Cannabidiol, a Cannabis sativa constituent, inhibits cocaine-induced seizures in mice: Possible role of the mTOR pathway and reduction in glutamate release

Gobira, Pedro H.; Vilela, Luciano R.; Gonçalves, Bruno D.C.; Santos, Rebeca P.M.; de Oliveira, Antonio C.; Vieira, Luciene B.; Aguiar, Daniele C.; Crippa, José A.; Moreira, Fabricio A.

doi:10.1016/j.neuro.2015.08.007

Cited by 89Cannabis and Cannabinoid ResearchEpilepsy research and treatmentForensic Toxicology and Drug Analysis

Cannabidiol, a Cannabis sativa constituent, inhibits cocaine-induced seizures in mice: Possible role of the mTOR pathway and reduction in glutamate release

Gobira, Pedro H., Vilela, Luciano R., Gonçalves, Bruno D.C., Santos, Rebeca P.M., de Oliveira, Antonio C., Vieira, Luciene B., Aguiar, Daniele C., Crippa, José A. +1 more·2015·NeuroToxicology

DOI 10.1016/j.neuro.2015.08.007

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Abstract

Cannabidiol (CBD), a major non-psychotomimetic constituent of Cannabis sativa, has therapeutic potential for certain psychiatric and neurological disorders. Studies in laboratory animals and limited human trials indicate that CBD has anticonvulsant and neuroprotective properties. Its effects against cocaine neurotoxicity, however, have remained unclear. Thus, the present study tested the hypothesis that CBD protects against cocaine-induced seizures and investigated the underlying mechanisms. CBD (30 mg/kg) pre-treatment increased the latency and reduced the duration of cocaine (75 mg/kg)-induced seizures in mice. The CB1 receptor antagonist, AM251 (1 and 3mg/kg), and the CB2 receptor antagonist, AM630 (2 and 4 mg/kg), failed to reverse this protective effect, suggesting that alternative mechanisms are involved. Synaptosome studies with the hippocampus of drug-treated animals revealed that cocaine increases glutamate release, whereas CBD induces the opposite effect. Finally, the protective effect of this cannabinoid against cocaine-induced seizure was reversed by rapamycin (1 and 5mg/kg), an inhibitor of the mammalian target of rapamycin (mTOR) intracellular pathway. In conclusion, CBD protects against seizures in a model of cocaine intoxication. These effects possibly occur through activation of mTOR with subsequent reduction in glutamate release. CBD should be further investigated as a strategy for alleviating psychostimulant toxicity.

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In a collaborative animal study, CBD protects against cocaine-induced seizures.
“In a collaborative animal study, we found that CBD protects against cocaine-induced seizures, possibly through activation of the mTOR pathway, with the concomitant reduction in glutamate release (144).”
From Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age (2018) · cites this paper as [144]
CBD's protection against cocaine-induced seizures may occur through activation of the mTOR pathway with concomitant reduction in glutamate release.
“In a collaborative animal study, we found that CBD protects against cocaine-induced seizures, possibly through activation of the mTOR pathway, with the concomitant reduction in glutamate release (144).”
From Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age (2018) · cites this paper as [144]

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Authors: Gobira, P. H., Vilela, L. R., Gonçalves, B. D. C., Santos, R. P. M., de Oliveira, A. C., Vieira, L. B., Aguiar, D. C., Crippa, J. A., & Moreira, F. A.
Affiliations: Universidade Federal de Minas Gerais (BR)
Universidade de São Paulo (BR)
ORCID: Gobira, Pedro H.
Vilela, Luciano R.
Vieira, Luciene B.
Aguiar, Daniele C.
Venue: NeuroToxicology
Publisher: Elsevier BV
Published: 2015-09
Volume: 50
Pages: 116-121
ISSN: 0161-813X (ISSN-L)
DOI: 10.1016/j.neuro.2015.08.007
OpenAlex: W1176583637
Cited by: 89
References: 52
Citations by year: 2025: 3 · 2024: 6 · 2023: 13 · 2022: 8 · 2021: 13 · 2020: 16 · 2019: 13 · 2018: 8 · 2017: 6 · 2016: 2 · 2015: 1
FWCI: 4.10
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: NeuroToxicology (publishedVersion)
PubMed (publishedVersion)
Funders: FAPEMIG (APQ-01728-13, APQ-01611-13, APQ-01995-14)
CNPq (449578/2014-3)
Topics: Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Forensic Toxicology and Drug Analysis
Keywords: cannabidiol, cocaine-induced seizures, mTOR signaling, glutamate release, CB1 receptor, CB2 receptor, rapamycin, hippocampus, anticonvulsant activity, neuroprotection
MeSH terms: Anesthetics, Local, Animals, Antiemetics, Cannabidiol, Cocaine, Disease Models, Animal, Dose-Response Relationship, Drug, Immunosuppressive Agents, Indoles, Male, Seizures, Signal Transduction, Glutamic Acid, Sirolimus, Mice, TOR Serine-Threonine Kinases

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Cannabidiol, a Cannabis sativa constituent, inhibits cocaine-induced seizures in mice: Possible role of the mTOR pathway and reduction in glutamate release

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