THC-COOH11-nor-9-carboxy-Δ9-tetrahydrocannabinol acid

Formula

C₂₁H₂₈O₄

Molar mass

344.40 g·mol⁻¹

CAS

64280-14-4

PubChem CID

107885

Origin

No natural occurrence in the cannabis plant. The molecule forms exclusively in the body, as the terminal phase I metabolite of Δ9-THC, whatever the route of exposure. It is also prepared in the laboratory as a certified analytical standard, a use that constitutes the bulk of its lawful production.

InChIKey

YOVRGSHRZRJTLZ-UHFFFAOYSA-N

Editorial estimate, not clinical.

11-nor-9-carboxy-Δ9-tetrahydrocannabinol acid is the terminal metabolite of Δ9-THC and the central molecule of the whole toxicology of cannabis. It forms by oxidation of 11-hydroxy-THC, itself arising from the hydroxylation of THC by CYP2C9, then conjugates massively to glucuronic acid before urinary and faecal elimination. Unlike its two precursors, it is devoid of activity at the CB1 receptor: the acid function makes it too polar to reach central targets, and it therefore produces no intoxicating effect. Its interest lies elsewhere. Its persistence in the body far exceeds that of THC, because it is released slowly from the lipid compartments where THC had accumulated. Urinary monitoring in adolescent and young adult users maintained in biologically verified abstinence has measured a median half-life on the order of two days and a median detection window of about ten days, with considerable individual dispersion. That variability explains why no urinary concentration makes it possible to date a use, and why normalisation to creatinine has become common practice for distinguishing a new intake from mere residual elimination. The series of acid analogues with modified side chains has moreover opened a distinct therapeutic route, that of non-intoxicating acidic cannabinoids with an anti-inflammatory aim.

There is no plant route for this molecule. It forms in two stages in the liver: Δ9-THC is first hydroxylated at position 11 by CYP2C9 to give 11-OH-THC, itself active, then that primary alcohol is oxidised into a carboxylic acid. The product is subsequently very largely conjugated to glucuronic acid on the acid function, the form in which it is excreted. Cytosolic enzymes also take part in that last oxidative step, alongside the cytochromes P450.

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

Class

Semi-synthetic cannabinoid

Origin

No natural occurrence in the cannabis plant. The molecule forms exclusively in the body, as the terminal phase I metabolite of Δ9-THC, whatever the route of exposure. It is also prepared in the laboratory as a certified analytical standard, a use that constitutes the bulk of its lawful production.

Status

Narcotic: generic clause

1. 1.Fraser et Worth 2004 : profils d'excrétion urinaire du THC-COOH et du 11-OH-THC rapportés à la créatininePMID 15240035
2. 2.Schuster et coll. 2020 : élimination urinaire du THC-COOH pendant un mois d'abstinence vérifiéePMID 31535597
3. 3.Zurier et coll. 1998 : l'acide diméthylheptyl-THC-11-oïque, analogue acide anti-inflammatoire non psychotropePMID 9433882