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The interplay of cannabinoid and NMDA glutamate receptor systems in humans: preliminary evidence of interactive effects of cannabidiol and ketamine in healthy human subjects.

Abstract

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.

CONCLUSION

These data describe a complex pattern of psychopharmacologic interactions between CBD and ketamine at the doses of each agent studied in this experiment.

Links

  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Department of Neuroscience and Behavior, University of São Paulo, Ribeirão Preto, Brazil. jhallak@fmrp.usp.br

    , , , , , , , , ,

    Source

    MeSH

    Adult
    Behavioral Symptoms
    Blood Pressure
    Cannabidiol
    Cannabinoid Receptor Antagonists
    Double-Blind Method
    Excitatory Amino Acid Antagonists
    Heart Rate
    Humans
    Ketamine
    Male
    Psychiatric Status Rating Scales
    Receptors, Cannabinoid
    Receptors, N-Methyl-D-Aspartate
    Time Factors
    Young Adult

    Pub Type(s)

    Journal Article
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, Non-P.H.S.

    Language

    eng

    PubMed ID

    21062637

    Citation

    TY - JOUR T1 - The interplay of cannabinoid and NMDA glutamate receptor systems in humans: preliminary evidence of interactive effects of cannabidiol and ketamine in healthy human subjects. AU - Hallak,Jaime E C, AU - Dursun,Serdar M, AU - Bosi,Daniel C, AU - de Macedo,Ligia Ribeiro Horta, AU - Machado-de-Sousa,João Paulo, AU - Abrão,João, AU - Crippa,José A S, AU - McGuire,Phillip, AU - Krystal,John H, AU - Baker,Glen B, AU - Zuardi,Antonio W, Y1 - 2010/11/07/ PY - 2010/6/1/received PY - 2010/11/1/revised PY - 2010/11/1/accepted PY - 2010/11/7/aheadofprint PY - 2010/11/11/entrez PY - 2010/11/11/pubmed PY - 2011/5/4/medline SP - 198 EP - 202 JF - Progress in neuro-psychopharmacology & biological psychiatry JO - Prog. Neuropsychopharmacol. Biol. Psychiatry VL - 35 IS - 1 N2 - 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. CONCLUSION: These data describe a complex pattern of psychopharmacologic interactions between CBD and ketamine at the doses of each agent studied in this experiment. SN - 1878-4216 UR - https://www.unboundmedicine.com/medline/citation/21062637/abstract/The_interplay_of_cannabinoid_and_NMDA_glutamate_receptor_systems_in_humans:_preliminary_evidence_of_interactive_effects_of_cannabidiol_and_ketamine_in_healthy_human_subjects_ L2 - http://linkinghub.elsevier.com/retrieve/pii/S0278-5846(10)00416-1 ER -