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RecruitingNCT07777328Updated Aug 20, 2026

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

An interventional study of 5-hydroxytryptophan (food supplement) 200mg and 5-hydroxytryptophan (food supplement) 300mg in Attention Deficit and Hyperactivity Disorder (ADHD), Attention Deficit Hyperactivity Disorder in Adults and Attention Deficits, sponsored by University of Sheffield. Recruiting at 1 site in United Kingdom. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-08-20.

Sponsored by University of Sheffield · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
150
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study summary

The aim of this project is to look at the impact of 5-Hydroxytryptophan (5-HTP) on distractibility. 5-HTP is the precursor to the neurotransmitter serotonin and is a chemical that the body produces naturally. There is evidence that distractibility is associated with a decreased level of serotonin. This research aims to see if giving people 5-HTP will alter their distractibility, which will form part of an initial assessment as to whether 5-HTP could be used to support people with attention problems. The study involves completing a short survey about mental health and behaviours, and if eligible, participation in an in-person study at the University of Sheffield. The in-person session involves completing some cognitive tasks to look at eye movement, taking 5-HTP or a sugar tablet with no active ingredients, and then completing the tasks again after a 90-minute wait.

Read the detailed description

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.

02

Conditions studied

  • Attention Deficit and Hyperactivity Disorder (ADHD)
  • Attention Deficit Hyperactivity Disorder in Adults
  • Attention Deficits

Keywords

  • 5-Hydroxytryptophan
  • Serotonin
  • ADHD
  • microsaccades
  • eye tracking
  • attention
03

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

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

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
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
150 participants (estimated)

Study arms

  • Experimental
    High ADHD traits - 200mg 5-HTP

    Participants who have reported high levels of ADHD traits, and have been randomly allocated to the group receiving 200 mg 5-HTP, administered orally in tablet form.

    Dietary Supplement: 5-hydroxytryptophan (food supplement) 200mg

  • Experimental
    High ADHD traits - 300mg 5-HTP

    Participants who have reported high levels of ADHD traits, and have been randomly allocated to the group receiving 300 mg 5-HTP, administered orally in tablet form.

    Dietary Supplement: 5-hydroxytryptophan (food supplement) 300mg

  • Placebo comparator
    High ADHD traits - Placebo

    Participants who have reported high levels of ADHD traits, and have been randomly allocated to the group receiving placebo. Placebo consists of 2 sucrose-lactose tablets, administered orally.

    Other: Placebo

  • Active comparator
    Low ADHD traits - 200mg 5-HTP

    Participants who have reported low levels of ADHD traits, and have been randomly allocated to the group receiving 200 mg 5-HTP, administered orally in tablet form.

    Dietary Supplement: 5-hydroxytryptophan (food supplement) 200mg

  • Active comparator
    Low ADHD traits - 300mg 5-HTP

    Participants who have reported low levels of ADHD traits, and have been randomly allocated to the group receiving 300 mg 5-HTP, administered orally in tablet form.

    Dietary Supplement: 5-hydroxytryptophan (food supplement) 300mg

  • Placebo comparator
    Low ADHD traits - placebo

    Participants who have reported low levels of ADHD traits, and have been randomly allocated to the group receiving placebo. Placebo consists of 2 sucrose-lactose tablets, administered orally.

    Other: Placebo

Interventions

  • Dietary supplement5-hydroxytryptophan (food supplement) 200mg

    200mg 5-HTP delivered in two tablets. Tablets obtained from Nature's Best supplements. Each tablet contains 3982mg of Griffonia seed extract, providing 100mg of 5-HTP. The tablets consist of calcium carbonate, griffonia seed extract, Anti-caking Agents (Silicon Dioxide, Stearic Acid, \& Magnesium Stearate) and Tablet Coating (Hydroxypropyl Methylcellulose, Glycerol).

    Also known as: 5-HTP

  • Dietary supplement5-hydroxytryptophan (food supplement) 300mg

    300mg 5-HTP delivered in three tablets. Tablets obtained from Nature's Best supplements. Each tablet contains 3982mg of Griffonia seed extract, providing 100mg of 5-HTP. The tablets consist of calcium carbonate, griffonia seed extract, Anti-caking Agents (Silicon Dioxide, Stearic Acid, \& Magnesium Stearate) and Tablet Coating (Hydroxypropyl Methylcellulose, Glycerol).

