Theanine (L-theanine, 5-N-ethyl-L-glutamine, delta-glutamylethylamide; gamma-glutamylethylamide) is an amino acid found in green tea.
Theanine crosses the blood-brain barrier.
1. Neurophsiological effect of theanine¶
L-theanine has a neurophysiological effect as:
-
Glutamate reuptake inhibitors
- Theanine has a strong effect on the glutamine transporter and inhibits glutamine reuptake, which in turn suppresses the conversion of glutamine into glutamate by glutaminase.
- competitive low-affinity glutamate receptor antagonist in the hippocampus
- very weakly antagonistic to glutamate AMPA and glutamate kainate receptors.
- binds to GABA-A receptors
- increased gene expression with a large effect size
- in the hippocampus
- EGR1 (Early growth response protein 1; also ZNF268 = Zinc finger protein 268 or NGFI-A = Nerve growth factor-induced protein A)
- MAO-A (monoamine oxidase A; breaks down serotonin, dopamine and noradrenaline)
- ANXA9 (Annexin A9)
- S100a10 (Calcium-binding protein A10; P11)
- GABRB2 (GABA-A receptor beta-2 subunit)
- CHRM2 (muscarinic acetylcholine receptor M2)
- in the amygdala
- GABRA4 (GABA-A receptor alpha-4 subunit)
- SLC5A7 (high-affinity choline transporter; solute carrier family 5 member 7)
-
DRD2 (D2 dopamine receptor gene)
-
DRD1a (D1a dopamine receptor gene)
- GLRA2 (glycine receptor alpha 2)
- CHRNA6 (nicotinic receptor / choline receptor alpha 6)
- HTR3A (serotonin 3A receptor)
- CHRNB4 (nicotinic receptor / choline receptor beta 4)
- GABRD (GABA-A receptor subunit delta)
- PRIMA1 (Proline Rich Membrane Anchor 1)
- CHRNA3 (nicotinic receptor / choline receptor alpha 3)
L-theanine is safe in daily doses of 200 to 400 mg over a period of up to 8 weeks.
2. Behavioral effect of theanine¶
Theanine has a calming and relaxing effect, also better than the benzodiazepine alprazolam, but not anxiolytic. According to other studies, theanine has an anxiolytic and stress-inhibiting effect, although the anxiolytic effect does not appear to be due to an effect on the GABA-A receptor.
Caffeine and gallate catechins, which are abundant in tea, inhibit the relaxing effect of theanine.
Theanine inhibited the deterioration of cognitive functions in older people and could have neuroprotective effects to prevent Parkinson’s disease.
L-theanine administration promoted the release of dopamine and noradrenaline in the hippocampus of mice and stimulated protein kinase A (PKA) phosphorylation. The long-term potentiation in the hippocampus improved by L-theanine in an Alzheimer’s mouse model could be impaired by a PKA inhibitor. L-theanine probably improves memory and long-term potentiation in the hippocampus of Alzheimer’s mice via the dopamine D-1/D-5 receptor PKA pathway. L-theanine could be considered as a candidate for the treatment of Alzheimer’s disease.
Theanine counteracted a caffeine-induced increase in blood pressure, but had no effect on mood.
3. L-theanine for ADHD¶
Apparently, theanine increases the dopamine level in the striatum. Except for improved learning abilities, the behavior of the mice that received theanine for 3 months was unchanged.
Direct administration of theanine into the striatum of mice significantly increased dopamine in a dose-dependent manner. The increase in dopamine was attenuated by a previously administered calcium-free ring buffer. If the ring buffer also contained the non-NMDA glutamate receptor antagonist MK-801, the significant increase in dopamine due to L-theanine was maintained. When an NMDA glutamate receptor antagonist was given instead, this significantly inhibited theanine-induced dopamine release in the striatum. Theanine altered the concentrations of noradrenaline, 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5HIAA) only in the striatum, but not in other brain regions.
Theanine caused a significant increase in serotonin and dopamine in the brain, particularly in the striatum, hypothalamus and hippocampus.
A very small study on 5 boys with ADHD investigated the effect of L-theanine (2.5 mg/kg) and caffeine (2.0 mg/kg) (alternative, combined and placebo):
L-theanine alone
- improved overall cognition
- tend to worsen inhibitory control (increased stop-signal response time)
Caffeine alone
- worsens inhibitory control
L-theanine and caffeine combined
- improved overall cognitive performance
- improved the signal sensitivity to the Go signal (the d-prime in the Go/NoGo task)
- tended to improve inhibitory control
- reduced the task-related reactivity of the default mode network associated with mind wandering
A randomized placebo-controlled study found improved directed attention with L-theanine and even more with a combination of L-theanine and caffeine.
400 mg L-theanine (200 mg each in the morning and at noon) improved sleep quality in a randomized, double-blind, placebo-controlled study in boys with ADHD. Actigraph measurements showed a significantly higher percentage of sleep and sleep efficiency achieved, along with a non-significant trend towards less activity during sleep. Sleep latency and other sleep parameters remained unchanged. No significant adverse events occurred.
There is no research on the use of L-theanine in relation to other ADHD symptoms.
