Anticonvulsant-Convulsant Effects of Delta-9-Tetrahydrocannabinol

  • Paul Consroe
  • Byron Jones
  • Hugh LairdII
  • Jeff Reinking

Abstract

It is fairly well established that delta-9-tetrahydrocannabinol (delta-9-THC), the major psychoactive constituent of marihuana, has anticonvulsant properties. A summary of the reported effects of delta-9-THC in laboratory animals for a variety of experimentally induced seizure paradigms is presented in Table 1. In general, behavioral seizures in rodents, frogs, and cats, and electrographic seizures in rats and cats produced by electrical stimulation are prevented by delta-9-THC. Additionally, auditory, tactile (reflex), and in some cases pentylenetetrazol (PTZ) induced seizures in rodents are also blocked by the cannabinoid.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Barratt, E. S., & Adams, P. The effects of chronic marijuana administration on brain functioning in cats. In J. M. Singh, L. Miller, & H. Lai (Eds.), Drug addiction: Experimental pharmacology. Mount Kisco, N.Y.: Futura Press, 1972.Google Scholar
  2. Boggan, W. O., Steele, R. A., & Freedman, D. X. Delta-9-Tetrahydrocannabinol effect on audiogenic seizure susceptibility. Psychopharmacologia, 1973, 29, 101–106.PubMedCrossRefGoogle Scholar
  3. Boyd, E. S., Boyd, E. H., & Brown, L. E. The effects of some drugs on an evoked response senstitive to tetrahydrocannabinols. Journal of Pharmacology and Experimental Therapeutics, 1974, 189, 748–758.PubMedGoogle Scholar
  4. Boyd, E. S., Boyd, E, H., Muchmore, J. S., & Brown, L. E. Effects of two tetrahydrocannabinols and of pentobarbital on cortico-cortical evoked responses in the squirrel monkey. Journal of Pharmacology and Experimental Therapeutics, 1971, 176, 480–488.PubMedGoogle Scholar
  5. Braude, M. C. Toxicology of cannabinoids. In W. D. M. Paton and J. Crown (Eds.), Cannabis and its derivatives: Pharmacology and experimental psychology. London: Oxford University Press, 1972.Google Scholar
  6. Chesher, G. B., & Jackson, D. M. Anticonvulsant effects of cannabinoids in mice: Drug interactions within cannabinoids and cannabinoid interactions with phenytoin. Psychopharmacologia, 1974, 37, 255–264.PubMedCrossRefGoogle Scholar
  7. Consroe, P. F., Jones, B. C., & Chin, L. Delta-9-Tetrahydrocannabinol, EEG and behavior: The importance of adaptation to tne testing milieu. Pharmacology, Biochemistry and Behavior, 1975, 3, 173–177.CrossRefGoogle Scholar
  8. Consroe, P. F., & Man, D. P. Effects of delta-8-and delta-9-tetrahydrocannabinol on experimentally induced seizures. Life Sciences, 1973, 13, 429–439.CrossRefGoogle Scholar
  9. Consroe, P. F., Man, D. P., Chin, L., & Picchioni, A. L. Reduction of audiogenic seizure by delta-8-and delta-9-tetrahydrocannabinols. Journal of Pharmacy and Pharmacology, 1973, 25, 764–765.PubMedCrossRefGoogle Scholar
  10. Consroe, P. F., Wood, G. C., & Buchsbaum, H. Anticonvulsant nature of marijuana smoking. Journal of the American Medical Association, 1975, 234, 306–307.PubMedCrossRefGoogle Scholar
  11. Corcoran, M. E., McCaughran, J. A., & Wada, J. A. Acute antiepileptic effects of delta-9-tetrahydrocannabinol in rats with kindled seizures. Experimental Neurology, 1973, 40, 471–483.PubMedCrossRefGoogle Scholar
  12. Cox, B., Ham, M. T., Loskota, W. J., & Lomax, P. The anticonvulsant activity of cannabinoids in seizure sensitive gerbils. Proceedings of the Western Pharmacology Society, 1975, 18, 154–157.PubMedGoogle Scholar
  13. Davis, J. P., & Ramsey, H. H. Antiepileptic actions of marijuana-active substances. Federation Proceedings, 1949, 8, 284. (Abstract)Google Scholar
