Combining L-theanine and Paraxanthine for Transient Improvement of Cognitive Deficits Among Patients With Attention Deficit Hyperactivity Disorder and Autism Spectrum Disorder: A Series of Translational Pilot Neuroimaging Studies

Improving cognitive functions, including how fast the brain processes information, staying focused, and controlling impulsive actions, has been a topic of interest for centuries. These functions are frequently impaired in developmental or neurological conditions like attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Although medications like amphetamines can help manage cognitive deficits, they often carry significant side effects, risk of addiction, and high costs. Consequently, many individuals and families turn to complementary and alternative treatments. For instance, people with neurodevelopmental conditions, including ADHD, may consume more caffeinated beverages in the hope of boosting cognitive performance. This highlights the need for the exploration of commonly available alternative approaches to determine their efficacy. This study specifically aims to investigate an alternative approach that could serve as a more affordable, integrative, and complementary treatment modality for ADHD and ASD.

Findings of recent controlled cognitive and fMRI studies corroborate the findings of others to indicate that intake of two constituents of tea and coffee, namely L-theanine and caffeine, improves sustained attention in healthy young adult males by decreasing mind wandering. Interestingly, when administered together, L-theanine and caffeine synergistically acted to reduce mind wandering while engaged in a cognitively demanding task. Given the low cost and safety, oral administration of the L-theanine-caffeine combination seems to be a promising strategy to alleviate ADHD-associated impairments of sustained attention. However, regular high consumption of caffeine has adverse effects, such as jitteriness and sleep disturbance due to its metabolites, and the metabolism of caffeine has individual variability.

Paraxanthine is an active metabolite of caffeine that has cognitive benefits without adverse effects and predictable metabolism. However, the effects of the L-theanine-paraxanthine combination on improving cognitive deficits of adults with ADHD and ASD have not been examined. It is expected that combining theanine with paraxanthine instead of caffeine would result in more predictable, consistent, and possibly more marked improvements. There is a critical need to establish the efficacy and mechanisms of action of the L-theanine-paraxanthine combination in order to improve ADHD and ASD-related cognitive deficits. Therefore, the investigators plan to conduct a randomized, single-blinded, repeated-measures crossover trial to answer the following research questions.