The Effect of 5-hydroxytryptophan on ADHD Traits and Eye Movements

The overarching aim of this project is to assess the efficacy and suitability of 5-hydroxytryptophan, a nutritional supplement and precursor to serotonin, as a potential therapeutic for ADHD traits. 5-hydroxytryptophan is a metabolic product produced in the body following consumption of foods with high levels of the amino acid tryptophan, found in soy products, egg whites, and other high-protein foods. Both tryptophan and 5-hydroxytryptophan are metabolic precursors to serotonin, a neurotransmitter that is essential for the regulation of sleep, emotional state, aggression, and, most relevantly, the regulation of attention. Serotonin levels have been shown to be significantly reduced in individuals with ADHD, and some theories suggest that this is linked to reduced serotonin synthesis; of particular interest is the step where tryptophan is converted to 5-hydroxytryptophan, both the rate-limiting step of serotonin synthesis and a possible genetic locus of change in ADHD. 5-hydroxytryptophan can be readily obtained from health shops as a supplement, derived from the seeds of the edible plant Griffonia Simplicifolia, which has been long used in traditional medicine, and its ability to be absorbed easily from the intestinal tract and skip the rate-limiting step of synthesis makes it an attractive possible therapeutic. Pre-clinical work where 5-hydroxytryptophan was administered to Rhesus Macaques found that the supplement increased attention in animals with a low baseline level of attention, highlighting a possible benefit to supplementation.

Although theoretically promising, our previous empirical study failed to find any effect of 5-hydroxytryptophan supplementation on individuals with high or low levels of ADHD-like traits. The study had several limitations, a significant one being that tasks that were meant to assess distractibility did not show a distractor effect, and did not provide discrimination between high and low ADHD trait groups. As such, we aim to attempt to re-assess the impact of 5-hydroxytryptophan with tasks that are better established as being ADHD-sensitive, particularly those of microsaccades and ocular motor behaviour, alongside a distractor task established in a previous pilot. Our primary study design also only considered one dose of 5-hydroxytryptophan, whereas in this iteration, we will use two different doses of 5-hydroxytryptophan to better establish a dose-response effect. Finally, given the heterogeneity of ADHD-traits and comorbidity with other neurodevelopmental and psychiatric conditions, we intend to better characterise the affective state of the cohort in order to better control for confounds and co-morbidity in the final data set.

The proposed study will be conducted in two parts:

A pre-screen survey to determine participant eligibility:

AIM = to assess the eligibility and ADHD traits of potential participants.

In-person participation in a randomised, double-blind trial at the University of Sheffield, where participants will ingest either intervention or placebo and complete cognitive tasks pre- and post-administration.

AIM = to determine the impact of 5-hydroxytryptophan supplementation on cognitive and oculomotor behaviour of individuals with high and low levels of ADHD traits.

Inclusion criteria

• 18-65 years of age
• Normal or corrected to normal vision with contact lenses.
• Score of <9 or >14 on the ASRS v5 (assessed in pre screen questionnaire)

Exclusion criteria

• Current use of psychostimulant medication or medication for the treatment of ADHD
• Current use of medications known to impact the serotonergic system (e.g., SSRIs).
• Smoking or vaping
• Pregnancy
• Breast feeding
• Lactose intolerance
• Veganism
• Dyslexia