The interplay of cannabinoid and NMDA glutamate receptor systems in humans: preliminary evidence of interactive effects of cannabidiol and ketamine in healthy human subjects.
BACKGROUND
Interactions between glutamatergic and endocannabinoid systems may contribute to schizophrenia, dissociative states, and other psychiatric conditions. Cannabidiol (CBD), a cannabinoid-1/2 (CB1/2) receptor weak partial agonist or antagonist, may play a role in the treatment of schizophrenia.


OBJECTIVE
This study tested the hypothesis that CBD would attenuate the behavioral effects of the NMDA receptor antagonist, ketamine, in healthy human subjects.


METHODS
Ten male healthy volunteers were evaluated twice in a randomized order. In both sessions they received ketamine (bolus of 0.26 mg/kg/1 min followed by IV infusion of 0.25mg/kg over 30 min) preceded by either CBD (600 mg) or placebo. Psychopathology was assessed using the Brief Psychiatric Rating Scale (BPRS) and the CADSS (Clinician Administered Dissociative States Scale) at regular intervals from 30 min before to 90 min after ketamine administration.


RESULTS
CBD significantly augmented the activating effects of ketamine, as measured by the activation subscales of the BPRS. However, CBD also showed a non-significant trend to reduce ketamine-induced depersonalization, as measured by the CADSS.


CONCLUSIONS
These data describe a complex pattern of psychopharmacologic interactions between CBD and ketamine at the doses of each agent studied in this experiment.
Department of Neuroscience and Behavior, University of São Paulo, Ribeirão Preto, Brazil. jhallak@fmrp.usp.br
Jaime E C
JE
Hallak
Serdar M
SM
Dursun
Daniel C
DC
Bosi
Ligia Ribeiro Horta
LR
de Macedo
João Paulo
JP
Machado-de-Sousa
João
J
Abrão
José A S
JA
Crippa
Phillip
P
McGuire
John H
JH
Krystal
Glen B
GB
Baker
Antonio W
AW
Zuardi
D000328:Adult; D001526:Behavioral Symptoms / Q000139:chemically induced*; D001794:Blood Pressure / Q000187:drug effects; D002185:Cannabidiol / Q000494:pharmacology*; D063387:Cannabinoid Receptor Antagonists; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D011569:Psychiatric Status Rating Scales; D043882:Receptors, Cannabinoid / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013997:Time Factors; D055815:Young Adult
D063387:Cannabinoid Receptor Antagonists; D018691:Excitatory Amino Acid Antagonists; D043882:Receptors, Cannabinoid; D016194:Receptors, N-Methyl-D-Aspartate; D002185:Cannabidiol; D007649:Ketamine