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In vivo metabolism of the methyl homologues of delta-8-tetrahydrocannabinol, delta-9-tetrahydrocannabinol and abn-delta-8-tetrahydrocannabinol in the mouse.
Biomed Environ Mass Spectrom. 1988 Apr 01; 15(7):389-98.BE

Abstract

Methyl-delta-8-tetrahydrocannabinol (methyl-delta-8-THC), methyl-delta-9-THC and abn-methyl-delta-8-THC were synthesized by condensation of orcinol and (1S)-cis-verbenol and were administered to male Charles River CD-1 mice. Extracted hepatic metabolites were isolated by chromatography on Sephadex LH-20 and examined by gas chromatography/mass spectrometry as trimethylsilyl (TMS), (2H9)TMS and methyl ester/TMS derivatives. In addition, metabolic fractions were reduced with lithium aluminium deuteride to convert carboxylic acids to alcohols for structural correlation. Metabolites from methyl-delta-8-THC were similar with respect to the positions substituted to those produced by higher homologues; the major metabolite was methyl-delta-8-THC-11-oic acid. abn-Methyl-delta-8-THC was metabolized in a different manner. The location of the aromatic methyl group at the position adjacent to ring fusion appeared to inhibit metabolism at C(11) to a considerable extent and also to reduce the amount of the resulting alcohol from being oxidized to a carboxylic acid. This caused other metabolic pathways to become dominant, with the result that a compound containing a hydroxy group at the gem-methyl position was the major metabolite. Hydroxylation at this position has not been confirmed with any other cannabinoid, although it is thought to result in trace concentrations of hydroxy metabolites from some compounds. Metabolism of methyl-delta-9-THC was also similar to that of the higher homologues, with the exception that less metabolism occurred at C(8) and a higher percentage of the total metabolic fraction was accounted for by the 11-oic acid metabolite. Minor metabolites were mainly dihydroxy compounds and hydroxylated derivatives of delta-9-THC-11-oic acid.

Authors+Show Affiliations

University Department of Pharmacology, Oxford, UK.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

2839260

Citation

Brown, N K., and D J. Harvey. "In Vivo Metabolism of the Methyl Homologues of Delta-8-tetrahydrocannabinol, Delta-9-tetrahydrocannabinol and Abn-delta-8-tetrahydrocannabinol in the Mouse." Biomedical & Environmental Mass Spectrometry, vol. 15, no. 7, 1988, pp. 389-98.
Brown NK, Harvey DJ. In vivo metabolism of the methyl homologues of delta-8-tetrahydrocannabinol, delta-9-tetrahydrocannabinol and abn-delta-8-tetrahydrocannabinol in the mouse. Biomed Environ Mass Spectrom. 1988;15(7):389-98.
Brown, N. K., & Harvey, D. J. (1988). In vivo metabolism of the methyl homologues of delta-8-tetrahydrocannabinol, delta-9-tetrahydrocannabinol and abn-delta-8-tetrahydrocannabinol in the mouse. Biomedical & Environmental Mass Spectrometry, 15(7), 389-98.
Brown NK, Harvey DJ. In Vivo Metabolism of the Methyl Homologues of Delta-8-tetrahydrocannabinol, Delta-9-tetrahydrocannabinol and Abn-delta-8-tetrahydrocannabinol in the Mouse. Biomed Environ Mass Spectrom. 1988 Apr 1;15(7):389-98. PubMed PMID: 2839260.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vivo metabolism of the methyl homologues of delta-8-tetrahydrocannabinol, delta-9-tetrahydrocannabinol and abn-delta-8-tetrahydrocannabinol in the mouse. AU - Brown,N K, AU - Harvey,D J, PY - 1988/4/1/pubmed PY - 1988/4/1/medline PY - 1988/4/1/entrez SP - 389 EP - 98 JF - Biomedical & environmental mass spectrometry JO - Biomed Environ Mass Spectrom VL - 15 IS - 7 N2 - Methyl-delta-8-tetrahydrocannabinol (methyl-delta-8-THC), methyl-delta-9-THC and abn-methyl-delta-8-THC were synthesized by condensation of orcinol and (1S)-cis-verbenol and were administered to male Charles River CD-1 mice. Extracted hepatic metabolites were isolated by chromatography on Sephadex LH-20 and examined by gas chromatography/mass spectrometry as trimethylsilyl (TMS), (2H9)TMS and methyl ester/TMS derivatives. In addition, metabolic fractions were reduced with lithium aluminium deuteride to convert carboxylic acids to alcohols for structural correlation. Metabolites from methyl-delta-8-THC were similar with respect to the positions substituted to those produced by higher homologues; the major metabolite was methyl-delta-8-THC-11-oic acid. abn-Methyl-delta-8-THC was metabolized in a different manner. The location of the aromatic methyl group at the position adjacent to ring fusion appeared to inhibit metabolism at C(11) to a considerable extent and also to reduce the amount of the resulting alcohol from being oxidized to a carboxylic acid. This caused other metabolic pathways to become dominant, with the result that a compound containing a hydroxy group at the gem-methyl position was the major metabolite. Hydroxylation at this position has not been confirmed with any other cannabinoid, although it is thought to result in trace concentrations of hydroxy metabolites from some compounds. Metabolism of methyl-delta-9-THC was also similar to that of the higher homologues, with the exception that less metabolism occurred at C(8) and a higher percentage of the total metabolic fraction was accounted for by the 11-oic acid metabolite. Minor metabolites were mainly dihydroxy compounds and hydroxylated derivatives of delta-9-THC-11-oic acid. SN - 0887-6134 UR - https://www.unboundmedicine.com/medline/citation/2839260/In_vivo_metabolism_of_the_methyl_homologues_of_delta_8_tetrahydrocannabinol_delta_9_tetrahydrocannabinol_and_abn_delta_8_tetrahydrocannabinol_in_the_mouse_ L2 - https://antibodies.cancer.gov/detail/CPTC-GMNN-1 DB - PRIME DP - Unbound Medicine ER -