Sarcosine (N-Methylglycine) in Schizophrenia Research

Table of Contents

1. What Sarcosine Is and How It Acts
2. Where Sarcosine Comes From in the Body
3. The First Schizophrenia Trials, 2004 to 2010
4. Sarcosine Compared Directly With D-Serine
5. The Clozapine Exception
6. Longer and Combined Trials
7. What the Pooled Analyses Found
8. Depression and Obsessive-Compulsive Disorder Trials
9. The Prostate-Cancer Marker Controversy
10. Safety as the Studies Report It
11. What Is Not Known
12. Key Research Papers
13. Connections
14. Featured Videos

What Sarcosine Is and How It Acts

Sarcosine is a small amino acid, N-methylglycine: the glycine molecule with a methyl group on its nitrogen. A 2009 laboratory study describes it as an amino acid involved in one-carbon metabolism, the set of reactions that move single carbon units (such as methyl groups) between molecules (Zhang 2009).

Its interest for brain research comes from the N-methyl-D-aspartate (NMDA) receptor, one of the main receptors for the brain's chief excitatory messenger, glutamate. The N-methyl-D-aspartate receptor opens only when glutamate and a second molecule, a co-agonist such as glycine or D-serine, are bound at the same time. A long-standing theory, called the N-methyl-D-aspartate receptor hypofunction hypothesis, holds that this receptor works too weakly in schizophrenia (Tsai 2004).

The research describes two ways sarcosine can strengthen the receptor's signal:

• Blocking glycine clean-up. Nerve cells and their support cells remove glycine from around synapses with a pump called the glycine transporter type 1 (GlyT1). The 2004 trial report calls sarcosine "an endogenous antagonist" of the glycine transporter type 1, which "potentiates glycine's action" at the receptor's glycine site (Tsai 2004). Later trial authors describe the same effect as increasing glycine concentration around the receptors (Strzelecki 2015, spectroscopy study).
• Acting at the glycine site itself. In cultured mouse nerve cells, sarcosine itself acted as a co-agonist at the receptor's glycine binding site. It did not behave exactly like glycine: the receptor desensitized less with sarcosine, calcium rises inside the cells were larger, and the electrical currents decayed faster. Nerve-cell death driven by the receptor was similar with both (Zhang 2009). These are findings in cells in a dish.

So the sources describe sarcosine both as a glycine transporter type 1 inhibitor and, in cell studies, as a co-agonist in its own right. Which of the two matters more in a living human brain at the doses tested has not been settled in the studies read for this page.

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Where Sarcosine Comes From in the Body

The body makes sarcosine from glycine. The enzyme that does this is glycine N-methyltransferase (Sreekumar 2009; Cernei 2013), which takes the methyl group from S-adenosylmethionine, the body's main methyl donor (described in the full text of the Cernei 2013 review; see also the SAM-e page). The same review describes a second route: choline is broken down through betaine to dimethylglycine, and dimethylglycine is converted to sarcosine by the enzyme dimethylglycine dehydrogenase (full text of Cernei 2013).

Sarcosine is then turned back into glycine by sarcosine dehydrogenase. A 2012 genetics paper calls sarcosine "a key intermediate in 1-carbon metabolism" and reports that changes in the gene for sarcosine dehydrogenase are linked to sarcosinemia, an inherited trait in which sarcosine runs high in blood and urine (Bar-joseph 2012). A 2013 case report describes sarcosinemia as a rare inborn error that may stay unnoticed until later life but has, in rare cases, been reported with disability of nervous-system development; its 19-year-old patient had dystonia, developmental delay and cognitive impairment, and two years of the drug memantine did not help (Benarrosh 2013).

Blood levels change with age and diet in research settings. A 2018 study in rodents and humans found circulating sarcosine lower with aging and higher with dietary restriction (eating less), and higher in a long-lived dwarf mouse strain; in cultured cells sarcosine switched on autophagy, the cell's recycling process (Walters 2018).

Food. The sources read for this page describe sarcosine as made and broken down inside the body and, in the trials, given as a measured powder. None of them reports measured amounts of sarcosine in everyday foods, so this page lists no food sources. Its parent molecule, glycine, is found in protein foods and collagen-rich foods such as bone broth; see the Glycine page.

