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]
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 receptorCB1, 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]
^
abKraemer 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.
PMID17468860.
S2CID32917584.
^
abHuestis 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.
ISBN3-540-22565-X.
PMID16596792.
^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.
PMID1338215.