At the Royal Veterinary College, Lodge linked his interests in anaesthesia and glutamate receptors by making the key discovery that the dissociative anaesthetics, ketamine and phencyclidine,[6] selectively blocked NMDA receptors. He related NMDA receptor antagonism to psychotomimetic effects. This provided a basis for the glutamate hypothesis of schizophrenia and redirected pharmaceutical search for schizophrenia therapies. David was recruited as a director of Eli Lilly's neuroscience program, where he helped develop glutamate receptor approaches to brain diseases, resulting in clinical trials, e.g. for schizophrenia, some of which are ongoing. As of 2016, Lodge's research concerns the mechanism of action of new ‘legal highs’ and the consequences of spontaneous mutations in glutamate receptors.