Δ4-THCΔ4-tetrahydrocannabinol (Δ6a,7-THC)

Formula

C₂₁H₃₀O₂

Molar mass

314.23 g·mol⁻¹

CAS

59042-44-3

PubChem CID

91936925

Origin

A positional isomer of tetrahydrocannabinol, obtained by chemical means and not isolated from the plant. Δ9-THC and Δ8-THC differ by the position of the single double bond of the terpene ring; that of the present compound is elsewhere again, between positions 6a and 7 in the dibenzopyran numbering, which moves the point of unsaturation to the ring junction.

InChIKey

UQOUHXDCXBITSF-GDBMZVCRSA-N

Editorial estimate, not clinical.

Δ4-THC, more often designated Δ6a,7-THC in the chemical literature, presents a singular situation: it is an internationally controlled substance whose pharmacology is essentially unknown. Schedule I of the 1971 convention on psychotropic substances does not mention only Δ9-THC; it enumerates six constitutional isomers by their full chemical designation, with their stereochemical variants, and this molecule is one of them. It was obtained in 1975 by Arnone, Merlini and Servi, not as a therapeutic candidate but as a by-product of work on routes of access to the natural forms of tetrahydrocannabinol: condensing a phenolic precursor and a terpene precursor in acid medium forms the dibenzopyran skeleton, but the final position of the double bond depends on the precursor and on the conditions, so that the chemistry of THC spontaneously produces its own isomers. The Expert Committee on Drug Dependence of the World Health Organization examined those six isomers in 2018 and its finding deserves quoting as it stands: three of them, including this one, have not been assessed in any detail for their toxicity, and the committee indicates that they may never have been tested for pharmacological activity. Only Δ8-THC and Δ6a,10a-THC have been administered to humans in pure form, with effects of the same nature as those of Δ9-THC but less intense. International control of these molecules therefore rests on their structural kinship with Δ9-THC rather than on data of their own, a situation the committee itself notes in stressing that no critical review has ever been conducted on them.

An entirely chemical route, described here by class only. The compound arises from the condensation of a phenolic precursor of the olivetol type with a monoterpene precursor, in the presence of an acid catalyst, a generic reaction forming the dibenzopyran skeleton whose outcome depends on the nature of the terpene precursor and on the conditions used. It is that dependence which explains why work on the synthesis of the natural forms also produces their positional isomers.

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

Class

Semi-synthetic cannabinoid

Origin

A positional isomer of tetrahydrocannabinol, obtained by chemical means and not isolated from the plant. Δ9-THC and Δ8-THC differ by the position of the single double bond of the terpene ring; that of the present compound is elsewhere again, between positions 6a and 7 in the dibenzopyran numbering, which moves the point of unsaturation to the ring junction.

Status

Narcotic: named in schedule

1. 1.Comité d'experts de la pharmacodépendance de l'OMS, 41e réunion 2018 : examen critique des isomères du THC
2. 2.Arnone, Merlini et Servi 1975 : synthèse du (+)-Δ4-tétrahydrocannabinol, Tetrahedron 31(24) 3093DOI 10.1016/0040-4020(75)80154-2