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Effect of cannabidiol and of other Cannabis sativa compounds on hippocampal seizure discharges

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The natural Cannabis sativa compounds, cannabidiol, cannabinol, δ 9- and δ 8-tetrahydrocannabinol, in that order of potency, decreased the susceptibility of rat dorsal hippocampus to seizure discharges caused by afferent stimulation. The drugs were effective following both intraperitoneal injection and topical application. They were more active, on a dose basis, than the well-known antiepileptic agents mysoline and diphenylhidantoin. Within the dose range effective in depressing hippocampal seizures, they had no effect on hippocampal evoked responses. This suggested that they might act by interfering with K+ release from hippocampal cells, which is known to be the causative factor in hippocampal seizures. This point was investigated using cannabidiol, which was found to effectively block the release of K+ from the hippocampus caused by afferent stimulation.

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With financial help from the Escola Paulista de Medicina, through a personal grant to one of us (I.I.), from the Consejo Nacional de Investigaciones Científicas y Técnicas of Argentina (grant Nℴ 3917), and from the Secretaría de Salud PÚblica de la Nación, Instituto Nacional de Farmacología of Argentina, through a special contract.

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Izquierdo, I., Orsingher, O.A. & Berardi, A.C. Effect of cannabidiol and of other Cannabis sativa compounds on hippocampal seizure discharges. Psychopharmacologia 28, 95–102 (1973).

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