In relation to these findings, Dr. Paul Morrison (King's College London) is currently testing the NO-based compound glyceryl trinitrate (GTN) for its ability to improve the cognitive symptom domain of patients experiencing acute psychosis and who are requiring hospitalization (Clinicaltrials.gov Identifier: NCT02906553). Glyceryl trinitrate is another nitrovasodilator drug that has been used to treat angina and other cardiac conditions including myocardial infarction and congestive heart failure. The biotransformation of GTN involves both enzymatic and nonenzymatic pathways that are linked to the pharmacokinetic and pharmacodynamics properties of the drug (138, 196). The metabolic conversion of GTN to NO may also improve downstream glutamate signaling. This clinical trial aims to assess the role of the NO system in cognition and will initiate a sublingual GTN spray 0.4 mg dose, once per day for 3 days or matching placebo formulation spray not containing GTN before the patients are initiated on antipsychotic medication. Glyceryl trinitrate in sublingual spray formulation is a much more convenient and less invasive approach to drug delivery than intravenous infusion of SNP in patients with schizophrenia and may be a promising approach to further improve treatment-resistant cognitive symptoms in the illness.