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The First Schizophrenia Trials, 2004 to 2010

Nearly all early sarcosine trials came from one research group working in Taiwan and the United States. Every trial below gave sarcosine by mouth, and every one except the 2008 dose comparison added it to antipsychotic medicine the patients were already taking. Symptoms were usually measured with the Positive and Negative Syndrome Scale (PANSS), a standard rating of hallucinations and delusions (positive symptoms), withdrawal and flat emotion (negative symptoms), and general symptoms.

• Tsai 2004 — stable patients, 38 people, 6 weeks. Sarcosine 2 g a day or placebo was added to stable antipsychotic treatment; 20 of the patients took risperidone. The sarcosine group improved significantly on positive, negative, cognitive and general symptoms, and the same was seen when only the risperidone-treated patients were analysed. No significant side effect was noted (Tsai 2004).
• Lane 2005 — acute relapse, 65 inpatients, 6 weeks. People admitted with a sudden worsening of schizophrenia received sarcosine 2 g a day, D-serine 2 g a day, or placebo, all together with risperidone. Sarcosine reduced Positive and Negative Syndrome Scale total scores more than placebo (P = .04) and more than D-serine (P < .001), and did better than placebo on the Scale for the Assessment of Negative Symptoms. D-serine with risperidone did not differ from risperidone alone in any area measured (Lane 2005).
• Lane 2008 — sarcosine alone, 20 people, 6 weeks. This was the one trial of sarcosine without an antipsychotic. Twenty acutely ill people who were not taking antipsychotic medicine were randomly given 2 g or 1 g of sarcosine a day. People on 2 g were more likely to respond (a fall of 20% or more in the Positive and Negative Syndrome Scale total), particularly those who had never taken an antipsychotic, but the dose-by-time analysis showed no significant difference between the two doses. There was no placebo group. Both doses were well tolerated with minimal side effects (Lane 2008).
• Lane 2010 — chronic schizophrenia, 60 people, 6 weeks. Sarcosine 2 g a day, D-serine 2 g a day or placebo was added to antipsychotic treatment. Sarcosine beat placebo on all four main measures: Positive and Negative Syndrome Scale total (p = 0.005), negative symptoms (p = 0.021), quality of life (p = 0.025) and global functioning (p = 0.042). D-serine did not differ from placebo on any measure. All treatments were well tolerated (Lane 2010).

These trials were small. The largest had 65 people split three ways, so each group held roughly 20. Positive results in small trials from a single group are the kind of finding that later, larger trials have often failed to repeat in this field; a 2025 review of treatments for thinking problems in schizophrenia notes "numerous phase 2/3 failures of compounds that showed initial promise in small-scale studies" (Sehatpour 2025).

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Sarcosine Compared Directly With D-Serine

Two of the trials above are the only head-to-head comparisons of sarcosine and D-serine found for this page. In both, at the same dose of 2 g a day, sarcosine did better and D-serine did not differ from placebo or from the antipsychotic alone (Lane 2005; Lane 2010). The authors concluded that, at the doses tested, a glycine transporter type 1 inhibitor may work better than a direct glycine-site agonist.

The other side: the D-serine pages on this site describe D-serine trials using weight-based doses (30 to 60 mg per kg of body weight, about 2 to 4 g for a 70-kg adult) did report benefits, and later dose research argues that 2 g of D-serine may simply be too low to engage the receptor reliably. Those trials and the dose argument are on D-Serine in Schizophrenia Research. The comparison therefore tells us how the two performed at one fixed dose, not which is better in general.

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The Clozapine Exception

Clozapine is the antipsychotic used for schizophrenia that has not responded to other medicines (see Clozapine). In 2006 the same group tested sarcosine 2 g a day or placebo in 20 inpatients on stable clozapine doses for 6 weeks. Sarcosine produced no greater improvement than placebo at weeks 2, 4 or 6. It was well tolerated (Lane 2006).

The authors noted that earlier studies had also found no added benefit from D-serine, glycine or D-cycloserine with clozapine, and suggested that clozapine may already strengthen N-methyl-D-aspartate receptor signalling, leaving little room for an add-on. Every pooled analysis described below reached the same result: the benefit was seen with antipsychotics other than clozapine and not with clozapine (Tsai 2010; Singh 2011; Chang 2020; Goh 2021; Marchi 2021). One pooled analysis found that glycine added to clozapine made positive symptoms worse (Singh 2011).

