11-Hydroxy-THC: Difference between revisions
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'''11-Hydroxy-Δ<sup>9</sup>-tetrahydrocannabinol''' ('''11-OH-Δ<sup>9</sup>-THC''', alternatively numbered as '''7-OH-Δ<sup>1</sup>-THC'''), usually referred to in [[cannabis culture]] as '''11-hydroxy-THC''' is the main active [[metabolite]] of [[tetrahydrocannabinol]] (THC), which is formed in the body after |
'''11-Hydroxy-Δ<sup>9</sup>-tetrahydrocannabinol''' ('''11-OH-Δ<sup>9</sup>-THC''', alternatively numbered as '''7-OH-Δ<sup>1</sup>-THC'''), usually referred to in [[cannabis culture]] as '''11-hydroxy-THC''' is the main active [[metabolite]] of [[tetrahydrocannabinol]] (THC), which is formed in the body after cannabis is consumed.<ref name=Kraemer2007>{{cite journal | vauthors = Kraemer T, Paul LD | title = Bioanalytical procedures for determination of drugs of abuse in blood | journal = Analytical and Bioanalytical Chemistry | volume = 388 | issue = 7 | pages = 1415–1435 | date = August 2007 | pmid = 17468860 | doi = 10.1007/s00216-007-1271-6 | s2cid = 32917584 }}</ref><ref name=Huestis2005>{{cite book | vauthors = Huestis MA | title = Cannabinoids | chapter = Pharmacokinetics and metabolism of the plant cannabinoids, delta9-tetrahydrocannabinol, cannabidiol and cannabinol | series = Handbook of Experimental Pharmacology | volume = 168 | pages = 657–690 | date = 2005 | issue = <!-- none --> | pmid = 16596792 | doi = 10.1007/3-540-26573-2_23 | isbn = 3-540-22565-X }}</ref> |
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After [[cannabis consumption]], THC is [[hydroxylation|metabolized]] inside the body by [[cytochrome P450]] enzymes such as [[CYP2C9]] and [[CYP3A4]] into 11-hydroxy-THC and then further metabolized by cytochrome enzymes to form [[11-nor-9-carboxy-THC]] which is inactive at the CB<sub>1</sub> receptors;<ref name=Huestis2005/> and further [[Glucuronidation|glucuronidated]] to form 11-nor-Δ<sup>9</sup>-tetrahydrocannabinol-9-carboxylic acid glucuronide (Δ<sup>9</sup>-THC-COOH-glu)<ref name="Stout_2014">{{cite journal | vauthors = Stout SM, Cimino NM | title = Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review | journal = Drug Metabolism Reviews | volume = 46 | issue = 1 | pages = 86–95 | date = February 2014 | pmid = 24160757 | doi = 10.3109/03602532.2013.849268 | s2cid = 29133059 | url = https://zenodo.org/record/1093138 }}</ref> in the liver, from where it is subsequently excreted through feces and urine (via [[bile]] from the liver).<ref name="Grotenhermen_2003">{{cite journal | vauthors = Grotenhermen F | title = Pharmacokinetics and pharmacodynamics of cannabinoids | journal = Clinical Pharmacokinetics | volume = 42 | issue = 4 | pages = 327–360 | date = 2003 | pmid = 12648025 | doi = 10.2165/00003088-200342040-00003 | s2cid = 25623600 }}</ref> Both metabolites, along with THC, can be assayed in blood drug tests.<ref name=Kraemer2007/> |
After [[cannabis consumption]], THC is [[hydroxylation|metabolized]] inside the body by [[cytochrome P450]] enzymes such as [[CYP2C9]] and [[CYP3A4]] into 11-hydroxy-THC and then further metabolized by cytochrome enzymes to form [[11-nor-9-carboxy-THC]] which is inactive at the CB<sub>1</sub> receptors;<ref name=Huestis2005/> and further [[Glucuronidation|glucuronidated]] to form 11-nor-Δ<sup>9</sup>-tetrahydrocannabinol-9-carboxylic acid glucuronide (Δ<sup>9</sup>-THC-COOH-glu)<ref name="Stout_2014">{{cite journal | vauthors = Stout SM, Cimino NM | title = Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review | journal = Drug Metabolism Reviews | volume = 46 | issue = 1 | pages = 86–95 | date = February 2014 | pmid = 24160757 | doi = 10.3109/03602532.2013.849268 | s2cid = 29133059 | url = https://zenodo.org/record/1093138 }}</ref> in the liver, from where it is subsequently excreted through feces and urine (via [[bile]] from the liver).<ref name="Grotenhermen_2003">{{cite journal | vauthors = Grotenhermen F | title = Pharmacokinetics and pharmacodynamics of cannabinoids | journal = Clinical Pharmacokinetics | volume = 42 | issue = 4 | pages = 327–360 | date = 2003 | pmid = 12648025 | doi = 10.2165/00003088-200342040-00003 | s2cid = 25623600 }}</ref> Both metabolites, along with THC, can be assayed in blood drug tests.<ref name=Kraemer2007/> |
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Revision as of 02:48, 13 April 2024
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| Clinical data | |
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| Drug class | Cannabinoid |
| Legal status | |
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| CAS Number | |
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| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.164.583 |
| Chemical and physical data | |
| Formula | C21H30O3 |
| Molar mass | 330.468 g·mol−1 |
| 3D model (JSmol) | |
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11-Hydroxy-Δ9-tetrahydrocannabinol (11-OH-Δ9-THC, alternatively numbered as 7-OH-Δ1-THC), usually referred to in cannabis culture as 11-hydroxy-THC is the main active metabolite of tetrahydrocannabinol (THC), which is formed in the body after cannabis is consumed.[1][2]
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 cytochrome enzymes to form 11-nor-9-carboxy-THC 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 blood drug tests.[1]
11-hydroxy-THC can be formed after consumption of cannabis from inhalation (vaping and smoking) and oral (swallowed or sublingual) use, although levels of 11-hydroxy-THC are typically higher when oral forms of the plant are used.[5][6]
Pharmacology
Like 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
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 known 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
- ^ 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.
- ^ 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.
- ^ 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.
- ^ Grotenhermen F (2003). "Pharmacokinetics and pharmacodynamics of cannabinoids". Clinical Pharmacokinetics. 42 (4): 327–360. doi:10.2165/00003088-200342040-00003. PMID 12648025. S2CID 25623600.
- ^ 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.
- ^ 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.
- ^ 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.