Abstract
The distribution of Δ1-tetrahydrocannabinol (Δ1-THC, I) in tissues has been widely studied by radiochemical methods, and substantial accumulations have been found in certain organs, notably liver, lung, spleen, kidney, and adrenal gland [1,18,19]. Nevertheless, comparatively little is known about the nature of the accumulated material, although it is apparent that both Δ1-THC and various metabolites are present. Differences in the relative concentrations of the metabolites in tissues, particularly lung and liver, have been recognized [16], suggesting biotransformation of Δ1-THC at several sites. Several of the reported hydroxylated metabolites, in particular 7-OH-Δ1-THC (II), possess pharmacological activity [9,11], and one metabolite, 1,2-epoxide (VII) [3,12], is potentially chemically active [10]. The structures of a number of metabolites are still unknown and could contribute to the overall activity of the drug (Table 9.1) [13].
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Agurell, S., J. Dahmén, B. Gustafsson, V.-B. Johansson, K. Leander, I. Nilsson, J. L. G. Nilsson, M. Nordqvist, C. H. Ramsay, A. Ryrfeldt, F. Sandberg, M. Widman (1972) Metabolic fate of tetrahydrocannabinol. Cannabis and Its Derivatives: Pharmacology and Experimental Psychology (W. D. M. Paton and J. Crown, eds.). London: Oxford University Press, pp. 16–36.
Ben-Zvi, Z. and S. Burstein (1974) 7-Oxo-Δ1-tetrahydrocannabinol: a novel metabolite of Δ1-tetrahydrocannabinol. Res. Commun. Chem. Pathol. Pharmacol.8:223.
Ben-Zvi, Z. and S. Burstein (1975) Transformation of Δ1-tetra-hydrocannabinol (THC) by rabbit liver microsomes. Biochem. Pharmacol.24:1130.
Biller, J. E. and K. Biemann (1974) Reconstructed mass spectra, a novel approach for the utilization of gas chromatograph-mass spectrometer data. Anal. Lett.7:515.
Binder, M., S. Agurell, K. Leander, and J.-E. Lindgren (1974) Zur identification potentieller metabolite von cannabis-inhaltstoffen: kernresonanz- und massenspektroskopische Untersuchungen an seiten-kettenhydroxylierten cannabinoiden. Helv. Chim. Acta57:1626.
Burstein, S. H. (1973) Labeling and metabolism of the tetrahydrocannabinols. Marijuana: Chemistry, Pharmacology, Metabolism and Clinical Effects (R. Mechoulam, ed.). New York: Academic Press, pp. 167–190.
Burstein, S. H., J. Martinez, J. Rosenfeld, and T. Wittstruck (1972) The urinary metabolites of Δ1-THC. Cannabis and Its Derivatives (W. D. M. Paton and J. Crown, eds.). London: Oxford University Press, pp. 39–49.
Burstein, S. H., J. Rosenfeld, and T. Wittstruck (1972) Isolation and characterization of two major urinary metabolites of delta (1)-tetrahydrocannabinol. Science176:422.
Christensen, H. D., R. I. Freudenthal, J. T. Gidley, R. Rosenfeld, G. Boegli, L. Testino, D. R. Brine, C. G. Pitt, and M. E. Wall (1971) Activity of Δ8- and Δ9-tetrahydrocannabinol and related compounds in the mouse. Science172:165.
Daly, J. W., D. M. Jerina, and B. Witkop (1972) Arene oxides and the NIH shift: the metabolism, toxicity and carcinogenicity of aromatic compounds. Experientia28:1129.
Gill, E. W., G. Jones, and D. K. Lawrence (1973) Contribution of the metabolite 7-hydroxy-Δ1-tetrahydrocannabinol towards the pharmacological activity of Δ1-tetrahydrocannabinol in mice. Biochem. Pharmacol.22:175.
Gurny, O., D. E. Maynard, R. G. Pitcher, and R. W. Kierstead (1972) Metabolism of (-)-Δ9 and (-)-Δ8-tetrahydrocannabinol by monkey liver. J. Am. Chem. Soc.94:7928.
Jones, G., M. Widman, S. Agurell, and J.-E. Lindgren (1974) Monohydroxylated metabolites of Δ1-tetrahydrocannabinol in mouse brain. Acta Pharm. Suec.11:283.
Maynard, D. E., O. Gurny, R. G. Pitcher, and R. W. Kierstead (1971) (-)-Δ8-Tetrahydrocannabinol. Two novel in vitro metabolites. Experientia27:1154.
McCloskey, J. A., R. N. Stillwell, and A. M. Lawson (1968) Use of deuterium-labeled trimethylsilyl derivatives in mass spectrometry. Anal. Chem.40:233.
Nakazawa, K. and E. Costa (1971) Metabolism of Δ9-tetrahydro-cannabinol by lung and liver homogenates of rats treated with methylcholanthrene. Nature234:48.
Nordqvist, M., S. Agurell, M. Binder, and I. M. Nilsson (1974) Structure of an acidic metabolite of Δ1-tetrahydrocannabinol isolated from rabbit urine. J. Pharm. Pharmacol.26:471.
Ryrfeldt, Å., C H. Ramsay, I. M. Nilsson, M. Widman, and S. Agurell (1973) Whole-body autoradiography of Δ1-tetrahydrocannabinol and Δ1(6)-tetrahydrocannabinol in mouse. Pharmacokinetic aspects of Δ1-tetrahydrocannabinol and its metabolites. Acta Pharm. Suec.10:13.
Truitt, E. B., Jr. and M. Braude (1974) Research Advances in Alcohol and Drug Problems (R. J. Gibbins, Y. Israel, H. Kalant, R. E. Popham, W. Schmidt, and R. G. Smart, eds.), vol. 1. New York: Wiley, p. 199.
Wall, M. E. (1971) The in vitro and in vivo metabolism of tetrahydrocannabinol (THC). Ann. N.Y. Acad. Sci.191:23.
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Harvey, D.J., Paton, W.D.M. (1976). Examination of the Metabolites of Δ1-Tetrahydrocannabinol in Mouse Liver, Heart, and Lung by Combined Gas Chromatography and Mass Spectrometry. In: Nahas, G.G., Paton, W.D.M., Idänpään-Heikkilä, J.E. (eds) Marihuana. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-51624-5_9
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