11-Hydroxy-THC

For the isomer of this chemical inherited from Δ⁸-tetrahydrocannabinol, see 11-Hydroxy-Delta-8-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]

11-Hydroxy-THC

Clinical data
Drug class	Cannabinoid
Legal status
Legal status	UK: Class B
Identifiers
IUPAC name (6aR,10aR)-9-(Hydroxymethyl)-6,6-dimethyl-3-pentyl- 6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-ol
CAS Number	36557-05-8 N
PubChem CID	37482
ChemSpider	34385 Y
UNII	9VY04N5SLB
KEGG	C22778
CompTox Dashboard (EPA)	DTXSID50190061
ECHA InfoCard	100.164.583
Chemical and physical data
Formula	C21H30O3
Molar mass	330.468 g·mol−1
3D model (JSmol)	Interactive image
SMILES Oc2cc(cc1OC(C3CC/C(=C\C3c12)CO)(C)C)CCCCC
InChI 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 Y Key:YCBKSSAWEUDACY-UHFFFAOYSA-N Y
NY (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 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

Like Δ⁹-THC, 11-hydroxy-THC is a partial agonist at the cannabinoid receptor CB₁, but with significantly higher binding affinity (K_i = 0.37 nM compared to Δ⁹-THC K_i = 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 (E_max = 28% vs. E_max = 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% for 11-OH-Δ⁹-THC vs. 100% for GC376).^[8]

See also

• 11-Hydroxy-Delta-8-THC
• 11-Hydroxyhexahydrocannabinol
• 3'-Hydroxy-THC
• 7-Hydroxycannabidiol
• 8,11-Dihydroxytetrahydrocannabinol
• 11-OH-CBN
• Cannabis edible
• Delta-11-Tetrahydrocannabinol

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.