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Longer and Combined Trials

• The Polish Sarcosine Study (PULSAR), 6 months. This was the longest controlled study found. In one report, 50 people with stable schizophrenia on constant antipsychotic doses were randomly given sarcosine or placebo for six months. Brain spectroscopy (a scanner method that measures chemicals in a brain area) of the left dorsolateral prefrontal cortex showed higher ratios of N-acetylaspartate, a marker of nerve-cell health, and myo-inositol, a marker of glial-cell activity, in the sarcosine group. The authors report "simultaneous improvement of clinical symptoms" and describe sarcosine, 2 g daily, as seeming to be an effective add-on (Strzelecki 2015, spectroscopy study). A second report from the same study, with 30 people on 2 g of sarcosine and 29 on placebo, found no effect on any heart-and-metabolism measure or body-composition measure after six months (Strzelecki 2015, metabolic study).
• Open-label dose and blood-level study, Israel. Sarcosine was added for 22 stable patients, 5 at 2 g a day and 17 at 4 g a day, with no placebo group. After one week, positive symptoms and general symptoms improved significantly. Blood levels peaked about 1½ to 2½ hours after a dose and fell by half in about an hour. The authors called the study a short, small pilot (Amiaz 2015).
• Sarcosine plus sodium benzoate, 12 weeks. Sodium benzoate, a food preservative, blocks D-amino acid oxidase, the enzyme that breaks down D-serine (see Sodium Benzoate). In a 12-week double-blind trial in chronic schizophrenia, sarcosine 2 g a day plus benzoate 1 g a day was compared with sarcosine 2 g a day alone and with placebo. The combination, but not sarcosine alone, improved cognitive and global functioning, even though clinical symptoms had not improved (Lin 2017). The abstract does not give the number of participants.

Benzoate alone has its own trial: 52 people with chronic schizophrenia given 1 g a day of sodium benzoate or placebo for 6 weeks; benzoate produced a 21% improvement in the Positive and Negative Syndrome Scale total score (Lane 2013).

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What the Pooled Analyses Found

Pooled analyses (meta-analyses) combine the results of several trials. Several have looked at sarcosine alone and at the wider group of agents that strengthen the N-methyl-D-aspartate receptor: sarcosine, D-serine, glycine, D-cycloserine, sodium benzoate and others. Their results point in the same general direction but disagree on how sure the finding is.

Sarcosine on its own

• Chang 2020 — 7 trials, 326 participants. Sarcosine relieved overall clinical symptoms more than its comparators (standardized mean difference 0.51; 95% confidence interval 0.26 to 0.76). Trials of patients with stable symptoms showed an effect of 0.53. For overall cognitive function the effect was 0.27 and not statistically significant (confidence interval −0.06 to 0.60, p = 0.10). Benefit was seen with first- and second-generation antipsychotics except clozapine. One author of this analysis led most of the original trials.
• Marchi 2021 — 6 trials, 234 adults, all using 2 g a day. Sarcosine showed no significant effect at any of the pre-set time points (2, 4, 6 or more than 6 weeks), which the authors attribute to marked differences between the trials. In subgroups, symptom severity fell after 6 weeks in people with chronic schizophrenia (standardized mean difference −0.36) and in people without treatment resistance, that is, not on clozapine (−0.31).

