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The effect of 5-hydroxytryptophan, a serotonin precursor, on adults with high levels of Attention Deficit Hyperactivity Disorder traits: A randomised, controlled trial.

  • 2026-05-20
  • PloS one 21(5)
    • Eleanor Jackson
    • Timothy Riley
    • Paul G Overton

Study Design

Type
Randomized Controlled Trial (RCT)
Sample size
n = 56
Population
adults with high (N=56) and low (N=56) levels of ADHD traits
Methods
randomised, controlled trial, acute 5-hydroxytryptophan administration compared to placebo, 1:1 allocation, baseline and 90 min post-administration testing using Eriksen flanker and N-back with auditory distractor
Blinding
Double-blind
Duration
acute (single dose, 90 min post-administration testing)

Background

Although several effective therapies exist for Attention Deficit Hyperactivity Disorder (ADHD), current pharmaceutical treatment carries a high risk of misuse and high levels of discontinuation, evidencing a need for alternatives. One possible avenue is serotonergic intervention, particularly within the serotonin synthesis pathway, where there are several potential loci of dysfunction in ADHD. This study aimed to assess the efficacy of acute 5-hydroxytryptophan, a serotonin precursor, in reducing distractibility in adults with high levels of ADHD traits.

Trial design and methods

The study consisted of a randomised, controlled trial to assess the effects of acute 5-hydroxytryptophan administration compared to placebo. Participants consisted of individuals with high (N = 56) and low (N = 56) levels of ADHD traits, determined using the Adult ADHD self-report scale screener (ASRS v1.1), with randomised allocation to intervention or placebo in a 1:1 ratio. Both participants and investigators delivering the trial were blind to the allocation. Baseline testing of distractibility using a task-relevant (Eriksen flanker) and novel task-irrelevant (N-back coupled with an auditory stimulus) paradigm was completed, participants were given the intervention or placebo, and tasks were repeated 90 min post-administration.

Results and conclusions

The flanker and N-back task found few differences between individuals with high and low levels of ADHD traits, and the N-back task did not produce a distractor effect as initially predicted. 5-hydroxytryptophan produced no significant positive effect in any measure of distractibility that differed between individuals with high or low ADHD traits. Only accuracy on silent trials in the N-back task was affected by 5-hydroxytryptophan administration: placebo participants showed an improvement in performance and 5-hydroxytryptophan-administered participants did not. 19.6% of participants in the 5-hydroxytryptophan group experienced adverse events of fatigue, nausea or vomiting. Although 5-hydroxytryptophan did not elicit a positive effect on ADHD traits,further work should be conducted with measures more sensitive to ADHD traits to fully understand the impact of 5-hydroxytryptophan supplementation on the condition.

Research Insights

  • Griffonia→Improved Delayed Memory

    Only accuracy on silent trials in the N-back task was affected by 5-hydroxytryptophan administration: placebo participants showed an improvement in performance and 5-hydroxytryptophan-administered participants did not.

    Effect
    Neutral
    Effect size
    Small
    Dose
    not specified (acute administration)
  • Griffonia→Reduced Distractibility

    The flanker and N-back task found few differences between individuals with high and low levels of ADHD traits, and the N-back task did not produce a distractor effect as initially predicted. 5-hydroxytryptophan produced no significant positive effect in any measure of distractibility that differed between individuals with high or low ADHD traits.

    Effect
    Neutral
    Effect size
    Small
    Dose
    not specified (acute administration)

Adverse Events Reported

  • Griffonia→fatigue

    19.6% of participants in the 5-hydroxytryptophan group experienced adverse events of fatigue, nausea or vomiting.

    Finding
    Reported
  • Griffonia→nausea

    19.6% of participants in the 5-hydroxytryptophan group experienced adverse events of fatigue, nausea or vomiting.

    Finding
    Reported
  • Griffonia→vomiting

    19.6% of participants in the 5-hydroxytryptophan group experienced adverse events of fatigue, nausea or vomiting.

    Finding
    Reported
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