D-Serine

Also called D-Ser, dextro-serine, NMDA co-agonist D-serine.

Best grade D across 8 graded outcomes Amino acid Last checked Oct 21, 2026

The short answer

From 12 sources

D-serine is a brain signalling amino acid tested mainly as an add-on in psychiatric trials. One dose improved some attention and memory tests in healthy adults (grade D), but the largest trial, 195 people with schizophrenia on 2 g/day for 16 weeks, found no benefit over placebo, and a 2 g/day depression trial was also null overall.

Every graded outcome on this page

8 rows · line = participants

Grade DSpatial memory and problem solving (healthy older adults)Cognitionn 50
Grade DAuditory learning (pitch plasticity) during cognitive remediation in schizophreniaSchizophrenian 45
Grade DDepressive symptoms, anxiety and anhedonia (add-on in major depression)Depressionn 44
Grade DSymptoms and cognition at 30–120 mg/kg/day (schizophrenia, no placebo)Schizophrenian 42
Grade DMood, attention and verbal memory after one dose (healthy young adults)Cognitionn 35
Grade DNegative symptoms in people at clinical high risk of psychosisPsychosis riskn 35
Grade DAnxiety and PTSD symptom scoresAnxietyn 22
No effectNegative symptoms and cognition in schizophrenia (add-on to antipsychotics)Schizophrenian 195
5 more graded outcomes, in the evidence chapter

Key facts

What it is: The D-form of serine, a natural co-agonist at the glycine site of NMDA glutamate receptors^1,3
Largest trial: 195 adults with schizophrenia, 2 g/day added to antipsychotics for 16 weeks: no difference from placebo on negative symptoms or cognition³
Pooled schizophrenia data: A 2025 network meta-analysis (148 trials, 12,339 patients) listed add-on D-serine 2–4 g/day among agents with moderate-to-high certainty of benefit in one or more outcome domains; the largest single trial was null^12,3
Healthy adults: One 2.1 g dose raised blood D-serine at least 200-fold at 2 hours and improved some attention and verbal-memory scores¹
Usual trial dose: 30 mg/kg/day (about 2 g/day); 60–120 mg/kg/day only in a pilot trial and an open-label study with laboratory monitoring^3,7,4,5
Depression trial: 2 g/day added to usual care for 6 weeks did not beat placebo overall in 44 inpatients⁶
Kidney signal: Kidney tubule damage at high doses in rats (not mice or rabbits); one person in human studies had abnormal kidney values that resolved after stopping⁹

What it is

D-serine is the mirror-image form of the amino acid serine; in the brain it helps switch on NMDA glutamate receptors.

How it works

Proposed

NMDA receptors need a co-agonist bound at their glycine site before glutamate can open them, and D-serine is one of the body's own co-agonists. Trials test oral D-serine on the theory that stronger NMDA signalling could support learning and some psychiatric symptoms; whether usual oral doses change brain signalling enough to matter has not been shown.^1,3,4

Forms

Form

The form on this page
Form	Elemental %	Absorption (human data)	GI tolerance	Studied for
D-serine powder or capsules	Varies¹Not applicable (single compound; no elemental fraction)	A single 2.1 g oral dose raised serum D-serine at least 200-fold at 2 hours; plasma levels rose with dose across 30–120 mg/kg/day.^1,5	Reported as well tolerated in the healthy-adult, schizophrenia, PTSD and depression trials, which ran laboratory safety checks.^1,3,7,6	Cognition in healthy adults; add-on trials in schizophrenia, psychosis risk, depression and PTSD

What the human research says

Human trials only, one row per outcome. The form line shows what each trial actually tested. Grades follow our evidence-grading policy.

Trial map

8 graded outcomes, largest study first

8 graded outcomes: 6 improved, 2 no effect. The largest, a 2012 randomized trial of 195 people on negative symptoms and cognition in schizophrenia (add-on to antipsychotics), found no effect. Outcomes that improved came from smaller studies: a median of 39 people, against 120 for no effect.

