Eric Witherspoon1, Sean Quinlan1, Patrick A Forcelli2,3,4. 1. Department of Pharmacology and Physiology, Georgetown University, New Research Building W209B, Washington, DC, 20057, USA. 2. Department of Pharmacology and Physiology, Georgetown University, New Research Building W209B, Washington, DC, 20057, USA. paf22@georgetown.edu. 3. Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC, USA. paf22@georgetown.edu. 4. Department of Neuroscience, Georgetown University, Washington, DC, USA. paf22@georgetown.edu.
Abstract
BACKGROUND: The treatment of epilepsy during early life poses unique challenges-first-line therapies leave many individuals with poorly controlled seizures. In response to the pharmaco-resistance of current first-line anti-seizure drugs (ASDs) during early life, new therapies have emerged. One such therapy is cannabidiol (CBD). While well studied in adult models of epilepsy, it is poorly studied in immature animals. Here we assessed the efficacy of CBD in immature rodent models of the epilepsies. METHODS: Pups were pre-treated with CBD (1, 10, 50, 100, 200 mg/kg) and assessed for anticonvulsant efficacy using two well-established anti-seizure screening models: the pentylenetetrazole (PTZ) and maximal electroshock (MES) models. We assessed drug efficacy in postnatal day (P)7 and P21 rats. RESULTS: In the PTZ model, CBD delayed seizure onset in adolescent but not neonatal rats. By contrast, higher doses of CBD reduced seizure duration in both neonatal and adolescent rats in the MES model. The effects of CBD in both models were modest but consistent. CONCLUSION: Efficacy of CBD increased in older as compared to younger animals, producing an age-, model-, and dose-dependent suppression of seizures. These data suggest neonatal seizures (modeled by P7 treatment) may be less responsive to CBD. They also suggest preferential efficacy against tonic seizures as compared to partial motor seizures.
BACKGROUND: The treatment of epilepsy during early life poses unique challenges-first-line therapies leave many individuals with poorly controlled seizures. In response to the pharmaco-resistance of current first-line anti-seizure drugs (ASDs) during early life, new therapies have emerged. One such therapy is cannabidiol (CBD). While well studied in adult models of epilepsy, it is poorly studied in immature animals. Here we assessed the efficacy of CBD in immature rodent models of the epilepsies. METHODS: Pups were pre-treated with CBD (1, 10, 50, 100, 200 mg/kg) and assessed for anticonvulsant efficacy using two well-established anti-seizure screening models: the pentylenetetrazole (PTZ) and maximal electroshock (MES) models. We assessed drug efficacy in postnatal day (P)7 and P21 rats. RESULTS: In the PTZ model, CBD delayed seizure onset in adolescent but not neonatal rats. By contrast, higher doses of CBD reduced seizure duration in both neonatal and adolescent rats in the MES model. The effects of CBD in both models were modest but consistent. CONCLUSION: Efficacy of CBD increased in older as compared to younger animals, producing an age-, model-, and dose-dependent suppression of seizures. These data suggest neonatal seizures (modeled by P7 treatment) may be less responsive to CBD. They also suggest preferential efficacy against tonic seizures as compared to partial motor seizures.
Authors: Nicholas A Jones; Andrew J Hill; Imogen Smith; Sarah A Bevan; Claire M Williams; Benjamin J Whalley; Gary J Stephens Journal: J Pharmacol Exp Ther Date: 2009-11-11 Impact factor: 4.030
Authors: Catherine V Kulick; Samuel B Gutherz; Veronica C Beck; Natalia Medvedeva; Colin Soper; Patrick A Forcelli Journal: Eur J Pharmacol Date: 2014-09-22 Impact factor: 4.432
Authors: Pabitra Hriday Patra; Melissa Barker-Haliski; H Steve White; Benjamin J Whalley; Sarah Glyn; Haramrit Sandhu; Nicholas Jones; Michael Bazelot; Claire M Williams; Alister James McNeish Journal: Epilepsia Date: 2018-12-26 Impact factor: 5.864