Study Summary

Fourteen healthy participants were included in this randomized, double-blind, cross-over study investigating the cerebral correlates of alertness in the human 5HT2A agonist and N-methyl-D-aspartic acid (NMDA) antagonist models of psychosis. Participants were administered both placebo and active drug [dimethyltryptamine (DMT) or S-ketamine] in two sessions with a 2-4 hour break between both conditions and a washout period of at least 14 days between sessions. Subjective drug effects were assessed using the Hallucinogenic Rating Scale (HRS) and the Abnormer psychischer Zustand (APZ) altered states of consciousness questionnaire. Schizophrenia-like symptoms were assessed using the the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of Negative Symptoms (SANS), and the Schizophrenia Proneness Instrument – Adult version (SPI-A). Visual and auditory alertness was also measured using a target-detection task with brain images being obtained through fMRI. Study results show that both drugs induced psychotic symptoms similar to those of schizophrenia. The intensity of hallucinogenic effect was similar for both drugs, with visual alterations being more pronounced after DMT. Overall, the administration of DMT led to decreased activation during both visual and auditory modalities, while S-ketamine increased activation during the auditory modality. An analysis of cue benefits revealed an attentional impairment particularly accompanied by DMT administration.