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. 1976 Jan;56(1):43–48. doi: 10.1111/j.1476-5381.1976.tb06957.x

Tolerance to the cardiovascular effects of delta9-tetrahydrocannabinol in the rat.

M D Adams, L D Chait, J T Earnhardt
PMCID: PMC1666746  PMID: 1252665

Abstract

1. Daily intraperitoneal injections of delta9-tetrahydrocannabinol (delta9-THC, 10 mg/kg) resulted in tolerance to the effects of the cannabinoid on body weight and body temperature within 1-2 weeks of treatment. 2. Tolerance failed to develop to the suppression of spontaneous motor activity produced by delta9-THC during 28 days of treatment with the cannabinoid (10 mg/kg, i.p. per day). 3. Following treatment with vehicle for 28 days, intravenous administration of delta9-THC in anaesthetized rats produced a transient pressor response followed by a sustained hypotension and bradycardia. 4. Tolerance to the hypotensive and negative chronotropic responses to intravenous delta9-THC was readily apparent in animals which had received daily intraperitoneal injections of delta9-THC (10 mg/kg) for 28 days. 5. Tolerance failed to develop to the pressor actions of intravenous delta9-THC after 28 days of preptreatment. 6. There was no difference in the pressor response to intravenous noradrenaline in vehicle-treated animals (1.0 ml/kg, i.p., per day for 28 days) and delta9-THC-treated animals (10 mg/kg, i.p., per day for 28 days).

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Selected References

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

  1. BURN J. H., RAND M. J. The action of sympathomimetic amines in animals treated with reserpine. J Physiol. 1958 Dec 4;144(2):314–336. doi: 10.1113/jphysiol.1958.sp006104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Birmingham M. K. Reduction by 9-tetrahydrocannabinol in the blood pressure of hypertensive rats bearing regenerated adrenal glands. Br J Pharmacol. 1973 May;48(1):169–171. doi: 10.1111/j.1476-5381.1973.tb08236.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cavero I., Buckley J. P., Jandhyala B. S. Hemodynamic and myocardial effects of (-)-delta9-trans-tetrahydrocannabinol in anesthetized dogs. Eur J Pharmacol. 1973 Nov;24(2):243–251. doi: 10.1016/0014-2999(73)90078-2. [DOI] [PubMed] [Google Scholar]
  4. Cavero I., Solomon T., Buckley J. P., Jandhyala B. S. Studies on the bradycardia induced by (-)- -trans-tetrahydrocannabinol in anesthetized dogs. Eur J Pharmacol. 1973 Jun;22(3):263–269. doi: 10.1016/0014-2999(73)90025-3. [DOI] [PubMed] [Google Scholar]
  5. Davis W. M., Moreton J. E., King W. T., Pace H. B. Marihuana on locomotor activity: biphasic effect and tolerance development. Res Commun Chem Pathol Pharmacol. 1972 Jan;3(1):29–35. [PubMed] [Google Scholar]
  6. Dewey W. L., Jenkins J., O'Rourke T., Harris L. S. The effects of chronic administration of trans- 9 -tetrahydrocannabinol on behavior and the cardiovascular system of dogs. Arch Int Pharmacodyn Ther. 1972;198(1):118–131. [PubMed] [Google Scholar]
  7. Graham J. D., Lewis M. J., Li D. M. The effect of delta1-tetrahydrocannabinol on the release of (3H-(-)-noradrenaline from the isolated vas deferens of the rat. Br J Pharmacol. 1974 Oct;52(2):233–236. doi: 10.1111/j.1476-5381.1974.tb09705.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Graham J. D., Li D. M. Cardiovascular and respiratory effects of cannabis in cat and rat. Br J Pharmacol. 1973 Sep;49(1):1–10. [PMC free article] [PubMed] [Google Scholar]
  9. Hardman H. F., Domino E. F., Seevers M. H. General pharmacological actions of some synthetic tetrahydrocannabinol derivatives. Pharmacol Rev. 1971 Dec;23(4):295–315. [PubMed] [Google Scholar]
  10. Järbe T. U., Henriksson B. G. Acute effects of two tetrahydrocannabinols (delta9-THC and delta8-THC) on water intake in water deprived rats: implications for behavioral studies on marijuana compounds. Psychopharmacologia. 1973 Jun 29;30(4):315–322. doi: 10.1007/BF00429190. [DOI] [PubMed] [Google Scholar]
  11. Lomax P. Acute tolerance to the hypothermic effect of marihuana in the rat. Res Commun Chem Pathol Pharmacol. 1971 Mar;2(2):159–167. [PubMed] [Google Scholar]
  12. Manning F. J., McDonough J. H., Jr, Elsmore T. F., Saller C., Sodetz F. J. Inhibition of normal growth by chronic administration of delta-9-tetrahydrocannabinol. Science. 1971 Oct 22;174(4007):424–426. doi: 10.1126/science.174.4007.424. [DOI] [PubMed] [Google Scholar]
  13. McMillan D. E., Harris L. S., Frankenheim J. M., Kennedy J. S. l-delta-9-trans-tetrahydrocannabinol in pigeons: tolerance to the behavioral effects. Science. 1970 Jul 31;169(3944):501–503. [PubMed] [Google Scholar]
  14. Nahas G. G., Schwartz I. W., Adamec J., Manger W. M. Tolerance of delta-9-tetrahydrocannabinol in the spontaneously hypertensive rat. Proc Soc Exp Biol Med. 1973 Jan;142(1):58–60. doi: 10.3181/00379727-142-36957. [DOI] [PubMed] [Google Scholar]
  15. Sofia R. D. A paradoxical effect for 1 -tetrahydrocannabinol on rectal temperature in rats. Res Commun Chem Pathol Pharmacol. 1972 Sep;4(2):281–288. [PubMed] [Google Scholar]
  16. Sofia R. D., Barry H., 3rd Acute and chronic effects of delta9-tetrahydrocannabinol on food intake by rats. Psychopharmacologia. 1974;39(3):213–222. doi: 10.1007/BF00421028. [DOI] [PubMed] [Google Scholar]
  17. Williams R. B., Ng L. K., Lamprecht F., Roth K., Kopin I. J. 9 -Tetrahydrocannabinol: a hypotensive effect in rats. Psychopharmacologia. 1973;28(3):269–274. doi: 10.1007/BF00429307. [DOI] [PubMed] [Google Scholar]

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