Sarcosine among the other receptor-strengthening agents

• Tsai and Lin 2010 — about 800 people in 26 trials. Overall effect size on total symptoms 0.40; by symptom area, depressive 0.40, negative 0.38, cognitive 0.28, positive 0.26 and general 0.26. Glycine, D-serine and sarcosine each improved several symptom areas; D-cycloserine improved none. People on risperidone or olanzapine improved; people on clozapine did not.
• Singh and Singh 2011 — 29 trials, 1,253 people with chronic schizophrenia. For the whole group of agents, the effect was small for negative symptoms (−0.27) and medium for total symptoms (−0.40). Sarcosine's effect on total symptoms was −0.41. Added to antipsychotics other than clozapine, sarcosine's effect was −0.39 for negative symptoms and −0.53 for total symptoms. With clozapine, none of the agents helped.
• Goh 2021 — 40 double-blind, placebo-controlled trials, 4,937 patients. Added to antipsychotics, the agents improved several symptom types, particularly negative symptoms, with satisfactory side effects. Of the seven agents analysed, glycine, D-serine and sarcosine had better treatment profiles than the rest. The benefit appeared only with antipsychotics other than clozapine.
• Liang 2025 (network meta-analysis) — 148 trials, 12,339 patients, comparing many add-on agents at once and grading certainty. Sarcosine 2,000 mg a day showed benefit with moderate to high certainty in one or more areas and was one of three agents (with memantine and N-acetylcysteine) effective across several outcome areas. The combination of sarcosine 2,000 mg and benzoate 1,000 mg a day showed the largest gain in overall cognitive function (standardized mean difference 1.08; 95% confidence interval 0.45 to 1.71). Other agents ranked first for other outcomes: piracetam for total symptoms, benzoate for positive symptoms and memantine for negative symptoms.

A note on reading these numbers: a standardized mean difference of about 0.2 is usually called small, 0.5 medium and 0.8 large. Most of the sarcosine effects above fall between small and medium, they come from a few hundred people in total, and the trials differed a great deal from one another (Marchi 2021).

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Depression and Obsessive-Compulsive Disorder Trials

• Huang 2013 — depression, 40 people, 6 weeks. A randomized, double-blind trial compared sarcosine with the antidepressant citalopram in major depressive disorder. Sarcosine improved scores on the Hamilton Depression Rating Scale, the Clinical Global Impression and the Global Assessment of Function more than citalopram, and sarcosine-treated patients were more likely and quicker to reach remission and less likely to drop out. In rats, sarcosine produced the behavioural changes that standard antidepressants produce in these tests. The authors called the findings preliminary (Huang 2013).
• Padhan 2024 — depression, 60 people, 8 weeks. A double-blind trial in India added sarcosine or placebo to a selective serotonin reuptake inhibitor antidepressant. Both groups improved on the Montgomery-Åsberg Depression Rating Scale: by 13.3 points with sarcosine and 8.7 points with placebo, a difference of 4.6 points in favour of sarcosine (p = 0.003). Response (p = 0.007) and remission (p = 0.038) were more common with sarcosine, and blood glycine and brain-derived neurotrophic factor rose more (Padhan 2024).
• Wu 2011 — obsessive-compulsive disorder, 26 people, 10 weeks, open label. Sarcosine 500 to 2,000 mg a day was given alone or added to existing treatment, with no placebo group. In the 25 people analysed, Yale-Brown Obsessive Compulsive Scale scores fell from an average of 27.6 to 22.7, a mean drop of 19.8%; 8 people (32%) improved by more than 35%. One person withdrew because of a passing headache (Wu 2011).

Two of the three were small, and the obsessive-compulsive disorder study had no comparison group, so improvement there cannot be separated from the natural course of the illness or expectation.

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The Prostate-Cancer Marker Controversy

This is a separate story from the psychiatry trials. It concerns sarcosine as a measurable sign (a biomarker) of prostate cancer, not as a supplement.

• The 2009 Nature paper. Researchers measured more than 1,126 metabolites in 262 samples linked to prostate cancer (42 tissue samples and 110 each of urine and plasma). Sarcosine was "highly increased" as prostate cancer progressed to spread (metastasis) and could be detected in urine. In cells, sarcosine levels were higher in invasive prostate cancer cell lines; adding sarcosine to benign prostate cells, or blocking the enzyme that breaks it down, made them behave invasively, and blocking the enzyme that makes it reduced invasion (Sreekumar 2009). The PubMed record lists an erratum published in 2013.
• The 2010 urine study that did not confirm it. Urine sarcosine was measured after a standard rectal examination in 106 men with prostate cancer, 33 men whose biopsies found no cancer and 12 healthy people. The median sarcosine level was 13% lower in the cancer group, it was not linked to tumour stage or grade, and it did not distinguish cancer from no cancer better than the standard prostate-specific antigen (PSA) blood test, and did worse than the percent-free prostate-specific antigen test. The authors concluded it "cannot be considered as a suitable marker" (Jentzmik 2010).
• Serum. A 2010 report was titled "Serum sarcosine is not a marker for prostate cancer" (Struys 2010).
• A large prospective study, 2013. In a large cancer-screening trial, stored blood from 1,122 men who later developed prostate cancer was compared with 1,112 men who did not. Men in the highest quarter of sarcosine had a modestly higher risk (odds ratio 1.30; 95% confidence interval 1.02 to 1.65). The link was seen for non-aggressive cancer (1.44) but not for aggressive cancer (1.03; confidence interval 0.73 to 1.47) (Koutros 2013) — the opposite of the original idea that sarcosine marks aggressive spread.
• Advanced disease, 2013. In 52 men with metastatic, hormone-resistant prostate cancer treated with chemotherapy, serum sarcosine was higher than in men without that stage (median 0.81 vs 0.52 nmol/µl) and independently predicted worse survival (Lucarelli 2013). This was a small look-back study.

