, Volume 33, Issue 1, pp 53–70 | Cite as

Pharmacological interaction between cannabidiol and δ9-tetrahydrocannabinol

  • I. G. Karniol
  • E. A. Carlini
Animal Studies


The pharmacological interaction between cannabidiol (CBD) and (−)δ9-trans-tetrahydrocannabinol (δ9-THC) has been studied in rabbits, mice and rats by administering mixtures containing varying amounts of both substances. CBD blocked the following effects of δ9-THC: catatonia in mice, corneal areflexia in rabbits, the increased defecation and decreased ambulation after chronic treatment and exposures of rats in an open field arena, and the aggressiveness of rats previously stressed by REM sleep deprivation. On the other hand, CBD potentiated the δ9-THC-induced analgesia in mice and the δ9-THC-impairing effect on climbing rope performance of rats.

These interactions are tentatively explained by postulating that CBD directly antagonizes the excitatory effects and/or indirectly potentiates the depressant effects of δ9-THC.

Key words

δ9-THC-Cannabidiol Cannabinoid Compounds Pharmacological Interaction 


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  1. Alves, C. N., Goyos, A. C., Carlini, E. A.: Aggressiveness induced by marihuana and other psychotropic drugs in REM sleep deprived rats. Pharmac. Biochem. Behav. 1, 183–190 (1973)Google Scholar
  2. Berger, H. J., Krantz, J. C.: Phenitrone: ineffective blockade of (−) trans-δ 9-tetrahydrocannabinol in mice and dogs. J. Pharm. Pharmacol. 24, 492–493 (1972)Google Scholar
  3. Bueno, O. F. A., Carlini, E. A.: Dissociation of learning in marihuana tolerant rats. Psychopharmacologia (Berl.) 25, 49–56 (1972)Google Scholar
  4. Buxbaum, D. M.: Analgesic activity of δ 9-tetrahydrocannabinol in the rat and mouse. Psychopharmacologia (Berl.) 25, 278–280 (1972)Google Scholar
  5. Carlini, E. A.: Tolerance to chronic administration of Cannabis sativa (marihuana) in rats. Pharmacology 1, 135–142 (1968)Google Scholar
  6. Carlini, E. A.: Acute and chronic behavioral effects of Cannabis saliva. In: Drugs and Society, symposium at 5th International Congress of Pharmacology, vol. 1. Basel: Karger (in press)Google Scholar
  7. Carlini, E. A., Hamaoui, A., Bieniek, D., Korte, F.: Effects of (−) δ 9-trans-tetrahydrocannabinol and a synthetic derivative on maze performance of rats. Pharmacology 4, 359–368 (1970a)Google Scholar
  8. Carlini, E. A., Santos, M., Claussen, U., Bieniek, D., Korte, F.: Structure activity relationship of four tetrahydrocannabinols and the pharmacological activity of five semi-purified extracts of Cannabis sativa. Psychopharmacologia (Berl.) 18, 82–93 (1970b)Google Scholar
  9. Carlini, E. A., Masur, J., Karniol, I. G., Leite, J. R.: Cannabis sativa: is it possible to consider behavioural animal data as experimental models for some effects on humans? In: Cannabis and its derivatives-pharmacology and experimental psychology. W. D. M. Paton and J. Crown, eds., pp. 154–175. London: Oxford University Press 1972Google Scholar
  10. Carlini, E. A., Masur, J.: Development of aggressive behavior in rats by chronic administration of Cannabis sativa (marihuana). Life Sci. 8 (part I), 607–620 (1969)Google Scholar
  11. Doorenbos, N. J., Fetterman, P. S., Quimby, M. W., Turner, C. E.: Cultivation, extraction, and analysis of Cannabis sativa L. Ann. N.Y. Acad. Sci. 191, 3–14 (1971)Google Scholar
  12. Drew, W. G., Miller, L. L., Wickler, A.: Effect of δ 9-THC on open field activity of the rat. Psychopharmacologia (Berl.) 23, 289–299 (1972)Google Scholar
  13. Eddy, N. B., Leimbach, D.: Synthetic analgesics. II. Dithienylbutenyl- and dithienylbutylamines. J. Pharmacol. exp. Ther. 107, 385–393 (1953)Google Scholar
  14. Fernandes, M., Schabarek, A., Coper, H., Hill, R.: Modification of THC-actions by cannabinol (CBN) and cannabidiol (CBD) in the rat. Psychopharmacologia (Berl.) 26 (Suppl.), 130 (1972)Google Scholar
  15. Fetterman, P. S., Keith, E. S., Waller, C. W., Guerrero, O., Doorenbos, N., Quimby, M. W.: Mississippi-grown Cannabis sativa L.: preliminary observation on chemical definition of phenotype and variations in tetrahydrocannabinol content versus age, sex, and plant part. J. pharm. Sci. 60, 1246–1249 (1971)Google Scholar
  16. Grisham, M. G., Ferraro, D. P.: Biphasic effects of δ 9-tetrahydrocannabinol on variable interval schedule performance in rats. Psychopharmacologia (Berl.) 27, 163–170 (1972)Google Scholar
  17. Izquierdo, I., Berardi, A. C., Orsingher, O.: Effect of cannabidiol and of other Cannabis sativa compounds on hippocampal seizure discharges. Psychopharmacologia (Berl.) 28, 95–102 (1973)Google Scholar
