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Epilepsy Behav. 2017 Oct;75:29-35. doi: 10.1016/j.yebeh.2017.07.014. Epub 2017 Aug 16.

Anticonvulsant effect of cannabidiol in the pentylenetetrazole model: Pharmacological mechanisms, electroencephalographic profile, and brain cytokine levels.

Author information

1
Graduate School in Neuroscience, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Brazil.
2
Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Brazil.
3
Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Brazil.
4
Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Brazil.
5
Department of Internal Medicine, School of Medicine, Universidade Federal de Minas Gerais, Brazil. Electronic address: Antonio.L.Teixeira@uth.tmc.edu.
6
Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Brazil. Electronic address: fabriciomoreira@icb.ufmg.br.

Abstract

Cannabidiol (CBD), the main nonpsychotomimetic compound from Cannabis sativa, inhibits experimental seizures in animal models and alleviates certain types of intractable epilepsies in patients. Its pharmacological profile, however, is still uncertain. Here we tested the hypothesis that CBD anticonvulsant mechanisms are prevented by cannabinoid (CB1 and CB2) and vanilloid (TRPV1) receptor blockers. We also investigated its effects on electroencephalographic (EEG) activity and hippocampal cytokines in the pentylenetetrazole (PTZ) model. Pretreatment with CBD (60mg/kg) attenuated seizures induced by intraperitoneal, subcutaneous, and intravenous PTZ administration in mice. The effects were reversed by CB1, CB2, and TRPV1 selective antagonists (AM251, AM630, and SB366791, respectively). Additionally, CBD delayed seizure sensitization resulting from repeated PTZ administration (kindling). This cannabinoid also prevented PTZ-induced EEG activity and interleukin-6 increase in prefrontal cortex. In conclusion, the robust anticonvulsant effects of CBD may result from multiple pharmacological mechanisms, including facilitation of endocannabinoid signaling and TRPV1 mechanisms. These findings advance our understanding on CBD inhibition of seizures, EEG activity, and cytokine actions, with potential implications for the development of new treatments for certain epileptic syndromes.

KEYWORDS:

Anticonvulsants; Cannabinoids; Cannabis sativa; Epilepsy; Seizure

PMID:
28821005
DOI:
10.1016/j.yebeh.2017.07.014
[Indexed for MEDLINE]

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