The anticonvulsant effects of cannabidiol in experimental models of epileptic seizures: From behavior and mechanisms to clinical insights

Lazarini-Lopes, Willian; Silva, Raquel A. Do Val-da; Silva-Júnior, Rui Milton Patrício da; Leite, João Pereira; García-Cairasco, Norberto

doi:10.1016/j.neubiorev.2020.01.014

Cited by 59 publications

(52 citation statements)

References 159 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…CBD has shown effectiveness in the clinical scenario for epilepsies but its effects on epilepsy-related comorbidities are scarce, even in basic research. More detailed and complex behavioral evaluation about CBD effects on seizures and epilepsyrelated comorbidities are required [28].…”

Section: Discussionmentioning

confidence: 99%

Effects of endocannabinoids in pentylenetetrazole induced seizures in mice

Yücel¹,

Aktuna

Keskil

2020

Acta Medica Alanya

View full text Add to dashboard Cite

Amaç: Pentilentetrazol (PTZ) yaygın antikonvülzan olduğu varsayılan ilaçların değerlendirilmesi için kullanılan bir maddedir ve sinir liflerinin tekrarlayan şekilde uyarılmasını ve refrakter süresinin kısaltılmasını sağlar. Anandamid, nöronlarda sentezlenen ve depolarizasyon sırasında atılan bir endokannabinoiddir ve çok hızlı bir şekilde inaktive olur. Epilepsi gibi sinirsel bozukluklarda, yüksek anandamid düzeyleri gözlenmiştir. Etanol akut bir uygulama sonrası, antikonvülsif etkisi olan bir psikoaktif maddedir, ancak yüksek dozlarda tekrar tekrar verilmesi prokonvülsan etkiye yol açar. Bu çalışmada amacımız endokannabinoidlerin farelerde PTZ kaynaklı epileptik nöbetleri indükleyen anandamidin etkisini, kannabinoid reseptörlerinin tiplerini belirleyerek araştırmaktı. Materyal ve metod: Küçük hayvan deney modelimizde, 25-35 gr ağırlığında otuz iki İsviçre albino erkek fare kullanıldı. Çalışma sırasında, deney hayvanları; kontrol, anandamid, anandamidin sentetik analoğu (WIN 55.212-2) ve etanol olarak rastgele dört gruba ayrıldı. Epileptik atakların sayısı, ilk epileptik atak süresi, epileptik atakların toplam süresi ve PTZ enjeksiyonundan sonraki ilk ataktaki bekleme, mortalite ve alevlenme gelişim süresi her grupla karşılaştırıldı. Bulgular: WIN 55.212-2, anandamid ve etanol gruplarının tümünde mortalite oranı ve nöbet süresi anlamlı olarak daha düşüktü. PTZ enjeksiyonu öncesi etanol ve anandamid uygulandığında gecikme süreleri anlamlı olarak yüksek bulundu; ancak gruplar arasında bir fark yoktu. Bununla birlikte, benzer bir ilişki WIN 55.212-2 ve etanol arasında da mevcut değildi. Sonuç: Endokannabinoid anandamid'in gözlenen antiepileptik etkisinin, çözücüsü olan etanol'ün etkisine bağlı olduğu söylenebilir; fakat bu etki de analoğu olan WIN 55.212-2 ile gözlenmemiştir. Her iki endokannabinoid de kannabinoid reseptörlerini etkilese de, bunların etkileri arasındaki söz konusu fark, onların farklı farmakokinetik, metabolizma ya da yıkım ürünlerine veya aktif metabolitlerine de bağlı olabilir.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of endocannabinoids in pentylenetetrazole induced seizures in mice

Yücel¹,

Aktuna

Keskil

2020

Acta Medica Alanya

View full text Add to dashboard Cite

show abstract

“…CBD has been shown to be effective against generalized tonic, clonic, tonic-clonic seizures and on drug-resistant epilepsy models, manifesting behavioral, EEG and neuroprotective effects in both acute and chronic protocols of experimental animal models (Lazarini-Lopes et al, 2020).…”