  14. deJong, R. H. Physiology and Pharmacology of Local Anaesthesia. Springfield, III.: Charles C. Thomas, 1970.Google Scholar
  15. Domino, E. F. Neuropsychopharmacologic studies of marijuana: Some synthetic and natural THC derivatives in animals and man. Annals of the New York Academy of Sciences, 1971, 191, 166–191.CrossRefGoogle Scholar
  16. Dwivedi, C., & Harbison, R. D. Anticonvulsant activities of delta-8 — and delta-9-tetrahydrocannabinol and uridine. Toxicology and Applied Pharmacology, 1975, 31, 452–458.PubMedCrossRefGoogle Scholar
  17. Feeney, D. M., Wagner, H. R., McNamara, M. C., & Weiss, G. Effects of tetrahydrocannabinol on hippocampal evoked afterdischarges in cats. Experimental Neurology, 1973, 41, 357–365.PubMedCrossRefGoogle Scholar
  18. Fried, P. A., & McIntyre, D. C. Electrical and behavioral attenuation of the anti-convulsant properties of delta-9-THC following chronic administration. Psychopharmacologia, 1973, 31, 215–227.PubMedCrossRefGoogle Scholar
  19. Fujimori, M., & Himwich, H. E. Delta-9-Tetrahydrocannabinol and the sleep-wakefulness cycle in rabbits. Physiology and Behavior, 1973, 11, 291–295.PubMedCrossRefGoogle Scholar
  20. Fujimori, M., Trusty, D. M., & Himwich, H. E. Delta-9-Tetrahydrocannabinol: Electroencephalographic changes and autonomic responses in the rabbit. Life Sciences, 1973, 12, 553–563.PubMedCrossRefGoogle Scholar
  21. Fujimoto, J. M. Modification of the effects of delta-9-tetrahydrocannabinol by phenobarbital pretreatment in mice. Toxicology and Applied Pharmacology, 1972, 23, 623–634.PubMedCrossRefGoogle Scholar
  22. Garriott, J. C., Forney, R. B., Hughes, F. W., & Richards, A. B. Pharmacologic properties of some Cannabis related compounds. Archives Internationales de Pharmacodynamie et de Therapie, 1968, 171, 425–434.PubMedGoogle Scholar
  23. Heath, R. G. Marijuana: Effects on deep and surface electroencephalograms of rhesus monkeys. Neuropharmacology, 1973, 12, 1–14.PubMedCrossRefGoogle Scholar
  24. Izquierdo, I., Orsingher, O. A., & Berardi, A. C. Effect of cannabidiol and of other Cannabis sativa compounds on hippocampal seizure discharges. Psychopharmacologia, 1973, 28, 95–102.PubMedCrossRefGoogle Scholar
  25. Karler, R., Cely, W., & Turkanis, S. A. The anticonvulsant activity of cannabidiol and cannabinol. Life Sciences, 1973, 13, 1527–1531.PubMedCrossRefGoogle Scholar
  26. Karler, R., Cely, W., & Turkanis, S. A. Anticonvulsant activity of delta-9-tetrahydrocannabinol and its 11-hydroxy and 8α, 11-dihydroxymetabolites in the frog. Research Communications in Chemical Pathology and Pharmacology, 1974, 9, 441–452. (a)PubMedGoogle Scholar
  27. Karler, R., Cely, W., & Turkanis, S. A. Anticonvulsant properties of delta-9-tetrahydrocannabinol and other cannabinoids. Life Sciences, 1974, 15, 931–947. (b)PubMedCrossRefGoogle Scholar
  28. Karler, R., Cely, W., & Turkanis, S. A. A study of the development of tolerance to an anticonvulsant effect of delta-9-tetrahydrocannabinol and cannabidiol. Research Communications in Chemical Pathology and Pharmacology, 1974, 9, 23–39. (c)PubMedGoogle Scholar
  29. Karler, R., Cely, W., & Turkanis, S. A. A study of the relative anticonvulsant and toxic activities of delta-9-tetrahydrocannabinol and its congeners. Research Communications in Chemical Pathology and Pharmacology, 1974, 7, 353–358. (d)PubMedGoogle Scholar
  30. Keeler, M. H., & Reifler, C. F. Grand mal convulsions subsequent to marijuana use: Case report. Diseases of the Nervous System, 1967, 28, 474–475.PubMedGoogle Scholar
