Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

BACKGROUND: Activation of the glutamate N-methyl-D-aspartate receptor with its co-agonist D-serine has been shown to improve subjective mood in healthy volunteers. D-alanine is another potent N-methyl-D-aspartate receptor co-agonist which arises from the natural breakdown of host gut microbes, and is predominantly sequestered in the pituitary. This may suggest that D-alanine influences the neuroendocrine stress response which may then impact on emotion. AIMS: The current study explored the effects of D-serine and D-alanine on emotional processing, cognition and the levels of the stress hormone cortisol in healthy volunteers. METHODS: In a double-blind, placebo-controlled randomised study, participants (n=63) received a single oral dose of either D-serine, D-alanine (60 mg/kg) or placebo and then performed the Emotional Test Battery and N-back task (two hours post-administration) and provided saliva samples at fixed intervals. RESULTS: Subjects administered with D-alanine were faster at identifying facial expressions of fear, surprise and anger, and at categorising negative self-referential words. Participants on D-alanine also showed a trend to recall more words than placebo in a memory task. D-serine did not have any meaningful effects in any of the tasks. Neither amino acid had a significant effect on salivary cortisol or working memory. CONCLUSION: This study is the first to suggest that D-alanine can modulate emotional cognitive processing after a single dose. The lack of findings for D-serine nevertheless contrasts a previous study, emphasising a need for further investigation to clarify discrepancies. A better understanding of the physiological actions of D-amino acids would be beneficial in evaluating their therapeutic potential.

Original publication




Journal article


J Psychopharmacol

Publication Date



D-amino acids, cognition, cortisol, emotional processing