By sizeTable

1Negative symptoms and cognition in schizophrenia (add-on to antipsychotics)

No effect · No-effect grade · RCT, 195 people, 2012

Adults with schizophrenia or schizoaffective disorder stable on antipsychotics, with persistent negative symptoms (multicenter)

Dose, result and source

Every graded outcome on this page, largest study first
Outcome	Found	People	Study	Who was studied
Negative symptoms and cognition in schizophrenia (add-on to antipsychotics)	No effect	195	No-effect grade · RCT, 2012	Adults with schizophrenia or schizoaffective disorder stable on antipsychotics, with persistent negative symptoms (multicenter)
Spatial memory and problem solving (healthy older adults)	Improved	50	Grade D · Crossover RCT, 2016	Healthy older adults (Brazil)
Auditory learning (pitch plasticity) during cognitive remediation in schizophrenia	Improved	45	Grade D · RCT, 2023	Adults with schizophrenia or schizoaffective disorder on stable antipsychotics (USA)
Depressive symptoms, anxiety and anhedonia (add-on in major depression)	No effect	44	Grade D · RCT, 2025	Adult inpatients with moderate-to-severe major depression (Switzerland)
Symptoms and cognition at 30–120 mg/kg/day (schizophrenia, no placebo)	Improved	42	Grade D · Open-label trial, 2010	Adults with schizophrenia or schizoaffective disorder stable on antipsychotics (USA)
Negative symptoms in people at clinical high risk of psychosis	Improved	35	Grade D · Pilot RCT, 2015	People aged 13–35 at clinical high risk of schizophrenia (4 US centres)
Mood, attention and verbal memory after one dose (healthy young adults)	Improved	35	Grade D · Crossover RCT, 2015	Healthy adults aged 23–29 (Israel)
Anxiety and PTSD symptom scores	Improved	22	Grade D · Crossover RCT, 2009	Outpatients with chronic PTSD (Israel)

Every graded row

8 rows

Showing 8 of 8 outcomes. Human trials only.

Grade DSpatial memory and problem solving (healthy older adults)CognitionImprovedCrossover RCT
n 50 · 2016

Improved Groton Maze learning test performance improved versus placebo, more so in people whose blood D-serine rose most; other cognitive tests and mood did not change.

Design: Crossover RCT, n = 50, 2016
Population: Healthy older adults (Brazil)
Form: Oral D-serine
Dose: Not stated in the abstract
Duration: Not stated in the abstract (crossover with placebo)
Source: Reference 2 · PubMed 26933803 (opens PubMed)

Grade DAuditory learning (pitch plasticity) during cognitive remediation in schizophreniaSchizophreniaImprovedRCT
n 45 · 2023

Improved Overall treatment effect on plasticity improvement (p = .014), largest at 80 and 100 mg/kg (d > 0.67); the within-group change at 120 mg/kg was not significant. Mismatch negativity was larger at 100 mg/kg than placebo (d = 1.0).

Design: RCT, n = 45, 2023
Population: Adults with schizophrenia or schizoaffective disorder on stable antipsychotics (USA)
Form: Oral D-serine
Dose: 80, 100 or 120 mg/kg once weekly with auditory training (12 D-serine and 3 placebo per dose cohort)
Duration: 3 weekly visits
Source: Reference 10 · PubMed 36958998 (opens PubMed)

Grade DDepressive symptoms, anxiety and anhedonia (add-on in major depression)DepressionNo effectRCT
n 44 · 2025

No effect Depression, anxiety and anhedonia scores fell in both groups with no significant difference overall; in a subgroup analysis, people with severe depression improved more on D-serine.

Design: RCT, n = 44, 2025
Population: Adult inpatients with moderate-to-severe major depression (Switzerland)
Form: Oral D-serine
Dose: 2 g/day added to usual treatment
Duration: 6 weeks
Source: Reference 6 · PubMed 40436209 (opens PubMed)

Grade DSymptoms and cognition at 30–120 mg/kg/day (schizophrenia, no placebo)SchizophreniaImprovedOpen-label trial
n 42 · 2010

Improved Symptom and neuropsychological scores improved across doses, with larger cognitive gains at 60 mg/kg/day or more; there was no placebo group.

Design: Open-label trial, n = 42, 2010
Population: Adults with schizophrenia or schizoaffective disorder stable on antipsychotics (USA)
Form: Oral D-serine
Dose: 30, 60 or 120 mg/kg/day
Duration: 4 weeks
Source: Reference 5 · PubMed 20541910 (opens PubMed)

Grade DMood, attention and verbal memory after one dose (healthy young adults)CognitionImprovedCrossover RCT
n 35 · 2015

Improved Self-rated sadness and anxiety were lower, attention (CPT-IP) improved and one verbal-memory measure improved versus placebo; the dose was well tolerated.