  31. Killam, K. F., & Killam, E. K. The action of tetrahydrocannabinol on EEG and photomyoclonic seizures in the baboon. Fifth International Congress on Pharmacology, 1972, 124. (Abstract)Google Scholar
  32. Lemberger, L., Martz, R., Rodda, B., Forney, R., & Rowe, H. Comparative pharmacology of delta-9-tetrahydrocannabinol and its metabolite, 11-OH delta-9-tetrahydrocannabinol. Journal of Clinical Investigation, 1973, 52, 2411–2417.PubMedCrossRefGoogle Scholar
  33. Lipparini, F., Scotti de Carolis, A., & Longo, V. G. A neuropharmacological investigation of some trans-tetrahydrocannabinol derivatives. Physiology and Behavior, 1969, 4, 527–532.CrossRefGoogle Scholar
  34. Litchfield, J. T., & Wilcoxon, F. A. A simplified method of evaluating dose-effect experiments. Journal of Pharmacology and Experimental Therapeutics, 1949, 96, 99–133.PubMedGoogle Scholar
  35. Loewe, S., & Goodman, L. S. Anticonvulsant action of marihuana-active substances. Federation Proceedings, 1947, 6, 352. (Abstract)Google Scholar
  36. Luthra, Y. K., & Rosenkrantz, H. Cannabinoids: Neurochemical aspects after oral chronic administration to rats. Toxicology and Applied Pharmacology, 1974, 27, 158–168.PubMedCrossRefGoogle Scholar
  37. Luthra, Y. K., Rosenkrantz, H., Heyman, I. A., & Braude, M. C. Differential neurochemistry and temporal pattern in rats treated orally with delta-9-tetrahydrocannabinol for periods up to six months. Toxicology and Applied Pharmacology, 1975, 32, 418–431.PubMedCrossRefGoogle Scholar
  38. Martinez, J. L., Stadnicki, S. W., & Schaeppi, U. H. Delta-9-tetrahydrocannabinol: Effects on EEG and behavior of rhesus monkeys. Life Sciences, 1972, 11, 643–651.CrossRefGoogle Scholar
  39. McCaughran, J. A., Corcoran, M. E., & Wada, J. A. Anticonvulsant activity of delta-8-and delta-9-tetrahydrocannabinol in rats. Pharmacology, Biochemistry and Behavior, 1974, 2, 227–233.CrossRefGoogle Scholar
  40. Meldrum, B. S., Fariello, R. G., Puil, E. A., Derouaux, M., & Naquet, R. Delta-9-Tetrahydrocannabinol and epilepsy in the photosensitive baboon, Papio papio. Epilepsia, 1974, 15, 255–264.PubMedCrossRefGoogle Scholar
  41. Moreton, J. E., & Davis, W. M. Electroencephalographic study of the effects of tetrahydrocannabinols on sleep in the rat. Neuropharmacology, 1973, 12, 897–907.PubMedCrossRefGoogle Scholar
  42. O’shaughnessy, W. B. On the preparation of Indian hemp orgunjah. Transactions of the Medical and Physical Society of Bombay, 1842, 8, 421–461.Google Scholar
  43. Perez-Reyes, M., & Wingfield, M. Cannabidiol and electroencephalographic epileptic activity. Journal of the American Medical Association, 1974, 230, 1635.PubMedCrossRefGoogle Scholar
  44. Pirch, J. H., Cohn, R. A., Barnes, P. R., & Barratt, E. S. Effects of acute and chronic administration of marijuana extract on the rat electrocorticogram. Neuropharmacology, 1972, 11, 231–240.PubMedCrossRefGoogle Scholar
  45. Reynolds, J. R. Therapeutic uses and toxic effects of Cannabis indica. Lancet, 1890, 1, 637–638.CrossRefGoogle Scholar
  46. Rosenkrantz, H., & Braude, M. C. Acute, subacute and 23-day chronic marijuana inhalation toxicities in the rat. Toxicology and Applied Pharmacology, 1974, 28, 428–441.PubMedCrossRefGoogle Scholar
  47. Rosenkrantz, H., Sprague, R. A., Fleischman, R. W., & Braude, M. C. Oral delta-9-tetrahydrocannabinol toxicity in rats treated for periods up to six months. Toxicology and Applied Pharmacology, 1975, 32, 399–417.CrossRefGoogle Scholar
