Ketamine produces a short-lived (<30 minutes) increase in psychotic symptoms in both healthy volunteers and people with schizophrenia, with the magnitude of positive-symptom change similar across groups despite different baselines. In healthy volunteers, ketamine raised scores on both the psychosis and withdrawal subscales of the Brief Psychiatric Rating Scale, whereas in schizophrenic volunteers only positive symptoms increased. Seventy percent of patients reported an exacerbation of previously experienced positive symptoms. The similarity between ketamine-induced symptoms and patients' own positive symptoms suggests ketamine offers a unique human psychosis model, potentially more valid than the amphetamine model for studying schizophrenia.
Ketamine, a drug that blocks NMDA receptors, produces schizophrenia-like symptoms in healthy people but does not disrupt sensory gating in the same way schizophrenia does. In a randomized double-blind crossover study, 16 healthy men received a 60-minute infusion of either ketamine (0.5 mg/kg) or saline. Ketamine caused robust dissociative and negative symptoms, but it did not impair prepulse inhibition (PPI) of the startle reflex; instead, it significantly enhanced PPI in the first block. These results indicate that ketamine's clinical effects are not coupled with the PPI disruption seen in schizophrenia.