Design: Crossover RCT, n = 35, 2015
Population: Healthy adults aged 23–29 (Israel)
Form: Oral D-serine
Dose: 2.1 g single dose
Duration: Single dose per session (crossover with placebo)
Source: Reference 1 · PubMed 25554623 (opens PubMed)

Grade DNegative symptoms in people at clinical high risk of psychosisPsychosis riskImprovedPilot RCT
n 35 · 2015

Improved Negative-symptom scores improved more than with placebo (effect size d=0.68, p=0.03). Across both groups, 2 participants left for laboratory-confirmed adverse events and 2 converted to psychosis.

Design: Pilot RCT, n = 35, 2015
Population: People aged 13–35 at clinical high risk of schizophrenia (4 US centres)
Form: Oral D-serine
Dose: 60 mg/kg/day in divided doses
Duration: 16 weeks
Source: Reference 4 · PubMed 26360284 (opens PubMed)

Grade DAnxiety and PTSD symptom scoresAnxietyImprovedCrossover RCT
n 22 · 2009

Improved Hamilton Anxiety and Mississippi PTSD scale scores improved versus placebo; the main clinician PTSD scale (CAPS) showed only a trend (p=0.07). Well tolerated.

Design: Crossover RCT, n = 22, 2009
Population: Outpatients with chronic PTSD (Israel)
Form: Oral D-serine
Dose: 30 mg/kg/day, alone or added to medication
Duration: 6 weeks per period
Source: Reference 7 · PubMed 19366490 (opens PubMed)

No effectNegative symptoms and cognition in schizophrenia (add-on to antipsychotics)SchizophreniaNo effectRCT
n 195 · 2012

No effect Both groups improved, with no significant difference between D-serine and placebo on negative symptoms (11.4% vs 14.8%) or MATRICS cognition (6.8% vs 6.1%). D-serine was well tolerated.

Design: RCT, n = 195, 2012
Population: Adults with schizophrenia or schizoaffective disorder stable on antipsychotics, with persistent negative symptoms (multicenter)
Form: Oral D-serine
Dose: 2 g/day
Duration: 16 weeks
Source: Reference 3 · PubMed 22795211 (opens PubMed)

What the numbers add up to

Each point is worked out from the data and the sources numbered on this page, with the arithmetic shown under it. It adds no new data and is not medical advice.

The biggest trial was null

The only adequately powered single trial (195 people with schizophrenia, 2 g/day for 16 weeks) found no difference from placebo, even though pooled analyses of smaller trials favour add-on D-serine.^3,11,12

Healthy-adult data are short-term

Both healthy-adult studies were small crossover tests, one of a single dose; neither tested months of use.^1,2

Weight-based doses add up

At 30 mg/kg/day a 70 kg adult would take about 2.1 g; the 120 mg/kg/day arm would be about 8.4 g a day.⁵

Studied doses

Doses used in research, shown against the official limits. They describe the studies, not a recommendation for you.

Studied doses in research, not advice. These are amounts used in research, not personal advice. Your clinician or pharmacist can say what fits you.

Doses studied in human trials

Doses studied in human trials ranged from a single 2.1 g dose in healthy adults to 30 mg/kg/day (about 2 g/day) for 6–16 weeks in controlled trials; 60–120 mg/kg/day was used only with laboratory monitoring, in a 4-week open-label study, a 16-week pilot trial and a 3-week trial of once-weekly doses.^{1,3,6,7,4,5,10}

When trials measured an effect

2 outcomes

How long trials ran before effects were measured
Outcome	Measured at	Basis
Mood and attention in healthy adults	Same day as a single 2.1 g dose (blood D-serine up at least 200-fold at 2 hours)	35-person crossover study¹
Auditory learning in schizophrenia	After the first weekly dose, sustained over the next two	45-person randomized trial, 80–120 mg/kg once weekly¹⁰

Interactions and safety

Published interactions only: each row cites a source. No row means none was found in our sources, not that a combination is safe.

What D-Serine meets

1 cited row

Medicines 1

D-Serine1 medicine · 0 supplements

Supplements and foods 0

No supplement rows in our sources.

