11-Hydroxy-Δ9-tetrahydrocannabinol (11-OH-Δ9-THC, alternatively numbered as 7-OH-Δ1-THC), usually referred to as 11-hydroxy-THC is the main active metabolite of tetrahydrocannabinol (THC), which is formed in the body after Δ9-THC is consumed.[1][2]
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| Drug class | Cannabinoid |
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| ECHA InfoCard | 100.164.583 |
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| Formula | C21H30O3 |
| Molar mass | 330.468 g·mol−1 |
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After cannabis consumption, THC is metabolized inside the body by cytochrome P450 enzymes such as CYP2C9 and CYP3A4 into 11-hydroxy-THC and then further metabolized by dehydrogenase [which?] and CYP2C9 enzymes to form 11-nor-9-carboxy-THC (THC-COOH) which is inactive at the CB1 receptors;[2] and further glucuronidated to form 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid glucuronide (Δ9-THC-COOH-glu)[3] in the liver, from where it is subsequently excreted through feces and urine (via bile from the liver).[4] Both metabolites, along with THC, can be assayed in drug tests.[1]
11-hydroxy-THC can be formed after consumption of THC from inhalation (vaping, smoking) and oral (by mouth, edible, sublingual) use, although levels of 11-hydroxy-THC are typically higher when eaten compared to inhalation.[5][6]
Pharmacology
editLike Δ9-THC, 11-hydroxy-THC is a partial agonist at the cannabinoid receptor CB1, but with significantly higher binding affinity (Ki = 0.37 nM compared to Δ9-THC Ki = 35 nM).[7] With respect to cAMP inhibition at CB1 it displays a similar efficacy to that of Δ9-THC (EC50 = 11 nM vs. EC50 = 5.2 nM, respectively), but a lower maximum response (Emax = 28% vs. Emax = 70%).[7]
Research
editIn an in vitro analysis by the University of Rhode Island on cannabinoids it was found that 11-OH-Δ9-THC had the 3rd highest 3C-like protease inhibitor activity against COVID-19 out of all the cannabinoids tested within that study but not as high as the antiviral drug GC376 (56% for 11-OH-Δ9-THC vs. 100% for GC376).[8]
See also
editReferences
edit- ^ a b Kraemer T, Paul LD (August 2007). "Bioanalytical procedures for determination of drugs of abuse in blood". Analytical and Bioanalytical Chemistry. 388 (7): 1415–1435. doi:10.1007/s00216-007-1271-6. PMID 17468860. S2CID 32917584.1415-1435&rft.date=2007-08&rft_id=https://api.semanticscholar.org/CorpusID:32917584#id-name=S2CID&rft_id=info:pmid/17468860&rft_id=info:doi/10.1007/s00216-007-1271-6&rft.aulast=Kraemer&rft.aufirst=T&rft.au=Paul, LD&rfr_id=info:sid/en.wikipedia.org:11-Hydroxy-THC" class="Z3988">
- ^ a b Huestis MA (2005). "Pharmacokinetics and metabolism of the plant cannabinoids, delta9-tetrahydrocannabinol, cannabidiol and cannabinol". Cannabinoids. Handbook of Experimental Pharmacology. Vol. 168. pp. 657–690. doi:10.1007/3-540-26573-2_23. ISBN 3-540-22565-X. PMID 16596792.657-690&rft.date=2005&rft_id=info:pmid/16596792&rft_id=info:doi/10.1007/3-540-26573-2_23&rft.isbn=3-540-22565-X&rft.aulast=Huestis&rft.aufirst=MA&rfr_id=info:sid/en.wikipedia.org:11-Hydroxy-THC" class="Z3988">
- ^ Stout SM, Cimino NM (February 2014). "Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review". Drug Metabolism Reviews. 46 (1): 86–95. doi:10.3109/03602532.2013.849268. PMID 24160757. S2CID 29133059.86-95&rft.date=2014-02&rft_id=https://api.semanticscholar.org/CorpusID:29133059#id-name=S2CID&rft_id=info:pmid/24160757&rft_id=info:doi/10.3109/03602532.2013.849268&rft.aulast=Stout&rft.aufirst=SM&rft.au=Cimino, NM&rft_id=https://zenodo.org/record/1093138&rfr_id=info:sid/en.wikipedia.org:11-Hydroxy-THC" class="Z3988">
- ^ Grotenhermen F (2003). "Pharmacokinetics and pharmacodynamics of cannabinoids". Clinical Pharmacokinetics. 42 (4): 327–360. doi:10.2165/00003088-200342040-00003. PMID 12648025. S2CID 25623600.327-360&rft.date=2003&rft_id=https://api.semanticscholar.org/CorpusID:25623600#id-name=S2CID&rft_id=info:pmid/12648025&rft_id=info:doi/10.2165/00003088-200342040-00003&rft.aulast=Grotenhermen&rft.aufirst=F&rfr_id=info:sid/en.wikipedia.org:11-Hydroxy-THC" class="Z3988">
- ^ Huestis MA, Henningfield JE, Cone EJ (1992). "Blood cannabinoids. I. Absorption of THC and formation of 11-OH-THC and THCCOOH during and after smoking marijuana". Journal of Analytical Toxicology. 16 (5): 276–282. doi:10.1093/jat/16.5.276. PMID 1338215.276-282&rft.date=1992&rft_id=info:doi/10.1093/jat/16.5.276&rft_id=info:pmid/1338215&rft.aulast=Huestis&rft.aufirst=MA&rft.au=Henningfield, JE&rft.au=Cone, EJ&rfr_id=info:sid/en.wikipedia.org:11-Hydroxy-THC" class="Z3988">
- ^ Karschner EL, Schwilke EW, Lowe RH, Darwin WD, Herning RI, Cadet JL, Huestis MA (October 2009). "Implications of plasma Delta9-tetrahydrocannabinol, 11-hydroxy-THC, and 11-nor-9-carboxy-THC concentrations in chronic cannabis smokers". Journal of Analytical Toxicology. 33 (8): 469–477. doi:10.1093/jat/33.8.469. PMC 3159863. PMID 19874654.469-477&rft.date=2009-10&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3159863#id-name=PMC&rft_id=info:pmid/19874654&rft_id=info:doi/10.1093/jat/33.8.469&rft.aulast=Karschner&rft.aufirst=EL&rft.au=Schwilke, EW&rft.au=Lowe, RH&rft.au=Darwin, WD&rft.au=Herning, RI&rft.au=Cadet, JL&rft.au=Huestis, MA&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3159863&rfr_id=info:sid/en.wikipedia.org:11-Hydroxy-THC" class="Z3988">
- ^ a b Zagzoog A, Cabecinha A, Abramovici H, Laprairie RB (26 August 2022). "Modulation of type 1 cannabinoid receptor activity by cannabinoid by-products from Cannabis sativa and non-cannabis phytomolecules". Frontiers in Pharmacology. 13: 956030. doi:10.3389/fphar.2022.956030. PMC 9458935. PMID 36091813.
- ^ Liu C, Puopolo T, Li H, Cai A, Seeram NP, Ma H (September 2022). "Identification of SARS-CoV-2 Main Protease Inhibitors from a Library of Minor Cannabinoids by Biochemical Inhibition Assay and Surface Plasmon Resonance Characterized Binding Affinity". Molecules. 27 (18): 6127. doi:10.3390/molecules27186127. PMC 9502466. PMID 36144858.