  18. Jones, G., Pertwee, R. G.: A metabolic interaction in vivo between cannabidiol and δ 9-tetrahydrocannabinol. Brit. J. Pharmacol. 45, 375–377 (1972)Google Scholar
  19. Karniol, I. G., Carlini, E. A.: The content of (−)δ 9-trans-tetrahydrocannabinol (δ 9-THC) does not explain all biological activity of some Brazilian marihuana samples. J. Pharm. Pharmacol. 24, 833–835 (1972)Google Scholar
  20. Krantz, J. C., Berger, H. J., Welch, B. L.: Blockade of (−)-trans-δ 9-tetrahydro-cannabinol depressant effect by cannabinol in mice. Amer. J. Pharm. 143, 149–152 (1971)Google Scholar
  21. Kudrin, A. N., Davydova, O. N.: Elimination of hashish intoxication with phenitrone in dogs. Farmakol. Toksikol. 31, 549–552 (1968)Google Scholar
  22. Kumar, R.: Extinction of fear II: effects of chlordiazepoxide and chlorpromazine on fear and exploratory behaviour in rats. Psychopharmacologia (Berl.) 19, 297–312 (1971)Google Scholar
  23. Lapa, A. J., Sampaio, C. A. M., Timo-Iaria, C., Valle, J. R.: Blocking action of tetrahydrocannabinol upon transmission in the trigeminal system of the eat. J. Pharm. Pharmacol. 20, 373–376 (1968)Google Scholar
  24. Lomax, P., Campbell, C.: Phenitrone and marihuana induced hypothermia. Experientia (Basel) 27, 1191–192 (1971)Google Scholar
  25. Masur, J.: Sex differences in “emotionality” and behavior of rats in the open field. Behav. Biol. 7, 749–754 (1972)Google Scholar
  26. Masur, J., Martz, R. M. W., Carlini, E. A.: Effects of acute and chronic administration of Cannabis sativa and (−)δ 9-trans-tetrahydrocannabinol on the behavior of rats in an open field arena. Psychopharmacologia (Berl.) 19, 388–397 (1971)Google Scholar
  27. Mechoulam, B.: Marihuana chemistry. Science 168, 1159–1166 (1970)Google Scholar
  28. Mechoulam, B., Ben-Zvi, Z., Shani, A., Zemler, H., Levy, S., Edery, H., Grunfeld, Y.: Cannabinoids and cannabis activity. In: Cannabis and its derivatives-pharmacology and experimental psychology. W. D. M. Paton and J. Crown, eds., pp. 1–15. London: Oxford University Press 1972Google Scholar
  29. Morden, B., Mitchell, G., Dement, W.: Selective REM sleep deprivation and compensation phenomena in the rat. Brain Res. 5, 339–349 (1967)Google Scholar
  30. Paton, W. D. M., Pertwee, B. G.: Effects of cannabis and certain of its constituents on pentobarbitone sleeping time and phenazone metabolism. Brit. J. Pharmacol. 44, 250–261 (1972)Google Scholar
  31. Pertwee, R. G.: In the discussion of the paper by W. D. M. Paton, R. G. Pertwee and D, Temple: The general pharmacology of cannabinoids. In: Cannabis and its derivatives-pharmacology and experimental psychology. W. D. M. Paton and J. Crown, eds., pp. 50–75. London: Oxford University Press 1972Google Scholar
  32. Potvin, R. J., Fried, P. A.: Acute and chronic effects on rats of (−)δ 1-trans-tetrahydrocannabinol on unlearned motor tasks. Psychopharmacologia (Berl.) 26, 369–378 (1972)Google Scholar
  33. Silva, M. T. A., Carlini, E. A., Claussen, U., Korte, F.: Lack of cross-tolerance in rats among (−)δ 9-trans-tetrahydrocannabinol, cannabis extract, mescaline and lysergic acid diethylamide (LSD-25). Psychopharmacologia (Berl.) 13, 332–340 (1968)Google Scholar
  34. Small, E.: Infertility and chromosomal uniformity in Cannabis. Canad. J. Bot. 50, 1947–1949 (1972)Google Scholar
  35. Spaulding, T. C., Ford, R. D., Dewey, W. L., McMillan, D. E., Harris, L. S.: Some pharmacological effects of phenitrone and its interaction with δ 9-THC. Europ. J. Pharmacol. 19, 310–317 (1972)Google Scholar
  36. Stein, L., Berger, B. D.: Paradoxical fear-increasing effects of tranquilizers: evidence of repression in the rat. Science 166, 253–256 (1969)Google Scholar
  37. Turner, C. A., Hadley, K.: Constituents of Cannabis sativa L.: absence of cannabidiol in an african variant. J. pharm. Sci. 62, 251–255 (1973)Google Scholar
  38. Valle, J. R.: Pharmacological approaches to the study of the cannabis problem. Int. J. Addict. 4, 623–647 (1969)Google Scholar
  39. Valle, J. R., Souza, J. A., Hyppolito, N.: Bioassay of cannabis preparations based on abolition of the rabbit blink reflex. Farmaco 22, 27–36 (1967)Google Scholar
  40. De Vree, T. B., Breimer, D. D., Van Ginneken, C. A. M., Van Bossum, J. M.: Identification in hashish of tetrahydrocannabinol, cannabidiol and cannabinol analogs with a methyl side-chain. J. Pharm. Pharmacol. 24, 7–12 (1972)Google Scholar
  41. Waller, C. W.: Chemistry of marhuana. Pharmacol. Bev. 23, 265–271 (1971)Google Scholar

Copyright information

© Springer-Verlag 1973

Authors and Affiliations

  • I. G. Karniol
    • 1
  • E. A. Carlini
    • 1
  1. 1.Departamento de PsicobiologiaEscola Paulista de MedioinaSÃo PauloBrasil

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