Semantic Priming after Ketamine Acutely in Healthy Volunteers and Following Chronic Self-Administration in Substance Users

Background Ketamine is used acutely as a model of schizophrenia. It has been suggested that chronic ketamine may also mimic aspects of this disorder, in particular impaired cognitive function. As semantic processing deficits are considered central to cognitive impairments in schizophrenia, this study aimed to characterize semantic impairments following both acute and chronic ketamine. Methods We examined the acute effects of two doses of ketamine (Experiment 1) using a double-blind, placebo-controlled, independent group design with 48 volunteers. Ketamine’s chronic effects (Experiment 2) were explored in 16 ketamine users and 16 poly-drug controls. A semantic priming task with a frequency (high and low) and stimulus onset asynchrony (SOA: short–200 msec, long–750 msec) manipulation was used. Results In Experiment 1, acute ketamine produced inverse priming at the long SOA. In Experiment 2, ketamine users showed inverse priming for low-frequency words at the long SOA compared to poly-drug controls. Conclusions The inverse priming effect at the long SOA induced by acute ketamine was indicative of controlled processing impairments. In ketamine users, there was also an indication of controlled processing impairments. Decreased priming for low-frequency words suggested that long-term ketamine abuse results in damage to the semantic store.