A 2013 review still described sarcosine as a "potential" marker and focused on ways to measure it (Cernei 2013). Taken together, the follow-up studies read for this page split: some found no use as a diagnostic marker, others found weak or stage-specific links. No study read for this page tested whether taking sarcosine by mouth affects prostate cancer in people. The cell results above are findings in cells only.

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Safety as the Studies Report It

• Short trials. In the 6-week schizophrenia trials, sarcosine at 1 or 2 g a day was described as well tolerated, with no significant side effect or minimal side effects (Tsai 2004; Lane 2006; Lane 2008; Lane 2010). The 2013 depression trial reported no significant side effects (Huang 2013). The pooled analysis of Tsai and Lin (2010) found no significant side effect or safety concern across the receptor-strengthening agents.
• Six months. In the Polish study, six months of 2 g a day caused no change in any measured heart-and-metabolism or body-composition value compared with placebo (Strzelecki 2015, metabolic study). The authors point out how common metabolic abnormalities are in people with schizophrenia, which is why they measured this.
• Higher dose. An open-label study gave 4 g a day to 17 people for a short period; the authors called sarcosine "a safe compound" in that setting (Amiaz 2015).
• Mood switching with antidepressants. Two case reports from the Polish study describe mood effects when sarcosine was added to antidepressant and antipsychotic medicines. A 34-year-old woman on olanzapine and venlafaxine developed drug-induced hypomania (less need for sleep, raised mood, libido and activity) after 10 to 12 weeks of 2 g a day; it settled within about a week after her venlafaxine dose was halved (Strzelecki 2015, hypomania case). A 23-year-old man on quetiapine and citalopram developed increased drive, inner tension and irritability two to four weeks after starting 2 g a day; it eased when the dose was lowered to 1 g (Strzelecki 2014). The authors attribute both to an interaction between glutamate and serotonin signalling.
• Headache. One of 26 people in the obsessive-compulsive disorder study withdrew because of a passing headache (Wu 2011).
• Inherited high sarcosine. Sarcosinemia, a genetic condition with lifelong high sarcosine, has been reported in rare cases with nervous-system disability (Benarrosh 2013). It is a different situation from short-term supplementation, and the trials above did not report such effects.

The trials were short and small, so rare or slow-developing side effects would not have been detected.

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What Is Not Known

• No approval as a medicine. None of the sources read for this page describes approval of sarcosine as a treatment for schizophrenia, depression or any other condition by a drug regulator. A 2019 editorial in the British Journal of Psychiatry describes it as "freely sold as a dietary supplement," calls it "a biologically rational treatment for schizophrenia," and states that the small number of studies "provide some evidence for its efficacy" (Curtis 2019). That is one psychiatrist's published opinion, not a guideline.
• Long-term effects. The longest controlled study lasted six months (Strzelecki 2015). Effects over years are not known.
• Replication. Most positive schizophrenia trials came from one research group, and all were small. The largest pooled analysis of sarcosine alone found no significant overall effect because the trials differed so much (Marchi 2021). The authors of several analyses call for larger trials.
• Cognition. Sarcosine alone did not significantly improve overall cognitive function in pooled data (Chang 2020); the cognitive signal came from the sarcosine-plus-benzoate combination (Lin 2017; Liang 2025).
• Dose and brain engagement. A 2025 review argues that many agents of this kind failed later because nobody confirmed the dose was reaching and acting on the receptor in the brain, and lists sarcosine among the "first-generation" glycine transport inhibitors (Sehatpour 2025). No trial read for this page measured sarcosine's effect on the receptor directly in patients.
• Depression and obsessive-compulsive disorder. Two small depression trials and one uncontrolled obsessive-compulsive disorder study exist. Whether the findings hold in larger trials is unknown.
• Prostate. Whether blood or urine sarcosine is a useful cancer marker remains disputed, and no human study read for this page addresses sarcosine supplements and prostate cancer.

