, Volume 40, Issue 4, pp 285–295 | Cite as

Comparative analgesic activity of various naturally occurring cannabinoids in mice and rats

  • R. Duane Sofia
  • Heidi B. Vassar
  • Linda C. Knobloch
Animal Studies


The analgesic effectiveness of δ9-tetrahydrocannabinol (THC), a crude marihuana extract (CME), cannabinol (CBN), cannabidiol (CBD), morphine SO4 and aspirin following oral administration was directly compared in mice using the acetic-induced writhing and hot plate tests and the Randall-Selitto paw pressure test in rats. THC and morphine were equipotent in all tests except that morphine was significantly more potent in elevating pain threshold in the uninflamed rat hind paw. In terms of THC content, CME was nearly equipotent in the hot plate and Randall-Selitto tests, but was 3 times more potent in the acetic acid writhing test. On the other hand, CBN, like aspirin, was only effective in reducing writhing frequency in mice (3 times more potent than aspirin) and raising pain threshold of the inflamed hind paw of the rat (equipotent with aspirin). CBD did not display a significantly analgesic effect in any of the test systems used. The results of this investigation seem to suggest that both THC and CME possess narcotic-like analgesic activity similar to morphine, while CBN appears to be a non-narcotic type analgesic like aspirin.

Key words

δ9-Tetrahydrocannabinol (THC) Analgesic Crude Marihuana Extract (CME) Narcotic-Like Cannabinol (CBN) Non-Narcotic-Like Cannabidiol (CBD) 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bicher, H. I., Mechoulam, R.: Pharmacological effects of two active constituents of marihuana. Arch. int. Pharmacodyn. 172, 24–31 (1968)Google Scholar
  2. Blumberg, H., Wolf, P. S., Dayton, H. B.: Use of the writhing test for evaluating analgesic activity of narcotic antagonists. Proc. Soc. exp. Biol. (N.Y.) 118, 763–766 (1965)Google Scholar
  3. Burstein, S. H.: Labeling and metabolism of the tetrahydrocannabinols. In: Marihuana chemistry, pharmacology, metabolism and clinical effects. R. Mechoulam, ed., pp. 167–190. New York: Academic Press 1973Google Scholar
  4. Buxbaum, D. M.: Analgesic activity of δ9-tetrahydrocannabinol in the rat and mouse. Psychopharmacologia (Berl.) 25, 275–280 (1972)Google Scholar
  5. Chesher, G. B., Dahl, C. J., Everingham, M., Jackson, D. M., Marchant-Williams, H., Starmer, G. A.: The effect of cannabinoids on intestinal motility and their antinociceptive effect in mice. Brit. J. Pharmacol. 49, 588–594 (1973)Google Scholar
  6. Dewey, W. L., Harris, L. S., Kennedy, J. S.: Some pharmacological and toxicological effects of l-trans-δ8 and l-trans-δ9-tetrahydrocannabinol in laboratory rodents. Arch. int. Pharmacodyn. 196, 133–145 (1972)Google Scholar
  7. Eddy, N. B., Leimbach, D.: Synaptic analgesics. II. Dithienylburenyl- and dithienylbutylamines. J. Pharmacol. exp. Ther. 107, 385–393 (1953)Google Scholar
  8. Goldstein, A.: Biostatistics—An Introductory Text, p. 144. New York: MacMillan Comp. 1964Google Scholar
  9. Izquierdo, I., Orsingher, O. A., Berardi, A. C.: Effect of cannabidiol and of other Cannabis sativa compounds on hippocampal seizure discharges. Psychopharmacologia (Berl.) 28, 95–102 (1973)Google Scholar
  10. Karler, R., Cely, W., Turkanis, S. A.: The anticonvulsant activity of cannabidiol and cannabinol. Life Sci. 13, 1527–1531 (1973)Google Scholar
  11. Karniol, I. G., Carlini, E. A.: Pharmacological interaction between cannabinol and δ9-tetrahydrocannabinol. Psychopharmacologia (Berl.) 33, 53–70 (1973)Google Scholar
