Fifteen healthy subjects were included in this randomized, double-blind, crossover study comparing the psychological effects of serotonin 5HT-2A agonist N,N-dimethyltryptamine (DMT) and N-methyl-d-aspartate antagonist (NMDA) S-ketamine. Participants were administered low- and high-dose S-ketamine and DMT intravenously in a pseudorandomized order in two sessions with a washout period of 2 hours between doses and 2-4 weeks between sessions. Subjective drug effects were assessed using the Hallucinogen Rating Scale (HRS) and the Abnormer Psychischer Zustand (APZ) Altered States of Consciousness. Schizophrenia-like psychotic symptoms were assessed using three clinician rating scales: The Scale for the Assessment of Negative Symptoms (SANS), The Scale for the Assessment of Positive Symptoms (SAPS), and the Schizophrenia Prediction Instrument - Adult Version (SPI-A). The intensity of global psychological effect was similar for DMT and S-Ketamine. Positive symptoms of schizophrenia were more pronounced following DMT, whereas more negative symptoms were more pronounced after S-ketamine.