Jörg Daumann – Pharmacological modulation of attentional processes in the DMT and ketamine model of psychosis

Deficits in attentional functions are counted among the core cognitive symptoms in schizophrenic patients. Pharmacologic challenges with hallucinogens have been used as models for psychosis. In this talk, I give an overview of our studies on the pharmacological modulation of DMT and ketamine on different aspects of attentional functions. We investigated prepulse inhibition of the startle reflex (PPI), mismatch negativity (MMN), and visual and auditory alertness as well as spatial orienting of attention combined with fMRI. Data of fifteen healthy subjects were collected in randomized, double-blind, crossover studies. Ketamine increased PPI, whereas DMT had no significant effects on PPI. Ketamine decreased and DMT tended to decrease startle magnitude. Furthermore, we found blunted MMN after both drugs. However, the reduction in MMN activity was overall more pronounced after ketamine intake, and only ketamine had a significant impact on the frontal source of MMN. Administration of DMT and ketamine led to different cortical activations during the performance of both tasks. The ketamine model and the DMT model of psychosis display distinct neurocognitive profiles. These findings are in line with the view of the two classes of hallucinogens modeling different aspects of psychosis.