What is the effect of L-theanine-caffeine combination on selective attention in adolescents with attention deficit hyperactive disorder compared to methylphenidate and placebo

1.Participants will be selected from child psychiatry outpatient clinics in Teaching Hospital Peradeniya and Sirimavo Bandaranayake Specialized Children Hospital with prior approval from relevant authorities. The study (behavioral and EEG tests) will be conducted in the Clinical Neurophysiology and Cognitive Neuroscience (CLINCON) laboratory at the Department of Physiology, Faculty of Medicine, University of Peradeniya.

2.The proposed study is a double-blind three-way crossover trial i.e., the same participant is given one treatment, and after a washout period, the other (this is the standard in crossover trials). The treatment order is counterbalanced in a Latin Square design.

3.Intervention

Active treatment: L-theanine-caffeine combination. Dose: 2.5mg per kg body weight of L-theanine and 2.0mg per kg body weight of caffeine powder incorporated into gelatin capsules Route: Orally Single dose, post-dose test will be carried out after 45 minutes ingestion of the active treatment Frequency- once

Control: Placebo Gelatin capsule with starch equivalent to the weight of L-theanine-caffeine combination given to each participant. Route- Orally Single dose post-dose test will be carried out after 45 minutes ingestion of the placebo.

Standard therapy: methylphenidate Dose – standard dose prescribed by the psychiatrist in a Gelatin capsule Route- Orally Single dose. (This will also be the positive control, because theanine-caffeine combination is given a supplement)

The proposed study is a double-blind study where both the participant and the test administrator will be blind to the treatment given. Participant will be blinded by giving all the treatments inside a gelatin capsule and the test administrator will be blinded by giving the treatment to the participant by a third person.

Participants must meet all of the inclusion criteria given in order to be eligible to participate in the study

1. Patients diagnosed with attention deficit hyperactive disorder by a psychiatrist.
2. 10-19 years old, boys and girls
3. Patients who have responded to methylphenidate.
4. Normal, or corrected-to-normal vision and normal hearing.

All individuals meeting any of the exclusion criteria at baseline will be excluded from study participation

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.Physical, neurological or concurrent psychiatric impairments (except ADHD) that could affect cognitive and motor functions 4.Intake of psychoactive substances which have the potential to affect cognitive functions and those which may interact with caffeine (other than their medications for ADHD) 5.Current / past diagnosis of tics or other forms of dyskinesia 6.Regular intake of medication that could alter visual, auditory, cognitive or motor functions (except stimulants) 7.History of head injury that resulted in loss of consciousness / history of brain surgery 8.Intake of drugs containing caffeine, other phosphodiesterase inhibitors or adenosine receptor blockers within the past 3 months 9.Intake of medications which are known to have pharmacological interactions with caffeine within the past 3 months 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.Unwillingness or inability to entirely refrain from use of electronic devices during study visits 13.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 14.Unwillingness or inability to follow written, on-screen and verbal instructions given by the study team