Influence of Two Tetrahydrocannabinols (THC’s) on the Activity of Biotransformation Enzymes

  • M. ten Ham
  • Engelina M. den Tonkelaar
  • J. M. Koomen
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 35)


The majority of the reports concerning tolerance to the effects of cannabis, describe a rather rapidly developing tolerance. Already Loewe (1950) mentioned a weakening of the Cannabis ataxia after a few administrations. Later on, tolerance was found by Carlini (1968) and Silva c.s.(1968), using cannabis extract, and by McMillan (1970 a,b), Moreton (1970) and Ten Ham (1972), using tetrahydrocannabinol (Δ9-THC).


Liver Weight Liver Homogenate Lysergic Acid Biotransformation Enzyme Cross Tolerance 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Brodle, B.B., Axelrod, J.: The fate of aminopyrine in man and methods for the estimation of aminopyrine and its metabolites in biological materials. J.Pharmacol.Exptl.Therap. 99, 171 (1950).Google Scholar
  2. 2.
    Burstein, S.H., Kupfer, D.: Hydroxylation of trans-Δ1-tetrahydrocannabinol by a hepatic microsomal monooxygénase. Chem.-Biol. Interactions 3, 316 (1971).CrossRefGoogle Scholar
  3. 3.
    Carlini, E.A.: Tolerance to chronic administration of Cannabis sativa (marihuana) in rats. Pharmacology 1, 135–142 (1968).CrossRefGoogle Scholar
  4. 4.
    Chari-Briton, A., Brino, T.: Effect of Δ1-tetrahydrocannabinol on ATP-ase activity of rat liver mitochondria. Biochem.Pharmacol. 20, 473–475 (1971).CrossRefGoogle Scholar
  5. 5.
    Cohen, G.M., Peterson, D.W., Mannering, G.J.: Interactions of Δ9-tetrahydrocannabinol with the hepatic, microsomal drug metabolizing system. Life Sci. 10, 1207–1215 (1971).CrossRefGoogle Scholar
  6. 6.
    Gariott, J.C., King, J.L., Forney, L.B., Hughes, F.W.: Effects of some tetrahydrocannabinols on hexobarbital sleeping time and amphetamine induced hyperactivity in mice. Life Sci. 6, 2119–2128 (1967).CrossRefGoogle Scholar
  7. 7.
    Ham, M.ten: Dierexperimenteel onderzoek van twee bestanddelen van Cannabis Sativa L.:Δ8-en Δ9-tetrahydrocannabinol. Thesis, Utrecht, pag. 55-59 (1972).Google Scholar
  8. 8.
    Kew, M.C., Behrson, J., Lieuw, S.: Possible hepatotoxicity of Cannabis. Lancet I, 578–579 (1969).CrossRefGoogle Scholar
  9. 9.
    Lemberger, L., Axelrod, J., Kopin, I.J.: Metabolism and deposition of Δ9-tetrahydrocannabinol in man. Pharmacol.Rev. 23, 371–380 (1971).Google Scholar
  10. 10.
    Lipparini, F., Scotti di Carolis, A., Longo, V.G.: A neuropharmacial investigation of some trans-tetrahydrocannabinol derivates. Physiol. Behav. 4, 527–532 (1969).CrossRefGoogle Scholar
  11. 11.
    Loewe, S.: Cannabis-Wirkstoffe und Pharmakologie der Cannabinole. Arch.Exptl.Path.Pharmakol. 211, 175–193 (1950).Google Scholar
  12. 12.
    McMillan, D.E., Harris, L.S., Frankenheim, J.M., Kennedy, J.S.: l-Δ9-trans-tetrahydrocannabinol in pigeons: tolerance to behavioural effects. Science 169, 501–503 (1970a).CrossRefGoogle Scholar
  13. 13.
    McMillan, D.E., Harris, L.S., Turk, R.F., Kennedy, J.S.: Development of marked behavioural tolerance to 1Δ9tetrahydrocannabinol (Δ9-THC) and cross tolerance to Δ8-tetrahydrocannabinol (Δ8-THC) in the pigeon. Pharmacologist 12, 322 (1970b).Google Scholar
  14. 14.
    Moreton, J.E., Davis, W.M.: Effects of Δ9tetrahydrocannabinol on locomotor activity and on phases of sleep. Pharmacologist 12, 258 (1970).Google Scholar
  15. 15.
    Nakazawa, K., Costa, E.: Metabolism of Δ9tetrahydrocannabinol by lung and liver homogenates of rats treated with methylcholanthrene. Nature 234, 48–49 (1971).CrossRefGoogle Scholar
  16. 16.
    Nilsson, I.M., Agurell, S., Nilsson, J.L.G., Ohlson, A., Sandberg, F., Wahlquist, M.: Δ1-te trahydrocannabinol: structure of a major metabolite. Science 168, 1228–1229 (1970).CrossRefGoogle Scholar
  17. 17.
    Phillips, R.N., Brown, D.J., Marty, R., Hubbard, J.D., Forney, R.B.: Subacute toxicity of aqueous-suspended Δ9-tetrahydrocannabinol in rats. Toxicol.Appl.Pharmacol. 22, 45–49 (1972).CrossRefGoogle Scholar
  18. 18.
    Silva, M.T.A., Carlini, E.A., Claussen, U., Körte, F.: Lack of cross tolerance in rats among (−)Δ9trans-tetrahydrocannabinol (Δ9-THC), Cannabis extract, mescaline and lysergic acid diethylamide (LSD-25). Psychopharmacologia 13, 332–340 (1968).CrossRefGoogle Scholar
  19. 19.
    Tonkelaar, E.M.den, Klap-van Dijk, A., Wit, S.L.: Determination of rat liver hexobarbital oxidase activity with a gaschromatographic method. Biochem.Pharmacol. 18, 262–265 (1969).CrossRefGoogle Scholar
  20. 20.
    Tonkelaar, E.M.den, Kroes, R.: Onderzoek naar de subacute toxiciteit van tetrachloorkoolstof en dimethylnotrosamine met behulp van leverfunctieproeven. Berichten uit het Rijks Instituut voor de Volksgezondheid 33, 231–235 (1971).Google Scholar
  21. 21.
    Wall, M.E., Brine, D.R., Brine, G.A., Pitt, G.G., Freudenthal, R.I., Christensen, H.D.: Isolation, structure and biological activity of several metabolites of Δ9-tetrahydrocannabinol. J.Am. Soc. 92, 3466–3468 (1970).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1973

Authors and Affiliations

  • M. ten Ham
    • 1
  • Engelina M. den Tonkelaar
    • 1
  • J. M. Koomen
    • 1
  1. 1.National Institute of Public HealthBilthovenThe Netherlands

Personalised recommendations