THC-HSΔ9-THC hemisuccinate

Formula

C₂₅H₃₄O₅

Molar mass

414.50 g·mol⁻¹

CAS

52855-15-9

PubChem CID

162707

Origin

A semi-synthetic compound, absent from cannabis. It is obtained by esterification of the phenol of Δ9-THC with succinic acid, an operation that leaves a free carboxylic acid function and allows salts to be formed. It was the subject of pharmaceutical development in suppository form, without leading to a marketing authorisation.

InChIKey

YVOODUUYDJKFDY-RTBURBONSA-N

Editorial estimate, not clinical.

Δ9-THC hemisuccinate is a prodrug of tetrahydrocannabinol designed for rectal administration, a chemical answer to a real pharmacokinetic problem: by the oral route THC shows a bioavailability of only about ten per cent, largely consumed by the hepatic first-pass effect. Esterification of the phenol with succinic acid leaves a free acid function, hence the possibility of forming salts and improving the formulation. The mechanism is that of a strict prodrug: the ester crosses the rectal mucosa then hydrolyses so fast that it is not detectable in plasma, where THC and its metabolites are found instead. In monkeys, the bioavailability of Δ9-THC from this formulation was estimated at 13.5 per cent, with a mean residence time raised to 5.8 hours against 3 hours after intravenous administration. In humans, the study published in 2018 in Medical Cannabis and Cannabinoids reports systemic exposure to Δ9-THC markedly higher than that obtained by capsule, with an area under the curve multiplied by 2.44. Development did not result in a marketed medicine.

No plant route. The compound is a monoester of Δ9-THC: the phenol function at position 1 of the benzo[c]chromene skeleton is esterified by butanedioic acid, whose second acid function remains free. That free acid function is what makes the formation of water-soluble salts possible. It is described here by chemical class only.

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

Class

Semi-synthetic cannabinoid

Origin

A semi-synthetic compound, absent from cannabis. It is obtained by esterification of the phenol of Δ9-THC with succinic acid, an operation that leaves a free carboxylic acid function and allows salts to be formed. It was the subject of pharmaceutical development in suppository form, without leading to a marketing authorisation.

Status

Narcotic: generic clause

1. 1.Pharmacocinétique et tolérance du Δ9-THC-hémisuccinate en suppositoire (2018)PMID 34676321
2. 2.Biodisponibilité rectale du Δ9-THC à partir de l'ester hémisuccinate chez le singe (1991)PMID 1664466
3. 3.Contourner l'effet de premier passage pour l'usage thérapeutique des cannabinoïdes (1993)PMID 8383856