Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and 11-Hydroxy-THC: Difference between pages

{{Short description|Active metabolite of Δ9-THC}}

{{For|the isomer of this chemical inherited from [[Delta-8-tetrahydrocannabinol|Δ⁸-tetrahydrocannabinol]]|11-Hydroxy-Delta-8-THC}}

{{Infobox drug

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 477208799

| image2 = 11-Hydroxy-THC-3D-balls.png

| alt2 = 11-Hydroxy-THC molecule

| legal_UK = Class B

| routes_of_administration =

| excretion =

| CAS_number_Ref = {{cascite|changed|??}}

| CAS_number = 36557-05-8

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 9VY04N5SLB

| KEGG = C22778

| class = [[Cannabinoid]]

'''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.<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>

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 [[dehydrogenase]] {{which|date=April 2024}} and [[CYP2C9]] enzymes to form [[11-nor-9-carboxy-THC]] (THC-COOH) which is inactive at the CB₁ receptors;<ref name=Huestis2005/> and further [[Glucuronidation|glucuronidated]] to form 11-nor-Δ⁹-tetrahydrocannabinol-9-carboxylic acid glucuronide (Δ⁹-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 drug tests.<ref name=Kraemer2007/>

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.<ref name="Huestis_1992">{{cite journal | vauthors = Huestis MA, Henningfield JE, Cone EJ | title = Blood cannabinoids. I. Absorption of THC and formation of 11-OH-THC and THCCOOH during and after smoking marijuana | journal = Journal of Analytical Toxicology | volume = 16 | issue = 5 | pages = 276–282 | date = 1992 | pmid = 1338215 | doi = 10.1093/jat/16.5.276 }}</ref><ref name="Karschner_2009">{{cite journal | vauthors = Karschner EL, Schwilke EW, Lowe RH, Darwin WD, Herning RI, Cadet JL, Huestis MA | title = Implications of plasma Delta9-tetrahydrocannabinol, 11-hydroxy-THC, and 11-nor-9-carboxy-THC concentrations in chronic cannabis smokers | journal = Journal of Analytical Toxicology | volume = 33 | issue = 8 | pages = 469–477 | date = October 2009 | pmid = 19874654 | pmc = 3159863 | doi = 10.1093/jat/33.8.469 }}</ref>

== Pharmacology ==

Like Δ⁹-THC, 11-hydroxy-THC is a partial agonist at the [[cannabinoid receptor]] [[Cannabinoid receptor type 1|CB₁]], but with significantly higher [[Ligand (biochemistry)#Receptor/ligand binding affinity|binding affinity]] (K_i = 0.37&nbsp;nM compared to Δ⁹-THC K_i = 35&nbsp;nM).<ref name="Zagzoog2022">{{cite journal | vauthors = Zagzoog A, Cabecinha A, Abramovici H, Laprairie RB | title = Modulation of type 1 cannabinoid receptor activity by cannabinoid by-products from ''Cannabis sativa'' and non-cannabis phytomolecules | journal = Frontiers in Pharmacology | volume = 13 | pages = 956030 | date = 26 August 2022 | pmid = 36091813 | doi = 10.3389/fphar.2022.956030 | pmc = 9458935 | doi-access = free }}</ref> With respect to [[Cyclic adenosine monophosphate|cAMP]] inhibition at CB₁ it displays a similar efficacy to that of Δ⁹-THC (EC₅₀ = 11&nbsp;nM vs. EC₅₀ = 5.2&nbsp;nM, respectively), but a lower maximum response (E_max = 28% vs. E_max = 70%).<ref name="Zagzoog2022" />

== 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).<ref>{{cite journal | vauthors = Liu C, Puopolo T, Li H, Cai A, Seeram NP, Ma H | title = 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 | journal = Molecules | volume = 27 | issue = 18 | page = 6127 | date = September 2022 | pmid = 36144858 | pmc = 9502466 | doi = 10.3390/molecules27186127 | doi-access = free }}</ref>

== 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 ==

{{reflist}}

{{Cannabinoids}}

{{Cannabinoidergics}}

{{DEFAULTSORT:Hydroxy-THC, 11-}}

[[Category:Cannabinoids]]

[[Category:Benzochromenes]]

[[Category:Primary alcohols]]

[[Category:Phenols]]

[[Category:Diols]]

[[Category:Recreational drug metabolites]]