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 & biological psychiatry January 15, 2011 DOI: 10.1016/j.pnpbp.2010.11.002 (opens in new tab)
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.