L-theanine for ADHD

Theanine (L-theanine, 5-N-ethyl-L-glutamine, delta-glutamylethylamide; gamma-glutamylethylamide) is an amino acid found in green tea.¹
Theanine crosses the blood-brain barrier.²

• 1. Neurophsiological effect of theanine
• 2. Behavioral effect of theanine
• 3. L-theanine for ADHD

1. Neurophsiological effect of theanine¶

L-theanine has a neurophysiological effect as:

• Glutamate reuptake inhibitors³
  • 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.²
• competitive low-affinity glutamate receptor antagonist in the hippocampus³
  • very weakly antagonistic to glutamate AMPA and glutamate kainate receptors.²
• binds to GABA-A receptors³
• increased gene expression with a large effect size⁴
  • 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.⁵

2. Behavioral effect of theanine¶

Theanine has a calming and relaxing effect,⁶ also better than the benzodiazepine alprazolam, but not anxiolytic.⁷ According to other studies, theanine has an anxiolytic and stress-inhibiting effect,⁵ although the anxiolytic effect does not appear to be due to an effect on the GABA-A receptor.⁸
Caffeine and gallate catechins, which are abundant in tea, inhibit the relaxing effect of theanine.⁹

Theanine inhibited the deterioration of cognitive functions in older people² and could have neuroprotective effects to prevent Parkinson’s disease.¹⁰

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.¹¹

Theanine counteracted a caffeine-induced increase in blood pressure, but had no effect on mood.¹²

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.¹³

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.¹⁴

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):¹⁵

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.¹⁶

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.¹⁷

There is no research on the use of L-theanine in relation to other ADHD symptoms.