11-Hydroxy-THC

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]

For the isomer of this chemical inherited from Δ8-tetrahydrocannabinol, see 11-Hydroxy-Delta-8-THC.
11-Hydroxy-THC
11-Hydroxy-THC molecule
Clinical data
Drug classCannabinoid
Legal status
Legal status
Identifiers
  • (6aR,10aR)-9-(Hydroxymethyl)-6,6-dimethyl-3-pentyl- 6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-ol
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
ECHA InfoCard100.164.583
Chemical and physical data
FormulaC21H30O3
Molar mass330.468 g·mol−1
3D model (JSmol)
  • Oc2cc(cc1OC(C3CC/C(=C\C3c12)CO)(C)C)CCCCC
  • InChI=1S/C21H30O3/c1-4-5-6-7-14-11-18(23)20-16-10-15(13-22)8-9-17(16)21(2,3)24-19(20)12-14/h10-12,16-17,22-23H,4-9,13H2,1-3H3 checkY
  • Key:YCBKSSAWEUDACY-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

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 the dehydrogenase and CYP2C9 enzyme 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] where it is excreted in both feces and urine.[4] Both compounds, 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

Like Δ9-THC, 11-hydroxy-THC is a partial agonist at the cannabinoid receptor CB1 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

In 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% 11-OH-Δ9-THC vs 100% GC376).[8]

See also

References
  1. 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.
  2. 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.
  3. 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.
  4. Grotenhermen F (2003). "Pharmacokinetics and pharmacodynamics of cannabinoids". Clinical Pharmacokinetics. 42 (4): 327–360. doi:10.2165/00003088-200342040-00003. PMID 12648025. S2CID 25623600.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
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