Hypericum extract reverses S-ketamine-induced changes in auditory evoked potentials in humans - Possible implications for the treatment of schizophrenia

Auditory evoked potentials (AEP) provide a correlate of cognitive dysfunction in schizophrenia. Both cognitive dysfunction and AEP-characteristics might be related to reduced glutamatergic neurotransmission as induced by glutamate-antagonist like ketamine. Hypericum extract LI160 has demonstrated a ketamine-antagonising effect. We examined whether LI160 reverses changes of a low dose ketamine on AEP in healthy subjects. We performed a double-blind randomized treatment with either 2 x 750 mg LI160 or placebo given one week, using a crossover design, in 16 health subjects. A test-battery including AEPs, the oculodynamic test (ODT) and a cognitive test were performed before and after an infusion with 4 mg of S-ketamine over a period of 1 hour. S-ketamine lead to a significant decrease in the N100-P200 peak to peak (ptp) amplitude after the placebo treatment, whereas ptp was significantly increased by S-ketamine infusion in the LI160 treated subjects. The ODT and the cognitive testing revealed no significant of ketamine-infusion and therefore no interaction between treatment groups. AEP measures are sensitive means to assess the effect of low dose ketamine. Provided that ketamine mimics cognitive deficits in schizophrenia, LI160 might be effective to treat these symptoms.