Behavioral and Cognitive Effects of the N-methyl-D-aspartate Receptor (NMDAR) Co-agonist D-serine in Healthy Humans

Behavioral and Cognitive Effects of the N-methyl-D-aspartate Receptor (NMDAR) Co-agonist D-serine in Healthy Humans

The efficacy of compounds having agonistic activity at the glycine site associated with the N-methyl-D-aspartate receptor (NMDAR) is presently assessed in psychiatric disorders. In contrast to NMDAR antagonists, the neuropsychiatric effects of NMDAR agonists in the healthy human organism are not known. The investigators studied neuropsychiatric and neurochemical effects of the NMDAR-glycine site obligatory co-agonist D-serine (DSR) in healthy subjects using a randomized, controlled crossover challenge design including a baseline assessment day and two treatment administration days (DSR and placebo in randomized order). Thirty-five subjects aged 23-29 years participated in the study and received a 2.1g orally administered DSR dose. The main outcome measures were the changes in scores of mood-related Visual Analogue Scale (VAS), Continuous Performance Test - Identical Pairs (CPT-IP), and Rey Auditory Verbal Learning Test (RAVLT).

The study employed a randomized, double-blind, placebo controlled crossover design according to which, following a baseline assessment session, subjects were tested under two acute treatment conditions on two separate days. Following the baseline assessment day, 16 subjects were randomized, using a computer-generated random number sequence, to receive during test day 1 DSR and 19 to receive placebo. During test day 2, these two groups of subjects were crossed over to receive the alternative experimental treatment. The time intervals between the baseline assessment day, test day 1 and test day 2 were two to three weeks and 1 month respectively, in order to avoid the possibility of any carry-over effects.

Inclusion Criteria:

• healthy volunteers

Exclusion Criteria:

• history of psychiatric, medical, neurological illness or substance abuse