Advertisement

Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Effect of subchronic treatment with (−) δ8-trans-tetrahydrocannabinol (δ8-THC) on food intake, body temperature, hexobarbital sleeping time and hexobarbital elimination in rats

Abstract

In a series of experiments in rats it was possible to prove that δ 8-THC has the same type of effectiveness as the stereo-isomeric δ 9-THC.

Body temperature was reduced to 35.5‡ C 90 min after injection of 10 mg/kg δ 8-THC; 5 mg/kg δ 8-THC extended the duration of hexobarbital sleeping time from 119 min in control animals to 205 min. Following treatment with δ 8-THC for 9 and 10 days the effects on hypothermia and prolongation of sleeping time were less pronounced than in acute experiments. Body temperature dropped to 36.4‡ C 90 min p.i. and the duration of hexobarbital sleeping time was only extended to 156 min. This attenuation of effects after subchronic THC treatment was regarded as due to the development of tolerance.

In order to exclude the possibility that the extension of sleeping time might be due to an effect of THC on hexobarbital metabolism, the hexobarbital concentration in cerebral tissue and blood was determined 30, 60, 90 and 120 min after the administration of 100 mg/kg hexobarbital-Na. There was no difference in hexobarbital elimination between rats treated with THC in a single dose or over a 10-day period and control animals.

This is a preview of subscription content, log in to check access.

References

  1. Bose, B. C., Saifi, A. Q., Bhagwat, A. W.: Effect of cannabis indica on hexobarbital sleeping time and tissue respiration of rat brain. Arch. int. Pharmacodyn. 141, 520 (1963).

  2. Brodie, B. B., Burns, J. J., Mark, L. C., Lief, P. A., Bernstein, E., Papper, E. M.: Fate of pentobarbital in man, dog and a method of its estimation. J. Pharmacol. exp. Ther. 109, 26 (1953).

  3. Carlini, A. E.: Tolerance to chronic administration of cannabis sativa (marihuana) in rats. Pharmacology 1, 135 (1968).

  4. Coper, H., Deyhle, G., Herrath, D. v., Veit, J.: Zum Mechanismus der schlafverlÄngernden Wirkung verschiedener Pharmaka. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path. 260, 366 (1968).

  5. Dagirmanjian, R., Boyd, E. S.: Some pharmacological effects of two tetrahydrocannabinols. J. Pharmacol. exp. Ther. 135, 25 (1962).

  6. Dewey, W. L., Harris, L. S., Howes, J. F., Kennedy, J. S., Andersen, R. N.: personal information.

  7. Krantz, J. C., Jr., Berger, H. J., Welch, B. L.: Blockade of (−)-Trans-δ 9-Tetrahydrocannabinol depressant effect by cannabinol in mice. Amer. J. Pharm. 143, 149–152 (1971).

  8. Garattini, S.: Effects of a cannabis extract on gross behaviour. In: Hashish: its Chemistry and pharmacology. CIBA Foundation. London: J. & A. Churchill, Ltd. 1965.

  9. Garriott, J. C., Forney, R. B., Hughes, F. W., Richards, A. B.: Pharmacologic properties of some cannabis related compounds. Arch. int. Pharmacodyn. 171, 425 (1968).

  10. Garriott, J. C., King, L. J., Forney, R. B., Hughes, F. W.: Effects of some tetrahydrocannabinols on hexobarbital sleeping time and amphetamine induced hyperactivity in mice. Life Sci. 6, 2119 (1967).

  11. Gill, E. W., Paton, W. D. M., Pertwee, R. G.: Preliminary experiments on the chemistry and pharmacology of cannabis. Nature (Lond.) 228, 134 (1970).

  12. Grunfeld, Y., Edery, H.: Psychopharmacological activity of the active constituents of hashish and some related cannabinoids. Psychopharmacologia (Berl.) 14, 200 (1969).

  13. Holtzman, D., Lovell, R. A., Jaffe, J. H., Freedman, D. X.: 1-δ 9-tetrahydrocannabinol: Neurochemical and behavioral effects in the mouse. Science 163, 1464 (1969).

  14. Klinger, W.: ToxizitÄt, Narkotische Wirkung, Aufwachkonzentration im Blut, Elimination aus dem Blut und Biotransformation von Hexobarbital bei Ratten unterschiedlichen Alters nach Induktion mit Barbital und CCl4-SchÄdigung. Arch. int. Pharmacodyn. 184, 5 (1970).

  15. Kubena, R., Barry III., H.: Interactions of δ 1-tetrahydrocannabinol with barbiturates and methamphetamine. J. Pharmacol. exp. Ther. 173, 94 (1970).

  16. Loewe, S.: Cannabiswirkstoffe und Pharmakologie der Cannabinole. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 211, 175 (1950).

  17. Lomax, P.: Acute tolerance to the hypothermic effect of marihuana in the rat. Res. Comm. Chem. Path. Pharmacol. 2, 159 (1971).

  18. Manning, F. J., McDonough, J. H., Jr., Elsmore, T. F., Saller, Ch., Sodetz, F. J.: Inhibition of normal growth by chronic administration of δ 9-Tetrahydrocannabinol. Science 174, 424 (1971).

  19. McMillan, E. E., Harris, L. S., Frankenheim, J. M., Kennedy, J. S.: 1-δ 9-trans-tetrahydrocannabinol in pigeons: Tolerance to the behavioral effects. Science 169, 501 (1970).

  20. Miras, C. J.: Some aspects of cannabis action. In: Hashish: its chemistry and pharmacology. CIBA Foundation. London: J. & A. Churchill, Ltd. 1965.

  21. Remmer, H.: Geschlechtsspezifische Unterschiede in der Entgiftung von Evipan und Thiopental bei Ratten. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 233, 173 (1958).

  22. Remmer, G.: Der beschleunigte Abbau von Pharmaka in den Lebermikrosomen unter Einflu\ von Luminal. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 235, 279 (1959).

  23. Sofia, R. D., Barry III, H.: Depressant effect of δ 1-tetrahydrocannabinol enhanced by inhibition of its metabolism. Europ. J. Pharmacol. 13, 134 (1970).

Download references

Author information

Additional information

We are indebted to the Bundesministerium für Jugend, Familie und Gesundheit for financial support.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Rating, D., Broermann, I., Honecker, H. et al. Effect of subchronic treatment with (−) δ8-trans-tetrahydrocannabinol (δ8-THC) on food intake, body temperature, hexobarbital sleeping time and hexobarbital elimination in rats. Psychopharmacologia 27, 349–357 (1972). https://doi.org/10.1007/BF00429388

Download citation

Key words

  • δ 8-THC
  • Hexobarbital
  • Tolerance