Reference summary

Interactions

1 agent

Published interactions, grouped by kind
Agent	What the source says	Evidence
Medicines1
Clozapine	In a meta-analysis of 40 placebo-controlled trials (4,937 patients) of seven NMDA-receptor add-ons including D-serine, the add-ons as a group were effective only with antipsychotics other than clozapine. This is a class-level finding on benefit, not a D-serine-specific test or a safety interaction.¹¹	Review

Check with what you take

Kept on this device only

Add what you take. We list every interaction our evidence profiles cite between D-Serine and your picks, and between your picks.

Add a supplement or medicine

Most cited:

Add a supplement or medicine you take to check it against D-Serine.

Starting from one medicine? The interaction checker rates how serious each pair is, on a curated list of 19 entries for 11 medicines. This cabinet has no severity rating: it lists every interaction row our supplement pages cite.

Who should be careful

5 groups

People on psychiatric medicines: Every patient trial gave D-serine on top of prescribed medicines under specialist supervision, and the largest trial found no benefit over placebo. It is not a treatment for schizophrenia, psychosis or depression outside a supervised trial.^3,6
Kidney disease: High doses (over 500 mg/kg) reliably damage kidney tubules in rats, though not in mice or rabbits. Across published human studies a safety review found one person with abnormal kidney values, which resolved within days of stopping; trials checked kidney labs throughout.⁹
Higher doses: Doses of 60 mg/kg/day and above were tested only with laboratory monitoring; in one such trial 2 participants stopped for laboratory-confirmed adverse events.^4,5
Pregnancy and breastfeeding: No reliable data: the cited trials give no safety data for pregnancy or breastfeeding, and D-serine has no LactMed entry.^1,3
Children and teenagers: Only one cited trial included teenagers (from age 13), under specialist care.⁴

Reading the label, and the cost per dose

Compare any product you already have by the amount it delivers, not by capsule count or front-of-pack weight.

How to read the label

2 checks

Label dose vs studied dose

Controlled trials used about 2 g/day (30 mg/kg/day). The healthy-adult attention and memory results came from a single 2.1 g dose, not daily use.^3,7,1

D-serine is not L-serine

L-serine is the common dietary form and a precursor the body uses to make D-serine; results for one form do not transfer to the other, or to phosphatidylserine.^8,2

Have the bottle? Photograph its Supplement Facts panel and see each line, d-serine included, beside the doses and forms the trials used in Label X-Ray.

Cost per studied dose, without the sales pitch

Your numbers, no product data

Price paid ($)Servings per containerD-serine per serving (mg)

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Frequently asked questions

Short answers to common questions; the numbers link to the sources below.

Common questions

5 answers

Does D-serine improve memory?

In two small crossover studies of healthy adults it improved some attention or spatial-memory tests, while most other tests did not change. No long-term trial in healthy people exists.^1,2

Does D-serine help depression or anxiety?

A 6-week trial of 2 g/day in 44 inpatients with major depression was null overall. A 22-person PTSD crossover trial reported lower anxiety scores.^6,7

Is D-serine safe?

Trials of up to 16 weeks described it as well tolerated, with laboratory monitoring. Concern comes from rats, whose kidneys are damaged by high doses; across human studies one person had abnormal kidney values that resolved after stopping. Doses above 30 mg/kg/day were tested only under supervision, and long-term safety data are lacking.^3,4,5,9

Is D-serine the same as L-serine?

No. L-serine is the dietary form and a precursor of D-serine. The two have been tested in different conditions, so their results are not interchangeable.⁸

What did the schizophrenia trials find?

The largest trial (195 adults, 2 g/day added to antipsychotics for 16 weeks) found no difference from placebo. Pooled analyses of smaller trials favour add-on D-serine; one found NMDA-receptor add-ons as a group helped only with antipsychotics other than clozapine. Higher-dose pilot studies were small.^3,11,12,4,5

Sources

12 sources: trial abstracts, NIH fact sheets and reference databases. Numbers in the text link here.

