Skip to main content

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


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.

This is a preview of subscription content, access via your institution.


  1. Barcik, J. D.: Hippocampal afterdischarge and conditioned emotional response. Psychon. Sci. 20, 297–298 (1971).

    Google Scholar 

  2. Davis, J. P., Ramsey, H. H.: Antiepileptic action of marihuana-active substances. Fed. Proc. 8, 284–285 (1949).

    Google Scholar 

  3. Garriott, J. C., Forney, R. B., Hughes, F. W., Richards, A. B.: Pharmacologic properties of some Cannabis related compounds. Arch. int. Pharmacodyn. 171, 425–434 (1968).

    Google Scholar 

  4. Green, J. D.: The hippocampus. Physiol. Rev. 44, 561–608 (1964).

    Google Scholar 

  5. Izquierdo, I.: Hippocampal physiology: experiments on regulation of its electrical activity, on the mechanism of seizures, and on a hypothesis of learning. Behav. Biol. 7, 669–698 (1972).

    Google Scholar 

  6. Izquierdo, I., Berardi, A. C.: Effect of various Cannabis Sativa compounds on the seizure threshold of rat hippocampus. IV. Symp. on Medicinal Plants of Brazilian Origin, Sao Paulo, april 1972; J. R. Valle and E. A. Carlini, chairmen; abstracts., p. 17.

  7. Izquierdo, I., Nasello, A. G.: Pharmacological evidence that hippocampal facilitation, posttetanic potentiation and seizures may be due to a common mechanism. Exp. Neurol. 27, 399–409 (1970).

    Google Scholar 

  8. Izquierdo, I., Nasello, A. G.: Pharmacology of the brain: the hippocampus, learning and seizures. Progr. Drug Res. 16, 211–228 (1972).

    Google Scholar 

  9. Izquierdo, I., Nasello, A. G., Marichich, E. S.: Effects of potassium on rats hippocampus: the dependence of hippocampal evoked and seizure activity on extracellular potassium levels. Arch. int. Pharmacodyn. 187, 318–328 (1970).

    Google Scholar 

  10. Izquierdo, I., Orsingher, O. A.: A physiological difference in the hippocampus of rats with a low inborn learning ability. Psychopharmacologia (Berl.) 23, 386–396 (1972).

    Google Scholar 

  11. Izquierdo, I., Orsingher, O. A., Levin, L. E.: Hippocampal potassium release upon stimulation and learning capacity of rats. Behav. Biol. 7 (in press) (1972).

  12. Izquierdo, I., Orsingher, O. A., Ogura, A.: Hippocampal facilitation and RNA build-up in response to stimulation in rats with a low inborn learning ability. Behav. Biol. 7, 699–707 (1972).

    Google Scholar 

  13. Korte, F., Sieper, H.: Recent results of hashish analysis. In: Hashish: its chemistry and pharmacology; G. E. W. Wolstenholme and J. Knight, eds, pp. 15–30 London: Churchill 1965.

    Google Scholar 

  14. Loewe, S., Goodman, L. S.: Anticonvulsant action of marihuana-active substances. Fed. Proc. 6, 352 (1947).

    Google Scholar 

  15. Marichich, E. S., Izquierdo, I.: Potassium loss from rat hippocampus during electrical activity. Arch. int. Pharmacodyn. 196, 353–356 (1972).

    Google Scholar 

  16. Orsingher, O. A., Fulginiti, S.: Effects of Cannabis Sativa on learning in rats. Pharmacology 3, 337–344 (1970).

    Google Scholar 

  17. Valle, J. R.: Pharmacological appraches to the study of the Cannabis problem. Intern. J. Addict. 4, 623–647 (1969).

    Google Scholar 

Download references

Author information



Additional information

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.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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).

Download citation

Key words

  • Cannabidiol
  • Cannabis
  • Marihuana
  • Potassium Release
  • Hippocampus
  • Hippocampal Seizures
  • Epilepsy