Psychological effects of (S)-ketamine and N,N-dimethyltryptamine (DMT): a double-blind, cross-over study in healthy volunteers
This double-blind study (n=9) of the psychological effects of esketamine and DMT found the positive effects of DMT, and the negative effects of ketamine most resembling those symptoms of schizophrenia.
Authors
- Gouzoulis-Mayfrank, E.
- Heekeren, K.
- Neukirch, A.
Published
Abstract
Introduction
Pharmacological challenges with hallucinogens are used as models for psychosis in experimental research. The state induced by glutamate antagonists such as phencyclidine (PCP) is often considered as a more appropriate model of psychosis than the state induced by serotonergic hallucinogens such as lysergic acid diethylamide (LSD), psilocybin and N,N-dimethyltryptamine (DMT). However, so far, the psychological profiles of the two types of hallucinogenic drugs have never been studied directly in an experimental within-subject design.
Methods
Fifteen healthy volunteers were included in a double-blind, cross-over study with two doses of the serotonin 5-HT2A agonist DMT and the glutamate N-methyl-d-aspartate (NMDA) antagonist (S)-ketamine.
Results
Data are reported for nine subjects who completed both experimental days with both doses of the two drugs. The intensity of global psychological effects was similar for DMT and (S)-ketamine. However, phenomena resembling positive symptoms of schizophrenia, particularly positive formal thought disorder and inappropriate affect, were stronger after DMT. Phenomena resembling negative symptoms of schizophrenia, attention deficits, body perception disturbances and catatonia-like motor phenomena were stronger after (S)-ketamine.
Discussion
The present study suggests that the NMDA antagonist model of psychosis is not overall superior to the serotonin 5-HT2A agonist model. Rather, the two classes of drugs tend to model different aspects or types of schizophrenia. The NMDA antagonist state may be an appropriate model for psychoses with prominent negative and possibly also catatonic features, while the 5-HT2A agonist state may be a better model for psychoses of the paranoid type.
Research Summary of 'Psychological effects of (S)-ketamine and N,N-dimethyltryptamine (DMT): a double-blind, cross-over study in healthy volunteers'
Introduction
Gouzoulis-Mayfrank and colleagues frame the study within a long tradition of using hallucinogenic drugs as pharmacological models of psychosis. Earlier research established that classic serotonergic hallucinogens (for example LSD, psilocybin, DMT) act mainly at serotonin 5-HT2A receptors and tend to produce experiences that differ phenomenologically from schizophrenia (more visual phenomena, preserved affect and social engagement), whereas PCP-like drugs (PCP, ketamine) are NMDA receptor antagonists and have been argued to induce a more schizophrenia-like state with thought disorder, negative symptoms and motor abnormalities. Despite this conceptual distinction, no prior experimental within-subject comparison had directly contrasted the psychological profiles produced by a serotonergic agonist and an NMDA antagonist in the same healthy volunteers. The present study therefore set out to compare intravenous N,N-dimethyltryptamine (DMT, a 5-HT2A agonist) with (S)-ketamine (an NMDA antagonist) in a randomised, double-blind, cross-over design. The investigators hypothesised that neither agent would be an overall superior model of psychosis; rather, (S)-ketamine would provoke more negative and cognitive-like phenomena, while DMT would produce more positive symptom-like phenomena (for example thought disorder and perceptual hallucinations). The comparison used dose-titrated infusions to obtain comparable overall intensities of subjective effect across the two drug states.
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Study Details
- Study Typeindividual
- Journal
- Compounds
- Topics
- APA Citation
Gouzoulis-Mayfrank, E., Heekeren, K., Neukirch, A., Stoll, M., Stock, C., Obradovic, M., & Kovar, K. (2005). Psychological effects of (S)-ketamine and N,N-dimethyltryptamine (DMT): a double-blind, cross-over study in healthy volunteers. Pharmacopsychiatry, 38(6), 301-311. https://doi.org/10.1055/s-2005-916185
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