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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

Jackson E, Riley T, Overton PG

PloS one, 2026

56 participants

Abstract

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…

How strong is the evidence?

Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 56 participants or records.

How the five levels of evidence work. The level is assigned automatically from the abstract and can be wrong, so check the paper.

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