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Pharmacological interaction between cannabidiol and δ9-tetrahydrocannabinol

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Abstract

The pharmacological interaction between cannabidiol (CBD) and (−)δ 9-trans-tetrahydrocannabinol (δ 9-THC) has been studied in rabbits, mice and rats by administering mixtures containing varying amounts of both substances. CBD blocked the following effects of δ 9-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 δ 9-THC-induced analgesia in mice and the δ 9-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 δ 9-THC.

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References

  • 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 

  • 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 

  • Bueno, O. F. A., Carlini, E. A.: Dissociation of learning in marihuana tolerant rats. Psychopharmacologia (Berl.) 25, 49–56 (1972)

    Google Scholar 

  • Buxbaum, D. M.: Analgesic activity of δ 9-tetrahydrocannabinol in the rat and mouse. Psychopharmacologia (Berl.) 25, 278–280 (1972)

    Google Scholar 

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

    Google Scholar 

  • 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)

  • 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 

  • 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 

  • 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 1972

    Google Scholar 

  • 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 

  • 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 

  • 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 

  • Eddy, N. B., Leimbach, D.: Synthetic analgesics. II. Dithienylbutenyl- and dithienylbutylamines. J. Pharmacol. exp. Ther. 107, 385–393 (1953)

    Google Scholar 

  • 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 

  • 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 

  • 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 

  • 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 

  • 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 

  • 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 

  • 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 

  • Kudrin, A. N., Davydova, O. N.: Elimination of hashish intoxication with phenitrone in dogs. Farmakol. Toksikol. 31, 549–552 (1968)

    Google Scholar 

  • 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 

  • 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 

  • Lomax, P., Campbell, C.: Phenitrone and marihuana induced hypothermia. Experientia (Basel) 27, 1191–192 (1971)

    Google Scholar 

  • Masur, J.: Sex differences in “emotionality” and behavior of rats in the open field. Behav. Biol. 7, 749–754 (1972)

    Google Scholar 

  • 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 

  • Mechoulam, B.: Marihuana chemistry. Science 168, 1159–1166 (1970)

    Google Scholar 

  • 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 1972

    Google Scholar 

  • Morden, B., Mitchell, G., Dement, W.: Selective REM sleep deprivation and compensation phenomena in the rat. Brain Res. 5, 339–349 (1967)

    Google Scholar 

  • 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 

  • 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 1972

    Google Scholar 

  • 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 

  • 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 

  • Small, E.: Infertility and chromosomal uniformity in Cannabis. Canad. J. Bot. 50, 1947–1949 (1972)

    Google Scholar 

  • 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 

  • Stein, L., Berger, B. D.: Paradoxical fear-increasing effects of tranquilizers: evidence of repression in the rat. Science 166, 253–256 (1969)

    Google Scholar 

  • 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 

  • Valle, J. R.: Pharmacological approaches to the study of the cannabis problem. Int. J. Addict. 4, 623–647 (1969)

    Google Scholar 

  • 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 

  • 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 

  • Waller, C. W.: Chemistry of marhuana. Pharmacol. Bev. 23, 265–271 (1971)

    Google Scholar 

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Authors and Affiliations

  1. Departamento de Psicobiologia, Escola Paulista de Medioina, SÃo Paulo, Brasil

    I. G. Karniol & E. A. Carlini

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  1. I. G. Karniol
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  2. E. A. Carlini
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Work partially aided by Conselho Nacional de Pesquisas (CNPq)

With a fellowship from FundaÇÃo de Amparo à Pesquisa do Estado de SÃo Paulo (FAPESP)

Pesquisador conferencista-bolsista do CNPq.

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Karniol, I.G., Carlini, E.A. Pharmacological interaction between cannabidiol and δ9-tetrahydrocannabinol. Psychopharmacologia 33, 53–70 (1973). https://doi.org/10.1007/BF00428793

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  • DOI: https://doi.org/10.1007/BF00428793

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