Section: Historical Review Of the Use Of Cannabis To Treat Pediatric mentioning

confidence: 99%

Cannabidiol Treatment for Refractory Epilepsies in Pediatrics

et al. 2020

View full text Add to dashboard Cite

Cannabis extracts in oil are becoming increasingly available, and, during the last years, there has been growing public and scientific interest about therapeutic properties of these compounds for the treatment of several neurologic diseases, not just epilepsy. The discovered role of the endocannabinoid system in epileptogenesis has provided the basis to investigate the pharmacological use of exogenously produced cannabinoids, to treat epilepsy. Although, physicians show reluctance to recommend Cannabis extracts given the lack of high-quality safety available data, from literature data cannabidiol (CBD) results to be a promising and safe anticonvulsant drug with low side-effect. In particular, according to early studies, CBD can reduce the frequency of seizures and lead to improvements in quality of life in children affected by refractory epilepsy. So, for these reasons, the detailed study of the interactions between CBD and anticonvulsant drugs (AEDs) administered simultaneously in polytherapy, is arousing increasing interest, to clarify and to assess the incidence of adverse effects and the relation between dose escalation and quality of life measures. To date, in pediatric age, CBD efficacy and safety is not supported by well-designed trials and strong scientific evidence are not available. These studies are either retrospective or small-scale observational and only during the last years Class I evidence data for a pure form of CBD have been available, as demonstrated in placebo-controlled RCTs for patients affected by Lennox-Gastaut syndrome and Dravet syndrome. It is necessary to investigate CBD safety, pharmacokinetics and interaction with other AEDs alongside performing double-blinded placebo-controlled trials to obtain conclusive data on its efficacy and safety in the most frequent epilepsies in children, not just in the epileptic encephalopathy. This review was aimed to revise the available data to describe the scientific evidence for CBD in Pediatric Epilepsies.

show abstract

“…The primary aims of epilepsy treatment are to prevent seizures, to avoid adverse effects, and to facilitate patients to have active lives (4). Despite the variety of these drugs available for the treatment of epilepsy, pharmacological approaches cannot control seizures in all cases (5). However, many antiepileptic drugs used in the treatment may have interactions with some important drugs or drug groups such as antibiotics, anticoagulants, oral contraceptives, salicylates, cimetidine and isoniazid (6).…”

Section: Introductionmentioning

confidence: 99%

The effects of hydrogen sulfide, carbon monoxide and nitric oxide on pentylenetetrazole-induced seizures in rats

Eroğlu

Ünel

Harmanci

et al. 2020

Kahramanmaraş Sütçü İmam Üniversitesi Tıp Fakültesi Dergisi

View full text Add to dashboard Cite

Objective: The present study aimed to investigate the anticonvulsant effects of bioactive gas mediator's hydrogen sulfide (H2S), carbon monoxide (CO) and nitric oxide (NO) in pentylenetetrazole (PTZ)-induced convulsions in rats. Material and Methods: Eighty male Wistar-Albino rats randomly divided into ten groups. Convulsions were induced by administering 60 mg/kg PTZ intraperitonally (i.p). Diazepam (1 and 2 mg/kg), sodium hydrosulfide (NaHS, 5 and 10 mg/kg), CO releasing molecule-2 (CORM-2, 5 and 10 mg/kg), L-arginine (LARG, 30 and 100 mg/kg) and L-NG-Nitro arginine methyl ester (L-NAME, 30 mg/kg) were administered 30 minutes after PTZ. Seizure latency, seizure duration and seizure score were evaluated. Data were analyzed by the Kruskal Wallis test followed by posthoc analyses with Tukey. Any p value <0.05 was considered statistically significant. Results: NaHS (10 mg/kg) significantly reduced seizure duration and seizure in comparison with PTZ similar to diazepam (2 mg/kg), but it did not cause any significant change in seizure latency. Other agents did not significantly change seizure latency, seizure duration, and seizure score compared to PTZ. Conclusion: NaHS may be protective in PTZ-induced seizures. More research is needed to investigate the mechanisms underlying this effect.

show abstract

The anticonvulsant effects of cannabidiol in experimental models of epileptic seizures: From behavior and mechanisms to clinical insights

Cited by 59 publications

References 159 publications

Effects of endocannabinoids in pentylenetetrazole induced seizures in mice

Effects of endocannabinoids in pentylenetetrazole induced seizures in mice

Cannabidiol Treatment for Refractory Epilepsies in Pediatrics

The effects of hydrogen sulfide, carbon monoxide and nitric oxide on pentylenetetrazole-induced seizures in rats

Contact Info

Product

Resources

About