The initial iteration of the glutamate hypothesis of psychosis/schizophrenia was based on the similarities between the effects of the NMDA receptor antagonists phencyclidine (PCP) and ketamine, and the symptoms of psychosis/schizophrenia [107, 120]. According to the hypothesis, the schizophrenia-like effects of these compounds was related to their capacity to induce NMDA receptor hypofunction. Therefore, the effects of cannabinoids on reducing glutamate release may provide one mechanism by which they produce psychosis.
