, and were assessed on anxiety, sleep quality, and cognition outcomes. Results revealed that adjunctive L-theanine did not outperform placebo for anxiety reduction on the HAMA (p = 0.73) nor insomnia severity on the Insomnia Severity Index (ISI; p = 0.35). However, LT treated participants reported greater self-reported sleep satisfaction than placebo (ISI item 4; p = 0.015). Further, a separation in favour of L-theanine was noted on the ISI in those with non-clinical levels of insomnia symptoms (ISI ≤ 14; p = 0.007). No significant cognitive effects (trail making time and the modified emotional Stroop) were revealed. While this preliminary study did not support the efficacy of L-theanine in the treatment of anxiety symptoms in GAD, further studies to explore the application of L-theanine in sleep disturbance are warranted.

Keywords: Anxiety; GAD; L-theanine; Randomised controlled trial; Sleep.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents / pharmacology*
  • Anxiety Disorders / complications
  • Anxiety Disorders / drug therapy*
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / etiology
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Glutamates / administration & dosage
  • Glutamates / pharmacology*
  • Humans
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care*
  • Plant Preparations / administration & dosage
  • Plant Preparations / pharmacology*
  • Sleep Initiation and Maintenance Disorders / drug therapy*
  • Sleep Initiation and Maintenance Disorders / etiology


  • Antidepressive Agents
  • Glutamates
  • Plant Preparations
  • theanine