5-hydroxytryptophan, a serotonin precursor, as a novel treatment for adults with Attention Deficit Hyperactivity Disorder: A randomised, double-blind trial.

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 a 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 double-blind, randomised trial to assess the effects of acute 5-hydroxytryptophan administration compared to placebo. Participants consisted of a group 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. Baseline testing of distractibility using a task-relevant (Eriksen flanker) and novel task-irrelevant (N-back coupled with auditory stimulus) paradigm was completed, participants were given the intervention or placebo, and tasks were repeated 90 mins post-administration.Results and conclusions: Tasks of distractibility found few differences between individuals with high and low levels of ADHD traits. 5-hydroxytryptophan produced no significant effect in any measure of distractibility that differed between individuals with high or low ADHD traits. 19.6% of participants in the 5-hydroxytryptophan group experienced side effects of fatigue, nausea or vomiting. Further work needs to be conducted with measures more sensitive to ADHD status to understand the impact of 5-hydroxytryptophan supplementation fully.Ethics: The study was approved by the University Research Ethics at the University of Sheffield on the 4th of March 2024 (RN 058170).