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

Vilela, Luciano; Lima, Isabel Vieira de Assis; Kunsch, Érica B.; Pinto, Hyorrana Priscila Pereira; Miranda, Aline Silva de; Vieira, Érica Leandro Marciano; Oliveira, Antônio Carlos Pinheiro de; Moraes, Márcio Flávio Dutra; Moreira, Fabrício A.

doi:10.1016/j.yebeh.2017.07.014

Cited by 98 publications

(67 citation statements)

References 49 publications

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“…Several studies support that CBD could be effective in the control of epilepsy . Results obtained from experimental models reveal that CBD reduces the seizure activity and delays the epileptogenesis process, effects associated with neuroprotection . CBD in oral solution (Epidiolex ® ) is considered a therapy to control seizures associated with the Lennox‐Gastaut syndrome, Dravet syndrome, and infantile spasms .…”

Section: Is Cannabidiol a New Hope For Drug‐resistant Epilepsy?mentioning

confidence: 99%

Is cannabidiol a drug acting on unconventional targets to control drug‐resistant epilepsy?

Rocha¹,

Frías‐Soria²,

Ortíz

et al. 2020

Epilepsia Open

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Cannabis has been considered as a therapeutic strategy to control intractable epilepsy. Several cannabis components, especially cannabidiol (CBD), induce antiseizure effects. However, additional information is necessary to identify the types of epilepsies that can be controlled by these components and the mechanisms involved in these effects. This review presents a summary of the discussion carried out during the 2nd Latin American Workshop on Neurobiology of Epilepsy entitled “Cannabinoid and epilepsy: myths and realities.” This event was carried out during the 10th Latin American Epilepsy Congress in San José de Costa Rica (September 28, 2018). The review focuses to discuss the use of CBD as a new therapeutic strategy to control drug‐resistant epilepsy. It also indicates the necessity to consider the evaluation of unconventional targets such as P‐glycoprotein, to explain the effects of CBD in drug‐resistant epilepsy.

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Section: Is Cannabidiol a New Hope For Drug‐resistant Epilepsy?mentioning

confidence: 99%

Is cannabidiol a drug acting on unconventional targets to control drug‐resistant epilepsy?

Rocha¹,

Frías‐Soria²,

Ortíz

et al. 2020

Epilepsia Open

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“…In preclinical studies CBD has been shown to reduce neuronal hyperexcitability through modulation of voltage-or ligand-gated ion channels, by blocking orphan GPR55, by inhibiting certain enzymes, and through modulation of adenosine mediated signalling, cytokine expression and TNFα release. 15,[33][34][35][36] Nevertheless, the precise mechanisms of action(s) of CBD are yet to be elucidated. In several animal models of epilepsy, the anticonvulsant properties of PHT and CBD have shown similarities in many, though not all, respects.…”

Section: Phytocannabinoids As Anticonvulsant Agentsmentioning

confidence: 99%

Towards Understanding the Phenytoin-like Antiepileptic Effect of Cannabidiol and Related Phytocannabinoid Metabolites Insights from Molecular Modeling

Ujváry¹,

Lopata²

2018

Preprint

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<div> Cannabidiol (CBD), a nonpsychotropic constituent of <i>Cannabis sativa</i>, has recently been approved by the US FDA for the treatment of certain forms of pediatric epilepsy. The mechanism by which CBD exerts its antiepileptic effects, however, is not known. Herein we describe the results of molecular modeling studies comparing the stereoelectronic properties of phenytoin (PHT) with those of CBD and its carboxylic acid metabolite, as well as of 7-hydroxycannabidivarin. Also, the cyclohexenecarboxylic acid core of 7-COOH-CBD perfectly mimics the unsaturated bioactive metabolite of the commonly used antiepileptic valproic acid was also noted. We propose that C–7 oxidized phytocannabinoid metabolites are involved in the phenytoin-like anticonvulsant effects of the parent phytocannabinoid drugs.</div>

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“…Results of the anecdotal data and early clinical trials suggest improvement in about 50% to 60% of patients who took various cannabis extracts for TRE, including those who were treated with purified cannabidiol (CBD) [31]. Cannabis produces dozens of compounds; termed phytocannabinoids, among which cannabidiol (CBD) is one of the major secondary metabolites lacking the ∆9-tetrahydrocannabinol (∆9-THC) psychoactive effects [32]. Thus it is considered the main nonpsychotomimetic compound of the Cannabis Sativa plant [33].…”

Section: Introductionmentioning

confidence: 99%

“…It inhibits experimental seizures in animal models and improves certain types of intractable epilepsies in patients. However, its pharmacological profile for the treatment of epilepsy is still uncertain [32]. Emphasis on the endocannabinoid mechanisms underlying the neurotherapeutics of CBD in epilepsy is the most common explanation.…”

Section: Introductionmentioning

confidence: 99%

Cannabis Influences the Putative Cytokines-Related Pathway of Epilepsy among Egyptian Epileptic Patients

et al. 2019

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The study aims to investigate: (1) the prevalence of cannabis among epileptic patients seen at Mansoura University Hospital, (2) serum levels and gene expression of cytokines in epilepsy patients and the controls. and (3) the possibility that cannabis use affects the cytokine levels in epilepsy patients, triggering its future use in treatment. We recruited 440 epilepsy patients and 200 controls matched for age, gender, and ethnicity. Of the epileptic patients, 37.5% demonstrated lifetime cannabis use with a mean duration of 15 ± 73 years. Serum levels of interleukin IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, and tumor necrosis factor-α (TNF-α), were analyzed and gene expression analysis was conducted only for those cytokines that were different between groups in the serum analysis. The “Epilepsy-only” patients had significantly higher serum and mRNA levels of IL-1α, β, IL-2,6,8, and TNF-α compared to the controls and the “Cannabis+Epilepsy” group (p = 0.0001). IL-10 showed significantly lower levels in the “Epilepsy-only” patients compared to the controls and “Cannabis+Epilepsy” (p = 0.0001). Cannabis use is prevalent among epilepsy patients. Epilepsy is characterized by a pro-inflammatory state supported by high serum and gene expression levels. Cannabis users demonstrated significantly lower levels of inflammatory cytokines compared to epilepsy non-cannabis users which might contribute to its use in the treatment of resistant epilepsy.

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

Cited by 98 publications

References 49 publications

Is cannabidiol a drug acting on unconventional targets to control drug‐resistant epilepsy?

Is cannabidiol a drug acting on unconventional targets to control drug‐resistant epilepsy?

Towards Understanding the Phenytoin-like Antiepileptic Effect of Cannabidiol and Related Phytocannabinoid Metabolites Insights from Molecular Modeling

Cannabis Influences the Putative Cytokines-Related Pathway of Epilepsy among Egyptian Epileptic Patients

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