  48. Segal, M. Central implantation of cannabinoids: Induction of epileptiform discharges. European Journal of Pharmacology, 1974, 77, 40–45.CrossRefGoogle Scholar
  49. Segal, M., & Barak, Y. Central excitatory effects of delta-1-and delta-6-tetrahydrocannabinol. Brain Research, 1972, 42, 547–548. (Abstract)CrossRefGoogle Scholar
  50. Segal, M., & Kennev, A. F. Delta-1-and delta-1(6)-tetrahydrocannabinol: Preliminary observations on similarities and differences in central pharmacological effects in the cat. Experientia, 1972, 28, 816–819.PubMedCrossRefGoogle Scholar
  51. Shaw, J. On the use of Cannabis indica in tetanus, hydrophobia, cholera with remarks on its effects. Madras Medical Journal, 1843, 5, 74–80.Google Scholar
  52. Sofia, R. D., Kubena, R. K., & Barry, H. Comparison of four vehicles for intraperitoneal administration of delta-1-tetrahydrocannabinol. Journal of Pharmacy and Pharmacology, 1971, 23, 889–891. (a)PubMedCrossRefGoogle Scholar
  53. Sofia, R. D., Solomon, T. A., & Barry, H. The anticonvulsant activity in delta-1-tetrahydrocannabinol in mice. Pharmacologist, 1971, 13(2), 246. (Abstract) (b)Google Scholar
  54. Sofia, R. D., Kubena, R. K., & Barry H. Comparison among four vehicles and four routes for administering delta-9-tetrahydrocannabinol. Journal of Pharmaceutical Sciences, 1974, 63, 939–941.PubMedCrossRefGoogle Scholar
  55. Stadnicki, S. W., Schaeppi, U., Rosenkrantz, H., & Braude, M. C. Delta-9-Tetrahydrocannabinol: Subcortical spike bursts and motor manifestations in a Fischer rat treated orally for 109 days. Life Sciences, 1974, 14, 463–472.PubMedCrossRefGoogle Scholar
  56. Thompson, G. R., Mason, M. M., Rosenkrantz, H., & Braude, M. C. Chronic oral toxicity of cannabinoids in rats. Toxicology and Applied Pharmacology, 1973, 25, 373–390. (a)PubMedCrossRefGoogle Scholar
  57. Thompson, G. R., Rosenkrantz, H., Fleischman, R. W., & Braude, M, C Effects of delta-9-tetrahydrocannabinol administered subcutaneously to rabbits for 28 days. Toxicology, 1975, 4, 41–51.PubMedCrossRefGoogle Scholar
  58. Thompson, G. R., Rosenkrantz, H., Schaeppi, U. H., & Braude, M. C. Comparison of acute oral toxicity of cannabinoids in rats, dogs and monkeys. Toxicology and Applied Pharmacology, 1973, 25, 363–372. (b)PubMedCrossRefGoogle Scholar
  59. Turkanis, S. A., Cely, W., Olsen, D. M., & Karler, R. Anticonvulsant properties of cannabidiol. Research Communications in Chemical Pathology and Pharmacology, 1974, 8, 231–246.PubMedGoogle Scholar
  60. Turkanis, S. A., & Karler, R. Influence of cannabinoids on post-tetanic potentiation (PTP) at a bullfrog paravertebral ganglion. Federation Proceedings, 1975, 34 (3), 782. (Abstract)Google Scholar
  61. Wada, J. A., Sato, M., & Corcoran, M. E. Antiepileptic properties of delta-9-tetrahydrocannabinol. Experimental Neurology, 1973, 39, 157–165.PubMedCrossRefGoogle Scholar
  62. Woodbury, D, M. Mechanisms of action of anticonvulsants. In H. Jasper, A. Ward, & A. Page (Eds.), Basic Mechanisms of the Epilepsies. Boston: Little, Brown, 1969.Google Scholar
  63. Woodbury, L. A., & Davenport, V. D. Design and use of a new electroshock seizure apparatus, and analysis of factors altering seizure threshold and pattern. Archives Internationales de Pharmacodynamie et de Therapie, 1952, 92, 97–107.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1976

Authors and Affiliations

  • Paul Consroe
    • 1
  • Byron Jones
    • 1
  • Hugh LairdII
    • 1
  • Jeff Reinking
    • 1
  1. 1.Department of Pharmacology and ToxicologyUniversity of Arizona College of PharmacyTucsonUSA

Personalised recommendations