Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1979 Nov;67(3):379–385. doi: 10.1111/j.1476-5381.1979.tb08691.x

The oral activity of delta'-tetrahydrocannabinol and its dependence on prostaglandin E2.

J W Fairbairn, J T Pickens
PMCID: PMC2043943  PMID: 574040

Abstract

1 delta'-trans-Tetrahydrocannabinol (THC) is more active orally in mice than previously thought, as cataleptic responses occur at doses from 0.06 mg/kg upwards, with peak activity at 2 to 4 h after dosing. These doses and peaks correspond well with the effects in man. 2 Comparison with chlorpromazine in mice shows that chlorpromazine and THC are equipotent as cataleptics during the first 2 h after dosing; thereafter the THC activity increases to a peak when it is 5.67 times as active as chlorpromazine. 3 The cataleptic effect of THC is abolished by aspirin, indomethacine, diffunisal and phenylbutazone which inhibit the biosynthesis of prostaglandins and is restored by exogenous prostaglandin E2 (PGE2) but not PGE1 and PGF2 alpha. This suggests that the effect of THC depends upon the presence of PGE2. 4 In contrast, the cataleptic effect of chlorpromazine is not affected by pretreatment with aspirin. 5 THC is very much less active intraperitoneally than orally; our results suggest this is not due to poor absorption or extraction into fat depots. 6 Cannabidiol has no cataleptic effect.

Full text

PDF
379

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bennett A., Murray J. G., Wyllie J. H. Occurrence of prostaglandin E2 in the human stomach, and a study of its effects on human isolated gastric muscle. Br J Pharmacol Chemother. 1968 Feb;32(2):339–349. [PubMed] [Google Scholar]
  2. Collier H. O., Dinneen L. C., Johnson C. A., Schneider C. The abdominal constriction response and its suppression by analgesic drugs in the mouse. Br J Pharmacol Chemother. 1968 Feb;32(2):295–310. doi: 10.1111/j.1476-5381.1968.tb00973.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Hannah J., Ruyle W. V., Jones H., Matzuk A. R., Kelly K. W., Witzel B. E., Holtz W. J., Houser R. W., Shen T. Y., Sarett L. H. Discovery of diflunisal. Br J Clin Pharmacol. 1977 Feb;4 (Suppl 1):7S–13S. doi: 10.1111/j.1365-2125.1977.tb04508.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ho B. T., Fritchie G. E., Englert L. F., McIsaac W. M., Idänpän-Heikkilä J. E. Marihuana: importance of the route of administration. J Pharm Pharmacol. 1971 Apr;23(4):309–310. doi: 10.1111/j.2042-7158.1971.tb08666.x. [DOI] [PubMed] [Google Scholar]
  5. Hollister L. E., Richards R. K., Gillespie H. K. Comparison of tetrahydrocannabinol and synhexyl in man. Clin Pharmacol Ther. 1968 Nov-Dec;9(6):783–791. doi: 10.1002/cpt196896783. [DOI] [PubMed] [Google Scholar]
  6. Isbell H., Gorodetzsky C. W., Jasinski D., Claussen U., von Spulak F., Korte F. Effects of (--)delta-9-trans-tetrahydrocannabinol in man. Psychopharmacologia. 1967;11(2):184–188. doi: 10.1007/BF00401256. [DOI] [PubMed] [Google Scholar]
  7. Jones R. T. Marihuana-induced "high": influence of expectation, setting and previous drug experience. Pharmacol Rev. 1971 Dec;23(4):359–369. [PubMed] [Google Scholar]
  8. Kiplinger G. F., Manno J. E. Dose-response relationships to cannabis in human subjects. Pharmacol Rev. 1971 Dec;23(4):339–347. [PubMed] [Google Scholar]
  9. Majerus P. W., Stanford N. Comparative effects of aspirin and diflunisal on prostaglandin synthetase from human platelets and sheep seminal vesicles. Br J Clin Pharmacol. 1977 Feb;4 (Suppl 1):15S–18S. doi: 10.1111/j.1365-2125.1977.tb04509.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Malor R., Chesher G. B., Jackson D. M. The effect of delta9-tetrahydrocannabinol on plasma concentrations of non-esterified fatty acids in the mouse. J Pharm Pharmacol. 1976 Aug;28(8):652–654. doi: 10.1111/j.2042-7158.1976.tb02823.x. [DOI] [PubMed] [Google Scholar]
  11. Perez-Reyes M., Lipton M. A., Timmons M. C., Wall M. E., Brine D. R., Davis K. H. Pharmacology of orally administered 9 -tetrahydrocannabinol. Clin Pharmacol Ther. 1973 Jan-Feb;14(1):48–55. doi: 10.1002/cpt197314148. [DOI] [PubMed] [Google Scholar]
  12. Pertwee R. G. The ring test: a quantitative method for assessing the 'cataleptic' effect of cannabis in mice. Br J Pharmacol. 1972 Dec;46(4):753–763. doi: 10.1111/j.1476-5381.1972.tb06900.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Piper P. J., Vane J. R. Release of additional factors in anaphylaxis and its antagonism by anti-inflammatory drugs. Nature. 1969 Jul 5;223(5201):29–35. doi: 10.1038/223029a0. [DOI] [PubMed] [Google Scholar]
  14. Roth G. J., Stanford N., Majerus P. W. Acetylation of prostaglandin synthase by aspirin. Proc Natl Acad Sci U S A. 1975 Aug;72(8):3073–3076. doi: 10.1073/pnas.72.8.3073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Rothschild M., Rowan M. G., Fairbairn J. W. Storage of cannabinoids by Arctia caja and Zonocerus elegans fed on chemically distinct strains of Cannabis sativa. Nature. 1977 Apr 14;266(5603):650–651. doi: 10.1038/266650a0. [DOI] [PubMed] [Google Scholar]
  16. Sallan S. E., Zinberg N. E., Frei E., 3rd Antiemetic effect of delta-9-tetrahydrocannabinol in patients receiving cancer chemotherapy. N Engl J Med. 1975 Oct 16;293(16):795–797. doi: 10.1056/NEJM197510162931603. [DOI] [PubMed] [Google Scholar]
  17. Stone C. A., Van Arman C. G., Lotti V. J., Minsker D. H., Risley E. A., Bagdon W. J., Bokelman D. L., Jensen R. D., Mendlowski B., Tate C. L. Pharmacology and toxicology of diflunisal. Br J Clin Pharmacol. 1977 Feb;4 (Suppl 1):19S–29S. doi: 10.1111/j.1365-2125.1977.tb04510.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES