treatment of inflammatory conditions (Gallily et al. 2015 ).”The preference of plant
phytocannabinoid preparations over synthetically-derived drug substance continues
at present, with a particular high-CBD content Cannabis sativa L. strain
(Charlotte’s Web) with less than 0.3% THC becoming an increasingly preferred
source of phytocannabinoids for treating seizures and a range of other medical
conditions.
11.3 In Vivo Preclinical and Clinical Studies
of Cannabidiol as an Antiepileptic Agent
Preclinical laboratory animal studies suggest that CBD and other phytocannabinoid
constituents of cannabis can provide therapeutic benefit in a wide variety of seizure
disorders in man (Consroe and Wolkin 1977 ; Jones et al. 2012 ; Devinsky et al.
2014 ). In rats, for example, both CBD andD^9 -THC increase the number of afferent
stimuli required to elicit a hippocampal seizure (Izquierdo et al. 1973 ) and are
anticonvulsant in maximal electroshock, a model of partial seizure with secondary
generalization (Wallace et al. 2001 ). CBD also reduces seizure severity and lethality
in the pentylenetetrazole model of generalized seizures (Jones et al. 2012 ), and is
effective in the acute pilocarpine-induced model of temporal lobe seizure and the
penicillin-induced model of partial seizure in rats (Jones et al. 2010 ). Other phy-
tocannabinoids and synthetic cannabinoids, including D^9 -THC, D^8 -THC and
WIN-55212-2, share this anticonvulsant activity. However, studies using the
specific CB1 receptor competitive antagonist SR141716A demonstrated that the
anticonvulsant effects of WIN 55212-2 andD^9 -THC are CB1 receptor-mediated,
while the anticonvulsant activity of CBD is not (Wallace et al. 2001 ). CBD pre-
treatment also attenuated tonic convulsions in mice and other laboratory animal
species caused by electroshock,c-aminobutyric acid (GABA) antagonists or inhi-
bitors of GABA synthesis (Carlini et al. 1973 ; Consroe et al. 1982 ; Shirazi-zand
et al. 2013 ). These early studies showed that CBD produces anticonvulsant activity
across several models in a dose dependent fashion, with efficacy comparable to
phenytoin, phenobarbital and other antiepileptics.
In early clinical studies and in anecdotal reports, CBD treatment in epileptics
showed mixed results. In some studies, it provided moderate relief of seizure fre-
quency and was relatively well-tolerated (Mechoulam and Carlini 1978 ; Cunha
et al. 1980 ), but in other studies no significant therapeutic effects were observed
(Ames and Cridland 1986 ). In at least one report, CBD administration to an
epileptic patient appeared to exacerbate abnormal epileptic electroencephalographic
activity (Perez-Reyes and Wingfield 1974 ). This variance in therapeutic efficacy in
small-scale clinical trials may not be surprising because of several factors in
addition to the small sample sizes. There are epileptic syndromes and intractable
epilepsies of different causes and types. In addition, one-third of patients with
epilepsy have a treatment-resistant form, and in some instances, several existing
11 Cannabidiol as a Treatment for Seizures, Convulsions and Epilepsy 255