Sources cited on this page

12 sources

1Behavioral and cognitive effects of the N-methyl-D-aspartate receptor co-agonist D-serine in healthy humans: initial findings.Crossover RCT J Psychiatr Res, 2015 · PMID 25554623
2The effect of D-serine administration on cognition and mood in older adults.Crossover RCT Oncotarget, 2016 · PMID 26933803
3A multicenter, add-on randomized controlled trial of low-dose d-serine for negative and cognitive symptoms of schizophrenia.RCT J Clin Psychiatry, 2012 · PMID 22795211
4D-serine for the treatment of negative symptoms in individuals at clinical high risk of schizophrenia: a pilot, double-blind, placebo-controlled, randomised parallel group mechanistic proof-of-concept trial.Pilot RCT Lancet Psychiatry, 2015 · PMID 26360284
5High dose D-serine in the treatment of schizophrenia.Open-label trial Schizophr Res, 2010 · PMID 20541910
6Adjunctive d-serine treatment for major depressive disorder: A randomized clinical trial.RCT J Affect Disord, 2025 · PMID 40436209
7Pilot controlled trial of D-serine for the treatment of post-traumatic stress disorder.Crossover RCT Int J Neuropsychopharmacol, 2009 · PMID 19366490
8Potential benefits of l-serine in children with GRIN2B loss-of-function variants: Randomized n-of-1 trials.RCT Mol Genet Metab, 2025 · PMID 41265180
9D-Serine: A Cross Species Review of Safety.Systematic review Front Psychiatry, 2021 · PMID 34447324
10Dose-Dependent Augmentation of Neuroplasticity-Based Auditory Learning in Schizophrenia: A Double-Blind, Placebo-Controlled, Randomized, Target Engagement Clinical Trial of the NMDA Glutamate Receptor Agonist d-serine.RCT Biol Psychiatry, 2023 · PMID 36958998
11Efficacy of N-methyl-D-aspartate receptor modulator augmentation in schizophrenia: A meta-analysis of randomised, placebo-controlled trials.Meta-analysis J Psychopharmacol, 2021 · PMID 33406959
12Augmentation with glutamatergic modulators for schizophrenia: A network meta-analysis.Meta-analysis Prog Neuropsychopharmacol Biol Psychiatry, 2025 · PMID 40945815

What changed

Every dated change to this page: what changed, who made it and why.

Change log

4 entries

Dated changes to this page
Date	Change	Who and why
Oct 21, 2026evidence, key facts, interactions, who should avoid, studied doses, insights, time to effect, FAQ, questions, related	Added a 2023 randomized trial of once-weekly 80–120 mg/kg D-serine with auditory training in schizophrenia (grade D; n and safety from PMC full text), a 2021 meta-analysis of 40 placebo-controlled trials and a 2025 network meta-analysis of 148 trials (cited in key facts and FAQ, not graded rows, as neither abstract gives a D-serine-specific n). Added the clozapine interaction (NMDA-receptor add-ons as a class showed no benefit with clozapine) from the 2021 meta-analysis. Checked LiverTox and LactMed (no D-serine entries) and made the pregnancy note explicit. Replaced the FAQ item that repeated the page's own "What is" question; added time-to-effect rows, page questions and the focus goal-hub link. Searched 2023–2026 PubMed: no newer D-serine trials in healthy adults, depression or PTSD.	Writer: Kymata Health EditorialTrigger: A–Z audit against docs/supplements/AUDIT-STANDARD.md
Oct 17, 2026all	First draft. Every PMID checked against NCBI E-utilities esummary (title, journal and year taken from the record) and abstracts read for each cited row.	Writer: Kymata Health EditorialTrigger: new page
Oct 17, 2026all	Adversarial review pass: every number in each evidence row's result, dose, duration, n and population fields was machine-checked against its PubMed abstract, and figures not in an abstract were confirmed in the PMC full text (noted per row). Unverified study-country, funding and mechanism wording was removed or sourced, rows whose sample size could not be confirmed were dropped, and retraction, erratum and expression-of-concern flags were checked on every PMID (two errata, noted on their rows; no retractions). Page set indexable.	Writer: Kymata Health EditorialTrigger: review
Oct 17, 2026safety	Independent review: added the rat kidney-toxicity signal and human kidney-lab finding from a 2021 cross-species safety review (PMID 34447324, checked via esummary), a kidney-disease caution, and clearer wording that patient use belongs in supervised trials.	Writer: Kymata Health EditorialTrigger: review

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D-Serine

Medicines 1

Supplements and foods 0

Clozapine