Effects of the hallucinogen psilocybin on habituation and prepulse inhibition of the startle reflex in humans

Schizophrenic patients exhibit deficits in indices of sensorimotor gating, such as habituation and prepulse inhibition (PPI) of the startle reflex. Ha llucinogenic drug-induced states are putative models for the early and acut e stages of schizophrenic and schizophrenia-spectrum disorders. Hallucinoge nic drugs have been shown to disrupt PPI and/or retard habituation of the s tartle reflex in animal models of schizophrenia, consistent with the view o f hallucinogen-induced states as 'model psychoses'. We evaluated the effect s of the hallucinogen psilocybin on PPI and habituation of the startle refl ex in a double-blind, placebo-controlled human study with 12 healthy subjec ts. In contrast to animal studies, in our small human sample, psilocybin in creased PPI, while having no clear effect on habituation (n = 6). These fin dings must be considered preliminary because several factors, including dos e regimens and experimental parameters, may influence the results of studie s on startle plasticity. Further investigations both with psychotic patient s in different stages of the disease and with human and animal models of sc hizophrenia are needed in order to explore the effects of hallucinogens on sensorimotor gating and the relationship between information processing in hallucinogenic drug-induced states and the naturally occurring psychoses. B ehav Pharmacol 1998; 9:561-566 (C) 1998 Lippincott Williams & Wilkins.