Effects of L-theanine and Caffeine on Attention and Attention-related Brain Activity of Children With Attention Deficit Hyperactivity Disorder

Effects of L-theanine and Caffeine on Attention and Attention-related Brain Activity of Male Children and Adolescents With Attention Deficit Hyperactivity Disorder: a proof-of- Concept fMRI Study.

L-theanine and caffeine are two natural constituents of tea. Both of these compounds are among the U.S. Food and Drug Administration's list of Generally Recognized as Safe (GRAS) substances. Results of several clinical trials the PI and his team has conducted are consistent with results of many others to indicate that oral intake of each of 2.5 mg/kg body weight of L-theanine and 2.0 mg/kg body weight of caffeine is associated with improved attention in adults. Furthermore, there is evidence to suggest that, when taken in combination, L-theanine and caffeine seem to have additive effects in improving attention in adults. However, the specific actions of these substances have not been examined in children and adolescents with attention deficit hyperactivity disorder (ADHD), who are characterized by impaired attention, hyperkinesia and impulsivity.

Therefore, the investigators plan to study the functional activity of brains (both at rest and when performing standard tasks designed to measure attention) in children diagnosed with ADHD using functional magnetic resonance imaging, after they consume either 2.5 mg/kg of L-theanine, 2.0 mg/kg of caffeine and their combination as compared to a placebo (water). Based on our previous findings, the investigators expect to observe improvements (speed of responding and accuracy) in standard tests of attention with intake of L-theanine, caffeine and their combination as compared to the placebo. The investigators also expect to observe decreased functional activity in brain regions that typically show increased activity during mind wandering with intake of L-theanine, caffeine and their combination.

Inclusion Criteria:

1. Children and adolescents (age 8-17 years)
2. Male
3. Diagnosed with ADHD by a clinician (e.g. a psychiatrist or a pediatrician)
4. Responded to stimulants (i.e. the symptoms of ADHD have improved in the past with a prescription of stimulants)

Exclusion Criteria:

1. Gross impairment of vision or hearing that would prevent the participants from performing neuropsychological tasks
2. Inability to read and follow written instructions
3. WISC-V IQ score of < 80
4. Physical, neurological or concurrent psychiatric impairments (except ADHD) that could affect cognitive and motor functions
5. Regular intake of medication that could alter visual, auditory, cognitive or motor functions (except stimulants)
6. History of head injury that resulted in loss of consciousness / history of brain surgery
7. Intake of drugs containing caffeine, other phosphodiesterase inhibitors or adenosine receptor blockers within the past 3 months
8. Intake of medications which are known to have pharmacological interactions with caffeine within the past 3 months
9. Current / past diagnosis of tics or other forms of dyskinesia
10. History of development of headache, drowsiness, anxiety, insomnia or nausea following intake of caffeine or caffeine containing beverages
11. Current / past history of smoking and / or alcohol or drug abuse
12. Absolute contraindications to undergo MRI
13. Unwillingness or inability to entirely refrain from use of electronic devices during study visits
14. Unwillingness or inability to refrain from intake of L-theanine and caffeine containing food or beverages within the 24 hours prior to each study visit
15. Unwillingness or inability to follow written, on-screen and verbal instructions given by the study team