11-Hydroxyhexahydrocannabinol (11-OH-9α-HHC and 11-OH-9β-HHC, or alternatively 7-OH-HHC under the monoterpenoid numbering system) is an active metabolite of
tetrahydrocannabinol (THC) and a metabolite of the trace cannabinoid
hexahydrocannabinol (HHC).[1][2][3]
In a pathway that parallels the metabolism of the THC family of cannabinoids, following ingestion HHC undergoes hepatic metabolism by
cytochrome p450 (predominantly the
CYP3A4 isozyme, with some contribution from
CYP2C9 and
CYP2C19) to a multitude of oxygenated derivatives, including
8-OH-HHC and 11-OH-HHC. C11-oxidation is the major pathway of THC and HHC metabolism.[4]
Like other 11-OH cannabinoid metabolites, 11-OH-9β-HHC retains activity comparable to HHC itself while the 9α-isomer is significantly less active.[5] However, upon formation it is rapidly metabolized further to the inactive 11-carboxylates, producing a shortened half-life within the body and lowering its bioavailability considerably through first-pass metabolism.[6][7]
The 11-OH-9β-HHC isomer is the structurally related methylene homologue of 11-Nor-9β-hydroxyhexahydrocannabinol also known as
9-Nor-9β-hydroxyhexahydrocannabinol.[8][9]
HU-243 is a synthetic analog of 11-OH-9β-HHC in which the natural n-pentyl side chain is replaced with a geminal-dimethylheptyl substitution. This significantly increases HU-243s binding affinity for the
CB1 and
CB2 receptors.[10]
^Järbe TU, Hiltunen AJ, Lander N, Mechoulam R (August 1986). "Cannabimimetic activity (delta 1-THC cue) of cannabidiol monomethyl ether and two stereoisomeric hexahydrocannabinols in rats and pigeons". Pharmacology, Biochemistry, and Behavior. 25 (2): 393–399.
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10.1016/0091-3057(86)90015-8.
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^Harvey DJ, Martin BR, Paton WD (1978). "Comparative in vivo Metabolism of Δ1-tetrahydrocannabinol (Δ1-THC), cannabidiol (CBD) and cannabinol (CBN) by Several Species". In Frigerio A (ed.). Recent Developments in Mass Spectrometry in Biochemistry and Medicine. Boston, MA: Springer US. pp. 161–184.
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10.1007/978-1-4613-3991-5_13.
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^Lewis J, Molnar A, Allsop D, Copeland J, Fu S (January 2016). "Rapid elimination of Carboxy-THC in a cohort of chronic cannabis users". International Journal of Legal Medicine. 130 (1): 147–152.
doi:
10.1007/s00414-015-1241-z.
PMID26233612.
S2CID25318521.