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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.

Jaime E. C. Hallak, Serdar Dursun, Daniel C Bosi, Ligia Ribeiro Horta de Macedo, João Paulo Machado‐de‐Sousa, João Abrão, José A. Crippa, Phillip McGuire, John H. Krystal, Glen B. Baker, Antonio W. Zuardi

Progress in Neuro-Psychopharmacology and Biological Psychiatry January 15, 2011 DOI: 10.1016/j.pnpbp.2010.11.002 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized crossover trial Peer reviewed
Sample size 10
Population Healthy male volunteers
Interventions Cannabidiol (CBD) Ketamine
Dose CBD 600 mg; ketamine bolus of 0.26 mg/kg/1 min followed by IV infusion of 0.25 mg/kg over 30 min
Duration Assessments from 30 min before to 90 min after ketamine administration
Measures Brief Psychiatric Rating Scale (BPRS), Clinician Administered Dissociative States Scale (CADSS)
Topics CBD Esketamine Ketamine
Key findings CBD significantly augmented the activating effects of ketamine as measured by the activation subscales of the BPRS, while showing a non-significant trend to reduce ketamine-induced depersonalization on the CADSS.

Abstract

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. This study tested the hypothesis that CBD would attenuate the behavioral effects of the NMDA receptor antagonist, ketamine, in healthy human subjects. 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. 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. These data describe a complex pattern of psychopharmacologic interactions between CBD and ketamine at the doses of each agent studied in this experiment.

Comparable studies

Other randomized controlled trials on CBD, most cited first.

Study Year Design Participants
Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment Healthy participants 2012 Randomized controlled trial n = 48
Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing Healthy, English-native, right-handed men who had used cannabis 15 times or less in... 2009 Double-blind, randomized, placebo-controlled crossover trial n = 15
Inverted U-Shaped Dose-Response Curve of the Anxiolytic Effect of Cannabidiol during Public Speaking in Real Life Healthy subjects aged 18 to 35 years 2017 Randomized controlled trial n = 60
Acute Effects of a Single, Oral dose of d9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) Administration in Healthy Volunteers Healthy male subjects 2012 Randomized controlled trial n = 16
Modulation of Mediotemporal and Ventrostriatal Function in Humans by Δ9-Tetrahydrocannabinol Healthy, native English-speaking, right-handed men of white race/ethnicity who had used... 2009 Randomized controlled trial n = 15

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CBD Esketamine Ketamine