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Marihuana and Medicine pp 91–103Cite as

Absorption, Distribution, and Biotransformation of the Cannabinoids

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Abstract

This paper describes the occurrence, properties, distribution, metabolism, and excretion of the cannabinoids. Over 60 of these compounds have been identified in the plant Cannabis sativa, the major ones being the pharmacologically active Δ9-tetrahydrocannabinol (Δ9-THC), its biosynthetic precursor, cannabidiol (CBD), and the degradation product, cannabinol (CBN). Once absorbed, usually by smoking, these lipophilic compounds partition into the fatty tissues of the body where they can remain for a considerable time. The half-life of the drug is measured in days or even weeks. Various estimates of the half-life in humans are discussed in the paper.

All cannabinoids are good substrates for the cytochrome P450 mixed function oxidases. Biotransformation of Δ9-THC and its synthetic isomer, Δ8-THC, give mono-, di-, and tri-hydroxy metabolites and further oxidation leads to a series of acids, carbonyl compounds, and their hydroxy derivatives. Primary sites of hydroxylation in both isomers are the side-chain and the allylic carbon atoms of the alicyclic ring leading to Δ9-THC-11-oic acid as the major human metabolite from Δ9-THC. Lower homologues yield greater proportions of acidic metabolites, whereas higher homologs are metabolized mainly to hydroxy compounds. β-Oxidation and related oxidations of the aliphatic chain lead to a series of chain-shortened metabolites, most of which are additionally hydroxylated in the alicyclic ring or at C-11. Large species-related differences in bio-transformation are seen, particularly in the sites of initial hydroxylation. Several of the monohydroxy metabolites, particularly the 11- and 3’-hydroxy THCs show comparable pharmacological activity to that of the parent drug whereas polysubstituted metabolites are inactive. Phase II metabolism is mainly by conjugation with glucuronic acid.

Other cannabinoids are metabolised similarly. CBD yields additional metabolites as the result of hydroxylation and epoxidation of the iso-propene group but CBN yields fewer metabolites as the aromatic rings do not appear to be hydroxylated. Cannabichromene and cannabigerol again show extensive, species-related hydroxylation of their alkyl chains.

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  1. David J. Harvey
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Editors and Affiliations

  1. Department of Anesthesiology, New York University School of Medicine, USA

    Gabriel G. Nahas MD, PhD, DSc  & Kenneth M. Sutin MD, MS  & 

  2. Department of Biochemistry, Oxford University, USA

    David Harvey PhD

  3. Faculty of Pharmacy, University of Uppsala, Sweden

    Stig Agurell PhD, PharmD, DSc

  4. NYU School of Medicine, USA

    Nicholas Pace MD  & Robert Cancro MD  & 

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Harvey, D.J. (1999). Absorption, Distribution, and Biotransformation of the Cannabinoids. In: Nahas, G.G., Sutin, K.M., Harvey, D., Agurell, S., Pace, N., Cancro, R. (eds) Marihuana and Medicine. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-710-9_10

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  • DOI: https://doi.org/10.1007/978-1-59259-710-9_10

  • Publisher Name: Humana Press, Totowa, NJ

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