Psychological effects of (S)-ketamine and N,N-dimethyltryptamine (DMT): a double-blind, cross-over study in healthy volunteers.
BACKGROUND
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.


CONCLUSIONS
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.
Gouzoulis-Mayfrank
E
E
Department of Psychiatry and Psychotherapy, University of Cologne, Kerpener Strasse 62, Cologne, Germany. e.gouzoulis@uni-koeln.de
Heekeren
K
K
Neukirch
A
A
Stoll
M
M
Stock
C
C
Obradovic
M
M
Kovar
K-A
KA
D000328:Adult; D003071:Cognition / Q000187:drug effects; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D006212:Hallucinations / Q000139:chemically induced / Q000523:psychology; D006213:Hallucinogens / Q000494:pharmacology*; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007649:Ketamine / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D004130:N,N-Dimethyltryptamine / Q000494:pharmacology*; D011569:Psychiatric Status Rating Scales; D011594:Psychometrics; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012565:Schizophrenic Psychology; D013237:Stereoisomerism
D018691:Excitatory Amino Acid Antagonists; D006213:Hallucinogens; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D004130:N,N-Dimethyltryptamine