8-Hydroxyhexahydrocannabinol
8-Hydroxyhexahydrocannabinols are active primary metabolites of hexahydrocannabinol in animals and trace phytocannabinoids. The 8-OH-HHCs are produced in notable concentrations following HHC administration in several animal species, including humans. They have drawn research interest for therapeutic use & their role in HHC toxicology and stereoisomeric probes of the cannabinoid drug/receptor interaction.
Like Δ9-THC and Δ8-THC, HHC is processed by cytochrome P450 to a series of oxygenated derivatives, some of which maintain activity. While 11-OH-HHC and its downstream products are the major metabolites of HHC metabolism, hydroxylation at C8 plays a varyingly significant role in animal species. Metabolite ratios are also subject to interspecies variation, with one study finding mice hepatocytes preferentially produced 8α-OH-HHC while hamster hematocytes evidenced the opposing selectivity.
While 11-OH-HHC is quickly oxidized to the inactive, water-soluble 11-COOH-HHC, further oxidation of 8-OH instead yields the 8-oxo derivatives, which are then conjugated and excreted.