  12. Kaymakcalan, S., Turker, R. K., Turker, M. N.: Analgesic effect of δ9-tetrahydrocannabinol in the dog. Psychopharmacologia (Berl.) 35, 123–128 (1974)Google Scholar
  13. Koster, R., Anderson, M., deBeer, E. J.: Acetic acid for analgesic screening. Fed. Proc. 18, 412 (1959)Google Scholar
  14. Layman, J. M., Milton, A. S.: Some actions of δ1-tetrahydrocannabinol at cholinergic junctions. Brit. J. Pharmacol. 41, 379P (1971)Google Scholar
  15. Litchfield, J. T., Jr., Wilcoxon, F.: A simplified method of evaluating dose-effect experiments. J. Pharmacol. exp. Ther. 96, 99–113 (1949)Google Scholar
  16. Mechoulam, R.: Marihuana chemistry. Science 168, 1159–1166 (1970)Google Scholar
  17. Paton, W. D. M., Pertwee, R. G.: The pharmacology of Cannabis in animals. In: Marijuana chemistry, pharmacology, metabolism and clinical effects. R. Mechoulam, ed., pp. 191–285. New York: Academic Press 1973Google Scholar
  18. Randall, L. O., Selitto, J. J.: A method for measurement of analgesic activity on inflamed tissue. Arch. int. Pharmacodyn. 111, 409–419 (1957)Google Scholar
  19. Raz, A., Schurr, A., Livne, A.: The interaction of hashish components with human erythrocytes. Biochim. biophys. Acta (Amst.) 274, 269–271 (1972)Google Scholar
  20. Scheckel, C. L., Boff, E., Dahlen, P., Smart, T.: Behavioral effects in monkeys of racemates of two biologically active marihuana constituents. Science 160, 1467–1469 (1968)Google Scholar
  21. Segelman, A. B., Sofia, R. D., Segelman, F. H., Harakal, J. J., Knobloch, L. C.: Cannabis sativa L. (Marijuana) V: Pharmacological evaluation of marijuana aqueous extract and volatile oil. J. pharm. Sci. 63, 962–964 (1974)Google Scholar
  22. Sofia, R. D., Dixit, B. N., Barry, III, H.: The effects of δ1-tetrahydrocannabinol on serotonin metabolism in the rat brain. Life Sci. 10, 425–436 (1971)Google Scholar
  23. Sofia, R. D., Kubena, R. K., Barry, III, H.: Comparison of four vehicles for intraperitoneal administration of δ1-tetrahydrocannabinol. J. Pharm. Pharmacol. 23, 889–891 (1971)Google Scholar
  24. Sofia, R. D., Solomon, T. A., Barry, III, H.: The anticonvulsant activity of δ1-tetrahydrocannabinol in mice. Pharmacologist 13, 246 (1971)Google Scholar
  25. Sofia, R. D., Nalepa, S. D., Harakal, J. J., Vassar, H. B.: Antiedema and analgesic properties of δ9-tetrahydrocannabinol (THC). J. Pharmacol. exp. Ther. 186, 646–655 (1973)Google Scholar
  26. Sofia, R. D., Knobloch, L. C., Vassar, H. B.: The anti-edema activity of various naturally occurring cannabinoids. Res. Comm. Chem. Path. Pharmacol. 6, 909–918 (1973)Google Scholar
  27. Sofia, R. D., Kubena, R. K., Barry, III, H.: Comparison among four vehicles and four routes for administering δ9-tetrahydrocannabinol. J. Pharm. Sci. (in press)Google Scholar
  28. Swingle, K. F., Grant, T. J., Kvam, D. C.: Quantal responses in the Randall-Selitto assay. Proc. Soc. exp. Biol. (N.Y.) 137, 536–538 (1971)Google Scholar
  29. Welch, B. L., Welch, A. S., Messiha, F. S., Berger, H. J.: Rapid depletion of adrenal epinephrine and elevation of telencephalic serotonin by (−)-trans-δ9-tetrahydrocannabinol in mice. Res. Comm. Chem. Path. Pharmacol. 2, 382–391 (1971)Google Scholar
  30. Winter, C. A., Flataker, L.: Nociceptive thresholds as affected by parenteral administration of irritants and of various antinociceptive drugs. J. Pharmacol. exp. Ther. 148, 373–379 (1965)Google Scholar

Copyright information

© Springer-Verlag 1975

Authors and Affiliations

  • R. Duane Sofia
    • 1
  • Heidi B. Vassar
    • 1
  • Linda C. Knobloch
    • 1
  1. 1.Wallace LaboratoriesDepartment of Pharmacology and ToxicologyCranbury

Personalised recommendations