Electrical and behavioral attenuation of the anti-convulsant properties of δ9-THC following chronic administrations

Abstract

The anti-convulsant properties of δ 9-trans-tetrahydrocannabinol (δ 9-THC) were examined in rats subjected to daily convulsions induced by direct electrical stimulation of either the anterior limbic cortex or the amygdala. During the development of the convulsions (kindling) and during the repeated daily injections of δ 9-THC, electroencephalographic records were taken. THC was administered daily until the animals were behaviorally tolerant. The drug had, initially, a very pronounced effect on the sub-cortical seizures and a slightly lesser effect on the cortical seizures—either stopping them entirely or reducing their duration. However, as the animals became tolerant to THC (defined behaviorally and electrically), the anti-convulsant properties of the drug diminished.

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References

  1. Carlini, E. A.: Tolerance to chronic administration of Cannabis satua (marihuana) in rats. Pharmacology 1, 135–142 (1968).

    Google Scholar 

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

    Google Scholar 

  3. DeSalva, S. J.: Tolerance development to anticonvulsive drugs. J. Pharmacol. exp. Ther. 116, 15–16 (1956).

    Google Scholar 

  4. Fried, P. A., Nieman, G. W.: Inhalation of Cannabis smoke in rats. Pharmacol. Biochem. Behav. (in press).

  5. Frey, H. H., Kampmann, E.: Tolerance to anticonvulsant drugs. Acta pharmacol. (Kbh.) 22, 159–171 (1965).

    Google Scholar 

  6. Gaoni, Y., Mechoulam, R.: Isolation, structure, and partial synthesis of an active constituent of hashish. J. Amer. chem. Soc. 86, 1646–1647 (1964).

    Google Scholar 

  7. Goddard, G. V., McIntyre, D. C., Leech, C. K.: A permanent change in brain function resulting from daily electrical stimulation. Exp. Neurol. 25, 295–330 (1969).

    Google Scholar 

  8. Indian Hemp Drugs Commission Report, 1893–1894, Marihuana, Introduction by J. Kaplin. Silver Spring, Maryland: Thomas Jefferson Co. 1969.

  9. Killam, K. F., Killam, E. K.: The action of tetrahydrocannabinol on EEG and photomyoclonic seizures in the baboon. Fifth Int. Cong. Pharm. 124 (1972).

  10. Lipparini, F., Scotti de Carolis, A., Longo, V. G.: A neuropharmacological investigation of some trans-tetrahydrocannabinol derivatives. Physiol. Behav. 4, 527–532 (1969).

    Google Scholar 

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

    Google Scholar 

  12. Mechoulam, R.: Marihuana chemistry. Science 168, 1159–1166 (1970).

    Google Scholar 

  13. Molino, A., McIntyre, D. C.: Another inexpensive headplug for the electrical recording and/or stimulation of rats. Physiol. Behav. 9, 273–275 (1972).

    Google Scholar 

  14. O'Shaugnessy, W. B.: On the preparation of the Indian Hemp or Gunjah (Cannabis Indica): The effect on the animal system in health, and their utility in the treatment of tetanus and other convulsive diseases. Trans. med. Phys. Soc. Bombay 8, 421–461 (1842).

    Google Scholar 

  15. Potvin, R., Fried, P. A.: Acute and chronic effects on rats of (−)δ 9 ′trans-tetra-hydrocannabinol on unlearned motor tasks. Psychopharmacologia (Berl.) 26, 369–378 (1972).

    Google Scholar 

  16. Shannon, M. E., Fried, P. A.: The macro- and microdistribution and polymorphic electroencephalographic effects of δ 9-tetra-hydrocannabinol in the rat. Psychopharmacologia (Berl.) 27, 141–156 (1972).

    Google Scholar 

  17. Vanderwolf, C. H.: Limbic-diencephalic mechanisms of voluntary movement. Psychol. Rev. 78, 83–113 (1971).

    Google Scholar 

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This work was supported by Medical Research Council Grant -MRC-DA-13 and National Health and Welfare Grant 1215-5-54 to P. A. Fried.

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Fried, P.A., McIntyre, D.C. Electrical and behavioral attenuation of the anti-convulsant properties of δ9-THC following chronic administrations. Psychopharmacologia 31, 215–227 (1973). https://doi.org/10.1007/BF00422512

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Key words

  • δ 9-Tetrahydrocannabinol
  • Anticonvulsant
  • Tolerance
  • EEG