    Also known as: 5-HTP

  • OtherPlacebo

    Unmedicated lactose-sucrose tablets provided by Ainsworth's homoeopathic remedies

05

What researchers measure

Primary outcomes

  1. Change in distractibility - microsaccades

    Frequency of microsaccades in a simple fixation task

    Time frame: pre and 90 minutes post administration

  2. Change in distractibility - reaction time

    Measurement of reaction time on a visual search task with varying auditory stimuli.

    Time frame: pre and 90 minutes post administration

  3. Change in distractibility- fixations

    Number of fixations on distractor letters in a visual search task with varying auditory stimuli.

    Time frame: pre and 90 minute post administration

06

Study locations

1 of 1 sites recruiting
  • University of Sheffield
    Sheffield, South Yorkshire S10 2TN, United Kingdom
    Recruiting
07

References and documents

Publications

  • Weinberg-Wolf H, Fagan NA, Anderson GM, Tringides M, Dal Monte O, Chang SWC. The effects of 5-hydroxytryptophan on attention and central serotonin neurochemistry in the rhesus macaque. Neuropsychopharmacology. 2018 Jun;43(7):1589-1598. doi: 10.1038/s41386-017-0003-7. Epub 2018 Jan 30. PubMed 29463909 ↗
  • Vigliante I, Mannino G, Maffei ME. Chemical Characterization and DNA Fingerprinting of Griffonia simplicifolia Baill. Molecules. 2019 Mar 15;24(6):1032. doi: 10.3390/molecules24061032. PubMed 30875930 ↗
  • Panagiotidi M, Paul O, Tom S. Increased microsaccade rate in individuals with ADHD traits. J Eye Mov Res. 2017 Mar 4;10(1):10.16910/jemr.10.1.6. doi: 10.16910/jemr.10.1.6. PubMed 33828642 ↗
  • Turner EH, Loftis JM, Blackwell AD. Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan. Pharmacol Ther. 2006 Mar;109(3):325-38. doi: 10.1016/j.pharmthera.2005.06.004. Epub 2005 Jul 14. PubMed 16023217 ↗
  • Lovejoy LP, Krauzlis RJ. Inactivation of primate superior colliculus impairs covert selection of signals for perceptual judgments. Nat Neurosci. 2010 Feb;13(2):261-6. doi: 10.1038/nn.2470. Epub 2009 Dec 20. PubMed 20023651 ↗
  • Lindseth G, Helland B, Caspers J. The effects of dietary tryptophan on affective disorders. Arch Psychiatr Nurs. 2015 Apr;29(2):102-7. doi: 10.1016/j.apnu.2014.11.008. Epub 2014 Dec 9. PubMed 25858202 ↗
  • Jackson E, Riley T, Overton PG. The effect of 5-hydroxytryptophan, a serotonin precursor, on adults with high levels of Attention Deficit Hyperactivity Disorder traits: A randomised, controlled trial. PLoS One. 2026 May 20;21(5):e0349512. doi: 10.1371/journal.pone.0349512. eCollection 2026. PubMed 42160304 ↗
  • Jackson EF, Riley TB, Overton PG. Serotonin dysfunction in ADHD. J Neurodev Disord. 2025 Apr 22;17(1):20. doi: 10.1186/s11689-025-09610-y. PubMed 40264019 ↗
  • Birdsall TC. 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Altern Med Rev. 1998 Aug;3(4):271-80. PubMed 9727088 ↗

Individual participant data

Plan to share: Yes — IPD regarding group allocation, ASRS scores, and measures on microsaccades and visual search tasks will be shared following completion of the study.

Supporting information: Study protocol, Sap

08

Registry details

Key details

Study ID
NCT07777328
Lead sponsor
University of Sheffield
Responsible party
Eleanor Jackson (Researcher and Investigator, University of Sheffield) — Principal investigator
First posted
Aug 20, 2026
Start date
Nov 25, 2025
Primary completion
Feb 2027 (estimated)
Completion
Jun 2027 (estimated)
Last update
Aug 20, 2026

Study contacts

Eleanor F Jackson
Contact
efjackson1@sheffield.ac.uk
+447908873415
Paul G Overton, Professor
Contact
p.g.overton@sheffield.ac.uk

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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