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Key Research Papers

1. Tsai G, Lane HY, Yang P, Chong MY, Lange N. Glycine transporter I inhibitor, N-methylglycine (sarcosine), added to antipsychotics for the treatment of schizophrenia. Biol Psychiatry. 2004;55(5):452-6. PubMed PMID: 15023571
2. Lane HY, Chang YC, Liu YC, Chiu CC, Tsai GE. Sarcosine or D-serine add-on treatment for acute exacerbation of schizophrenia: a randomized, double-blind, placebo-controlled study. Arch Gen Psychiatry. 2005;62(11):1196-204. PubMed PMID: 16275807
3. Lane HY, Huang CL, Wu PL, Liu YC, Chang YC, Lin PY, Chen PW, Tsai G. Glycine transporter I inhibitor, N-methylglycine (sarcosine), added to clozapine for the treatment of schizophrenia. Biol Psychiatry. 2006;60(6):645-9. PubMed PMID: 16780811
4. Lane HY, Liu YC, Huang CL, Chang YC, Liau CH, Perng CH, Tsai GE. Sarcosine (N-methylglycine) treatment for acute schizophrenia: a randomized, double-blind study. Biol Psychiatry. 2008;63(1):9-12. PubMed PMID: 17659263
5. Lane HY, Lin CH, Huang YJ, Liao CH, Chang YC, Tsai GE. A randomized, double-blind, placebo-controlled comparison study of sarcosine (N-methylglycine) and D-serine add-on treatment for schizophrenia. Int J Neuropsychopharmacol. 2010;13(4):451-60. PubMed PMID: 19887019
6. Lin CY, Liang SY, Chang YC, Ting SY, Kao CL, Wu YH, Tsai GE, Lane HY. Adjunctive sarcosine plus benzoate improved cognitive function in chronic schizophrenia patients with constant clinical symptoms: A randomised, double-blind, placebo-controlled trial. World J Biol Psychiatry. 2017;18(5):357-368. PubMed PMID: 26691576
7. Lane HY, Lin CH, Green MF, Hellemann G, Huang CC, Chen PW, Tun R, Chang YC, Tsai GE. Add-on treatment of benzoate for schizophrenia: a randomized, double-blind, placebo-controlled trial of D-amino acid oxidase inhibitor. JAMA Psychiatry. 2013;70(12):1267-75. PubMed PMID: 24089054
8. Strzelecki D, Podgórski M, Kałużyńska O, Stefańczyk L, Kotlicka-Antczak M, Gmitrowicz A, Grzelak P. Adding Sarcosine to Antipsychotic Treatment in Patients with Stable Schizophrenia Changes the Concentrations of Neuronal and Glial Metabolites in the Left Dorsolateral Prefrontal Cortex. Int J Mol Sci. 2015;16(10):24475-89. PubMed PMID: 26501260
9. Strzelecki D, Kałużyńska O, Szyburska J, Wlazło A, Wysokiński A. No changes of cardiometabolic and body composition parameters after 6-month add-on treatment with sarcosine in patients with schizophrenia. Psychiatry Res. 2015;230(2):200-4. PubMed PMID: 26343833
10. Amiaz R, Kent I, Rubinstein K, Sela BA, Javitt D, Weiser M. Safety, tolerability and pharmacokinetics of open label sarcosine added on to anti-psychotic treatment in schizophrenia - preliminary study. Isr J Psychiatry Relat Sci. 2015;52(1):12-5. PubMed PMID: 25841105
11. Strzelecki D, Szyburska J, Rabe-Jabłońska J. Two grams of sarcosine in schizophrenia - is it too much? A potential role of glutamate-serotonin interaction. Neuropsychiatr Dis Treat. 2014;10:263-6. PubMed PMID: 24523591
12. Strzelecki D, Szyburska J, Kotlicka-Antczak M, Kałużyńska O. Hypomania after augmenting venlafaxine and olanzapine with sarcosine in a patient with schizophrenia: a case study. Neuropsychiatr Dis Treat. 2015;11:533-6. PubMed PMID: 25784808
