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.
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CBD (600 mg) attenuated depersonalization symptoms induced by the NMDA receptor antagonist ketamine in a double-blind, placebo-controlled trial.
“In a double blind, placebo-controlled trial, CBD (600 mg) was shown to attenuate depersonalization symptoms induced by the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine, which increases glutamate release at low doses (80).”
From Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age (2018) · cites this paper as [80]
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“…↓MBP Granjeiro et al., 2011 Rats Stress (restraint) 15, 30 or 60 nmol intracisternal Pre-stress Pre-stress and during 1 hr post-stress No change in MBP or HR Hallak et al., 2011 Human Healthy volunteers 600mg Oral Pre-test Pre-drug and at 30 min interval for 2.30 h post-drug No change in SBP, DBP…”
BackgroundMethodInfluential
- Authors
- Hallak, J. E. C., Dursun, S. M., Bosi, D. C., de Macedo, L. R. H., Machado-de-Sousa, J. P., Abrão, J., Crippa, J. A. S., McGuire, P., Krystal, J. H., Baker, G. B., & Zuardi, A. W.
- Affiliations
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (BR)
- Universidade de São Paulo (BR)
- Yale University (US)
- Corresponding author
- Hallak, Jaime E.C.
- Venue
- Progress in Neuro-Psychopharmacology and Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2011-01
- Volume
- 35
- Issue
- 1
- Pages
- 198-202
- ISSN
- 0278-5846 (ISSN-L)
- OpenAlex
- W2067909880
- Cited by
- 83
- References
- 47
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 1 · 2023: 8 · 2022: 9 · 2021: 6 · 2020: 6 · 2019: 6 · 2018: 2 · 2017: 5 · 2016: 4 · 2015: 10 · 2014: 3 · 2013: 5 · 2012: 6
- FWCI
- 4.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Progress in Neuro-Psychopharmacology and Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- National Council for Scientific and Technological Development (CNPq — Brazil)
- State of São Paulo Research Foundation (FAPESP)
- National Institute on Alcohol Abuse and Alcoholism (K05 AA 14906-05, 2P50 AA 012870-08, R01 AA017173-02)
- National Center for Research Resources (NCRR 1UL1RR024139)
- U.S. Department of Veterans Affairs
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- cannabidiol, ketamine, NMDA receptor antagonism, endocannabinoid system, glutamatergic system, drug interactions, schizophrenia, dissociative states, depersonalization, psychopathology, Brief Psychiatric Rating Scale
- MeSH terms
- Adult, Behavioral Symptoms, Blood Pressure, Cannabidiol, Double-Blind Method, Heart Rate, Humans, Ketamine, Male, Psychiatric Status Rating Scales, Time Factors, Receptors, N-Methyl-D-Aspartate, Excitatory Amino Acid Antagonists, Receptors, Cannabinoid, Young Adult, Cannabinoid Receptor Antagonists
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