Theanine (L-theanine, 5-N-ethyl-L-glutamine, delta-glutamylethylamide; gamma-glutamylethylamide) is an amino acid found in green tea.
Theanine passes the blood-brain barrier.
1. Neuropsiological effect of theanine
L-theanine acts neurophysiologically as:
Glutamate reuptake inhibitor
- Theanine acts strongly on the glutamine transporter and inhibits glutamine reuptake, which in turn suppressed the conversion of glutamine to 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 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; degrades serotonin, dopamine, and norepinephrine)
- 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 for up to 8 weeks, he said.
2. Behavioral effect of theanine
Theanine has a sedative and relaxing effect, moreover this better than the benzodiazepine alprazolam, but not anxiolytic. According to other studies, theanine has anxiolytic and stress-inhibiting effects, whereby the anxiolytic effect does not appear to occur through action on the GABA-A receptor.
Caffeine and gallate catechins, which are abundant in tea, inhibit the relaxing effects of theanine.
Theanine inhibited the deterioration of cognitive functions in elderly subjects and may be parkinsonism preventive due to neuroprotective effects.
L-theanine administration promoted the release of dopamine and norepinephrine in mouse hippocampus and stimulated protein kinase A (PKA) phosphorylation. The long-term potentiation in the hippocampus improved by L-theanine in an Alzheimer’s disease mouse model could be impaired by a PKA inhibitor. It is likely that L-theanine improves memory and long-term potentiation in the hippocampus of Alzheimer’s disease mice via the dopamine D-1/D-5 receptor PKA pathway. L-theanine may 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 dopamine levels in the striatum. Except for improved learning abilities, the behavior of mice receiving theanine for 3 months was unchanged.
Direct theanine administration into the striatum of mice significantly increased dopamine in a dose-dependent manner. The dopamine increase was attenuated by a previously given calcium-free ring buffer. If the ring buffer also contained the non-NMDA glutamate receptor antagonist MK-801, the significant dopamine increase by 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 norepinephrine, 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, especially in striatum, hypothalamus and hippocampus.
A very small study of 5 boys with ADHD examined the effects of L-theanine (2.5 mg/kg) and caffeine (2.0 mg/kg) (alternative, combined, and versus placebo):
- improved overall cognition
- tend to worsen inhibitory control (increased stop-signal reaction time)
- worsens the 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
- decreased the task-related reactivity of the default mode network associated with mind wandering
A randomized placebo-controlled trial found improved directed attention with L-theanine and even more so with a combination of L-theanine with 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 measures showed a significantly higher percentage of sleep and sleep efficiency achieved, along with a nonsignificant trend toward less activity during sleep. Sleep latency and other sleep parameters remained unchanged. No significant adverse events occurred.
There are no studies on the use of L-theanine in relation to other ADHD symptoms.