13. Tsai GE, Lin PY. Strategies to enhance N-methyl-D-aspartate receptor-mediated neurotransmission in schizophrenia, a critical review and meta-analysis. Curr Pharm Des. 2010;16(5):522-37. PubMed PMID: 19909229
14. Singh SP, Singh V. Meta-analysis of the efficacy of adjunctive NMDA receptor modulators in chronic schizophrenia. CNS Drugs. 2011;25(10):859-85. PubMed PMID: 21936588
15. Chang CH, Lin CH, Liu CY, Chen SJ, Lane HY. Efficacy and cognitive effect of sarcosine (N-methylglycine) in patients with schizophrenia: A systematic review and meta-analysis of double-blind randomised controlled trials. J Psychopharmacol. 2020;34(5):495-505. PubMed PMID: 32122256
16. Marchi M, Galli G, Magarini FM, Mattei G, Galeazzi GM. Sarcosine as an add-on treatment to antipsychotic medication for people with schizophrenia: a systematic review and meta-analysis of randomized controlled trials. Expert Opin Drug Metab Toxicol. 2021;17(4):483-493. PubMed PMID: 33538213
17. Goh KK, Wu TH, Chen CH, Lu ML. Efficacy of N-methyl-D-aspartate receptor modulator augmentation in schizophrenia: A meta-analysis of randomised, placebo-controlled trials. J Psychopharmacol. 2021;35(3):236-252. PubMed PMID: 33406959
18. Liang CW, Cheng HY, Tseng MM. Augmentation with glutamatergic modulators for schizophrenia: A network meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2025;142:111495. PubMed PMID: 40945815
19. Sehatpour P, Kantrowitz JT. Finding the Right Dose: NMDA Receptor-Modulating Treatments for Cognitive and Plasticity Deficits in Schizophrenia and the Role of Pharmacodynamic Target Engagement. Biol Psychiatry. 2025;97(2):128-138. PubMed PMID: 39218136
20. Curtis D. A possible role for sarcosine in the management of schizophrenia. Br J Psychiatry. 2019;215(6):697-698. PubMed PMID: 31685041
21. Huang CC, Wei IH, Huang CL, Chen KT, Tsai MH, Tsai P, Tun R, Huang KH, Chang YC, Lane HY, Tsai GE. Inhibition of glycine transporter-I as a novel mechanism for the treatment of depression. Biol Psychiatry. 2013;74(10):734-41. PubMed PMID: 23562005
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26. Benarrosh A, Garnotel R, Henry A, Arndt C, Gillery P, Motte J, Bakchine S. A young adult with sarcosinemia. No benefit from long duration treatment with memantine. JIMD Rep. 2013;9:93-96. PubMed PMID: 23430553
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PubMed Topic Searches

1. PubMed: sarcosine and schizophrenia, randomized trials
2. PubMed: glycine transporter type 1 inhibitors in schizophrenia
3. PubMed: N-methyl-D-aspartate receptor add-on agents, meta-analyses
4. PubMed: sarcosine and depression
5. PubMed: sarcosine as a prostate-cancer biomarker

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Connections

• Amino Acid Derivatives — the category this page belongs to
• Glycine — the parent amino acid and its own schizophrenia trials
• D-Serine — the other natural co-agonist at the same receptor
• D-Serine in Schizophrenia Research — the D-serine trials and the dose question
• D-Serine and N-Methyl-D-Aspartate Receptor Co-Agonism — how the receptor and its co-agonists work
• Schizophrenia — the condition these trials studied
• Clozapine — the antipsychotic with which sarcosine showed no added effect
• Sodium Benzoate — the preservative tested with sarcosine
• SAM-e (S-Adenosylmethionine) — the methyl donor used to make sarcosine

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