11-OH-CBN11-Hydroxycannabinol

Formula

C₂₁H₂₆O₃

Molar mass

326.40 g·mol⁻¹

CAS

30432-08-7

PubChem CID

3082311

Origin

No notable natural occurrence in the plant. The molecule forms in the body as a hepatic phase I metabolite of cannabinol, and it is prepared chemically for the purposes of research and analysis. It should be recalled here that the cannabinol from which it comes is not itself a biosynthetic product of hemp: it results very largely from the oxidation of THC during drying and storage, which the reference literature regards as a conservation artefact rather than as a native constituent.

InChIKey

YDKZOUNVEIGJPO-UHFFFAOYSA-N

Editorial estimate, not clinical.

11-hydroxycannabinol is the major metabolite of cannabinol, formed in the liver by hydroxylation of the methyl at position 11. It illustrates a rule that holds throughout the cannabinoid series: that hydroxylation does not destroy affinity for the receptors, it increases it. Where cannabinol is a mediocre ligand, its metabolite binds CB1 with an inhibition constant of 38.0 nanomolar and CB2 with 26.6 nanomolar, in the measurements of Rhee and colleagues. Its functional profile is more singular: an agonist on the CB1 pathway, where it inhibits adenylyl cyclase with a median effective concentration of 58.1 nanomolar, it fails to activate the CB2 pathway and behaves there as an antagonist. The same study showed that moving to the dimethylheptyl side chain turns this modest compound into a very potent agonist of both receptors, with affinities falling below the nanomolar, a result that fed all the subsequent medicinal chemistry of substituted cannabinols. One caveat must accompany the reading of this entry: the cannabinol from which the molecule derives is very largely an oxidation product of THC occurring in storage, and not a biosynthetic constituent of hemp, so that the whole cannabinol class belongs more to conservation chemistry than to botany.

There is no plant route for this molecule. It forms in the liver by hydroxylation of the methyl borne by carbon 11 of cannabinol, a reaction analogous to the one that turns Δ9-THC into 11-hydroxy-THC. The skeleton of cannabinol being entirely aromatised on its terpene ring, the resulting molecule retains that planar character, unlike the hydroxylated metabolites of the tetrahydrocannabinols.

Sources: EUR-Lex, UNODC, CND, ANSM, IUPHAR/BPS, ChEBI, EUDA. Our method.

Class

Semi-synthetic cannabinoid

Origin

No notable natural occurrence in the plant. The molecule forms in the body as a hepatic phase I metabolite of cannabinol, and it is prepared chemically for the purposes of research and analysis. It should be recalled here that the cannabinol from which it comes is not itself a biosynthetic product of hemp: it results very largely from the oxidation of THC during drying and storage, which the reference literature regards as a conservation artefact rather than as a native constituent.

Status

Unscheduled

1. 1.Rhee et coll. 1997 : dérivés du cannabinol, liaison aux récepteurs CB1 et CB2 et inhibition de l'adénylylcyclasePMID 9379442
2. 2.Yamamoto et coll. 1987 : activité pharmacologique du cannabinol et de son métabolite majeur le 11-hydroxycannabinolPMID 3664823