Two classes of hallucinogenic drugs model different aspects of schizophrenia-like symptoms. In a double-blind crossover study, fifteen healthy volunteers received both the serotonin 5-HT2A agonist DMT and the glutamate NMDA antagonist (S)-ketamine. Nine subjects completed both sessions. DMT produced stronger positive symptoms resembling schizophrenia, such as formal thought disorder and inappropriate affect. (S)-ketamine produced stronger negative symptoms, attention deficits, body perception disturbances, and catatonia-like motor phenomena. The findings suggest neither drug model is overall superior; rather, each models distinct symptom profiles: DMT models paranoid-type psychoses, while (S)-ketamine models psychoses with prominent negative and catatonic features.
Schizophrenia patients show reduced prepulse inhibition (PPI) of the startle reflex, but hallucinogen models of psychosis in healthy volunteers do not replicate this effect. In a double-blind crossover study with 15 healthy volunteers, the serotonergic hallucinogen DMT had no significant effect on PPI, while the NMDA antagonist S-ketamine increased PPI and decreased startle magnitude. Neither drug affected the attentional modulation of PPI. These results highlight differences between human hallucinogen models and both animal models and schizophrenia itself.